Introduction Artemisia kurramense has been used for gastrointestinal and inflammatory conditions, but no attempt has been made to explore the possible computational molecular mechanism against Helicobacter pylori-associated gastric pathogenesis. This study aimed to develop a computational hypothesis of the therapeutic potential of A. Kurramense by combining the phytochemical profiling based on LC-HRMS with network pharmacology, molecular docking and density functional theory (DFT) analysis. Methods LC-HRMS profiling of three extracts of A. Kurramense resulted in the identification of 40 phytochemicals, of which 37 were unique across all three extracts analyzed. Oral bioavailability and drug-likeness screening were carried out for the identified compounds, which were then subjected to target prediction, disease-associated target intersection, protein–protein interaction (PPI) network analysis, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, molecular docking study and density functional theory (DFT) calculation. Results Integrated analysis identified 131 common therapeutic targets, with AKT1, PIK3CA, and EGFR as prominent hub targets. Functional enrichment identified the PI3K-Akt pathway as the top enriched pathway, followed by cancer pathways, HIF-1, FoxO, MAPK and apoptosis pathways. Key regulatory proteins in the PI3K-Akt network were AKT1, PIK3CA, EGFR, PIK3R1 and TP53. The prioritized phytochemicals showed good predicted binding affinity with AKT1, with the greatest affinity for quercetin (AK-7) (−10.047 kcal/mol). At the same time, the DFT analysis revealed favourable electronic properties and chemical reactivity of the prioritized compounds. Conclusion The computational results support a hypothesis that A. Kurramense is a multi-target modulator of host inflammatory, survival, oxidative-stress, and apoptosis-related signaling pathways, with the PI3K-Akt signaling pathway as a potential central mechanism of action. Some prioritized phytochemicals, such as quercetin, are promising for further investigation. However, these are computational predictions and further studies to validate the anti-H. pylori activity, target engagement, pathway modulation, and gastric protective effects require appropriate in vitro and in vivo studies.
Garcinia cowa Roxb. a Southeast Asian edible medicinal plant, have traditionally been used to manage diabetes mellitus (DM). Its leaves are rich in chamuangone, a major bioactive polyprenylated benzophenone. Thereby, this study aimed to develop standardized chamuangone-enriched extract (CEE) from its leaves for antidiabetic evaluation. CEE was prepared by microwave-assisted extraction (MAE), along with column chromatography, and standardized by HPLC analysis. The antihyperglycemic and antihyperlipidemic assessment of CEE was conducted via computational, in vitro enzyme (α–glucosidase and pancreatic lipase) inhibitory, and in vivo assays using nicotinamide–streptozotocin (NA–STZ)-induced male diabetic rats. Experimentally, the diabetic rats were divided into five groups (n = 6). Group I was given vehicle; group II received repaglinide (1 mg/kg); and groups III, IV, and V were orally administered with CEE at 25, 50, and 100 mg/kg, respectively, for 28 days. CEE, containing 67.0 ± 2.0% w/w of chamuangone, demonstrated strong docking scores against α-glucosidase (−8.0 kcal/mol) and pancreatic lipase (−8.5 kcal/mol), corroborating in-vitro enzyme inhibitory activities (IC50 = 3.41 and 11.14 µg/mL, respectively). Molecular dynamics (MD) simulations revealed stable complexation of chamuangone with α-glucosidase (RMSD: 0.19 nm and RMSF: 0.10 nm), unlike pancreatic lipase (RMSD: 0.33 nm and RMSF: 0.18 nm). Finally, CEE (25, 50, and 100 mg/kg) ameliorated insulin, fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), food/water intake, body mass index, cholesterol, triglycerides, high/low density lipoproteins, aspartate aminotransferase, alanine aminotransferase, creatinine, and blood urea nitrogen levels in diabetic rats. Overall, this study highlights the promising potential of CEE in the management of DM.
