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  • Study on enhanced anti-hepatocellular carcinoma effect of Fuzi polysaccharide combined with lenvatinib through promoting M1 polarization of tumor-associated macrophages

    LU Lin-zhu;HUANG Zhen;GUO Qian-qian;TAN Nian-hua;LYU Chang-jun;YI Chun;TIAN Xue-fei;Hunan Provincial Key Laboratory of Translational Medicine in Chinese Medicine, Key Laboratory of Chinese Medicine Prevention and Treatment of Tumor Mechanism in Hunan, School of Integrative Chinese and Western Medicine, Hunan University of Chinese Medicine;College of Traditional Chinese Medicine, Hunan Traditional Chinese Medical College;the First Affiliated Hospital of Hunan University of Chinese Medicine;Medica

    To investigate the role of Fuzi polysaccharide(FPS) in combination with lenvatinib(LEN) in regulating tumor-associated macrophage(TAM) polarization to enhance the anti-hepatocellular carcinoma(HCC) efficacy, the non-toxic concentrations of FPS and LEN on RAW264.7 cells were screened by cell counting kit-8(CCK-8). The co-culture system of RAW264.7 and Hepa1-6 cells was established, and flow cytometry was used to detect changes in M1 and M2 macrophage phenotypes. Quantitative real-time polymerase chain reaction(qRT-PCR) was performed to assess the mRNA expression levels of M1-associated factors, inducible nitric oxide synthase(iNos) and interleukin 12b(IL-12b), as well as M2-associated factors arginase 1(Arg-1) and IL-10. The effects of macrophages treated with FPS and LEN on HCC cell proliferation, migration, invasion, and apoptosis were evaluated by 5-ethynyl-2′-deoxyuridine(EdU) staining, wound healing assay, Transwell invasion assay, and Annexin V/PI double-staining flow cytometry. A C57BL/6 subcutaneous HCC xenograft mouse model was established to observe the tumor growth, body weight, spleen index, and tumor-infiltrating macrophage polarization. CCK-8 assay showed that 50-200 mg·L~(-1) FPS and 1-5 μmol·L~(-1) LEN had no inhibitory effects on RAW264.7 macrophages. Flow cytometry and qRT-PCR results demonstrated that 200 mg·L~(-1) FPS + LEN significantly increased the proportion of M1 macrophages(P<0.01) and the M1/M2 ratio(P<0.01), upregulated the expressions of M1-associated genes iNos and IL-12b(P<0.01), reduced the proportion of M2 macrophages(P<0.01), and inhibited the expressions of M2-associated genes Arg-1 and IL-10(P<0.01). Functional assays revealed that macrophages of the FPS + LEN group inhibited Hepa1-6 proliferation(P<0.01), promoted apoptosis(P<0.01), and reduced migration and invasion(P<0.01). In vivo experiments showed that compared to those of the LEN group, the tumor volume was significantly reduced(P<0.05), and the spleen index was significantly increased(P<0.05) in the FPS + LEN group. The body weight was not decreased, and the proportion of M1 macrophages and the M1/M2 ratio in the tumors were significantly increased in the FPS + LEN group(P<0.01). In conclusion, FPS combined with LEN enhances the anti-HCC effect by promoting the M1 polarization of TAMs.

    2025 18 v.50 [Abstract][OnlineView][Download 2373K]

  • Mechanism of total flavonoids from Astragali Complanati Semen in treating chronic liver injury based on intestinal flora

    WANG Yang;ZHOU Rui-na;LEI Li-yan;YUE Zheng-gang;CHEN Lin;Shaanxi Collaborative Innovation Center of Chinese Medicine Resources Industrialization, State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Innovative Drug Research Center,Shaanxi University of Chinese Medicine;

    Based on the intestinal flora perspective, this study aims to explore the therapeutic mechanism of total flavonoids from Astragali Complanati Semen(TFACS) on chronic liver injury(CLI). Mouse CLI models were constructed by intraperitoneal injection of carbon tetrachloride. The mice were randomly divided into four groups as follows: a blank group, a model group, a silybin group, and TFACS(50 or 100 mg·kg~(-1)) groups. The corresponding drugs were administered to each group for 6 consecutive weeks. Sixteen hours after the final administration, serum and cecal contents were collected in each group. Serum liver function indexes were determined by the automatic biochemical analyzer. The liver lesions and collagen deposition were observed by hematoxylin-eosin and Masson staining. The intestinal flora components were analyzed by 16S rDNA sequencing technology. The short chain fatty acids(SCFAs) content was analyzed by GC-MS. The cecum tissue was observed by fluorescent staining. The results show that, compared with the model group, Bacteroidetes was decreased significantly at the phylum level under the TFACS intervention. Under the TFACS intervention, Firmicutes and Proteobacteria were increased significantly. At the genus level, TFACS promotes the proliferation of Lactobacillus. At the species level, TFACS significantly increases the abundance of Roseburia faecis, while decreasing the Alistipes onderdonkii and Clostridium leptum level. In addition, TFACS intervention significantly increases the contents of SCFAs, including propionic acid, acetic acid, isovaleric acid, isobutyric acid, caproic acid, and valeric acid in intestinal contents of CLI mice, while up-regulating the expression of key structural proteins of intestinal tight junctions [occludin, and zonula occludens-1(ZO-1)]. In addition, TFACS intervention effectively promotes the adhesion complex formation between intestinal epithelial cells, thereby improving intestinal barrier function. In conclusion, TFACS can improve intestinal flora composition, SCFAs formation, and intestinal barrier integrity in CLI mice, providing a research basis for TFACS′ anti-CLI mechanism.

    2025 18 v.50 [Abstract][OnlineView][Download 2544K]

  • Role and mechanism of Renqing Mangjue in attenuating hepatic fibrosis via PRMT1/H4R3me2a/PAI-1/MCP-1 epigenetic regulatory axis based on network pharmacology and experimental validation

    XIAO Zi-qing;MA Zhao-chen;ZOU Jie;XU Ming-zhu;CHEN Pei-ping;ZHANG Chu;YANG Yi-xin;HUANG Feng-yu;WANG Hai-ping;LIU Ying;ZHANG Yan-qiong;LIN Na;HUANG Feng;YANG Zhu-ya;College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine;Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences;Arura Tibetan Medicine Co.Ltd.;

    The current study aims to elucidate the underlying pharmacological mechanisms of the Tibetan medicine Renqing Mangjue against hepatic fibrosis using a research strategy integrating network pharmacology and experimental verification. Through the combination of a rat hepatic fibrosis model induced by diethylnitrosamine(DEN) and the analysis of clinical transcriptome data from the GEO database, the characteristics of its pharmacological effects were objectively evaluated, and its mechanism of action was systematically analyzed. The experimental results showed that the intervention of Renqing Mangjue significantly reduced the levels of serum hepatic fibrosis markers, including procollagen type Ⅲ(PCⅢ), collagen type Ⅳ(Ⅳ-C), and laminin(LN). Specifically, the medium-dose group showed a decrease of 37.8%, 47.1%, and 36.6% respectively compared with the model group(all P < 0.05) and a reduced collagen deposition in the liver tissue. The mechanism study found that it down-regulated the expressions of protein arginine methyltransferase 1(PRMT1), histone H4 arginine 3 dimethylation(H4R3me2a), plasminogen activator inhibitor-1(PAI-1), and monocyte chemoattractant protein 1(MCP-1) and inhibited the PRMT1/H4R3me2a/PAI-1/MCP-1 signaling axis, thereby inhibiting the activation of hepatic stellate cells and the excessive deposition of the extracellular matrix. This study is the first to clarify that Renqing Mangjue may exert an anti-hepatic fibrosis effect through the epigenetic regulation pathway, providing an experimental basis for its clinical application and offering a new paradigm for modern research on Tibetan medicine compounds.

