1.Rehmanniae Radix Iridoid Glycosides Protect Kidneys of Diabetic Mice by Regulating TGF-β1/Smads Signaling Pathway
Hongwei ZHANG ; Ming LIU ; Huisen WANG ; Wenjing GE ; Xuexia ZHANG ; Qian ZHOU ; Huani LI ; Suqin TANG ; Gengsheng LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):56-66
ObjectiveTo investigate the protective effect of Rehmanniae Radix iridoid glycosides (RIG) on the kidney tissue of streptozotocin (STZ)-induced diabetic mice and explore the underlying mechanism. MethodsTwelve of 72 male C57BL/6J mice were randomly selected as the normal group, and the remaining 60 mice were fed with a high-fat diet for six weeks combined with injection of 60 mg·kg-1 STZ for 4 days to model type 2 diabetes mellitus. The successfully modeled mice were randomized into model, metformin (250 mg·kg-1), catalpol (100 mg·kg-1), low-dose RIG (RIG-L, 200 mg·kg-1) and high-dose RIG (RIG-H, 400 mg·kg-1) groups (n=11). Mice in each group were administrated with corresponding drugs, while those in the normal group and model group were administrated with the same dose of distilled water by gavage once a day. After 8 weeks of intervention, an oral glucose tolerance test (OGTT) was performed, and the area under the curve (AUC) was calculated. After mice were sacrificed, both kidneys were collected. The body weight, kidney weight, and fasting blood glucose (FBG) were measured. Biochemical assays were performed to measure the serum levels of triglycerides (TG), total cholesterol (TC), serum creatinine (SCr), and blood urea nitrogen (BUN). Enzyme-linked immunosorbent assay (ELISA) was employed to determine the serum level of fasting insulin (FINS), and the insulin sensitivity index (ISI) and homeostatic model assessment for insulin resistance (HOMA-IR) were calculated. The pathological changes in kidneys of mice were observed by hematoxylin-eosin staining and Masson staining. The immunohistochemical method (IHC) was employed to assess the expression of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), transforming growth factor-β1 (TGF-β1), and collagen-3 (ColⅢ) in the kidney tissue. The protein levels of TGF-β1, cell signal transduction molecule 3 (Smad3), matrix metalloproteinase-9 (MMP-9), and ColⅢ in kidneys of mice were determined by Western blot. ResultsCompared with the normal group, the model group showcased decreased body weight and ISI (P<0.01), increased kidney weight, FBG, AUC, FINS, HOMA-IR, TC, TG, SCr, and BUN (P<0.01), glomerular hypertrophy, capsular space narrowing, and collagen deposition in the kidney, up-regulated protein levels of IL-1, IL-6, TNF-α, TGF-β1, ColⅢ, and Smad3 (P<0.01), and down-regulated protein level of MMP-9 (P<0.01) in the kidney tissue. Compared with the model group, the treatment groups had no significant difference in the body weight and decreased kidney weight (P<0.05, P<0.01). The FBG level declined in the RIG-H group after treatment for 4-8 weeks and in the metformin, catalpol, and RIG-L groups after treatment for 6-8 weeks (P<0.01). The AUC in the RIG-L, RIG-H, and metformin groups decreased (P<0.05, P<0.01). The levels of TC, SCr, and BUN in the serum of mice in each treatment group became lowered (P<0.05, P<0.01). The level of TG declined in the RIG-L, RIG-H, and metformin groups (P<0.05, P<0.01). The serum level of FINS declined in the catalpol, RIG-L, and metformin groups (P<0.01). Compared with the model group, the treatment groups showed decreased HOMA-IR (P<0.01), increased ISI (P<0.01), alleviated pathological changes in the kidney tissue, and down-regulated expression of IL-1 and TGF-β1. In addition, the protein levels of IL-6, TNF-α, and ColⅢ in the RIG-H and metformin groups and IL-6 and TNF-α in the RIG-L group were down-regulated (P<0.05, P<0.01), and the protein levels of IL-6, TNF-α, and ColⅢ in the catalpol group and ColⅢ in the RIG-L group showed a decreasing trend without statistical difference. The protein levels of TGF-β1, Smad3, and ColⅢ in the RIG-H and metformin groups were down-regulated (P<0.01). Compared with that in the model group, the protein level of MMP-9 was up-regulated in each treatment group (P<0.01). ConclusionRIG can improve the renal structure and function of diabetic mice by regulating the TGF-β1/Smads signaling pathway.
