Coreopsis tinctoria Nutt. (commonly known as Kunlun snow chrysanthemum) is a traditional medicinal and edible plant distributed mainly in the high-altitude regions of Xinjiang, China. In traditional medical practices, the dried flower heads (capitula) of C. tinctoria have been widely consumed as an herbal tea for clearing heat, detoxifying, and alleviating inflammatory conditions. In traditional medical theory, the accumulation of "heat and toxins" is closely associated with skin disorders, oxidative damage, and premature aging. However, direct ethnobotanical evidence for its skin-specific or topical use remains limited. Therefore, the present study investigated the skin-protective potential of the dried flower heads of C. tinctoria as an ethnopharmacology-guided extension of its documented heat-clearing, detoxifying, and inflammation-related traditional uses. This study aimed to screen and identify active constituents from the dried flower heads of C. tinctoria and to evaluate their multi-target skin-protective activities related to melanogenesis, oxidative stress, and extracellular-matrix degradation, thereby providing pharmacological evidence for its potential skin-protective applications. A lysozyme-assisted ligand-fishing approach was established by immobilizing tyrosinase, elastase, and hyaluronidase onto lysozyme-modified filter paper to screen potential enzyme inhibitors from the dried flower extract. The isolated compounds were evaluated using α-MSH-induced B16 melanoma cells, UVB-induced HaCaT keratinocytes, and human dermal fibroblasts (HDFs). Western blot analysis, molecular docking, and network pharmacology were used to explore possible mechanisms and structure-related interactions. Fourteen compounds were successfully isolated and identified. In cell-free enzyme assays, quercetagetin-7-O-β-glucoside (2) and okanin (8) showed measurable tyrosinase inhibitory activity, with IC50 values of 78.3 ± 0.0 μM and 66.2 ± 0.4 μM, respectively. Naringenin (12) and luteolin (14) showed elastase inhibitory activity, with IC50 values of 162 μM and 143 μM, respectively. Compound 2 reduced melanin content in the α-MSH-treated B16 cells from 167% to 91.5%, compared to 100% of the untreated normal cells set as control group. Compound 8 exhibited strong radical-scavenging activity (for DPPH· IC50 = 4.23 μM). Several flavonoids also attenuated UVB-induced oxidative-stress-related changes in HaCaT cells and modulated photo-damage-related protein expression in HDFs. The identified multi-target enzyme inhibitors and bioactive flavonoids provide a material basis for the anti-photoaging properties of the flowers of C. tinctoria. These findings support an ethnopharmacology-guided extension of its traditional heat-clearing and detoxifying use into modern skin-protection research, while further studies are required to clarify compound uptake, skin permeability, and in vivo efficacy.
Rheumatoid arthritis (RA) is a systemic autoimmune disorder in which persistent synovitis drives progressive joint damage, often leading to functional limitation and a reduced quality of life. Caulophyllum robustum Maxim. (C. robustum) has long been used in traditional medicine to manage RA. Although increasing experimental evidence has demonstrated its therapeutic potential, relevant studies remain fragmented across various fields. This review aims to systematically integrate current knowledge on the ethnopharmacology, phytochemistry, pharmacokinetics, anti-RA pharmacological mechanisms, and applications of emerging technologies related to C. robustum. By synthesizing evidence across multiple disciplines, we seek to clarify its material basis, mechanistic rationale, and therapeutic relevance in RA, thereby providing guidance for future research and drug development. To compile evidence on C. robustum, we searched multiple databases (Web of Science, PubMed, Google Scholar, Baidu Scholar, and CNKI) and additionally consulted classical Chinese medical texts. To date, more than 100 compounds have been isolated and identified from C. robustum, among which triterpenoid saponins and alkaloids represent the principal bioactive constituents associated with anti-RA activity. Notably, saponin components exhibit interconversion and biotransformation behaviors in vivo. Pharmacokinetic studies indicate rapid absorption but relatively slow elimination of key active constituents. Mechanistically, C. robustum extracts and representative components exert anti-RA effects by suppressing inflammatory responses, attenuating synovial hyperplasia, inhibiting pannus formation, protecting bone integrity, and restoring immune homeostasis. These actions appear to involve coordinated regulation of several pathways, notably NF-κB, MAPK, JAK/STAT, and PI3K/Akt signaling. In addition, molecular docking, biomolecular interaction analyses, and multi-omics approaches provide further preclinical evidence that saponins and alkaloids from C. robustum interact with key targets, including HDACs and CD81. Through complementary, multi-target, and network-level regulation, these components collectively contribute to its anti-RA pharmacological activity. This review provides a comprehensive and integrated overview of C. robustum, systematically consolidating research progress across diverse disciplines. By identifying current knowledge gaps and unresolved issues, it highlights critical directions for future investigation. Notably, all current pharmacological evidence for C. robustum is drawn exclusively from preclinical studies, with human pharmacokinetic or clinical validation still urgently needed.
