Ligustrazine-Oleanolic Acid Glycine Derivative, G-TOA, Selectively Inhibited the Proliferation and Induced Apoptosis of Activated HSC-T6 Cells.

Hepatic fibrosis is a naturally occurring wound-healing reaction, with an imbalance of extracellular matrix (ECM) during tissue repair response, which can further deteriorate to hepatocellular carcinoma without timely treatment. Inhibiting activated hepatic stellate cell (HSC) proliferation and inducing apoptosis are the main methods for the treatment of liver fibrosis. In our previous study, we found that the TOA-glycine derivative (G-TOA) had exhibited more significant inhibitory activity against HepG2 cells and better hydrophilicity than TOA, ligustrazine (TMP), and oleanolic acid (OA). However, inhibiting activated HSC proliferation and inducing apoptosis by G-TOA had not been reported. In this paper, the selective cytotoxicity of G-TOA was evaluated on HSC-T6 cells and L02 cells, and apoptosis mechanisms were explored. It was found that G-TOA could selectively inhibit the proliferation of activated HSC-T6 cells, induce morphological changes, early apoptosis, and mitochondrial membrane potential depolarization, increase intracellular free calcium levels, downregulate the expression of NF-κB/p65 and COX-2 protein, and decrease the ratio of Bcl-2/Bax, thereby inducing HSC-T6 cell apoptosis. Thence, G-TOA might be a potential antifibrosis agent for the therapy of hepatic fibrosis, provided that it exerts anti-fibrosis effects on activated HSC-T6 cells.

Visualizing research trends and identifying hotspots of herbal components for treating cardiovascular diseases: A bibliometric analysis from 2000 to 2023.

OBJECTIVE: The objective of this study was to investigate the global research trends in herbal medicine for the treatment of cardiovascular disease (CVD) from 2000 to 2023. A bibliometric approach was employed to analyze international collaborations, knowledge structures, emerging trends, and research frontiers. METHOD: The Web of Science (WOS) core collection was utilized as the database, employing the search formula (((TS = (traditional Chinese medicine)) OR TS = (Chinese herbal medicinal ingredient)) OR TS = (Chinese herbal medicinal constituent)) AND TS = (cardiovascular disease) to conduct the search. The search period spanned from January 1, 2000, to February 14, 2023, and the literature type included articles and reviews. RESULTS: A total of 1478 papers were included in the analysis after searching the WOS database and excluding conference proceedings, news articles, retractions, editorials, and letters. China demonstrated the highest number of publications, followed by the United States and Taiwan (China). The institution with the highest publications was the Chinese Academy of Medical Sciences. China, the United States, and India were the main countries involved in research in this field, and there was significant collaboration among them. The hotspots related to herbal components for treating cardiovascular diseases from 2000 to 2023 included systematic reviews, ischemic reperfusion injury, global burden, type 2 diabetes, and protection. CONCLUSION: This paper provides a reference for the future development of herbal research in cardiovascular aspects by revealing the current status, hotspots, and trends of global herbal research in cardiovascular factors over more than 20 years. Identification of potential collaborators and institutions can assist researchers in exploring new directions for future research and discovering new perspectives for potential collaborations in this field.

Mining Important Herb Combinations of Traditional Chinese Medicine against Hypertension Based on the Symptom-Herb Network Combined with Network Pharmacology.

Although data mining methods are extensively used in the rule analysis of famous old traditional Chinese medicine (TCM) experts' prescriptions for the treatment of hypertension, most of them only mine the association between herbs and herbs, ignoring the importance of symptoms in the disease. This study collected 439 cases of hypertension treated by famous old TCM experts from the FangNet platform. Using the structure network algorithm, the symptom-herb network was constructed, which redefined the importance of herb in disease. Based on the network, 21 driver herbs, 76 herb pairs, and 41 symptom-herb associations were mined. Finally, the basic prescription composed of Gouteng (Uncariae Ramulus cum Uncis), Huanglian (Coptidis Rhizoma), Chuanxiong (Chuanxiong Rhizoma), Gegen (Puerariae Lobatae Radix), Danggui (Angelicae Sinensis Radix), and Huangqin (Scutellariae Radix) was found. These herbs are the most significant among all herbs, and they have a potential correlation with each other. To further verify the rationality of the data mining results, we adopted the network pharmacology method. Network pharmacological analysis shows that the five core targets in the basic prescription include IL6, VEGFA, TNF, TP53, and EGF, which link 10 significant active compounds and 7 important KEGG pathways. It was predicted that anti-inflammatory, antioxidant, vascular endothelial protection, emotion regulation, and ion channel intervention might be the main mechanisms of the basic prescription against hypertension. This study reveals the prescription rule of famous old TCM experts for treating hypertension from a new perspective, which provides a new approach to inherit the academic experience of famous old TCM experts and develop new drugs.