2.Effect of Stattic on the survival of mouse heart allograft by regulating memory CD4+T cell-mediated acute rejection
Shiliang LI ; Yi FENG ; Ming FANG ; Yan ZHOU
Organ Transplantation 2025;16(1):74-82
Objective To investigate the effect and mechanism of the signal transducer and activator of transcription 3 (STAT3) inhibitor Stattic on the rejection of mouse heart allograft. Methods BALB/c mice (donors) were used to transplant skin onto C57BL/6 mice (recipients). Four weeks later, memory CD4+ T cells (CD4+Tm) were isolated from the recipient mice's spleens. Mixed lymphocyte reaction experiment was conducted with C57BL/6 mouse splenocytes and CD4+Tm, and the EdU method was used to detect the effect of Stattic on CD4+Tm cell proliferation. A C57BL/6 mouse heart transplant (HTx) model was constructed, and the experiment was divided into four groups: Non-HTx group, HTx group, Tm/HTx group, and Tm/HTx+Stattic group. The survival of heart allografts in mice was observed daily. Hematoxylin-eosin staining was used to observe the histopathology of the heart allografts. Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression levels of interferon (IFN)-γ, interleukin (IL)-2, IL-10, and transforming growth factor-β1 (TGF-β1) messenger RNA (mRNA) in the heart allografts. Enzyme-linked immunosorbent assay was used to detect the levels of IFN-γ, IL-2, IL-10, and TGF-β1 in the serum. Flow cytometry was used to detect the levels of CD4+Tm (CD4+CD44+CD62L+) in splenic lymphocytes. And Western blotting was used to detect the expression levels of STAT3 and p-STAT3 proteins in the heart allografts. Results When the concentration of Stattic exceeded 2.5 μmol/L, it could inhibit the proliferation of CD4+Tm cells. Compared with the HTx group, the Tm/HTx group showed shorter survival time of heart grafts, more severe histopathological damage, increased serum IFN-γ and IL-2 levels, decreased IL-10 and TGF-β1 levels, increased relative expression of IFN-γ and IL-2 mRNA, decreased relative expression of IL-10 and TGF-β1 mRNA in the heart allografts, increased proportion of CD4+Tm in splenic lymphocytes, and increased p-STAT3/STAT3 ratio in the heart allografts (all P<0.05). Compared with the Tm/HTx group, the Tm/HTx+Stattic group showed longer survival time of heart grafts, less severe histopathological damage, decreased serum IFN-γ and IL-2 levels, increased IL-10 and TGF-β1 levels, decreased relative expression of IFN-γ and IL-2 mRNA, increased relative expression of IL-10 and TGF-β1 mRNA in the heart allografts, decreased proportion of CD4+Tm in splenic lymphocytes, and decreased p-STAT3/STAT3 ratio in the heart allografts (all P<0.05). Conclusions Stattic may prolong the survival time of mouse heart allografts, and its mechanism may be related to the inhibition of CD4+Tm- mediated acute rejection.
3.Analysis of Clinical Consistency of Animal Models of Attention Deficit Hyperactivity Disorder Based on Characteristics of Clinical Diseases and Syndromes in Traditional Chinese and Western Medicine
Xinyue XIE ; Xiaomian LIU ; Ming LI ; Mengfei WANG ; Rongyi ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):270-278
ObjectiveBased on a new method for animal model evaluation, this study aims to analyze the characteristics of diseases and syndromes of existing animal models of attention deficit hyperactivity disorder (ADHD) from both traditional Chinese medicine (TCM) and western medical perspectives and propose suggestions for improvement. MethodsA systematic search of the China National Knowledge Infrastructure (CNKI) and PubMed was conducted for literature on ADHD animal models. According to TCM and western medical diagnostic criteria, core and accompanying symptoms of the models were assigned with scores to comprehensively evaluate the clinical consistency. ResultsThe selection of experimental animals for ADHD models primarily involved rodents, with modeling methods including genetic, chemical induction, and environmental induction. The average consistency of clinical diseases and syndromes with TCM and western medicine was 45.19% and 49.42%, respectively. The spontaneously hypertensive (SHR) rats and nicotine/smoking models had the highest consistency with TCM, while the social isolation models had the highest consistency with western medicine. Most models were guided by western medicine theories, which can meet the surface validity and structural validity requirements of western medicine but lacked precise differentiation of TCM syndromes. ConclusionExisting ADHD animal models primarily focus on a single genotype or environmental factor, lacking comprehensive consideration of multigenic interactions and environmental factors. Moreover, the selection of model evaluation indicators is relatively singular, primarily focusing on "disease" indicators, while TCM "syndrome" indicators have not been fully considered. It is recommended to introduce a "formula-to-syndrome" approach in the preparation of TCM models for ADHD and establish and improve an evaluation system of animal models combining diseases and syndromes, so as to provide a solid foundation for future experimental research.
