Polycyclic heterocyclic quinones derivatives (PHQs) containing oxazole and thiazoline rings were synthesized in this work. During the synthesis of PHQs containing thiazoline ring, we obtained a crystal structure of product of alkylation reaction, and unexpectedly found that its molecular structure (9-1) differed that expected (9-3). 2D NMR and DFT calculations confirmed that the molecular structure of the product is indeed 9-1 and not 9-3, leading us to infer that the product of cyclization reaction is endo-N type compound 8-1 rather than exo-N type compound 8-3. This inference contradicts with patent literature and our recent research. Compounds 8-3, 4a, and 4b are known to be exo-N type, exhibiting δ values of 1HNMR (δ values for short) of NH group in about 11 ppm, whereas the δ values of product of the cyclization reaction obtained in this study was 9.08 ppm, suggesting its molecular structure is endo-N type (8-1). Subsequent comparison of calculated and experimental δ values further validated this inference. Patent literature and our recent research both reported that the molecular structures of products of cyclization reaction (MS-pc for short) were exo-N type with the δ values being about 9.0 ppm. Since these δ values were of endo-N type structure, these previous reports on MS-pc were incorrect. Additionally, we propose and confirm that another product of the alkylation reaction has the molecular structure 9-2. During the structural determination process, we found that lone pair electrons of N (or O, S) atom significantly influence the δ values, which is result of compression effect of lone pair electrons (CELP). CELP plays a crucial role in assign of peaks in 1HNMR, and its existence was confirmed by crystal structure of compound 4b. Finally, this study evaluates the anticancer activity of the 18 synthesized compounds, demonstrating that the quinoid structure is a privileged structure of anticancer activity. The introduction of groups with alkylating ability, quaternary phosphonium (ammonium) salt groups, and sulfur atom may enhance the anticancer activity of quinone derivatives.

The clinical management of ulcerative colitis (UC) remains a significant challenge in modern gastroenterology. Flavonoids have emerged as promising therapeutic candidates due to their broad spectrum of pharmacological activities; however, their precise efficacy in the treatment of UC has yet to be substantiated by systematic clinical evidence. This study conducted a systematic review and meta-analysis to comprehensively evaluate the therapeutic effects of flavonoids in animal models of UC and their potential mechanisms of action. A comprehensive literature search and screening process was conducted across the PubMed, Web of Science, and Embase databases, covering the period from database inception to August 1, 2024. The SYRCLE risk of bias assessment tool was utilized to evaluate the methodological quality of the included studies. Data analysis was performed using STATA 15.1 software, and a time-dose response model was applied to explore the potential dose-response relationship between flavonoid administration and UC outcomes. Ultimately, 33 studies involving a total of 600 experimental animals were included in the analysis. The overall results demonstrated that flavonoids significantly reduced DAI, HS, MPO, MDA, TNF-α, IL-1β, IL-6, iNOS, COX-2, and Spleen Index, while markedly increasing body weight, CL, SOD, GSH, CAT, IL-10, ZO-1, and occludin levels. Time-dose effect analysis revealed that within the dose range of 3.2-400 mg/kg, a significantly enhanced therapeutic outcome can be achieved when combined with an intervention period of 3 to 49 days. Therefore, flavonoids may exert protective effects against UC through anti-inflammatory and antioxidant mechanisms, as well as by modulating intestinal barrier function and gut microbiota. However, the efficacy and safety of flavonoids in treating UC require further validation through extensive clinical trials.

