• Advances in liposome-delivered neuroprotective agents in treatment of ischemic stroke

    DONG Jia-hao;GAO Zi-han;HAN Fei;LIU Ming-rui;QIAN Bing-lu;CAO Wen-xuan;LIU Ying-jiao;School of Pharmacy,Jiangxi University of Chinese Medicine;

    The clinical efficacy of ischemic stroke is severely limited by the difficulty in targeted delivery of neuroprotective agents across the blood-brain barrier to the ischemic region. Liposomes, with their unique bilayer structure, can carry both hydrophilic and hydrophobic drugs and have excellent biocompatibility, modifiability, and high efficiency in crossing the blood-brain barrier, which have become a key strategy to break through the bottleneck of drug delivery in ischemic stroke treatment. This paper systematically reviews the structural properties of liposomes, their targeted delivery mechanisms, and their cutting-edge applications in ischemic stroke therapy in the past decade, focusing on the precise accumulation of neuroprotective agents in the ischemic region by surface-modified liposomes through the synergistic strategy of active/passive targeting, especially in piggybacking on the active ingredients of TCM. The paper analyzes in depth the latest advances of modified liposomes in inhibiting neuroinflammation, attenuating ischemia/reperfusion injury, combining with tissue plasminogen activator and biomimetic modification of delivery systems. It aims to provide a new theoretical framework for the precise and individualized treatment of ischemic stroke and to provide a reference for the development of neuroprotective agent delivery systems based on liposome technology.

    2025 22 v.50 [Abstract][OnlineView][Download 425K]

  • Research progress on prevention and treatment of Alzheimer′s disease with Danggui Shaoyao San

    SUN Chen-xi;HAN Xin-yuan;XIAO Yi-tong;LIU Yi-xiao;YE Tian-yuan;College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine;Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine;

    Alzheimer′s disease is a neurodegenerative disorder associated with aging. In traditional Chinese medicine(TCM), it is classified as a syndrome of root deficiency and branch excess. Danggui Shaoyao San, a classic formula traditionally used to treat gynecological disorders, has the effects of promoting blood circulation, removing blood stasis, opening orifices, awakening the mind, strengthening the spleen, resolving phlegm, and tonifying Qi to nourish the spirit. Modern clinical studies have found that Danggui Shaoyao San can slow the progression of Alzheimer′s disease and has great potential for clinical application. Recent studies indicate that Danggui Shaoyao San treats Alzheimer′s disease through multi-target and multi-level mechanisms. These include clearing amyloid β(Aβ) plaques and abnormally phosphorylated tau protein, maintaining brain-gut homeostasis, reducing oxidative stress, and regulating autophagy. Its key components, paeoniflorin and ferulic acid, have also been reported to exert antioxidant, anti-inflammatory, and anti-apoptotic effects, eliminate pathological products, and regulate the cholinergic system in the brain. This paper traces the classic formula of Danggui Shaoyao San, conducts a theoretical integration of ancient and modern medical systems, and systematically summarizes and analyzes the research related to the treatment of Alzheimer′s disease using Danggui Shaoyao San and its key components. It aims to provide a valuable reference for further research and modern application of Danggui Shaoyao San in the treatment of Alzheimer′s disease.

    2025 22 v.50 [Abstract][OnlineView][Download 333K]

  • Prevention and treatment of acute kidney injury, renal interstitial fibrosis, and diabetic kidney disease by regulating endoplasmic reticulum stress with traditional Chinese medicine: a review

    HUANG Si-yu;WANG Xi-xi;CHEN Guan-ting;CHEN Kai-li;CHEN Xu;ZHANG Lin-qi;Nephrology Department, the First Affiliated Hospital of Henan University of Chinese Medicine;the First Clinical Medical College,Henan University of Chinese Medicine;

    As the primary excretory organ responsible for maintaining internal homeostasis, renal dysfunction constitutes the pathological foundation of kidney injury. Renal cells are rich in endoplasmic reticulum(ER) structures, making endoplasmic reticulum stress(ERS) a central mechanism in regulating renal homeostasis. Numerous studies have revealed that aberrant activation of ERS leads to abnormal programmed cell death(PCD) in intrinsic renal cells and is closely associated with the progression of various kidney diseases. Consequently, suppressing ERS has emerged as a promising therapeutic direction in renal disease research. TCM offers wide clinical applicability and demonstrates advantages such as multi-target regulation, efficacy enhancement, and toxicity reduction. Accumulating research demonstrates that TCM ameliorates pathological renal damage by modulating ERS in kidney cells, thereby attenuating disease progression. Based on the regulatory mechanisms of ERS signaling pathways, this review focuses on the mechanistic actions of TCM in modulating ERS and its downstream PCD. It summarizes current evidence on the roles of Chinese herbal monomers and compound formulas for treating acute kidney injury(AKI), renal interstitial fibrosis(RIF), and diabetic kidney disease(DKD) by targeting ERS, aiming to provide novel perspectives for innovative clinical prevention and treatment strategies in renal diseases.

    2025 22 v.50 [Abstract][OnlineView][Download 143K]

  • Research progress on regulation of mitochondrial homeostasis in vascular aging mechanism and intervention by traditional Chinese medicine

    ZHONG Bo-yu;CHEN Zhuo-er;HU Qiong-wen;HUANG Xin;YAO Jia-mei;ZHONG Guang-wei;CHENG Shao-wu;Medical School, Hunan University of Chinese Medicine;Department of Geriatrics, Xiangya Hospital, Central South University;

    The pathogenesis of vascular aging is complex, and its pathological mechanisms mainly include mitochondrial dysfunction, oxidative stress, epigenetic changes, telomere dysfunction, endothelial dysfunction, and chronic inflammation. However, the pathological mechanism of vascular aging has not yet been fully elucidated. Mitochondria are key organelles regulating metabolism in eukaryotic cells. The imbalance of mitochondrial homeostasis leads to abnormal vascular function. Therefore, regulating mitochondrial homeostasis is considered an important target for the prevention and treatment of vascular aging in the future. Many studies have elucidated that traditional Chinese medicine(TCM) formulas, single herbs, and active components can specifically regulate mitochondrial homeostasis in vascular cells by affecting apoptosis or autophagy, thereby delaying vascular aging. This paper reviewed the role of mitochondrial homeostasis regulation in the pathogenesis of vascular aging from several aspects, including mitochondrial dynamics, mitophagy, mitochondrial biogenesis, and mitochondrial oxidative stress. It also summarized research progress on TCM and its extracts that protect mitochondrial function, maintain mitochondrial homeostasis, and delay vascular aging. These findings provide new ideas and methods for preventing and treating vascular aging with TCM from the perspective of mitochondrial homeostasis.

    2025 22 v.50 [Abstract][OnlineView][Download 256K]

  • Advances in natural products of Fritillaria plants

    WANG Shu-hui;MA Xu-ran;DONG Hui-wen;ZHANG Guo-wu;LIANG Hong;ZHANG Qing-ying;TU Peng-fei;State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University;Institute of Pharmacy, Shandong University of Traditional Chinese Medicine;Shangri-La Tianquan Chuanbei Technology Co., Ltd.;

    The traditional Chinese medicine(TCM) known as Beimu, including Fritillariae Cirrhosae Bulbus, Fritillariae Thunbergii Bulbus, Fritillariae Hupehensis Bulbus, Fritillariae Ussuriensis Bulbus, and Fritillariae Pallidiflorae Bulbus, possesses significant medicinal value with a long history of use, has a substantial market demand, and serves as a crucial subject of research. According to Chinese Pharmacopoeia(2020 edition), the dried bulbs of eleven Fritillaria species are the sources of Beimu. The characteristic and active ingredients steroidal alkaloids in Fritillaria species are among the natural products to be investigated earliest globally. These compounds play a pivotal role in the development of natural products and demonstrate a diverse range of pharmacological effects. This review delves into the natural products found in Fritillaria species and their pharmacological properties. Based on literature and the research achievements of the authors′ research group, this paper comprehensively summarizes, for the first time, the structural types, physicochemical properties, and spectral characteristics of steroidal alkaloids in Fritillaria species. In-depth analyses reveal that Fritillaria species contain a rich diversity of steroidal alkaloids with varied structural types, and these active ingredients hold promising potential for research on antitussive, anti-pneumonia, and acute lung injury treatment. Additionally, developing effective quality control methods based on steroidal alkaloids is crucial for the development of TCM Beimu and the standardized management of its related cultivated species.

    2025 22 v.50 [Abstract][OnlineView][Download 1654K]

  • Randomized, double-blind, double-simulated, parallel controlled clinical trial of Dingkundan Oral Liquid in treating primary dysmenorrhea with cold coagulation and blood stasis

    MA Kun;HUANG Tian-jiao;ZHOU Zhi-yu;WANG Ling;LUO Jie;TAO Yu;ZHANG Han;SUN Li-hua;GAO Cong;Xiyuan Hospital, China Academy of Chinese Medical Sciences;the First Clinical Medical College of Heilongjiang University of Chinese Medicine;Tianjin University of Traditional Chinese Medicine;Guang′anmen Hospital, China Academy of Chinese Medical Sciences;