    2025 18 v.50 [Abstract][OnlineView][Download 3234K]

  • Effect of Bupleuri Radix-Paeoniae Radix Albae combination on HMGB1/RAGE/NF-κB signaling pathway in rats with cholestatic hepatitis

    CHEN Zi-rui;ZHANG Meng-jie;LIU Yun-fan;CAO Na-na;WANG Ya-jing;WEN Ya-qian;WANG Xi;CHAI Tian-chuan;College of Pharmacy,Hebei University of Chinese Medicine;Hebei International Joint Research Center for Utilization and Quality Evaluation of TCM Resources;Hebei Provincial Hospital of Traditional Chinese Medicine/National Traditional Chinese Medicine Workers′ Inheritance Studio;

    To explore the effect of the combination of Bupleuri Radix and Paeoniae Radix Alba on the high mobility group box-1 protein(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-κB(NF-κB) signaling pathway in rats with cholestatic hepatitis induced by rifampicin(RFP). Forty-two male SD rats were randomly divided into the normal group, the Bupleuri Radix-Paeoniae Radix Alba group(C-B group), the RFP group, the ursodeoxycholic acid(UDCA)+RFP group(UDCA+RFP group), the Bupleuri Radix+RFP group(C+RFP group), the Paeoniae Radix Alba+RFP group(B+RFP group), and the Bupleuri Radix-Paeoniae Radix Alba+RFP group(C-B+RFP group). RFP was administered by gavage to establish a cholestatic hepatitis model, and the corresponding drugs were administered simultaneously in the treatment groups for 14 days. The physiological state and body weight of the rats were observed and recorded daily. After the experiment, hematoxylin-eosin(HE) staining was used to observe the pathological morphology of the liver; the terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL) method was used to observe the apoptosis of liver cells; the activities or contents of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), total bilirubin(TBIL), direct bilirubin(DBIL), and total bile acids(TBA) in serum were detected. The mRNA and protein expression levels of HMGB1, RAGE, NF-κB p65, interleukin(IL)-1β, tumor necrosis factor(TNF)-α, IL-6, glucose-regulated protein 78(GRP78), and CCAAT/enhancer-binding protein homologous protein(CHOP) were detected by quantitative real-time polymerase chain reaction(qRT-PCR) and Western blot. The results show that compared with the normal group, RFP group exhibited decreased body weight, listlessness, disordered hepatic cord structures, present inflammatory cells, and increased numbers of apoptotic cells. The serum activities or contents of ALT, AST, ALP, TBIL, DBIL, and TBA were significantly increased. The mRNA and protein expression levels of HMGB1/RAGE/NF-κB signaling pathway factors, IL-1β, TNF-α, IL-6, GRP78, and CHOP were also significantly increased, indicating the successful establishment of the cholestatic hepatitis model. Compared with the RFP group, the UDCA+RFP, C+RFP, B+RFP, and C-B+RFP groups showed increased body weight, improved abnormal pathological conditions in liver tissue, and decreased activities or contents of serum ALT, AST, ALP, TBIL, DBIL, and TBA. The mRNA and protein expression levels of HMGB1/RAGE/NF-κB signaling pathway factors, IL-1β, TNF-α, IL-6, GRP78, and CHOP in liver tissue were also decreased. Compared with the C-B+RFP group, the ALT activity and the protein expression levels of HMGB1, RAGE, IL-6, and GRP78 were significantly higher in the C+RFP and the B+RFP groups. In conclusion, the combination of Bupleuri Radix and Paeoniae Radix Alba alleviates endoplasmic reticulum stress through the HMGB1/RAGE/NF-κB signaling pathway and reduces inflammatory responses, thereby exerting hepatoprotective effects.

    2025 18 v.50 [Abstract][OnlineView][Download 1483K]

  • Mechanism of triptolide-induced hepatic cell lipotoxicity based on lipophagy

    LIU Shan;SU Yue-rui;LI Hong-yan;ZHOU Kun;HAN Bo;REN Jin-hong;LI Peng-cheng;WEI Yan-ming;College of Chinese Medicine and Food Engineering, Shanxi University of Chinese Medicine;Yangquan Municipal Center for Disease Control and Prevention;Shanxi Institute of Energy;College of Basic Medicine, Shanxi University of Chinese Medicine;Shanxi Provincial Key Laboratory of Innovative Drugs for Major Diseases Based on Inflammatory Response,Shanxi University of Chinese Medicine;

    This study aimed to investigate the effects of triptolide on lipophagy and to explore the role and underlying mechanism of lipophagy in triptolide-induced hepatocellular injury. HL7702 human normal hepatocytes and C57BL/6J mice were treated with 25, 50, or 100 nmol·L~(-1 )or 0.4, 0.6, or 0.8 mg·kg~(-1) triptolide, respectively. Additionally, HL7702 cells were co-treated with Ras-related protein 7(Rab7) small interfering RNA(siRNA) and 50 nmol·L~(-1) triptolide. Cell viability was assessed by calcein AM/PI double staining, and liver histopathological changes were observed using hematoxylin-eosin(HE) staining. Lipid droplet content was examined via oil red O and nile red staining. Commercial kits were used to measure the content of triglycerides(TG), total cholesterol(TC), free fatty acids(FFAs), glutathione(GSH), and malondialdehyde(MDA), the activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST), and the levels of mitochondrial membrane potential(MMP) and intracellular reactive oxygen species(ROS). The expression of microtubule-associated protein 1 light chain 3Ⅱ(LC3Ⅱ), selective autophagy adaptor p62, Rab7, and perilipin 2(Plin2) were detected by qRT-PCR or Western blot. The results showed that in vitro, 25,50 and 100 nmol·L~(-1) triptolide significantly reduced the cell survival rate, upregulated the expression of Rab7 and LC3Ⅱ, downregulated the expression of p62 and Plin2, reduced the content of TG, TC, GSH and MMP, and increased the content of FFAs, MDA and ROS. In vivo, 0.4,0.6 and 0.8 mg·kg~(-1) triptolide increased the activity of ALT and AST in serum, caused liver tissue damage, upregulated the expression of Rab7 and LC3Ⅱ, downregulated the expression of p62, decreased the content of TG, TC and GSH, and increased the content of FFAs and MDA. Rab7 siRNA significantly increased the levels of TG, TC and MMP, decreased the levels of FFAs and ROS, and increased the cell survival rate. In conclusion, triptolide at certain concentrations may induce Rab7-mediated lipophagy to promote lipid droplet degradation, thereby causing hepatocellular lipotoxicity, leading to mitochondrial dysfunction and oxidative stress.

    2025 18 v.50 [Abstract][OnlineView][Download 2033K]

  • Research progress on polysaccharide utilization loci from traditional Chinese medicine by carbohydrate-active enzymes within human intestinal flora

    GUO Long-ming;BAI Guang-jian;TIAN Xin;HU Hui-ping;WANG Ya-qi;CHEN Shao-dan;Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine;National Health Commission Science and Technology Innovation Platform for Nutrition and Safety of Microbial Food, Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sc

    Polysaccharides are crucial bioactive components of traditional Chinese medicine(TCM). The bioavailability and health effects of traditional Chinese medicine(TCM) polysaccharides are fundamentally governed by the metabolism regulation of carbohydrate-active enzymes(CAZymes) within the human intestinal flora. This review systematically summarized the classification and functional distribution of CAZymes in intestinal flora, as well as the dynamic regulatory mechanisms by which their encoded polysaccharide utilization loci(PULs) recognize and degrade TCM polysaccharides. Through synergistic interactions between substrate-binding modules(CBMs) and catalytic domains, CAZymes precisely recognize glycosidic bond types and spatial conformations of polysaccharides and then convert these complex polysaccharides into oligosaccharides, short-chain fatty acids(SCFAs), and other metabolites. These metabolites subsequently influence host health via immune regulation, metabolic homeostasis, and intestinal barrier repair. Furthermore, the review proposed that future research should focus on elucidating three-dimensional structures of CAZymes-polysaccharide complexes, exploring cross-phylum cooperative metabolic mechanisms, and developing microbiota-directed TCM polysaccharide delivery systems. This work systematically elucidated the core mechanisms of gut CAZymes-mediated TCM polysaccharide metabolism, providing theoretical foundations for clarifying the pharmacodynamic material basis of TCM and advancing innovative drug development of TCM polysaccharides.

    2025 18 v.50 [Abstract][OnlineView][Download 2899K]

  • Research progress on Chinese herbal medicine-derived exosome-like nanovesicles for treatment of ulcerative colitis

    NING Hang;HUANG Xin-yu;ZHENG Ling;LIN Xiao-yuan;ZHU Ying;XU Yin;the First Hospital of Hunan University of Chinese Medicine;School of Traditional Chinese Medicine, Hunan University of Chinese Medicine;

    Ulcerative colitis(UC), a chronic inflammatory bowel disease, exhibits a globally increasing incidence. Current therapeutic strategies are limited by low drug bioavailability and systemic side effects. This study systematically explored the challenges posed by the unique gastrointestinal environment in UC patients for oral drug delivery, including extreme pH conditions, degradation by digestive enzymes, metabolism mediated by intestinal flora, and obstruction from the intestinal mucosal barrier. It further highlighted the potential of Chinese herbal medicine-derived exosome-like nanovesicles(CHMELNs) as a novel drug delivery system. CHMELNs, produced by plant cells of Chinese herbal medicines, primarily consist of proteins, RNA, lipids, and bioactive phytochemicals. They demonstrate advantages such as low immunogenicity, high stability, and inherent targeting capabilities. Their small particle size(30-500 nm), negative surface charge, and lipid bilayer membrane structure enable penetration through the intestinal mucus layer, resistance to extreme pH and enzymatic degradation, and adhesion to intestinal epithelial cells via electrostatic interactions. Engineered modifications of CHMELNs, such as surface functionalization or drug loading, significantly enhance their targeting efficacy and therapeutic outcomes. Animal and cellular experiments have demonstrated that CHMELNs alleviate UC by modulating intestinal flora, suppressing inflammatory pathways, and promoting mucosal repair. Future research should focus on systematic characterization, safety validation, scalable production, and multimodal combination therapies to advance clinical translation. CHMELNs not only provide an efficient delivery platform for UC treatment but also open new avenues for the modernization of TCM and the development of natural pharmaceuticals.