BackgroundThe genus Salvia L. constitutes a core medicinal resource in China’s diverse ethnic medical systems. However, a systematic and comparative understanding of how ecological adaptation-particularly among high-altitude ethnomedicinal species-translates into specific ethnomedicinal value remains lacking.ObjectiveTo address this gap, we developed and validated a “habitat-phytochemistry-pharmacological effect” linkage model, testing the hypothesis that environmental stressors driven by altitudinal gradients induce chemical differentiation among Salvia species, which in turn underlies their distinct pharmacological properties and traditional therapeutic uses.MethodsWe conducted a multidimensional analysis of 32 Salvia species documented in the Dictionary of Chinese Ethnic Medicine. This integrated systematic literature review, verification of altitudinal distributions using the Global Biodiversity Information Facility (GBIF), phenological characterization based on the Flora of China, and phytochemical profiling cross-referenced with the Human Metabolome Database (HMDB) and PubChem.ResultsThese species are used by 17 ethnic minority groups in China, primarily for cardiovascular and cerebrovascular diseases, gynecological disorders, and wound healing, guided by the principles of “activating blood circulation to resolve stasis” and “clearing heat and detoxifying.” Our findings support the habitat-adaptation hypothesis: biologically, species diverge into spring-flowering types (low-altitude, used predominantly by Miao and Zhuang communities) and summer-flowering types (high-altitude; widely employed in Tibetan medicine). Chemically, this divergence corresponds to marked compositional differences-low-altitude species are enriched in flavonoids, whereas high-altitude species accumulate higher levels of phenolic acids, consistent with adaptive responses to intense UV radiation at elevation. Functional compartmentalization was also observed: roots preferentially accumulate lipophilic diterpenoid quinones (associated with antitumor and antiplatelet effects) and hydrophilic phenolic acids (linked to antioxidant and antifibrotic activities), while aerial parts are rich in flavonoids (antibacterial and antitussive) and triterpenoids (immunomodulatory). Pharmacologically, Salvia species exhibit broad bioactivities - including anticancer, anti - inflammatory, hepatoprotective, and cardioprotective effects - mediated by multiple compound classes (terpenoids, phenolic acids, polysaccharides) acting through diverse pathways. Clinical evidence further corroborates a direct alignment between traditional efficacy concepts and molecular mechanisms: “activating blood circulation to resolve stasis” corresponds to diterpenoid quinone–mediated antitumor activity, and “clearing heat and detoxifying” aligns with phenolic acid-driven anti-inflammatory effects.ConclusionThis study successfully validates the “habitat-phytochemistry-pharmacological effect” linkage model, demonstrating a strong correlation between the ethnomedicinal value of Salvia species and their ecological traits, phytochemical profiles, and pharmacological actions. The model provides a robust framework for ethnopharmacology-guided natural product discovery. Future work should prioritize mechanistic studies of key active constituents and rigorous pharmacological validation of their traditional uses.

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.

Objective Ischemic stroke (IS), a leading cause of disability and mortality worldwide, results from cerebral vascular occlusion and is associated with profound energy metabolism disorders, including oxidative phosphorylation, glycolysis, and fatty acid metabolism. Herba Siegesbeckiae (HS), a traditional Chinese medicinal herb, has shown neuroprotective potential by modulating metabolic and inflammatory pathways,but its mechanisms in IS remain unclear. Methods Active compounds of HS were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Potential targets were predicted using GeneCards, DisGeNET, and SwissTargetPrediction and filtered for genes related to energy metabolism in IS. A protein-protein interaction network was constructed using STRING and analyzed with Cytoscape 3.9.1 Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed with the clusterProfiler package in R ,and molecular docking with AutoDock Vina evaluated compounds-target affinities. Results Nine active compounds and 252 potential target genes were identified. Among 21 core targets, IL6, CYP3A4, and PPARG showed the highest network centrality. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated enrichment in inflammatory regulation, lipid metabolism, and oxidative stress-related pathways. Molecular docking showed strong binding affinities, with hederagenin demonstrating the most stable interaction with CYP3A4. Conclusion HS may regulate energy metabolism in IS through multi-target, multi-pathway mechanisms, exerting neuroprotective effects via anti-inflammatory and metabolic regulation.

