ETHNOPHARMACOLOGICAL RELEVANCE:Propolis is a honey bee-derived resinous substance used in traditional medicine across many cultures to treat inflammatory and immune-related ailments. Its documented anti-inflammatory and immunomodulatory actions suggest potential value in autoimmune disease, yet its effects in type 1 diabetes (T1D) have not been examined. AIM OF THE STUDY:To investigate whether dietary propolis modulates immune responses and alters the progression of autoimmune diabetes in non-obese diabetic (NOD) mice. MATERIALS AND METHODS:Female NOD mice (n = 66) received standard chow or chow supplemented with 1.8% or 3.6% (w/w) raw Danish propolis from 4 to 30 weeks of age. Diabetes incidence was monitored longitudinally. At 14 weeks, pancreatic insulitis, T cell subsets in pancreatic lymph nodes and spleen, serum cytokines, and gut microbiota composition were assessed. RESULTS:Propolis delayed diabetes onset, significantly reducing incidence at 17 weeks, although cumulative incidence converged by 30 weeks. High-dose propolis reduced pancreatic immune infiltration and decreased CD4+ T helper cells in pancreatic lymph nodes, with a non-significant trend toward increased splenic T cell counts. Serum IL-10 and IFN-γ were elevated, while IL-4 was reduced. Akkermansia muciniphila abundance was increased. CONCLUSIONS:Dietary propolis delayed autoimmune diabetes onset in NOD mice, although cumulative incidence converged by the end of the study, and was associated with changes in immune parameters and gut microbiota composition. These findings support further investigation of propolis as a candidate for modulating disease progression in autoimmune T1D, though the underlying mechanisms remain to be established.
ETHNOPHARMACOLOGICAL RELEVANCE:Morinda officinalis Radix (MOR), a traditional Chinese medicinal herb used as both medicine and food, has long been used to tonify kidney function and has attracted increasing attention for its potential benefits in bone metabolic disorders. AIM OF THE STUDY:This review provides a comprehensive and up-to-date overview of the ethnopharmacological applications, phytochemistry, pharmacological activities, pharmacokinetics, safety profile, and quality control of MOR in the prevention and treatment of osteoporosis. MATERIALS AND METHODS:A systematic literature search was conducted in Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), and the National Science and Technology Library (NSTL). Studies on the traditional applications, clinical effects, phytochemistey, pharmacology, pharmacokinetics, toxicology, and quality control of MOR in relation to osteoporosis were included. After screening, 215 eligible publications were analyzed. RESULTS:In Traditional Chinese Medicine, MOR is believed to exert anti-osteoporotic effects by regulating kidney and liver functions. Eleven clinical trials, mainly involving herbal combinations, reported beneficial effects in patients with primary osteoporosis, with on evident adverse reactions. More than 190 compounds have been identified in MOR, with polysaccharides, iridoids, and anthraquinones as the major constituents and priority candidate quality markers. Experimental studies indicate that extracts and active compounds improve bone homeostasis by modulating osteoblast-osteoclast coupling. Pharmacokinetic evidence suggests wide tissue distribution after oral administration, influenced by sex and processing methods. Toxicological evaluations demonstrate a generally favorable safety profile. CONCLUSION:MOR exhibits multi-targeted anti-osteoporotic effects with promising therapeutic potential. Future research should emphasize well-designed clinical trials of MOR monotherapy, integrated multi-omics approaches, and develop advanced delivery systems to facilitate clinical translation and drug development.
ETHNOPHARMACOLOGICAL RELEVANCE:Chaenomeles speciosa (Sweet) Nakai, a traditional remedy for "Bi-syndrome", possesses potent anti-inflammatory and analgesic activities. It is widely utilized in Traditional Chinese Medicine (TCM) and ethnic medical systems of Mongolian, Tibetan, and Miao nationalities. AIM OF THE STUDY:However, in practical application, Chaenomeles speciosa is frequently confused with its related species Chaenomeles sinensis. This study aims to establish a holistic strategy to screen and validate Quality Markers (Q-markers) for Chaenomeles speciosa by integrating metabolomics, GNPS-guided isolation, and in vivo anti-inflammatory assay. MATERIALS AND METHODS:Initially, a plant metabolomics strategy was employed to screen differential markers. Then, GNPS molecular networking was utilized for the targeted isolation of differential markers from the core active fractions. Next, the anti-inflammatory effects of candidates from Chaenomeles speciosa on LPS-induced Tg(fli1:EGFP) zebrafish were evaluated by confocal microscopy and assessment of inflammatory factor levels. Finally, the selected Q-markers were quantified across 26 batches using a validated HPLC method. RESULTS:A total of 134 components were characterized, with 15 differential markers prioritized to distinguish Chaenomeles speciosa from Chaenomeles sinensis. GNPS-guided targeted isolation successfully yielded 9 of the 15 differential markers, along with 8 additional constituents. Zebrafish screening identified oleanolic acid, chlorogenic acid, procyanidin B1, (-)-epicatechin, naringenin chalcone, apigenin, and diosmetin as potential Q-markers. The established HPLC method proved rapid and robust for routine quality control across 26 batches of Chaenomeles speciosa.
