Am J Chin Med. 2021 Jul 8:1-19. doi: 10.1142/S0192415X21500695. Online ahead of print.

ABSTRACT

14-Deoxy-11,12-didehydroandrographolide (deAND), a bioactive component of Andrographis paniculata, has antidiabetic activity. AMP-activated protein kinase (AMPK) regulates glucose transport and ameliorates insulin resistance. The aim of the present study was to investigate whether activation of AMPK is involved in the mechanism by which deAND ameliorates insulin resistance in muscles. deAND amounts up to 40 [Formula: see text]M dose-dependently activated phosphorylation of AMPK[Formula: see text] and TBC1D1 in C2C12 myotubes. In addition, deAND significantly activated phosphorylation of LKB1 at 6 h after treatment, and this activation was maintained up to 48 h. deAND increased glucose uptake at 18 h after treatment, and this increase was time dependent up to 72 h. Compound C, an inhibitor of AMPK, suppressed deAND-induced phosphorylation of AMPK[Formula: see text] and TBC1D1 and reversed the effect on glucose uptake. In addition, the expression of GLUT4 mRNA and protein in C2C12 myotubes was up-regulated by deAND in a time-dependent manner. Promotion of GLUT4 gene transcription was verified by a pGL3-GLUT4 (837 bp) reporter assay. deAND also increased the nuclear translocation of MEF-2A and PPAR[Formula: see text]. After 16 weeks of feeding, the high-fat diet (HFD) inhibited phosphorylation of AMPK[Formula: see text] and TBC1D1 in skeletal muscle of obese C57BL/6JNarl mice, and deactivation of AMPK[Formula: see text] and TBC1D1 by the HFD was abolished by deAND supplementation. Supplementation with deAND significantly promoted membrane translocation of GLUT4 compared with the HFD group. Supplementation also significantly increased GLUT4 mRNA and protein expression in skeletal muscle compared with the HFD group. The hypoglycemic effects of deAND are likely associated with activation of the LKB1/AMPK[Formula: see text]/TBC1D1/GLUT4 signaling pathway and stimulation of MEF-2A- and PPAR[Formula: see text]-dependent GLUT4 gene expression, which account for the glucose uptake into skeletal muscle and lower blood glucose levels.

PMID:34240660 | DOI:10.1142/S0192415X21500695

Inflammopharmacology. 2021 Jul 7. doi: 10.1007/s10787-021-00843-6. Online ahead of print.

ABSTRACT

STZ is a glucosamine-nitrosourea compound, causes dysfunctioning of insulin receptors in the brain and disrupts glucose metabolism, produces cognitive decline and AD-like symptoms. ICV injection of STZ causes accumulation of Aβ and cognitive dysfunctions. Andrographolide (ANDRO) is a major bioactive constituent of Andrographis paniculata, has various biological activities such as antioxidant, anti-inflammatory, anti-cholinesterase, and neuroprotective properties. The study aimed to evaluate the neuroprotective effect of ANDRO against ICV-STZ induced AD-like symptoms in rats. To conduct the study, the Wistar rat received two injections of STZ (3 mg/kg) through the ICV route. Rats were treated with three different doses of ANDRO (15, 30, and 60 mg/kg, p.o.) and donepezil (5 mg/kg, p.o.) for 14 days. The behavioral impairments were analyzed on weekly basis. Subsequently, rats were sacrificed for the assessment of biochemical (MDA, Nitrite, GSH, SOD, Catalase and AChE), neuroinflammatory markers (IL-1β, IL-16, and TNF-α), neurotransmitters (glutamate and GABA), level of Aβ_1-42 and p tau in the hippocampus on day 21st. Our result indicated that ANDRO treatment provided a protective effect against STZ induced behavioral deficits and changes in the biochemical, neuroinflammatory mediators, and neurotransmitters of the hippocampus. Further, ANDRO also reduced the level of Aβ_1-42 and p tau in the rat hippocampus. These findings suggested that the antioxidant, anti-inflammatory, anti-cholinesterase potential of ANDRO contributed to its neuroprotective effect as well as promising therapeutic candidate for the treatment of cognitive impairment and AD-like symptoms.

PMID:34235591 | DOI:10.1007/s10787-021-00843-6

Planta. 2021 Jul 5;254(2):23. doi: 10.1007/s00425-021-03674-5.

ABSTRACT

Greening of in vitro callus cultures and andrographolide over-accumulation was achieved by manipulating light exposure and media composition, when the biosynthetic cascade was channeled through the DXP pathway. Andrographolide, the primary biologically active compound of Andrographis paniculata, is produced through coordinated action of two pathways, the classical cytosolic mevalonate pathway and the alternative plastidial non-mevalonate pathway (Deoxy-xylulose Phosphate pathway). In vitro callus cultures of A. paniculata are useful sources of production, as well as, manipulation of andrographolide, and the present study was designed to explore the strategy of pathway inhibition for its overproduction. When the cytosolic mevalonate pathway blocker, lovastatin, was applied to callus cultures of A. paniculata, andrographolide production was enhanced in comparison to untreated control. In contrast, treatment of the callus tissue with the DXP-pathway blocker, fosmidomycin, led to depletion in andrographolide production. The present study also showed that silver nitrate, a potent elicitor of andrographolide production in in vitro callus culture, when added in combination with the pathway inhibitors resulted in alterations in andrographolide production. The highest andrographolide production was obtained in callus treated with a combination of silver nitrate and lovastatin, indicating a predominant role of the plastidial DXP pathway in andrographolide biosynthesis. A positive co-relation with chlorophyll content and andrographolide production in in vitro callus cultures (untreated and treated) observed also supported the above assumption. It could be inferred from this study that greening of callus tissue through organellar organization was a potent strategy for enhancing andrographolide accumulation in callus tissues of A. paniculata.

PMID:34223986 | DOI:10.1007/s00425-021-03674-5

J Basic Clin Physiol Pharmacol. 2021 Jun 25;32(4):497-504. doi: 10.1515/jbcpp-2020-0440.

ABSTRACT

OBJECTIVES: This study was designed to evaluate the potential of Andrographis paniculata ethanolic extract to inhibit the increase in proliferation and induction of abnormal cell death.

METHODS: The hyperplasia stage as an early stage of cancer development was induced by oral administration of 20 mg/Kg BW DMBA to SD rats twice a week for 5 weeks. There were five groups in this study include negative control, positive control, and treatment groups of DMBA induction followed by administration of A. paniculata ethanolic extract in doses equivalent to 10, 30 or 100 mg/Kg BW andrographolide once per day for 6 consecutive weeks. On the last day, rats were sacrificed, lung and colon tissues were collected. Histological examination by HE staining and immunohistochemistry using p53, telomerase, and caspase-3 antibodies were aimed at observing hyperplasia state in these tissues.

RESULTS: DMBA induction to SD rats was able to produce hyperplasia in lung parenchymal and colon epithelial tissue. This can be showed by the increasing number of proliferated cells and as indicated by the number of brown-colored nuclei with sharper intensity. As well telomerase appears to be overexpressed strongly, while p53 and caspase-3 show low intensity. The administration of A. paniculata extract for 6 weeks showed a decrease in the number of cells that actively proliferate, a decrease in telomerase activity, and an increase in caspase-3 levels which indicate cellular death activity.

CONCLUSIONS: A. paniculata ethanolic extract can inhibit the development of cancer at the hyperplasia stage by reducing telomerase activity and increasing apoptosis, marked by an increase of caspase-3 expressions.

PMID:34214295 | DOI:10.1515/jbcpp-2020-0440

Molecules. 2021 Jun 3;26(11):3379. doi: 10.3390/molecules26113379.

ABSTRACT

With the trend for green technology, the study focused on utilizing a forgotten herb to produce an eco-friendly coating. Andrographis paniculata or the kalmegh leaves extract (KLE) has been investigated for its abilities in retarding the corrosion process due to its excellent anti-oxidative and antimicrobial properties. Here, KLE was employed as a novel additive in coatings and formulations were made by varying its wt%: 0, 3, 6, 9, and 12. These were applied to stainless steel 316L immersed in seawater for up to 50 days. The samples were characterized and analyzed to measure effectiveness of inhibition of corrosion and microbial growth. The best concentration was revealed to be 6 wt% KLE; it exhibited the highest performance in improving the ionic resistance of the coating and reducing the growth of bacteria.

PMID:34205014 | PMC:PMC8199900 | DOI:10.3390/molecules26113379

Environ Pollut. 2021 Jun 23;287:117635. doi: 10.1016/j.envpol.2021.117635. Online ahead of print.

ABSTRACT

The presence of atrazine, a triazine herbicide, and its residues in agriculture soil poses a serious threat to human health and environment through accumulation in edible plant parts. Hence, the present study focused on atrazine induced stress amelioration of Andrographis paniculata, an important medicinal plant, by a plant growth promoting and atrazine degrading endophytic bacterium CIMAP-A7 inoculation. Atrazine has a non-significant effect at a lower dose while at a higher dose (lower: 25 and higher: 50 mg kg^-1) 22 and 36% decrease in secondary metabolite content and plant dry weight of A. paniculata was recorded, respectively. Endophyte CIMAP-A7 inoculation significantly reduced atrazine soil content, by 78 and 51% at lower and a higher doses respectively, than their respective control treatments. Inoculation of CIMAP-A7 exhibited better plant growth in terms of increased total chlorophyll, carotenoid, protein, and metabolite content with reduced atrazine content under both atrazine contaminated and un-contaminated treatments. Atrazine induced oxidative stress in A. paniculata was also ameliorated by CIMAP-A7 by reducing stress enzymes, proline, and malondialdehyde accumulation under contaminated soil conditions than un-inoculated treatments. Furthermore, the presence of atrazine metabolites deisopropylatrazine (DIA) and desethylatrazine (DEA) strongly suggests a role of CIMAP-A7 in mineralization however, the absence of these metabolites in uninoculated soil and all plant samples were recorded. These findings advocate that the amelioration of atrazine induced stress with no/least pesticide content in plant tissues by plant-endophyte co-interactions would be efficient in the remediation of atrazine contaminated soils and ensure safe crop produce.

PMID:34182386 | DOI:10.1016/j.envpol.2021.117635

Chem Zvesti. 2021 Jun 21:1-12. doi: 10.1007/s11696-021-01746-0. Online ahead of print.