Ethnopharmacological relevance Hypecoi Erecti Herba, derived from plants of the genus Hypecoum (Papaveraceae), includes two source species: Hypecoum leptocarpum Hook.f. & Thomson and Hypecoum erectum L. It is widely distributed across northern, northwestern, and southwestern China, Mongolia, Russia, and many South and West Asian countries. In traditional medical systems, particularly Tibetan and Mongolian medicine, it is characterized by a bitter taste and cold property, and has been extensively used to treat sore throat, tracheitis, cholecystitis, cough, hepatitis, bronchitis, and joint pain. Aim of the study This review aims to systematically consolidate the latest research progress on Hypecoi Erecti Herba, encompassing its traditional uses, phytochemistry, pharmacological activities, quality control, and clinical applications. Furthermore, it seeks to discuss the clinical translation of hospital-based preparations and propose novel hypotheses regarding its potential mechanisms of action. Material and methods A comprehensive literature search was conducted focusing on H. leptocarpum and H. erectum. Databases including PubMed, Web of Science, the American Chemical Society (ACS), and Science Direct were searched, resulting in the identification and screening of 94 relevant papers published between 1972 and November 19, 2025. Results Pharmacological studies have demonstrated that Hypecoi Erecti Herba possesses a broad spectrum of bioactivities, including analgesic, anti-inflammatory, antimicrobial, hepatoprotective, antioxidant, antiviral, antitumor, and allelopathic effects. Through various analytical techniques, such as column chromatography (CC) for isolation, and high-performance liquid chromatography (HPLC), ultraviolet (UV) spectroscopy, and infrared (IR) spectroscopy for characterization, approximately 90 alkaloids have been identified from this herb. The herb contains not only alkaloids but also flavonoids, volatile oils, phenolic compounds, polysaccharides, and aromatic constituents, for which quality control markers, including flavonoids, alkaloids, polysaccharides, and trace elements, have been established. Furthermore, based on network pharmacology, we speculate that active components in Hypecoi Erecti Herba may exert therapeutic effects against pharyngitis and cholecystitis by modulating the PI3K-AKT signaling pathway, potentially through the regulation of the “Heta” and “Khi” balance in the body. Conclusions This review provides a comprehensive and systematic synthesis of current knowledge on Hypecoi Erecti Herba, covering its botany, traditional uses, phytochemistry, pharmacology, mechanisms, and quality control. To advance the field, future work should focus on constructing a bencao-based knowledge graph, applying Blocks-Based Molecular Network (BBMN) technology, integrating Syndrome-Formula Metabolomics with artificial intelligence, adopting electronic sensory systems for quality assessment, and deepening research into habitat ecology and resource sustainability. These integrated efforts will be crucial for unlocking the herb's full medicinal potential, ensuring its sustainable utilization, and contributing to the broader ethnopharmacological literature.

Escin Ia is a barrigenol-type triterpenoid specific to Aesculus seeds and is widely utilized in clinical practice for the treatment of cerebral edema, swelling, and venous insufficiency. Here, we fully elucidated its biosynthetic pathway by identifying ten previously uncharacterized enzymes from Aesculus chinensis. AcCYP716BX1/2 catalyze the C-22α and C-28 hydroxylation of the β-amyrin scaffold, and AcCYP714E67 mediates the C-24 hydroxylation to produce protoaescigenin. Sequential glycosylation at the 2’-O and 4’-O positions is catalyzed by AcUGT94AK1/3/6 and AcUGT87AZ3, respectively, forming aesculuside B. AcCCL3 catalyzes the formation of tigloyl-CoA, and AcBAHD13/17 catalyze the C-21β tigloylation of aesculuside B to yield desacetylescin Ia. These enzymes significantly broaden the catalytic versatility of their respective gene families. Finally, we successfully reconstructed the complete pathway in Nicotiana benthamiana, enabling the heterologous production of escin Ia. This work fully elucidates the biosynthesis of escin Ia and establishes a foundation for the green production of barrigenol-type triterpenoid saponins. Escin Ia is a clinically important triterpenoid saponin from Aesculus chinensis. Here the authors identify ten biosynthetic enzymes and reconstitute the Escin 1a production in Nicotiana benthamiana.

Xueshan Jinluohan Pain-Relief Liniment (XJPL) is a Tibetan topical compound preparation composed of 11 medicinal materials. Its current quality standard relies mainly on thin-layer chromatographic identification, which is insufficient to comprehensively characterize its complex chemical composition, marker constituents from key medicinal materials, and batch-to-batch quality consistency. In this study, 17 batches of XJPL were analyzed by ultra-performance liquid chromatography coupled with quadrupole-Exactive Orbitrap high-resolution mass spectrometry (UPLC-Q-Exactive Orbitrap MS) for systematic chemical profiling. An integrated quality evaluation method was further developed by combining high-performance liquid chromatography (HPLC) fingerprinting, similarity evaluation, chemometric analysis, and multicomponent quantification. A total of 139 chemical constituents were confirmed by reference standards or putatively characterized, including alkaloids, flavonoids, phenolics, terpenoids, organic acids, lactones, and other compounds, indicating the coexistence of multiple medicinal-material-derived and structurally diverse constituents in XJPL. The HPLC fingerprint established for the 17 batches contained 23 common peaks, among which 10 representative constituents were assigned, and similarity evaluation indicated a high degree of overall chemical consistency among batches. Hierarchical cluster analysis (HCA), principal component analysis (PCA), and orthogonal partial least squares-discriminant analysis (OPLS-DA) further revealed batch-related differences and suggested that common peaks corresponding to gentiopicroside, loganic acid, and related constituents contributed substantially to sample differentiation. On this basis, quantitative methods were established for representative constituents covering phenolic acids, iridoid glycosides, carotenoid glycosides, and Corydalis-derived alkaloids. Overall, this study improves the quality evaluation framework for XJPL by integrating chemical profiling, holistic fingerprint assessment, batch-difference characterization, and multicomponent quantitative control, providing experimental support for quality standard improvement and manufacturing quality control.

