Context Ginkgolic acid (GAC), one of the major active constituents of Ginkgo biloba L. (Ginkgoaceae) extract, has been reported as a potential anticancer agent. Objective To investigate the effect of GAC on the viability of human hepatocellular carcinoma (HCC) cells and to identify its primary target and underlying mechanism. Materials and methods Human HCC cell lines and an orthotopic HCC mouse model were employed. The mechanism of GAC was elucidated through integrated analyses of cell viability, RNA sequencing, and biomarkers. The primary target of GAC was identified by drug affinity responsive target stability (DARTS) coupled with LC-MS/MS and further validated using molecular docking (MD), cellular thermal shift assay (CETSA), and microscale thermophoresis (MST) assay. Mechanistic roles were confirmed using genetic approaches, including gene knockdown and the construction of mutant plasmids. A KFERQ reporter system was used to detect the activity of chaperone-mediated autophagy (CMA). Results GAC effectively inhibits the viability of HCC by triggering ferroptosis. HSPA8 was identified as the direct target of GAC. The binding of GAC with HSPA8 enhances its interaction with glutathione peroxidase 4 (GPX4), which leads to the degradation of GPX4 via CMA. This process depleted glutathione (GSH) and caused lipid peroxidation, finally inducing ferroptosis in HCC cells. Furthermore, GAC suppressed tumor growth in an orthotopic HCC model, increased lipid peroxidation, and GPX4 degradation in tumor tissues. Discussion and conclusions Our results revealed a novel mechanism by which GAC induces ferroptosis in HCC cells through direct targeting of HSPA8 and promoting CMA-dependent GPX4 degradation. These findings suggest GAC-mediated ferroptosis as a potential therapeutic strategy against HCC and expand the pharmacological application of CMA-targeted cancer therapies.

Context Moringa oleifera Lam. (Moringaceae) and Ganoderma lucidum (Curtis) P. Karst. (Ganodermataceae) are two natural resources with established neuroprotective properties. However, whether their combination is safe and has neuroprotective effects against dementia remains unexplored. Objective This study aimed to investigate the phytochemical composition, toxicity profile, and neuroprotective activity of fermented M. oleifera and G. lucidum mixture (FMG) in scopolamine-induced dementia model rats. Methods FMG was produced by fermentation with Bacillus subtilis. A state of cognitive impairment was induced in rats via daily intraperitoneal administration of scopolamine (4 mg/kg) for 28 days. Following a two-week treatment period, cognitive function was assessed using the Y-maze. Postmortem analyses included biochemical assays to measure brain acetylcholinesterase (AChE) activity and oxidative stress markers, and histological examination of the hippocampus. Results LC-MS analysis revealed a rich phytochemical profile. The no-observed-adverse-effect level (NOAEL) was 200 mg/kg/day, while the lowest-observed-adverse-effect level (LOAEL) was 600 mg/kg/day. Treatment at the 200 mg/kg dose significantly reversed memory deficits, restoring spontaneous alternation from 29.1% in scopolamine-treated rats to 82.6% (p < 0.05). This behavioral recovery was correlated with a significant reduction in brain AChE activity, a normalization of lipid peroxidation (TBARS) levels, and the restoration of hippocampal neuronal architecture. Discussion and conclusions The restorative effects of FMG are mediated by a dual mechanism involving the enhancement of central cholinergic and antioxidant systems. These results suggest that FMG possesses neuroprotective and antioxidant properties and could be a promising candidate for the management of cognitive deficits.

Context The growing multidrug resistance (MDR) of Pseudomonas aeruginosa presents a pressing global health challenge and demands novel solutions. Medicinal plants offer a largely untapped reservoir of structurally diverse compounds with promising antibacterial and adjuvant potential. Objective This study investigated Sida acuta Burm.f. (Malvaceae) as a reservoir of dual-target phytochemicals capable of modulating resistance. Materials and methods An integrated workflow combining LC/Q-TOF-MS metabolomic profiling, molecular docking (MD), dynamics simulations (MDS), and microbiological assays was applied to the ethyl acetate fraction of the aerial parts (SAAP–EA). Results Metabolomic analysis identified 35 compounds, including biochanin A (BCA), resveratrol (RSV), methyl gallate (MG), 3-hydroxycinnamic acid (3-HCA), and azelaic acid (AZA), with favorable drug-likeness. Their toxicity predictions indicated low risks of acute toxicity (LD50 >900 mg/kg), mutagenicity, and carcinogenicity, but flagged a potential nephrotoxicity risk requiring further investigation. MD and MDS revealed stable RSV and BCA binding to both BamB (outer membrane biogenesis) and OprM (efflux), while 3-HCA and AZA preferentially targeted OprM with higher affinities than reference inhibitors. Hydrogen-bonding supported specificity and complex stability. Experimentally, SAAP–EA showed potent bactericidal activity against clinical MDR P. aeruginosa (MIC 32–256 µg/mL) and synergized with β-lactams, fluoroquinolones, and tetracyclines, achieving up to 64-fold MIC reductions at sub-inhibitory doses. The dual inhibition of membrane assembly and efflux likely underlies the observed resistance-breaking effects, facilitating intracellular antibiotic accumulation. Discussion and conclusions These findings establish a mechanistic basis for translating ethnopharmacology into therapeutic strategies against MDR Gram-negative pathogens. Future work should prioritize in vivo validation and preclinical optimization of lead dual-target adjuvants.