Imperata cylindrica is a perennial botanical drug with both ecological impacts and diverse utilization values. As a traditional Chinese medicine, its rhizome is widely applied in traditional medical systems of various countries, which can cool blood to arrest bleeding and clear away heat to induce diuresis. Modern research has isolated and characterized 141 chemical metabolites from Imperata cylindrica, mainly including flavonoids and triterpenoids. These metabolites have been associated with multiple bioactivities, including anti-inflammatory, antioxidant, and immunomodulatory effects, and many proprietary Chinese medicines containing its rhizome have been applied in clinical practice. Imperata cylindrica also shows good application prospects in food processing, agriculture and animal husbandry, and ecological restoration. However, current research is limited by insufficient characterization of active metabolites, inadequate studies on isolated metabolites, and a predominance of in vitro and preclinical evidence. In the future, efforts should focus on the in-depth development and pharmacological verification of active metabolites, improving the cell-animal experimental system, promoting industrial application in multiple fields, and counteracting its invasion status through resource utilization to achieve a win-win situation of ecology and economy.
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. 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. 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. 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. 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.
Prospero autumnale L. is a Mediterranean medicinal plant traditionally employed for inflammatory and neurological disorders. Nonetheless, its safety profile, toxicity, and application for treating inflammation and pain are yet to be comprehensively established. This investigation aimed to assess the bioactivity and toxicity of extracts derived from its aerial (AgP) and underground (UgP) parts. The phytochemical constituents of various P. autumnale extracts were analyzed using LC-MS/MS, and their phenolic content was quantified. The biological activities were evaluated through in vitro assays-including antioxidant, anti-inflammatory, acetylcholinesterase-inhibitory, and photoprotection assessments-and in vivo experiments, including evaluations of acute oral toxicity, anti-inflammatory, and analgesic effects. UgP extracts demonstrated significant antioxidant activity, with the methanolic extract exhibiting the highest reducing and superoxide scavenging capacities. Dichloromethane and ethyl acetate extracts performed exceptionally well in ABTS and DPPH assays. The aqueous extract from AgP exhibited noteworthy anti-inflammatory and analgesic effects, surpassing diclofenac in vitro and demonstrating efficacy in vivo. It also showed considerable acetylcholinesterase inhibition, while the ethyl acetate extract displayed high photoprotective potential. The acute toxicity was moderate (LD50: 300-400 mg/kg), indicating dose-dependent risks. LC-MS/MS analysis revealed diverse phenolics potentially contributing to both therapeutic and adverse effects. This research enhances the medicinal prospects of P. autumnale, provides new perspectives on plant utilization, and suggests its potential as a natural anti-inflammatory agent. However, due to moderate toxicity and dose-dependent effects, cautious application is advised. These findings underscore the importance of toxicological evaluation alongside bioactivity screening in ethnopharmacology to ensure safety.
