International Journal of Pharmacology - Current Issue

Impact of Tacrolimus Versus Cyclosporine on Overall Response, Complete Remission and Relapse in Nephrotic Syndrome: A Systematic Review and Meta-Analysis

09 April, 2026

Background and Objective: Nephrotic syndrome requires effective treatment to reduce symptoms and prevent recurrence. As immunosuppressants, tacrolimus and cyclosporine are commonly used, although research on their efficacy and outcomes is continuing. Patients diagnosed with nephrotic syndrome were included in this meta-analysis to determine the impact that immunosuppressants such as tacrolimus and cyclosporine have on the overall response, full remission and recurrence of the condition. Materials and Methods: The Embase, PubMed and Cochrane Library databases were searched to do this systematic review and meta-analysis. Using predefined criteria, records were screened for relevance, the risk of bias was assessed with Cochrane and Newcastle-Ottawa tools and data was extracted for meta-analysis. The included studies were limited to those comparing tacrolimus with cyclosporine in nephrotic syndrome patients regarding overall response, complete remission and relapse rates. Results: The qualitative and quantitative synthesis comprised 8 investigations. The meta-analysis of the overall response, complete remission and relapse yielded no statistically significant difference between tacrolimus and cyclosporine. The relative risk (RR) for overall response was 1.03 (95% CI [0.97, 1.10], p = 0.34; for complete remission, 1.1057 (95% CI [0.9986, 1.2244], p = 0.05) and for relapse was 1.17 (95% CI [0.79, 1.74], p = 0.43). The entire response data displayed a minimal probability of publication bias, as indicated by the funnel plot. Conclusion: This examination found no significant difference in nephrotic syndrome response, complete remission or recurrence rates between tacrolimus and cyclosporine. These findings suggest that patient environment and clinical factors may affect drug choice. Investigating these outcomes requires further research and high-quality investigations.

Effects of Levosimendan on Hemodynamics and Prognosis in Patients with Sepsis: A Meta-Analysis and Systematic Review

09 April, 2026

Sepsis represents a critical issue that arises when the body’s immune system excessively reacts to an infection, resulting in harm to organs and tissues. Comprehending host-microorganism interactions is essential for formulating novel therapies and evaluating disease advancement. Therefore, this meta-analysis was intended to examine the impact of levosimendan on mortality and haemodynamics in sepsis patients. This meta-analysis examined Embase, PubMed, Cochrane Library, Web of Science, China National Knowledge Network (NKI) and Wanfang Database Data, Chinese Biomedical Literature Database (CBM) and VIP Database for levosimendan, sepsis and septic shock. This research examined publicly accessible clinically randomised controlled trials of levosimendan in sepsis patients, measuring left ventricular ejection fraction, work index, cardiac index and lactate level-all data integration, publication bias detection and sensitivity analysis were carried out. In this meta-analysis, 15 studies were involved. According to the findings, there was no statistically significant variance (p>0.05) in the 28-day death rate between the levosimendan-treated sepsis patients and the control category. Levosimendan, however, can lower the left ventricular function index, raise the left ventricular ejection fraction, enhance the cardiac index and successfully lower lactate levels in sepsis patients.However, the drug has shown positive effects in improving hemodynamic parameters and therefore, more clinical trials are necessary to verify the value of levosimendan in managing hemodynamic problems associated with sepsis.

Cyclosporine Transporter Pharmacogenomic Effect in Transplantation: An Updated Systematic Review

09 April, 2026

Cyclosporine (CsA) is commonly used in organ transplantation based on its immunosuppressant activity. Monitoring CsA fluctuation in the blood level is important as it belongs to drugs with narrow safety margin windows. Its low level may result in loss of immunosuppressant activity leading to rejection. In contrast, a high CsA level may result in CsA-related adverse effects. The CsA absorption is controlled mainly by ABCB1 and ABCB2 transporters. The current study aims to investigate the gene controlling CsA absorption among transplanted patients. A literature review was conducted from January, 2000 to November, 2024 using Scopus, Embase, as well as PubMed bibliography. The research focuses on cyclosporine, transplantation, pharmacogenetics and pharmacogenomics. The current research items were met by 482 which were subjected to the exclusion of duplication or unfit research papers that resulted in 48 final research papers, which were then analyzed. Hence, found a strong association between some ABCB1 gene polymorphisms and CsA blood level, while some results nullify that. These findings necessitate the need for a genome-wide association study with multi-centers with different ethnicities for better understanding and accurate conclusions of the CsA dosing based on genetic variability.