4.Analysis of Clinical Consistency of Animal Models of Attention Deficit Hyperactivity Disorder Based on Characteristics of Clinical Diseases and Syndromes in Traditional Chinese and Western Medicine
Xinyue XIE ; Xiaomian LIU ; Ming LI ; Mengfei WANG ; Rongyi ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):270-278
ObjectiveBased on a new method for animal model evaluation, this study aims to analyze the characteristics of diseases and syndromes of existing animal models of attention deficit hyperactivity disorder (ADHD) from both traditional Chinese medicine (TCM) and western medical perspectives and propose suggestions for improvement. MethodsA systematic search of the China National Knowledge Infrastructure (CNKI) and PubMed was conducted for literature on ADHD animal models. According to TCM and western medical diagnostic criteria, core and accompanying symptoms of the models were assigned with scores to comprehensively evaluate the clinical consistency. ResultsThe selection of experimental animals for ADHD models primarily involved rodents, with modeling methods including genetic, chemical induction, and environmental induction. The average consistency of clinical diseases and syndromes with TCM and western medicine was 45.19% and 49.42%, respectively. The spontaneously hypertensive (SHR) rats and nicotine/smoking models had the highest consistency with TCM, while the social isolation models had the highest consistency with western medicine. Most models were guided by western medicine theories, which can meet the surface validity and structural validity requirements of western medicine but lacked precise differentiation of TCM syndromes. ConclusionExisting ADHD animal models primarily focus on a single genotype or environmental factor, lacking comprehensive consideration of multigenic interactions and environmental factors. Moreover, the selection of model evaluation indicators is relatively singular, primarily focusing on "disease" indicators, while TCM "syndrome" indicators have not been fully considered. It is recommended to introduce a "formula-to-syndrome" approach in the preparation of TCM models for ADHD and establish and improve an evaluation system of animal models combining diseases and syndromes, so as to provide a solid foundation for future experimental research.
5.Clinical efficacy of valve surgery for infective endocarditis in 343 patients: A retrospective study in a single center
Shuanglei ZHAO ; Zhou LIU ; Bin WANG ; Zhaoqing SUN ; Mingxiu WEN ; Qianxian LI ; Yi HU ; Wenjian JIANG ; Jie HAN ; Jiangang WANG ; Ming GONG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(08):1133-1139
Objective To analyze the clinical efficacy of valve surgeries for infective endocarditis and the affecting factors, and compare the early- and long-term postoperative outcomes of different surgery approaches. Methods The patients with infective endocarditis who underwent valve replacement/valvuloplasty in our hospital from 2010 to 2022 were retrospectively collected. The clinical data of the patients were analyzed. Results A total of 343 patients were enrolled, including 197 patients with mechanical valve replacement, 62 patients with bioprosthetic valve replacement, and 84 patients with valvuloplasty. There were 238 males and 105 females with an average age of (44.2±14.8) years. Single-valve endocarditis was present in 200 (58.3%) patients, and multivalve involvement was present in 143 (41.7%) patients. Sixty (17.5%) patients had suffered thrombosis before surgery, including cerebral embolisms in 32 patients. The mean follow-up time was (60.6±43.8) months. Early mortality within one month after the surgery occurred in 17 (5.0%) patients, while later mortality occurred in 19 (5.5%) patients. Eight (2.3%) patients underwent postoperative dialysis, 13 (3.8%) patients suffered postoperative stroke, 6 patients underwent reoperation, and 3 patients suffered recurrence of infective endocarditis. Smoking (P=0.002), preoperative embolisms (P=0.001), duration of surgery (P=0.001), and postoperative dialysis (P=0.001) were risk factors for early mortality, and left ventricular ejection fraction ≥60% (P=0.022) was protective factor for early mortality. New York Heart Association classification Ⅲ-Ⅳ (P=0.010) and ≥3 valve procedures (P=0.028) were risk factors for late mortality. The rate of composite endpoint events was significantly lower in the valvuloplasty group than that in the valve replacement group. Conclusion For patients with infective endocarditis, smoking and preoperative embolisms are associated with high postoperative mortality, multiple-valve surgery is associated with a poorer prognosis, and valvuloplasty has advantages over valve replacement and should be attempted in the surgical management of patients with infective endocarditis.
6.Identification of blood-entering components of Anshen Dropping Pills based on UPLC-Q-TOF-MS/MS combined with network pharmacology and evaluation of their anti-insomnia effects and mechanisms.