    Dingkundan has the effect of warming Yang, dispelling cold, activating blood, resolving stasis, and relieving pain. It is used for treating dysmenorrhea, amenorrhea, menopausal disorders, infertility, and postpartum diseases caused by cold coagulation and blood stasis. Dingkundan Pills have some shortcomings, such as inconvenient administration, high sugar content, and slow absorption. Dingkundan Oral Liquid is a new dosage form developed on the basis of the pills, with a good taste, fast absorption, and convenient use, while there is no relevant research now. To evaluate the efficacy and safety of Dingkundan Oral Liquid in the treatment of primary dysmenorrhea with cold coagulation and blood stasis, a randomized controlled, double-blind, and double-simulated clinical trial was conducted. One hundred and eight subjects were randomized into test group, control group, and placebo group at a ratio of 1∶1∶1, with 36 subjects in each group. The test group, control group, and placebo group were treated with Dingkundan Oral Liquid + Ibuprofen Sustained Release Capsules simulator, Ibuprofen Sustained Release Capsules + Dingkundan Oral Liquid simulator, and two drug simulants, respectively. The course of treatment was 3 menstrual cycles. The effectiveness indicators included primary efficacy indicators [visual analogue scale(VAS) score difference], secondary efficacy indicators [total effective rate, COX menstrual symptom scale(CMSS) score difference, traditional Chinese medicine(TCM) syndrome score difference, single symptom disappearance rate, menstrual serum prostaglandin F_(2α)(PGF_(2α)), PGF_(2α)/prostaglandin E_2(PGE_2), thromboxane B_2(TXB_2), 6-keto-prostaglandin-F_(1α)(6-keto-PGF_(1α)), and pulsatility index(PI) and resistance index(RI) of uterine artery flow]. Safety was evaluated based on clinical adverse reactions/events, vital signs, and laboratory tests. The results of the clinical trial showed that after 3 menstrual cycles of treatment, VAS scores difference of the three groups had statistically significant differences, and test group and control group demonstrated significantly better therapeutic effects than placebo group. Full analysis set(FAS) of the difference between the two groups was 0.33, 95%CI[-0.19, 0.86], and per-protocol set(PPS) was 0.35, 95%CI[-0.27, 0.97]. The non-inferiority test was valid. There were statistically significant differences in total response rate, CMSS score difference, efficacy regarding TCM symptoms difference, single symptom disappearance rates, serum or plasma levels of PGF_(2α), PGF_(2α)/PGE_2, TXB_2, and 6-keto-PGF_(1α), and PI and RI of uterine artery flow among the 3 groups. In terms of safety, no adverse reactions were observed in the 3 groups, and no obvious abnormalities were observed in liver and kidney function or electrocardiogram. According to the results, Dingkundan Oral Liquid is effective in the treatment of primary dysmenorrhea with cold coagulation and blood stasis, and its therapeutic effect is not inferior to that of Ibuprofen Sustained Release Capsules commonly used in clinical practice. Moreover, Dingkundan Oral Liquid has better therapeutic effects on TCM symptoms and accompanying symptoms of dysmenorrhea, with more stable long-term curative effect, demonstrating a clinical promotion and application value.

    2025 22 v.50 [Abstract][OnlineView][Download 133K]

  • Mechanism of Bushen Culuan Formula in improving premature ovarian insufficiency by promoting angiogenesis induction in KGN through regulation of CXCR4/HIF-1α signaling pathway

    MA Kun;MA Lin-na;LUO Jie;GAO Cong;FAN Xiao-di;LI Jia-ni;GAO Shan-feng;SUN Li-hua;Xiyuan Hospital, China Academy of Chinese Medical Sciences;Experimental Research Center, China Academy of Chinese Medical Sciences;Institute of Basic Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences;Beijing University of Chinese Medicine;

    This study aimed to investigate the mechanism by which the Bushen Culuan Formula(BSCL) promotes angiogenesis induction in KGN via the CXCR4/HIF-1α signaling pathway. A cell model was established by treating KGN with triptolide, and based on this model, the optimal concentration of the CXCR4 inhibitor(AMD3100) was determined. CCK-8 assay was used to detect the effects of different concentrations of BSCL-medicated serum on the viability of KGN. After the optimal concentrations of each reagent were determined, KGN were divided into five groups: control group, triptolide group, AMD3100 group, BSCL group, and inhibitor group to corresponding interventions under different conditions. The migration ability, invasion ability, apoptosis rate, expression levels of intracellular related proteins, and secretion levels of pro-angiogenic factors were evaluated in each group. These results suggest that although the 10% BSCL-medicated serum could not regulate KGN through the Ang1/Tie2 pathway, it target and regulate the CXCR4/HIF-1α signaling pathway, enhance migration and invasion, significantly reduce early and total apoptosis rates, enhance the viability of granulosa cells within the follicle and promoting the high-level secretion of angiogenesis-inducing signaling factors such as CD34, VEGFA, EPO, and Ang2, to achieve the purpose of improving early-onset ovarian insufficiency caused by impaired ovarian angiogenesis.

    2025 22 v.50 [Abstract][OnlineView][Download 549K]

  • Mechanism of Bushen Culuan Decoction in regulating SIRT1 signaling pathway to improve mitochondrial function and premature ovarian failure

    MA Kun;LI Jia-ni;FAN Xiao-di;MA Lin-na;SUN Li-hua;Xiyuan Hospital, China Academy of Chinese Medical Sciences;Beijing University of Chinese Medicine;Institute of Basic Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences;Experimental Research Center, China Academy of Chinese Medical Sciences;

    Premature ovarian failure(POF) has been a global public health concern with a rising incidence, severely affecting women′s reproductive health and quality of life. This study aims to investigate the mechanisms by which Bushen Culuan Decoction(BCD) ameliorates ovarian mitochondrial dysfunction to improve POF. Fifty female BALB/c mice were randomly divided into control group, model group, positive drug group, low-, and high-dose BCD group. POF mouse model was established by subcutaneous injection of D-gal. Body weight and gonadal indices were observed, and changes in the estrous cycle were monitored. The level of FSH, E_2, and LH in serum was measured using ELISA. Ovarian tissue morphology and follicle counts were assessed via HE staining. In vitro model of human ovarian granulosa cells(KGN) injury was established to quantify mitochondrial number and ROS level. Protein expression of SIRT1 and PGC-1α was analyzed using Western blot. The results showed that compared with control group, model group reduced body weight gain, disordered estrous cycles, decreased ovarian and uterine indices, elevated serum FSH and LH levels, reduced E_2 level, decreased number of follicles at all developmental stages, and increased number of atretic follicles. Compared with model group, BCD group increased in ovarian and uterine indices, decreased in serum FSH and LH levels, increased in E_2 level, and decreased number of atretic follicles in mice. In vitro, BCD increased mitochondrial number, reduced ROS production, and upregulated SIRT1 and PGC-1α expressions in KGN. In conclusion, BCD improves the estrous cycle, increases ovarian and uterine indices, lowers serum FSH and LH levels, elevates E_2 level, reduces the number of atretic follicles, and protects ovarian function in POF mice. These effects may be associated with activation of the SIRT1 signaling pathway, thereby improving mitochondrial function and reducing oxidative stress in KGN.

    2025 22 v.50 [Abstract][OnlineView][Download 897K]

  • Mechanism of Fuke Qianjin Capsules in treating pelvic inflammatory disease based on network pharmacology and experimental verification

    LI Qian;HUANG Tian-jiao;GAO Cong;WANG Ling;LI Jia-ni;MA Kun;Xiyuan Hospital, China Academy of Chinese Medical Sciences;First School of Clinical Medicine, Heilongjiang University of Chinese Medicine;Beijing University of Chinese Medicine;

    This study aims to investigate the mechanism of Fuke Qianjin Capsules in treating pelvic inflammatory disease(PID) based on network pharmacology and animal experiments. The potential targets and signaling pathways of Fuke Qianjin Capsules in regulating PID were predicted by network pharmacology. The mouse model of PID was constructed and administered with different doses of Fuke Qianjin Capsules. After treatment, the uterus tissue of mice was observed for the pathological changes by HE staining. The level of IL-6 and TNF-α in the peripheral blood was measured by ELISA. The protein expression in the TLR4/PI3K/Akt/NF-κB signaling pathways was determined by Western blot. Network pharmacology indicated that a total of 78 compounds, 152 targets, 1 632 PID targets, and 72 intersection targets of "drug-disease" were obtained from Fuke Qianjin Capsules. The main active ingredients included β-sitosterol, stigmasterol, luteolin, and catechin. The key targets included TNF, IL-6, TP53, IL-1β, and CASP3. PI3K/Akt, IL-17, and lipid metabolism/atherosclerosis signaling pathways were mainly involved in the treatment. Animal experiments showed that compared with the model group, Fuke Qianjin Capsules alleviated the uterine inflammatory lesions, reduced pathological damage in the uterus tissue, and decreased the serum level of IL-6 and TNF-α, down-regulated the protein level of TLR4, PI3K, Akt, and NF-κB p65 in PID mice. These findings suggest that Fuke Qianjin Capsules can exert therapeutic effects on PID via multiple components, targets, and pathways. Meanwhile, Fuke Qianjin Capsules may reduce the inflammation and attenuate the uterine injuries of PID mice by inhibiting TLR4/PI3K/Akt/NF-κB signaling pathways.

    2025 22 v.50 [Abstract][OnlineView][Download 454K]

  • Chinese materia medica resource biodiversity in Guangxi based on the fourth national survey of Chinese materia medica resources

    KE Fang;LI Xin-hao;XIE Yue-ying;WANG Chun-li;ZHANG Xiao-bo;HUANG Xue-yan;PENG Yu-de;YU Li-ying;National Engineering Research Center for Sounthwest Endangered Medicinal Materials Resources Development,National Center for TCM Interitance and Innovation, Guangxi TCM Resources General Survey and Data Collection Key Laboratory, Guangxi Botanical Garden of Medicinal Plants;National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences;

    On the basis of the data from the fourth national survey of Chinese materia medica resources and thematic investigations in Guangxi Zhuang Autonomous Region, this study systematically classifies the Chinese materia medica resources in Guangxi by integrating modern taxonomic systems(e.g., APG Ⅳ) with GIS technology, utilizing analytical tools such as Origin 2022, R language, and PAST 4.17. It comprehensively elucidated the family/genus-level composition, geographical distribution, spatiotemporal variations, and conservation status and evaluated the biodiversity of medicinal plant resources. Key findings are summarized as follows. The resource inventory identified a total of 7 542 Chinese materia medica species in Guangxi, which included 6 354 medicinal plant species, 1 021 medicinal animal species, 118 medicinal fungal species, and 49 medicinal minerals. The medicinal plants were dominated by 11 families(e.g., Asteraceae and Fabaceae) and core genera(e.g., Ficus and Rubus). Distribution hotspots were concentrated in northwestern, northern, and central Guangxi, with regional heterogeneity driven by Karst landforms and mountainous habitats. A total of 429 species of rare and endangered medicinal plants belonging to 212 genera of 88 families were identified. Compared with the third national survey, the fourth national survey identified 2 858 new medicinal plant species, 512 new medicinal animal species, and 33 new medicinal fungal species. A systematic analysis was conducted to elucidate the driving forces behind the dynamic changes in medicinal plant resources across Guangxi. This pioneering survey systematically documents the baseline status and biodiversity dynamics of medicinal plant resources in Guangxi, establishing a data foundation for the conservation and sustainable utilization of these resources and the high-quality development of the TCM industry in Guangxi.