Antitumoral Effect of Tomentosin from Inula viscosa Plant on Mice with Ehrlich Acid Tumor

09 April, 2026

Background and Objective: Spontaneous or transplantable tumor models are kinetically similar to human cancer types and play a role in understanding the biology of carcinogenesis and in the development of chemo-preventive and chemo-suppressive drugs. In this study, the effect of tomentosin isolated from the Inula viscosa plant against Ehrlich ascites tumor (EAT), was carried out. Materials and Methods: Inula viscosa (Asteraceae) was collected from the vicinity of Kilis 7 Aralık University, Kilis, Turkiye and tomentosin was isolated. In this study, 7 groups of 6 mice were used in each group. The EAT was taken from stock mice and counted in a Cedex XS cell counter (Roche) and administered intraperitoneally to tumor groups in 0.2 mL PBS (phosphate-buffered saline) once at the beginning of the study. Tomentosin was administered intraperitoneally to groups in 3 doses (25, 50 and 100 mg/kg). Average weight change, total oxidant capacity (TOS), total antioxidant capacity (TAS) and superoxide dismutase enzyme (SOD) activity were examined. The liver, small intestine, large intestine and stomach were taken from sacrificed animals and examined histopathologically. The findings were statistically evaluated using ANOVA followed by Dunnett’s Multiple Comparisons test in SPSS 17, with significance set at p<0.05. Results: The weight changes, SOD and TAS results of mice showed that tomentosin at a dose of 100 mg/kg reduced the tumor. It was determined that tumors in groups where tomentosin was administered together with tumors were morphologically reduced and this reduction was directly proportional to the dose of tomentosin. In the group in which 100 mg/kg tomentosin dose and Ehrlich ascites tumor were administered together, histopathological examination of kidney, small intestine, large intestine and stomach tissues showed less tumor involvement compared to other doses. Conclusion: Weight, biochemical and histological evaluations supported each other that tomentosin is effective in reducing tumors and it is thought that this study will be useful for future studies.

Combination Therapy of Trastuzumab and Lapatinib in Chemorefractory HER2-Positive Metastatic Colorectal Cancer: An Efficacy and Safety Analysis

09 April, 2026

Background and Objective: In patients with colorectal cancer, some genetic abnormalities are identified in the blood, tumors or metastasis. The prognosis of Human Epidermal Growth Factor Receptor 2 (HER2) in colorectal cancer as a biomarker is uncertain. The use of human epidermal growth factor 2 in treating the receptors targeted with epidermal growth factor has shown a negative response. Hence patients who have HER2-positive colorectal cancer may have very few treatment options and also show poor prognosis. The objectives of the study were to evaluate efficacy and safety with 15 months follow-up of the combination of trastuzumab and lapatinib in patients with HER2+ metastatic colorectal cancer. Materials and Methods: A total of 36 patients with HER2+ metastatic colorectal cancer received 4 mg/kg of trastuzumab which is a loading dose and then followed by 2 mg/kg dose once a week and a 1,000 mg/kg dose of oral lapatinib per day until there is evidence of the progressions of the disease (s). Safety parameters evaluated for 15 months follow-up. Results: Out of 36 patients, 3 patients (8.3%) had a complete response, 18 patients (50%) had a partial response and 15 patients (41.6%) had shown to have reached an objective response rate. Among 36 enrolled patients, stable disease was found in 9 patients (25%) and 12 patients had disease for more than 3 months (33.34%). Overall, the disease was controlled in 26 patients. The adverse effects of the patients included gastrointestinal, dermatological, nutritional disorders, paronychia, hand-foot syndrome and very few cases of conjunctivitis, an increase in bilirubin in the blood and a decrease in left ventricular ejection fraction. Conclusion: The combination of trastuzumab and lapatinib is effective against HER2+ positive metastatic colorectal cancer with manageable adverse effects.