Aim of the study The present study aimed to evaluate the gastroprotective effects of Berberine Sulphate against ethanol-induced gastric ulceration in BALB/c mice and to investigate the underlying antioxidant and anti-inflammatory mechanisms. Materials and methods Thirty-six male BALB/c mice were randomly allocated into six experimental groups. Berberine Sulphate (10, 20, and 40 mg/kg) and omeprazole (20 mg/kg) were orally administered for four consecutive days before induction of gastric ulcer using a single oral administration of 75% ethanol (0.2 mL/animal). Gastric pH, total acid secretion, ulcer index, histopathological alterations, antioxidant biomarkers (GSH and SOD), and inflammatory gene expression (TNF-α, IL-1β, IL-6, and NF-κB) were subsequently evaluated. Results Results have shown that Berberine Sulphate has a significant gastroprotective effect in maintaining the anatomical vasculature of the stomach at the highest doses. The Berberine Sulphate groups demonstrated a dose-dependent increase in gastric pH with the highest Berberine Sulphate (6.87-6.95), reflecting its potent acid-suppressing effects. Berberine Sulphate also significantly restored antioxidant enzyme levels (GSH and SOD) and suppressed pro-inflammatory gene expression (TNF-α, IL-1β, IL-6, and NF-κB) in a dose-dependent manner. These pH, acid content, and ulcer score results correlate with the histopathological and gross anatomy findings, confirming the protective role of Berberine Sulphate in maintaining gastric mucosal integrity. Conclusion Our findings have suggested that Berberine Sulphate can be a potential candidate for the treatment of acute heavy ethanol-induced gastric ulcers. Although the findings provide comprehensive mechanistic evidence for the gastroprotective effects of Berberine Sulphate, further studies incorporating protein-level validation, additional oxidative stress biomarkers, and quantitative histopathological assessment are required.
ETHNOPHARMACOLOGICAL RELEVANCE:Products derived from Santalum species have been valued for centuries in religious practices and traditional Chinese and Indian medicine for treating various conditions, including inflammatory and skin disorders. AIM OF THE STUDY:This study investigated the impact of two essential oils, S. album L. and S. spicatum (R.Br.) A.DC. on bacterial isolates obtained from skin samples, as well as their impact on mammalian cells and enzymes involved in the eicosanoid cascade. MATERIALS AND METHODS:Chemical composition was analyzed by GC-MS. Antibacterial activity against clinical isolates was assessed by broth microdilution to determine minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC). Cytotoxicity in HaCaT and HFF-1 cells was evaluated using the MTT and ROS assays. Inhibition of 5-lipoxygenase (5-LOX), cyclooxygenase (COX), and phospholipase A2 (PLA2) was also determined. RESULTS:α-Santalol and β-santalol were identified in both essential oils, with higher relative abundance in S. album. Both oils were active against Gram-positive isolates, with MIC values of 15.625-62.5 μg mL-1 and MBC values of 31.25-125 μg mL-1, showing bactericidal activity. No evident cytotoxicity and inhibition of ROS was observed below 500 μg mL-1. Both oils inhibited 5-LOX (S. album, 82.29 ± 8.85 μg mL-1; S. spicatum, 121.33 ± 52.03 μg mL-1) and PLA2 (100.12 ± 41.36 and 114.21 ± 17.25 μg mL-1, respectively), while S. spicatum also showed COX inhibitory activity. CONCLUSIONS:These findings demonstrate in vitro antibacterial activity against Gram-positive clinical isolates and modulation of eicosanoid-related enzymes, supporting further investigation of the biological relevance of both essential oils in inflammatory processes.
ETHNOPHARMACOLOGICAL RELEVANCE:Zhigancao Decoction (ZGCT), also known as Fumai Decoction, is a classical traditional Chinese medicine formula recorded in Shanghan Lun and has long been used for the treatment of "palpitations" and "irregular pulse," corresponding to arrhythmias in modern medicine. Although ZGCT has shown beneficial effects against cardiac arrhythmias, its absorbed bioactive constituents and the underlying mechanisms involved in ischemic heart failure (IHF)-related ventricular arrhythmias (VAs) remain unclear. AIM OF THE STUDY:This study aimed to characterize the chemical profile of ZGCT and identify its circulating and cardiac constituents using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), to identify key pathways through transcriptomic analysis, and evaluate the effects of ZGCT on IHF-related VAs in rats while exploring the potential involvement of myocardial fibrosis and TGF-β/Smad signaling. MATERIALS AND METHODS:UPLC-Q-TOF-MS was employed to characterize the chemical constituents of ZGCT extract and to identify its absorbed components in rat serum and myocardial tissue after administration, thereby defining its in vivo bioactive basis. RNA sequencing (RNA-seq)-based transcriptomic profiling was then performed on myocardial tissues from the control, model, and ZGCT-treated groups to identify differentially expressed genes, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to screen candidate signaling pathways underlying ZGCT activity. In addition, a rat model of IHF was established by permanent ligation of the left anterior descending coronary artery. Rats were randomly assigned to the control, model, low-, medium-, and high-dose ZGCT, metoprolol, SB-431542(a selective TGF-β receptor type I inhibitor), and SB-431542 plus ZGCT groups. Cardiac function was evaluated by echocardiography; ventricular arrhythmia susceptibility, conduction velocity, and electrical conduction dispersion were assessed by burst pacing and multichannel electrical mapping; infarct size and myocardial fibrosis were determined by 2,3,5-triphenyltetrazolium chloride (TTC), hematoxylin and eosin (H&E), and Masson's trichrome staining; and the expression of TGF-β1, phosphorylated Smad3 (p-Smad3), Smad7, and matrix metalloproteinase 2 (MMP2) was measured by Western blotting and RT-qPCR. RESULTS:UPLC-Q-TOF-MS identified 113 constituents in the ZGCT extract in vitro, of which 80 were detected in serum and 53 were distributed in myocardial tissue after administration. Transcriptomic analysis revealed that ZGCT predominantly regulated the extracellular matrix (ECM)-receptor interaction and TGF-β signaling pathways, with the TGF-β pathway emerging as a putative key target. In IHF rats, ZGCT significantly improved cardiac function and reduced both the incidence and duration of ventricular arrhythmias. Multichannel electrical mapping further demonstrated that ZGCT reversed IHF-induced slowing of conduction velocity and increased conduction dispersion. Mechanistically, ZGCT downregulated the expression of TGF-β1, p-Smad3, and MMP2, while upregulating Smad7. SB-431542 elicited anti-fibrotic and pathway-related molecular changes comparable to those of ZGCT, further supporting a role for TGF-β/Smad signaling in the anti-fibrotic effects of ZGCT. CONCLUSIONS:ZGCT reduced ventricular arrhythmia susceptibility and improved conduction abnormalities in IHF rats in association with attenuation of myocardial fibrosis and modulation of transforming growth factor-β/Smad-related signaling. However, these findings were obtained from a single batch of ZGCT, and further multi-batch validation is required to confirm its chemical consistency and pharmacological reproducibility.