    2025 22 v.50 [Abstract][OnlineView][Download 1061K]

  • Effects of understory environmental factors on dynamic variations in yield and active constituent content of Epimedium pubescens

    ZHANG Hong-biao;WEN Ding-mei;QIN Feng-yuan;SUO Feng-mei;LI Dou-dou;GUO Bao-lin;Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College;Shandong University of Traditional Chinese Medicine;

    Elucidating the effects of understory environmental factors on the yield and active constituent content of medicinal plants is essential for standardizing understory cultivation techniques in medicinal plant production. This study focused on Epimedium pubescens cultivated under forest canopies. By dynamically monitoring understory environmental factors across three plantations(Phellodendron amurense, Camptotheca acuminata, and Phoebe zhennan) and open-field cultivation(CK), this study assessed variations on different spatial scales(varying forest stands and understory positions) and temporal scales. Dynamic sampling and analysis of E. pubescens yields and flavonol glycoside content were conducted, elucidating the dynamic variation characteristics and influencing factors of both the yield and active constituent content of E. pubescens in understory cultivation. The results demonstrated that:(1)The spatial variations in understory environmental factors depended on tree species characteristics and stand density, while maintaining consistent patterns across temporal scales.(2)The yields of E. pubescens and the total flavonol glycoside content in the inter-row space of the three plantations were comparable to those of CK, while the yield of E. pubescens in the inter-row space increased by 90%(P. amurense), 101%(C. acuminata), and 107%(P. zhennan), respectively, compared with that under the canopy.(3)Understory air humidity was the environmental factor contributing most significantly to the yield formation of E. pubescens. The harvest yield could be quantitatively expressed by an exponential function of air humidity(y=0.167 7e~(0.072 4x), P<0.05, R~2=0.45). These findings provide theoretical guidance and technical support for the understory cultivation of E. pubescens and similar medicinal plants.

    2025 22 v.50 [Abstract][OnlineView][Download 675K]

  • Rapid prediction of phenolic acid content in Salviae Miltiorrhizae Radix et Rhizoma by hyperspectral imaging

    LUAN Mei-qi;XIONG Feng;DAI Yao-yao;ZHAN Zhi-lai;HONG Jia-shun;NING Zhi-gui;BAI Rui-bin;YANG Jian;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;Evaluation and Research Center of Dao-di Herbs of Jiangxi Province;

    This study aims to establish a model for rapid non-destructive quantitation of main phenolic acids in Salviae Miltiorrhizae Radix et Rhizoma by hyperspectral imaging combined with chemometric methods. Hyperspectral imaging was performed for 420 Salviae Miltiorrhizae Radix et Rhizoma samples collected from Shandong, Hebei, Shanxi, Sichuan, and Anhui. Original spectral data(ORI) were preprocessed by first derivative(D1), second derivative(D2), savitzky-golay(SG) smoothing, multiplicative scattering correction(MSC), and standard normal variate(SNV) algorithms. Models for predicting the content of salvianolic acid B, lithospermic acid, danshensu, salvianolic acid Y, and rosmarinic acid were constructed via partial least squares regression(PLSR), backpropagation neural network(BPNN), and random forest regression(RFR). Additionally, iterative retained information variable(IRIV), successive projections algorithm(SPA), uninformative variables elimination(UVE), and variable iterative space shrinkage approach(VISSA) were employed for feature extraction to refine model efficiency. The results demonstrated that the PLSR model exhibited the best predictive performance. Significant differences in the number of wavelengths selected by different feature extraction methods directly impacted model performance. Therefore, preprocessing methods should be combined adaptively with appropriate feature extraction techniques to enhance model robustness. The optimal models for each component were as follows. VISSA-D1-PLSR models were selected for predicting salvianolic acid B, lithospermic acid, and salvianolic acid Y, with prediction set coefficient of determination(R_p~2) values of 0.942, 0.818, and 0.797 and residual predictive deviation(RPD) values of 4.158, 2.308, and 2.186, respectively. For danshensu and rosmarinic acid, the full-spectrum SG-PLSR models demonstrated the best performance, with R_p~2 values of 0.803 and 0.702 and RPD values of 2.162 and 1.782, respectively. This study demonstrates that HSI technology combined with chemometric methods can provide reliable technical support for predicting multiple phenolic acids in Salviae Miltiorrhizae Radix et Rhizoma and the real-time rapid evaluation of this medicinal material.

    2025 22 v.50 [Abstract][OnlineView][Download 1630K]

  • Cloning and functional study of diterpene synthase genes in Rhododendron molle

    LIU Zheng;WANG Xin-meng;WANG Rong-feng;GAO Wei;WANG Jia-dian;HU Ya-ting;HUANG Lu-qi;School of Traditional Chinese Medicine, Capital Medical University;Beijing Ditan Hospital, Capital Medical University;National 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;

    Rhododendri Mollis Flos is a Chinese herbal medicine derived from Rhododendron molle(Ericaceae), with diterpenoids being its primary bioactive constituents. Diterpene synthases are key enzymes in the biosynthetic pathway of diterpenoids. Transcriptome analysis of R. molle identified two ent-copalyl diphosphate synthase(CPS) genes(RmTPS33 and RmTPS64) and one ent-kaurene synthase(KS) gene(RmTPS65). Full-length cloning, bioinformatics analysis, and functional characterization of these three genes yielded the following results.(1) The open reading frames of RmTPS33, RmTPS64, and RmTPS65 were 2 280, 2 476, and 2 370 bp, encoding 759, 819, and 789 amino acid residues, respectively.(2)Multiple sequence alignment and phylogenetic analysis demonstrated that both RmTPS33 and RmTPS64 contained conserved CPS family motifs(LHS, PNV, and DxDD) and belonged to the TPS-c subfamily. RmTPS65 possessed conserved α-domain motifs(DDxxD and NSE/DTE) of class Ⅰ diterpene synthases and was classified into the TPS-e/f subfamily.(3) Functional assays confirmed that both RmTPS33 and RmTPS64 catalyzed the protonation-induced cyclization of GGPP to form ent-CPP, with RmTPS33 exhibiting higher catalytic activity than RmTPS64. RmTPS65 catalyzed the diphosphate elimination of ent-CPP to produce a single product, 16α-hydroxy-ent-kaurane. Furthermore, protein engineering of RmTPS33 and RmTPS64 suggested that their activity divergence stemmed from variant amino acids within functional domains. This study successfully cloned three diterpene synthases gene(RmTPS33, RmTPS64, and RmTPS65), expanding the current diterpene synthase gene repository and establishing a foundation for investigating biosynthetic pathway genes of active compounds in R. molle.

    2025 22 v.50 [Abstract][OnlineView][Download 1242K]

  • Cloning and functional characterization of O-methyltransferase gene in flavonoid synthesis pathway of Chrysanthemum indicum

    HE Zhao-yin;HE Hai-lang;XU Yu-zhen;ZHAN Ruo-ting;MA Dong-ming;the Research Center of Chinese Herbal Resource, Key Laboratory of Chinese Medicinal Resources from Lingnan, Ministry of Education, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine;

    Research has demonstrated that the O-methylation of secondary metabolites is mainly catalyzed by O-methyltransferases(OMTs). The oxygen-methylated flavonoids in plants of Asteraceae are the most abundant. However, the evolutionary pathway of the new biosynthetic capacity of flavonoids in Chrysanthemum indicum remains unknown. In this study, the methyltransferase gene CiCOMT27 was cloned from C. indicum and expressed in Escherichia coli, and the recombinant protein was isolated and purified by column chromatography. UPLC analysis showed that CiCOMT27 could transfer the methyl group from S-adenosyl-L-methionine(SAM) to the 4′-OH of luteolin and quercetin to form diosmetin and tamarixetin, and to the 3′-OH of eriodictyol to form homoeriodictyol. In addition, CiCOMT27 could catalyze the 7-OH methylation of hispidulin and scutellarein to form their corresponding methoxy derivatives, indicating that CiCOMT27 had the function of catalyzing methylation at multiple sites. When luteolin was used as the substrate, the conversion rate was as high as over 80%, and when eriodictyol, hispidulin, and scutellarein were used as substrates, the conversion rate could also reach about 60%. In addition, molecular docking experiments were conducted between CiCOMT27 and the physiological substrate luteolin of C. indicum. The results showed that luteolin was more likely to bind to CiCOMT27 at the 4′-OH site, which supported at the structural level that the CiCOMT27 had a significant preference for flavonoid substrates with hydroxyl substituents. This study provides a new molecular mechanism explanation for the structural diversity of flavonoids in C. indicum and lays a foundation for the directed design of specific methylated flavonoid derivatives.

    2025 22 v.50 [Abstract][OnlineView][Download 1213K]

  • Analysis of characteristic volatile components in Coptidis Rhizoma, Euodia rutaecarpa-processed Coptidis Rhizoma, and E. rutaecarpa juice by HS-GC-IMS and chemometrics

    MENG Ling-bang;YAN Lin;JIA Zhe;LI Ying;CHENG Ying-ying;WANG Yun;JIN Min;ZHANG Cun;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences;Guang′anmen Hospital,China Academy of Chinese Medical Sciences;

    This study aims to systematically compare the volatile components of raw Coptidis Rhizoma, Euodia rutaecarpa-processed Coptidis Rhizoma, and E. rutaecarpa juice, identify characteristic volatile markers of E. rutaecarpa-processed Coptidis Rhizoma, and elucidate the chemical basis of its "pungent" odor. The volatile components were analyzed by using headspace-gas chromatography-ion mobility spectrometry(HS-GC-IMS) and identified via the National Institute of Standards and Technology(NIST) 2020 and IMS databases. Chemical fingerprints of the three samples were compared by using VOCal 04.07 software and the Gallery Plot plugin. Chemometric analysis of the three samples was performed by SIMCA 14.1 software, with variables of variable importance in projection(VIP)>1.0, P<0.05, and fold change(FC)>1.2 or <0.83 as characteristic volatile markers of E. rutaecarpa-processed Coptidis Rhizoma. Relative odor activity values(ROAV) were calculated to evaluate odor contributions of the three samples. A total of 161 volatile components were detected by HS-GC-IMS, with 124 identified, including esters, ketones, aldehydes, and 12 other chemical categories. Common major volatile classes in raw Coptidis Rhizoma, E. rutaecarpa-processed Coptidis Rhizoma, and E. rutaecarpa juice were esters, ketones, aldehydes, terpenes, and alcohols. After processing, E. rutaecarpa-processed Coptidis Rhizoma exhibited reduced relative peak intensities in eight categories(esters, ketones, aldehydes, terpenes, alcohols, organic acids, ethers, and phenols) and increased intensities in four categories(heterocyclic compounds, sulfur-containing compounds, alkenes, and aromatic hydrocarbons), likely due to the addition of E. rutaecarpa juice. Chemometric analysis and fingerprinting showed distinct differences among the three samples, with the clustering of each sample differentiated clearly. ROAV analysis revealed significant increases in pungent-related components, such as 1-penten-3-one, n-pentanal dimer, 2-butylfuran, and methyl thiocyanate in E. rutaecarpa-processed Coptidis Rhizoma, which correlated with the introduction of E. rutaecarpa juice. The processing of E. rutaecarpa-processed Coptidis Rhizoma significantly altered the composition of volatile components by introducing chemical constituents from E. rutaecarpa juice and promoting chemical reactions, thereby enhancing the characteristic "pungent" odor profile. The study provides a reference for the scientific processing of E. rutaecarpa-processed Coptidis Rhizoma decoction pieces.