Molecular and Functional Analysis of TXNDC11 in Neuro2a Neuroblastoma Cells: A Potential Drug Target in ER Stress-Associated Disorders

09 April, 2026

Background and Objective: Thioredoxin-Domain Containing 11 (TXNDC11), a member of the thioredoxin superfamily, is suggested to interact with EDEM2 and is implicated in the modulation of ERAD processes. However, reports on its expression and function are limited. This study investigates the role of TXNDC11 in the regulation of endoplasmic reticulum (ER) stress responses and ER-associated degradation (ERAD) in Neuro2a neuroblastoma cells. Materials and Methods: The CRISPR/Cas9 technology was applied to generate TXNDC11-deficient Neuro2a cell lines to explore the protein's influence on cellular responses under stress conditions induced by agents such as thapsigargin (Tg), tunicamycin (Tm) and brefeldin A (BFA). Statistical analysis of changes in the expression of each mRNA and protein is carried out using one-way ANOVA followed by the Tukey-Kramer test. Results: The study findings indicated that TXNDC11 deficiency does not significantly alter the transcriptional response of classical ER stress markers (ATF3, GADD153, GRP78, Herp and sXBP1) but does lead to increased expression of the ER-phagy receptor FAM134B, suggesting a compensatory mechanism within the ER-phagy pathway. Furthermore, comparative proteomic analysis showed a marked decrease in EDEM2 protein levels, suggesting a specific role of TXNDC11 in modulating the activity of ER-localized mannosidases involved in N-glycoprotein degradation. Moreover, the differential expression of ERAD and ER-phagy components in TXNDC11-deficient cells highlights the balance between protein folding, degradation and cellular homeostasis. Conclusion: This study on TXNDC11 and FAM134B expression analysis suggests that ERAD and ER-phagy are associated with ER homeostasis under pathophysiological conditions. Furthermore, examining the interaction between TXNDC11 and FAM134B could be valuable as a potential biomarker in neurodegenerative diseases and cancers.

Mechanism of Quercetin Mediating PI3K/Akt/mTOR Pathway in Alleviating Cerebral Vascular Stenosis Caused by Vascular Endothelial Cell Injury

09 April, 2026

Background and Objective: Venous stenosis can be accelerated by damage to vascular endothelial cells, which in turn leads to the ischemic death of brain cells such as cerebrovascular endothelial cells. This study explored the impact of Quercetin (Que) on the physiological responses of human brain microvascular endothelial cells (HBVECs) to oxygen-glucose deprivation (OGD). Materials and Methods: The HBVECs were randomly divided into Control group (CG, conventional culture), OGD group (OGDG), Que-5, 10 and 20 (supplemented with 5, 10 or 20 μmol/L Que). Cell proliferation, apoptosis, inflammation and oxidative damage factors and the expression of PI3K/Akt/mTOR pathway proteins were detected. The SNK-q test and One-way Analysis of Variance (ANOVA) were adopted (p-value below 0.05). Results: With the increase of Que concentration, DPPH and ABTS free radical (FR) scavenging rate (SR) increased. As against the CG, in the OGDG, the cell survival rate (CSR) dropped while the apoptosis rate (AR) rose; TNF-α, IL-6 and IL-1β, oxidative stress (OS) factors ROS, MDA and 8-OHdG were increased and SOD was decreased; damage genes VCAM-1, ICAM-1 and EDN-1 was increased; Bax, Caspase-3, p-PI3K, p-Akt and p-mTOR rose visibly and Bcl-2 dropped. However, when the Que group (QG) was compared with the OGDG, a reverse trend was observed (all p<0.05). The changes in cell biological behavior after Que treatment were concentration-dependent. Conclusion: The Que has antioxidant properties and can promote proliferation, inhibit apoptosis, improve inflammation and OS and alleviate cell damage in HBVECs cell injury model induced by OGD.

Effect of High Dose Folic Acid Supplementation on the Prevention of Pre-Eclampsia in Pregnancy with Hypertension