Traditional sensory evaluation of traditional Chinese medicine (TCM) and medicinal and food homologous products has long relied on human observation of appearance, color, aroma, and taste. However, this approach is highly subjective, difficult to quantify, and often lacks reproducibility across evaluators. Intelligent sensory systems, including the electronic nose, electronic tongue, and machine vision, provide objective and digitized sensory information for TCM quality evaluation. Nevertheless, these platforms generate high-dimensional and heterogeneous datasets, creating a strong demand for efficient artificial intelligence (AI)-based analytical tools. This review summarizes recent advances in the application of machine learning and deep learning methods, such as support vector machine, random forest, convolutional neural network, and long short-term memory networks, for intelligent sensory evaluation of TCM. Particular emphasis is placed on how AI supports feature extraction, pattern recognition, classification, regression, and multisource data fusion across electronic nose, electronic tongue, and machine vision systems. Representative applications in raw material authentication, geographical origin discrimination, processing monitoring, and quality grading are also discussed. In addition, the current challenges related to data standardization, sensor drift, model robustness, and interpretability are highlighted. Overall, this review provides an integrated overview of AI-enabled intelligent sensory technologies and clarifies their potential to advance TCM quality evaluation toward a more objective, efficient, and holistic framework.

Aconitum pendulum Busch (Tiebangchui), a traditional Chinese medicinal herb, is recognized for its diverse pharmacological properties and for its significant toxicity. The Zanba stir-frying processing method is commonly employed to mitigate toxicity and enhance efficacy; however, the underlying chemical principles remain insufficiently studied. In order to address this issue, a phytochemical investigation was conducted on the diterpenoid alkaloids present in Zanba-processed Tiebangchui. Eleven diterpenoid alkaloids were isolated by means of chromatographic techniques, including silica gel column chromatography. Their structures were elucidated by extensive spectroscopic analysis (single-crystal X-ray diffraction, IR, HR-ESI-MS) and comparison with literature data. The compounds were identified as 12-epi-turpelline (1), 12-epi-napelline (2), 12-acetyl-napelline (3), azitine (4), flavaconitine (5), nagarutine C (6), nagarutine D (7), 16-epi-pyroaconine (8), spicatine B (9), 3-deoxyaconitine (10), and napelline (11). Notably, compound 1 was characterized as a novel alkaloid. Additionally, compounds 3-9 were isolated from this processed material for the first time. These findings provide crucial chemical insights into the detoxification mechanism of Zanba processing. Subsequent pharmacological evaluation revealed that compounds 10 and 11 exhibit notable anti-inflammatory activities. Moreover, given the structural analogy between the novel alkaloid 1 and the active compound 11, compound 1 is proposed as a promising lead for future structure-activity relationship studies and semi-synthetic modification.