    2025 18 v.50 [Abstract][OnlineView][Download 1924K]

  • Pathogenesis and therapeutic advances in skeletal muscle atrophy associated with chronic heart failure: a discussion from perspective of heart Yin deficiency

    LI Si-jing;LI Zi-ru;ZHANG Xiao-jiao;HE Xing-ling;CHEN Jia-hui;DONG Xiao-ming;LONG Wen-jie;LIU Jian-hong;LIAO Hui-li;LU Lu;YANG Zhong-qi;NI Shi-hao;National Key Laboratory of Traditional Chinese Medicine Syndrome, the First Affiliated Hospital of Guangzhou University of Chinese Medicine;Guangdong Clinical Research Institute of Chinese Medicine;Lingnan Medical Research Center, Guangzhou University of Chinese Medicine;Geriatrics Department, the First Affiliated Hospital of Guangzhou University of C

    Chronic heart failure(CHF) represents the terminal phase of severe cardiovascular diseases, with concomitant skeletal muscle atrophy significantly compromising patients′ motor function and quality of life, as well as increasing risks of adverse clinical outcomes. Current therapeutic agents and interventions targeting CHF-associated muscle atrophy remain limited. Grounded in a holistic approach and syndrome differentiation, traditional Chinese medicine(TCM) offers unique advantages in managing CHF comorbidities. This review explored the pathological mechanisms underlying skeletal muscle atrophy in CHF through the lens of the "heart Yin deficiency" theory in TCM. A pathogenic triad was proposed, encompassing collateral malnutrition due to Yin deficiency, toxin-stasis interaction, and physical-mental exhaustion. The triad was examined in relation to modern biomedical mechanisms including neuroendocrine dysregulation, oxidative stress-inflammation, microcirculatory dysfunction, and protein metabolic imbalance, highlighting the central role of heart Yin deficiency in disease progression. From the therapeutic perspective of nourishing heart Yin, the multi-target effects of herbal compound formulae and acupuncture therapy in improving cardiac function and alleviating muscle atrophy were analyzed. This analysis aims to provide both theoretical foundations and practical guidance for the clinical management of CHF with skeletal muscle atrophy.

    2025 18 v.50 [Abstract][OnlineView][Download 1278K]

  • Analysis of role of PI3K/Akt signaling pathway in intrauterine adhesion fibrosis based on theory of "dry blood in uterus"

    HONG Dan-dan;ZUO Wen-ting;WANG Hai-dan;ZHAO Yu-qin;SHANG Ting-ting;XU Xin-qi;ZHAI Yi-fei;GUO Hong-yu;Affiliated Hospital of Nanjing University of Chinese Medicine;Traditional Chinese Medicine Obstetrics and Gynecology Reproductive Clinical Medicine Innovation Center;

    Intrauterine adhesion(IUA) is a disease of partial or total occlusion of the uterine cavity due to trauma-and(or) infection-caused partial or complete damage to the basal layer of the endometrium. IUA ranks as one of the major causes of menstrual disorder, infertility, or recurrent miscarriage, gravely menacing women′s physical and mental health. At present, the pathological mechanism of IUA remains unclear. However, endometrial fibrosis is an acknowledged hypothesis. The phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway, as one of the significant signaling pathways involved in the pathological process of IUA, can partake in the fibrosis process by mediating inflammatory responses, oxidative stress responses, apoptosis, and autophagy. Regulating the PI3K/Akt signaling pathway to decelerate the fibrosis process might potentially be a viable therapeutic strategy for IUA. Traditional Chinese medicine(TCM) holds that deficiency, heat, and blood stasis represent the main pathological factors of IUA. The pathological characteristic of IUA is consistent with the pathogenesis of dry blood in TCM theory. Thus, dry blood can be considered a key pathological mechanism for the onset and development of IUA. Considering the unique physiological and pathological traits of the uterus, this study further proposed the TCM theory of "dry blood in uterus". Moreover, the endometrial fibrosis process mediated by the PI3K/Akt signaling pathway bears certain resemblances to the pathological process of IUA triggered by "dry blood in uterus". In light of this, this paper, for the first time, thoroughly analyzed the deep-seated connection between the PI3K/Akt signaling pathway and the pathogenesis of IUA fibrosis from the perspective of the TCM theory of "dry blood in uterus". The aim is to offer a theoretical basis and research direction for the treatment of IUA and relevant drug research.

    2025 18 v.50 [Abstract][OnlineView][Download 1120K]

  • Research advances in key mitochondrial injury targets and mechanisms of traditional Chinese medicine intervention in ischemic stroke

    OU Chang-ze;CHEN Bin-bin;LIU Xin-li;WANG Hong-bin;XIE Hu;LONG Hua-jun;Hunan University of Chinese Medicine;the First Affiliated Hospital of Hunan University of Chinese Medicine;Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine(the Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine);

    Ischemic stroke is one of the most severe vascular diseases in the central nervous system, with its pathogenesis involving acute cerebrovascular occlusion leading to local cerebral ischemia and hypoxia, triggering complex pathophysiological cascading reactions. Mitochondrial dysfunction serves as the critical pathological foundation of disease progression, primarily manifesting as significantly enhanced oxidative stress, cellular metabolic disorders, abnormal apoptotic signal activation, amplified inflammatory cascades, and mitochondrial dynamic imbalance. The molecular mechanisms of mitochondrial injury involve multiple key signaling pathways: mitochondrial electron transport chain dysfunction generating substantial reactive oxygen species, calcium overload disrupting mitochondrial membrane potential, and mitochondrial dynamic imbalance leading to fragmentation-fusion disequilibrium. Studies have confirmed that from single herbal active ingredients to compound preparations and even acupuncture and moxibustion, traditional Chinese medicine(TCM) demonstrates multidimensional and multilevel synergistic neuroprotective effects. Focusing on the epidemiological trend of ischemic stroke with a rising incidence, this study delves into mitochondrial dysfunction, the core molecular pathological mechanism of disease occurrence and progression. By systematically elaborating on the multi-target and multi-mechanism intervention strategies of TCM in the neurological protection domain, this study reveals the complex molecular network of mitochondrial damage and highlights the unique therapeutic advantages of TCM in regulating mitochondrial membrane potential, inhibiting oxidative stress, optimizing energy metabolism, and reducing cellular apoptosis. It explores a novel molecular target system for treating ischemic stroke, offering a new theoretical foundation for integrative medicine research.

    2025 18 v.50 [Abstract][OnlineView][Download 1704K]

  • Potential evaluation of 40% prothioconazole-tebuconazole suspension concentrate for resistance management of Alternaria spp. causing Alternaria leaf spot of ginseng

    YU Hui;ZHOU Li-lin;CHEN Xiao-lin;ZHANG Kai-xin;SHAO Shuai;JIANG Ming-en;GUO Shu-liu;CHEN Chang-qing;LU Bao-hui;HE Rong-lin;GAO Jie;College of Plant Protection, Jilin Agricultural University;Jilin Provincial Ginseng and Deer Antler Office (Jilin Provincial Traditional Chinese Medicine Industry Development Center);State-Local Joint Engineering Research Center of Ginseng Breeding and Application;

    Forty percent prothioconazole-tebuconazole suspension concentrate(SC) has been registered to control multiple crop diseases in China. This study aims to evaluate its efficacy for the control of Alternaria leaf spot of ginseng, so as to lay the foundation for the management of resistance of Alternaria spp. causing Alternaria leaf spot of ginseng to fungicides. The study first detected its antifungal activity against three species(A. alternata, A. panax, and A. tenuissima) and biochemical activity against A. alternata and then determined its efficacy against Alternaria leaf spot of ginseng in vitro. Field experiments lasting for one year at three locations were conducted to evaluate its field efficacy against Alternaria leaf spot of ginseng. Spearman′s correlation analysis was used to determine the cross-resistance of 40% prothioconazole-tebuconazole SC with eight commonly used fungicides. The results showed that prothioconazole-tebuconazole had a good inhibitory effect on mycelial growth and spore germination of the three Alternaria species, and the inhibitory effect on mycelial growth was stronger than that on spore germination. The treatment with prothioconazole-tebuconazole at the concentrations of 0.1, 1.0, and 10.0 μg·mL~(-1) resulted in deformity of mycelia, shortened germ tubes of conidia, reduced content of DNA and soluble proteins, and decreased permeability of cell membrane of A. alternata. Under in vitro conditions, the protective and curative effects of 40% prothioconazole-tebuconazole SC in the concentration range of 50-150 μg·mL~(-1) on Alternaria leaf spot of ginseng were 65.45%-100.00% and 65.58%-96.36%, respectively, which were significantly better than those of tebuconazole at the same concentration. There was no cross-resistance between prothioconazole-tebuconazole and the eight fungicides(difenoconazole, propiconazole, tebuconazole, iprodione, pyraclostrobin, azoxystrobin, kresoxim-methyl, and mancozeb). These eight fungicides were widely used to prevent and control Alternaria leaf spot of ginseng, and A. panax causing Alternaria leaf spot of ginseng had resistance to them. The results of the field experiments at three locations showed that 40% prothioconazole-tebuconazole SC was more effective than difenoconazole, propiconazole, tebuconazole, and iprodione 7, 15, and 30 d after its last application and had long effective duration. In conclusion, 40% prothioconazole-tebuconazole SC had high antifungal activity and biochemical activity against Alternaria spp. and better efficacy for the prevention and control of Alternaria leaf spot of ginseng in the field than the commonly used fungicides to which Alternaria spp. were resistant, and no cross-resistance was found between 40% prothioconazole-tebuconazole SC and the fungicides. It can be used for resistance management of Alternaria spp.