09 April, 2026

Background and Objective: Pre-eclampsia is a very dangerous pregnancy condition that significantly elevates the possibility of early mortality for both the mother and the infant. The purpose of the experiment was to investigate the contradictory evidence about whether folic acid may decrease the incidence of pre-eclampsia. Materials and Methods: As 1500 pregnant women were randomly selected for the clinical investigation. The 750 women were assigned to the folic acid and placebo groups. From randomization (8 to 16 weeks) until delivery, group 1 got 4 mg of folic acid and group 2 received a placebo daily. Participants were examined for <50, 50-75 and >75% compliance levels. The 4 follow-ups were scheduled: 24-26, 34-36, post-birth and 42 days post-partum. The research sought to quantify pre-eclampsia rates. Secondary outcome assessments were early preterm delivery, stillbirth, neonatal death, perinatal mortality, early-onset sepsis and NICU hospitalisation for 24 hrs or more. Results: The study found that the occurrence of pre-eclampsia was comparatively lower in the folic acid group than in the placebo group (5.3 vs. 10%), with a risk ratio (RR) of 0.53 and a 95% confidence interval (CI) of 0.53 to 0.79. Furthermore, the occurrence of secondary outcomes was decreased in the folic acid group in comparison to the placebo group. Conclusion: The study findings provide evidence that high-dose folic acid intake can be an effective preventive measure for pre-eclampsia in pregnant women with hypertension.

Efficacy and Safety of Topiroxostat in Patients with Chronic Kidney Disease and Hyperuricemia: A Meta-Analysis

09 April, 2026

Background and Objective: Hyperuricemia (HUA) and chronic renal disease occurrences have both been sharply increasing in recent years, which have seriously affected public health. This meta-analysis compares topiroxostat in patients with chronic kidney disease and hyperuricemia. Materials and Methods: The machine searches eight databases to find studies on topiroxostat’s impact on individuals with chronic renal disease and HUA, both domestically and overseas. Utilising RevMan 5.3 software, data analysis was carried out following a thorough assessment of the quality of the literature. Results: A total of seven articles were included in this meta-analysis. All of them were thought of as controlled experiments. The test category’s uric acid levels significantly changed from the control group (SMD: -2.12; 95% Cl: -2.68, -1.56; p<0.01), as per 4 studies. The Estimated Glomerular Filtration Rate (eGFR) (SMD: 0.62; 95% Cl: -3.98, 5.23; p = 0.790), systolic blood pressure (SMD: -0.20; 95% Cl: -5.23, 4.83; p = 0.938), diastolic blood pressure (SMD: -0.76; 95% Cl: -4.42, 2.91, p = 0.685), urine protein positive rate (SMD: 0.55; 95% Cl: 0.25, 1.22; p = 0.143) and ADR (SMD: 1.16; 95% Cl: 0.78, 1.72; p = 0.459). Conclusion: According to current study findings, topiroxostat may be useful for treating HUA and chronic renal disease in individuals, as evidenced by uric acid. However, topiroxostat did not significantly improve the levels of eGFR, BP and protein-positive rate of urine and the above conclusions need to be verified by more high-quality studies.

Carvacrol Inhibits the Proliferation and Extracellular Matrix Deposition of Keloid Fibroblasts Through Nrf2/GPX4 and TGF-β1/Smad Signaling Pathways

09 April, 2026

Background and Objective: Keloid (KD) is a kind of fiber proliferative disease, usually caused by abnormal wound healing after a burn, trauma or infection and characterized by proliferation of cells and excessive deposition of extracellular matrix (ECM) in keloid fibroblasts (KFs). This study investigated the effect of carvacrol (CV) on the proliferation and ECM deposition of KFs. Materials and Methods: The proliferation of KFs was determined by scratch assay and cloning assay. The contents of iron, MDA and GSH were measured in KFs. The expressions of Nrf2/GPX4 and TGF-β1/Smad proteins were detected using Western blotting. All data were analyzed by GraphPad Prism 9.0 software. Results: The CV showed the ability to inhibit cell proliferation and migration, it promoted the expressions of iron and MDA and inhibited the expression of GSH in KFs. The CV promoted ferroptosis of KFs by inhibiting the protein expressions of Nrf2, HO-1, GPX4 and xCT. It also inhibited collagen deposition of KFs by inhibiting protein levels of collagen I, collagen III, fibronectin, α-SMA, p-Smad2 and p-Smad3. Conclusion: The CV promoted ferroptosis of KFs by regulating Nrf2/GPX4 signaling pathway to inhibit cell proliferation and regulated TGF-β1/Smad signaling pathway to inhibit ECM deposition.