ETHNOPHARMACOLOGICAL RELEVANCE:Xiaoqinglong Decoction (XQLD), a classic herbal formula for respiratory diseases, is clinically effective against chronic obstructive pulmonary disease (COPD). However, whether its anti-inflammatory effects involve modulation of macrophage immunometabolism remains unknown. AIM OF THE STUDY:This study investigated whether XQLD suppresses M1 macrophage polarization in COPD by modulating glycolysis-related pathways. MATERIALS AND METHODS:COPD was induced in rats by alternate intratracheal instillation of papain (Papa) and lipopolysaccharide (LPS). After modeling, the rats received XQLD at high, medium, and low doses, while a separate group received dexamethasone as the positive control. Therapeutic effects on pulmonary function and lung pathology were evaluated, along with M1 polarization by immunofluorescence and other assays. Core pathways were identified through transcriptomic-metabolomic integration. In vitro, XQLD-containing serum was used to treat THP-1-derived M1 macrophages, and M1 polarization, glycolytic indicators, and MET/AKT/HK2 pathway proteins were assessed following treatment with 2-DG, HK2 overexpression, or HGF. RESULTS:XQLD dose-dependently improved pulmonary function and lung pathology, and reduced M1 infiltration. Multi-omics identified MET and HK as central nodes; XQLD reversed aberrant MET/AKT/HK2 expression in vivo. In vitro, XQLD-containing serum inhibited M1 polarization, glycolytic flux, and HGF-induced MET/AKT/HK2 signaling, with its effects partially reversed by HK2 overexpression. CONCLUSION:XQLD attenuates M1 macrophage-driven airway inflammation by normalizing the MET/AKT/HK2 signaling-metabolic axis and suppressing, at least in part, HK2-dependent glycolysis. These findings provide a novel immunometabolic mechanism for the traditional anti-inflammatory efficacy of XQLD in COPD.
ETHNOPHARMACOLOGICAL RELEVANCE:Gancao Qinlian Granules (GQG) are a granulated formulation of the classical prescription Gancao Xiexin Tang, originally documented by Zhang Zhongjing in the Treatise on Febrile and Miscellaneous Diseases (Shang Han Za Bing Lun, c. 220 CE). This formula comprises six medicinal components: Glycyrrhiza glabra L. (Gancao), the radix of Scutellaria baicalensis Georgi (Huangqin), Ziziphus jujuba Mill. (Dazao), the rhizomes of Zingiber officinale Roscoe (Ganjiang), the dried tuber of Pinellia ternata (Thunb.) Breit (Banxia), and the rhizoma of Coptis chinensis Franch (Huanglian). GQG has been extensively employed in traditional and contemporary clinical practice for the treatment of ulcerative colitis (UC). Nevertheless, its candidate bioactive constituents and underlying mechanisms of action remain incompletely elucidated. AIM OF THE STUDY:To comprehensively characterize the chemical composition of GQG and elucidate its therapeutic mechanisms against UC through an integrated strategy combining network pharmacology prediction, serum/colon/fecal multi-omics profiling (metabolomics and microbiome), and experimental validation. MATERIALS AND METHODS:Initially, GQG was analyzed by UHPLC-Q-Exactive Orbitrap MS under negative/positive ion modes, with compound identification via mzCloud, HMDB, and literature matching. C57BL/6 mice (n = 8/group) were induced with UC using 3% dextran sulfate sodium (DSS) for 15 days. UC-related targets from GeneCard, PharmGkb, TTD, and OMIM were integrated to construct compound-target-pathway networks (Cytoscape 3.10.1). Secondly, GQG (9 g/kg/d, 12 g/kg/d, 15 g/kg/d) or mesalazine (300 mg/kg) was administered orally for 10 days. Disease severity was assessed daily via Disease Activity Index (DAI: weight loss, stool consistency, bleeding). Post-euthanasia, colon length was measured, and histopathology (H&E, Alcian Blue-Periodic Acid Schiff staining) analyzed mucosal damage and goblet cell depletion. Colon IL-1β levels were quantified by immunohistochemistry (IHC). Then, serum, fecal, and colonic tissue samples underwent UHPLC-Q-Exactive Orbitrap MS-based untargeted metabolomics. Differentially expressed metabolites (DEMs) were identified (VIP >1, p < 0.05) and pathways enriched via KEGG. Fecal 16S rDNA sequencing (Illumina NovaSeq) analyzed microbial α/β-diversity and differential taxa (LEfSe, LDA score >3). Subsequently, Integrated component analysis, network pharmacology, and metabolomics data to obtain the mechanism by which GQG improves UC, and verify the related target proteins through IHC and Western blot. Finally, obtain the candidate bioactive constituents in GQG through molecular docking, and verify the efficacy of these bioactive constituents with their targets on a cellular model. RESULTS:Chemical profiling revealed 121 constituents in GQG, with 53 flavonoids (43.8%) including core