Context The pharmacological effects of Kaempferia parviflora have been extensively documented. A solid self-microemulsifying drug delivery system (SMEDDS) has been developed to address limitations such as poor water solubility and low bioavailability. Objective This study evaluated the safety and anti-aging efficacy of the solid SMEDDS containing K. parviflora extract (KPS-SMEDDS) in rats. Materials and methods A sub-chronic toxicity study was performed to assess the safety of KPS-SMEDDS. Healthy rats (n = 10/group) received oral doses of 125, 250, or 500 mg/kg body weight daily for 90 days. Clinical signs, body weight, hematological and biochemical parameters, and major organ histopathology were evaluated. Separately, the anti-aging effects of KPS-SMEDDS were investigated in a different cohort of rats (n = 9/group) with D-galactose-induced aging. Rats received intraperitoneal D-galactose (50 mg/kg/day) and oral KPS-SMEDDS at the same doses for 60 days. Oxidative stress markers, hormone levels, histopathology, and the expression of proteins related to aging, apoptosis, and inflammation were assessed. Results No significant changes were observed in clinical signs, body weight, organ weights, hematological or biochemical parameters, or histopathology in KPS-SMEDDS-treated rats, indicating its safety. KPS-SMEDDS treatment significantly improved testicular weight, reduced malondialdehyde levels, normalized hormone levels, and restored testicular structure in rats with D-galactose-induced aging. Additionally, it upregulated SIRT-1 and Bcl-2, downregulated SA-β-gal, p53, and caspase-3, and modulated inflammatory cytokines (TNF-α, IL-6, and IL-10). Discussion and conclusion KPS-SMEDDS was well-tolerated in rats and exerted protective effects against D-galactose-induced aging. These findings support its potential as a safe, natural anti-aging agent and highlight the value of formulation enhancement in traditional herbal medicine.

Context cAMP-induced intestinal chloride secretion plays a pivotal role in the pathogenesis of secretory diarrheas. Objective In this study, we investigated the antisecretory effects of α,β-dehydromonacolin K, a derivative of lovastatin from Aspergillus sclerotiorum, on cAMP-induced chloride secretion in human T84 cells and fluid secretion in human colonoids. Materials and Methods Short-circuit current analyses and swelling assays were used to investigate the effects of α,β-dehydromonacolin K on chloride transport and fluid secretion, respectively. Proteomic analyses were performed to determine the potential anti-diarrheal mechanisms of α,β-dehydromonacolin K. Results In T84 cells, α,β-dehydromonacolin K inhibited cAMP-induced chloride secretion with an IC50 of ∼ 6.32 μM. Apical chloride current analyses demonstrated that α,β-dehydromonacolin K inhibited CFTR chloride channels stimulated by cAMP agonists with an IC50 of ∼ 1 μM. Basolateral potassium current analyses indicated that α,β-dehydromonacolin K had no effect on basolateral potassium channel activities. In a three-dimensional (3D) model of human colonoids, α,β-dehydromonacolin K (20 µM) suppressed both cAMP-induced and calcium-induced fluid secretion by ∼ 70%. Proteomic analyses of human colonoids revealed that α,β-dehydromonacolin K interacted with 33 proteins, including those associated with non-sense-mediated mRNA decay (NMD). Notably, the inhibitory effects of α,β-dehydromonacolin K on cAMP-induced chloride and fluid secretion were significantly diminished in the presence of SMG1i, an inhibitor of serine/threonine-protein kinase SMG1 involved in NMD, suggesting that α,β-dehydromonacolin K inhibits cAMP-induced chloride-driven fluid secretion in human intestinal epithelial cells by mechanisms involving SMG1-dependent NMD pathways. Discussion and conclusions α, β-Dehydromonacolin K represents a promising class of natural compounds that exert antisecretory effects in human intestinal epithelia via a novel mechanism of action involving SMG1 in NMD pathways.