Design, Synthesis Optimization and Anticancer Activity of Small Molecule Kinase Inhibitors

09 April, 2026

Background and Objective: The development of inhibitors targeting protein kinases (PKs) has emerged as a pivotal field in drug research. In this context, a comprehensive analysis of kinase structural attributes has led to the proposal of a pyrimidine-linked biphenyl core (PBC) pharmacophore model aimed at bridging the adenine-binding region and the hydrophobic pocket left vacant by the DFG segment rotation. Materials and Methods: Building upon this, a Suzuki One-Pot Reaction was employed to synthesize 20 derivative compounds, among which F1 and F2 exhibited heightened tumor inhibitory potential (IC₅₀<10 μM). These synthesized compounds were subjected to a Thiazolyl Blue (MTT) assay to assess their impacts on cell proliferation. Meanwhile, the in vivo anticancer effects were validated through rat tumor xenograft experiments. Immunofluorescence staining of tumor tissues in rats was utilized to observe DNA damage and cell apoptosis. Additionally, liver and kidney tissues were subjected to Hematoxylin-Eosin (H&E) staining to evaluate the influence of the inhibitors on rat liver and kidney cells. Results: The pronounced antiproliferative capabilities of F1 and F2 against tumor cells, while exerting minimal influence on normal human cells, indicating substantial tumor cell-selective toxicity (p<0.001). After 24 hrs of exposure to F1 and F2, a notable increase in tumor cell apoptosis was observed, with MTT assays showing an IC₅₀ of 2.9 μm for F1 and 8.0 μm for F2, signifying significant tumor cell inhibition. Compared to the control (Ctrl) group, the levels of γH2AX signal and relative protein expression in the F1 and F2 group were significantly higher (p<0.001). However, there were no significant toxic side effects observed in the rat liver and kidney tissues (p>0.001). Conclusion: In summary, the PBC pharmacophore model opened novel avenues for developing relevant drugs for PK inhibitors. In the future, compound design and optimization based on this model hold promise for delivering new effective drugs for diseases like cancer.

Effect of Electricity on the Expression of CGRP and its Receptor RAMP1 in Rat IBS-C Model and its Mechanism of Action

09 April, 2026

Background and Objective: Irritable Bowel Syndrome (IBS), a common chronic functional disorder, poses a severe risk of increasing physical and mental health concerns. The current animal study was carried out to investigate how electricity affects CGRP and RAMP1 expression and its mode of action. Materials and Methods: In this study, intragastric ice-water techniques were followed. Each group’s rats’ mental state, weight, faeces mass, auricle colour, hair colour and quality, activity level, water and food intake and bowel movement frequency were observed. The leftover small intestine and stomach propulsion of gavaged rats were investigated and ELISA and western blotting were conducted. Results: Rat behaviour before and after treatment was evaluated for each group. The rats in the model and electroacupuncture groups had considerably poorer general condition ratings (p<0.05) than the blank group. In comparison to the blank group, the model rats had a substantial increase (p<0.05) in stomach residual rate and a decrease (p<0.05) in small intestine propulsion rate. Electroacupuncture significantly increased intestinal propulsion rate (p<0.05) and decreased stomach residual rate compared to the model group. Electroacupuncture increased plasma CGRP and SP in both groups. Electroacupuncture significantly altered TRPV1, PAR4, CGRP, RAMP1 and SP mRNA and proteins in all groups. Compared to the blank group, model rats had substantially greater (p<0.05) mRNA and protein expressions of TRPV1, PAR4, CGRP, SP and RAMP1 in their colon tissues. Conclusion: Electroacupuncture regulates TRPV1, PAR4, CGRP, RAMP1 and SP expression, which may help IBS-C stomach pain patients.

Effects of Loading TAB2 siRNA and Cisplatin Nano-Liposomes Mediated Macrophage Polarization on Drug Resistance, Proliferation and Metastasis of Ovarian Cancer Cells