    2025 22 v.50 [Abstract][OnlineView][Download 1215K]

  • Hepatotoxicity of cinnabar and its compound in mice after administration based on content of metal elements in vivo

    ZHUO Yu-zhou;DAI Zhi-hui;HAN Zi-yan;ZHANG Xin-hui;LIU Yu-yan;ZHU Bing-qian;CHEN Li-jun;WU Jia-yi;CHAI Zhuo-yu;Mineral Medicine Research Center,Guizhou University of Traditional Chinese Medicine;State Key Laboratory of Critical Mineral Research and Exploration,Institute of Geochemistry,Chinese Academy of Sciences;

    The toxic effects of mercury and trace metal elements in cinnabar on the liver of mice were investigated, and the toxicity of cinnabar was compared with that of mercury(Hg) and selenium(Se), in order to provide suggestions for the safe use of cinnabar. Male KM mice were divided into control group, low-dose(50 mg·kg~(-1)) and high-dose(200 mg·kg~(-1)) cinnabar groups, cinnabar tranquilizing pill(ZSASW) group(600 mg·kg~(-1)), HgS group(50 mg·kg~(-1)),Hg(NO_3)_2 group(1.2 mg·kg~(-1)), Na_2SeO_3 group(1 mg·kg~(-1)), HgS-Na_2SeO_3 group(HgS: 50 mg·kg~(-1), Na_2SeO_3: 1 mg·kg~(-1)), ZS-Na_2SeO_3 group(ZS: 50 mg·kg~(-1), Na_2SeO_3: 1 mg·kg~(-1)), and ZSASW-Na_2SeO_3 group(ZSASW: 600 mg·kg~(-1), Na_2SeO_3: 1 mg·kg~(-1)), with eight mice in each group. They were administered intragastrically for one month continuously. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in the liver tissue of mice. The apoptosis of liver cells in mice was analyzed by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) method. The content of alanine aminotransferase(ALT), aspartate aminotransferase(AST), and gamma-glutamyl transferase(γ-GT) in the serum of mice was detected by an automatic biochemical analyzer. The content of trace metal elements in the liver of mice was determined by inductively coupled plasma mass spectrometry(ICP-MS). The content of Hg and Se in the liver of mice was determined by a cold atomic absorption spectrometer and an atomic fluorescence spectrometer, respectively. The results showed that the liver cells of mice in the high-dose cinnabar group, the Na_2SeO_3 group, and the Hg(NO_3)_2 group had different degrees of swelling and blurred or shrunken cell boundaries. The TUNEL experiment results showed that some liver cells in the high-dose cinnabar group, the Na_2SeO_3 group, and the Hg(NO_3)_2 group had a tendency to be larger than other cells. The ALT content in the low-dose cinnabar group was significantly lower than that in the control group, and the γ-GT content in the liver of mice in the Na_2SeO_3 group was also significantly lower than that in the control group. However, the γ-GT level in the serum of mice in the HgS-Na_2SeO_3 group and the Hg(NO_3)_2 group was significantly higher than that in the control group, and the AST content in the liver of mice in the Na_2SeO_3 group was also significantly higher than that in the control group. There was no significant difference in the content of trace metal elements in the liver of mice in each drug administration group compared with that in the control group. The trace metal elements with the highest content in the liver of mice were magnesium(Mg), calcium(Ca), and iron(Fe). The elements with the lowest content were scandium(Sc), titanium(Ti), vanadium(V), chromium(Cr), manganese(Mn), cobalt(Co), nickel(Ni), and strontium(Sr). The relative standard deviation(RSD) of Hg content in the liver of mice in each drug administration group compared with that in the control group was 136%. The highest Hg content was found in the mice in the high-dose cinnabar group, which was 16.66 μg·g~(-1), and the lowest Hg content was found in the liver of mice in the HgS-Na_2SeO_3 group, which was 0.5 μg·g~(-1). The RSD value of Se element content in the liver of mice in each administration group compared with that in the control group was 10.63%. The lowest Se content was in the ZSASW group, which was 3.50 μg·g~(-1), and the highest was in the ZSASW-Na_2SeO_3 group, which was 4.95 μg·g~(-1). The above experiments indicated that the toxicity of cinnabar and its compound ZSASW was much lower than that of Hg(NO_3)_2 and Na_2SeO_3. The content of Hg element in the liver was positively correlated with the administration dose, and Se element had a certain antagonistic effect on Hg element. When cinnabar was used scientifically under the guidance of a physician with the correct dosage and administration time, it was safe and non-toxic.

    2025 22 v.50 [Abstract][OnlineView][Download 767K]

  • Chemical constituents from fruits of Morus nigra distributed in Xinjiang and their inhibitory effects on proliferation of synovial fibroblasts

    CHEN Xin-li;WANG Sha-sha;GU Shu-miao;GAO Qing;JIANG Ke-jin;ZENG Xi;ABDULLA Yu-suf;FU Yan-hui;Laboratory of Xinjiang Native Medicinal and Edible Plant Resource Chemistry, Kashi University;Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education, Hainan Normal University;Engineering Research Center for Industrialization of Southern Medicinal Plants Resources of Hainan Province, Hainan Normal University;Key Laboratory of Research and Development of Tropical Fruit and Vegetab

    The chemical constituents from the fruits of Morus nigra distributed in Xinjiang were investigated by various chromatographic separation methods, including silica gel column chromatography, reversed-phase silica gel column chromatography, Sephadex LH-20 gel column chromatography, and preparative high-performance liquid chromatography. Based on the physicochemical properties and spectroscopic data of the isolated compounds, as well as literature data, 15 compounds were identified as morusnigrane A(1), 4-hydroxylonchocarpin(2), isobavachalcone(3), euchrenone a7(4), apigenin(5), medicarpin(6),(3R)-vestitol(7), pinnatifidanin CⅡ(8), pinnatifidanin CⅠ(9),(+)-lyoniresinol(10), artotonkin(11), resveratrol(12), 4-hydroxycinnamic acid(13), myrrhain A(14), and 2,5-di-tert-butylphenol(15). Compound 1 was a new 2-arylbenzofuran, and compounds 7-9, 14, and 15 were isolated from the genus Morus for the first time. 2-Arylbenzofurans 1 and 11, flavonoids 2-4, lignans 8 and 9, and phenolic acid 14 showed inhibitory effects on the proliferation of MH7A synovial fibroblasts with the IC_(50) values ranging from(5.17±0.05) to(152.97±0.20) μmol·L~(-1), displaying the potential of anti-rheumatoid arthritis.

    2025 22 v.50 [Abstract][OnlineView][Download 213K]

  • A new phenolic glycoside from roots of Aconitum pendulum

    DONG Dan;CHEN Si-qi;JIANG Nuan;YU Hao;MA Min;College of Pharmacy, Qinghai Minzu University;Qinghai Provincial Key Laboratory of Phytoresource Chemistry Research on the Tibetan Plateau;Modern Plateau Bio-pharmaceutical Industry College;

    Ten compounds were isolated from the 95% ethanol extract of the roots of Aconitum pendulum using silica gel chromatography, gel chromatography, and semi-preparative high-performance liquid chromatography. Their structures were identified by various spectroscopic methods, including UV, IR, HR-ESI-MS, and NMR. The compounds were identified as two phenolic compounds: 4-[α-L-arabinofuranosyl-(1→6)-β-D-glucopyranosyloxy]-3-methoxypropiophenone(1) and corchoionoside C(2); two lignans:(+)-oxabicyclooctalignan(3) and(-)-oxabicyclooctalignan(4); five diterpenoid alkaloids: benzoylaconine(5), 14-benzoyl-8-O-methylaconine(6),(-)-(A-b)-14α-benzoyloxy-N-ethyl-13β,15α-dihydroxy-1α,6α,8β,16β,18-pentamethoxyaconitane(7), smirnotine A(8), and aconitine(9); and one coumarin compound: scopoletin(10). Among them, compound 1 is a novel phenolic glycoside, while compounds 3, 4, 7, 8, and 10 were isolated from A. pendulum for the first time. The anti-inflammatory activities of the compounds were evaluated using an LPS-induced RAW264.7 macrophage inflammation model. Compounds 5, 6, and 10 inhibited LPS-induced nitric oxide(NO) production in the cells, with IC_(50) values of(34.1±1.3),(28.0±1.0), and(20.3±1.7) μmol·L~(-1), respectively.