bioactive markers (e.g., licoflavone B, licuroside). In DSS-induced ulcerative colitis mice, GQG (12 g/kg/d) exerted potent therapeutic effects: reducing disease activity index, attenuating colon shortening, restoring goblet cells, and suppressing colon IL-1β. Mechanistically, GQG remodeled gut microbiota composition and function, increasing beneficial taxa (Muribaculaceae, Lactobacillus). This microbiota restructuring directly drove metabolic reprogramming. Suppression of pro-inflammatory metabolism: purine degradation (hypoxanthine), tryptophan-derived uremic toxins (kynurenine), pathogenic bile acids (deoxycholic acid). Integrative analysis of the microbiota-metabolite axis reveals that GQG extract can regulate the NF-κB/NLRP3 inflammasome cascade through p-NF-κB p65 expression, NLRP3 assembly (NLRP3, Caspase-1), and ASC speck formation. Combined with molecular docking, six key components in GQG exhibit high affinity for critical targets. In vitro cellular experiments demonstrate that these core candidate bioactive components effectively inhibit key targets within the target pathway. CONCLUSIONS:GQG ameliorates UC by modulating gut microbiota structure and function, restoring microbial co-metabolism (e.g., SCFA synthesis, bile acid homeostasis), and subsequently inhibiting the NF-κB/NLRP3 inflammasome axis. This integrated approach substantiates the ethnopharmacological application of GQG for UC.
ETHNOPHARMACOLOGICAL RELEVANCE:Curcuma phaeocaulis Valeton (Zingiberaceae) (henceforth referred to as C. phaeocaulis) is a medicinal plant. Its dried rhizome is one of three botanical sources officially recognised as Ezhu (Curcumae Rhizoma) in the Chinese Pharmacopoeia, the other two being C. kwangsiensis and C. wenyujin. The C. phaeocaulis rhizome (henceforth referred to as C. phaeocaulis rhizome) has a long history of use in traditional medicine for promoting qi circulation, dispelling blood stasis, removing food accumulation, and alleviating pain. The present review focuses on C. phaeocaulis due to the following reasons: it is the traditional Dao-di (geo-authentic) herb in Sichuan; it has the longest documented history of medicinal use among the three; and its vinegar processing has been mechanistically investigated in greater depth. The properties of this substance lend support to its clinical application for epigastric and abdominal pain, gynecological masses, and chest discomfort. AIM OF THE REVIEW:This review provides a comprehensive overview of the traditional uses, phytochemistry, pharmacology, and processing of the C. phaeocaulis rhizome, with an emphasis on the scientific basis of vinegar processing and future research directions. METHODS:A comprehensive literature search was conducted using major electronic databases (PubMed, Web of Science, CNKI, and Wanfang) up to May 2026, with search terms including "C. phaeocaulis", "Ezhu", and "vinegar processing". Further information was obtained from established texts including the Zhonghua Bencao and the Dictionary of Chinese Ethnic Medicine. RESULTS:The C. phaeocaulis rhizome is characterised by its warm properties, pungent flavour, and affinity for the Liver and Spleen meridians. The Sichuan province is renowned for its production of the material that is regarded as the Dao-di (geo-authentic) herb. In clinical practice, vinegar processing is commonly applied to enhance its therapeutic effects. Phytochemically speaking, the rhizome contains volatile oils, predominantly sesquiterpenoids, including curcumol, germacrone, and β-caryophyllene, while curcuminoids are present only in trace amounts. A plethora of pharmacological studies have demonstrated the following activities: antitumor, antiplatelet, anti-inflammatory, analgesic, and hepatoprotective. Mechanistic investigations of vinegar processing have revealed that it reduces and transforms volatile oil components; additionally, the acidic environment may help stabilise curcuminoids, an effect that may partly explain the enhanced analgesic, anti-inflammatory, and anticoagulant activities of the processed herb. DISCUSSION:Contemporary research on the C. phaeocaulis rhizome has evolved from documenting traditional applications to elucidating underlying mechanisms. Network pharmacology and bioinformatics have been increasingly applied to predict active targets and pathways. Nevertheless, the field still requires standardised methodologies and rigorous pharmacological validation. It is recommended that future studies concentrate on the identification of species-specific quality markers, the clarification of the in vivo metabolic fate of bioactive components, and the advancement of clinical translation, with particular emphasis on the treatment of chronic diseases and oncology.