Context Turmeric (Curcuma longa) is widely used as a spice and in dietary/food supplements and herbal medicines. Reports assessing the authenticity of commercial products have shown that the ingredient is subject to adulteration with, among others, artificial dyes, undeclared diluents, and synthetic curcumin. Objective This scoping review summarizes published data on adulteration of turmeric products sold as spice and dietary or food supplements to estimate the prevalence of non-authentic turmeric on the market. Methods This scoping review was based on a literature analysis from Google Scholar, PubMed, ScienceDirect, Scopus, and Web of Science databases, covering publications from 2000 to 2025. Article selection was performed according to PRISMA-ScR guidelines. After the initial search, specific countries were added to refine the search. Of the 375 publications retrieved, 347 were eliminated as duplicates or because they lacked information on turmeric adulteration, adulteration of commercial products, or did not provide the number of adulterated samples. An additional 19 papers were found searching the citations, or by using Google Search with the keywords “Curcuma longa”, “turmeric”, “government report”, and “adulteration”. One more report from the CVUA Stuttgart was found using the keywords “Kurkuma”, “Verfälschung”, and “Report”. In total, 48 papers were included in the review. Results A total of 48 publications representing 2235 commercial turmeric samples were included in the study. The overall adulteration rate was 20.0%, with spice samples having a slightly lower percentage of adulterated samples (20.4%) than dietary and food supplements (22.0%). Conclusion Adulteration of turmeric remains a concern on markets worldwide.

Context The traditional Japanese medicine Hangeshashinto (HST) is a multicompound drug used for stomatitis. The identification of HST’s active ingredients is essential for understanding its mechanism of action and establishing pharmacological quality control markers, but remains unclear due to its multicomponent drug. Objective To systematically explore anti-inflammatory ingredients in HST using a combined approach involving a cell-based bioassay and multicomponent analysis, and to identify potential quality marker compounds. Materials and methods A cell-based bioassay modeling stomatitis was established using human oral keratinocytes (HOK), with interleukin (IL)-1β–induced prostaglandin E2 (PGE2) as an inflammatory indicator. The PGE2 inhibitory effects of quality-controlled 101 HST manufacturing lots were compared. Multicomponent analysis was performed on the 101 HST samples, correlating the intensity of 121 component peaks with the pharmacological activities. Ingredients with the highest correlation coefficients were validated for their PGE2 inhibitory effects. Results A total of 101 HST samples (30 µg/mL: approximately IC50) showed consistent inhibition of IL-1β–induced PGE2 production in HOK (41.33%–67.38% with 100% as IL-1β). Correlation analysis between PGE2 inhibitory activities and peak intensity of 121 components revealed the contribution of each ingredient to the pharmacological effect. Eight ingredients (glycycoumarin, neoglycyrol, [6]-shogaol, [8]-shogaol, [10]-shogaol, [6]-gingerol, [8]-gingerol, and [10]-gingerol) with the highest correlation coefficients (below −0.30) exhibited PGE2-inhibitory potential. Conclusion The standardization of current quality control markers contributes to the stability of HST’s anti-inflammatory effects. The eight components discovered by this integrated analysis method may become novel quality control marker ingredients for further improving the pharmacological quality of HST.

Context The global rise in bacterial resistance to existing antibiotics has led to increased mortality rates and escalating healthcare costs, underscoring the urgent need for new classes of antibacterial agents that can act synergistically with current antimicrobials. Objective This study aimed to isolate bioactive compounds from Satureja hortensis L. (Lamiaceae) and evaluate their effects in combination with ciprofloxacin (CIP), ampicillin (AMP), gentamicin (GEN), and tetracycline (TET). Materials and methods The adjuvant potential of naringenin (N), 5,6-dihydroxy-7,3′,4′-trimethoxyflavone (TMF), cilicione-a (Cil), rosmarinic acid (Rs), rosmarinic acid methyl ester (MRs), and fulgidic acid was evaluated by determining the minimum inhibitory concentrations (MICs) of selected antibiotics in presence of sub-inhibitory concentrations of these compounds. The assays were performed against ten bacterial strains using the twofold broth microdilution method. Test samples were prepared in 96-well microtiter plates, incubated at 37 °C for 18 h, and dimethyl sulfoxide was used as the solvent control. Results N, Rs, and MRs reduced the MIC value of GEN from 0.78 µM to 0.097 µM against the drug-resistant Escherichia coli AG100 strain. Additionally, the combinations of N and MRs with CIP reduced its MIC from 3.125 µM to 0.39 µM against Klebsiella pneumoniae. A MIC reduction (from 50 µM to 12.5 µM) was observed against the methicillin- and oxacillin-resistant Staphylococcus aureus strain when N, Cil, Rs, and MRs were combined with AMP. The MIC changed from 0.125 µM to 0.03125 µM against Bacillus subtilis when N and TMF were combined with GEN. Discussion and conclusions These findings highlight the potential of such combinations to enhance antibiotic efficacy, lower the required dosages, and contribute to mitigating the emergence of antimicrobial resistance.