09 April, 2026

Background and Objective: Tumor cell reduction surgery combined with cisplatin chemotherapy can achieve remission in ovarian cancer (OC) patients, but most patients will experience recurrence. This work investigated the effects of co-loading Small Interfering RNA (siRNA) targeting transforming growth factor-beta activated kinase 1 binding protein 2 (TAB2) and cisplatin in nano-liposomes, mediated by macrophage M2 polarization, on drug-resistant OC cell proliferation and migration. Materials and Methods: Bone Marrow-Derived Macrophage (BMDM) was obtained from mouse bone marrow and interleukin-5 induced M2 polarization of the cells. A cisplatin-resistant OC cell model (ID8/R) was prepared using the cisplatin gradient exposure method. Normal culture was used as the Ctrl group and co-loaded negative control, TAB2 siRNA and cisplatin-loaded nanoliposomes (siNC-DDP-LNP and siTAB2-dDP-LNP) were transfected to detect the activation status of M2 type BMDM. The BMDM-conditioned medium was added and cell proliferation and migration were detected. Results: The prepared siNC-DDP-LNP and siTAB2-DDP-LNP possessed similar circular morphology with a PS of around 100 nm. The siRNA EE was >90% and the drug LC was >0.14 μg/μL. After transfection, the siTAB2-DDP-LNP group showed a great reduction in TAB2 (p<0.05). Following BMDM identification, the M1 type markers (iNOS and TNF-α expression, average fluorescence intensity (FI) of CD80 and CD86) decreased, while the M2 type markers (Arg1 and Mgl1 expression, average FI of CD206 and CD163) increased, with sharp differences (p<0.05). After transfection with BMDM conditioned medium and nano-liposomes, the siTAB2-DDP-LNP group presented greatly increased average FI values of CD80, CD86 and CD40, decreased cell viability and reduced count of migrated cells, exhibiting great differences after comparison (p<0.05). Conclusion: The siTAB2/DDP-LNP effectively activated tumor-associated macrophage polarization, thereby achieving effective killing of drug-resistant OC cells (OCCs).

N-Methylcoclaurine Suppresses Hepatocellular Carcinoma by Inhibiting Protein Disulfide Isomerase in vitro and in vivo

09 April, 2026

Background and Objective: Plumula Nelumbinis (PN) or Lianzixin, is a well-established anti-tumor medicine included by Chinese Pharmacopoeia. Modern pharmacological studies have confirmed that benzylisoquinoline alkaloids are the major anti-tumor components of PN. However, the detailed mechanism remained unclear. This study aimed to evaluate the in vitro and in vivo anti-tumor effects of N-methylcoclaurine (N-MC), a potential natural protein disulfide isomerase (PDI) inhibitor isolated from PN. Materials and Methods: Insulin turbidity assay and molecular docking analysis were conducted for the PDI inhibition study of N-MC. The MTT, scratch assay and transwell assays were performed to evaluate the in vitro effects of N-MC on HepG2 cells. For the in vivo effects of N-MC, the H22-bearing mice model was generated with 40 ICR mice and treated with different doses of N-MC (10, 20 and 40 mg/kg b.wt.). The ANOVA and LSD were performed for the comparisons between groups. Results: The N-MC exhibited a concentration-dependent inhibitory effect on PDI, with an IC₅₀ of 3.91 μM. The N-MC could fit the active pocket of PDI surrounded by Phe 249, Phe 304, Ile 318, Leu 320, Met 324, Lys 436, Val 437 and His 438, with a calculated binding energy of -8.2 kcal/mol. The N-MC effectively inhibited cell migration and invasion of HepG2 cells in a dose-dependent manner. In the H22 tumor-bearing ICR mice model, N-MC also exhibited dose-dependent tumor suppression quantified by tumor inhibition rates and cell number index. Conclusion: The N-MC exhibits the ability to inhibit tumor proliferation, migration and invasion through the inhibition of PDI activity in vitro and effectively suppresses tumor growth in vivo. These findings suggest that N-MC is a promising candidate for anti-tumor drugs through inhibiting PDI.

Exploring the Mechanism of Action of Ru-Pi-Xiao on Treating Mammary Gland Hyperplasia Based on Network Pharmacology and Molecular Docking Technology