ETHNOPHARMACOLOGICAL RELEVANCE:Diabetic retinopathy (DR), a predominant microvascular complication of diabetes mellitus, is pathologically characterized by endothelial dysfunction and blood-retinal barrier (BRB) disruption. Asiaticoside (AC), a bioactive phytochemical constituent derived from traditional Chinese medicinal herbs, has shown promising therapeutic potential against a spectrum of diabetic complications. Nevertheless, the explicit molecular targets and the detailed pharmacological mechanisms underlying the protective effects of this herbal ingredient against DR have not yet been fully elucidated. AIM OF THE STUDY:This study aimed to investigate the therapeutic effects and underlying mechanisms of AC in attenuating the progression of DR by targeting Cyclin D1 (CCND1) to negatively regulate the PI3K-AKT-mTOR pathway and activating mitophagy, thereby providing a promising therapeutic strategy for DR treatment. MATERIALS AND METHODS:C57BL/6J mice were utilized to establish diabetic mouse model via intraperitoneal injection of streptozotocin (STZ) then treated with AC. Human microvascular endothelial cells (HMECs) were exposed to high glucose (HG; 35 mM) to construct high-glucose model and treated with AC, mitophagy inhibitor 3-MA, mitophagy agonist CCCP and PI3K agonist 740-YP. Genetic knockdown via siRNA was performed to validate CCND1 effect on cellular senescence and mitophagy. The senescence level of retina, mice visual contrast sensitivity and retinal vascular leakage were evaluated by western blotting, immunofluorescence, OptoDrum eyes tracker system and evans blue staining respectively. Cell viability, cellular senescence, cell migratory capacity, apoptosis, mitophagy, mitochondrial morphology, mitochondrial function, and ultrastructural changes were assessed by CCK8 assays, wound-healing assay, western blotting, immunofluorescence, and transmission electron microscopy (TEM) respectively. RESULTS:AC treatment significantly lowered the visual contrast threshold by approximately 18% and reduced retinal vascular leakage in diabetic mice. In vitro, AC ameliorated high glucose-induced endothelial cell senescence, attenuated cellular and mitochondrial dysfunction as well as reactive oxygen species (ROS) production, and induced mitophagy. Bioinformatics analysis identified CCND1 as one of the key senescence-related genes upregulated in DR, AC intervention significantly inhibited its overexpression. Furthermore, knockdown of CCND1 recapitulated the protective effects of AC, enhancing mitophagy and suppressing senescence phenotypes. Mechanistically, AC treatment or CCND1 knockdown inhibited high glucose-induced activation of the PI3K-AKT-mTOR signaling pathway, while the PI3K agonist 740 YP completely reversed these beneficial effects of AC. CONCLUSION:We firstly revealed that AC attenuates DR progression by alleviating cellular senescence in HMECs by modulating CCND1. Notably, the present study is the first to explore the pathological role of CCND1 in DR beyond its classical cell-cycle regulatory function, which provides a novel and promising therapeutic target and intervention strategy for DR treatment.
ETHNOPHARMACOLOGICAL RELEVANCE:Cistus salviifolius L. (Cistaceae) has long been employed in Mediterranean traditional medicine for the topical treatment of skin disorders, including infections, wounds, and inflammatory conditions. Despite its recognized ethnobotanical relevance, its antidermatophytic potential remains insufficiently characterized. AIM OF THE STUDY:This study aimed to pharmacologically validate the traditional use of C. salviifolius against cutaneous fungal infections by evaluating the antifungal activity of a polyphenol-rich extract against dermatophytes, investigating its mechanism of action, and assessing its skin-protective properties in a reconstructed human epidermis (RHE) model. MATERIALS AND METHODS:Antifungal activity was determined by broth microdilution assays following EUCAST guidelines to establish minimum inhibitory and fungicidal concentrations. Ultrastructural alterations were examined by transmission electron microscopy (TEM). The extract was further evaluated in dermatophyte-infected RHE through fungal DNA quantification, transepithelial electrical resistance measurements, histological analysis, and cytokine release assays. Antioxidant activity and inhibition of extracellular matrix-degrading enzymes were also assessed. RESULTS:The extract showed selective fungicidal activity against dermatophytes, with MIC values of 78 mg/L against Trichophyton rubrum and Microsporum canis. TEM revealed severe cellular damage, including extensive vacuolization, membrane detachment, and cytoplasmic disorganization. In the RHE model, topical treatment reduced fungal burden, preserved epidermal barrier integrity, and attenuated IL-1α and IL-8 release, particularly against T. rubrum. Additionally, the extract displayed strong antioxidant activity and significantly inhibited collagenase, elastase, and hyaluronidase. CONCLUSIONS:These findings provide pharmacological support for the traditional use of C. salviifolius in skin infections and identify this polyphenol-rich extract as a promising multifunctional candidate for topical dermatophytosis management.
ETHNOPHARMACOLOGICAL RELEVANCE:Pearl powder has been used for centuries in Traditional Chinese Medicine for its detoxifying, regenerative, and anti-aging properties. This study evaluates the antioxidant efficacy and safety of pearl powder derived from Hong Kong pearl oysters (Pinctada imbricata). AIM OF THE STUDY:The present study aimed to perform a comprehensive multiscale physicochemical characterization of pearl powder and to investigate it's in vivo antioxidant activity and subacute oral toxicity in C57BL/6J mice. MATERIALS AND METHODS:The powder was characterized using Raman spectroscopy, high-resolution transmission electron microscopy (HR-TEM), atomic force microscopy (AFM), BET surface area analysis, and X-ray photoelectron spectroscopy (XPS). In vivo antioxidant activity was assessed in male C57BL/6J mice (n = 12 per group) administered pearl powder orally at 250, 500, and 1000 mg/kg body weight daily for 4 weeks using FRAP, TEAC, ORAC, and MDA assays. A 28-day subacute toxicity study was conducted according to OECD Guideline 407 (500-1000 mg/kg b.w., n = 5/sex/group). RESULTS:Dose-dependent increases in FRAP, TEAC, and ORAC, together with reduced MDA levels, were observed especially in liver, kidney, and spleen (p < 0.05 to p < 0.0001). The toxicity study showed no mortality, clinical signs, or histopathological changes. Minor non-adverse biochemical variations lacked supporting pathology, establishing a No Observed Adverse Effect Level (NOAEL) of 500 mg/kg b.w. CONCLUSION:These findings demonstrate pearl powder's potent antioxidant activity with a favourable safety profile, supporting its development as a natural therapeutic agent for oxidative stress-related conditions. Nonetheless, confirmation through clinical studies will be important to substantiate these preclinical observations.
