Journal of Basic and Applied Pharmacology

In Vitro Inhibition of Migration and Adhesion in Cholangiocarcinoma Cells by Ovalitenin A through PI3K Modulation

2025-11-23T12:44:18+07:00

Ovalitenin A, a chalcone extracted from the roots of Millettia brandisiana Kurz, has exhibited cytotoxic properties in various human cancer cells. However, the effects of this on cholangiocarcinoma (CCA), an aggressive malignancy of the bile duct epithelium, are still not well understood. This study investigated the anti-metastatic potential of ovalitenin A and its associated molecular mechanisms in CCA cells. Sulforhodamine B (SRB), wound-healing, and adhesion assays were used to test cell viability, migration, and adhesion, respectively. Western blotting was performed to quantify phosphorylated PI3K and VEGF proteins, and qRT-PCR was used to measure MMP-9 and TIMP-1 mRNA. Ovalitenin A suppressed the proliferation of CCA cells in a concentration-dependent manner. Following 24 hours of treatment, it markedly diminished cell migration and adhesion. Network pharmacology analysis found 32 common targets between ovalitenin A and CCA utilizing the SwissTargetPrediction and GeneCards databases. Moreover, protein–protein interaction analysis revealed a robust association among these targets, indicating the involvement of PI3K-related signaling pathways. PIK3CA and MMP-family proteins were prioritized as candidate targets based on their centrality within the network and their well-established roles in CCA progression, metastasis, and extracellular matrix remodeling. As predicted, treatment of ovalitenin A reduced the levels of phosphorylated PI3K and VEGF proteins and lowered the ratio of MMP-9 to TIMP-1 mRNA. These findings suggest that ovalitenin A may reduce CCA metastasis, possibly by altering PI3K signaling and its downstream molecular effectors.

Anti-inflammatory Effects of Southern Thai Red Curry Paste Extracts on an Inflamed Intestinal Cell Model

2026-05-12T20:49:10+07:00

This study aimed to investigate the anti-inflammatory activities of Southern Thai red curry paste extracts in both lipopolysaccharide (LPS)-activated macrophages and an in vitro inflamed intestinal epithelium model. The red curry paste, in both fresh and dried forms, was extracted using ethanol (EtOH). The anti-inflammatory effects were evaluated in LPS-stimulated RAW 264.7 murine macrophages and a co-culture model of human intestinal Caco-2 cells and RAW 264.7 cells. Among all extracts, the dried red curry ethanol extract (DR-EtOH) demonstrated the highest potency in inhibiting nitric oxide (NO) production in RAW 264.7 cells, with an IC₅₀ value of 220 ± 60 mg/mL, and significantly suppressed tumor necrosis factor-alpha (TNF-α) levels. Western blot analysis revealed that the both fresh (FR-EtOH) and dried (DR-EtOH) forms significantly inhibited the expression of inducible nitric oxide synthase (iNOS) protein. In the inflamed intestinal cell model, FR-EtOH at 125 mg/mL effectively attenuated macrophage-induced intestinal epithelial dysfunction, as indicated by maintaining transepithelial electrical resistance (TEER) values and reducing in interleukin-8 (IL-8) levels. These findings provide scientific evidence for the anti-inflammatory properties of Southern Thai red curry paste in both fresh and dried forms. This knowledge supports its potential development as functional foods or nutraceuticals for the prevention or mitigation of inflammatory gastrointestinal diseases.

Association between Telomere Length and Risk of Ischemic Stroke: A Systematic Review and Meta-analysis

2026-05-26T12:08:36+07:00

Ischemic stroke remains a leading contributor to death and long-term disability worldwide. Because telomere shortening reflects biological aging and cumulative cellular stress, telomere length has been proposed as a marker that might be related to stroke susceptibility. This study was undertaken to synthesize the available evidence on the relationship between telomere length and ischemic stroke risk. PubMed, Scopus, and CINAHL were searched for eligible studies, and seven studies met the inclusion criteria. These comprised one cohort study, one case-control study, and five Mendelian randomization studies. In pooled analyses, telomere length showed no significant association with ischemic stroke overall (OR = 1.00, 95% CI 0.92-1.07; p = 0.90), and the results remained non-significant in analyses by ischemic stroke subtype. No significant differences were identified between study-design subgroups. Overall, the current evidence does not support a causal association between telomere length and ischemic stroke. Given the small evidence base and the variation across prior studies, additional well-designed investigations are still needed to clarify whether telomere biology has any meaningful role in stroke development.