09 April, 2026

Background and Objective: Ru-Pi-Xiao is a classic Chinese medicine prescription, which has a remarkable effect in treating mammary gland hyperplasia. However, the primary constituents and underlying mechanisms of Ru-Pi-Xiao have yet to be fully elucidated. This study aims to provide an initial exploration of the potential mechanisms by which Ru-Pi-Xiao exerts its therapeutic effects on MGH through the application of network pharmacology and molecular docking techniques. Materials and Methods: Relevant targets of active ingredients and diseases were carried out through TCMSP, Gene Cards, DisGeNET and NCBI databases. Drug targets and disease targets were taken to make Venn diagrams, PPI network diagrams were made in the STRING database with shared targets, Core targets and compound drug-active ingredient-target network diagrams were drawn through Cytoscape software. The Metascape platform was used for GO enrichment analysis and KEGG analysis. Molecular docking was performed with AutoDockTools. Results: About 110 active ingredients and 147 intersecting genes were screened. The main biological processes were response to peptide, enzyme-linked receptor protein signaling pathway, protein phosphorylation, gland development and positive regulation of transferase activity. “Proteoglycans in cancer”, “JAK-STAT signaling pathway”, “Calcium signaling pathway” and other pathways were involved in the treatment. The core targets were “TP53”, “SRC”, “STAT3”, “AKT1”, “PIK3CA” and so on. Molecular docking revealed good binding ability between the active compounds and screened targets. Among them, Quercetin has good binding activity with TP53 and AKT1 and 6-Hydroxykaempferol has good binding activity with SRC and PIK3CA. Conclusion: The Ru-Pi-Xiao may exert its therapeutic effects on MGH through multi-components, multi-targets and multi-pathways.

Acidified Bile Acid-Induced ROS Facilitates Stemness and Proliferation of Gastric Cancer Cells

09 April, 2026

Background and Objective: Acidified bile acids facilitate the growth of gastric cancer (GC) by cancer Myelocytomatosis (c-Myc). Reactive oxygen species (ROS) produced during oxidative stress in the body are closely related to tumor development, so the research aims to elucidate whether acidified bile acids regulate GC progression in a ROS-dependent manner. Materials and Methods: The GC cells were exposed to bile salts (100 μM chenodeoxycholic acid and deoxycholic acid) in acidic medium (pH = 5.5) for 10 min per day over 60 weeks to mimic the acidified bile acid environment in vitro. Cell proliferation and stemness were estimated by 5-ethynyl-2'-deoxyuridine and sphere-forming assays. Some genes were analyzed at the mRNA or protein levels by reverse transcription-quantitative polymerase chain reaction and western blotting. The ROS production and telomerase activity were detected by the fluorescence probe dihydroethidium and telomere repeat amplification protocol. Elimination of ROS was performed with N-acetyl-L-cysteine (NAC) to evaluate the function of ROS. Results: Acidified bile acids facilitated GC cell proliferation and stemness, accompanied by increased protein levels of PCNA, Oct4 and CD44. Acidified bile acids induced ROS production, along with elevated mRNA levels of Telomerase Reverse Transcriptase (TERT), protein levels of c-Myc and telomerase activity. The NAC treatment reversed acidified bile acids-mediated effects on the proliferation, stemness and ROS production of GC cells, with accompanying changes in TERT mRNA levels, c-Myc protein levels and telomerase activity. Conclusion: Acidified bile acids enhanced telomerase activity through c-Myc in a ROS-dependent manner, thereby contributing to GC cell proliferation and stemness.

Lupeol Protects Neuronal Injury Against Spinal Cord Injury in Rat Models via Targeting Nf-κB/NLRP3 Activation

09 April, 2026

Background and Objective: Spinal cord injury (SCI) is a severe traumatic disorder that threatens life and has long-term consequences, affecting a large number of people worldwide. Scientists have confirmed Lupeol’s involvement in a variety of ailments. The current research examines Lupeol’s efficacy in treating SCI in rats. Materials and Methods: This research split 30 animals into 3 groups: Sham, SCI (pentobarbital anesthesia at 35 mg/kg doses) and Lupeol (50 mg/kg p.o., for 21 days). Laminectomy was used to induce T9-T10 SCI in animals. After that, locomotor function in animals, pro-inflammatory cytokine analysis, spinal cord edema volume measurement, TUNEL labelling and western blot analysis were performed. Results: Lupeol was evaluated by measuring the Basso, Beattie, Bresnahan (BBB) score and spinal cord edema. The protein level of the inflammatory pathway in spinal tissue was quantified using western blot examination. Lupeol therapy substantially reduced the BBB score suppression caused by SCI (p<0.05). The SCI animals treated with Lupeol showed substantially reduced edema (p<0.01) compared to the model group. Lupeol significantly reduced cellular apoptosis in SCI animals. Lupeol therapy reduced SCI-induced IL-1β/-6/TNF-α upregulation. In Lupeol-treated animals, SCI-induced p-IκB suppression, Phosphorylated NF-κB (p-NF-κB) and Phosphorylated NLRP3 (p-NLRP3) upregulation were markedly reduced. Lupeol dramatically reduced caspase-1 and TLR4 in SCI animals. Conclusion: The study’s results demonstrate that administering Lupeol protects against damage to neurons and inflammation in animals with spinal cord injuries via controlling the NF-κB/NLRP3 pathway.