ETHNOPHARMACOLOGICAL RELEVANCE:Helicteres ovata is a native Brazilian species belonging to a genus traditionally used for the treatment of inflammatory and pain-related disorders. However, its pharmacological studies remain scarce. AIM OF THE STUDY:This study investigated the phytochemical profile, inorganic composition, antinociceptive activity, and safety of a 60% hydroethanolic extract of Helicteres ovata in murine models of paclitaxel-induced neuropathic pain. MATERIALS AND METHODS:Phytochemical dereplication was performed using UPLC-ESI-TOF-MS/MS, and elemental analysis via ICP-MS. Antinociceptive effects were evaluated using hot plate and von Frey assays in paclitaxel-sensitized mice. Opioid and cannabinoid pathways involvement was assessed using naltrexone and AM251, respectively. TNF-α and CXCL-1 modulation was determined in central and peripheral tissues. Histological and morphometric analyses were conducted on the sciatic nerve and dorsal root ganglia. Cytotoxicity was assessed via the Artemia salina lethality assay, and acute oral toxicity was evaluated in BALB/c mice (2000 mg/kg). RESULTS:The extract contained flavonoids, xanthones, phenolic acids, and essential minerals including potassium, magnesium, and phosphorus. It reduced mechanical allodynia and thermal hyperalgesia in a dose-dependent manner. Its antinociceptive effect was attenuated by naltrexone and AM251, indicating opioid and cannabinoid pathways involvment. The extract modulated pro-inflammatory cytokine and preserved neural morphology. Moderate cytotoxicity was observed at 48 h in A. salina, but no adverse effects were detected in acute toxicity model. CONCLUSION:Helicteres ovata extract exhibits significant antiallodynic effect in chemotherapy-induced neuropathic pain, mediated by inflammatory and neuromodulatory pathways. It is well tolerated in vivo and holds promise as a phytotherapeutic candidate for neuropathic pain management.
Ethnopharmacological relevance Cinnamomum verum has been extensively utilized in both traditional medicinal practices and culinary preparations. Nevertheless, its safety profile concerning embryonic development remains inadequately documented. Aim of the study This study aimed to evaluate the embryotoxic potential and teratogenic effects of the Cinnamomum verum aqueous extract using the zebrafish (Danio rerio) embryo model. Materials and methods Zebrafish embryos were exposed to a concentration range of C. verum aqueous extract spanning 0.12 mg/mL to 8.0 mg/mL. Survival and hatching rates, morphometric parameters (eye area, total length, head dimensions, distance from mouth to anus), cardiac function (heart rate and heart area), yolk sac and swim bladder areas, spontaneous movements, and caudal fin regeneration were assessed. Results C. verum aqueous extract induced concentration-dependent embryotoxicity characterized by reduced hatching rates and increased mortality (median lethal concentration = 1.132 mg/mL at 96 h post-fertilization). Morphological abnormalities included impaired somatic and craniofacial development. Neurodevelopmental toxicity was evidenced by decreased ocular area, reduced interocular distance, and diminished spontaneous movement. No alterations in pigmentation were observed. Cardiac function exhibited changes at higher concentrations. In addition, increased yolk sac area and reduced swim bladder size were observed at concentrations near the lethality threshold. The capacity for caudal fin regeneration remained preserved. Conclusions The aqueous extract of C. verum exhibits concentration-dependent embryotoxicity and teratogenicity in zebrafish, affecting survival, morphological development, neuromuscular activity, and cardiac function. These findings suggest potential developmental risks and support further investigations into toxicity mechanisms and translational implications for vertebrate development.
ETHNOPHARMACOLOGICAL RELEVANCE:Platycodon grandiflorus (PG) is a traditional herb widely used for respiratory infections. Newcastle disease virus (NDV) is a highly contagious and devastating pathogen that causes severe economic losses to the poultry industry. Platycodin D (PD), a bioactive component of PG, has not been investigated for its antiviral activity against NDV. AIM OF THE STUDY:We investigated the antiviral activity of PD against NDV and elucidated its underlying host-targeted mechanisms. MATERIALS AND METHODS:The anti-NDV activity of PD was evaluated in vitro and in vivo. Transcriptomic and network pharmacology were employed to map PD-targeted pathways. Mechanistic dissection was achieved by examining MAPK signaling cascade, NLRP3 inflammasome assembly, inflammatory cytokine profiling, apoptosis regulation, and type I interferon response. RESULTS:PD significantly inhibited NDV replication in vitro and in vivo, reducing viral loads and tissue injury in infected chickens. Transcriptomic profiling combined with network pharmacology analysis identified inflammation-, apoptosis-, and interferon-related pathways as major targets of PD, with MAPK signaling emerging as a central regulatory node. Mechanistic studies demonstrated that PD suppressed NDV-induced activation of the MAPK pathway and NLRP3 inflammasome assembly, leading to decreased production of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and IL-18). In parallel, PD attenuated virus-induced apoptosis through upregulation of the anti-apoptotic protein Bcl-2. Moreover, PD enhanced antiviral immunity by promoting IFN-α/β expression and STAT1 phosphorylation. CONCLUSION:PD restricts NDV infection by coordinately modulating host inflammatory, apoptotic, and innate antiviral signaling pathways, supporting its potential as a host-targeted antiviral candidate for the control of Newcastle disease.