    2025 22 v.50 [Abstract][OnlineView][Download 183K]

  • A new lignan from Syringa pinnatifolia and its cardioprotective activity in vitro

    DING Qiu-yuan;XIAO Yi-ze;SUN Jing-jing;HUANG Mei-wen;GAO Xiao-li;HE Dan;CHAI Xing-yun;Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine;Sichuan College of Traditional Chinese Medicine;

    This study aims to investigate the chemical constituents of Syringa pinnatifolia. The lignan subfraction I_3 was isolated and purified by the ODS column chromatography and semi-preparative HPLC and structurally elucidated by ~1H-NMR, ~(13)C-NMR, 2D NMR, MS, and ECD data analysis. The protective effect was evaluated based on the model of oxygen-glucose deprivation(OGD)-induced injury in HL-1 cardiomyocytes. Two lignans were isolated and identified as(-)-alashinol A(1) and alashinol A(2), of which 1 was a new lignan and exhibited a significant protective effect against the OGD-induced injury in HL-1 cardiomyocytes. A new lignan with cardioprotective activity in vitro was described in the stem of S. pinnatifolia, which provided a reference for clarifying the pharmacological substances of this herbal medicine.

    2025 22 v.50 [Abstract][OnlineView][Download 225K]

  • Effect of Jiawei Duhuo Jisheng Mixture in improving mitophagy to treat knee osteoarthritis based on PINK1/Parkin pathway

    YE Zi-feng;YUAN Yi-wei;WEN Zhi;TAN Xu-yi;OU Liang;XU Xiao-tong;KUANG Gao-yan;LU Min;Hunan University of Chinese Medicine;the First Hospital of Hunan University of Chinese Medicine;Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine;

    This study aims to investigate the effects of Jiawei Duhuo Jisheng Mixture on mitochondrial autophagy in the cartilage of rabbits with knee osteoarthritis(KOA) based on the PTEN-induced kinase 1(PINK1)/Parkinson protein(Parkin) pathway and explore its potential mechanism in improving cartilage lesions. A KOA model was established by fixing a high-molecular resin plaster bandage on the right hind limb of the rabbits for six weeks. After successful modeling, the modeling group was randomly divided into a model group, a celecoxib group, and low-and high-dose groups of Jiawei Duhuo Jisheng Mixture, with eight rabbits in each group. The celecoxib group was administered celecoxib by gavage at a single dose of 0.009 3 g·kg~(-1). The low-and high-dose groups of Jiawei Duhuo Jisheng Mixture were given Jiawei Duhuo Jisheng Mixture at single doses of 6.8 mL·kg~(-1)(4.515 2 g·kg~(-1)) and 27.2 mL·kg~(-1)(18.060 8 g·kg~(-1)), respectively. Administered once daily for six weeks, the rabbits in each group then underwent behavioral testing. After sample collection, the gross morphological changes of the knee articular cartilage were observed with the naked eye. Hematoxylin-eosin(HE) staining was used to detect pathological changes in cartilage tissue, which were quantitatively evaluated by using the Lequesne MG score, Pelletier score, and Mankin score. Transmission electron microscopy was used to observe the ultrastructural changes of chondrocyte mitochondria. Flow cytometry was used to detect the mitochondrial membrane potential(Δψm) and the average fluorescence intensity of reactive oxygen species(ROS) in chondrocytes and calculate the percentage of cells with low Δψm. Western blot was used to detect the expression level of mitochondrial autophagy-related proteins in cartilage tissue, including PINK1, Parkin, selective autophagy adapter protein 62(P62), light chain 3(LC3)Ⅱ/LCⅠ, mitochondrial outer membrane translocase 20(TOM20), collagen type Ⅱ alpha 1(COL2A1), aggrecan(ACAN), matrix metalloproteinase(MMP)-9, and MMP-13. Immunohistochemistry(IHC) was used to detect the expression of PINK1, Parkin, and LC3B in cartilage tissue. The results showed that, compared with the blank group, the model group exhibited marked knee joint swelling and damage, tissue fibrosis, sparse chondrocyte distribution, and indistinct and incomplete tide marks. The Lequesne MG, Pelletier, and Mankin scores increased significantly. Autophagosomes were reduced, and mitochondria were morphologically abnormal. The percentage of chondrocytes with low Δψm, ROS average fluorescence intensity, and the expression of P62, TOM20, MMP-9, and MMP-13 proteins in cartilage tissue rose significantly, while the expression of PINK1, Parkin, LC3Ⅱ/LCⅠ, COL2A1, and ACAN proteins in cartilage tissue decreased significantly. Compared with the model group, the celecoxib and both Jiawei Duhuo Jisheng Mixture groups showed improved knee articular cartilage surface, relatively intact tide marks, and denser chondrocytes. Their Lequesne MG, Pelletier, and Mankin scores dropped significantly. Autophagosomes increased, and mitochondrial swelling and damage eased. The percentage of chondrocytes with low Δψm, ROS average fluorescence intensity, and the expression of P62, TOM20, MMP-9, and MMP-13 proteins in cartilage tissue decreased significantly, while the expression of PINK1, Parkin, LC3Ⅱ/LCⅠ, COL2A1, and ACAN proteins in cartilage tissue increased significantly. In conclusion, Jiawei Duhuo Jisheng Mixture can effectively activate the PINK1/Parkin pathway to promote mitochondrial autophagy and alleviate articular cartilage damage in rabbits with KOA, thus slowing the progression of KOA.

    2025 22 v.50 [Abstract][OnlineView][Download 718K]

  • Mechanism of Buyang Huanwu Decoction and Didang Decoction in treatment of chronic kidney disease based on ATF6/TXNDC5-regulated "macrophage-myofibroblast transformation" pathway

    FAN Li-fei;LIN Min;GUO Yu-qin;WENG Man-hua;WU Yu-sen;QUAN Ke-zhi;CHEN Xiao-ping;LU Yu-hui;College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine;

    This study aims to investigate the mechanism of Buyang Huanwu Decoction and Didang Decoction regulating activating transcription factor 6(ATF6)/thioredoxin domain containing 5(TXNDC5) signaling axis to mediate macrophage-myofibroblast transformation(MMT) pathway in chronic kidney disease. Twenty-four SPF SD rats were randomly divided into a blank group(n=9) and a modeling group(n=15). The chronic kidney disease model was established by gavage of adenine for 28 days. After successful modeling, the modeling group was randomly divided into a model group and a Buyang Huanwu Decoction and Didang Decoction group. The blank group and the model group were treated with the same volume of physiological saline, and the Buyang Huanwu Decoction and Didang Decoction group was treated by gavage of Buyang Huanwu Decoction and Didang Decoction(13.8 g·kg~(-1)) daily for 28 days. The 24 h urine was collected on the 28th and 56th days of the experiment, and the 24 h urine protein content was detected. After the last administration, all rats were weighed and anesthetized. The kidney weight of the rats was measured, and the renal index was evaluated. The content of serum creatinine(Scr) and blood urea nitrogen(BUN) was detected by an automatic biochemical analyzer, and the concentrations of serum interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and arginase-1(Arg-1) were detected by enzyme-linked immunosorbent assay. The pathological changes of renal tissue were observed by hematoxylin-eosin staining and Masson staining, and the collagen volume fraction(CVF) was calculated. Transmission electron microscopy(TEM) was used to observe the ultrastructural changes of mitochondria in rat renal tissue cells. Multiplex immunofluorescence was used to detect the co-localization of cluster of differentiation 68(CD68)~+α-smooth muscle actin(α-SMA)~+ and CD68~+α-SMA~+collagen type Ⅰ(COL-Ⅰ)~+ in the kidney. Moreover, real-time quantitative polymerase chain reaction was utilized to quantify the mRNA levels of ATF6, TXNDC5, transforming growth factor-β1(TGF-β1), and α-SMA in renal tissue, and the protein levels of ATF6, TXNDC5, and TGF-β1 in the renal tissue were determined by Western blot. The results showed that compared with the blank group, the model group showed a significantly decreased body weight and significantly increased 24 h urine protein, kidney weight, and renal index. The serum levels of Scr, BUN, IL-1β, and TNF-α were significantly increased, while the serum levels of IL-10 and Arg-1 were significantly decreased. Furthermore, the pathological changes of renal tissue were severe, and CVF was significantly increased. The mitochondrial structure of kidney tissue was disordered. High expression of CD68~+α-SMA~+ cells was found in renal tissue, and CD68~+α-SMA~+ MMT cells significantly co-expressed COL-Ⅰ. Finally, the expression of α-SMA mRNA in renal tissue was significantly increased, and the mRNA and protein expression levels of ATF6, TXNDC5, and TGF-β1 in renal tissue were significantly increased. Buyang Huanwu Decoction and Didang Decoction significantly increased the body weight and the levels of IL-10 and Arg-1 in the serum of chronic kidney disease rats and significantly decreased the content of 24 h urine protein, kidney weight, renal index, and the serum levels of Scr, BUN, IL-1β, and TNF-α. The pathological damage of renal tissue was significantly improved, and the CVF was significantly decreased. The ultrastructural damage of renal tissue was significantly improved, as evidenced by TEM. Moreover, Buyang Huanwu Decoction and Didang Decoction decreased the expression of CD68~+α-SMA~+ and CD68~+α-SMA~+COL-Ⅰ~+ in renal tissue and down-regulated the expression level of α-SMA mRNA and the mRNA and protein levels of ATF6, TXNDC5, and TGF-β1 in renal tissue. In conclusion, Buyang Huanwu Decoction and Didang Decoction can regulate ATF6/TXNDC5 signaling pathway, down-regulate TGF-β1 expression, reduce the occurrence of MMT in chronic kidney disease, reduce renal fibrosis, and improve renal injury, so as to play a protective role in kidney.