ABSTRACT

ABSTRACT: The quantitative analysis of andrographolides in Andrographis paniculata plant materials is essential for pharmaceutical factories. This analysis cannot be done for all samples due to the conventional process using the extraction and HPLC methods requires a long analysis time and sample destruction. Therefore, near-infrared spectroscopy (NIRS) was employed to classify the class of A. paniculata and to determine the content of two active ingredients, andrographolide (AP1) and dehydroandrographolide (AP3) in A. paniculata, rapidly and non-destructively. One hundred twenty dried powder samples were obtained from aerial parts, branches, leaves, and branches mixed with leaves. The NIR absorption scans were collected from a broad spectral region (1000-2500 nm). Then, the scanned samples were extracted and analyzed for their AP1 and AP3 contents using an HPLC reference method. The success classification model based on AP1 level was developed using the second derivative pretreated NIR spectra of the entire wavelength region using the Partial Least Squares-Discriminant Analysis (PLS-DA) method. The NIR calibration models were developed and tested for quantitative analysis with 50 independent samples. The models were identified for the analysis of the AP1 content with excellent performance (correlation coefficient (R) = 0.98; standard error of validation (SEV) = 0.24%) and for the analysis of the AP3 content at a good level of efficiency (R = 0.93; SEV = 0.15%). This study showed that NIR spectroscopic method offers rapid analysis for the selection of A. paniculata that meets the requirement in bioactive amount.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11696-021-01746-0.

PMID:34177074 | PMC:PMC8215322 | DOI:10.1007/s11696-021-01746-0

J Basic Clin Physiol Pharmacol. 2021 Jun 25. doi: 10.1515/jbcpp-2020-0381. Online ahead of print.

ABSTRACT

OBJECTIVES: Andrographis paniculata tablets (AS201-01) have previously been shown to have potent bioactivity as an antimalarial and to produce no unwanted side effects in animal models. Here, we present the phase 1 clinical trial conducted to evaluate the safety of AS201-01 tablets in healthy volunteers.

METHODS: The study was a randomized, double-blind controlled cross-over, a placebo-controlled design consisting of a 4-day treatment of AS201-01 tablets. A total of 30 healthy human volunteers (16 males and 14 females) were divided into two groups, and each group was given 4 tablets, twice daily for 4 days. Group 1 received AS201-01, while group 2 received placebo tablets. Volunteers were given a physical examination before the treatment. The effects of AS201-01 on random blood glucose, biochemical, and hematological as well as urine profiles were investigated.

RESULTS: There were no changes in observed parameters as a result of AS201-01 being administered. Statistical analysis showed no significant difference (p>0.05) between the test and control group regarding hematology profile, biochemical profile, and random blood glucose. Increased appetite and better sleep, which categorized as grade 1 adverse event was reported after treatment with AS201-01 tablet.

CONCLUSIONS: The outcome supports our previous observation that the AS201-01 tablet, given twice a day for 4 days, is safe and nontoxic.

PMID:34171938 | DOI:10.1515/jbcpp-2020-0381

Int Immunopharmacol. 2021 Jul;96:107808. doi: 10.1016/j.intimp.2021.107808. Epub 2021 May 30.

ABSTRACT

Alzheimer's disease is a devastating neurodegenerative disorder, with no disease-modifying treatment available yet. There is increasing evidence that neuroinflammation plays a critical role in the pathogenesis of AD. Andrographolide (Andro), a labdane diterpene extracted from the herb Andrographis paniculata, has been reported to exhibit neuroprotective property in central nervous system diseases. However, its effects on Aβ and Aβ-induced neuroinflammation have not yet been studied. In the present study, we found that Andro administration significantly alleviated cognitive impairments, reduced amyloid-β deposition, inhibited microglial activation, and decreased the secretion of proinflammatory factors in APP/PS1 mice. Furthermore, transcriptome sequencing analysis revealed that Andro could significantly decrease the expression of Itgax, TLR2, CD14, CCL3, CCL4, TLR1, and C3ar1 in APP/PS1 mice, which was further validated by qRT-PCR. Our results suggest that Andro might be a potential therapeutic drug for AD by regulating neuroinflammation.

PMID:34162168 | DOI:10.1016/j.intimp.2021.107808

Vegetos. 2021 Jun 15:1-9. doi: 10.1007/s42535-021-00214-0. Online ahead of print.

ABSTRACT

Present piece of work has been performed with an aim to engender genetic variations in Andrographis paniculata (Burm f.) Nees and Phyllanthus niruri L. since both plants own low or very poor genetic variations due to wild nature. A. paniculata and P. niruri both are magnificent hepatoprotective wild medicinal plants which have been used since ancient times as an ethnomedicine to cure several common and chronic ailments with the high competence and less side effects. UV-B radiations induce mutations because they are absorbed by major biomolecule predominantly by proteins and nucleic acids chiefly DNA. Owing to enormous potential as herbal medicines, both plants i.e. Andrographis and Phyllanthus have been selected for mutation breeding experiments using Ultraviolet-B radiations (UV-B) as a mutagen. When germinating seedlings of A. paniculata and P. niruri were reached up to 1-3 cm, they were treated with UV-B radiations for 0 min, 10 min, 20 min and 30 min with a recovery period of one hour at room temperature and were planted in earthen pots in triplicates. During observations, significant variations in growth and pigment content have been observed in both plants (A. paniculata and P. niruri) in a dose based manner. A wide spectrum of chlorophyll phenodeviants (chlorophyll deficient mutants) in M₂ generation such as xantha, xanthoviridis, alboviridis, virscent and chlorina mutants in A. paniculata and variegated plant, xanthoviridis, xantha and albino mutants in P. niruri have also been observed. Out of all the chlorophyll mutants obtained, few were lethal hence not survived later, while rest were survived till different stages of development. On the basis of occurrence of chlorophyll phenodeviants in Andrographis and Phyllanthus, mutagenic effectiveness and efficiency of different doses of UV-B rays have been indexed. The practice of indexing of effectiveness and efficiency of any mutagen is being used for the successful execution of mutation breeding programs to find the optimum dose that may facilitate induction of a multitude of other lucrative mutations.

PMID:34149208 | PMC:PMC8204301 | DOI:10.1007/s42535-021-00214-0

J Cancer Res Ther. 2021 Apr-Jun;17(2):484-490. doi: 10.4103/jcrt.JCRT_325_19.

ABSTRACT

INTRODUCTION: Andrographis echioides is a prevalently used medicinal herb in South Asian countries. Scientific researches with the extracts of A. echioides revealed its antipyretic, anti-inflammatory, antimicrobial, ulceroprotective, and hepatoprotective properties. This study was done to elucidate antiproliferative and antiangiogenic potential of ethanolic extracts of A. echioides (EEAE) by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and chorioallantoic membrane (CAM) assay.

MATERIALS AND METHODS: EEAE was prepared using Soxhlet apparatus with ethanol after being sun-dried and powdered. MCF 7 (human invasive breast ductal carcinoma) cell lines retaining attributes of differentiated mammary epithelium with both estrogen and progesterone receptors were treated with EEAE, and antiproliferative effect was seen using Mosmann method of MTT assay using 5-fluorouracil (5-FU) as a comparator. The evaluation of antiangiogenic potential of EEAE was done by comparing mean vessel density (MVD) in chick CAM after treatment with EEAE, thalidomide, and vascular endothelial growth factor (VEGF) using CAM assay, an in ovo assay.

RESULTS: EEAE displayed antiproliferative activity from low to high concentrations with MTT assay. The IC₅₀ of EEAE and 5-FU was 62.5 and 15.6 μg/ml, respectively (P < 0.05). The exhibition of its antiangiogenic activity increased proportionately with increasing concentration. VEGF increased MVD by 45.94%; thalidomide decreased it by 53.76%. There was a decrease of MVD by 5.91%, 20.46%, and 35.95% at concentrations of 25, 50, and 100 μg of EEAE, respectively.

CONCLUSION: EEAE possessed significant antiangiogenic and antiproliferative activity, making them a promising substrate in the development of a novel anticancer drug and can be successfully used in the therapy of various cancers after establishment of the anticancer effects in animal models and subsequently in clinical trials.

PMID:34121696 | DOI:10.4103/jcrt.JCRT_325_19

Heliyon. 2021 May 10;7(5):e07002. doi: 10.1016/j.heliyon.2021.e07002. eCollection 2021 May.

ABSTRACT

Andrographis paniculata (Burm f.) Nees is a tropical plant native to Southeast Asia that has been used as an effective remedy for a wide variety of illnesses in traditional Chinese and Ayurvedic medicine. The antimicrobial activity of its crude extract had been shown to be due to its quorum quenching activity. The study determined the effect of purified extracted compounds from the leaf of A. paniculata, namely: andrographolide, 14-deoxyandrographolide, 14-deoxy-12-hydroxyandrographolide and neoandrographolide on quorum sensing-mediated virulence mechanisms in clinical isolates of metallo-β-lactamase (MβL)-producing Pseudomonas aeruginosa. Their effect on the expression of the lasR gene, which codes for LasR, a transcription activator protein of the quorum sensing system in P. aeruginosa was also determined using RT-qPCR. All the pure compounds significantly decreased the biofilm formation, protease production and swarming motility of the P. aeruginosa isolates compared to the untreated controls (p < 0.05). Results of the RT-qPCR assay showed that all compounds significantly downregulated the expression of lasR compared to the untreated control (p < 0.05), supporting the position that the lower virulence activities of the treated group were due to quorum quenching activity of the pure compounds. Multiple comparisons using Tukey's HSD analysis revealed that the means of the relative expression of lasR of the isolates treated with the different compounds were not significantly different from each other (p > 0.05), suggesting equal potencies. Results show the potential of the isolated pure compounds from A. paniculata for use as antimicrobial agents as a result of their quorum quenching activities.

PMID:34027192 | PMC:PMC8131311 | DOI:10.1016/j.heliyon.2021.e07002

Oncol Lett. 2021 Jul;22(1):523. doi: 10.3892/ol.2021.12784. Epub 2021 May 12.