ETHNOPHARMACOLOGICAL RELEVANCE:Cimicifugae Rhizoma was used for the treatment of asthma in traditional Chinese medicine. The triterpenoid partition of Cimicifugae Rhizoma, named as 'Ximingting', is commercially used for perimenopausal syndrome. However, the anti-asthma constituents and mechanism of Cimicifugae Rhizoma, as well as the therapeutic effect of 'Ximingting' on asthma remain unknown. AIM OF THE STUDY:This study aims to illustrate anti-asthma constituents of Cimicifugae Rhizoma and 'Ximingting', and explore the underlying molecular mechanisms. MATERIALS AND METHODS:The ethyl acetate fraction of Cimicifugae Rhizoma extract (EAEC) was prepared accroding to the manufacturing process of 'Ximingting'. The chemical composition of EAEC were analyzed by UPLC-MS/MS. An ovalbumin (OVA)-induced asthma mouse model was used for evaluating the bioassay in vivo. Network pharmacology was adopted for predicting anti-asthmatic targets/pathways, validated by molecular docking, ELISA, Western blot, qRT-PCR, immunofluorescence, and flow cytometry. RESULTS:Fifty-eight constituents (mainly triterpenoids) were identified in EAEC. EAEC significantly attenuated OVA-induced airway inflammatory infiltration, reduced inflammatory cytokines, and restored Th1/Th2 balance in mice. Network pharmacology indicated that anti-asthmatic effect of EAEC was related to inflammation, oxidative stress, and T-cell differentiation. Further experiments demonstrated that EAEC activated Keap1-Nrf2 signaling to enhance antioxidant capacity, and inhibited STAT6 phosphorylation and GATA3 expression, thereby blocking CD4+ T cell differentiation into Th2 cells. CONCLUSION:Triterpenoids in Cimicifugae Rhizoma exert anti-asthmatic effects by activating Keap1-Nrf2 pathway against oxidative stress and regulating STAT6/GATA3 pathway to balance immunity. These findings reveal the anti-asthmatic mechanism of Cimicifugae Rhizoma and suggest the potential of 'Ximingting' for further anti-asthmatic investigation.
ETHNOPHARMACOLOGICAL RELEVANCE:Dendrobium nobile Lindl. (DNL), a traditional Chinese medicine used for over two millennia, is attached for nourishing Yin, clearing heat, and promote fluid production. Despite its hepatoprotective potential, the underlying mechanisms need to be further explored. AIM OF THE STUDY:This study aimed to investigate the protective effects and further elucidate the mechanisms of Dendrobium nobile Lindl. aqueous extract (DNAE) from two different geographical origins (Chishui and Haikou) against acute alcoholic liver injury (AALI) using an integrated approach, with a particular focus on the modulation of bile acid metabolism via the enterohepatic FXR signaling pathway. MATERIALS AND METHODS:In this study, an acute alcoholic liver injury (AALI) mouse model was established by a single intragastric administration of 53% alcohol, following 14 consecutive days of pretreatment with DNAE from Chishui or Haikou. Physiological and pathological changes were evaluated, and the hepatic BA profiles were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Chemical compositional differences between DNL from Chishui and Haikou were characterized by UPLC-Q/TOF-MS and GC. The expression levels of genes involved in BA synthesis and metabolism were measured in both liver and intestine by quantitative real-time PCR (qRT-PCR). Additionally, Fxr-knockout mice were employed to verify the role of FXR in the observed effects. RESULTS:DNAE from both Chishui and Haikou origins significantly ameliorated alcohol-induced physiological and pathological alterations. The chemical composition of DNL, particularly the profile of secondary metabolites and the content of dendrobine, remains largely consistent between Chishui and Haikou origins. DNAE restored the metabolic balance of hepatic BAs by reducing primary BAs (CA, CDCA, βMCA, αMCA) and secondary BAs (DCA, LCA). Notably, DNAE derived from Chishui exhibited a more pronounced regulatory effect, specifically in enhancing the abundance of taurine-conjugated BAs. Consistently, DNAE pretreatment upregulated the hepatic BA synthase genes Cyp8b1 and Cyp7a1, downregulated the BA metabolism-associated genes Fxr and Shp. In Fxr-knockout mice, DNAE treatment did not attenuate alcohol-induced liver injury. Interestingly, DNAE increased the expression of intestinal BA metabolism genes Fxr and Fgf15, triggered extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) signaling to downregulate Cyp7a1 expression and inhibits BA synthesis. CONCLUSION:DNAE from both Chishui and Haikou origins alleviates acute alcoholic liver injury in mice by modulating bile acid metabolism via the enterohepatic FXR signal pathway, with the Chishui origin showing a more potent regulatory effect on taurine-conjugated BA abundance.
