Cardiac fibrosis(CF) is a cardiac pathological process characterized by excessive deposition of extracellular matrix(ECM). When the heart is damaged by adverse stimuli, cardiac fibroblasts are activated and secrete a large amount of ECM, leading to changes in cardiac fibrosis, myocardial stiffness, and cardiac function declines and accelerating the development of heart failure. There is a close relationship between heart yin deficiency and cardiac fibrosis, which have similar pathogenic mechanisms. Heart Yin deficiency, characterized by insufficient Yin fluids, causes the heart to lose its nourishing function, which acts as the initiating factor for myocardial dystrophy. The deficiency of body fluids leads to stagnation of blood flow, resulting in blood stasis and water retention. Blood stasis and water retention accumulate in the heart, which aligns with the pathological manifestation of excessive deposition of ECM, as a tangible pathogenic factor. This is an inevitable stage of the disease process. The lingering of blood stasis combined with water retention eventually leads to the generation of heat and toxins, triggering inflammatory responses similar to heat toxins, which continuously stimulate the heart and cause the ultimate outcome of CF. Considering the syndrome of heart Yin deficiency, traditional Chinese medicine capable of nourishing Yin, activating blood, and promoting urination can reduce myocardial cell apoptosis, inhibit fibroblast activation, and lower the inflammation level, showing significant advantages in combating CF.
Humans ; Fibrosis/drug therapy* ; Animals ; Yin Deficiency/metabolism* ; Myocardium/metabolism* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use*

This study aimed to construct an evidence map and conduct a comprehensive analysis of clinical research literature on the treatment of pulmonary fibrosis with proprietary Chinese medicines published over the past three decades, so as to systematically evaluate the effectiveness and limitations of existing evidence and provide a scientific basis for subsequent clinical practice, research directions, and policy-making. A systematic search was conducted across 7 databases in both Chinese and English from the inception of the databases to June 1, 2024. The clinical research characteristics and methodological quality of the included literature were assessed. A total of 123 pieces of literature were ultimately included, comprising 108 interventional studies, 3 observational studies, 10 secondary study, and 2 expert consensuses. These studies involved 33 kinds of proprietary Chinese medicines, with Danhong Injection being the most widely used. Most studies had a duration of 1-3 months and a sample size ranging from 50 to 100 cases, and they were often used in combination with steroids or conventional western medicine. There was a common phenomenon of off-label use of proprietary Chinese medicines. The main outcome indicators included pulmonary function, blood gas analysis, and total effective rate, with issues such as insufficient safety reporting, lack of distinctive traditional Chinese medicine(TCM) features, absence of long-term outcome indicators, and strong subjective evaluation. In terms of methodological quality assessment, randomized controlled trial(RCT) had biases in randomization and outcome indicator measurement and a risk of selective reporting. Meta-analysis lacked reporting on protocol registration, literature exclusion lists, and disclosure of conflicts of interest. Expert consensuses lacked standards in terms of rigor, scientific basis, and applicability. The quality of clinical research evidence on the treatment of pulmonary fibrosis with proprietary Chinese medicines urgently needs improvement. It is recommended that future research should pay more attention to the scientific and rigorous design to enhance the standardization and reproducibility of the research. At the same time, it should integrate TCM theories to establish an outcome indicator evaluation system suitable for the treatment of pulmonary fibrosis with proprietary Chinese medicines, so as to fully explore the potential of proprietary Chinese medicines in treating pulmonary fibrosis.
Drugs, Chinese Herbal/administration & dosage* ; Humans ; Pulmonary Fibrosis/drug therapy* ; Medicine, Chinese Traditional