Ethnopharmacological relevance Acute myocardial infarction (AMI) significantly increases the global health and economic burden. Although Western drug therapies have successfully reduced mortality in patients with acute myocardial injury, they are not without drawbacks, including a range of adverse effects. Although Rhizoma Corydalis (YHS) has been used in China for over a thousand years to prevent cardiac conditions, its precise preventive and therapeutic effects on AMI areremain unclear, necessitating further research into its mechanisms of action. Aim of the study To assess the therapeutic potential of YHS against AMI, this study seeks to identify its active components and thereby establish its pharmacological basis. Materials and methods In this study, an AMI model was established in mice by tail vein injection of doxorubicin (DOX). Network pharmacology and UHPLC-Q Exactive Orbitrap HRMS technology were used to predict the active constituents, target molecules, and mechanisms of action of YHS against AMI. Echocardiography, histopathological examination, and serum biochemical assays were utilized to assess the therapeutic benefits of YHS and its main active component TP on the AMI mice model. The effects of YHS on the signaling pathways and gene expression profile in AMI were investigated by transcriptome analysis. ROS staining, Western blotting, PCR, and immunofluorescence were utilized to validate the mechanisms of YHS in preventing AMI. Results According to our research, DOX-induced changes in body weight and cardiac indices were considerably improved by both YHS and its main active component TP, which also successfully decreased levels of lactate dehydrogenase (LDH) and creatine kinase MB isoenzyme (CK-MB). YHS and TP significantly improved the low EF and FS levels brought on by DOX overdose, according to echocardiography. Myofibrillar disarray, myocardial cell nuclear atrophy, and inflammatory cell infiltration in the heart were all improved by YHS and TP, according to histological study. The NOD-like receptor pathway, which included important proteins like Nox2, TXNIP, NLRP3, and Caspase-1, may be the basis for YHS's ACT-improving mechanism, according to network pharmacology prediction and transcriptomics research. In addition, DHE staining, immunofluorescence detection, PCR, and Western blot experiments demonstrated that YHS improved AMI in mice by inhibiting DOX-activated Nox2, lowering excessive ROS production, suppressing TXNIP translocation, and reducing inflammasome expression (including NLRP3 and Caspase-1). Conclusion According to research, YHS successfully reduced doxorubicin-induced acute myocardial injury by blocking the NOD-like receptor pathway, lowering levels of reactive oxygen species (ROS) and the important oxidative stress gene Cybb, and decreasing the production of inflammasomes. This work offered fresh perspectives on the pharmacological activities of traditional Chinese medicine in treating AMI from a variety of angles by first revealing the intricate processes by which YHS prevented AMI at the levels of oxidative stress and inflammasome.
Centella asiatica (CA) is widely used to support skin health, yet heterogeneous sourcing and cultivation conditions can cause batch-to-batch variability in phytochemical profiles, complicating reproducible evaluation and standardized development. Moreover, anti-photoaging-related activity may be modest or inconsistent when aqueous extraction is applied, highlighting the need for cultivars that retain activity under water-based processing. In this study, a newly registered cultivar, Giant Centella asiatica (GCA), was compared with conventional CA for its anti-photoaging-related activity and associated mechanism under UVB-induced conditions. Water extracts of GCA and CA were assessed for chemical antioxidant capacity and total phenolic/flavonoid contents, and their effects on UVB-induced matrix metalloproteinase-1 (MMP-1)-related responses were examined in HaCaT keratinocytes using western blotting and AP-1/MMP-1 promoter luciferase assays. Under the present assay conditions, UVB increased MMP-1 protein levels by approximately 16-fold, and GCA reduced the UVB-induced signal by 74% at 20 μg/mL, whereas CA showed only 5% inhibition at the same concentration. Activity of GCA was further supported in a 3D human skin equivalent model by assessing UVB-driven MMP-1 levels and collagen-associated tissue changes. GCA showed higher chemical radical-scavenging capacity and higher phenolic and flavonoid contents than CA, and it more effectively reduced UVB-induced MMP-1-related responses, accompanied by reduced phosphorylation of c-Raf, MEK1/2, and ERK and by decreased AP-1/MMP-1 transactivation. In the 3D skin model, GCA attenuated UVB-induced MMP-1 upregulation and collagen-associated tissue changes. LC/MS-MS-guided isolation coupled with NMR identified rimanoside, a water-soluble trisaccharide and candidate marker constituent, which dose-dependently inhibited UVB-induced MMP-1 expression (IC50: 20.89 μM) and was associated with reduced ERK phosphorylation under the present assay conditions. Quantitative analysis further showed that rimanoside was present at a higher level in GCA than in CA under identical extraction conditions. Overall, GCA showed stronger anti-photoaging-related activity than CA under the present in vitro and 3D skin-equivalent model conditions, and rimanoside may serve as an active water-soluble constituent and candidate marker compound for future standardization of GCA. Further phytochemical standardization and in vivo validation remain necessary.