    2025 22 v.50 [Abstract][OnlineView][Download 1006K]

  • Effect of Zuogui Jiangtang Jieyu Decoction in improving lactate production in hippocampal astrocytes with diabetes-associated depression via H3K18 lactylation modification-mediated CDH1 expression

    XIONG Yao;LI Wei;LEI Shi-hui;WANG Jin-xi;LIU Jian;LIN Xiao-yuan;YI Jian;WANG Yu-hong;YANG Hui;the First Hospital of Hunan University of Chinese Medicine;Hunan University of Chinese Medicine;

    This study aims to elucidate the underlying mechanism through which Zuogui Jiangtang Jieyu Decoction(ZGJTJYD) modulates histone 3 lysine 18 lactylation(H3K18la) modification and enhances astrocytic lactate production in the rat hippocampus with diabetes-associated depression. Sprague Dawley(SD) rats were randomly divided into a normal group, a model group, and high-, medium-, and low-dose ZGJTJYD groups. After 28 days of administration by gavage, the fasting blood glucose(FBG) was quantified by using glucometer strips. The insulin was assayed via enzyme-linked immunosorbent assay(ELISA), and the insulin resistance index(HOMA-IR) was calculated. Depressive-like behaviors were assessed by a forced swim test(FST) and an open field test(OFT). The expression of cadherin 1(CDH1) mRNA was analyzed by reverse transcription polymerase chain reaction(RT-PCR). In a subsequent independent experiment, rats were randomized into a normal group, a model group, a sham group, a L-lactate group, a ZGJTJYD group, and a 2-deoxy-D-glucose(2-DG) group. After intervention, depressive-like behaviors were assessed. Astrocyte proliferation was quantified via dual immunofluorescence staining for glial fibrillary acidic protein(GFAP) and 5-bromo-2′-deoxyuridine(Brdu), while the hippocampal lactate content was measured by ELISA. The expression of cyclin B1, H3K18la, CDH1, and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3) was analyzed by Western blot. The results showed that compared with the normal group, the model group exhibited significantly elevated FBG, insulin, and HOMA-IR(P<0.01). The immobility time in FST was significantly prolonged, and activity in OFT was significantly reduced(P<0.01). Compared with the model group, the high-and medium-dose ZGJTJYD groups exhibited significantly reduced FBG, insulin, and HOMA-IR(P<0.01), shortened immobility time, and increased activity(P<0.01). RT-PCR analysis demonstrated that compared to the model group, the ZGJTJYD groups displayed significantly downregulated expression of CDH1 mRNA(P<0.05). Compared with the model group, the ZGJTJYD groups exhibited significantly enhanced hippocampal lactate content(P<0.05), stimulated astrocyte proliferation(P<0.01), upregulated expression of cyclin B1, H3K18la, and PFKFB3 proteins(P<0.05 or P<0.01), and suppressed CDH1 expression(P<0.01). Strikingly, these effects were reversed by 2-DG. Compared with the sham group, lateral intracerebroventricular injection of L-lactate elevated the hippocampal lactate content and the H3K18la expression(P<0.05 or P<0.01), promoted astrocyte proliferation(P<0.01), increased the expression of cyclin B1 and PFKFB3, and reduced the CDH1 expression(P<0.05 or P<0.01). Therefore, ZGJTJYD increases the PFKFB3 expression and promotes lactate production in the hippocampus of rats with diabetes-associated depression. This therapeutic effect may be linked to the increased hippocampal H3K18la modification and the inhibited CDH1 expression, which in turn promotes astrocyte proliferation.

    2025 22 v.50 [Abstract][OnlineView][Download 649K]

  • Mechanism of Spatholobi Caulis in inhibiting microglial activation to intervene neuropathic pain through TLR4/MyD88/NF-κB signaling

    WU Jing;LIANG Da-yi;ZHANG Di;WANG Fang-fang;WANG Wen-jing;WANG Long;TANG Ting;CHEN Peng;School of Basic Traditional Chinese Medicine, Guizhou University of Traditional Chinese Medicine;College of the Second Clinical Medicine, Heilongjiang University of Chinese Medicine;School of Traditional Chinese Medicine, Jinan University;School of Pharmacy, Southwest Medical University;

    Based on network pharmacology and molecular docking combined with animal experimental validation, this study aims to explore the mechanism of action of Spatholobi Caulis in the treatment of neuropathic pain(NP). Ultra-high-performance liquid chromatography Q-Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) was used to identify the chemical constituents of Spatholobi Caulis, analyze the core drug-disease targets, and perform pathway enrichment and molecular docking validation. Forty-eight male Sprague Dawley(SD) rats were randomly divided into a sham group, a model group, high-dose, medium-dose, and low-dose groups of Spatholobi Caulis, and a positive control group of Pregabalin, with eight rats in each group. The NP model was established by chronic constriction injury(CCI) to the sciatic nerve of rats in all groups except the sham group in which only the sciatic nerve was exposed without ligation. Dosing was initiated after the behavioral measurements on the 5th day following modeling and was administered for 14 days. On one day before surgery, the 3rd and 5th days after CCI, and the 3rd, 7th, 11th, and 14th days after drug administration, the mechanical withdrawal threshold(MWT) and thermal withdrawal latency(TWL) of the experimental rats were measured by electronic Von Frey and a plantar test apparatus to assess changes in pain behavior. Immunohistochemistry was utilized to detect the expression of ionized calcium binding adapter molecule 1(Iba1) in spinal cord tissue. Enzyme-linked immunosorbent assay(ELISA) was used to detect the level of interleukin-6(IL-6), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α) in spinal cord tissue, and Western blot and immunofluorescence were used to detect the expression of Toll-like receptor 4(TLR4), myeloid differentiation primary response 88(MyD88), nuclear factor kappaB(NF-κB) p65, phosphorylated NF-κB(p-NF-κB) p65, IL-6, IL-1β, TNF-α, and Iba1 proteins in spinal cord tissue. The results indicated that a total of 150 compounds were identified in the Spatholobi Caulis, including 61 flavonoids, 23 isoflavonoids, 11 organic oxides, 5 coumarins, 5 linear 1,3-diphenylpropanes, and 45 other types of compounds. Network pharmacology analysis revealed that for NP treatment with Spatholobi Caulis, epidermal growth factor receptor(EGFR), protein kinase B(AKT1), signal transducer and activator of transcription 3(STAT3), TNF, cysteine-aspartic acid protease-3(CASP3), mitogen-activated protein kinase 3(MAPK3), and TLR4 were the core targets, and the regulatory effect on the TLR signaling pathway was the key mechanism. Experimental verification results showed that compared with the sham group, the model group exhibited significantly decreased MWT and TWL(P<0.01) and significantly increased expressions of TLR4, MyD88, NF-κB p65, p-NF-κB p65, Iba1, IL-1β, TNF-α, and IL-6 proteins in spinal cord tissue(P<0.01). Compared with the model group, the high-dose group of Spatholobi Caulis displayed significantly increased MWT and TWL in NP rats(P<0.05) and down-regulated expressions of TLR4, MyD88, NF-κB p65, p-NF-κB p65, Iba1, IL-1β, TNF-α, and IL-6 proteins in spinal cord tissue(P<0.05). The molecular docking results showed that multiple components had a good affinity for TLR4 and MyD88, and buddleoside had the highest affinity for TLR4 and MyD88. In summary, Spatholobi Caulis can inhibit microglia activation and alleviate NP by modulating the TLR4/MyD88/NF-κB signaling pathway.

    2025 22 v.50 [Abstract][OnlineView][Download 1106K]

  • Efficacy of Ganoderma lucidum spores in invigorating spleen via spleen meridian

    CHEN Ya-wen;WANG Lin-yuan;QIAO Hao-yi;HE Jing;ZHANG Qi;LI Lin-ze;WU Xiao-fang;ZHAO Xing-yu;WANG Chun;ZHANG Jian-jun;School of Chinese Materia Medica, Beijing University of Chinese Medicine;School of Traditional Chinese Medicine, Beijing University of Chinese Medicine;

    Based on the model of spleen deficiency, this study investigated the medicinal properties of spleen meridian tropism of Ganoderma lucidum spores and their efficacy of strengthening the spleen. Fifty SPF Kunming mice were randomly divided into a control group, a model group, an Atractylodes macrocephala group(1.1 g·kg~(-1)), a low-dose G. lucidum spores group(0.55 g·kg~(-1)), and a high-dose G. lucidum spores group(1.1 g·kg~(-1)). The mouse spleen deficiency model was established by fasting every other day, having adequate feed on the other days, and performing exhausted swimming every day for 21 consecutive days. From the first day of modeling, deionized water was given to mice in the control group and the model group in the morning of each day, and the corresponding medicine was given to the rest of the groups, with the medicines administered for 21 consecutive days. The physical signs and behavior, digestive function, energy metabolism, and immune regulation related symptoms of the mice were detected. The results showed that G. lucidum spores could improve the symptoms of spleen deficiency in mice, such as emaciation, lack of luster of fur, reduced food intake, huddling and laziness, make stools shaped and activity increased, enhance the body mass of the mice, increase their grip strength, and prolong the time of exhausted swimming. G. lucidum spores significantly increased serum D-xylose level, enhanced motilin(MTL) and gastrin(GAS) secretion, and decreased cholecystokinin(CCK), vasoactive intestinal peptide(VIP), and somatostatin(SST) mRNA expression levels in mice with spleen deficiency syndrome. G. lucidum spores elevated the levels of hepatic glycogen(LG), muscle glycogen(MG), and adenosine triphosphate(ATP), enhanced the activities of Na~+-K~+-ATPase, Ca~(2+)-Mg~(2+)-ATPase, lactate dehydrogenase(LDH), mitochondrial respiratory enzyme Ⅰ, mitochondrial respiratory enzyme Ⅳ, and ATPase, and reduced the accumulation of free fatty acid(FFA) and lactic acid(LA). G. lucidum spores increased thymus index, spleen index, elevated immunoglobulin A(IgA), immunoglobulin M(IgM), and immunoglobulin G(IgG) levels, decreased interleukin-6(IL-6), interleukin-1 beta(IL-1β), and tumor necrosis factor-α(TNF-α) levels, and improved splenic histopathological changes. The above results indicate that G. lucidum spores can improve the physical signs and behavior, digestive function, energy metabolism, and immune regulation of mice with spleen deficiency and have the medicinal properties of spleen meridian tropism and efficacy of strengthening the spleen.