Context Rheum palmatum L. (Rhubarb) has shown potential in managing Chronic Kidney Disease (CKD) but its protective mechanisms remain unclear. Objective This study investigates rhubarb’s therapeutic effects and underlying mechanisms in CKD. Materials and methods High-performance liquid chromatography (HPLC) established a rhubarb fingerprint to ensure quality control. Network pharmacology and Mendelian randomization identified primary CKD therapeutic targets. Inflammation, oxidative stress, and renal performance were assessed through ELISAs and biochemical tests. Renal structure and fibrosis were examined using hematoxylin-eosin and Masson staining. Protein expression related to fibrosis, apoptosis, and NF-κB pathway activity was measured via Western blotting. Discovery Studio 2019 (DS 2019) was used for molecular docking. Results HPLC fingerprinting confirmed high batch-to-batch consistency of rhubarb, identifying five key anthraquinones (aloe-emodin, rhein, emodin, chrysophanol, physcion) with similarity indices >0.91. Network pharmacology identified 19 active compounds targeting 2,597 CKD-related proteins, with 47 overlapping targets including IL6, TNF, TP53, CASP3, and IL1B as core nodes. MR analysis demonstrated a statistically significant causal association between TNF and CKD (OR = 1.02, p < 0.05), with positive trends for IL6 and CASP3. In CKD rat models, rhubarb significantly improved renal function by reducing blood urea nitrogen (BUN), serum creatinine (SCr), and uric acid (UA) levels (p < 0.05). Histopathology showed reduced glomerulosclerosis, tubular atrophy, interstitial fibrosis, and inflammatory infiltration after treatment. Rhubarb markedly decreased renal fibrosis markers including collagen I, collagen III, α-SMA, and TGF-β (p < 0.01). Pro-inflammatory cytokines IL-6, IL-1β, and TNF-α levels were significantly suppressed (p < 0.001). Antioxidant enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were restored, while lipid peroxidation (LPO) was reduced (p < 0.05). Rhubarb inhibited NF-κB pathway activation by lowering phosphorylated NF-κB and IκBα, and increasing total IκBα expression (p < 0.01). Apoptosis-related proteins showed upregulated Bcl-2 and downregulated Bax and cleaved caspase-3 expression (p < 0.05). Molecular docking confirmed strong binding affinities of rhubarb’s core compounds with key targets such as TNF and IL6, supporting their therapeutic roles. Conclusion Rhubarb significantly reduces renal impairment, fibrosis, inflammation, and apoptosis through the NF-κB pathway, supporting its traditional use and potential as an adjunct therapy for CKD.

Context Breast and liver cancers remain significant global health challenges, necessitating the discovery of novel anticancer agents. Marine cyanobacteria, such as Moorena producens belonging to the family: Oscillatoriaceae, are rich sources of bioactive compounds with potential anticancer properties. Objective This study aims to identify and characterize bioactive compounds from M. producens and evaluate their anticancer activity against breast and liver cancer cell lines. Materials and methods M. producens was collected and authenticated using 16S rRNA sequencing. The ethanolic extract was analyzed using LC-QTOF-MS/MS to identify the potential bioactive metabolites. Network pharmacology analysis was employed to predict the potential targets of these compounds. The crude extract was fractionated, and the fractions were screened for the anticancer activity against MCF-7 and HepG2 cell lines. Results LC-QTOF-MS/MS analysis identified 25 metabolites, including apocarotenoids, spirovetivane alkaloids, and toxins. Network pharmacology analysis suggested that malyngamide D, isomalyngamide I, mueggelone, 11,12-didehydrospironostoic acid, and 12-hydroxy-2-oxo-11-epi-hinesol were potential bioactive compounds targeting proto-oncogene tyrosine-protein kinase (Src), mitogen-activated protein kinase 3(MAPK3), and MAPK1 kinases. Molecular docking studies further supported these findings, with 11,12-didehydrospironostoic acid exhibiting strong binding affinities to Src and MAPK1 kinases. Among the nine fractions obtained, Fraction 1 showed the most potent anticancer activity against both MCF-7 and HepG2 cell lines, with IC50 values, 59.63 ± 7.1 and 149.23 ± 0.9 µg/mL, respectively. Discussion and conclusion The results of this study highlight the potential of M. producens as a source of novel anticancer compounds. Further investigation of the bioactive compounds in Fractions 1 and 2 may lead to the discovery of promising anticancer agents.