OBJECTIVE: To investigate the effect of Tongmai Hypoglycemic Capsule (THC) on myocardium injury in diabetic cardiomyopathy (DCM) rats. METHODS: A total of 24 Sprague Dawley rats were fed for 4 weeks with high-fat and high-sugar food and then injected with streptozotocin intraperitoneally for the establishment of the DCM model. In addition, 6 rats with normal diets were used as the control group. After modeling, 24 DCM rats were randomly divided into the model, L-THC, M-THC, and H-THC groups by computer generated random numbers, and 0, 0.16, 0.32, 0.64 g/kg of THC were adopted respectively by gavage, with 6 rats in each group. After 12 weeks of THC administration, echocardiography, histopathological staining, biochemical analysis, and Western blot were used to detect the changes in myocardial structure, oxidative stress (OS), biochemical indexes, protein expressions of myocardial fibrosis, and nuclear factor erythroid 2-related faactor 2 (Nrf2) element, respectively. RESULTS: Treatment with THC significantly decreased cardiac markers such as creatine kinase, lactate dehydrogenase, and creatine kinase-MB, etc., (P<0.01); enhanced cardiac function indicators including heart rate, ejection fraction, cardiac output, interventricular septal thickness at diastole, and others (P<0.05 or P<0.01); decreased levels of biochemical indicators such as fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, aspartate transaminase, (P<0.05 or P<0.01); and decreased the levels of myocardial fibrosis markers α-smooth muscle actin (α-SMA), and collagen I (Col-1) protein (P<0.01), improved myocardial morphology and the status of myocardial interstitial fibrosis. THC significantly reduced malondialdehyde levels in model rats (P<0.01), increased levels of catalase, superoxide dismutase, and glutathione (P<0.01), and significantly increased the expression of Nrf2, NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1, and superoxide dismutase 2 proteins in the left ventricle of rats (P<0.01). CONCLUSION THC activates the Nrf2 signaling pathway and plays a protective role in reducing OS injury and cardiac fibrosis in DCM rats.
Animals ; Diabetic Cardiomyopathies/physiopathology* ; Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Rats, Sprague-Dawley ; Myocardium/metabolism* ; Fibrosis ; Male ; Capsules ; Hypoglycemic Agents/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Rats ; Diabetes Mellitus, Experimental/drug therapy*

Fibrosis is characterized as an aberrant reparative process involving the direct replacement of damaged or deceased cells with connective tissue, leading to progressive architectural remodeling across various tissues and organs. This condition imposes a substantial burden, resulting in considerable morbidity and mortality. Ginseng (Panax ginseng C. A. Meyer), renowned for its medicinal properties, has been incorporated as a key component in Chinese patent medicines to mitigate fibrotic diseases. Ginsenosides, the primary bioactive compounds in ginseng, have garnered significant attention. Over the past five years, extensive research has explored the pharmaceutical potential of ginsenosides in diverse organ fibrosis conditions, including liver, myocardial, renal, and pulmonary fibrosis. Studies have elucidated that ginsenosides demonstrate potential effects on inflammatory responses stemming from parenchymal cell damage, myofibroblast activation leading to extracellular matrix (ECM) production, and myofibroblast apoptosis or inactivation. Additionally, potential downstream targets and pathways associated with these pathological processes have been identified as being influenced by ginsenosides. This review presents a comprehensive overview of the efficacious treatments utilizing ginsenosides for various tissue fibrosis types and their potential anti-fibrotic mechanisms. Furthermore, it offers a reference for the development of novel candidate drugs for future organ fibrosis therapies.
Ginsenosides/pharmacology* ; Humans ; Fibrosis/drug therapy* ; Animals ; Panax/chemistry* ; Drugs, Chinese Herbal/therapeutic use*

Five previously undescribed diterpenoids, named succipenoids D‒H (1‒5), along with four undescribed lignans, named succignans A‒D (6‒9), were isolated from the dichloromethane extract of Chinese medicinal succinum. Compounds 1‒5 were characterized as nor-abietane diterpenoids, while compounds 6‒9 were identified as lignans polymerized from two groups of phenylpropanoid units. The structures of these novel compounds, including their absolute configurations, were determined through spectroscopic and computational methods. Biological assessments of renal fibrosis demonstrated that compounds 6 and 7 effectively reduce the expression of proteins associated with renal fibrosis, including α-smooth muscle actin (α-SMA), collagen I, and fibronectin in transforming growth factor-β1 (TGF-β1) induced normal rat kidney proximal tubular epithelial cells (NRK-52e).
Animals ; Rats ; Lignans/isolation & purification* ; Diterpenes/isolation & purification* ; Fibrosis/drug therapy* ; Drugs, Chinese Herbal/pharmacology* ; Molecular Structure ; Cell Line ; Kidney Diseases/pathology* ; Transforming Growth Factor beta1/genetics* ; Kidney/metabolism* ; Actins/genetics* ; Fibronectins/genetics* ; Collagen Type I/genetics* ; Epithelial Cells/metabolism*