Xia-Xia REN ; Jin-Na YANG ; Xue-Jun LUO ; Hui-Ping LI ; Miao QIAO ; Wen-Jia WANG ; Yi HE ; Shui-Ping ZHOU ; Yun-Hui HU ; Rui-Ming LI
China Journal of Chinese Materia Medica 2025;50(7):1928-1937
This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals
;
Drugs, Chinese Herbal/administration & dosage*
;
Tandem Mass Spectrometry/methods*
;
Sleep Initiation and Maintenance Disorders/metabolism*
;
Mice
;
Network Pharmacology
;
Male
;
Chromatography, High Pressure Liquid
;
Humans
;
Protein Interaction Maps/drug effects*
;
Sleep/drug effects*
;
Female
;
Adult
7.Banxia Xiexin Decoction reshapes tryptophan metabolism to inhibit progression of colon cancer.
Yi-Fang JIANG ; Yu-Qing HUANG ; Heng-Zhou LAI ; Xue-Ke LI ; Liu-Yi LONG ; Feng-Ming YOU ; Qi-Xuan KUANG
China Journal of Chinese Materia Medica 2025;50(5):1310-1320
This study explores the effect and mechanism of Banxia Xiexin Decoction(BXD) in inhibiting colon cancer progression by reshaping tryptophan metabolism. Balb/c mice were assigned into control, model, low-dose BXD(BXD-L), and high-dose BXD(BXD-H) groups. Except the control group, the other groups were subcutaneously injected with CT26-Luc cells for the modeling of colon cancer, which was followed by the intervention with BXD. Small animal live imaging was employed to monitor tumor growth, and the tumor volume and weight were measured. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in mouse tumors. Immunohistochemistry was used to detect Ki67 expression in tumors. Immunofluorescence and flow cytometry were used to detect the infiltration and number changes of CD3~+/CD8~+ T cells in the tumor tissue. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interferon-gamma(IFN-γ) and interleukin-2(IL-2) in tumors. Targeted metabolomics was employed to measure the level of tryptophan(Trp) in the serum, and the Trp content in the tumor tissue was measured. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of indoleamine 2,3-dioxygenase 1(IDO1), MYC proto-oncogene, and solute carrier family 7 member 5(SLC7A5) in the tumor tissue. Additionally, a co-culture model with CT26 cells and CD8~+ T cells was established in vitro and treated with the BXD-containing serum. The cell counting kit-8(CCK-8) assay was used to examine the viability of CT26 cells. The content of Trp in CT26 cells and CD8~+ T cells, as well as the secretion of IFN-γ and IL-2 by CD8~+ T cells, was measured. RT-qPCR was used to determine the mRNA levels of MYC and SLC7A5 in CT26 cells. The results showed that BXD significantly inhibited the tumor growth, reduced the tumor weight, and decreased the tumor volume in the model mice. In addition, the model mice showed sparse arrangement of tumor cells, varying degrees of patchy necrosis, and downregulated expression of Ki67 in the tumor tissue. BXD elevated the levels of IFN-γ and IL-2 in the tumor tissue, while upregulating the ratio of CD3~+/CD8~+ T cells and lowering the levels of Trp, IDO1, MYC, and SLC7A5. The co-culture experiment showed that BXD-containing serum reduced Trp uptake by CT26 cells, increased Trp content in CD8~+T cells, enhanced IL-2 and IFN-γ secretion of CD8~+T cells, and down-regulated the mRNA levels of MYC and SLC7A5 in CT26 cells. In summary, BXD can inhibit the MYC/SLC7A5 pathway to reshape Trp metabolism and adjust Trp uptake by CD8~+ T cells to enhance the cytotoxicity, thereby inhibiting the development of colon cancer.
Animals
;
Tryptophan/metabolism*
;
Colonic Neoplasms/pathology*
;
Mice
;
Drugs, Chinese Herbal/administration & dosage*
;
Mice, Inbred BALB C
;
Humans
;
Cell Line, Tumor
;
Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism*
;
Female
;
Disease Progression
;
Cell Proliferation/drug effects*
;
Proto-Oncogene Mas
;
Male
8.Prescription pattern of traditional Chinese medicine for treatment of hypertensive left ventricular hypertrophy based on multivariate data mining.