ABSTRACT

The overall prognosis of advanced/metastatic gastric cancer (GC) remains poor despite the development of pharmacotherapy. Therefore, other treatment options, such as complementary and alternative medicine, should be considered to overcome this aggressive malignancy. Andrographis, which is a generally unharmful botanical compound, has gained increasing interest for its anticancer effects in multiple malignancies via the regulation of cancer progression-associated signaling pathways. In the present study, a series of in vitro experiments (cell proliferation, colony formation and apoptosis assays) was designed to elucidate the antitumor potential and mechanism of Andrographis in GC cells. The present study demonstrated that Andrographis exerted antitumor effects in GC cell lines (MKN74 and NUGC4) by inhibiting proliferation, reducing colony formation and enhancing apoptotic activity. Furthermore, it was demonstrated that the expression levels of the ferroptosis-associated genes heme oxygenase-1, glutamate-cysteine ligase catalytic and glutamate-cysteine ligase modifier were significantly upregulated after Andrographis treatment in both GC cell lines in reverse transcription-quantitative PCR experiments (P<0.05); this finding was further confirmed by immunoblotting assays (P<0.05). In conclusion, to the best of our knowledge, the present study was the first to demonstrate that Andrographis possessed antitumor properties by altering the expression levels of ferroptosis-associated genes, thereby providing novel insights into the potential of Andrographis as an adjunctive treatment option for patients with metastatic GC.

PMID:34025790 | PMC:PMC8130053 | DOI:10.3892/ol.2021.12784

Front Pharmacol. 2021 May 6;12:629833. doi: 10.3389/fphar.2021.629833. eCollection 2021.

ABSTRACT

Andrographis paniculata (Burm. F) Nees, has been widely used for upper respiratory tract and several other diseases and general immunity for a historically long time in countries like India, China, Thailand, Japan, and Malaysia. The vegetative productivity and quality with respect to pharmaceutical properties of Andrographis paniculata varies considerably across production, ecologies, and genotypes. Thus, a field deployable instrument, which can quickly assess the quality of the plant material with minimal processing, would be of great use to the medicinal plant industry by reducing waste, and quality grading and assurance. In this paper, the potential of near infrared reflectance spectroscopy (NIR) was to estimate the major group active molecules, the andrographolides in Andrographis paniculata, from dried leaf samples and leaf methanol extracts and grade the plant samples from different sources. The calibration model was developed first on the NIR spectra obtained from the methanol extracts of the samples as a proof of concept and then the raw ground samples were estimated for gradation. To grade the samples into three classes: good, medium and poor, a model based on a machine learning algorithm - support vector machine (SVM) on NIR spectra was built. The tenfold classification results of the model had an accuracy of 83% using standard normal variate (SNV) preprocessing.

PMID:34025404 | PMC:PMC8134700 | DOI:10.3389/fphar.2021.629833

Bioelectrochemistry. 2021 May 8;141:107840. doi: 10.1016/j.bioelechem.2021.107840. Online ahead of print.

ABSTRACT

Andrographolide, a bioactive naturally occurring labdane diterpenoid with outstanding antioxidant effects in medicine, has been isolated and purified from Andrographis paniculata, and applied in acid-chloride environments for the corrosion protection of carbon steel. Upon isolation, the phytochemical was identified by NMR and FTIR, while its corrosion inhibition evaluation was achieved by combined electrochemical and gravimetric experiments. The adsorption of andrographolide on carbon steel was examined by SEM, FTIR, and 3D surface measurement, and computational studies were used to describe the adsorption characteristics and properties. The experimental measurements revealed that andrographolide is an effective mixed-type corrosion inhibitor whose efficiency was dependent on both its concentration and the temperature of the environment, with maximum inhibition efficiency of 92.4% recorded for 2.0 g/L andrographolide after 48 h at 318 K. The adsorption of andrographolide and its anticorrosion capacity on carbon steel surface was confirmed by the employed surface analytical techniques, while molecular electrostatic potential, conceptual density functional theory, and molecular dynamics simulation predicted the quantum chemical details and binding properties of the phytochemical on Fe (110) surface at different temperatures.

PMID:34020400 | DOI:10.1016/j.bioelechem.2021.107840

Front Pharmacol. 2021 Apr 29;12:680589. doi: 10.3389/fphar.2021.680589. eCollection 2021.

ABSTRACT

Lung adenocarcinoma is the most common pathological type of lung cancer with poor patient outcomes; therefore, developing novel therapeutic agents is critically needed. Andrographolide (AD), a major active component derived from the traditional Chinese medicine (TCM) Andrographis paniculate, is a potential antitumor drug, but the role of AD in lung adenocarcinoma remains poorly understood. In the present study, we demonstrated that AD inhibited the proliferation of broad-spectrum lung cancer cell lines in a dose-dependent manner. Meanwhile, we found that a high dose of AD induced Noxa-dependent apoptosis in human lung adenocarcinoma cells (A549 and H1299). Further studies revealed that Noxa was transcriptionally activated by activating transcription factor 4 (ATF4) in AD-induced apoptosis. Knockdown of ATF4 by small interfering RNA (siRNA) significantly diminished the transactivation of Noxa as well as the apoptotic population induced by AD. These results of the present study indicated that AD induced apoptosis of human lung adenocarcinoma cells by activating the ATF4/Noxa axis and supporting the development of AD as a promising candidate for the new era of chemotherapy.

PMID:33995110 | PMC:PMC8117100 | DOI:10.3389/fphar.2021.680589

Plant Physiol Biochem. 2021 Jul;164:82-91. doi: 10.1016/j.plaphy.2021.04.016. Epub 2021 May 5.

ABSTRACT

Nitrogen (N) form affects secondary metabolites of medicinal plants, but the physiological and molecular mechanisms remain largely unknown. To fully understand the response of andrographolide biosynthesis to different N forms in Andrographis paniculata, the plants were fed with nutritional solution containing sole N source of nitrate (NO₃^-), ammonium (NH₄⁺), urea or glycine (Gly), and the growth, carbon (C) and N metabolisms and andrographolide biosynthesis were analyzed. We found that plants grown in urea and Gly performed greater photosynthetic rate and photosynthetic N use efficiency (PNUE) than those grown in NO₃^- and NH₄⁺. Organic N sources reduced the activities of enzymes involving in C and N metabolisms such as glutamine synthase (GS), glutamate synthase (GOGAT) and NADH-dependent glutamate dehydrogenase (NADH-GDH), invertase (INV), isocitrate dehydrogenase (ICDH) and glycolate oxidase (GO), resulting in reduced depletion of carbohydrates and increased starch accumulation. However, they enhanced andrographolide content by up-regulating the key genes in its biosynthetic pathway including HMGR, DXS, GGPS and ApCPS. Besides, NH₄⁺ decreased leaf SPAD value, contents of soluble protein and amino acids and GO activity, but increased photosynthetic rate and contents of soluble sugar and starch in comparison to NO₃^-. Andrographolide biosynthesis was also up-regulated. The results revealed that increasing accumulation of carbohydrates, especially starch, was beneficial to the biosynthesis of andrographolide; organic N sources decreased carbohydrate depletion by reducing N metabolism, and promoted plant growth and andrographolide biosynthesis synergistically.

PMID:33975147 | DOI:10.1016/j.plaphy.2021.04.016

Sci Rep. 2021 May 7;11(1):9752. doi: 10.1038/s41598-021-89257-6.

ABSTRACT

Inflammation is a key factor in the development and complications of various diseases because it has a complex pathogenesis. Andrographis paniculate (Burm. f.) Nees (Chuan Xinlian) is a well-known form of Traditional Chinese Medicine (TCM) applied in clearing heat and detoxification. Also, it is rich in bioactive lactones, with various anti-inflammatory activities. Here, network pharmacology combined with molecular biology experimental approach was used to predict and verify the potential molecular mechanism of Chuan Xinlian in treating inflammation. The bioactive ingredients of Chuan Xinlian were obtained from the TCMSP database and literature. Besides, the targets of Chuan Xinlian and inflammation were collected based on the multi-source databases and used to generate the PPI network. Network topology analysis and functional enrichment analysis were used to screen hub genes and their mechanisms. Molecular docking simulation was performed to evaluate the binding activity between the predicted hub genes and the bioactive ingredients. Additionally, LPS-induced NO production in RAW264.7 cell inflammatory response, RT-PCR and Western blot were used to validate the efficacy of the Chuan Xinlian in the treatment of inflammation. Network analysis outcomes indicated that five targets (IL-6, VEGFA, PTGST2, TNF-α, and MMP-9) were identified as the key targets of Chuan Xinlian in the treatment of inflammation. Further, molecular docking findings revealed that the majority of the bioactive ingredients exhibited a strong binding efficacy towards the predicted hub genes. Functional analysis results showed that the potential mechanisms were primarily concentrated in key pathways including cancer, immunology, and inflammation process. Moreover, RT-PCR and Western blot analysis indicated that Chuan Xinlian extract suppressed the production of inflammatory mediators with anti-inflammatory effects. Our study shows that Chuan Xinlian potentially exerts an anti-inflammatory effect via key pathways including cancer, immunology, and inflammation process. This suggests that Chuan Xinlian has a potential anti-inflammatory action, thereby providing a scientific reference for clinical studies.

PMID:33963245 | PMC:PMC8105393 | DOI:10.1038/s41598-021-89257-6

3 Biotech. 2021 May;11(5):228. doi: 10.1007/s13205-021-02766-z. Epub 2021 Apr 21.

ABSTRACT

Increasing evidence suggests a sizable involvement of hemotoxins in the morbidity associated with envenomation by the Indian spectacled cobra, Naja naja (N.N). This study investigates the ability of Indian polyvalent anti-snake venom (ASV), methanolic extract of Andrographis paniculata (MAP) and their combination in reversing the hemostatic abnormalities, viz. activated partial thromboplastin time(aPTT), prothrombin time(PT) and thrombin time(TT) in citrated plasma. These parameters were assessed in 2 groups of experiments. Group 1: Without the prior incubation of plasma with venom and Group 2: With prior incubation of plasma with venom for 90 min at 37°C. Venom caused significant (p < 0.001) prolongation in aPTT (175%), PT (49%) and TT (34%) in Group 1 and ASV could completely bring them back to normal. MAP showed a concentration-dependent reversal in aPTT, normalization of PT and prolongation of TT. When low concentration of ASV was supplemented with MAP, their combined effect in normalizing aPTT and PT improved by 37% and 26% respectively when compared to ASV alone. In Group 2, venom caused significant (p < 0.001) prolongation in aPTT (231%), PT (312%) and TT (245%). ASV had limited effect in reversing aPTT (52%), TT (31%) but completely normalized PT. MAP was marginally effective in reversing the prolonged aPTT and PT but caused further prolongation of TT. Combination of ASV and MAP was more effective than ASV alone in reversing venom-induced increase in aPTT (52%) and PT (29%). The study proved that, a drastic reduction of ASV by 70%, could be effectively supplemented by MAP in combating hemostatic abnormalities induced by NN venom.