Background Traumatic brain injury (TBI) continues to be a significant worldwide health issue, with its incidence increasing, especially in low- and middle-income countries. The complex TBI mechanism involves both primary and secondary injury processes mediated by excitotoxicity, oxidative stress, and neuroinflammation, leading to damage of the blood–brain barrier (BBB) and neuronal dysfunction. Biomarkers such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and tumor necrosis factor-alpha (TNF-α) have been widely explored to assess neuronal survival, neuroplasticity, and the degree of neuroinflammation in TBI. In recent years, increasing attention has been directed toward plant-derived compounds with neuroprotective potential. Centella asiatica (CA), cinnamon, and spirulina represent promising candidates because their ability as an antioxidant, anti-inflammatory, and neurotrophic factors. Experimental studies have demonstrated that bioactive compounds such as asiatic acid in CA, cinnamaldehyde in cinnamon, and phycocyanin in spirulina can cross the BBB and modulate key neuroprotective pathways. These include upregulation of BDNF and NGF, inhibition of TNF-α as an pro-inflammatory cytokines, and attenuation of neuronal damage through reduction of oxidative stress and apoptosis. Furthermore, several in vivo studies using rodent models of TBI support the efficacy of these natural extracts in enhancing histopathological recovery and modulating molecular responses in the acute phase of brain injury. This review highlights the therapeutic potential of CA, cinnamon, and spirulina as adjunctive treatments for TBI by focusing on their mechanisms of action through biomarker-based approaches, particularly targeting BDNF, NGF, and TNF-α. Continued exploration of these natural compounds could contribute to the development of novel, accessible, and effective treatment for neuroprotection and recovery in TBI.
Inflammation serves as a critical immune response to infection or injury; however, chronic inflammation contributes significantly to tissue damage, fibrosis, and systemic diseases like autoimmune disorders and inflammatory bowel disease. Furthermore, chronic low-grade inflammation, known as "inflammaging," is a hallmark of physiological decline during aging. While Punica granatum (pomegranate) peel is recognized for its diverse bioactive metabolites, the precise molecular mechanisms underlying its anti-inflammatory potential remain under-defined. This study utilized a computational approach to analyze 112 metabolites from pomegranate peel to predict their molecular targets using STITCH and SwissTargetPrediction, identifying 863 potential target genes. A total of 4986 inflammation-associated genes were compiled from multiple databases, and overlap analysis revealed 733 common genes. Among these, PDE4B and ABCC1 were shortlisted as a primary regulatory hub for inflammatory pathways for further investigation. Analysis of the protein–protein interaction (PPI) network, Gene Ontology (GO), and KEGG pathways indicated roles for PI3K-Akt signaling, apoptosis, and insulin resistance. Molecular docking and dynamics simulation analysis demonstrated strong binding affinities of compounds with pubchem ID 535560 and 569501 with PDE4B; and 69377 and 75487878 with ABCC1. These findings suggest that pomegranate peel metabolites may effectively mitigate inflammation by modulating these critical proteins, though subsequent in vitro and in vivo validation is essential.
Sepsis-induced acute kidney injury (S-AKI) is a life-threatening disease, which therapeutic strategies are supportive but not effective. Shengbaishao Gancao Decoction (SGD) is a traditional Chinese medicine, which has multiple beneficial effects on a variety of diseases. However, whether SGD has a therapeutic effect on S-AKI is unknown. The present study aims to comprehensively investigate the potential therapeutic effect of SGD on S-AKI and its molecular mechanisms. We used cecal ligation and puncture (CLP) to establish S-AKI model. SGD (22 and 44 g/kg) was orally administrated once a day for seven days prior to modeling. The kidney injury, systemic inflammation, and mitochondrial oxidative stress were measured and compared among different groups. Network pharmacology, proteomic analysis and molecular docking were performed to investigate the underlying pharmacological targets of SGD and the regulatory mechanisms. Administration of SGD decreased kidney injury, mitigated systemic inflammation and alleviated oxidative stress in septic mice. Network pharmacology, proteomic analysis and molecular docking predicted that SGD might protect against S-AKI by alleviating systemic inflammation and increasing antioxidant function through PI3K-AKT signaling pathway. Significance The development of effective therapeutic agents for S-AKI remains a critical unmet medical need. Although SGD has been widely recognized for its anti-inflammatory and renal properties, its therapeutic potential mechanisms in S-AKI remains unclear. In this study, we employed an integrative approach combining network pharmacology, proteomics, and molecular docking to unravel the protective mechanisms of SGD against S-AKI. These findings not only deepen the understanding of traditional Chinese medicine in addressing complex diseases but also provide a scientifically validated therapeutic strategy for the treatment of S-AKI.