    2025 18 v.50 [Abstract][OnlineView][Download 1237K]

  • Effects of different intercropping patterns on growth characteristics and secondary metabolites of Notopterygium incisum in alpine Tibetan area

    WANG Hong-lan;ZHU Wen-tao;YANG Ping;WANG Qi;DU Jiu-zhen;LIU Teng;JIANG Shun-yuan;ZHOU Yi;Sichuan Academy of Chinese Medicine Sciences;

    This study aims to screen the optimal intercropping pattern, so as to improve the quality of Notopterygii Rhizoma et Radix and the economic benefits of land use.Four planting patterns, namely, Notopterygium incisum monoculture(CK), broad bean‖N.incisum(CD-QH), lettuce‖N.incisum(WS-QH), and garlic‖N.incisum(DS-QH), were set up with row spacings of 20 cm×20 cm, 20 cm×30 cm, and 20 cm×40 cm to analyze the effect of different row spacings in different intercropping patterns on the growth characteristics and secondary metabolites of N.incisum.Reasonable intercropping spacing and patterns were explored.Compared with that of CK, the survival rate of N.incisum seedlings in CD-QH, WS-QH, and DS-QH patterns increased by more than 70%(P<0.05).The increases in N.incisum plant height, leaf length, and leaf width were the greatest in the CD-QH pattern with a row spacing of 20 cm×20 cm, which was 127.11%, 137.77%, and 92.37% higher than those of the CK treatment, respectively.All the three intercropping patterns helped to increase the fresh weight of underground parts and promote the elongation of main roots.Particularly, the CD-QH pattern with a 20 cm×20 cm row spacing had the best effects, which were 1.97 times and 1.54 times those of the CK treatment, respectively.The content of notopterol and isoimperatorin as well as the sum of the two in the three intercropping patterns with a 20 cm×20 cm or 20 cm×30 cm row spacing was significantly higher than that in the CK treatment(P<0.05), and the values were the greatest in the CD-QH pattern.The economic benefits of land under the three intercropping patterns with different row spacings were significantly higher than those of the CK treatment(P<0.05), and the economic benefits of the CD-QH pattern was the highest at a 20 cm×20 cm row spacing, which was 27 800 yuan·mu~(-1), 157.41% higher than that of the CK pattern.In summary, intercropping helps to promote the growth of the aboveground part and the underground part and the accumulation of secondary metabolites of N.incisum and improve the economic benefits of land.The best intercropping crop was broad bean, and the optimal row spacing was 20 cm×20 cm.

    2025 18 v.50 [Abstract][OnlineView][Download 1913K]

  • Genome-wide identification and expression pattern analysis of chalcone synthetase gene family in Eucommia ulmoides

    LIU Jun;CHENG Ting-ting;LIAN Cong-long;MA Rui;FENG Wei-meng;ZHANG Bao;WANG Li-li;CHEN Sui-qing;School of Pharmacy, Henan University of Chinese Medicine;Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao;

    Chalcone synthetase(CHS) is a key enzyme in the flavonoid biosynthesis pathway. To investigate the functions of CHS gene in Eucommia ulmoides, this study conducted a comprehensive identification of EuCHS gene family members based on the E. ulmoides genome data by using bioinformatics methods. Systematic analyses were performed on their physicochemical properties, evolutionary relationships, conserved motifs, gene structures, chromosomal localization, promoter cis-acting elements, and expression patterns, aiming to provide a theoretical foundation for further research on the functions of EuCHS genes. In this study, a total of four EuCHS gene family members were identified, named EuCHS1 to EuCHS4. The encoded amino acids ranges from 385 to 397 aa with relative molecular weights between 42 315.75 and 43 336.97, theoretical isoelectric points ranging from 5.72 to 8.06, instability index ranging from 39.35 to 53.82, and aliphatic indices from 90.91 to 94.25. All EuCHS proteins were hydrophilic, and subcellular localization analysis showed that they were located in the cytoplasm. Evolutionary analysis indicated that the EuCHS family members were divided into two subfamilies, Group Ⅰ and Group Ⅲ, with each containing two EuCHS members. Gene structure analysis showed that all EuCHS contained two exons. Cis-acting element analysis indicated that EuCHS family members might be involved in various biological processes, including growth and development, hormone regulation, and abiotic stress responses. Transcriptome and quantitative reverse transcription-polymerase chain reaction(qRT-PCR) data analysis showed that EuCHS exhibited tissue-specific expression patterns, with most genes showing the highest expression levels in leaves, particularly during the early stages of leaf development. These genes participated in the formation of E. ulmoides gum and the leaf color of ` Ziye′ E. ulmoides, as well as in floral organ development. Under drought stress, EuCHS1, EuCHS2, and EuCHS4 were upregulated, while EuCHS3 was downregulated. Gibberellic acid(GA_3) treatment suppressed EuCHS3 expression but induced EuCHS4 upregulation. Under abscisic acid(ABA) treatment, EuCHS1 and EuCHS3 were downregulated, while EuCHS2 and EuCHS4 exhibited an initial increase followed by a decrease in expression. This study identified four EuCHS gene family members with significant conservation and classified them into two subfamilies, Group I and Group Ⅲ. EuCHS genes displayed distinct expression differences across various tissues and developmental stages and were involved in abiotic stress responses in E. ulmoides. This study provides a theoretical basis for further exploring the functions of the CHS genes in E. ulmoides.

    2025 18 v.50 [Abstract][OnlineView][Download 2314K]

  • Transcriptomics-based mining of key genes for biosynthesis of iridoid glycosides in Morinda officinalis

    LU Xue-xue;HUANG Fei-ning;LYU Bing;LI Mei-huan;ZHAO Yu;HUANG Ding;TIAN Hui;Guangxi University of Chinese Medicine;

    In this study, Morinda officinalis roots(MG), stems(MJ), and leaves(MY) were used as test materials. The main iridoid glycosides in various tissues were analyzed qualitatively and quantitatively using high-performance liquid chromatography(HPLC). Simultaneously, combined with transcriptome data, metabolite and gene association analyses were conducted to identify key candidate genes in the iridoid glycoside biosynthetic pathway. The expression levels of these key candidate genes were further validated by fluorescence quantitative PCR(qRT-PCR). HPLC results indicated that the content of iridoid glycosides in MG and MJ was significantly higher than in MY, being approximately twice as much. Transcriptome sequencing revealed that 6 275, 10 108, and 7 330 differentially expressed genes(DEGs) were identified in the three comparative groups of MG vs MJ, MG vs MY, and MJ vs MY, respectively. Among the differential genes, 21 genes related to the iridoid glycoside biosynthetic pathway were annotated. Correlation analysis showed that the DXS, IDI, GES, 10-HGO, and IS genes were positively correlated with the content of iridoid glycosides(r>0.8), suggesting that these five genes are likely key candidates in the iridoid glycoside synthesis process. The results of qRT-PCR confirmed that the expression levels of these five key candidate genes in different tissues were consistent with the transcriptome data. In conclusion, this study provides an important theoretical foundation and research base for the in-depth exploration of the molecular mechanisms underlying the biosynthesis and regulation of iridoid glycosides in M. officinalis, as well as valuable insights for the cultivation and production of high-quality M. officinalis medicinal materials.

    2025 18 v.50 [Abstract][OnlineView][Download 1169K]

  • Catalytic mechanism of pterocarpan reductase in Lotus corniculatus

    YANG Chao;WANG Yong-jiang;HUANG Jian-ping;HUANG Sheng-xiong;Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences;University of Chinese Academy of Sciences;

    The roots of Lotus corniculatus, a Chinese medicinal herb, have been used in traditional Chinese medicine(TCM) to treat various diseases, including coughing due to wind-heat, fever due to Yin deficiency, eczema, and hemorrhoids. In recent years, pharmacological studies have revealed that the flavonoids in L. corniculatus, such as(-)-vestitol, exhibit antiviral, anticancer, and anti-inflammatory activities. However, the exploitation of its resources has been limited due to the low content in plants and the high difficulty of chemical synthesis. To guide the enhancement of the content of active substances such as(-)-vestitol in plants, this study investigated the catalytic mechanism of pterocarpan reductase(PTR) involved in the biosynthesis. Molecular docking and site-directed mutagenesis were employed to reveal the interaction modes between PTR and its substrates, which identified the crucial role of the lysine(Lys) residue in the catalytic process. The catalytic process of substrate is driven by the abstraction of the hydrogen atom of the hydroxyl group on the A-ring of the substrate, which leads to the formation of the transition state. Additionally, other amino acid residues, including isoleucine(Ile), phenylalanine(Phe), and tyrosine(Tyr), play crucial roles in the catalytic process through hydrophobic interactions, π-π stacking effects, and hydrogen bonding interactions, which provided a structural basis for understanding PTR catalytic characteristics. These findings not only give insights into the biosynthetic pathways of isoflavonoids in L. corniculatus but also offer a theoretical foundation for guiding the enhancement of flavonoid content in TCM, which are expected to promote the application and development of TCM in modern medicine.