PMID:33959471 | PMC:PMC8060375 | DOI:10.1007/s13205-021-02766-z

Phytother Res. 2021 Apr 30. doi: 10.1002/ptr.7145. Online ahead of print.

ABSTRACT

Andrographis paniculata is home to a rich variety of molecules especially andrographolide and its derivatives. Clinical properties of the andrographolide are multifarious and include: analgesic, antipyretic, antiretroviral, antiproliferative, antimalarial, antithrombotic, antihyperglycemic, antiurolethial, antilesihmaniasis, hepatoprotective, immune-modulatory, protective against alcohol induced toxicity and cardioproetcive activity and anticancer activity. Andrographolide, neoandrographolide, dehydroandrographolide and several natural and synthetic derivatives of it: 14-deoxy-11,12-didehydroandrographolide and 14-deoxyandrographolide, dehydroandrographolide succinic acid monoester (DAMS), 14-ά-lipoyl andrographolide (AL-1), 14-acetyl-3,9-isopropyl-ideneandrographolide, 14-acetylandrographolide, 3,14,19-triacetylandrographolide, and 3,9-isopropyl-idene andrographolide, are shown to possess significant antiviral activity against HIV, influenza A, HBV, HCV, HPP and HSV. Studies on SARS CoV 2 is restricted to in silico molecular docking studies on viral targets and selected host target proteins. The main targets of andrographolide and its derivatives are fusion and adsorption of virus to the host cell, binding to viral receptor and co-receptor, enzymes involved in DNA/RNA/Genome replication by the virus, translation, post-translation and reverse transcription. Andrographolide as a drug is yet to reach its full therapeutic potential since this molecule shows low bioavailability. Andrographolide therapy is in need of an appropriate delivery system that may increase its bioavailability. Further high-quality studies are needed to firmly establish the clinical efficacy of the plant.

PMID:33929758 | DOI:10.1002/ptr.7145

3 Biotech. 2021 Apr;11(4):177. doi: 10.1007/s13205-021-02729-4. Epub 2021 Mar 19.

ABSTRACT

Antibiotic resistance in the context of treating malarial infections is a major challenge in India. Home remedies such as thulasi leaves (Ocimum tenuiflorum), black pepper seeds (Piper nigrum), clove buds (Syzygium aromaticum), cinnamon bark (Cinnamomum verum), and nilavembu whole plant powder (Andrographis paniculata) were taken to explore antimalarial and methicillin-resistant Staphylococcus aureus (MRSA) activity. Among the five extracts, the best two extracts, C. verum and P. nigrum extract, showed the presence of Quercetin. Phytoniosomes were prepared by simple probe sonication with the two extracts and the resultant vesicles were in the size range of (319.7 nm). They showed significant (P < 0.001) antimalarial potency IC₅₀ at 5.25 µg/ml against P. falciparum 3D7. In addition, their cytotoxicity (TC₅₀) against Vero cell line was found to be > 100 µg/ml. The therapeutic index was found to be > 32 µg/ml. Phytoniosomes were converted to a capsule dosage form by lyophilization and this capsule was stable up to 90 days.

PMID:33927968 | PMC:PMC7979849 | DOI:10.1007/s13205-021-02729-4

Life (Basel). 2021 Apr 16;11(4):348. doi: 10.3390/life11040348.

ABSTRACT

Infectious disease (ID) is one of the top-most serious threats to human health globally, further aggravated by antimicrobial resistance and lack of novel immunization options. Andrographis paniculata (Burm. f.) Wall. ex Nees and its metabolites have been long used to treat IDs. Andrographolide, derived from A. paniculata, can inhibit invasive microbes virulence factors and regulate the host immunity. Controlled clinical trials revealed that A. paniculata treatment is safe and efficacious for acute respiratory tract infections like common cold and sinusitis. Hence, A. paniculata, mainly andrographolide, could be considered as an excellent candidate for antimicrobial drug development. Considering the importance, medicinal values, and significant role as antimicrobial agents, this study critically evaluated the antimicrobial therapeutic potency of A. paniculata and its metabolites, focusing on the mechanism of action in inhibiting invasive microbes and biofilm formation. A critical evaluation of the secondary metabolites with the aim of identifying pure compounds that possess antimicrobial functions has further added significant values to this study. Notwithstanding that A. paniculata is a promising source of antimicrobial agents and safe treatment for IDs, further empirical research is warranted.

PMID:33923529 | PMC:PMC8072717 | DOI:10.3390/life11040348

Int J Ophthalmol. 2021 Apr 18;14(4):497-503. doi: 10.18240/ijo.2021.04.03. eCollection 2021.

ABSTRACT

AIM: To explore the effect of the Andrographis paniculata (A. paniculata) polysaccharide on the proliferation and apoptosis of human retinoblastoma (RB) Y79 cells and its mechanism.

METHODS: The refined A. paniculata polysaccharide was obtained using techniques such as water extraction, ethanol precipitation, and decompression concentration. The inhibition effect of the A. paniculata polysaccharide on the proliferation of Y79 cells was detected by cell proliferation assay. Flow cytometry was used for the detection of cell apoptosis rate and cycle change. Real-time qunatitative polymerase chain reaction (RT qPCR)and Western blotting were used to detect the expression of cell apoptosis signal pathway-related factors (caspase-3, caspase-8, and caspase-9) and cell cycle signal pathway-related factors (CDK1 and cyclinB1) at the transcriptional and translational levels.

RESULTS: Infrared and ultraviolet spectrum scanning showed that the extracted drug was a polysaccharide with high purity. After being treated with different concentrations of A. paniculata polysaccharide for different periods of time, the Y79 cells showed different degrees of proliferation inhibition. Flow cytometric observations showed that the cell apoptosis rate and the proportion of cells blocked in the G2/M phase were significantly increased after A. paniculata polysaccharide treatment. Further analysis revealed that the mRNA and protein expression of caspase-3, caspase-8, and caspase-9 in the A. paniculata polysaccharide treatment groups increased significantly compared with that in the control groups, while the expression of CDK1 and cyclinB1 decreased significantly.

CONCLUSION: The A. paniculata polysaccharide could inhibit the proliferation and induce apoptosis of Y79 cells. Its possible mechanism is via the upregulation of caspase-3, caspase-8, and caspase-9 expression in the cell apoptotic signaling pathway and the downregulation of CDK1 and cyclinB1 expression in the cell cycle signaling pathway.

PMID:33875938 | PMC:PMC8025161 | DOI:10.18240/ijo.2021.04.03

J Nat Prod. 2021 Apr 23;84(4):1261-1270. doi: 10.1021/acs.jnatprod.0c01324. Epub 2021 Apr 12.

ABSTRACT

The coronaviruses disease 2019 (COVID-19) caused by a novel coronavirus (SARS-CoV-2) has become a major health problem, affecting more than 50 million people with over one million deaths globally. Effective antivirals are still lacking. Here, we optimized a high-content imaging platform and the plaque assay for viral output study using the legitimate model of human lung epithelial cells, Calu-3, to determine the anti-SARS-CoV-2 activity of Andrographis paniculata extract and its major component, andrographolide. SARS-CoV-2 at 25TCID₅₀ was able to reach the maximal infectivity of 95% in Calu-3 cells. Postinfection treatment of A. paniculata and andrographolide in SARS-CoV-2-infected Calu-3 cells significantly inhibited the production of infectious virions with an IC₅₀ of 0.036 μg/mL and 0.034 μM, respectively, as determined by the plaque assay. The cytotoxicity profile developed over the cell line representatives of major organs, including liver (HepG2 and imHC), kidney (HK-2), intestine (Caco-2), lung (Calu-3), and brain (SH-SY5Y), showed a CC₅₀ of >100 μg/mL for A. paniculata extract and 13.2-81.5 μM for andrographolide, respectively, corresponding to a selectivity index of over 380. In conclusion, this study provided experimental evidence in favor of A. paniculata and andrographolide for further development as a monotherapy or in combination with other effective drugs against SARS-CoV-2 infection.

PMID:33844528 | PMC:PMC8056600 | DOI:10.1021/acs.jnatprod.0c01324

Pak J Pharm Sci. 2020 Sep;33(5(Supplementary)):2347-2350.

ABSTRACT

The present study validates the antidiabetic potential of Andrographis echioides leaf extract (AeLE) on high fat diet-fed diabetic C57BL/6J mice. The male C57BL/6J mouse (age 6-8 weeks) were divided into 2 groups (lean control group and diabetic group). The lean control group (6 animals) was fed with standard diet pellets. The diabetic group animals (24 animals) were made diabetic by feeding a high-fat diet for 12 weeks. This group was then further divided into 4 groups of 6 animals each and treated orally (for 28 days) with vehicle (0.5%carboxymethyl cellulose), metformin 100mg/kg body weight and 2 different concentrations of test drug viz., 100mg/kg and 200mg/kg body weight. The results show a significant reduction in blood glucose and other biochemical parameters. After 28 days, the metformin and AeLE (200 mg/kg b.w) treated animals had an average serum glucose value of 129.69±1.97 mg/dl and 109.6±3.92 mg/dl, respectively. Also, the liver markers were positively affected by AeLE. In conclusion, A. echioides leaf extract was found to reduce hyperglycemia and significantly improve the biochemical profile of the mice.

PMID:33832910

J Ethnopharmacol. 2021 Jul 15;275:114054. doi: 10.1016/j.jep.2021.114054. Epub 2021 Apr 6.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Andrographis paniculata (Burm.f.) Nees is a medicinal herb of the Asian countries used in many traditional medicinal systems for the treatment of diarrhea, flu, leprosy, leptospirosis, malaria, rabies, upper respiratory infections, sinusitis, syphilis, tuberculosis and HIV/AIDS etc. AIM OF THE STUDY: This review aims to provide the comprehensive, accurate and authentic information on traditional uses, phytochemistry and pharmacological properties of various extracts/fractions as well as phytocostituents of A. paniculata. In addition, this review also aims to provide advance and sensitive analytical methods along with chemical markers used in the standardization of herbal products for quality control (QC)/quality assurance (QA).