Background Moringa stenopetala is a nutritionally rich medicinal plant widely used in traditional medicine for managing metabolic, infectious, inflammatory, and chronic diseases. Despite its extensive ethnomedicinal use, its pharmacological effects and safety profile are reported variably across experimental and regulatory studies. Objective To summarize the pharmacological activities, safety profile, and experimental evidence of Moringa stenopetala based on in vitro and in vivo studies. Methods A narrative synthesis of published experimental studies, including in vitro assays, in vivo animal models, toxicity studies, and chemical analyses, was performed. Studies evaluating metabolic, antimicrobial, cardiovascular, neurological, anticancer, reproductive, and toxicological outcomes were included. The findings were synthesized qualitatively. Results This review demonstrated that Moringa stenopetala possesses broad pharmacological activities in both in vitro and in vivo models. Leaf extracts at 250–500 mg/kg for 14–28 days significantly reduced blood glucose, improved lipid profiles, and restored pancreatic β-cells in diabetic animals. Antioxidant studies showed strong radical-scavenging activity and increased levels of endogenous antioxidant enzymes. Antimicrobial studies demonstrated potent antibacterial and antifungal effects, with MIC values as low as 0.31 mg/mL. Antiparasitic studies using 400 mg/kg for 7 days reduced parasitemia and improved survival in infected mice. Cardiovascular studies using 10–1000 mg/kg extracts showed antihypertensive, vasorelaxant, diuretic, and natriuretic effects. Additional studies reported analgesic, anti-inflammatory, anticonvulsant, neuroprotective, antidiarrheal, and anticancer activities. Toxicological evaluations showed favorable safety profiles, with LD50 values >5000 mg/kg and minimal organ toxicity. Conclusion Moringa stenopetala possesses broad pharmacological potential supported mainly by preclinical evidence. However, toxicity studies indicate possible dose-dependent safety concerns, particularly at high exposure levels. The absence of human clinical confirmation highlights the need for further translational and clinical research.
Type 2 diabetes mellitus (T2DM) is increasingly recognized as a chronic immunometabolic disorder driven by persistent inflammation and dysregulated glucose metabolism. Conventional nutrition paradigms, which focus primarily on macro- and micronutrients, fail to account for regulatory bioactive molecules that may influence host gene expression. Emerging evidence highlights edible plant-derived exosome-like nanoparticles (ELNs) as novel carriers of microRNA-like molecules capable of mediating cross-kingdom communication. This review synthesizes current knowledge on the biogenesis, molecular cargo, gastrointestinal stability, and systemic distribution of plant ELNs, emphasizing their role in modulating immunometabolic pathways relevant to diabetes. Preclinical evidence suggests that certain plant ELNs may retain structural integrity during gastrointestinal transit and may be internalized by intestinal cells and gut microbiota, although the efficiency and physiological relevance of these processes in humans remain uncertain. These molecules have been reported to regulate key targets involved in insulin signaling (e.g., IRS/PI3K/AKT), inflammation (e.g., NF-κB, NLRP3 inflammasome), and lipid metabolism. Functionally, plant ELNs may enhance insulin sensitivity, suppress pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), and promote macrophage polarization toward anti-inflammatory phenotypes. Additionally, they influence host metabolism indirectly via microbiome-mediated pathways. However, evidence supporting cross-kingdom RNA transfer in humans remains limited, and important questions regarding bioavailability, reproducibility, and physiological relevance are still unresolved. Overall, plant-derived ELNs represent an emerging area of research that expands current understanding of diet-derived gene-regulatory signals. Future integration of multi-omics approaches and artificial intelligence may facilitate the development of hypothesis-driven precision nutrition approaches, pending robust validation in human studies
Mucociliary clearance (MCC), which extrudes inhaled small particles from airways, is driven by the beating cilia. Two cellular activities, the ciliary-beat-frequency (CBF) and -distance (CBD, an index of amplitude), facilitate MCC; in addition, an epithelial activity, metachronal waves (MCWs), is suggested to facilitate it. In this study, beating cilia were observed in ciliated normal human bronchial/tracheal epithelial cells (c-NHBE cells) using high-speed video microscopy (HSVM) and the MCWs were detected by kymographs of beating cilia produced from HSVM video images. Ryukakusan (RKS, a Japanese herbal medicine facilitating MCC), which contains platycodon, licorice, apricot kernel and senega, was used for experiments, because it stimulated the MCWs with a small CBF increase in c-NHBE cells. RKS increased [Ca2+]i by activating TRPV4, leading to increase the MCW-wavelengths (MCW-Ls) and decreased [Cl-]i by activating Cl- channels, which led to an increase in CBD. Connexin43 activated by TRPV4 transmitted MCWs to adjacent cells, leading to increased MCW-Ls. In RKS-stimulated c-NHBE sheets, increases in the MCW-L and CBD enhanced the microbead transport rate from 245 µm/s to 340 µm/s (p < 0.001), while the CBD itself enhanced to 295 µm/s (p < 0.001). Thus, the tissue-scale MCWs (long MCW-Ls) enhanced the rates of ciliary microbead transport in c-NHBE sheets, and are an important epithelial function for facilitating MCC in airways. Thus, RKS increasing MCW-Ls and CBD appears to prevent oropharynx epithelia from injury and infections by inhaled particles.