Xuan-Yang WANG ; Yuan GAO ; Bin LI ; Rui YU ; Shi-Yang XIE ; Lu-Ye ZHOU ; Yu-Die SUN ; Ming-Jun ZHU
China Journal of Chinese Materia Medica 2025;50(6):1688-1698
This study explored the prescription pattern of traditional Chinese medicine(TCM) in the treatment of hypertensive left ventricular hypertrophy(LVH), so as to provide a relevant theoretical basis for the clinical diagnosis and treatment of hypertensive LVH. The study systematically searched the databases of CNKI, Wanfang, VIP, and SinoMed to screen out the qualified literature on TCM treatment of hypertensive LVH and used Microsoft Excel 2021 to establish the relevant prescription database. It also counted the frequency, property, flavor, and meridian affiliation of TCM in the prescriptions and classified their efficacy. The study used Lantern 5.0 and Rstudio software to analyze the hidden structural models and association rules of the high-frequency TCM with a frequency of >3.50% and adopted Origin 2024 software to visualize the data, so as to explore the prescription pattern of TCM in treating hypertensive LVH. The results showed that a total of 128 TCM prescriptions were included, involving 163 TCM with a total frequency of 1 242. The high-frequency TCM included Salviae Miltiorrhizae Radix et Rhizoma, Uncariae Ramulus Cum Uncis, Gastrodiae Rhizoma, Poria, and Chuanxiong Rhizoma, with the main efficacy from blood-activating and stasis-resolving herbs, tonic herbs, and liver-calming and wind-extinguishing herbs. The latent structure analysis(LSA) identified 10 latent variables, 20 latent classes, 7 comprehensive clustering models, and 23 core prescriptions. It was speculated that the common syndromes of hypertensive LVH included blood stasis obstructing the collaterals, ascending hyperactivity of liver Yang, Yin deficiency with Yang hyperactivity, and intermingled phlegm and blood stasis. The association rule analysis yielded 33 strong association rules, with the highest comprehensive association rule being Gastrodiae Rhizoma→Uncariae Ramulus Cum Uncis. Hypertensive LVH is characterized by asthenia in origin and asthenia in superficiality, with Yin deficiency and Qi deficiency as the origin and blood stasis and phlegm as the superficiality. Clinical treatment focuses on activating blood circulation, resolving stasis, tonifying Qi, and nourishing Yin, combined with syndrome-specific therapies such as calming wind and stopping convulsions, clearing heat, eliminating dampness and resolving phlegm, and promoting diuresis and reducing swelling.
Drugs, Chinese Herbal/therapeutic use*
;
Data Mining
;
Humans
;
Hypertension/complications*
;
Hypertrophy, Left Ventricular/physiopathology*
;
Medicine, Chinese Traditional
;
Drug Prescriptions
9.Mechanism of vanillic acid against cardiac fibrosis induced by isoproterenol in mice based on Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways.
Hai-Bo HE ; Mian WU ; Jie XU ; Qian-Qian XU ; Fang-Zhu WAN ; Hua-Qiao ZHONG ; Ji-Hong ZHANG ; Gang ZHOU ; Hui-Lin QIN ; Hao-Ran LI ; Hai-Ming TANG
China Journal of Chinese Materia Medica 2025;50(8):2193-2208
This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals
;
Isoproterenol/adverse effects*
;
Male
;
Mice
;
Signal Transduction/drug effects*
;
Vanillic Acid/administration & dosage*
;
Dynamins/genetics*
;
Mice, Inbred C57BL
;
Fibrosis/genetics*
;
Apoptosis/drug effects*
;
Mitochondria/metabolism*
;
NLR Family, Pyrin Domain-Containing 3 Protein/genetics*
;
Myocardium/metabolism*
;
Humans
10.Expert consensus on evaluation index system construction for new traditional Chinese medicine(TCM) from TCM clinical practice in medical institutions.
Li LIU ; Lei ZHANG ; Wei-An YUAN ; Zhong-Qi YANG ; Jun-Hua ZHANG ; Bao-He WANG ; Si-Yuan HU ; Zu-Guang YE ; Ling HAN ; Yue-Hua ZHOU ; Zi-Feng YANG ; Rui GAO ; Ming YANG ; Ting WANG ; Jie-Lai XIA ; Shi-Shan YU ; Xiao-Hui FAN ; Hua HUA ; Jia HE ; Yin LU ; Zhong WANG ; Jin-Hui DOU ; Geng LI ; Yu DONG ; Hao YU ; Li-Ping QU ; Jian-Yuan TANG
China Journal of Chinese Materia Medica 2025;50(12):3474-3482
Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards*
;
Humans
;
Consensus
;
Drugs, Chinese Herbal/therapeutic use*
;
Surveys and Questionnaires

Result Analysis
Print
Save
E-mail