    2025 18 v.50 [Abstract][OnlineView][Download 2556K]

  • Determination of moistening endpoint of Phellodendri Chinensis Cortex based on multi-source data fusion

    HUA Shu-tao;HE Shuang-feng;DAI Shi-qi;LIU Wei;ZHANG Ai-ling;LIU Lin-feng;LUO Xiao-jian;RAO Xiao-yong;Jiangxi University of Chinese Medicine;National Engineering Research Center for Manufacturing Technology of Solid Preparations of Traditional Chinese Medicine;

    This study aims to investigate the moistening mechanism of Phellodendri Chinensis Cortex via multiple characterization methods and characterize the moistening process and determine the endpoint based on multi-source data fusion. Low-field nuclear magnetic resonance(LF-NMR) was employed to investigate water migration and distribution patterns during the moistening process of Phellodendri Chinensis Cortex. The texture analysis was performed to monitor the hardness variations, and near-infrared spectroscopy(NIRS) was adopted to collect spectral data throughout the moistening process. The results showed that during the moistening process of Phellodendri Chinensis Cortex, water penetrated from the outer to the inner, and the content of semi-free water increased from 16.68% to 81.63% in the first 5 h. Meanwhile, the hardness decreased and gradually became stable after 5 h. The contents of berberine hydrochloride and phellodendrine hydrochloride changed mildly during the moistening process. The correlation analysis of LF-NMR parameters, hardness, water content, and chemical components demonstrated that total water content and semi-free water content exhibited correlations with hardness(P<0.05). Prediction models for water content and hardness were established based on near-infrared spectroscopy(NIRS). The models exhibited strong linear correlations(R~2>0.90), with root mean square errors of the calibration set and prediction set being closely aligned, indicating good robustness of the models. By integrating LF-NMR, texture analysis, and near-infrared spectral data, a prediction model for the moistening process and endpoint determination of Phellodendri Chinensis Cortex was established, providing a reference for non-destructive monitoring and endpoint determination in the moistening process of Chinese medicinal materials.

    2025 18 v.50 [Abstract][OnlineView][Download 2051K]

  • Isolation and characterization of supramolecules of Siwei Jianghuang Decoction and its effect on improving insulin resistance in HepG2 cells

    HUANG Xue-mei;LUO Yu-ting;ZONG Yi;PENG Jia-yan;MI Ma;CIDAN Nan-zhuo;FAN Gang;School of Pharmacy, Chengdu University of Traditional Chinese Medicine;University of Tibetan Medicine;School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine;

    The supramolecular substances in Siwei Jianghuang Decoction were isolated and characterized, and their effects and mechanisms in improving insulin resistance(IR) in HepG2 cells were investigated. The supramolecular substances were prepared using centrifugal dialysis, and their morphology was characterized by scanning electron microscopy(SEM) and laser particle size analysis. The chemical composition of supramolecular substances was analyzed using ultra-high performance liquid chromatography coupled with quadrupole exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap MS). An IR model was established in HepG2 cells by induction with glucosamine. Using glucose consumption as the evaluation index, the pharmacodynamic differences among different components of Siwei Jianghuang Decoction were assessed. The expression of proteins related to the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway was determined by Western blot. The results showed that uniformly sized, spherical supramolecular nanoparticles were present in Siwei Jianghuang Decoction, with an average particle size of(436.18 ± 7.68) nm. These supramolecular structures were mainly composed of alkaloids from Berberidis Cortex, polyphenols from Curcumae Longae Rhizoma and Phyllanthi Fructus, and flavonoids from Tribuli Fructus. Compared with the model group, the supramolecular substances significantly increased glucose consumption in HepG2 cells and upregulated the expression of phosphorylated PI3K(p-PI3K)/PI3K and phosphorylated Akt(p-Akt)/Akt. Moreover, they exhibited pharmacological activity equivalent to that of the original decoction. These findings suggest that the supramolecular substances are the key pharmacodynamic components of Siwei Jianghuang Decoction in improving IR, and their mechanism of action is associated with activation of the PI3K/Akt signaling pathway.

    2025 18 v.50 [Abstract][OnlineView][Download 1711K]

  • Ameliorative effect of refined polysaccharides from bran-fried Atractylodis Rhizoma on cyclophosphamide-induced immunosuppression and intestinal injury in mice by regulating linoleic acid metabolism

    NIE Wen-lyu;WANG Dong-peng;ZHONG Li-jiao;KE Chang;QU Ling-hang;LIU Yan-ju;School of Pharmacy, Hubei University of Chinese Medicine;Hubei Processing Engineering and Technology Center of Traditional Chinese Medicine Processing;Hubei Shizhen Laboratory;

    By using a mouse model with cyclophosphamide-induced immunosuppression and intestinal injury, this study evaluated the therapeutic advantages of refined polysaccharides from bran-fried Atractylodis Rhizoma in alleviating intestinal injury in immunosuppressed mice and explored its underlying mechanisms. Fifty male C57BL/6 mice were randomly divided into five groups: a normal group, a model group, a group of crude polysaccharides from bran-fried Atractylodis Rhizoma(1 200 mg·kg~(-1)), a group of refined polysaccharides from bran-fried Atractylodis Rhizoma(842 mg·kg~(-1)), and a positive control group(40 mg·kg~(-1) levamisole hydrochloride), with 10 mice in each group. The normal group was administered saline via gavage, while the other groups received their respective treatments for 15 consecutive days. Except for the normal group, all other groups were intraperitoneally injected with cyclophosphamide(80 mg·kg~(-1)) on days 8-10 to establish the immunosuppression and intestinal injury model. Body weight was monitored throughout the experiment. After the experiment, the spleen and thymus indices of mice were measured. Hematoxylin-eosin(HE) staining was used to evaluate pathological changes in the spleen, thymus, and small intestine tissue. Quantitative real-time polymerase chain reaction(qRT-PCR) was employed to detect the expression level of tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1β(IL-1β) mRNAs in the small intestine tissue. Alcian blue-periodic acid-Schiff(AB-PAS) staining and immunohistochemistry staining were used to assess the number of goblet cells and the expression of mucoprotein 2(MUC2) in the small intestine tissue. Immunofluorescence was performed to detect the expression of zonula occludens-1(ZO-1), occludin, and immunoglobulin A(IgA)-secreting cells in the small intestine tissue. Enzyme-linked immunosorbent assay(ELISA) was used to measure the content of secretory IgA(sIgA) in the small intestine tissue, and untargeted metabolomics was applied to analyze changes in metabolites in the small intestine tissue. The results showed that compared with those in the model group, the body weight, thymus index, spleen index, number of goblet cells, and the expression level of MUC2, TNF-α, IL-6, IL-1β, ZO-1, occludin, IgA-secreting cells, and sIgA were significantly increased in the groups of crude polysaccharides and refined polysaccharides from bran-fried Atractylodis Rhizoma. Refined polysaccharides from bran-fried Atractylodis Rhizoma demonstrated significantly stronger regulatory effects on the thymus index, ZO-1, occludin, and IL-6 compared to crude polysaccharides. Metabolomics analysis identified 13 differential metabolites in the model group and the groups of crude polysaccharides and refined polysaccharides from bran-fried Atractylodis Rhizoma, This involved 15 metabolic pathways, including unsaturated fatty acid biosynthesis, dicarboxylic acid metabolism, and linoleic acid metabolism. Among these, linoleic acid metabolism was identified as the primary metabolic pathway regulated by polysaccharides from bran-fried Atractylodis Rhizoma. Compared to crude polysaccharides, refined polysaccharides from bran-fried Atractylodis Rhizoma exhibited superior regulatory effects on metabolites in the small intestine tissue. In conclusion, the study demonstrates that both crude polysaccharides and refined polysaccharides from bran-fried Atractylodis Rhizoma can ameliorate cyclophosphamide-induced immunosuppression and intestinal injury, with refined polysaccharides showing superior efficacy. Its mechanism of action is closely related to the linoleic acid metabolism pathway.