Background Infertility affects 8–12% of couples globally, with a higher burden in developing regions where access to conventional fertility treatments is limited. This has fueled growing interest in complementary and alternative medicines such as medicinal plants. Garcinia kola (bitter kola), a native plant in West and Central Africa, is traditionally used to enhance reproductive health. This systematic review examined the potential of G. kola and its metabolites on fertility and their mechanisms of action. Method A PRISMA 2020 guided systematic review was conducted using databases including PubMed, Scopus, Web of Science, and Google Scholar, a grey literature. Peer-reviewed articles written in English involving rodent models that evaluated fertility outcomes were included. A deeper insight into the safety and toxicological profile of G. kola metabolites was provided by performing in silico screening using the SwissADME and pkCSM web servers. Result Thirty-four articles met the inclusion criteria. Most studies were conducted in Nigeria (91.18%), followed by South Africa and Egypt. Kolaviron and Hydroxybiflavanonol were the identified phytocompounds in the articles reviewed. These antioxidant metabolites demonstrated significant reproductive benefits by improving sperm quality, testicular histoarchitecture, and restoring reproductive hormone levels. Conclusion The review identifies kolaviron and Hydroxybiflavanonol as G. kola’s metabolites with the potential of improving reproductive health. Nonetheless, due to the varied pharmacokinetic and toxicological profiles of these metabolites, further clinical studies are needed to validate their efficacy, establish optimal dosing, and ensure safety in human populations.
Background: Internationally standardised Chinese medicine pattern classification is essential for interoperable integrative oncology research. The WHO ICD-11 Traditional Medicine Module provides a harmonised framework. However, the reproducibility and prognostic value of ICD-11-aligned Chinese medicine (CM) pattern classification in stage IV lung adenocarcinoma (LUAD-IV) remain uncertain across evolving systemic therapy eras. Methods: Two prospective real-world cohorts of newly diagnosed LUAD-IV patients from different therapeutic eras were analysed (2009–2018, n = 412; 2020–2024, n = 133).Eligible patients had ECOG performance status 0–1, complete survival follow-up data, and received systemic anticancer therapy plus Chinese herbal medicine from baseline.Baseline patterns were assigned using the China Association of Chinese Medicine (CACM) criteria and mapped to ICD-11 Traditional Medicine codes. Interobserver agreement was assessed in 50 randomly selected cases (Cohen's κ). Overall survival was analysed using Kaplan–Meier methods and multivariable Cox regression with time-dependent treatment covariates to address measured confounding and immortal-time bias. Results: Predominant baseline patterns were Lung–Spleen Qi deficiency (48% vs 37%), Qi–Yin deficiency (46% vs 26%), and Lung–Kidney deficiency (4%vs 32%) in the earlier and contemporary cohorts, respectively. Interobserver agreement was substantial (κ = 0.64 and κ = 0.68). Median overall survival increased from 24 to 48 months. Age ≥68 years, absence of EGFR-TKI or anti-VEGF therapy, and stage IVB disease independently predicted poorer survival, whereas baseline Chinese medicine patterns did not. Conclusions: ICD-11-aligned CACM pattern classification is reproducible across therapeutic eras but does not independently predict survival in LUAD-IV, supporting its use for standardised reporting and treatment individualisation rather than prognostic stratification.