fNIRS is an innovative and non-invasive tool for monitoring hemodynamic changes in the cerebral cortex. In recent years, it has become a widely used intervention method in the medical field for treating various diseases due to its portability and potential for long-term monitoring. This article systematically reviews the development history and technical principles of fNIRS, compares fNIRS with other imaging techniques, summarizes the application and research progress of fNIRS in the fields of neurofunction and brain function, clinical medicine, traditional Chinese medicine (TCM), and rehabilitation medicine, especially in exploring the neurobiological mechanisms of TCM syndromes, monitoring the central effects of acupuncture therapy, and evaluating the brain's response to TCM components. At the same time, it clarifies the shortcomings and deficiencies of fNIRS and discusses its future development, aiming to provide valuable insights and reference points for the future development of fNIRS.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disease driven by genetic, immune, and environmental factors, and its incidence continues to increase worldwide. The existing therapies often face the limitations of insufficient response, obvious side effects, and high medical burden, so it is urgent to develop safe and effective intervention strategies based on new targets. The aryl hydrocarbon receptor (AHR), a crucial environmental sensor, plays an essential role in preserving intestinal barrier function, modulating immune homeostasis, and facilitating microbiota-host interactions through the integration of ligand-mediated signals. Notably, natural products constitute a major source of AHR ligands and exhibit multiple therapeutic potentials to repair the intestinal barrier, modulate immunity, and remodel the microbiota through targeted activation of AHR. This provides a unique theoretical perspective for developing innovative therapeutic strategies. In this review, we systematically explore the fundamental relationship between AHR and IBD, and introduce the receptor's biological characteristics and regulatory mechanisms in detail. In addition, this article further emphasizes the pharmacological properties and molecular mechanisms of various natural products that target AHR as prospective treatments and evaluates their potential for clinical applications.

Sea buckthorn (Hippophae spp.) is a valuable medicinal and edible plant whose quality is highly dependent on its origin. Rapid species classification is therefore essential for quality assurance of sea buckthorn. This study developed an integrated method combining electronic eye (E-eye), electronic tongue (E-tongue), and near-infrared spectroscopy (NIRS) with machine learning for the rapid classification and quality evaluation of three Hippophae species. Individual models based on E-eye, E-tongue, and NIRS showed discriminative ability. Data fusion achieved 100.00% independent validation accuracy for all classifiers, with cross-validation accuracies of 100.00% for SVM and KNN and 94.74% for DT. Quantification of flavonoid glycosides revealed that H. rhamnoides subsp. sinensis contained the highest levels, while assessment of antioxidant activities showed that H. gyantsensis exhibited the strongest activity. The proposed data fusion strategy provides a rapid, accurate, and cost-effective solution for authentication and quality control of Hippophae, with promising applications in food and pharmaceutical industries.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation. RA has a global prevalence between 0.5 % and 1 % although its pathogenesis is not completely understood. Chinese herbal medicine such as Yunpi Jiedu Tongluo Qushi Granule (YJTQG) is one of the treatments for RA. However, the underlying mechanism of action is unclear. Here, analysis of clinical samples reveals that YJTQG can reduce the inflammatory factors and alleviate the symptoms of RA patients. Quantitative proteomic analysis of serum proteomes of RA patients identifies the potential therapeutic targets of YJTQG. We use biochemical experiments to validate several differentially expressed proteins, discover S100A8 as a possible therapeutic target of YJTQG, and analyze the correlation between S100A8 and several known RA biomarkers. Network pharmacology analysis discloses COX1/2 and NOS2 as potential targets of key compounds in YJTQG and protein-protein interaction network analysis reveals TNFα, IL-6, and STAT3 as possible core targets of YJTQG. Bioinformatic and patient sample analyses indicate that YJTQG may reduce S100A8 expression by suppressing its transcription. Mechanistically, we find that kaempferol and quercetin in YJTQG may reduce the expression of S100A8 by inhibiting the phosphorylation, nuclear translocation, and transcriptional activity of p65 in the lipopolysaccharide-stimulated RAW264.7 cells. Therefore, our work demonstrates that S100A8 is a potential therapeutic target of YJTQG for RA, which may provide a new direction for developing new treatments for RA patients.