    2025 18 v.50 [Abstract][OnlineView][Download 4379K]

  • A new jatrophane diterpenoid with anti-inflammatory activity from Euphorbia thymifolia

    LIU Yang-yang;LIANG Chang-he;CAO Jiang-ying;LU Guang-ying;ZHAO Dong-sheng;ZHAO Pan;DENG Zhi-peng;WANG Shi-jun;College of Pharmacy, Shandong University of Traditional Chinese Medicine;Shandong Co-Innovation Center of Classic Traditional Chinese Medicine Formula (Shandong University of Traditional Chinese Medicine);College of Traditional Chinese Medicine,Shandong University of Traditional Chinese Medicine;

    The 95% ethanol extract of the dried aerial parts of Euphorbia thymifolia was separated and purified by various chromatographic techniques, including MCI column chromatography, ODS column chromatography, and high-performance liquid chromatography(HPLC). The structures of the isolated monomeric compounds were determined by spectroscopic methods such as UV, IR, 1D NMR, 2D NMR, and MS. Ten compounds were isolated, namely euphthymifolone A(1), euphoscopin F(2), helioscopid D(3), euphoscopin L(4), euphoscopin E(5), helioscopinolide B(6), 2α-hydroxy helioscopinolide B(7), helioscopinolide A(8), anabellamide(9), and aurantiamide(10). Among them, compounds 1-5 are jatrophane-type diterpenoids, compounds 6-8 are abietane-type diterpenoids, and compounds 9 and 10 are alkaloids. Compound 1 is a new compound, while compounds 9 and 10 were isolated from this genus for the first time. Compound 1 showed certain nitric oxide(NO) inhibitory activity in lipopolysaccharide(LPS)-induced BV-2 cells[IC_(50)=(65.4±1.36)μmol·L~(-1)].

    2025 18 v.50 [Abstract][OnlineView][Download 1494K]

  • Chemical constituents, biological activity evaluation of Rhododendron tomentosum, and mechanisms of its anti-inflammatory, antioxidant, and anti-rheumatoid arthritis activities based on network pharmacology and molecular docking technology

    XIAO Su-ping;XIE Bin;LI Long-mei;LI Jia-shan;HE Jing-xin;LIANG Hong;LI Jian-hui;YU Shuang;GAO Yong-jian;WANG Ji-yong;ZHAO Run-huai;TU Peng-fei;School of Pharmaceutical Sciences, Peking University;China National Traditional Chinese Medicine Co., Ltd.;School of Pharmacy, Jiangxi University of Chinese Medicine;Beijing City University;Agriculture and Rural Bureau of the Administrative Office of Daxing′anling Region,Heilongjiang Province;Shimadzu Enterprise Management (China) Co., Ltd.;

    The volatile components of Rhododendron tomentosum were analyzed using GC-MS technology. Combined with non-volatile components previously identified by the research group and chemical constituents reported in the literature, network pharmacology and molecular docking techniques were employed to predict the core targets, signaling pathways, and key active constituents involved in the anti-inflammatory, antioxidant, and anti-rheumatoid arthritis(RA) effects of R. tomentosum. A comprehensive evaluation of the anti-inflammatory and antioxidant activities of its essential oils and various extracts was conducted. A total of 63 and 97 chemical constituents with peak area percentages greater than 0.1% were identified from the essential oils of the leaves and young branches of R. tomentosum, respectively, with 41 shared components. Network pharmacology analysis reveals that NF-κB, HIF-1α, IL-1β, and EGFR are core targets for the anti-inflammatory, antioxidant, and anti-RA effects of R. tomentosum, and that regulation of the PI3K/AKT and HIF-1 signaling pathways constitutes a key mechanism underlying these effects. Molecular docking results demonstrate that four constituents—lupeol, ascaridole, procyanidin B_2, and(-)-terpinen-4-ol—exhibit strong binding affinity with five key targets, i.e., NFKB1, KLF5, TOP2A, FPR1, and FPR2. The comprehensive ranking of the antioxidant and anti-inflammatory activities across different extracts was as follows: young branch essential oil > leaf essential oil > leaf aqueous extract > young branch aqueous extract > young branch ethanol extract > leaf ethanol extract. Notably, the activities of the young branch and leaf essential oils surpassed that of vitamin C. This study highlights the multi-component, multi-target, and multi-pathway characteristics of R. tomentosum, providing reliable insights for further elucidating its anti-inflammatory, antioxidant, and anti-RA mechanisms and a scientific basis for the further development and utilization of this species.

    2025 18 v.50 [Abstract][OnlineView][Download 5405K]

  • Mechanism of Buyang Huanwu Decoction in intervening diabetic pulmonary fibrosis via RAGE/MAPK3 pathway-mediated regulation of oxidative stress and lipid metabolism

    PAN Xiao-chuan;GUO Jun-feng;ZHOU Rui;LAN Pei-shu;DU Quan-yu;Hospital of Chengdu University of Traditional Chinese Medicine/College of Clinical Medicine,Chengdu University of Traditional Chinese Medicine;

    Diabetic pulmonary fibrosis(DPF) is a pulmonary complication of diabetes mellitus with complex pathogenesis, and effective treatments are urgently needed. Buyang Huanwu Decoction(BHD), a potential therapeutic agent for DPF, exhibits hypoglycemic, hypolipidemic, anti-fibrotic, and antioxidative stress effects. In this study, DPF rats were administered BHD via gavage for 3 weeks, and changes in body weight, random blood glucose from tail veins, lipid profiles, oxidative stress markers, and pulmonary collagen deposition were observed. Network pharmacology was employed to analyze the targets and mechanisms of BHD in regulating oxidative stress and lipid metabolism to intervene in DPF. Molecular docking and molecular dynamics simulations were conducted to assess the binding affinity of BHD′s active components to core DPF targets, and Western blot was used to detect BHD′s regulatory effects on key proteins in DPF rat lungs. The results showed that BHD reduced random blood glucose in DPF rats and alleviated hyperglycemia-induced weight loss, with the moderate-dose group exhibiting the most significant effects, comparable to the metformin group. BHD significantly decreased fasting serum levels of low-density lipoprotein cholesterol, triglycerides, and total cholesterol, enhanced the expression of antioxidative enzymes glutathione peroxidase and superoxide dismutase, and suppressed the oxidative end-product malondialdehyde. HE and Masson staining revealed that BHD intervention restored lung structure, reduced foam cell accumulation, and attenuated collagen deposition. Network pharmacology analysis identified mitogen-activated protein kinase 3(MAPK3), vascular endothelial growth factor A(VEGFA), and prostaglandin-endoperoxide synthase 2(PTGS2) as the primary targets of BHD in modulating oxidative stress and lipid metabolism to intervene in DPF. Enrichment analysis indicated that the advanced glycation end products/receptor for advanced glycation end products(AGE/RAGE) pathway in diabetic complications was the core pathway for BHD′s intervention in DPF. Molecular docking demonstrated that astragaloside Ⅳ and baicalein exhibited the strongest binding to PTGS2, while 6-hydroxykaempferol and formononetin showed the strongest binding to MAPK3; molecular dynamics simulations confirmed the stability of these four compound systems. Western blot results indicated that BHD significantly inhibited the activation of phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2) and reduced RAGE expression in DPF rat lungs. These findings suggest that BHD may exert anti-DPF effects by inhibiting RAGE, thereby influencing downstream ERK1/2 pathway activation, mitigating oxidative stress, lowering lipid levels, and reducing blood glucose.

    2025 18 v.50 [Abstract][OnlineView][Download 2064K]

  • Hyperoside alleviates myocardial ischemia-reperfusion injury in rats by activating PKC/mito KATP signaling pathway

    YANG Zhu;HE Shi-han;WANG Shu-fan;CAO Wen;LYU Qiu-yue;WU Jiang-ping;CHE Hui;WANG Guo-dong;HAN Jun;School of Pharmacy, Wannan Medical College;Anhui Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicine in Southern Anhui;Anhui Innovative Center for Drug Basic Research of Metabolic Diseases;Wuhu Modern Traditional Chinese Medicine and Functional Food Technology Research and Development Center;National Administration of Traditional Chinese Medicine,

    This study investigated the cardioprotective effects of hyperoside against myocardial ischemia-reperfusion injury(MIRI) and its impact on the protein kinase C(PKC)/mitochondrial ATP-sensitive potassium channel(mitoKATP) signaling pathway. A rat MIRI model was established by 30-minute left anterior descending coronary artery ligation followed by 2-hour reperfusion, while an in vitro MIRI model was created using H9c2 cardiomyocytes subjected to 12-hour hypoxia and 4-hour reoxygenation. The models were then treated with hyperoside alone or in combination with PKCα inhibitor bisindolylmaleimide I(BisI), PKCε inhibitor chelerythrine(CHE), or mitoKATP inhibitors 5-hydroxydecanoate(5-HD)/glibenclamide(GB). Myocardial infarct size was assessed by TTC staining; cardiomyocyte apoptosis was detected via TUNEL assay and flow cytometry; serum levels of creatine kinase-MB(CK-MB), superoxide dismutase(SOD), malondialdehyde(MDA), and adenosine triphosphate(ATP) were measured by ELISA; Western blot analyzed protein expression of nuclear factor erythroid 2-related factor 2(Nrf2), PKCε, inward rectifier potassium channel(Kir6.2), and caspase-3 in myocardial tissue and H9c2 cells; calcium ion(Ca~(2+)) levels were detected by immunofluorescence. Results demonstrated that hyperoside treatment significantly reduced myocardial infarct area, attenuated tissue edema, fiber disruption, inflammatory infiltration, and decreased apoptosis compared with the model group. Consistent with in vivo findings, hyperoside markedly reduced H9c2 cell apoptosis and Ca~(2+) concentration versus hypoxia/reoxygenation group. Both in vivo and in vitro experiments confirmed that hyperoside decreased MDA content and CK-MB activity, increased SOD activity and ATP levels, upregulated Nrf2, PKCε and Kir6.2 expression, while downregulating caspase-3. These beneficial effects were significantly abolished by co-administration of BisI, CHE, or 5-HD/GB. These findings suggest that hyperoside alleviates MIRI potentially through activating the PKC/mitoKATP signaling pathway.