MATERIALS AND METHODS: All relevant publications were considered within the years 1983-2020. The publications were searched from Google Scholar, PubChem, Chemspider, PubMed, Elsevier, Wiley, Web of Science, China Knowledge Resource Integrated databases and ResearchGate using a combination of various relevant keywords. Besides, relevant published books and chapters were also considered those providing an overview of extant secondary literature related to traditional knowledge, phytochemistry, pharmacology and toxicity of the plant.

RESULTS AND DISCUSSION: In this review, 344 compounds, including, terpenoid lactones, flavonoids, phenolic acids, triterpenes and volatile compounds were summarized out of which more than half of the compounds have no reported pharmacological activities yet. Terpenoid lactones and flavonoids are the major bioactive classes of compounds of A. paniculata which are responsible for pharmacological activities such as anticancer and antioxidant activities, respectively. Biosynthetic pathways and active sites for target proteins of both terpenoid lactones and flavonoids were considered. Analgesic, anticancer, antidiabetic, antifertility, antiinflammatory, antimalarial, antimicrobial, antioxidant, antipyretic, antiviral, antiretroviral, antivenom, cardioprotective, hepatoprotective, immunomodulatory and neuroprotective activities have been also reported. Andrographolide is a major characteristic active principle and responsible for most of the pharmacological activities. Therefore, andrographolide has been selected as a marker for the standardization of raw and marketed herbal products by TLC, HPTLC, HPLC, GC-MS, HPLC-MS and HPLC-MS/MS methods for QC/QA.

CONCLUSIONS: Conclusive evidence showed that the pharmacological activities reported in crude extracts and chemical markers are supporting and provides confidence in the traditional use of A. paniculata as a herbal medicine. The andrographolide could be used as a chemical marker for the QC/QA of raw and A. paniculata derived herbal products. Lactone ring in terpenoid lactone is an active site for targeted proteins. More efforts should be focused on the identification of the chemical markers from A. paniculata to provide a practical basis for QC/QA. Several aspects such as the mechanism of therapeutic potential, molecular docking technology and multi-target network pharmacology are very important for drug discovery and needed more investigation and should be considered. This compilation may be helpful in further study and QC/QA.

PMID:33831465 | DOI:10.1016/j.jep.2021.114054

Sci Rep. 2021 Apr 6;11(1):7548. doi: 10.1038/s41598-021-87283-y.

ABSTRACT

The high degree of morbidity and mortality in colorectal cancer (CRC) patients is largely due to the development of chemoresistance against conventional chemotherapeutic drugs. In view of the accumulating evidence that various dietary botanicals offer a safe, inexpensive and multi-targeted treatment option, herein, we hypothesized that a combination of Andrographis paniculata and Oligomeric Proanthocyanidins (OPCs) might interact together with regard to anti-tumorigenic activity in CRC. As a result, we demonstrated the enhanced anti-cancer activity between these two botanical extracts in terms of their ability to inhibit cancer cell growth, suppress colony formation and induce apoptosis. Furthermore, we validated these findings in subcutaneous xenograft model and in patient derived primary epithelial 3D organoids. Transcriptomic profiling identified involvement of metabolic pathways and ferroptosis-associated genes, including HMOX1, GCLC and GCLM, that may be responsible for the increased anti-tumorigenic activity by the two compounds. Collectively, our study provides novel evidence in support of the combinatorial use of andrographis and OPCs as a potential therapeutic option, perhaps as an adjunctive treatment to classical drugs, in patients with colorectal cancer.

PMID:33824419 | PMC:PMC8024269 | DOI:10.1038/s41598-021-87283-y

Carcinogenesis. 2021 Jun 21;42(6):814-825. doi: 10.1093/carcin/bgab027.

ABSTRACT

Colorectal cancer (CRC) ranks as the third leading cause of cancer-related deaths in the USA. 5-Fluorouracil (5FU)-based chemotherapeutic drug remains a mainstay of CRC treatment. Unfortunately, ~50-60% of patients eventually develop resistance to 5FU, leading to poor survival outcomes. Our previous work revealed that andrographis enhanced 5FU-induced anti-cancer activity, but the underlying mechanistic understanding largely remains unclear. In this study, we first established 5FU-resistant (5FUR) CRC cells and observed that combined treatment with andrographis-5FU in 5FUR cells exhibited superior effect on cell viability, proliferation, and colony formation capacity compared with individual treatments (P < 0.001). To identify key genes and pathways responsible for 5FU resistance, we analyzed genome-wide transcriptomic profiling data from CRC patients who either responded or did not respond to 5FU. Among a panel of differentially expressed genes, Dickkopf-1 (DKK1) overexpression was a critical event for 5FU resistance. Moreover, andrographis significantly downregulated 5FU-induced DKK1 overexpression, accompanied with enhanced anti-tumor effects by abrogating downstream Akt-phosphorylation. In line with in vitro findings, andrographis enhanced 5FU-induced anti-cancer activity in mice xenografts and patient-derived tumoroids (P < 0.01). In conclusion, our data provide novel evidence for andrographis-mediated reversal of 5FU resistance, highlighting its potential role as an adjunct to conventional chemotherapy in CRC.

PMID:33822896 | PMC:PMC8215595 | DOI:10.1093/carcin/bgab027

Molecules. 2021 Mar 24;26(7):1831. doi: 10.3390/molecules26071831.

ABSTRACT

Andrographolide is a labdane diterpenoid herb, which is isolated from the leaves of Andrographis paniculata, and widely used for its potential medical properties. However, there are no reports on the effects of andrographolide on the human suprapatellar fat pad of osteoarthritis patients. In the present study, our goal was to evaluate the innovative effects of andrographolide on viability and Tri-lineage differentiation of human mesenchymal stem cells from suprapatellar fat pad tissues. The results revealed that andrographolide had no cytotoxic effects when the concentration was less than 12.5 µM. Interestingly, andrographolide had significantly enhanced, dose dependent, osteogenesis and chondrogenesis as evidenced by a significantly intensified stain for Alizarin Red S, Toluidine Blue and Alcian Blue. Moreover, andrographolide can upregulate the expression of genes related to osteogenic and chondrogenic differentiation, including Runx2, OPN, Sox9, and Aggrecan in mesenchymal stem cells from human suprapatellar fat pad tissues. In contrast, andrographolide suppressed adipogenic differentiation as evidenced by significantly diminished Oil Red O staining and expression levels for adipogenic-specific genes for PPAR-γ2 and LPL. These findings confirm that andrographolide can specifically enhance osteogenesis and chondrogenesis of mesenchymal stem cells from human suprapatellar fat pad tissues. It has potential as a therapeutic agent derived from natural sources for regenerative medicine.

PMID:33805078 | PMC:PMC8037192 | DOI:10.3390/molecules26071831

Iran J Parasitol. 2021 Jan-Mar;16(1):43-51. doi: 10.18502/ijpa.v16i1.5510.

ABSTRACT

BACKGROUND: Placental malaria has ability to upregulate prostaglandin synthesis by increasing cyclooxygenase-2 (Cox-2) enzyme activity. Cox-2 and prostaglandin have a role in causing uterine contraction and therefore can cause abortion or preterm labor. Tablet AS201-01 containing the ethyl acetate fraction of Andrographis paniculata was tested in vivo on pregnant mice infected with Plasmodium berghei. AS201-01 inhibited the growth of P. berghei, increased TGF-β expression, decreased TLR-4 expression and apoptosis index of placental tissue in P. berghei infected pregnant mice and thus prevented placental malaria complications. These effects were correlated with the decrease of Cox-2 and prostaglandin expression.

METHODS: Twenty-four pregnant mice (Balb/c) were divided into 4 groups (n=6). Mice were maintained at Animal Laboratory of Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia in 2016. G1 were uninfected pregnant mice, G2 untreated infected pregnant mice, G3 infected pregnant mice treated with AS201-01, and G4 infected pregnant mice treated with DHP tablet. All infection groups (G2-G4) were inoculated with 1x10⁶ of P. berghei parasite on day 9 of gestation and treated on day 11. All mice were terminated at day 15 of gestation, and placental tissue was collected. Cytokine expression of Cox-2 and prostaglandin were evaluated using immunohistochemistry.

RESULTS: G3 was found to have lower Cox-2 and prostaglandin expression compared to G4 and G2, but higher compared to G1. Cox-2 and prostaglandin expression was significantly different among groups (P<0.001).

CONCLUSION: This study demonstrates the ability AS201-01 tablets have to decrease Cox-2 and prostaglandin expression on placental of P. berghei infected mice and therefore eliminates the adverse effects of placental malaria.

PMID:33786046 | PMC:PMC7988664 | DOI:10.18502/ijpa.v16i1.5510

Eur J Pharmacol. 2021 May 15;899:174056. doi: 10.1016/j.ejphar.2021.174056. Epub 2021 Mar 20.

ABSTRACT

Non-alcoholic Fatty Liver Disease (NAFLD) is one of the growing epidemics of the globe. This study was aimed to evaluate the anti-NAFLD effect of selected IAN derivatives using in silico, in vitro and in vivo models. In silico tools viz., DataWarrior, SwissADME and Gaussian 09 were used to predict the pharmacokinetic properties and electronic distribution patterns of the derivatives; docking analysis was done with Autodock against PPARα. Toxicities of the derivatives were assessed in HepG2 cells using MTT assay. Anti-NAFLD efficacies of the derivatives were assessed in free fatty acid induced steatotic HepG2 cells. In vivo anti-NAFLD effect of active isoandrographolide (IAN) derivative, 19-propionyl isoandrographolide (IAN-19P) was assessed in High Fat Diet fed rats. In silico and in vitro studies indicated that IAN-19P showed improved drug-likeness and drug score. The toxicity of IAN-19P to HepG2 cells was comparatively less than IAN and other derivatives. In free fatty acid induced steatotic HepG2 cells, treatment with IAN-19P significantly lowered intracellular triglyceride content and leakage of LDH and transaminases. Treating High Fat Diet fed animals with IAN-19P significantly lowered plasma lipids, transaminases, LDH and GGT levels. The treatment with IAN-19P upregulated the expressions of PPARα and CPT-1. IAN-19P did not produce any noticeable adverse effect till 2 g/kg concentration in acute and 250 mg/kg concentration in subacute toxicity studies. This study indicated the beneficial effect of IAN-19P for the treatment of NAFLD; however robust investigations are needed to establish the potential of IAN-19P to treat NAFLD.