This study aimed to investigate the ameliorative effect of Xinyang Tablets on myocardial fibrosis in uremic cardiomyopathy(UCM) using single-cell sequencing technology. UCM mouse models were established by 5/6 nephrectomy(NPM) and randomly divided into the model group, Xinyang Tablets group, and sham-operated(sham) group as the control. The Xinyang Tablets group received postoperative interventions of Xinyang Tablets(0.34 g·kg~(-1)). After eight weeks, the hearts of the mice in each group were disassociated and subjected to 10×Genomics single-cell sequencing. The data were subjected to t-SNE dimensionality reduction, K-means clustering, and CellMarker annotation prior to analyzing differential expression and cell differentiation trajectories using the Seurat and Monocle3 tools. Additionally, the CellChat tool was used to parse intercellular signaling communication. The results showed that a total of nine types of cells including fibroblasts, endothelial cells, and immune cells were identified in this study. The single-cell expression results of fibroblasts and Gene Ontology(GO) enrichment analysis showed that Xinyang Tablets regulated myocardial fibrosis factors and related signals. Mimetic timing analysis identified three major differentiation trajectories of mouse cardiac fibroblasts and identified the expression of secreted phosphoprotein 1(Spp1) as consistent with the fibroblast differentiation trajectory. Cellular interaction network analysis showed that the communication signals between mouse cardiac fibroblasts and other cells were weakened in the Xinyang Tablets group compared with the model group. The results of ligand-receptor interaction analysis showed that the interaction between myeloid cell-derived osteopontin(OPN) and cardiac fibroblasts and between myeloid cell Spp1 ligand and cardiac fibroblast receptor of mice in the Xinyang Tablets group was weakened compared with the model group. In conclusion, Xinyang Tablets may improve myocardial fibrosis in UCM by inhibiting both endogenous and exogenous OPN at the single-cell level.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Cardiomyopathies/pathology* ; Single-Cell Analysis ; Male ; Fibrosis/drug therapy* ; Myocardium/metabolism* ; Uremia/metabolism* ; Tablets ; Mice, Inbred C57BL ; Humans

This study systematically retrieved the clinical studies in the treatment of idiopathic pulmonary fibrosis(IPF) with traditional Chinese medicine(TCM) and employed evidence mapping to summarize the overall research status and deficiencies of TCM in treating IPF. CNKI, VIP, SinoMed, Wanfang, PubMed, Web of Science, Cochrane Library, and EMbase were searched for the relevant studies published from inception to February 20, 2024. The distribution characteristics of the evidence were analyzed and presented through charts combined with words. A total of 323 studies were included, including 295 randomized controlled trials(RCTs) and 28 Meta-analysis. The number of publications in this field rose with fluctuations, yet the proportion of core papers was low, and the research lacked the attention of foreign researchers. There were scant cross-regional collaboration between researchers and insufficient attention from relevant departments. The included RCT generally had low quality, with small sample sizes, short treatment courses, and insufficient attention to acute exacerbation and complications of IPF. In addition, few studies employed TCM alone, and the TCM syndromes remained to be standardized. A considerable number of outcome indicators were involved in the publications, while the majority of them failed to emphasize the disparity between primary and secondary outcome indicators. There were diverse reference standards for the comprehensive indicators among the outcome indicators, and insufficient attention was paid to long-term prognosis and health economic indicators. The included Meta-analysis concluded that TCM had potential clinical efficacy in treating IPF. However, the methodological credibility grading and the GRADE grading results of outcome indicators were low. The results suggested that TCM demonstrated certain advantages in the treatment of IPF, while the quality of the included studies was not high. In the future, clinical research protocols should be standardized and registered. Multicenter, large-sample, and follow-up clinical studies should be conducted. The research reports should refer to relevant reporting standards to improve the quality and generate high-level evidence, thus providing a reference for the clinical application of TCM in the treatment of IPF.
Humans ; Idiopathic Pulmonary Fibrosis/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic

Objective To investigate the therapeutic effect of targeting and killing CD248-positive myofibroblasts on bleomycin-induced pulmonary fibrosis in mice. Methods IgG78-DM1, an antibody-maytansine 1 (DM1) conjugate targeting CD248, was prepared. The drug conjugation efficiency was measured and calculated by UV spectrophotometer, and the identification of IgG78-DM1 was performed through SDS-PAGE and Western blot analysis. In vitro, the binding activity of IgG78-DM1 on CD248-positive myofibroblasts was detected by flow cytometry and the cytotoxicity of IgG78-DM1 to CD248-positive myofibroblasts was evaluated by CCK-8 assay. In vivo, C57BL/6 male mice were randomly divided into control group, idiopathic pulmonary fibrosis group, human IgG-DM1 (hIgG-DM1) control group, and IgG78-DM1 treatment group. Then, the mouse models with pulmonary fibrosis induced by bleomycin were constructed. Two weeks later, the animal models were intravenously injected with IgG78-DM1. After the treatment of two weeks, lung tissues were collected for Masson staining and Sirius Red staining to evaluate the degree of pulmonary fibrosis. Real-time fluorescence quantitative PCR was used to measure the expression levels of CD248, as well as markers of fibroblastic activation including alpha-smooth muscle actin (α-SMA) and type I collagen alpha 1 (COL1A1). The safety of IgG78-DM1 was preliminarily assessed by conducting liver and kidney function tests. Results IgG78-DM1 was successfully prepared, and its drug conjugation ratio was 3.2. The antibody structure remained stable after conjugation, allowing effective binding and cytotoxicity against CD248-positive myofibroblasts. After treatment with IgG78-DM1, the degree of pulmonary fibrosis in mice significantly reduced, accompanied by the decrease of the expression of CD248, α-SMA, and COL1A1. The liver and kidney function of the mice remained at normal levels compared to the normal control group. Conclusion IgG78-DM1 effectively inhibits pulmonary fibrosis in mice by targeting and killing CD248-positive myofibroblasts. The safety of this strategy is preliminarily assessed.
Humans ; Animals ; Mice ; Male ; Mice, Inbred C57BL ; Pulmonary Fibrosis/drug therapy* ; Myofibroblasts ; Antibodies ; Bleomycin ; Antigens, Neoplasm ; Antigens, CD

OBJECTIVE: To verify the effect of Buyang Huanwu Decoction (BHD) in ameliorating erectile dysfunction (ED) after radical prostatectomy (RP). METHODS: The composition of BHD was verified by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) analysis. Bilateral cavernous nerve crush injury (BCNI) in rats was used to mimic the neurovascular injury occurring after RP. By the envelope method, forty rats were randomly divided into 4 groups as follows: sham (cavernous nerves exposed only), model (BCNI), low-dosage BHD [LBHD, 12.8 g/(kg·d)], and high-dosage BHD [HBHD, 51.2 g/(kg·d)] groups, 10 rats in each group, feeding for 3 weeks respectively. Erectile function was evaluated by measuring intracavernosal pressure (ICP). Changes in the histopathology of corpus cavernosum (CC) were examined by hematoxylin-eosin staining. Meanwhile, the fibrosis of CC was measured by Masson's trichrome staining and Western blot was used to detect the expressions of collagen I, transforming growth factor beta 1 (TGF- β 1) and α-smooth muscle actin (α-SMA). Apoptosis index was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) and Western blot for determining the expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax). The oxidative stress in the CC were assessed by the superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS) levels. The proteins expression of c-Jun N-terminal kinase (JNK) and c-Jun were detected by Western blot. In addition, the expression of α-SMA and p-c-Jun in the CC was observed by double immunofluorescence staining. RESULTS: The UPLC-QTOF-MS/MS analysis showed that BHD contained calycosin-7-O- β -D-glucoside, ononin, calycosin and formononetin. Compared with the model group, LBHD and HBHD treatment improved the ICP and the circumference, area, and weight of CC (P<0.05 or P<0.01). Furthermore, LBHD and HBHD treatments increased CC smooth muscle content and decreased apoptosis index (P<0.05 or P<0.01). LBHD and HBHD also elevated SOD and expression level of α -SMA and Bcl-2, and reduced MDA and ROS levels, as well as expression of TGF- β 1, collagen I, Bax, p-c-JNK, p-JNK in the CC compared with the model group (P<0.05 or P<0.01). The double immunofluorescence staining showed that the fluorescence degree of p-c-Jun in both LBHD and HBHD treatment groups was significantly reduced, whereas the α -SMA expression increased (P<0.05 or P<0.01). CONCLUSIONS BHD can improve ED of rats with BCNI, which is related to inhibiting fibrosis, apoptosis, and oxidative stress of CC. The ROS/JNK/c-Jun signaling pathway may play an important role in the process.
Male ; Humans ; Rats ; Animals ; Reactive Oxygen Species ; Tandem Mass Spectrometry ; bcl-2-Associated X Protein ; Rats, Sprague-Dawley ; Erectile Dysfunction/drug therapy* ; Collagen ; Fibrosis ; Disease Models, Animal