    2025 18 v.50 [Abstract][OnlineView][Download 1611K]

  • Mechanism of Shengmai Injection in intervening in inflammatory response following cerebral ischemia based on MAPK signaling pathway

    LIU Jing-tong;CAI Qing-qing;HU Shao-wei;LI Xing-hong;ZHAO Ye;TANG Li-ying;WU Hong-wei;Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences;School of Pharmacy, Zunyi Medical University;

    This study aimed to evaluate the pharmacological effects of Shengmai Injection(SMI) on cerebral ischemia/reperfusion(I/R) injury and explore its underlying mechanisms in regulating inflammatory responses following cerebral ischemia. Male SD rats were randomly divided into a sham group, a model group, a low-dose SMI group(2 mL·kg~(-1)), a medium-dose SMI group(4 mL·kg~(-1)), a high-dose SMI group(6 mL·kg~(-1)), and a positive control group(Ginaton Injection at 4 mL·kg~(-1)), with 16 rats in each group. A rat model of middle cerebral artery occlusion/reperfusion(MCAO/R) was established using the intraluminal suture method. Drug administration began on the day of modeling and continued for three consecutive days. The therapeutic effects of SMI on brain injury in MCAO/R rats were evaluated using neurological function scoring, cerebral blood flow monitoring, cerebral infarction area determination, hematoxylin-eosin(HE) staining, and Nissl staining. The predominant therapeutic mechanisms and key signaling pathways involved in SMI treatment of cerebral ischemia in the rat model were explored using proteomic analysis. The expression of major indicators and related proteins was subsequently validated using enzyme-linked immunosorbent assay(ELISA) and Western blot. In addition, targeted metabolomics was employed to investigate downstream arachidonic acid metabolism of the related signaling pathways. Results show that compared with the sham group, the model group showed significantly increased neurological function scores and cerebral infarction area, accompanied by significantly decreased cerebral blood flow and Nissl body density. Compared with the model group, the SMI-treated groups showed significantly decreased neurological function scores and cerebral infarction area, accompanied by significantly increased cerebral blood flow and Nissl body density. The proteomic analysis results showed that the inflammatory response was the main process involved in SMI′s therapeutic effect on cerebral ischemia, with the mitogen-activated protein kinase(MAPK) signaling pathway identified as the key signaling pathway. ELISA and Western blot results showed that SMI significantly reduced the expression levels of inflammatory factors in brain tissue of MCAO/R rats, including tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-6(IL-6), with significantly regulated expression levels of phosphorylated JNK(p-JNK)/JNK and p-p38 MAPK/p38 MAPK. Targeted metabolomics further reveals that SMI significantly reduced the levels of arachidonic acid(AA) and its metabolites, such as prostaglandin D_2(PGD_2), prostaglandin E_2(PGE_2), 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], and 15(S)-hydroxyeicosatetraenoic acid [15(S)-HETE], and other pro-inflammatory mediators, accompanied by a reduced ratio of thromboxane B_2(TXB_2) to 6-keto-prostaglandin F_(1α)(6-keto-PGF_(1α)). In conclusion, SMI can effectively alleviate cerebral ischemia injury, primarily through modulation of the inflammatory response. The potential mechanism is closely related to the regulation of the MAPK signaling pathway and the downstream arachidonic acid metabolism.

    2025 18 v.50 [Abstract][OnlineView][Download 2305K]

  • Effect and mechanism of Guizhi Tongluo Tablets in alleviating cardiac inflammation and improving myocardial ischemia-reperfusion injury in mice by activating PI3K/Akt signaling pathway

    ZHANG Jing-yue;YAO Mei-dan;PANG Shu-jin;LI Jing;XU Fang;GUAN Zhuo-ji;WU Hui;FANG Hong-cheng;WANG Ling-jun;the First Affiliated Hospital of Guangzhou University of Chinese Medicine,National Key Laboratory of TCM Syndromes;Guangdong Clinical Research Institute of Traditional Chinese Medicine;Guangzhou University of Chinese Medicine;Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine;

    This study aimed to investigate the therapeutic effect and underlying mechanism of Guizhi Tongluo Tablets in myocardial ischemia-reperfusion injury(MIRI) by regulating the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway and inhibiting inflammatory response. Sixty healthy SPF-grade male C57BL/6J mice were randomly divided into sham group, model group, low-dose Guizhi Tongluo Tablets group, medium-dose Guizhi Tongluo Tablets group, high-dose Guizhi Tongluo Tablets group, and nicorandil group. The MIRI model was established by ligating the left anterior descending coronary artery for 30 min followed by reperfusion. Beginning on day 1 after the operation, the mice in the low-, medium-, and high-dose Guizhi Tongluo Tablets groups received 0.51, 1.03, and 2.06 g·kg~(-1)·d~(-1) by gavage, respectively. Mice in the nicorandil group were administered 2.28 mg·kg~(-1)·d~(-1) by gavage. Mice in the sham group and the model group received an equal volume of normal saline once daily by gavage for four consecutive weeks. Cardiac function was assessed via echocardiography. Laser speckle contrast analysis(LASCA) was used to evaluate the microvascular reperfusion in each group. Hematoxylin-eosin(HE) staining was used to observe pathological changes in cardiac tissue, while TUNEL staining was used to detect the apoptosis of cardiomyocytes. The expression levels of inflammatory cytokines interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in the myocardium were measured by qPCR and enzyme-linked immunosorbent assay(ELISA). Transcriptomic sequencing was conducted to identify differentially expressed genes, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis was used to determine the related pathways. The protein expression levels of PI3K, phosphorylated PI3K(p-PI3K), Akt, and phosphorylated Akt(p-Akt) were analyzed using the Jess automated protein analysis system. The results showed that compared with the sham group, the model group exhibited significantly reduced left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), increased infiltration of inflammatory cells in the heart tissue, disorganized cardiomyocyte arrangement, and significantly increased cardiomyocyte apoptosis. Expression levels of IL-1β, IL-6, and TNF-α were markedly upregulated, while the ratios of p-PI3K/PI3K and p-Akt/Akt were significantly decreased. Compared with the model group, mice in the Guizhi Tongluo Tablets groups showed significantly improved cardiac function, reduced inflammatory cell infiltration, partially restored cardiac structure, significantly decreased cardiomyocyte apoptosis and levels of IL-1β, IL-6, and TNF-α, along with significantly increased p-PI3K/PI3K and p-Akt/Akt levels. These findings suggest that Guizhi Tongluo Tablets can effectively prevent and treat MIRI, possibly by activating the PI3K/Akt signaling pathway and alleviating cardiac inflammation.