Degenerative diseases including Alzheimer’s disease, diabetes mellitus and hypertension remain major global health challenges due to their increasing prevalence, multifactorial pathogenesis and associated socioeconomic burden. Oxidative stress, chronic inflammation, endothelial dysfunction, protein glycation and metabolic dysregulation are recognized as critical pathological mechanisms underlying the initiation and progression of these disorders. Consequently, increasing attention has been directed toward medicinal plants possessing multi-target pharmacological activities and sustainable therapeutic potential. Eichhornia crassipes (water hyacinth), an invasive aquatic macrophyte widely distributed in tropical and subtropical regions, has emerged as a promising source of bioactive phytochemicals including flavonoids, phenolic acids, alkaloids, tannins, terpenoids and saponins with diverse biomedical applications. This review critically evaluates the phytochemical composition, pharmacological activities and therapeutic relevance of E. crassipes in the management of degenerative diseases. Available evidence demonstrates that extracts and bioactive compounds derived from E. crassipes exhibit significant antioxidant, anti-inflammatory, neuroprotective, antidiabetic and antihypertensive activities through multiple mechanisms including free radical scavenging, inhibition of acetylcholinesterase, α-glucosidase and angiotensin-converting enzyme, suppression of pro-inflammatory mediators and modulation of oxidative stress pathways. Preclinical studies involving in vitro antioxidant and enzyme inhibitory assays, cell-based investigations and animal models of oxidative stress, neurodegeneration and diabetes have further supported the therapeutic potential of the plant. The review also discusses the sustainable biomedical valorization of E. crassipes within a circular bioeconomy framework. Proposed strategies include invasive biomass harvesting, phytochemical extraction, bioactive compound isolation, nutraceutical and phytopharmaceutical development, environmental remediation and conversion into value-added functional products. Despite encouraging preclinical findings, important challenges remain regarding bioavailability, phytochemical standardization, toxicological profiling, pharmacokinetics, clinical validation and regulatory approval. Future studies integrating advanced extraction technologies, nanoformulation approaches, translational pharmacology and clinical investigations will be essential for transforming E. crassipes from an environmental nuisance into a safe, sustainable and clinically relevant biomedical resource.
Roughly one-fourth of all cancers world-wide are gastrointestinal (GI) cancers. The symptoms and outcomes of each type of GI cancer vary across individuals and depend on multiple factors, including the affected organs, affected individual’s age and gender, and dietary habits. Although there has been some progress in the way GI cancers are managed, there is still a great need for developing new treatment approaches through a better understanding of the underlying disease biology and treatment mechanisms of action. Phytochemicals are naturally occurring compounds obtained from plants and are known to affect cells, including various cancerous and healthy cells of the gastrointestinal system. Phytochemicals often affect molecular pathways of carcinogenesis in a highly context-dependent manner, and a clearer understanding of the involved mechanisms is needed for developing effective new cancer treatment modalities. The objective of this thematic review is to contextualize the existing literature and present a novel paradigm for studying how oncogenic molecular pathways in gastrointestinal (GI) cancers are affected by various phytochemicals found in select plants that are commonly used in traditional Indian ayurvedic practice. We have outlined an inter-disciplinary theoretical framework for identifying and addressing the current gaps in knowledge regarding the effectiveness of ayurvedic modalities for various GI cancers.
Overview Oxidative stress is a primary driver of acetaminophen (APAP) hepatotoxicity during an overdose. This study evaluated the protective potential of Naringenin (NGN), a citrus-derived flavonoid, against a toxic dose of APAP. Male Sprague-Dawley rats were pre-treated with NGN at doses of 50, 75, and 100 mg/kg before the administration of 600 mg/kg of APAP. Silymarin was utilized as a positive control. Biochemical restoration NRN treatment resulted in a significant, dose-dependent reduction in ALT, AST, and ALP levels. ALT recovery As the dosage increased, ALT levels improved from 27.50 to 24.50 U/L. The 100 mg/kg dose effectively restored ALT to the normal baseline of 25.0 U/L. Protein synthesis NGN prevented the characteristic albumin depletion, maintaining albumin levels between 3.75 and 3.90 g/dL, values statistically comparable to the healthy control group. Antioxidant and Oxidative Stress Profiles: NGN demonstrated a robust capacity to neutralize oxidative damage, with the 100 mg/kg dose acting as the most effective concentration. Enzymatic defense At the highest dose, SOD (40.70), TAC (65.70), and GST (38.90) levels were statistically indistinguishable from those of healthy rats. Lipid peroxidation All NGN dosages successfully reduced MDA levels (a marker of cellular oxidative damage) to within normal ranges. Anti-inflammatory and anti-apoptotic mechanisms The 100 mg/kg dose significantly modulated the molecular pathways responsible for cell death and inflammation: Immunoreactivity There was a profound decrease in COX-2 (94.17%) and caspase-3 (98.19%) expression. Furthermore, only mild immunoreactivity for IL-6 and VEGF was observed in a limited number of hepatocytes. Gene and Protein Expression: Western blot and mRNA analysis revealed that NGN significantly downregulated Bax, P53, TLR2, and TLR4, while supporting the expression of the anti-apoptotic protein Bcl2. Conclusion In summary, Naringenin exerts a potent hepatoprotective effect against APAP-induced acute liver injury. It achieves this by mitigating oxidative stress, inhibiting pro-inflammatory and apoptotic signaling pathways (TLRs/Caspase-3), and bolstering the endogenous antioxidant defense system to promote tissue regeneration.