Coronopus didymus (Brassicaceae) is a medicinal herb valued for its anti-inflammatory and hyperlipidemic properties; however, its antidiabetic potential remains entirely unexplored. Furthermore, despite the known therapeutic benefits of Azadirachta indica and the bioflavonoid quercetin, their evaluation in combination with C. didymus has never been investigated. To address this knowledge gap, this study pioneers the evaluation of C. didymus, A. indica, and quercetin-individually and as a novel combined formulation for the management of type 2 diabetes mellitus (T2DM). We employed an integrated approach utilizing in silico network pharmacology and molecular docking (targeting NOS3, AKT1, and PPARG), in vitro bioassays (antioxidant, α-amylase inhibition, hemolytic, and anticancer), and in vivo evaluation in streptozotocin-nicotinamide (STZ-NA)-induced diabetic mice. Network screening identified 100 overlapping targets between the quercetin and T2DM, prioritizing 15 key hub targets via protein-protein interaction and KEGG pathway enrichment analyses. Molecular docking confirmed strong binding affinities of the lead compounds to NOS3, AKT1, and PPARG. In vitro assays validated robust antioxidant, α-amylase inhibitory, and anticancer activities, while maintaining a safe hemolytic profile. In vivo trials demonstrated that while individual treatments effectively lowered blood glucose, the combined formulation exhibited superior hepatoprotective efficacy, profoundly reducing serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (p < 0.0001) toward baseline control levels compared to individual plant extracts, alongside enhancing serum antioxidants and ameliorating histopathological damage in hepatic and intestinal tissues. In conclusion, this study bridges a critical gap in ethnopharmacology by identifying the antidiabetic potential of C. didymus and demonstrating that its combination with A. indica and quercetin offers a potent, distinct hepatoprotective advantage, highlighting its potential as a targeted nutraceutical approach for managing T2DM and its associated hepatic complications.
Medicinal and edible plants are promising resources for low-toxicity therapeutics and precision nutrition. Lycium barbarum L. (goji berry), a quintessential medicine-food homologous herb with 2000 years of ethnopharmacological use, has attracted global attention. However, existing studies are limited by fruit-centric bias, lack of correlation between processing methods, component properties and bioactivities, and incomplete antitumor mechanistic understanding. This systematic review establishes a holistic research paradigm that integrates whole-plant resource utilization, processing-property-bioactivity associations, multi-target pharmacology, and clinical translation. We delineate tissue-specific distributions of core bioactives (polysaccharides, phenolics, carotenoids, alkaloids) and their synergistic networks underlying antioxidant, anti-inflammatory, hypoglycemic, and immunomodulatory effects. Critically, we systematically summarize preclinical evidence for the antitumor potential of goji berries, identifying four proposed non-overlapping cell death pathways (apoptosis, cell cycle arrest, ferroptosis, autophagy) and proposed unique roles in reversing multi-drug resistance, alleviating chemoradiotherapy toxicity, and serving as biocompatible nanocarriers, all of which remain predominantly at the preclinical stage. We further propose a three-stage evidence-based roadmap to address key translational bottlenecks. This review bridges the gap between traditional ethnopharmacology and modern precision nutrition, providing a scientific foundation for the sustainable development of the global goji berry industry.
The present ethnopharmacological study investigated the traditional medicinal uses of Alchemilla species distributed across different geobotanical regions of Azerbaijan. Field surveys were conducted in five mountainous regions of the country during 2024-2025, and ethnopharmacological data were collected from 125 informants through semi-structured interviews and questionnaire surveys. A total of 21 Alchemilla species belonging to the Rosaceae family were documented. Quantitative ethnobotanical indices, including Use Value (UV), Relative Frequency of Citation (RFC), Fidelity Level (FL), and Informant Consensus Factor (ICF), were applied to evaluate the ethnobotanical significance of the recorded species. The results revealed that Alchemilla species are mainly used for the treatment of digestive, hepatobiliary, respiratory, and skin disorders, as well as for the management of diabetes. The highest ICF value was recorded for antipyretic use (ICF = 1.00), whereas the greatest number of use reports was documented for digestive system disorders (Nur = 278). Alchemilla sericea, A. sericata, A. caucasica and A. grossheimii exhibited the highest UV and RFC values. The high quantitative ethnobotanical indices reflect the relative local importance of these species and the strong consensus among informants regarding their traditional medicinal uses. The findings demonstrate the important role of Alchemilla species in the traditional medicine of Azerbaijan and indicate that species with high ethnobotanical indices represent promising candidates for future phytochemical and pharmacological investigations.