OBJECTIVE: To observe whether metformin (MET) inhibits transforming growth factor-β₁ (TGF-β₁)/Smad3 signaling pathway by activating adenosine activated protein kinase (AMPK), so as to alleviate the pulmonary fibrosis caused by paraquat (PQ) poisoning in mice. METHODS: Male C57BL/6J mice were randomly divided into the Control group, PQ poisoning model group (PQ group), MET intervention group (PQ+MET group), AMPK agonist group (PQ+AICAR group), and AMPK inhibitor group (PQ+MET+CC group), according to a random number table method. A mouse model of PQ poisoning was established by one-time peritoneal injection of 1 mL PQ solution (20 mg/kg). The Control group was injected with the same volume of normal saline. After 2 hours of modeling, the PQ+MET group was given 2 mL of 200 mg/kg MET solution by gavage, the PQ+AICAR group was given 2 mL of 200 mg/kg AICAR solution by intraperitoneal injection, the PQ+MET+CC group was given 2 mL of 200 mg/kg MET solution by gavage and then 1 mL complex C (CC) solution (20 mg/kg) was intraperitoneally injected, the Control group and PQ group were given 2 mL of normal saline by gavage. The intervention was given once a day for 21 consecutive days. The 21-day survival rate of ten mice in each group was calculated, and the lung tissues of remaining mice were collected at 21 days after modeling. The pathological changes of lung tissues were observed under light microscope after hematoxylin-eosin (HE) staining and Masson staining, and the degree of pulmonary fibrosis was evaluated by Ashcroft score. The content of hydroxyproline in lung tissue and oxidative stress indicators such as malondialdehyde (MDA) and superoxide dismutase (SOD) were detected. The protein expressions of E-cadherin, α-smooth muscle actin (α-SMA), phosphorylated AMPK (p-AMPK), TGF-β₁ and phosphorylated Smad3 (p-Smad3) in lung tissue were detected by Western blotting. RESULTS: Compared with the Control group, the 21 days survival rate was significantly reduced, lung fibrosis and Ashcroft score were significantly increased in PQ group. In addition, the content of hydroxyproline, MDA and the protein expressions of α-SMA, TGF-β₁ and p-Smad3 in lung tissue were significantly increased, while the activity of SOD and the protein expressions of E-cadherin and p-AMPK were significantly decreased in PQ group. Compared with the PQ group, the 21 days survival rates of mice were significantly improved in the PQ+MET group and PQ+AICAR group (70%, 60% vs. 20%, both P < 0.05). The degree of pulmonary fibrosis and the Ashcroft score were significantly reduced (1.50±0.55, 2.00±0.63 vs. 6.67±0.52, both P < 0.05). The content of hydroxyproline and MDA in lung tissue, as well as α-SMA, TGF-β₁ and p-Smad3 protein expressions were significantly reduced [hydroxyproline (mg/L): 2.03±0.11, 3.00±0.85 vs. 4.92±0.65, MDA (kU/g): 2.06±1.48, 2.10±1.80 vs. 4.06±1.33, α-SMA/GAPDH: 0.23±0.06, 0.16±0.06 vs. 1.00±0.09, TGF-β₁/GAPDH: 0.28±0.03, 0.53±0.05 vs. 0.92±0.06 p-Smad3/GAPDH: 0.52±0.04, 0.69±0.06 vs. 1.11±0.10, all P < 0.05], SOD activity and the protein expressions of E-cadherin and p-AMPK were significantly increased [SOD (μmol/g): 39.76±1.35, 33.03±1.28 vs. 20.08±1.79, E-cadherin/GAPDH: 0.91±0.08, 0.72±0.08 vs. 0.26±0.04, p-AMPK/GAPDH: 0.62±0.04, 0.60±0.01 vs. 0.20±0.04, all P < 0.05]. However, these protective effects of MET were inhibited by the addition of AMPK inhibitor CC solution. CONCLUSIONS MET can effectively alleviate the degree of pulmonary fibrosis in mice poisoned with PQ, and its mechanism may be related to the activation of AMPK and inhibition of TGF-β₁/Smad3 signaling pathway, which can be inhibited by AMPK inhibitor CC.
Mice ; Male ; Animals ; Pulmonary Fibrosis/drug therapy* ; Paraquat ; AMP-Activated Protein Kinases/pharmacology* ; Metformin/pharmacology* ; Hydroxyproline/pharmacology* ; Saline Solution ; Mice, Inbred C57BL ; Lung/metabolism* ; Transforming Growth Factor beta1/pharmacology* ; Cadherins ; Superoxide Dismutase