Detection of Herbal Combinations and Pharmacological Mechanisms of Clinical Prescriptions for Coronary Heart Disease Using Data Mining and Network Pharmacology.

Though widely used in the treatment of coronary heart disease (CHD), the mechanism of traditional Chinese medicine (TCM) is still unclear because of its complex prescription rules. This study prospectively collected 715 prescriptions of TCM for the treatment of CHD. The characteristics of TCM in prescriptions were described and analyzed, and the rules of prescriptions were analyzed by using association rules. Frequency statistics showed that the high-frequency herbs with a frequency of more than 60% were Gan-cao, Huang-qi, Dang-gui, Chuan-xiong, Yan-hu-suo, and San-qi. The high-frequency herb combinations were summarized by using association rules. By using the method of the "Top N groups" to excavate the empirical prescriptions, the basic prescriptions for treating CHD were summarized. We named the intersection herbs of the basic prescriptions and the high frequency herbs as the core herbal prescription. To explore the possible mechanisms underlying the anti-CHD effect of the core herbal prescription, the bioactive components of core herbal prescription and their targets were screened out by using network pharmacology. Molecular docking was performed between the bioactive components and core targets. A total of 28 potential active ingredients and 5 core targets were identified for the treatment of CHD with core herbal prescription. The enrichment analysis results indicated that the mechanism of action mainly involved neuroactive ligand-receptor interaction and calcium signaling pathway. The commonly used herbal pairs for CHD with qi deficiency and blood stasis syndrome were Huang-qi and Dang-gui. The mechanism of action of common herbal pairs was also studied by network pharmacology. This study summarized the prescription rule of TCM in the treatment of CHD and may provide a new idea for the treatment of CHD.

Identifying potential therapeutic targets of Tang-Yi-Ping for the treatment of impaired glucose tolerance: a tandem mass tag-labeled quantitative proteomic analysis.

BACKGROUND: This study uses the tandem mass tag (TMT)-labeled quantitative proteomic analysis to identify potential therapeutic protein targets of a Chinese prescription called Tang-Yi-Ping (TYP) for the treatment of impaired glucose tolerance (IGT) in rats. METHODS: A total of 31 specific-pathogen free (SPF) male Wistar rats were used in our study. Ten were randomly selected as a control group, while 21 received a high-sugar and high-fat diet combined with an intraperitoneal injection of streptozotocin to establish IGT subjects. After eliminating 2 rats without successful modeling, 19 were randomly divided into a TYP group (n=9) and IGT model group (n=10). The TYP group was given a TYP decoction of 6.36 mg/kg-1/d-1. After 8 weeks of intervention, blood glucose-related indicators were measured, and cell morphology was observed by hematoxylin and eosin (HE) staining. TMT-labeled proteomic analysis was applied to detect the differentially expressed proteins (DEPs) in the pancreases of the three groups. The intersection of the DEPs in both the TYP group and IGT model group underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to identify the related biological functions and signal transduction pathways. Finally, western blot (WB) was used to verify the TMT proteomics results. RESULTS: TYP can effectively reduce blood glucose and improve islet morphology in IGT rats. We identified a total of 16 potential therapeutic protein targets of TYP, 4 of which were upregulated, while 12 were downregulated, including Rbp4, Fam3b, Flot2, etc. [fold change (FC) >1.1, P<0.05]. The significant signal transduction pathways included arginine and proline metabolism, glyceride metabolism, glycerophospholipid metabolism, mTOR, Wnt, and insulin signaling pathways. CONCLUSIONS: For anti-IGT therapy, we found TYP regulates 16 protein targets, multiple biological functions, and multiple signal transduction pathways. This study thus makes a significant contribution to identifying new potential therapeutic targets for treating IGT.