Salvia miltiorrhiza Bunge (Danshen) is a renowned traditional Chinese medicine widely used to promote blood circulation, remove blood stasis, and treat cardiovascular disorders. Sodium danshensu (SDSS), the stabilized sodium salt of Danshen's major water-soluble bioactive constituent, has been well-documented to possess antioxidant, anti-inflammatory, and cardiovascular protective properties, underpinning its considerable clinical potential. Nevertheless, whether SDSS protects against oxidative stress-induced cellular injury and the associated vascular damage remains insufficiently defined. This study aimed to investigate whether SDSS alleviates oxidative stress-induced endothelial dysfunction and vascular injury and to clarify the involvement of the SIRT1/p53 signaling pathway. An oxidative stress-related vascular injury model was established in C57BL/6J mice by intraperitoneal injection of tert-butyl hydroperoxide (t-BHP), and an in vitro model of oxidative stress-induced cellular injury was induced by hydrogen peroxide (H2O2) in human umbilical vein endothelial cells (HUVECs). Aortic structural changes and senescence marker expression were assessed by Masson's trichrome staining and Western blotting, respectively. Cellular senescence, proliferation, and migration were evaluated using SA-β-Gal staining, EdU incorporation, and wound healing assay, respectively. Oxidative stress was assessed by measuring intracellular reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity, and the glutathione (GSH/GSSG) ratio. Mitochondrial function was assessed by measuring mitochondrial membrane potential (MMP), ATP content, mitochondrial morphology (Mito-Tracker staining), and mitophagy (LC3/TOMM20 co-localization). Apoptosis was measured by flow cytometry. The interaction between SDSS and SIRT1 was investigated using molecular docking, molecular dynamics (MD) simulations, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) assay. The involvement of the SIRT1/p53 pathway was further examined using SIRT1 siRNA knockdown, the SIRT1 inhibitor EX527, and the SIRT1 agonist SRT1720. In t-BHP-induced mice, SDSS attenuated aortic collagen deposition and p53/p21 expression. In H2O2-exposed HUVECs, SDSS alleviated cellular senescence-like changes, restored proliferation and migration, reduced ROS accumulation, preserved MMP and ATP levels, maintained mitochondrial morphology, enhanced LC3B/TOMM20 co-localization, and attenuated apoptosis, as evidenced by reduced early apoptotic rate, decreased BAX, and increased Bcl-2 expression. Molecular docking combined with MD simulations provided computational support for a potential stable interaction between SDSS and SIRT1. CETSA and DARTS assays further supported an interaction between SDSS and SIRT1 and indicated that SDSS may stabilize SIRT1 protein. SDSS increased SIRT1 expression and promoted p53 deacetylation. The protective effects of SDSS were comparable to those of the SIRT1 agonist SRT1720, whereas SIRT1 siRNA or EX527 treatment markedly weakened the protective effects of SDSS in vitro and in vivo, supporting a role for the SIRT1/p53 axis in mediating the protective response. SDSS alleviates oxidative stress-induced vascular injury and endothelial dysfunction, and that these protective effects are associated with activation of the SIRT1/p53 pathway. These results offer preliminary correlative evidence supporting the traditional use of Danshen in cardiovascular protection, and suggest that SDSS warrants further investigation as a candidate for oxidative stress-associated vascular dysfunction.