ETHNOPHARMACOLOGICAL RELEVANCE:Lum medicinal bathing is a usage of external therapy in the Tibetan medicine system, Sowa Rigpa, specifically the application of herbal decoction to derive the bioactive compounds through skin absorption. Wuwei Ganlu (Five-Flavored Nectar) is one of the formulations used in treatment which is especially useful for the symptoms of rheumatoid arthritis (RA). The Four-Tantras (rGyud-bzhi), 8th-12th centuries, is the source of the preparation and clinical use of Wuwei Ganlu decoctions. In today's society, a standardized Tibetan herbal preparation called the Wuwei Ganlu Medicinal Bath Granules (WGMG) has been developed that maintains the core therapeutic characteristics of the traditional decoction while enhancing clinical applicability and standardization. It is composed of five kinds of Tibetan medicinal plants in equal proportions, the formula includes Juniperus formosana Hayata (Branch and Leaf), Rhododendron anthopogonoides Maxim (Flower), Myricaria germanica (L.). Desv. (Stem and Leaf), Ephedra saxatilis Royle ex Florin (Stem), and Artemisia sieversiana Ehrhart ex Willd. (Whole Plant). AIM OF THE STUDY:This study aimed to identify the active constituents of WGMG as well as understand the pharmacological mechanisms of WGMG in the treatment of collagen-induced arthritis (CIA) in rats. Furthermore, WGMG was screened for its core anti-inflammatory effects via the TLR4/NF-κB and NLRP3 signaling pathways. MATERIALS AND METHODS:UPLC-Q-TOF/MS was used to characterize chemical components of WGMG in rat serum and synovial fluid. Potential targets and the associated pathways were predicted using network pharmacology. CIA rats in vivo, were treated with WGMG via medicinal bath treatment at doses of 2.95, 5.90, and 11.8 g/L for 28 days. The effectiveness of the treatment was determined by looking at the arthritis scores, swelling measurements of the paws, and the serum cytokines that were measured by ELISA. Hematoxylin and eosin (H&E) and Safranin O-fast green staining were used to examine histopathological alterations. The Western blot, immunohistochemistry, and RT-PCR analyzes were used to uncover the underlying molecular mechanisms targeting on TLR4/NF-κB and NLRP3 inflammasome-related signaling molecules. RESULTS:The findings of the study revealed identification of a total of 89 compounds from WGMG, which were mainly composed of alkaloids, flavonoids, phenylpropanoids, phenolic acids and fatty acids. In addition, total of 28 and 21 compounds were respectively identified from serum and synovial fluid. Both serum and synovial fluid had eighteen common compounds such as kaempferol and trans-ferulic acid. The network pharmacology research indicates that 68 overlapping targets between WGMG components and RA were revealed. Moreover, TLR4/NF-κB was found to mediate the inflammation by regulating the signaling pathway. In CIA rats, WGMG-H group significantly decreased arthritis scores, paw swelling, and spleen index, indicating relievers of symptoms of arthritis. According to histopathological examination, WGMG-H reduced synovial hyperplasia, inflammatory cell infiltration, and cartilage erosion. Moreover, WGMG-H inhibited the serum levels of NF-κB, TNF-α, IL-1β, IL-18 while enhanced IL-4 levels. Mechanistically, the protein and mRNA expression of TLR4, NF-κB, NLRP3, ASC, and caspase-1 were downregulated by WGMG, with high-dose WGMG having therapeutic efficacy similar to dexamethasone. CONCLUSION:WGMG shows potent anti-inflammatory activity via inhibitory effect on NLRP3 inflammasome activation, which due to inhibition of TLR4/NF-κB signaling pathway. This pharmacological mechanism is likely attributed to the bioactive components kaempferol and trans-ferulic acid. This research shows how WGMG may work in the body. The authors hope their findings might lead to new treatments for rheumatoid arthritis.

This paper reports a well-designed and in-depth comparative study on the polysaccharide yields, contents, and antioxidant activities of two Hippophae species of great research value, namely, Hippophae rhamnoides subsp. sinensis Rousi and Hippophae gyantsensis (Rousi) Y. S. Lian. The total polysaccharides of H.rhamnoides subsp. sinensis and H. gyantsensis were obtained through hot water extraction. Yields were compared, and polysaccharide contents were accurately determined through phenol-sulfuric acid colorimetry and compared. Meanwhile, the antioxidant activity of the polysaccharides was evaluated through 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging. Results showed that the polysaccharide yield (percentage of crude extract relative to the raw material) of H.rhamnoides subsp. sinensis (1.18% ± 0.02%) was significantly lower than that of H. gyantsensis (3.12% ± 0.06%) (P < 0.01). The polysaccharide content (defined as pure polysaccharides in the extract) of H.rhamnoides subsp. sinensis (352.97±1.07 mg/g) was significantly higher than that of H. gyantsensis (300.21 ± 1.49 mg/g) (P < 0.01). The half-inhibitory concentration of the DPPH free radical scavenging activity of H.rhamnoides subsp. sinensis polysaccharides (0.026 ± 0.004 mg/mL) was slightly lower than that of H. gyantsensis polysaccharides (0.021 ± 0.004 mg/mL). However, no significant difference was found between the two Hippophae species (P > 0.05). This experiment clarified the differences in polysaccharide yield, content, and antioxidant activity between H.rhamnoides subsp. sinensis and H. gyantsensis. This work can provide a scientific basis for the quality evaluation of sea buckthorn and the further development of polysaccharide active components.