    2025 22 v.50 [Abstract][OnlineView][Download 624K]

  • Mechanisms of Danggui Buxue Decoction in alleviating myocardial injury caused by chronic intermittent hypoxia by activating AMPK/mTOR signaling pathway

    CHEN Jie;ZHANG Hao;LI Dong-li;SONG Ji-xian;GUO Ya-jing;JI En-sheng;Hebei University of Chinese Medicine;Hebei Technology Innovation Center of Traditional Chinese Medicine Combined Hydrogen Medicine;

    This study aimed to explore the molecular mechanism underlying the protective effect of Danggui Buxue Decoction(DBD) against myocardial injury induced by chronic intermittent hypoxia(CIH). A CIH model was established in Sprague-Dawley(SD) rats, and DBD was administered via intragastric gavage at low, medium, and high doses(3.6, 7.2, and 14.4 g·kg~(-1)·d~(-1)). An intermittent hypoxia(IH) model was established in H9c2 cells. Cells were treated with DBD-containing serum, DBD-containing serum combined with the AMPK inhibitor Compound C, or the AMPK activator A769662. Molecular docking was used to analyze the binding affinity and interaction between the main active components of DBD and the AMPK protein. Cardiac function, myocardial histopathological changes, and mitochondrial morphological alterations were detected in SD rats. In myocardial tissue and H9c2 cells, mitochondrial membrane potential(JC-1), the activity of mitochondrial respiratory complexes Ⅰ and Ⅱ, ATP content, and MDC fluorescence staining intensity were measured. The expression levels of mitophagy-related proteins(Beclin-1, LC3-Ⅱ, LC3-Ⅰ, Parkin, PINK1, P62), apoptosis-related proteins(Bcl-2, BAX, cleaved caspase-3, caspase-3, p-p70S6K, p70S6K, Cyt C), and proteins related to the AMPK/mTOR signaling pathway(p-AMPK, AMPK, p-mTOR, mTOR, p-ULK1, ULK1) were also detected. The results showed that DBD significantly improved cardiac function and alleviated myocardial injury in CIH rats. DBD and its medicated serum upregulated the expression of Beclin-1, LC3-Ⅱ/LC3-Ⅰ, Parkin, PINK1, Bcl-2/BAX, mitochondrial Cyt C, p-AMPK/AMPK, and p-ULK1/ULK1, while downregulating the expression of P62, cleaved caspase-3/caspase-3, and p-p70S6K/p70S6K, p-mTOR/mTOR. Additionally, DBD increased mitochondrial membrane potential, the activity of respiratory complexes I and Ⅱ, ATP levels, and MDC fluorescence intensity. The AMPK activator A769662 exerted therapeutic effects similar to those of DBD, whereas the AMPK inhibitor compound C significantly suppressed the therapeutic effect of DBD-containing serum. These findings suggest that DBD alleviates CIH-induced myocardial injury by activating the AMPK/mTOR signaling pathway, thereby promoting mitophagy and inhibiting mitochondria-mediated apoptosis.

    2025 22 v.50 [Abstract][OnlineView][Download 866K]

  • Protective effect of Shengmai Injection on oxygen-glucose deprivation/reoxygenation CMEC cells based on TXNIP/NLRP3/IL-1β signaling pathways

    WANG Yan;LIU Xin-tong;CHEN Wei;FENG Bao-wei;WANG Li-ying;LIU Si-tong;CUI Yan;CHEN Zhi-an;ZHANG Jia-qi;CAI Guang-yi;LI Yan-jie;LIU Zhi;Changchun University of Chinese Medicine;Shandong University of Traditional Chinese Medicine;Children′s Diagnosis and Treatment Center, Affiliated Hospital of Changchun University of Chinese Medicine;

    This study aims to investigate the role and mechanism of Shengmai Injection in oxygen-glucose deprivation/reoxygenation(OGD/R) microvascular endothelial cell injury based on mitochondrial dysfunction mediated by thioredoxin-interacting protein(TXNIP)/NOD-like receptor protein 3(NLRP3)/interleukin(IL)-1β signaling pathways. Human cardiac microvascular endothelial cells(CMEC) were cultured in vitro to establish the OGD/R model, and the experiments were performed in a normal group, a OGD/R group, OGD/R+low-dose(10 μL·mL~(-1)) and high-dose(30 μL·mL~(-1)) groups of Shengmai Injection, and OGD/R+mitochondria-targeted antioxidant agent(Mito-Tempo, 10 μmol·L~(-1)) group. The cell counting kit-8(CCK-8) method was used to screen the effective dose of Shengmai Injection on cells. The levels of IL-1β and nitric oxide(NO), along with the activity of endothelial nitric oxide synthase(eNOS) in cell supernatants, were measured by enzyme-linked immunosorbent assay(ELISA) across all groups. Additionally, the effects of low-and high-dose SMI on IL-1β, NO, and eNOS levels in cells were assessed in the absence of OGD/R treatment. In vitro blood vessel formation assay, cell scratch assay, and Transwell cell migration assay were performed to observe the effects of Shengmai Injection on cell tube formation and migration ability. The Annexin V-FITC apoptosis kit was used to detect the level of apoptosis. The fluorescent probe method and flow cytometry were used to detect the level of reactive oxygen species(ROS) of cells in each group, and the JC-1 mitochondrial membrane potential detection kit was used to detect the mitochondrial membrane potential levels in cells. The mRNA expression of related genes in the TXNIP/NLRP3/IL-1β signaling pathways was measured by using reverse transcription quantitative polymerase chain reaction(RT-qPCR). The expression of TXNIP, NLRP3, IL-1β, cleaved caspase-1, pro-caspase-3, and cleaved caspase-3 proteins was detected by Western blot, and the expression of NLRP3 and cleaved caspase-3 proteins was measured by immunofluorescence. The results showed that compared with the normal group, SMI-H(30 μL·mL~(-1)) significantly increased NO and eNOS levels without OGD/R treatment, but had minimal effect on IL-1β levels; compared with the OGD/R group, after model establishment, IL-1β level was significantly reduced, NO and eNOS levels were increased, cell tubularity, migration and cell viability were significantly increased, apoptosis rate and ROS level were significantly reduced, and mitochondrial membrane potential was increased in all groups, the expression levels of TXNIP,NLRP3,IL-1β,and cleaved caspase-1 genes and proteins were decreased, while the ratio of pro-caspase-3 to cleaved caspase-3 was increased. In conclusion, Shengmai Injection can ameliorate cell injury induced by OGD/R. Its mechanism of action may be associated with the inhibition of TXNIP/NLRP3/IL-1β signaling pathways and amelioration of mitochondrial dysfunction.

    2025 22 v.50 [Abstract][OnlineView][Download 1632K]

  • Mechanism of action of Shengjiang Pingchuan Zhike Pills in intervention of OVA-induced bronchial asthma in rats based on proteomics

    WU Tong;HE Teng-fei;WANG Cheng-juan;BAI Min;ZHAO Si-chao;LU Bao-tang;YAN Wen-rui;ZHANG Chang-xi;College of Traditional Chinese Medicine, Ningxia Medical University;Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education;Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine;

    To explore the mechanism of action of Shengjiang Pingchuan Zhike Pills in the treatment of bronchial asthma, this study used proteomics technology to analyze the key proteins and molecular mechanisms of the ovalbumin(OVA)-induced bronchial asthma in rats and experimentally verified the core differential proteins. Sixty specific-pathogen free(SPF) rats were selected and divided into a blank group and a model group. The model was established by intraperitoneal injection and nebulization of OVA and aluminum hydroxide mixed solution. After successful modeling, the rats were divided into a blank group, a model group, a positive control group, and low-dose, medium-dose, and high-dose groups of Shengjiang Pingchuan Zhike Pills, with 10 rats in each group. The general conditions of the rats in each group were observed. The pathological changes of lung tissue were observed by hematoxylin-eosin(HE) staining, and mucus secretion, as well as basement membrane destruction and thickening were examined by periodic acid-Schiff(PAS) staining. Differentially expressed proteins and molecular mechanisms were analyzed by proteomics. The content of cytokines in bronchoalveolar lavage fluid(BALF) was verified by enzyme-linked immunosorbent assay(ELISA). The location of goblet cells and nuclear translocation of nuclear factor-κB(NF-κB) were measured by immunofluorescence, and the pathways and expression level of key proteins were verified by Western blot. Compared with those of the model group, after the intervention of Shengjiang Pingchuan Zhike Pills, the number of wheezing, stridor, and coughing times decreased; the hair luster and mental state improved; the activity increased; the breathing frequency tended to be stable; the response to external stimuli and flexibility increased, and the body weight showed an increasing trend. Pathological staining showed that after the intervention, the inflammatory infiltration of asthma rats was reduced; the thickening of airway smooth muscle was alleviated; the mucus secretion was decreased; the destruction of the basement membrane was ameliorated, and the inflammatory score and PAS score were decreased. ELISA results indicated that the expression level of interleukin-4(IL-4), interleukin-5(IL-5), interleukin-13(IL-13), and interleukin-17(IL-17) in the high-dose group decreased, and the expression level of interferon(INF)-γ increased. Immunofluorescence results showed that the number of goblet cells and mucus secretion in the high-dose group decreased; the fluorescence of phospho-NF-κB(p-NF-κB) in the nucleus weakened, and some were distributed from the nucleus to the cytoplasm. Western blot results showed that the high-dose group exhibited the down-regulated expression of cathepsin S(CTSS), mucin 5AC(MUC5AC), and p-NF-κB/NF-κB proteins and the up-regulated expression of low-affinity immunoglobulin γFc region receptor Ⅱ-b(FCGR2B) protein. In conclusion, Shengjiang Pingchuan Zhike Pills may alleviate OVA-induced airway inflammation, goblet cell metaplasia, and mucus secretion by inhibiting the NF-κB pathway, which may be related to the down-regulation of CTSS and up-regulation of FCGR2B protein expression, thereby regulating the immune balance of Th1/Th2/Th17 cells.

    2025 22 v.50 [Abstract][OnlineView][Download 653K]

  • Xianglian Pills ameliorate ulcerative colitis combined with depression in mice via histone demethylation

    ZHAO Min;XIANG Dong-yang;WANG Jia-wei;BAO Xiao-jiang;JIN Zi-xiang;SUN Zhi-yi;DING Kang;YANG Xu;Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine;School of Integrative Medicine, Nanjing University of Chinese Medicine;

    The present work aims to study the mechanism by which Xianglian Pills(XLP) treat ulcerative colitis(UC) combined with depression. The mouse model of UC combined with depression was induced by dextran sulfate sodium(DSS) in combination with chronic unpredictable mild stress(CUMS). Fifty male C57BL/6 mice were randomized into control, model, XLP(2.7, 5.4 mg·g~(-1)), and 5-aminosalicylic acid+fluoxetine groups. The disease activity index(DAI) and colon length were monitored and pathologic examination was conducted to assess UC conditions in mice. The sucrose preference test, tail suspension test, and forced swimming test were performed to assess depressive-like behavior in mice. Microglia activation status was determined by immunofluorescence detection of ionized calcium-binding adaptor molecule 1(Iba-1). The levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, IL-6, and IL-23 in the cerebral cortical area and the colon tissue were determined by ELISA. The transcript levels of IL-6 and IL-23α were measured by RT-qPCR. The levels of lysine demethylase 5B(KDM5B) and trimethylation of histone H3 lysine 4(H3K4me3) were determined by Western blot. Chromatin immunoprecipitation was adopted to examine the binding of KDM5B to the promoters of IL-6 and IL-23α. The results showed that XLP treatment reduced DAI and protected the colonic tissue structure. XLP increased the sucrose preference rate and decreased the immobilization time and the number of Iba-1-positive cells, compared with the model group. Furthermore, XLP lowered the levels of TNF-α, IL-1β, IL-6, and IL-23, down-regulated the transcript levels of IL-6 and IL-23α and the protein level of H3K4me3 while up-regulating the protein level of KDM5B in the cerebral cortical area and the colon tissue, and increased the binding of KDM5B to the IL-6 and IL-23α promoters. XLP may affect H3K4me3 demethylation through KDM5B to reduce the production of inflammatory factors and alleviate the inflammatory response, thus ameliorating UC combined with depression.