    2025 18 v.50 [Abstract][OnlineView][Download 1704K]

  • Molecular mechanisms of ephedrine in alleviating rheumatoid arthritis by inhibiting macrophage polarization mediated by TLR8-MyD88-TRAF6 axis

    LUOBU Qiong-qing;MIG Dmar;TSHETAN Namdrol;CIWANG Renzeng;University of Tibetan Medicine;Dingqing County Tibetan Hospital;

    This study explored molecular mechanisms by which ephedrine(EPH) inhibits the Toll-like receptor 8(TLR8)-myeloid differentiation factor 88(MyD88)-tumor necrosis factor receptor-associated factor 6(TRAF6) axis-mediated macrophage polarization to affect rheumatoid arthritis(RA). Potential targets of EPH in treating RA via the macrophage pathway were predicted by using network pharmacology and bioinformatics analysis, and the effects of EPH on the stability of key targets were verified by drug affinity response target stability(DARTS) experiments. Human RA fibroblast-like synoviocytes(MH7A) were divided into a control group, a tumor necrosis factor-α(TNF-α) group, and a TNF-α + EPH group to assess the effects of EPH on cell proliferation, invasion, apoptosis, and TLR8 protein expression. Conditioned media(CM) from macrophages treated with different stimuli were collected to intervene in MH7A cells and were further divided into the M0 macrophage CM(M0-CM) group, M1 macrophage CM(M1-CM) group, EPH + M1-CM group, siNC + M1-CM group, and siTLR8 + M1-CM group. The concentrations of inducible nitric oxide synthase(iNOS) and arginase 1(Arg-1) in the cell culture supernatant, as well as the proliferation, invasion, and apoptosis rates of MH7A cells were measured. TLR8 was further upregulated in macrophages or combined with EPH intervention. The M0 group, M1 group, M1 + EPH group, vector + M1 group, TLR8 + M1 group, and TLR8 + EPH + M1 group were divided to analyze the expression levels of TLR8, MyD88, and TRAF6 proteins. An RA rat model was established by using Freund′s complete adjuvant(FCA) to evaluate the therapeutic effects of EPH on RA. TLR8 was identified as a key target for EPH in treating RA. Compared with the control group, the TNF-α group exhibited enhanced proliferation and invasion capabilities of MH7A cells, reduced apoptosis rate, and increased TLR8 protein expression, all of which were significantly inhibited by EPH intervention. Compared with the M0-CM group, the M1-CM group showed enhanced proliferation and invasion capabilities of MH7A cells and reduced apoptosis, which could be significantly reversed by EPH intervention or TLR8 expression inhibition. Additionally, compared with the vector + M1 group, the TLR8 + M1 group exhibited up-regulated expressions of TLR8, MyD88, and TRAF6 proteins in macrophages, which could be reversed by EPH intervention. EPH can improve joint damage in RA rats, inhibit M1 macrophage polarization, and reduce the expressions of TLR8, MyD88, and TRAF6 proteins in cartilage tissue.

    2025 18 v.50 [Abstract][OnlineView][Download 1884K]

  • Network Meta-analysis of different traditional Chinese medicine injections combined with conventional western medicine in treatment of coronary heart disease complicated with heart failure

    ZHANG Qi-long;WANG Ao-long;CUI Ru-yuan;WU Wen-jun;WEI Jing-jing;ZHA Xiao-hu;ZHANG Jun-yue;TAO Xiao-you;ZHU Ming-jun;Department of Cardiovascular Diseases, the First Affiliated Hospital of Henan University of Chinese Medicine;Henan University of Chinese Medicine;

    Network Meta-analysis was performed to evaluate the efficacy and safety of different traditional Chinese medicine(TCM) injections combined with conventional western medicine in the treatment of patients with coronary heart disease complicated with heart failure. Computer searches were conducted in CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science databases for randomized controlled trial(RCT) of TCM injections from database establishment to December 15, 2024. Literature meeting inclusion criteria were evaluated using the Cochrane risk of bias tool, with network Meta-analysis performed by RevMan 5.4 and Stata 16 software. 237 RCTs were finally included, involving 22 730 total samples and 17 TCM injections. Results show:(1) clinical total effective rate improvement, the top three surface under the cumulative ranking curve(SUCRA) rankings were Shuxuetong Injection + conventional western medicine, Sodium Tanshinone Ⅱ_A Sulfonate Injection + conventional western medicine, and Shuxuening Injection + conventional western medicine.(2) Left ventricular ejection fraction(LVEF) improvement, the top three SUCRA rankings were Xuesaitong Injection + conventional western medicine, Shenqi Fuzheng Injection + conventional western medicine, and Ginkgo Leaf Extract and Dipyridamole Injection + conventional western medicine.(3) Brain natriuretic peptide(BNP) reduction, the top three SUCRA rankings were Sofren Injection + conventional western medicine, Shenmai Injection + conventional western medicine, and Shuxuetong Injection + conventional western medicine.(4) N-terminal pro-brain natriuretic peptide(NT-proBNP) reduction, the top three SUCRA rankings were Shengmai Injection + conventional western medicine, Yiqi Fumai Injection + conventional western medicine, and Xinmailong Injection + conventional western medicine.(5) TCM syndrome efficacy improvement, the top three SUCRA rankings were Shenmai Injection + conventional western medicine, Xinmailong Injection + conventional western medicine, and Shenfu Injection + conventional western medicine.(6) Left ventricular end-diastolic diameter(LVEDD) reduction, the top three SUCRA rankings were Salvianolic Acids for Injection + conventional western medicine, Yiqi Fumai Injection + conventional western medicine, and Tanshinone Ⅱ_A Sodium Sulfonate Injection + conventional western medicine.(7) Cardiac output(CO) improvement, the top three SUCRA rankings were Shenqi Fuzheng Injection + conventional western medicine, Salvianolic Acids for Injection + conventional western medicine, and Shengmai Injection + conventional western medicine.(8) 6 min walk test(6MWT) improvement, the top three SUCRA rankings were Danhong Injection + conventional western medicine, Shenmai Injection + conventional western medicine, and Shenfu Injection + conventional western medicine.(9) High-sensitivity C-reactive protein(hs-CRP) reduction, the top three SUCRA rankings were Shenfu Injection + conventional western medicine, Xinmailong Injection + conventional western medicine, and Shengmai Injection + conventional western medicine. The results show that TCM injections combined with conventional western medicine can improve clinical efficacy in patients with coronary heart disease complicated with heart failure. However, given large differences in literature quality and study numbers, the above conclusions need to be verified by more high-quality clinical RCT.

    2025 18 v.50 [Abstract][OnlineView][Download 3741K]

  • Guidelines for post-marketing research on clinical safety of Chinese patent medicines

    WANG Zhi-fei;PENG Wen-xi;QIAO Meng;ZHAN Si-yan;XIONG Wei-yi;WANG Sheng-feng;XIE Yan-ming;REN Jing-tian;Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences;School of Public Health, Peking University;Center for Drug Reevaluation, National Medical Products Administration;

    Safety research is a central focus of post-marketing drug studies and a critical component of the lifecycle management of pharmaceutical products. Chinese patent medicines are widely used in clinical practice in China due to their clear efficacy and stable dosage forms. However, their post-marketing safety issues have become increasingly prominent. Post-marketing clinical safety research on Chinese patent medicines started relatively late. To enhance its scientific rigor and standardization, Center for Drug Reevaluation, National Medical Products Administration, in collaboration with Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, took the lead in developing the Guidelines for post-marketing research on clinical safety of Chinese patent medicines(hereinafter referred to as the Guidelines). The Guidelines were standardized under the jurisdiction of the China Association of Chinese Medicine and officially released and implemented on the National Group Standards Information Platform. The Guidelines align with advanced concepts and experiences in international post-marketing drug safety research, while fully considering the unique characteristics of safety studies, the national context of China, and the specific attributes of Chinese patent medicines. The Guidelines standardize the core elements of post-marketing clinical safety research on Chinese patent medicines, which include fundamental principles(compliance, scientific rigor, and ethical considerations), decision-making for research topics(timing of initiation, research foundation, research objectives, research questions, and research methods), study design, protocol implementation, quality control, data analysis, and summary reporting. Furthermore, the Guidelines provide methodological guidance for medical research institutions, marketing authorization holders, and pharmaceutical production and distribution enterprises, promoting standardization of research processes and normalization of evidence to enhance clinical decision-making regarding safe medication use.

    2025 18 v.50 [Abstract][OnlineView][Download 1492K]

  • Problems and suggestions in management of traditional Chinese medicine seed industry

    LI Ying;CHI Xiu-lian;WANG Hong-yang;YANG Cheng-min;ZENG Yan;CHENG Meng;ZHENG Bo-wen;LI Xiao-lin;YANG Guang;State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica,China Academy of Chinese Medical Sciences;Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College;China National Traditional Chinese Medicine Co.,Ltd.;

    Seed industry is a national strategic industry, and traditional Chinese medicine(TCM)seed industry is of great significance for the long-term development of TCM cause. There is a significant interactive relationship between institutional optimization and industrial evolution. Improving the management system of TCM seed industry and promoting its high-quality development are the foundation for ensuring the healthy development of TCM industry. This paper reviewed the evolution of TCM seed industry management in China, which indicated that the TCM industry had progressed from policy document management to a stage where there were laws to follow. The current management status of TCM seed industry was described from five aspects: germplasm resource protection, variety management, production and operation, seed supervision and management, and import and export management. After years of development, the TCM seed industry has achieved certain results in terms of germplasm resource protection, variety breeding, quality standard system construction, and seed enterprise cultivation. Meanwhile, there are still deficiencies in current management in terms of supporting laws and regulations, quality standards, supervision and management, and resource protection systems. To meet the requirements for the development of the modern seed industry, ensure the healthy development of the TCM seed industry, and maintain a stable TCM supply, measures and suggestions were proposed for management of the TCM seed industry, including improving management laws and regulations, quality supervision system, and variety management and promotion system, promoting standardized production and operation, supporting scientific and technological innovation in the seed industry, and establishing a sound germplasm resource protection system. It is expected to provide ideas for the formulation and implementation of policies and promote further management system improvement of the TCM seed industry.

    2025 18 v.50 [Abstract][OnlineView][Download 1029K]
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