PMID:33753108 | DOI:10.1016/j.ejphar.2021.174056

Evid Based Complement Alternat Med. 2021 Mar 8;2021:8848797. doi: 10.1155/2021/8848797. eCollection 2021.

ABSTRACT

OBJECTIVES: To determine the analgesic and antipyretic activities of a tablet derived from Andrographis paniculata ethyl acetate fraction (AS201-01) in animal models.

METHODS: The tablet derived from AS201-01 contains an equivalent of 35 mg andrographolide per tablet. Analgesic activity was determined using an acetic acid-induced writhing test on adult male mice. A writhe was recorded by a stopwatch and was defined as the stretching of the abdomen and/or stretching of at least one hind limb. For the determination of antipyretic activity, pyrexia was induced by subcutaneous injection of 15% w/v Brewer's yeast into adult male rats. Rectal temperature was monitored at 1, 2, 3, and 4 hours after treatment.

RESULTS: The results showed that the AS201-01 tablet had analgesic and antipyretic activity. In the acetic acid-induced writhing model, AS201-01 tablet exhibited significant analgesic effect with a 66.73% reduction in writhing response at a dose of 50 mg andrographolide/kg body weight compared to the negative control group. The tablet also showed a significant antipyretic effect. The maximum antipyretic effect was observed after the third hour of administration of the AS201-01 tablet at a dose of 100 mg andrographolide/kg body weight.

CONCLUSION: Tablet of Andrographis paniculata ethyl acetate fraction (AS201-01) exhibited analgesic and antipyretic activities.

PMID:33747115 | PMC:PMC7960022 | DOI:10.1155/2021/8848797

Comb Chem High Throughput Screen. 2021 Mar 10. doi: 10.2174/1386207324666210310140611. Online ahead of print.

ABSTRACT

BACKGROUND: Andrographis paniculata, commonly known as "Kalmegh", is an annual herbaceous plant from family Acanthaceae. The whole plant of A. paniculata has explored for multiple pharmacological activities and is scientifically recognized by in-vivo and in-vitro studies. Various biotechnologically engineered techniques have been explored to enhance the bioavailability of this plant.

OBJECTIVE: In this review, we aim to present comprehensive recent advances in the ethnopharmacology, phytochemistry, specific pharmacology, safety and toxicology and bioavailability of A. paniculata and its pure compounds. Possible directions for future research are also outlined in brief, which will encourage advance investigations on this plant.

METHODS: Information on the recent updates of the present review is collected from different electronic scientific databases such as Science Direct, PubMed, Scopus, and Google Scholar. All the composed information is classified into different sections according to the objective of the paper.

RESULTS: More than hundred research and review papers have been studied and incorporated in the present manuscript. After vast literature search of A. paniculata, we present a noteworthy report of various phytoconstituents present in plant, which are accountable for potential therapeutic properties of the plant. Forty-five of studied articles give general information about introduction, ethnobotany and traditional uses of the plant. Twenty-two papers enclosed information about the phytoconstituents present in different parts of A. paniculata and seventy-two papers briefly outlined the pharmacological activities like antioxidant, anti-dengue, anti-ulcerogenic, antifungal, some miscellaneous activities like activity against SARS-CoV-2, antidiarrhoeal. Nineteen studies highlighted the research work conducted by various researchers to increased bioavailability of A. paniculata and two studies reported the safety and toxicology of the plant.

CONCLUSION: This review incorporated the scientifically validated research work encompassing the ethnobotanical description of the subjected plant, phytochemical profile, various pharmacological activities, and recent approaches to enhance the bioavailability of active metabolites.

PMID:33745423 | DOI:10.2174/1386207324666210310140611

Mini Rev Med Chem. 2021 Mar 15. doi: 10.2174/1389557521666210315162354. Online ahead of print.

ABSTRACT

Andrographis paniculata (Burm.f.) Nees (Acanthaceae) is a herbaceous plant and commonly called 'King of Bitters'. It has gained attraction as a potential hepatoprotective agent and a natural molecule with various biological activities viz. anticancer, immunomodulatory, anti-inflammatory, antibacterial, neuroprotective, and so on. The andrographolide is one of the main diterpenoids responsible for the drug's bitter taste and various therapeutic activities. The poor cellular permeability, solubility and short biological half-life of its pure components limit its distribution to the target tissue. To conquer this obstacle, various researchers worldwide have been working on designing the synthetic derivatives of its active components and nanoformulations to improve the drug's efficiency and selectivity to develop more active leads for biomedical applications. This article discussed the recent research on synthetic derivatives, including their possible therapeutic applications and structure-activity relationship (SAR). Additionally, this article also presents the essential information concerning the various nanoformulations developed to increase the delivery of pure compound/plant extract to the target site, thereby improving the drug's efficacy for multiple ailments.

PMID:33719961 | DOI:10.2174/1389557521666210315162354

Physiol Plant. 2021 Mar 13. doi: 10.1111/ppl.13393. Online ahead of print.

ABSTRACT

Contaminations of heavy metals such as lead (Pb) and cadmium (Cd) in medicinal plants (MPs) not only restrict their safe consumption due to health hazards but also lower their productivity. Biochar amendments in the soil are supposed to immobilize the toxic metals, improve the soil quality and agricultural productivity. However, the impact of biochar on growth attributes, metal accumulation, pharmacologically active compounds of MPs, and health risk is less explored. An experiment was performed on three medicinal plants (Bacopa monnieri (L.), Andrographis paniculata (Burmf.) Nees, and Withaniasomnifera (L.)) grown in a greenhouse in soil co-contaminated with Pb and Cd (at two concentrations) without and with biochar amendments (2 and 4% application rates). The fractionation of Pb and Cd, plant growth parameters, stress enzymes, photosynthetic capacity, pharmacologically active compounds, nutrient content, uptake and translocation of metals, antioxidant activities, and metabolite content were examined in the three MPs. The accumulation of Pb and Cd varied from 3.25-228 mg kg¹ and 1.29-20.2 mg kg^-1 , respectively, in the three MPs, while it was reduced to 0.08-18 mg kg^-1 and 0.03-6.05 mg kg^-1 upon biochar treatments. Plants grown in Pb and Cd co-contaminated soil had reduced plant biomass (5-50% depending on the species) compared to control and a deleterious effect on photosynthetic attributes and protein content. However, biochar amendments significantly improved plant biomass (21-175%), as well as photosynthesis attributes, chlorophyll, and protein contents. Biochar amendments in Pb and Cd co-contaminated soil significantly reduced the health hazard quotient (HQ) estimated for the consumption of these medicinal herbs grown on metal-rich soil. An enhancement in secondary metabolite content and antioxidant properties was also observed upon biochar treatments. These multiple beneficial effects of biochar supplementation in Pb and Cd co-contaminated soil suggested that a biochar amendment is a sustainable approach for the safe cultivation of MPs. This article is protected by copyright. All rights reserved.

PMID:33713449 | DOI:10.1111/ppl.13393

Physiol Mol Biol Plants. 2021 Feb;27(2):223-235. doi: 10.1007/s12298-021-00952-0. Epub 2021 Feb 19.

ABSTRACT

The full length Andrographis paniculate 4-hydroxy 3-methyl 2-butenyl 4-diphosphate reductase (ApHDR) gene of MEP pathway was isolated for the first time. The ApHDR ORF with 1404 bp flanked by 100 bp 5'UTR and 235 bp 3'UTR encoding 467 amino acids (NCBI accession number: MK503970) and cloned in pET 102, transformed and expressed in E. coli BL21. The ApHDR protein physico-chemical properties, secondary and tertiary structure were analyzed. The Ramachandran plot showed 93.8% amino acids in the allowed regions, suggesting high reliability. The cluster of 16 ligands for binding site in ApHDR involved six amino acid residues having 5-8 ligands. The Fe-S cluster binding site was formed with three conserved residues of cysteine at positions C123, C214, C251 of ApHDR. The substrate HMBPP and inhibitors clomazone, paraquat, benzyl viologen's interactions with ApHDR were also assessed using docking. The affinity of Fe-S cluster binding to the cleft was found similar to HMBPP. The HPLC analysis of different type of tissue (plant parts) revealed highest andrographolide content in young leaves followed by mature leaves, stems and roots. The differential expression profile of ApHDR suggested a significant variation in the expression pattern among different tissues such as mature leaves, young leaves, stem and roots. A 16-fold higher expression of ApHDR was observed in the mature leaves of A. paniculata as compared to roots. The young leaves and stem showed 5.5 fold and fourfold higher expression than roots of A. paniculata. Our result generated new genomic information on ApHDR which may open up prospects of manipulation for enhanced diterpene lactone andrographolide production in A. paniculata.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-00952-0.

PMID:33707865 | PMC:PMC7907293 | DOI:10.1007/s12298-021-00952-0

Protoplasma. 2021 Mar 11. doi: 10.1007/s00709-021-01631-3. Online ahead of print.

ABSTRACT

Kalmegh [Andrographis paniculata (Burm.f.) Wall. ex Nees] is one of the most studied medicinal plants for pharmaceutical properties and phytochemistry. However, functional genomics studies in kalmegh are so far limited due to the unavailability of a robust tool for gene silencing. Here, we tested the application of virus-induced gene silencing (VIGS) in kalmegh using the well-known Tobacco rattle virus (TRV)-based vectors and achieved targeted silencing of phytoene desaturase (ApPDS) which is essential in plants for carotenoid biosynthesis that protects chlorophyll from photooxidation. ApPDS silencing in kalmegh leaves developed a typical photobleaching phenotype. The silencing of ApPDS was confirmed by analysing ApPDS transcript level and determining chlorophyll content in the leaves of VIGS seedlings. The analysis revealed ~30% reduction in chlorophyll content, and 40 to 60% reduction in ApPDS transcript level in the leaves of VIGS seedlings. These findings clearly demonstrated the applicability of VIGS in kalmegh using TRV-based vectors. The VIGS protocol presented in this study might be useful for studying gene function related to medicinal and agricultural traits in kalmegh.

PMID:33704567 | DOI:10.1007/s00709-021-01631-3

Saudi Pharm J. 2021 Feb;29(2):143-165. doi: 10.1016/j.jsps.2020.12.016. Epub 2021 Jan 7.