ETHNOPHARMACOLOGICAL RELEVANCE:The Lamiaceae family, commonly known as the mint or sage family, comprises a vast group of aromatic medicinal plants with a global distribution and a deeply entrenched history in traditional medicine systems worldwide. This systematic review and meta-analysis investigated the effects of Lamiaceae plants on anthropometric indices in metabolic syndrome patients. MATERIALS AND METHODS:We searched PubMed, Scopus, ISI Web of Science, ProQuest, SID, and MagIran from inception to July 15, 2025, for RCTs evaluating Lamiaceae plants versus placebo in adults (≥18 years) with metabolic syndrome or related conditions (obesity, type 2 diabetes, dyslipidemia, nonalcoholic fatty liver disease). Two reviewers independently screened records, extracted data, and assessed risk of bias using the Cochrane RoB 2.0 tool. Random-effects meta-analyses were performed, with subgroup analyses by intervention duration (≤8 vs. >8 weeks), metabolic status, and Lamiaceae genus. Certainty of evidence was evaluated using NutriGrade. This review followed PRISMA 2020 guidelines and was pre-registered (PROSPERO: CRD420251051273). RESULTS:Twenty eligible RCTs (n = 2445 participants) met inclusion criteria. Using the Cochrane RoB 2.0 tool, 50% of studies had unclear allocation concealment, and 10% had high performance bias risk. Random-effects meta-analysis demonstrated statistically significant reductions in size-based indices (BMI, weight) and proxies of central adiposity (WC, WHR), while changes in direct body composition (BFM) were not significant. Both short-term (≤8 weeks) and long-term (>8 weeks) consumption of Lamiaceae reduced BMI, with effects on WC and weight primarily in overweight/obese individuals. Subgroup analyses revealed that specific genera within the Lamiaceae family, particularly Salvia and Zataria, were effective in reducing BMI and WC (only Salvia). Meta-regression analysis revealed no significant linear associations between intervention duration, metabolic status, or Lamiaceae genus and the anthropometric changes. The NutriGrade assessment rated the overall confidence in the meta-evidence as high for the pooled estimates of BMI and weight and moderate for WHR. CONCLUSION:Lamiaceae supplementation is associated with modest reductions in size-based and central adiposity indices (BMI, WC, WHR) in adults with metabolic syndrome; exploratory subgroup analyses suggested potential signals for Salvia and Zataria, though based on limited trials. However, current evidence is insufficient to demonstrate significant changes in BFM or benefits in patients with diabetes, likely due to limited trial numbers, short durations, and indirect measurement methods. Therefore, Lamiaceae may be considered a supportive adjunct within multicomponent lifestyle interventions.
ETHNOPHARMACOLOGICAL RELEVANCE:Cistanche deserticola Ma (Orobanchaceae), a widely used botanical drug in Traditional Chinese Medicine, is traditionally utilized to moisten the intestines and relieve constipation, particularly for senile and deficiency-induced constipation. AIM OF THE STUDY:To evaluate the restorative effects of C. deserticola (CD) aqueous extract on functional constipation (FC) and elucidate its multi-omic mechanisms mediated by the gut microbiota-short-chain fatty acid (SCFA)-host axis. MATERIALS AND METHODS:The CD extract was phytochemically characterized via UPLC-Q-TOF-MS/MS. Loperamide induced FC mice were treated with physiologically relevant doses of CD extract (369 and 615 mg/kg/day). Efficacy was assessed via phenotypic, biochemical, and histopathological evaluations. Mechanisms were explored integrating 16S rRNA sequencing, targeted SCFA metabolomics, and colonic transcriptomics. Fecal microbiota transplantation (FMT) was conducted to verify microbiota dependency. Key signaling networks were validated using Western blotting and immunofluorescence. RESULTS:CD administration significantly accelerated intestinal transit, repaired mucosal barriers, restored gastrointestinal hormones, and mitigated oxidative and inflammatory stress. Microbiome profiling demonstrated CD reversed dysbiosis by enriching beneficial SCFA-producers (e.g., Lachnospiraceae NK4A136 group), correspondingly elevating colonic propionate and butyrate. FMT confirmed these therapeutic effects were microbiota-driven. Transcriptomic and molecular validations revealed that CD-mediated microecological restoration reactivated the Integrin αL/p-FAK/Filamin C mechanotransduction cascade and PDGFC/SGK1 signaling pathways, thereby promoting focal adhesion and structural mucosal repair. CONCLUSIONS:CD alleviates FC by concurrently remodeling the gut microbiota, enhancing SCFA production, and reactivating colonic mechanotransductive tissue repair networks. This provides a robust scientific rationale for its traditional ethnopharmacological use in constipation management.
ETHNOPHARMACOLOGICAL RELEVANCE:Saw palmetto (Serenoa repens) extract (SPE) originated from Native American traditional medicine and is now globally consumed for benign prostatic hyperplasia. Despite its popularity, its real-world safety profile regarding rare events and potential interactions remains incompletely characterized. AIM OF THE STUDY:To evaluate post-marketing safety signals of SPE using the FDA Adverse Event Reporting System (FAERS) database and preliminarily explore molecular targets related to SPE-aspirin interactions. MATERIALS AND METHODS:FAERS reports (2004-2025) listing SPE as a suspect drug were analyzed. Disproportionality analyses (reporting odds ratio (ROR), proportional reporting ratio (PRR), empirical Bayes geometric mean (EBGM), and Bayesian Confidence Propagation Neural Network (BCPNN)) were performed to identify safety signals. Logistic regression assessed factors associated with the reporting of haemorrhage and mortality. Network toxicology investigated molecular targets linking SPE, aspirin, and haemorrhage. RESULTS:Among 634 reports, hepatobiliary and blood/lymphatic disorders emerged as significant signals. Frequent adverse events included pruritus, cholestasis, confusion, and eosinophilia. Multivariate analysis indicated that age ≥75 and concomitant aspirin were associated with significantly elevated reporting odds for haemorrhage (OR 3.89; 2.28) and fatal outcomes (OR 2.87; 7.26). Network analysis revealed 46 shared targets enriched in clinically relevant pathways, particularly arachidonic acid metabolism and platelet activation, suggesting a potential pharmacological overlap affecting haemostasis. CONCLUSIONS:Real-world data demonstrate significant disproportionate reporting of hepatobiliary and hematological events with SPE. The increased reporting frequency of haemorrhage and fatal outcomes in elderly aspirin users warrants clinical vigilance. These findings, alongside the potential targets identified in silico, suggest that concurrent use in high-risk populations requires careful monitoring.