Xiegan-Liangxue-Jiedu decoction (XLJD) is an ethnopharmacological empirical prescription inherited from Gu's Surgery, a national intangible cultural heritage of Chinese ethnomedicine. Developed based on the classic TCM theory of Liver governing emotion, XLJD has been clinically used for centuries to treat psoriasis (PsO) via the principle of the TCM principle of "treating PsO from the Liver perspective", and has shown favorable efficacy in alleviating psychiatric comorbidities in psoriasis (PCP) by soothing the Liver and relieving emotional discomfort. To determine the therapeutic efficacy of XLJD and its potential mechanisms of action in PCP mice, and to reveal the modern pharmacological mechanism of the TCM theory of Liver governing emotion in the treatment of PCP. Mass spectrometry were used to elucidate XLJD's phytochemical profile and blood-absorbed components. The murine PCP model was established by exposure to CUMS and imiquimod. The efficacy of treating PsO was evaluated using PASI, HE staining, lymphocyte proliferation levels, cytokine levels, etc. Mental disorders were evaluated using the open field, elevated plus maze, and tail suspension tests. RNA-seq was performed to detect transcriptional changes in skin tissues, while lipidomics was applied to analyze serum lipids. Key genes and protein were validated using qPCR and Western-blotting, respectively. Acid sphingomyelinase (ASM) and M1/M2 microglia in the hippocampus were determined via immunofluorescence staining. Among the 142 compounds identified in XLJD, 21 were detected in the blood. XLJD significantly alleviated the severity of PsO-related indicators in PCP mice while ameliorating behavioral abnormalities and mitigating HPA axis hyperactivity. XLJD downregulated the transcription of genes involved in lipid metabolism and ameliorated abnormal sphingolipid (SP) metabolism. It inhibited lesions mediated by sphingosine-1-phosphate signaling in lesioned skin. In the hippocampus, XLJD reduced the proportion of M1 microglia and exerted potential neuroprotective effects by inhibiting ASM expression and activity. Based on the TCM theory of Liver governing emotion, XLJD alleviated PsO severity and improved associated mental dysfunctions concomitantly in PCP mice by regulating SP metabolism. This study verifies the scientific connotation of the ethnopharmacological principle of treating PsO from the Liver perspective and provides a new ethnopharmacological strategy for the clinical management of PCP.
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Caryocar coriaceum Wittm. (pequi) is traditionally used in Brazilian folk medicine to treat inflammatory and respiratory disorders. Its fixed oil exhibits antioxidant and anti-inflammatory properties, suggesting potential therapeutic applications in pulmonary diseases. To investigate the protective effects of Caryocar coriaceum fixed oil (CCFO) against e-cigarette aerosol-induced lung injury in mice. Twenty-four male Swiss mice were randomly assigned to four experimental groups (n = 6/group): control (GC; ambient air + vehicle), e-cigarette aerosol + vehicle (GFS), e-cigarette aerosol + 50 μL CCFO (GFP50), and e-cigarette aerosol + 100 μL CCFO (GFP100). Animals were exposed to e-cigarette aerosol for five consecutive days. Respiratory mechanics, bronchoalveolar lavage cellularity, oxidative stress biomarkers, arterial blood gases, morphometric and stereological parameters, collagen deposition, and lung histopathology were evaluated. E-cigarette aerosol exposure significantly impaired pulmonary function, increasing airway and tissue resistance and elastance while reducing static compliance, inspiratory capacity, and arterial oxygenation. These alterations were accompanied by inflammatory cell infiltration, oxidative stress, reduced mean linear intercept associated with increased septal volume density, alveolar septal thickening, edema, hemorrhage, and increased collagen deposition. CCFO treatment, particularly at 3,6 mg/kg, significantly attenuated these effects by improving respiratory mechanics and gas exchange, reducing leukocyte recruitment and oxidative stress markers, preserving lung architecture, and decreasing extracellular matrix deposition. Caryocar coriaceum fixed oil protected against e-cigarette aerosol-induced lung injury by attenuating inflammation and oxidative stress while preserving pulmonary structure and function in this acute murine model. These findings support the ethnopharmacological relevance of C. coriaceum and provide experimental evidence supporting further preclinical investigation of its potential for respiratory disorders associated with inhalation-induced lung injury.