ABSTRACT

Medicinal plants have gained much interest in the prevention and treatment of common human disease such as cold and fever, hypertension and postpartum. Bioactive compounds from medicinal plants were synthesised using effective extraction methods which have important roles in the pharmaceutical product development. Orthosiphon aristatus (OA), Eurycoma longifolia (EL) and Andrographis paniculata (AP) are among popular medicinal herbs in Southeast Asia. The major compounds for these medicinal plants are polar bioactive compounds (rosmarinic acid, eurycomanone and andrographolide) which have multiple benefits to human health. The bioactive compounds are used as a drug to function against a variety of diseases with the support of scientific evidence. This paper was intended to prepare a complete review about the extraction techniques (e.g. OA, EL and AP) of these medicinal plants based on existing studies and scientific works. Suitable solvents and techniques to obtain their major bioactive compounds and their therapeutic potentials were discussed.

PMID:33679177 | PMC:PMC7910186 | DOI:10.1016/j.jsps.2020.12.016

Heliyon. 2021 Feb 11;7(2):e06173. doi: 10.1016/j.heliyon.2021.e06173. eCollection 2021 Feb.

ABSTRACT

Medicinal plants are essential aspects of readily available primary healthcare remedies. Phytochemical constituents of medicinal plants cover a broad variety of chemical fields to explore medicines. This review highlights selected empirical data on traditional uses, phytochemistry, and pharmacological properties of Taunggyi medicinal plants, Andrographis paniculata, Physalis peruviana, and Cassia fistula. Historically, these plants have been used for many infections and diseases in Taunggyi. More than 361 chemical compounds have been isolated and identified from the selected plants. Some of the chemical constituents have substantial pharmacological properties. It is clear that these herbs have significant potential for useful natural supplements in many contemporary diseases. Thus, the aim of this review compiles an ethnobotanical survey and documentation of medicinal plants in Taunggyi (Myanmar). This review will also inspire Myanmar researcher's to further investigate the potential of these plants in their future work into new compound and new drugs.

PMID:33659733 | PMC:PMC7892936 | DOI:10.1016/j.heliyon.2021.e06173

Biochim Biophys Acta Gen Subj. 2021 Jun;1865(6):129885. doi: 10.1016/j.bbagen.2021.129885. Epub 2021 Feb 25.

ABSTRACT

BACKGROUND: Heat shock response (HSR), a component of cellular protein quality control mechanisms, is defective in different neurodegenerative conditions such as Parkinson's disease (PD). Forced upregulation of heat shock factor 1 (HSF1), an HSR master regulator, showed therapeutic promise in PD models. Many of the reported small-molecule HSF1 activators have limited functions. Therefore, identification and understanding the molecular bases of action of new HSF1 activating molecules is necessary.

METHOD: We used a cell-based reporter system to screen Andrographis paniculata leaf extract to isolate andrographolide as an inducer of HSF1 activity. The andrographolide activity was characterized by analyzing its role in different protein quality control mechanisms.

RESULT: We find that besides ameliorating the PD in MPTP-treated mice, andrographolide upregulated different machineries controlled by HSF1 and NRF2 in both cell and mouse brain. Andrographolide achieves these functions through mTORC1 activated via p38 MAPK and ERK pathways. NRF2 activation is reflected in the upregulation of proteasome as well as autophagy pathways. We further show that NRF2 activation is mediated through mTORC1 driven phosphorylation of p62/sequestosome 1. Studies with different cell types suggested that andrographolide-mediated induction of ROS level underlies all these activities in agreement with the upregulation of mTORC1 and NRF2-antioxidant pathway in mice.

CONCLUSION: Andrographolide through upregulating HSF1 activity ameliorates protein aggregation induced cellular toxicity.

GENERAL SIGNIFICANCE: Our results provide a reasonable basis for use of andrographolide in the therapy regimen for the treatment of PD.

PMID:33639218 | DOI:10.1016/j.bbagen.2021.129885

J Ethnopharmacol. 2021 May 23;272:113936. doi: 10.1016/j.jep.2021.113936. Epub 2021 Feb 18.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Synthetic drugs used for cancer treatment have side effects that may be immunosupressive, can cause liver, kidney and cardiac toxicity, and infertility and ovarian failure, among others. Thus, herbal drugs could be used in the cancer treatment as an adjuvant therapy. Andrographis paniculata (Burm.f.) Nees (AP) is one of the traditional herbs used in different alternative medicinal systems such as Ayurveda, Unani, Chinese, Malayi, Siddha, etc. for the treatment of various disorders and diseases including cancer.

AIM OF THE STUDY: The aim of writing this review is to highlight the medicinal importance of AP and its main phytoconstituent andrographolide (AG). The main emphasis was given on the anticancer activity of AG, its proposed mechanisms of action, novel approaches used to improve its biopharmaceutical properties with the perspective of evidence-based research, and its development as an adjuvant therapy for cancer treatment in future.

MATERIALS AND METHODS: Literature survey was conducted and research papers were retrieved from different databases such as Pubmed, Google Scholar, ACS, Wiley online library, ScienceDirect, Springer, and Scopus during 1970-2020. Research articles, review articles, and short communications, etc. were used for this purpose. The papers were selected on the basis of exclusion and inclusion criteria.

RESULTS: Different anticancer mechanisms of AG have been reportedly proven such as cell cycle arrest, apoptosis, NF-κβ inhibition, antiangiogenesis, cytokine inhibition, etc. whereas its pharmacokinetic properties showed its highly protein bound nature, Cyt P400 (CYP) inhibition, low aqueous solubility, poor oral bioavailability, etc. Different novel formulations of AG have been investigated to increase its bioavailability for better efficacy.

CONCLUSION: This review can provide knowledge about the potential applicability of AP or AG as an adjuvant therapy in cancer treatment. Further research is needed before making any conclusion about the efficacy in humans as an adjuvant therapy in cancer.

PMID:33610710 | DOI:10.1016/j.jep.2021.113936

J Ethnopharmacol. 2021 May 23;272:113954. doi: 10.1016/j.jep.2021.113954. Epub 2021 Feb 18.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Andrographis paniculata (Burm.f.) Nees is widely used all over the world, especially in subtropical regions such as India, Thailand, Vietnam, and China. As a traditional folk Chinese medicine, A. paniculata has been extensively utilized for the treatment of cold, fever, sore throat, cough, carbuncle, and sores, and it is commonly employed for 'clearing heat and resolving toxicity'. Typical symptoms of 'heat and toxicity' include swollen, painful gums, associated with virus-related diseases to a great extent. In vivo and in vitro experiments have demonstrated the potential antiviral properties of A. paniculata and identified its major active constituents against various viruses.

AIM OF THE STUDY: This review focuses on connecting the traditional 'clearing heat and resolving toxicity' effect to compelling recent research advances on the antiviral effects of A. paniculata, explaining its major antiviral mechanisms, and assessing the shortcomings of existing work. Besides, ethnobotany, ethnopharmacological uses, phytochemicals, and toxicology of A. paniculata have been researched.

MATERIALS AND METHODS: The information about A. paniculata was collected from various sources including classic books about Chinese herbal medicine, and scientific databases including WEB OF SCIENCE, PubMed, ScienceDirect, Springer, ACS, SCOPUS, CNKI, CSTJ, and WANFANG.

RESULTS: In this review, the underlying mechanisms of antiviral effect mainly involve the regulation of virus entry, gene replication, and synthesis of functionally mature proteins. Also, A. paniculata is a safe agent without obvious toxicity. Ethnobotany, ethnopharmacological uses, and chemical constituents have been summarized.

CONCLUSION: Andrographis paniculata (Burm.f.) Nees could be used as an imperative complementary medicine for the treatment of diverse virus infection, efforts should be made to gain insights into its antiviral properties.

PMID:33610706 | DOI:10.1016/j.jep.2021.113954

J Basic Clin Physiol Pharmacol. 2021 Feb 11. doi: 10.1515/jbcpp-2020-0162. Online ahead of print.

ABSTRACT

OBJECTIVES: The use of standard antimalarial drugs, such as dihydroartemisinin-piperaquine (DHP) for the treatment of malaria during pregnancy is limited due to the risk of teratogenicity. The alternative is therefore required although few exist. Here we show a phytopharmaceutical drug derived from Andrographis paniculata (AS201-01), which is effective as herbal antimalarial both in vitro and in vivo and may be a suitable alternative when used in complementary treatment with DHP.

METHODS: Plasmodium berghei infected pregnant BALB/c mice were divided into four groups: G1 (negative control), G2 (AS201-01), G3 (DHP), and G4 (combination of DHP and AS201-01). Pheripheral blood was collected during therapy for counting parasitemia. Placental samples were analyzed for the expression of IFN-γ, TNF- α, IL-10, placental parasite counts and foetal morphology.

RESULTS: Groups G4 and G3 both showed a 100% inhibition of peripheral parasitemia. However, the treatment in G4 was found to be less effective than that in G2 and G3 in preventing placental parasitemia. The G4 treatment was able to reduce the expression of IFN-γ and IL-10, whereas TNF-α was not significantly different from the control group. Foetal morphologic abnormalities were observed in all groups except G2; G4 showed lower percentage of abnormalities compared to G3 and G1.

CONCLUSIONS: A combination of A. paniculata tablet (AS201-01) with DHP has the potential to reduce the toxicity of DHP in malaria treatment.

PMID:33580999 | DOI:10.1515/jbcpp-2020-0162

Front Vet Sci. 2021 Jan 26;7:623710. doi: 10.3389/fvets.2020.623710. eCollection 2020.

ABSTRACT

A polyherbal feed mixture containing (Achyrantes aspera, Trachyspermum ammi, Citrullus colocynthis, Andrographis paniculata, and Azadirachta indica) was evaluated in growing calves through blood chemistry, blood biometry, and gene expression during the pre-ruminant to weaning period. Forty Holstein calves (initial BW 45.6 ± 3.2 kg; 22.8 ± 0.9 days post birth) from a dairy farm were randomly assigned to the following treatments: 0, 3, 4, and 5 g/d of a polyherbal mixture, dosed in colloid gels with gelatin. Calves were housed in individual outdoor boxes with ad libitum access to a 21.5% CP calf starter and water and fed individually with a mixture of milk and a non-medicated milk replacer (22% CP). Blood samples were collected on day 59 for blood chemistry, blood biometry, and gene expression analysis in leukocyte through microarray assays. Immunoglobulins were quantified by enzyme-linked immunosorbent assay. The animals treated with the polyherbal mixture showed a quadratic effect on final body weight, daily weight gain, final hip height, and final thoracic girth. The best performance results were obtained with a treatment dose of 4 g/d. The serum IgG increased linearly with the treatment doses. Gene set enrichment analysis of upregulated genes revealed that the three biological processes with higher fold change were tight junction, mucin type O-Glycan biosynthesis, and intestinal immune network for IgA production. Also, these upregulated genes influenced arachidonic acid metabolism, and pantothenate and CoA biosynthesis. Gene ontology enrichment analysis indicated that the pathways enriched were PELP1 estrogen receptor interacting protein pathways, nuclear receptors in lipid metabolism and toxicity, tight junction, ECM-receptor interaction, thyroid hormone signaling pathways, vascular smooth muscle contraction, ribosome function, glutamatergic synapse pathway, focal adhesion, Hippo, calcium, and MAPK signaling pathways.