An Assessment Safety of Acute and Chronic Oral Toxicity studies of High Cannabidiol (CBD) from Female Inflorescence of Cannabis sativa L. (Hemp) Extract in Sprague-Dawley Rats

2026-04-22T09:23:39+07:00

Cannabis sativa L. contains cannabidiol (CBD), a non-psychoactive cannabinoid with potential therapeutic effects including anxiolytic, hypnotic, and analgesic properties. With increasing global use of CBD-containing products, comprehensive evaluation of their long-term safety is essential. Although pharmacological studies support its benefits, data on the chronic toxicity of high-CBD hemp extracts remain limited. This study aimed to evaluate both the acute and chronic toxicities of high-CBD hemp extract derived from the feminized Candida (CD-1) hemp strain, containing 50.6 + 1.2 % w/w CBD, in accordance OECD guidelines. Acute toxicity was evaluated according to OECD Test Guideline 423 by administering a single dose of 5,000 mg/kg to female rats, which were then observed for 14 days to estimate the LD₅₀. Chronic toxicity was evaluated under OECD Test Guideline 452 in male and female Sprague-Dawley rats administered daily oral doses of 0, 10, 20, and 40 mg/kg b.w./day for 180 days. Hematological, clinical chemistry and urinalysis parameters remained within normal ranges. No mortality or severe toxicological signs were observed during the study period. However, significant reductions in body weight and feed consumption were observed in the medium- and high-dose groups of females as well as the high-dose group of the males, which may be associated with the pharmacological activity of CBD. Centrilobular hepatocyte hypertrophy was observed in both sexes, accompanied by hypertrophy of the pars distalis of the pituitary gland and follicular cell hypertrophy in males. These findings are regarded as adaptive and non‑adverse. Additional minimal to slight changes corresponded to spontaneous background alterations. These findings suggest that the high-CBD hemp extract exhibits low acute toxicity and does not induce significant chronic toxicity at doses up to 40 mg/kg/day in rats.

In Silico Study of Compounds from Four Tropical Medicinal Plants as Allosteric Gyrase Inhibitor of Multidrug-Resistant E. coli

2025-08-03T16:37:15+07:00

The enormity and economic implications due to Escherichia coli infections and its resistance to valued antibiotics including fluoroquinolones in poultry production demand urgent alternative drugs from medicinal plants with a novel mechanism of action. Fifteen identified compounds from the four tropical medicinal plants, Petiveria alliacea, Solanum erianthum, Alternanthera brasiliana, and Hoslundia opposita, were subjected to molecular docking against the DNA gyrase of E. coli using Schrödinger software. The 3-dimensional (3D) x-ray chrystallographic structure of DNA gyrase A of E. coli with PDB ID-8QQI was retrieved in a co-crystallized form with isoquinoline-5-sulfonamide from protein data bank (PDB). The ligands were docked into its allosteric site occupied by the co-crystallized ligand. Post docking analyses were carried out through molecular mechanics/generalized born surface area (MM/GBSA), pharmacophore modelling and docking validation. Absorption, distribution, metabolism, excretion and toxicity (ADMET) of the ligands were predicted with appropriate online servers. The docking scores (kcal/mol) revealed gallic acid (-8.37), chlorogenic acid (-7.97), catechin (-7.20) and caffeic acid (-7.02) to be best among others, and also better than that of the reference drug isoquinoline-5-sulfonamide (-3.54). Nevertheless, the co-crystallized ligand recorded higher ΔGbind value (-71.93 kcal/mol) than the hit compounds (-37.50, -36.47, -52.77 and -29.87 kcal/mol). Gallic acid, chlorogenic acid, catechin, and caffeic acid were deemed drug-like following their docking scores, favourable predicted pharmacokinetic, physicochemical and ADMET properties. They are thus suggested for further studies ranging from in vivo to hits optimization in order to validate the results from the present study.