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). 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. 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). 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. These findings demonstrate pearl powder's potent antioxidant activity with a favorable 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.
In South Africa, the Vhavenda tribe traditionally feed infants Tshiunza/Khongoḓoli, a very light, warm, and soft porridge prepared with medicinal plant concoctions. This practice is believed to prevent, manage, or treat various diseases and provide nutritional support. The aim of the study was to document the medicinal plants administered through soft porridge, including preparation methods and dosages for infant illnesses, among the Vhavenda tribe of Vhembe District, South Africa, and to determine the cytotoxicity of selected medicinal plants. Semi-structured interviews were conducted with caregivers, elderly women, and traditional healers. Cytotoxicity assay of five selected medicinal plants was conducted using the MTT assay on African monkey kidney cells (Vero cells). Seventy-two medicinal plants were documented, of which 38 were used in the preparation of Tshiunza/Khongoḓoli. Roots were the most frequently used plant part, and the dominant preparation method involved soaking plant material in water and using the extract to make the soft porridge. These plants were commonly used to treat fontanelle-related illnesses and stomach problems. Combretum molle R.Br. ex G.Don. and Gymnosporia buxifolia (L.) exhibited low cytotoxicity with IC50 of 476.7559 and 276.4863 μg/mL, respectively. This study provides novel ethnomedicinal evidence on medicinal plants administered through soft porridge, a culturally important infant-feeding practice among the Vhavenda people. However, the cytotoxicity of Combretum molle R.Br. ex G.Don. and Gymnosporia buxifolia (L.) underscores the need for further toxicological evaluation of medicinal plants used in infant foods, especially for infants under 3 months old, whose physiological and metabolic systems are still developing.
1-Deoxynojirimycin (DNJ), a naturally occurring alkaloid derived from mulberry leaves (Morus alba L.), is a powerful α-glucosidase inhibitor that has notable hypoglycemic effects. Nonetheless, the fundamental molecular mechanisms-especially diabetic cardiomyopathy (DCM)-are still not fully understood. This study sought to determine the cardioprotective effect of DNJ in diabetic cardiomyopathy and to elucidate the associated molecular mechanism. A high glucose-induced DCM model was established in H9C2 cells and db/db mice. DNJ was administered by gavage or coculture with cells. The molecular mechanism of DNJ activity and changes in the activity of the PI3K/AKT pathway were evaluated by echocardiography, tissue staining, transmission electron microscopy, fluorescence probes, biochemical kits, Western blotting, and transcriptome sequencing, and the pathway was verified by the use of inhibitors. In vivo tests initially demonstrated that DNJ may lower body weight and fasting blood glucose levels; enhance glucose tolerance and cardiac performance; diminish myocardial fibrosis, myocardial hypertrophy, and lipid accumulation; and reduce myocardial cell death in db/db mice. DNJ therapy improved the HG-induced reduction in H9C2 cell viability, reduced ROS levels, mitigated oxidative damage, and inhibited cell death. DNJ can restore HG-mediated suppression of ATP5B expression and ATP levels, potentially enhancing mitochondrial energy utilization. The therapeutic efficacy of DNJ may be contingent upon the PI3K/AKT pathway, underscoring its regulatory significance, particularly in mediating cellular responses to oxidative stress and promoting cell survival in H9C2 cells. Our preliminary findings suggest that DNJ may alleviate diabetic myocardial injury, possibly by triggering the PI3K/AKT pathway. This work offers a preliminary rationale for DNJ as a prospective treatment agent for DCM.
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. 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. 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 (9g/kg/d, 12g/kg/d, 15g/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. 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 (12g/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. 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.