ETHNOPHARMACOLOGY RELEVANVE:The seeds of Citrus reticulata Blanco (Juhe) are a valued traditional Chinese medicine (TCM) with a documented history of use spanning millennia. Traditionally, they have been used to treat hernia pain, orchalgia, and various breast disorders. This long-standing ethnopharmacological application underscores their importance and warrants further investigation into their pharmacological properties and therapeutic potential. AIM OF THE REVIEW:This review aims to systematically evaluate the current research on Juhe, with a specific focus on its botanical origins, pharmacognostic characteristics, traditional processing methods, phytochemical composition, pharmacological activities, quality control, and analytical techniques. By consolidating this information, we seek to clarify the scientific basis underlying its traditional applications and establish a solid foundation for future research and potential development. METHODS:A comprehensive literature search was conducted utilizing both canonical texts of traditional medicine (Zhonghua Ben cao, Dictionary of Chinese Ethnic Medicine) and major electronic databases (including PubMed, Web of Science, CNKI, and Wanfang). The search was performed with key terms such as "C. reticulata Blanco," "Juhe," and "salt processing." Relevant publications spanning from 2000 to the present, encompassing pharmacological, clinical, and ethnomedical studies, were systematically retrieved and critically evaluated. RESULT:Analysis of historical and modern sources reveals that Juhe processing has evolved from methods like stir-frying and wine-processing to the modern standard of crude and salt-processed forms. Its properties and functions have remained consistent: bitter, neutral, targeting the liver and kidney meridians, and used to regulate qi, dissipate nodules, and alleviate pain. Phytochemically, it is rich in limonoids, flavonoids, and fatty acids, which contribute to its anti-tumor, anti-inflammatory, analgesic, and antibacterial activities. Meriting particular note is that salt-processing markedly alters the profile of its bioactive constituents. DISCUSSION:Current research on Juhe remains limited, lacking sufficient depth. Concerted efforts are necessary to elucidate the pharmacodynamic material basis of both crude and processed Juhe, delineate the transformation pathways of chemical constituents during processing, and establish clear structure-activity relationships. These investigations are crucial for clarifying the mechanism underlying the processing tradition and will provide a scientific foundation for establishing standardized processing protocols, robust quality control, and guiding its rational clinical application.

Structural characterization of natural products in complex herbal extracts remains a major challenge in phytochemical analysis. In this study, we present a novel post-acquisition data-processing strategy—key ion diagnostics–neutral loss filtering (KID-NLF)—combined with ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) for systematic profiling of the medicinal plant Terminalia chebula. The strategy consists of four main steps. First, untargeted data are acquired in negative electrospray ionization (ESI−) mode. Second, a genus-specific diagnostic ion database is constructed by leveraging characteristic fragment ions (e.g., gallic acid, chebuloyl, and HHDP groups) and conserved substructures. Third, MS/MS data are high-resolution filtered using key ion diagnostics and neutral loss patterns (302 Da for HHDP; 320 Da for chebuloyl). Finally, structures are elucidated via detailed spectral analysis. The methanol extract of T. chebula was separated on a C18 column using a gradient of acetonitrile and 0.1% aqueous formic acid within 33 min. This separation enabled detection of 164 compounds, of which 47 were reported for the first time. Based on fragmentation pathways and diagnostic ions (e.g., m/z 169 for gallic acid, m/z 301 for ellagic acid, and neutral losses of 152, 302, and 320 Da), the compounds were classified into three major groups: gallic acid derivatives, ellagitannins (containing HHDP, chebuloyl, or neochebuloyl moieties), and triterpenoid glycosides. KID-NLF overcomes key limitations of conventional workflows—namely, isomer discrimination and detection of low-abundance compounds—by exploiting genus-specific structural signatures. This strategy demonstrates high efficiency in resolving complex polyphenolic and triterpenoid profiles and enables rapid annotation of both known and novel metabolites. This study highlights KID-NLF as a robust framework for phytochemical analysis in species with high chemical complexity. It also paves the way for applications in quality control, drug discovery, and mechanistic studies of medicinal plants.