Background Intestinal ischemia-reperfusion injury (IIRI) is a severe disorder which spreads beyond the intestine, triggering secondary injury to organs like the kidney as a result of mucosal barrier disruption, bacterial and endotoxin translocation. Basella alba, which has traditionally been utilized to treat gastrointestinal disorders, ulcers, wounds, kidney stone, diuresis, urinary tract infections, inflammation, and oxidative stress-related ailments, could be effective to prevent kidney damage. This current research investigated the preventive effects of methanolic leaf extract B. alba (MLEBA) on renal injury in rats after IIRI. Methods Thirty rats were divided into five groups: sham-operated, IIRI alone, two groups pretreated orally with 100 and 200 mg/kg dosages of MLEBA respectively, and a group pretreated with vitamin C (200 mg/kg) for two weeks before IIRI induction. Kidney function indices, oxidative stress and inflammatory markers, apoptotic indices, and histopathological changes were investigated. Results IIRI elevated serum creatinine, urea, malondialdehyde, myeloperoxidase, interleukin-6, interleukin-1β and TNF-α, while decreasing total protein and antioxidant enzyme activities. Caspase-1, -3, and -9 levels increased significantly. High-dose MLEBA markedly improved renal function, enhanced antioxidant enzyme activity, reduced levels of inflammatory mediators, and suppressed apoptosis, effects comparable to those of vitamin C treatment. Histology confirmed preserved renal architecture in treated groups Conclusion Basella alba leaf extract provides significant renoprotection against IIRI-induced renal injury, most likely by ameliorating inflammatory processes, oxidative stress, and apoptosis supporting its ethnomedicinal value for renal protection.
Objective: To identify and experimentally validate anti-inflammatory phytochemicals from Thai medicinal plants and to examine the relationship between in silico target prediction, enzymatic inhibition, and cellular activity. Methods: A systematic review was performed to identify Thai medicinal plants with documented traditional applications in the treatment of inflammatory conditions. Phytochemicals identified in the selected species were assessed via molecular docking simulations against critical enzymes involved in inflammation, specifically cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), xanthine oxidase (XOD), and inducible nitric oxide synthase (iNOS). Subsequent analyses of the selected compounds encompassed enzyme inhibition assays, molecular dynamics simulations, and cellular assays utilizing lipopolysaccharide-stimulated RAW 264.7 macrophages. Network pharmacology analysis was subsequently performed to explore pathway-level mechanisms associated with observed cellular effects. Results: Triptocalline A (TRP) and daphnoretin (DAP) were prioritized based on docking profiles and target coverage. Despite favorable predicted binding affinities, both compounds exhibited weak direct enzyme inhibition. Molecular dynamics simulations revealed target-dependent interaction stability but did not fully account for biochemical outcomes. In contrast, TRP demonstrated significant cellular anti-inflammatory activity by reducing nitric oxide (NO) production and suppressing iNOS expression at non-cytotoxic concentrations, whereas DAP showed limited effects. Network pharmacology analysis revealed that TRP-associated targets were enriched in immune- and cytokine-related signaling processes, including pathways linked to MAPK activation and interleukin-mediated responses, supporting a role for pathway-level modulation. Conclusions: This study demonstrates a clear disconnect between docking-predicted affinity and functional biological activity for complex phytochemicals. The findings highlight that anti-inflammatory effects of TRP are primarily mediated through pathway-level regulation, particularly involving the iNOS–NO axis, rather than direct enzymatic inhibition. Integrating computational, biochemical, cellular, and network-based analyses provides a more reliable framework for interpreting phytochemical activity and prioritizing bioactive compounds from traditional medicinal sources.