Effects of Ferulic Acid Regulation of the PI3k/Akt Signaling Pathway on the Proliferation, Migration or Apoptosis of U87-MG Cells Based on Bioinformatics

09 April, 2026

Background and Objective: Glioma is a common brain tumour. Most deadly brain tumours are malignant. Traditional glioma treatment includes surgical resection, radiation, chemotherapy and biological therapy. Through a series of in vitro research studies, this study was intended to assess the effects of ferulic acid (FA) on the proliferation and tumour features of U87-MG cells. Materials and Methods: The U87-MG cells were employed in this study. Blank and ferulic acid groups with concentrations of 1.25, 2.50 and 5.00 mmol/L were created. The FA’s effect on U87-MG cell apoptosis was examined by AM/PI staining after cell prolifer activity. The ELISA, cell migration, transwell invasion test, intracellular reactive oxygen species, cell apoptosis rate and western blot were assessed. Results: The application of FA decreased the proliferation of U87-MG cells, according to the results of the cell counting kit 8 test. Flow cytometry analysis also showed that FA sped up the death of cells and greatly increased the amount of reactive oxygen species inside cells. The phenotype of FA promoting apoptosis in U87-MG cells was consistent with the results of western blot analysis, which demonstrated that ferulic treatment with acid elevated the expression of apoptotic proteins (caspase-3 and caspase-9) and decreased the expression of cell cycle-related proteins (cyclin) in U87-MG cells. The FA suppressed U87-MG cell growth by blocking the PI3K/Akt signalling pathway, according to further detection of this pathway’s activity. Conclusion: The FA treatment boosted autophagy in U87-MG cells by increasing autophagy protein expression. The clinical treatment of gliomas changed with this discovery.

Virtual Screening of Representative Natural Products Library for TGF-β-Mediated Liver Cirrhosis: An in silico and in vitro Multi-Target Study

09 April, 2026

Background and Objective: Transforming Growth Factor Beta (TGF-β) significantly contributes to liver cirrhosis pathogenesis by promoting hepatic fibrosis. Drug discovery using molecular docking (MD) offers valuable insights into potential therapeutic candidates. This study investigated the early-stage discovery of potential natural drug candidates targeting the non-canonical TGF-β signaling pathway in liver cirrhosis pathogenesis. Materials and Methods: A virtual screening of the Korea Chemical Bank (KCB) natural compounds library was performed against key proteins, including TGF-β Receptor Type-1 (TGF-βR1), Focal Adhesion Kinase (FAK) and Phosphoinositide 3-Kinase (PI3K), using MD. Bioinformatics analysis identified additional targets such as Matrix Metallopeptidase 13 (MMP13) and explored pathway enrichments. The predicted Absorption, Distribution, Metabolism and Excretion (ADME) properties of promising compounds were evaluated. Experimental validation on HepG2 cells using RT-qPCR was conducted for the selected compounds. Results: TGF-βR1 binders from the KCB library exhibited higher binding affinities (-11.2 to -10.4 kcal/mol) than the reference inhibitor galunisertib (-10.0 kcal/mol). Bioinformatics identified MMP13 as a potential target for alcoholic liver cirrhosis, with enriched pathways related to cancer, p53 and PI3K-Akt signaling. Notably, dihydrosanguinarine (DHS) and eriocitrin showed promising inhibitory interactions with fibrogenic kinases. The ADMET analysis indicated DHS, trisindoline and α-Naphthoflavone (α-NF) as viable oral candidates. The RT-qPCR results highlighted luteolin’s inhibitory effects, whereas diosmetin and α-NF upregulated target gene expressions. Conclusion: In silico findings underscore the potential of promising natural compounds for liver cirrhosis therapy. However, further in vitro and in vivo studies are needed to confirm their antifibrotic efficacy and therapeutic value.