Mulberry leaf (Morus alba L.) has long been used in traditional Chinese medicine for treating "Xiaoke" (diabetes), as documented in "Compendium of Materia Medica" compiled by Li Shi-Zhen of the Ming Dynasty. Mulberry leaf flavonoids (MLF) are the major active components and have demonstrated anti-diabetic effects in modern studies. However, whether MLF alleviates type 2 diabetes mellitus (T2DM) by modulating the gut microbiota-bile acid axis and directly activating key metabolic receptors such as FXR remains unclear. This study aimed to investigate whether MLF ameliorates T2DM through remodeling the gut microbiota-bile acid axis and activating FXR signaling, and to identify potential flavonoid constituents within MLF that directly interact with FXR. db/db mice were treated with low- or high-dose MLF (300 or 600 mg/kg/day) or metformin for 10 weeks. Blood glucose, insulin sensitivity, lipid profiles, and hepatic pathology were assessed. Gut microbiota composition was analyzed by 16S rRNA sequencing, and bile acid profiles in serum, liver, ileum, and feces were quantified by targeted metabolomics. The expression of FXR/TGR5 signaling pathway components was determined by qRT-PCR and Western blot. Molecular docking was performed to screen for potential FXR modulator among MLF constituents, followed by in vitro validation using HepG2 and Caco-2 cells. MLF treatment significantly reduced fasting blood glucose, improved glucose tolerance and insulin resistance, lowered serum and hepatic lipid levels, and alleviated hepatic steatosis in db/db mice. MLF reshaped the gut microbiota by increasing beneficial genera (e.g., Alloprevotella, Roseburia) and decreasing the Firmicutes/Bacteroidetes ratio. Concurrently, MLF reprogrammed bile acid profiles across multiple organs, elevating non-12-OH bile acids (e.g., CDCA) and reducing the FXR antagonist Tβ-MCA, thereby activating intestinal and hepatic FXR/TGR5 signaling, upregulating FGF15 and SHP, and increasing serum GLP-1. Molecular docking identified Morusin as a candidate FXR ligand, and in vitro assays confirmed that both MLF and Morusin activated FXR and modulated downstream targets (BSEP, NTCP, ASBT, CYP7A1) in hepatocytes and intestinal cells. MLF alleviates T2DM by remodeling the gut microbiota-bile acid axis and activating FXR/TGR5 signaling. Morusin, a flavonoid constituent of MLF, is a potential FXR-modulating compound. These findings provide a modern mechanistic rationale for the traditional use of mulberry leaf in treating diabetes and support the development of MLF as a gut-targeted therapeutic strategy for T2DM.
Panax ginseng C.A. Mey. is traditionally utilized to "tonify Qi and replenish Blood," particularly in managing anemia-like syndromes. Panaxadiol saponins (PND) represent a standardized bioactive fraction from ginseng that embodies these historical properties. While PND is currently in Phase II clinical trials for aplastic anemia (AA), its systemic pharmacological mechanisms remain to be fully elucidated. This study aimed to evaluate the therapeutic efficacy of PND against immune-mediated AA, and delineate its potential systemic regulatory mechanisms involving the NLRP3-related signaling and gut-bone marrow crosstalk. An immune-mediated AA mouse model was established. Network pharmacology, 4D-DIA quantitative proteomics and 16S rDNA sequencing were integrated to identify responsive molecular pathways and candidate targets. Predicted target interactions were characterized via molecular dynamics (MD) simulations and further validated by cellular thermal shift assay (CETSA). Functional validation was performed in an LPS-induced primary bone marrow nucleated cells (BMNC) injury model using the NLRP3-specific inhibitor MCC950, to investigate the functional involvement of the NLRP3 axis in PND-mediated cytoprotection. PND partially restored peripheral blood counts and ameliorated CD4+/CD8+ T-cell imbalances in AA mice. Integrative analysis identified the NOD-like receptor (NLR) signaling pathway as a candidate key responsive node, with MD simulations and CETSA characterizing potential biophysical interactions between ginsenosides and the chaperone HSP90AA1. Concurrently, PND treatment improved intestinal barrier integrity and enriched beneficial microbiota, changes that were associated with attenuated systemic endotoxemia. In vitro functional rescue assays further demonstrated that NLRP3 signaling axis is functionally involved in the anti-inflammatory and cytoprotective effects of PND on BMNCs. PND facilitates hematopoietic recovery, an effect associated with the suppression of the NOD/NLRP3 inflammatory axis and a reduced systemic inflammatory burden. These findings suggest that PND holds potential as an adjunctive supportive strategy for immune-related cytopenias.