Breastfeeding remains the most reliable and sustainable source of nutrition for infants. However, insufficient milk production in postpartum mothers often necessitates the use of lactogenic agents. Pentadiplandra brazzeana Baill root (“osumada’’) has traditionally been used to stimulate lactation, although scientific evidence remains limited. This study investigated the effect of P. brazzeana root-supplemented diet (PBRSD) on selected lactogenic markers in postpartum female Wistar rats. Thirty rats were divided into six groups: Group I- non-pregnant rats fed a basal diet, Group II-lactating rats fed a basal diet (control), Group III- positive control diet (100 g/kg Trigonella foenum-graecum), Groups IV, V, and VI- PBRSD test diets at 50, 100, and 200 g/kg respectively. Serum levels of general estrogen, prolactin, oxytocin, follicle-stimulating hormone (FSH), and immunoglobulins A and G were determined using enzyme-linked immunosorbent assay. Expression of Alpha-2-glycoprotein 1, zinc-binding (Azgp1) gene was evaluated using quantitative real-time polymerase chain reaction. Data were analyzed using descriptive and inferential statistics at 5% significance level. PBRSD significantly increased (p< 0.05), estrogen, prolactin, oxytocin, FSH, and immunoglobulin G levels, while the weight and immunoglobulin A decreased compared with controls. Furthermore, PBRSD significantly upregulated (p < 0.05) Azgp1 (0.07 ± 0.04 in control to 1.15 ± 0.05 in treated rats) gene expression. These findings suggest that PBRSD positively influenced the selected lactogenic biomarkers— hormonal and immunological parameters, and Azgp1 gene expression—in postpartum Wistar rats. However, further studies measuring actual milk production are required to confirm its lactogenic efficacy.
Background Flavonoids are postulated to modulate the complex pathophysiological mechanisms underlying atrial fibrillation (AF), the most prevalent cardiac arrhythmia driven by an interplay of structural, electrical, and inflammatory processes. Current management strategies for AF primarily involve rhythm control procedures and pharmacological interventions, but emerging evidence suggests that flavonoid intake may offer adjunctive benefits owing to their antioxidant, anti-inflammatory, and anti-arrhythmic properties. Purpose While preclinical studies demonstrate promising effects on atrial remodeling and arrhythmogenesis, clinical data remain limited and heterogeneous. To this end, flavonoids remain underexplored, and their multifactorial actions on cardiac physiology warrant further investigation. Study design : This is a comprehensive review that synthesizes current preclinical and clinical evidence regarding the role of dietary flavonoids in the prevention and management of atrial fibrillation (AF). Methods We systematically surveyed and critically appraised recent literature on the mechanistic actions, efficacy, and safety of flavonoid subclasses in AF, as demonstrated in both experimental models and human studies. Results : Preclinical studies consistently demonstrate that flavonoids exert antioxidant, anti-inflammatory, and anti-arrhythmic effects, attenuating atrial fibrosis, modulating ion channel activity, and reducing arrhythmogenesis in experimental models of atrial fibrillation. However, available clinical data are limited and heterogeneous, with some observational studies suggesting a potential benefit of higher dietary flavonoid intake on AF risk, but robust evidence from randomized controlled trials is lacking. Conclusion clinical evidence remains limited and heterogeneous, underscoring the need for large-scale randomized trials to establish the therapeutic potential of flavonoids in AF.
Plant-derived natural products possess diverse pharmacological activities but their clinical translation is often limited by poor aqueous solubility, instability, low permeability, rapid clearance, and consequently low bioavailability. Mucoadhesive Drug Delivery Systems (MDDS) have emerged as a promising strategy to overcome these biopharmaceutical challenges by prolonging residence time at mucosal surfaces, enhancing absorption, enabling site-specific and controlled drug release, and improving therapeutic efficacy. This review provides a comprehensive overview of MDDS designed for plant-based natural products, covering fundamental mechanisms of mucoadhesion, types of mucoadhesive polymers, formulation approaches, routes of administration, and analytical strategies for characterization. Key delivery platforms, including Nanoparticles (NPs), liposomes, lipid-polymer hybrid systems, hydrogels, microspheres, and mucoadhesive films, are discussed in relation to their ability to enhance the pharmacokinetic and pharmacodynamic performance of phytochemicals. The review also summarizes current clinical trials, patented technologies, and commercially available products incorporating natural bioactives into mucoadhesive systems. Despite significant advances, challenges remain, including physicochemical variability of natural compounds, stability concerns, polymer selection, scale-up difficulties, and regulatory barriers. Emerging strategies such as thiolated polymers, stimuli-responsive systems, smart lipid-based carriers, advanced analytical tools, and AI-assisted formulation design offer new opportunities to further optimize MDDS for natural products. Overall, MDDS represent a versatile and translational platform capable of unlocking the therapeutic potential of phytochemicals and facilitating their progression from bench to clinical application.