PMID:33575280 | PMC:PMC7870704 | DOI:10.3389/fvets.2020.623710

Asian Pac J Cancer Prev. 2021 Feb 1;22(S1):3-8. doi: 10.31557/APJCP.2021.22.S1.3.

ABSTRACT

Paraquat (1,1'-dimethyl, 4,4'-bipyridinium dichloride; PQ), a commonly used herbicide worldwide, is both toxic and mutagenic. The mutagenic effect of PQ stems from its ability to redox-cycle, generating oxidative stress and subsequently oxidative DNA damage, which miscodes when replication is attempted. Andrographolide (AP1), the major constituent in the leaves of the herbaceous plant Andrographis paniculata, is a diterpenoid with reported antioxidant activity. The present study employed the mammalian cell line AS52 to investigate the protective effect of AP1 against PQ-induced mutagenesis. AP1 induced cytotoxicity in AS52 cells in a dose-dependent manner (IC50 = 15.7 µM), which allowed the selection of a non-lethal dose for the mutagenesis studies. While PQ was mutagenic in AS52 cells as evidenced by the increased levels of 6-TGr mutants, AP1 by itself did not increase the mutation frequency. However, co-treatment with AP1 (1-5 µM) or the antioxidant N-acetylcysteine (2 mM) almost completely counteracted the mutagenicity of PQ (10-100 µM) in AS52 cells. Taken together, these findings suggest that AP1, and likely by extension, A. paniculata extracts, are effective antioxidants that can protect against PQ-induced mutations, and thus could be a promising alternative treatment for PQ poisoning.

PMID:33576206 | DOI:10.31557/APJCP.2021.22.S1.3

J Diabetes Metab Disord. 2020 Nov 15;19(2):1543-1556. doi: 10.1007/s40200-020-00690-2. eCollection 2020 Dec.

ABSTRACT

BACKGROUND: This study sought to investigate anti-hyperglycemic potentials of free and bound phenolic-rich extracts of Andrographis paniculata (A. paniculata) leaves, commonly called "king of the bitter", a plant locally employed in folkloric alternative medicine.

METHOD: In vitro antioxidant potentials such as total phenolic and flavonoid contents were evaluated in addition to phosphomolybdenum reducing total antioxidant activity in bound and free polyphenol-rich extracts of A. paniculata. Also, following induction of diabetes through a single intraperitoneal injection of freshly prepared alloxan monohydrate (150 mg/kg body weight, b.w), diabetic rats were divided into seven (7) treatment groups with six rats each (n = 6) i.e. group 1 (normal control), 2 (diabetic untreated), 3 (5 mg/kg glibenclamide -treated control), while 4-7 were administered 50 and 100 mg/kg b.w of free and bound phenolic extracts of A. paniculata, respectively for twenty-one (21) days.

RESULTS: There was a significant (p < 0.05) difference in hematological indices, hepatic biomarkers, total protein, antioxidant enzymes activities, total thiol and fasting blood glucose levels of diabetic groups administered polyphenolic-rich extracts of A. paniculata compared to diabetic untreated control. Similarly, serum insulin levels, hexokinase and glucose-6-phoshatase activities were significantly (p < 0.05) improved in phenolic-rich extracts of A. paniculata-treated diabetic groups compared to diabetic untreated control. A significant (p < 0.05) reduction was as well observed in the levels of inflammatory biomarkers such as interleukin-6 (IL-6) and tumor necrosis factor (TNFα) among extract of A. paniculata administered diabetic groups compared diabetic untreated group.

CONCLUSIONS: Anti-hyperglycemic activities demonstrated by polyphenolic-rich extracts of A. paniculata when compared to glibenclamide and normal control, could possibly have been occasioned by β-cell protection, restoration of glycolytic enzymes as well as mitigation of inflammatory markers via antioxidant defensive/protective properties of the extracts.

PMID:33553038 | PMC:PMC7843849 | DOI:10.1007/s40200-020-00690-2

Front Genet. 2021 Jan 18;11:601689. doi: 10.3389/fgene.2020.601689. eCollection 2020.

ABSTRACT

Andrographolide, which is enriched in the leaves of Andrographis paniculata, has been known as "natural antibiotic" due to its pharmacological activities such as anti-inflammatory, antimicrobial and antioxidant effects. Several key enzymes in andrographolide biosynthetic pathway have been studied since the genome sequences were released, but its regulatory mechanism remains unknown. WRKY transcription factors proteins have been reported to regulate plant secondary metabolism, development as well as biotic and abiotic stresses. Here, WRKY transcription factors related to andrographolide biosynthesis were systematically identified, including sequences alignment, phylogenetic analysis, chromosomal distribution, gene structure, conserved motifs, synteny, alternative splicing event and Gene ontology (GO) annotation. A total of 58 WRKYs were identified in Chuanxinlian genome and phylogenetically classified into three groups. Moreover, nine WRKY genes underwent alternative splicing events. Furthermore, the combination of binding site prediction, gene-specific expression patterns, and phylogenetic analysis suggested that 7 WRKYs (ApWRKY01, ApWRKY08, ApWRKY12, ApWRKY14, ApWRKY19, ApWRKY20, and ApWRKY50) might regulate andrographolide biosynthesis. This study laid a foundation for understanding the regulatory mechanism of andrographolide biosynthesis and the improvement and breeding of Andrographis paniculata varieties.

PMID:33537059 | PMC:PMC7848199 | DOI:10.3389/fgene.2020.601689

J Genet Eng Biotechnol. 2021 Jan 26;19(1):20. doi: 10.1186/s43141-021-00122-5.

ABSTRACT

BACKGROUND: Andrographis alata (Vahl) Nees is a medicinal plant which was reported to have the highest concentration of neoandrographolide that has several therapeutic values. Natural populations of Andrographis alata are dwindling due to destruction of natural habitat and over exploitation. Therefore, in vitro propagation of Andrographis alata was undertaken, and successful method is presented here.

RESULTS: Micropropagation of Andrographis alata was realized on MS nutrient medium augmented with BAP (10 μM), and multiple shoots were regenerated from nodal explants. Induction of roots was attained from shoots on ¼ concentration of MS nutrient medium supplemented with IBA (1 μM). Randomly amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) analysis showed that there is genetic fidelity in the regenerated plants. Reverse phase high performance liquid chromatographic analysis of regenerated plants showed the presence of neoandrographolide, equivalent to that of mother plants.

CONCLUSIONS: Successful in vitro regeneration of Andrographis alata is presented here, and it is quite useful for its mass multiplication. The micropropagated plants are useful for restoration of plants in nature and for utilization by the pharmaceutical industry for extraction of neoandrographolide.

PMID:33496903 | PMC:PMC7835653 | DOI:10.1186/s43141-021-00122-5

Zhongguo Zhong Yao Za Zhi. 2020 Dec;45(24):5890-5897. doi: 10.19540/j.cnki.cjcmm.20200901.601.

ABSTRACT

Andrographis Herba is a commonly used plant medicine, and has been recorded in pharmacopeias of different countries. However, there are some differences in the quality standards. Based on this, this paper compare the quality standards of Andrographis Herba between Chinese Pharmacopoeia, Hong Kong Chinese Materia Medica Standards, United States Pharmacopoeia, European Pharmacopoeia and Indian Pharmacopoeia, including origin, botanical characteristics, identification(microscopic identification and chromatographic identification), content determination, specific test(such as impurities, loss on drying, extractives, pesticides, heavy metals, mycotoxins, and other items) and storage requirements, so as to provide a reference for studying international quality standards of Andrographis.

PMID:33496129 | DOI:10.19540/j.cnki.cjcmm.20200901.601

3 Biotech. 2021 Feb;11(2):44. doi: 10.1007/s13205-020-02578-7. Epub 2021 Jan 11.

ABSTRACT

The Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in outbreak of global pandemic, fatal pneumonia in human referred as Coronavirus Disease-2019 (Covid-19). Ayurveda, the age old practice of treating human ailments in India, can be considered against SARS-CoV-2. Attempt was made to provide preliminary evidences for interaction of 35 phytochemicals from two plants (Phyllanthus amarus and Andrographis paniculata used in Ayurveda) with SARS-CoV-2 proteins (open & closed state S protein, 3CLpro, PLpro and RdRp) through in silico docking analysis. The nucleotide analogue remdesivir, being used in treatment of SARS-CoV-2, was used as a positive control. The results revealed that 18 phytochemicals from P. amarus and 14 phytochemicals from A. paniculata shown binding energy affinity/dock score < - 6.0 kcal/mol, which is considered as minimum threshold for any compound to be used for drug development. Phytochemicals used for docking studies in the current study from P. amarus and A. paniculata showed binding affinity up to - 9.10 kcal/mol and - 10.60 kcal/mol, respectively. There was no significant difference in the binding affinities of these compounds with closed and open state S protein. Further, flavonoids (astragalin, kaempferol, quercetin, quercetin-3-O-glucoside and quercetin) and tannins (corilagin, furosin and geraniin) present in P. amarus have shown more binding affinity (up to - 10.60 kcal/mol) than remdesivir (up to - 9.50 kcal/mol). The pharmacokinetic predictions suggest that compounds from the two plants species studied in the current study are found to be non-carcinogenic, water soluble and biologically safe. The phytochemicals present in the extracts of P. amarus and A. paniculata might have synergistic effect with action on multiple target sites of SARS-CoV-2. The information generated here might serve as preliminary evidence for anti SARS-CoV-2 activity of phytochemicals present from P. amarus and A. paniculata and the potential of Ayurveda medicine in combating the virus.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-020-02578-7.

PMID:33457171 | PMC:PMC7799430 | DOI:10.1007/s13205-020-02578-7