Cinnamomum verum has been extensively utilized in both traditional medicinal practices and culinary preparations. Nevertheless, its safety profile concerning embryonic development remains inadequately documented. This study aimed to evaluate the embryotoxic potential and teratogenic effects of the Cinnamomum verum aqueous extract using the zebrafish (Danio rerio) embryo model. 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. 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. 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.
Paliurus ramosissimus (PR) is a traditional folk medicinal plant recorded in Zhonghua Bencao (Chinese Materia Medica) and local medicinal records. In this study, Paliurus ramosissimus extract (PRex) was defined as an ethanol extract prepared from PR leaves. PR leaves have traditionally been used for heat-clearing and detoxification and for relieving swelling and pain. These traditional uses are closely related to inflammation-associated conditions. Because colitis-associated colorectal cancer (CAC) is characterized by chronic intestinal inflammation and mucosal injury, PR provides an ethnopharmacological rationale for evaluating PRex in an experimental CAC model. This study aimed to evaluate the protective effects of PRex in an AOM/DSS-induced CAC mouse model and to explore whether PRex-related phenotypic changes are associated with PPAR-related metabolic pathways and gut microbiota alterations. An AOM/DSS-induced CAC mouse model was established. The main mechanistic analysis included the Control, Model, and PRex 820 mg/kg groups, while Wuwei Kushen and Aspirin were used as pharmacodynamic reference groups for phenotypic evaluation. Betulinic acid was used as a single-marker quality-control compound for HPLC-ELSD-based batch quality control of PRex. General condition, disease activity index (DAI), colon length, histopathological changes, and PCNA expression were evaluated. RNA-seq and 16S rRNA sequencing were performed to characterize host transcriptomic and gut microbiota changes. qRT-PCR and Western blotting were used for preliminary molecular assessment, and external GEO datasets were analyzed to provide contextual evidence for candidate gene expression and co-expression patterns. HPLC-ELSD analysis showed that the betulinic acid content in this batch of PRex was 63.6 mg/g. PRex was associated with partial phenotypic improvement, including increased colon length and reduced PCNA-positive proliferative activity. However, the total histopathological injury score showed only a non-significant decrease compared with the Model group. Transcriptomic analysis identified PRex-associated opposite-direction genes enriched mainly in metabolism-related pathways, including the PPAR signaling pathway, retinol metabolism, and glycolysis/gluconeogenesis. 16S rRNA sequencing showed that PRex treatment was associated with shifts in gut microbiota composition and PICRUSt2-predicted functional profiles. Exploratory comparison suggested a possible overlap between host transcriptomic pathways and predicted microbial functional pathways. qRT-PCR preliminarily supported the expression trends of PPARα, CD36, FABP4, and PCK1, while Western blotting provided supportive semi-quantitative information. PRex was associated with partial phenotypic improvement in AOM/DSS-induced CAC mice, mainly reflected by increased colon length and reduced PCNA-positive proliferative activity, whereas the total histopathological injury score was not significantly reduced. Transcriptomic analysis, 16S rRNA sequencing, and preliminary molecular assessment suggested that PRex intervention was associated with changes in PPAR-related metabolic pathways and gut microbiota profiles. PPARα, CD36, FABP4, and PCK1 may represent candidate molecules associated with PRex treatment. However, these findings should be interpreted as exploratory and hypothesis-generating, and further dose-response, toxicological, pharmacokinetic, and causal validation studies are required.