Exosomes are nano-sized extracellular vesicles secreted by diverse cell types that mediate intercellular communication through the transfer of proteins, lipids, and nucleic acids. Their ability to cross biological barriers and carry bioactive cargo has led to increasing interest in their use as targeted delivery systems for drugs, genes, and immunomodulatory molecules. Recently, plant-derived exosome-like nanoparticles, PLNs obtained from edible plants and medicinal herbs have emerged as a novel, biocompatible alternative to mammalian exosomes. PLNs exhibit low immunogenicity, enhanced safety, and scalable production, making them ideal candidates for clinical translation. This review synthesizes a wide body of experimental data on the biogenesis, molecular composition, and biological activity of PLNs, and provides a comparative assessment of their therapeutic applications across oncology, immunotherapy, regenerative medicine, and gene therapy. Technological advances in PLN engineering, isolation, and manufacturing are discussed, along with key translational barriers such as stability, regulatory standards, and delivery specificity. This review also discusses the scientific implications of PLNs in advancing precision medicine and propose future directions for their integration into next-generation nanotherapeutics.

ETHNOPHARMACOLOGICAL RELEVANCE:Myristica fragrans Houtt. (nutmeg) is an important ethnomedicinal resource with both dietary and therapeutic significance in traditional Asian medical systems. Its use dates back to its introduction into China around the 3rd-4th centuries CE. Classical medical texts document its core functions of "warming the middle jiao to promote qi flow, and astringing the intestines to relieve diarrhea." Modern research confirms that lignans and terpenoids are its primary active constituents, exerting significant gastrointestinal regulatory and neuroprotective effects through multi-target mechanisms, providing a scientific basis for its traditional applications. AIM OF THE STUDY:This paper aims to systematically review the herbal origins and historical evolution of M. fragrans, and comprehensively summarize recent advances in its botanical characterization, traditional uses, phytochemistry, pharmacological properties, and toxicology, thereby providing a solid foundation for the in-depth study and rational utilization of this resource. MATERIALS AND METHODS:A systematic search of Chinese and English databases (including SpringerLink, Web of Science, ACS Publications, PubMed, Elsevier ScienceDirect, CNKI) and patent platforms (Innojoy) was conducted. Furthermore, ancient and modern authoritative medical texts and standards, such as Compendium of Materia Medica (Bencao Gangmu), The Four Medical Tantras (Sibu Yidian), and Chinese Pharmacopoeia, were consulted and analyzed. RESULTS:Herbal textual research systematically revealed the evolution of the nomenclature, historical distribution, and medicinal parts of M. fragrans. M. fragrans is indigenous to Southeast Asia, with primary cultivation established in tropical regions including India and Malaysia. Introduced cultivation occurs in China's Hainan and Yunnan provinces. Phytochemical investigations have identified a total of 328 compounds, with lignans and phenylpropanoids such as macelignan and myristicin recognized as key bioactive substances. These components demonstrate multiple pharmacological activities, including neuroprotective, gastrointestinal regulatory, and hypoglycemic effects. However, attention is also required for its toxic constituents (myristicin) and the detoxification mechanisms involved in processing. Although processing procedures are standardized, the quality evaluation criteria for processed products (e.g., limits for toxic components, potency markers) still need refinement. Additionally, toxicological studies indicate concerns regarding its toxic constituents and metabolic pathways. Current clinical applications primarily involve its use in compound formulations, whereas the clinical translation of single constituents warrants further investigation. CONCLUSION:This review represents the first systematic integration of the herbalogy, chemistry, pharmacology, and toxicology of M. fragrans. It clarifies its medicinal history, identifies the main groups of active constituents and their multi-target mechanisms of action, and provides a critical appraisal of its safety profile. The salient contributions of this paper are Constructing a complete knowledge system bridging traditional knowledge and modern scientific evidence. Revealing the scientific connotation and existing research gaps regarding the processing theory of "reducing toxicity while preserving efficacy". Identifying key future research priorities-namely, establishing a comprehensive quality control system linking processing techniques, chemical characterization, and pharmacological/toxicological properties, and deeply elucidating the in vivo metabolic processes and molecular targets of active constituents. This effort is crucial for bridging the key evidence gap between traditional experience and standardized modern medicine.