    2025 22 v.50 [Abstract][OnlineView][Download 392K]

  • Mechanism study on Smilax glabra flavonoids in improving cardiac aging in rats by inhibiting S100A8/A9-mediated activation of p38 MAPK/NF-κB pathway

    PANG Zi-yao;ZHOU Ying;XU Shan-chun;HU Le-yi;CAI Zhao-wei;WANG De-jun;School of Pharmaceutical Sciences,Zhejiang Chinese Medical University;Zhejiang Provincial Hospital of Traditional Chinese Medicine;Laboratory Animal Research Center,Academy of Chinese Medical Science,Zhejiang Chinese Medical University;

    This study investigated the mechanism by which Smilax glabra flavonoids(SGF) ameliorate D-galactose(D-gal)-induced cardiac aging in rats through the regulation of the S100 calcium-binding protein A8/A9(S100A8/A9)-mediated p38 mitogen-activated protein kinase/nuclear factor-κB(p38 MAPK/NF-κB) inflammatory pathway, utilizing both in vivo and in vitro experiments. For the in vivo experiment, a cardiac aging model was established by subcutaneous injection of D-gal(150 mg·kg~(-1)·d~(-1)) into the neck and back of rats. The rats were randomly divided into a control group, a model(D-gal) group, a low-dose SGF(54 mg·kg~(-1)) group, a high-dose SGF(108 mg·kg~(-1)) group, and a vitamin E group. For the in vitro experiment, a cellular aging model was constructed by using D-gal-induced H9c2 cardiomyocytes, with the S100A8/A9 inhibitor paquinimod(PAQ) and S100A8/A9 overexpression plasmids employed to validate the underlying mechanisms. Cognitive function and physical strength were assessed by the Morris water maze and grip strength tests, while cardiac function was evaluated via echocardiography. The whole heart weight was measured to calculate the cardiac index. Oxidative stress markers, including superoxide dismutase(SOD), catalase(CAT), glutathione peroxidase(GSH-Px), and malondialdehyde(MDA), were detected in serum and cardiac tissue. Histopathological staining [HE, Masson, dihydroethidium(DHE)] and electron microscopy were used to observe myocardial structure and mitochondrial morphology. Cellular senescence was evaluated by β-galactosidase(SA-β-gal) staining, and molecular expression levels were determined by quantitative real-time polymerase chain reaction(qRT-PCR) and Western blot. In vivo results demonstrated that SGF effectively improved weight loss in D-gal-treated rats, shortened escape latency in the water maze, increased platform crossings, and significantly enhanced cardiac ejection fraction(EF) and fractional shortening(FS). Pathological analysis revealed that SGF markedly reduced myocardial fibrosis, reactive oxygen species(ROS)-positive areas, and SA-β-gal-positive cell counts in D-gal-treated rats. Additionally, SGF significantly upregulated antioxidant enzyme activity(SOD, CAT, and GSH-Px) while downregulating the protein expression of S100A8/A9, p-p38 MAPK, and p-NF-κB. It also suppressed the expression of senescence markers(cyclin dependent kinase inhibitor 1A [CDKN1A], CDKN2A, and tumor protein 53 [Tp53]) and inflammatory cytokines(interleukin [IL]-1β, IL-6, and tumor necrosis factor-α [TNF-α]). The in vitro experiment confirmed that SGF significantly decreased SA-β-gal-positive cell counts and the expression of senescence markers and inflammatory factors. The effects of PAQ intervention were similar to those of SGF; however, these effects were reversed by S100A8/A9 overexpression. In conclusion, SGF may inhibit the activation of the S100A8/A9-mediated p38 MAPK/NF-κB inflammatory pathway to further mitigate oxidative stress, mitochondrial dysfunction, and inflammatory responses, thereby alleviating D-gal-induced cardiac aging in rats.

    2025 22 v.50 [Abstract][OnlineView][Download 1797K]

  • Multicenter, randomized, open-label, and positive-controlled clinical trial of Pien Tze Huang Capsules combined with Compound Pien Tze Huang Hemorrhoid Ointment in postoperative management of mixed hemorrhoids

    HAN Shuang-shuang;QIAO Li-chao;JIANG Feng;LIN Xiong-qiang;XU Er-wei;YANG Bo-lin;Inflammatory Bowel Disease Center, Department of Anorectum, Affiliated Hospital of Nanjing University of Chinese Medicine;the First Clinical Medical College, Nanjing University of Chinese Medicine;Zhangzhou Pien Tze Huang Pharmaceutical Co., Ltd., Fujian Provincial Key Laboratory of Pien Tze Huang Natural Medicine Research and Development;

    Pien Tze Huang has the efficacy of clearing heat, removing toxins, cooling the blood, removing blood stasis, subduing swelling, and relieving pain. It is widely used in the treatment of acute viral hepatitis, carbuncles and furuncles, unidentified swelling and poison, blunt trauma, and various inflammations. To investigate the clinical efficacy and safety of Pien Tze Huang Capsules combined with Compound Pien Tze Huang Hemorrhoid Ointment in controlling the postoperative inflammatory response of wounds in patients undergoing surgery for mixed hemorrhoids, a multicenter, randomized, open-label, and positive-controlled clinical trial was conducted at 12 tertiary medical institutions in China. A total of 240 patients who underwent Milligan-Morgan hemorrhoidectomy for mixed hemorrhoids were enrolled and randomly assigned to the treatment or control group(1∶1). Both groups received sitz baths with Compound Jingjie for Fumigation and Washing as basic treatment. The treatment group additionally received Pien Tze Huang Capsules orally(2 capsules per dose, 3 times per day) and topical application of Compound Pien Tze Huang Hemorrhoid Ointment(2.5 g, twice per day), while the control group received topical Mayinglong Shexiang Hemorrhoid Ointment(2.5 g, twice per day). The treatment duration was 7 days. Primary efficacy endpoints included wound exudation scores, wound bleeding scores, and wound granulation tissue formation scores, and secondary endpoints included perianal edema scores, pain score using pain visual analogue scale(VAS) scores, postoperative analgesic use, and adverse events. Results showed that in the full analysis set(FAS), the wound exudation scores on postoperative day 7 was significantly lower in the treatment group compared to that in the control group(P<0.05). In the per-protocol set(PPS), the wound exudation scores on postoperative days 3 and 7 was also significantly lower in the treatment group(P<0.05). While the treatment group showed lower perianal edema scores and pain VAS scores than the control group, the differences were not statistically significant. No statistically significant differences were observed between the two groups in wound bleeding scores, wound granulation tissue formation scores, analgesic use rate or amount, or incidence of adverse reactions. A total of 56 adverse events were observed, with 25 in the treatment group and 31 in the control group. The incidence of adverse reactions was comparable between groups, with no statistically significant difference. No serious drug-related adverse events were observed in either group. The results suggest that the Pien Tze Huang Capsules combined with Compound Pien Tze Huang Hemorrhoid Ointment can reduce wound exudation after surgery for mixed hemorrhoids, playing a beneficial role in controlling postoperative inflammation. The treatment offers good safety and tolerability, showing great potential as a postoperative adjunctive therapy integrating traditional Chinese medicine and western medicine.

    2025 22 v.50 [Abstract][OnlineView][Download 135K]

  • Development of core outcome set for efficacy evaluation of traditional Chinese medicine treatment of early-stage respiratory virus infection with external cold and internal heat syndrome

    GAO Zhuo;TIAN Chen;LU Ting-ting;SHI Jia-heng;ZHAO Xin;QI Wen-sheng;LIU Jie;GE Long;Guang′anmen Hospital, China Academy of Chinese Medical Sciences;School of Nursing, Gansu University of Chinese Medicine;Department of Health Policy and Management, School of Public Health, Lanzhou University;Key Laboratory of Evidence-based Medicine,Gansu Province;Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences;

    This study constructed a core outcome set(COS) for traditional Chinese medicine(TCM) treatment of early-stage external cold and internal heat syndrome in respiratory viral infections, aiming to provide a reference for selecting outcomes in related clinical studies. A literature review was conducted to collect outcomes related to the early-stage external cold and internal heat syndrome in respiratory viral infections under TCM treatment from randomized controlled trials, systematic reviews, guidelines, and registered clinical trial protocols. Supplementary searches were performed in high-impact journals for systematic reviews on conventional medicine treatments for respiratory viral infections, as well as on the official websites of the Center for Drug Evaluation of the National Medical Products Administration and the US Food and Drug Administration, to develop the initial outcome pool. Two rounds of the Delphi surveys using a 9-point Likert scale were conducted to evaluate the importance of outcomes. The final outcomes were determined through a face-to-face expert consensus meeting. A total of 31 clinical studies, five systematic reviews, two guidelines, five registered clinical trial protocols, and eight new drug evaluation guidelines were included. After standardizing and sorting the outcomes, a pool of 34 outcomes was established. After two rounds of Delphi surveys, 17 outcomes were initially included. After the expert consensus meeting, 10 core outcome indicators were finally determined, including rate of progression to severe cases, time to major symptom improvement, time to resolution of all symptoms, dosage of antipyretic and analgesic medications, incidence of adverse events, time to viral clearance, mortality rate, quality of life, length of hospital stay, and time to normalization of body temperature.

    2025 22 v.50 [Abstract][OnlineView][Download 182K]
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