Fuzi decoction ameliorates pain and cartilage degeneration of osteoarthritic rats through PI3K-Akt signaling pathway and its clinical retrospective evidence.

BACKGROUND: Osteoarthritis (OA) is a difficult disease but the clinic lacks effective therapy. As a classic formula of traditional Chinese medicine (TCM), Fuzi decoction (FZD) has been clinically applied for treating OA-related syndromes, but its anti-OA efficacy and mechanism remain unclear. PURPOSE: To experimentally and clinically determine the anti-OA efficacy of FZD and clarify the underlying mechanism. METHODS: UPLC/MS/MS was applied to identify the main components of FZD. A monoiodoacetate (MIA)-induced OA rat model was employed to evaluate the in vivo efficacy of FZD against OA, by using pain behavior assessment, histopathological observation, and immunohistochemical analysis. Primary rat chondrocytes were isolated to determine the in vitro effects of FZD by using cell viability assay, wound healing assay, and real-time PCR (qPCR) analysis on anabolic/catabolic mRNA expressions. RNA sequencing (RNA-seq) and network pharmacology analysis were conducted and the overlapping data were used to predict the mechanism of FZD, followed by verification with qPCR and Western blot assays. Finally, a retrospective analysis was performed to confirm FZD's efficacy and safety in OA patients. RESULTS: The UPLC/MS/MS result showed that FZD contained atractylenolide I, benzoylhypaconitine, benzoylmesaconitine, benzoylaconitine, hypaconitine, mesaconitine, aconitine, lobetyolin, paeoniflorin, and pachymic acid. The in vivo data showed that FZD restored the cartilage degeneration in MIA-induced OA rats by ameliorating pain behavior parameters, recovering histopathological alterations, benefitting cartilage anabolism (up-regulating Col2 expression), and suppressing catabolism (down-regulating MMP13 and Col10 expressions). The in vitro data showed that FZD increased cell viability and wound healing capacity of chondrocytes, and restored the altered expressions of anabolic and catabolic genes of chondrocytes. The overlapping results of RNA-seq and network pharmacology analysis suggested that PI3K/Akt signaling mediated the anti-OA mechanism of FZD, which was verified by qPCR and Western blot experiments. Clinically, the anti-OA efficacy and safety of FZD were confirmed by the retrospective analysis on OA patients. CONCLUSION: The scientific innovation of this study was the determination of anti-OA efficacy of FZD by experimental and clinical evidence and the discovery of its mechanism by integrated RNA-seq, network pharmacology, and molecular experiments, which suggests FZD as a promising TCM agency for OA treatment.

Network Pharmacology and Experimental Validation to Reveal the Pharmacological Mechanisms of Liuwei Dihuang Decoction Against Intervertebral Disc Degeneration.

PURPOSE: To explore the pharmacological mechanisms of Liuwei Dihuang Decoction (LWDHD) against intervertebral disc (IVD) degeneration (IVDD) via network pharmacology analysis combined with experimental validation. METHODS: First, active ingredients and related targets of LWDHD, as well as related genes of IVDD, were collected from public databases. The protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed to predict the core targets and pathways of LWDHD against IVDD. Secondly, the IVDD model of mice treated with LWDHD was selected to validate the major targets predicted by network pharmacology. RESULTS: By searching the intersection of the active ingredient targets and IVDD targets, a total of 110 targets matched the related targets of 30 active ingredients in LWDHD and IVDD were retrieved. PPI network analysis indicated that 17 targets, including Caspase-3, IL-1ß, P53, etc., were hub targets. GO and KEGG enrichment analyses showed that the apoptosis pathway was enriched by multiple targets and served as the target for in vivo experimental study validation. The results of animal experiments revealed that LWDHD administration not only restored the decrease in disc height and abnormal degradation of matrix metabolism in IVDD mice but also reversed the high expression of Bax, Caspase-3, IL-1ß, P53, and low expression of Bcl-2, thereby inhibiting the apoptosis of IVD tissue and ameliorating the progression of IVDD. CONCLUSION: Using a comprehensive network pharmacology approach, our findings predicted the active ingredients and potential targets of LWDHD intervention for IVDD, and some major target proteins involved in the predictive signaling pathway were validated experimentally, which gave us a new understanding of the pharmacological mechanism of LWDHD in treating IVDD at the comprehensive level.

A systematic review and meta-analysis of clinical research on treating angina pectoris of coronary heart disease with traditional Chinese medicine to promote blood circulation and remove blood stasis.

BACKGROUND: Research has shown that traditional Chinese medicine (TCM) can achieve good results in the treatment of angina pectoris. In this study, we aimed to explore the therapeutic effect of TCM in the treatment of angina pectoris of coronary heart disease (CHD) through a literature search and meta-analysis. METHODS: The PubMed, Embase, CBM (China Biology Medicine) Web of Science databases were searched for studies on the treatment of angina pectoris of CHD with TCM. Inclusion and exclusion criteria were applied, and high-quality articles published from 2010.1 to 2021.8 were selected. The RevMan 5.3.5 software was used to evaluate the therapeutic effect indicators of TCM. RESULTS: Nine studies involving 824 patients were included in the meta-analysis, and the overall risk of literature bias was low. The results of meta-analysis showed that compared with conventional Western medicine, TCM + conventional Western medicine had a better efficacy indicators of angina pectoris using the fixed-effects model [odd rate (OR) =3.20, 95% confidence interval (CI): (2.09, 4.90), Z=5.35, P<0.00001]. The frequency of angina pectoris was measured by random-effects model, and the statistical results were [standard mean difference (SMD) =-1.85, 95% CI: (-2.29, -1.41), Z=8.22, P<0.00001]. The adverse events was measured by fixed-effects model, and the statistical results were [OR =0.48, 95% CI: (0.21, 1.08), Z=1.78, P=0.08]. DISCUSSION: The application of TCM in the treatment of angina pectoris of CHD can improve the therapeutic effect, reduce the frequency of angina pectoris, shorten the attack time, reduce serum total cholesterol, and improve the quality of life after treatment, but it has no obvious reducing effect on blood lipids.