Chinese medicinal formula Fu Xin decoction against chronic heart failure by inhibiting the NLRP3/caspase-1/GSDMD pyroptotic pathway.

BACKGROUND: Various heart diseases ultimately lead to chronic heart failure (CHF). In CHF, the inflammatory response is associated with pyroptosis, which is mediated by the NOD-like receptor protein 3 (NLRP3) inflammasome. Fu Xin decoction (FXD) is commonly used in clinical practice to treat CHF and improve inflammatory conditions. However, the specific pharmacological mechanisms of action for FXD in these processes have yet to be fully understood. PURPOSE: The objective of this study was to examine the protective mechanism of FXT against CHF, both in H9c2 cells and mice. METHOD: A CHF mouse model was established, and the effect of FXD was observed via gavage. Cardiac function was evaluated using echocardiography, while serum BNP and LDH levels were analyzed to assess the severity of CHF. Hematoxylin and eosin staining (H&E) and Masson staining were performed to evaluate myocardial pathological changes, and TdT-mediated dUTP Nick-End Labeling staining was used to detect DNA damage. Additionally, doxorubicin was utilized to induce myocardial cell injury in H9c2 cells, establishing a relevant model. CCK8 was used to observe cell viability and detect LDH levels in the cell supernatant. Subsequently, the expression of pyroptosis-related proteins was detected using immunohistochemistry, immunofluorescence, and western blotting. Finally, the pharmacological mechanism of FXD against CHF was further validated by treating H9c2 cells with an NLRP3 activator and inducing NLRP3 overexpression. RESULT: According to current research findings, echocardiography demonstrated a significant improvement of cardiac function by FXD, accompanied by reduced levels of BNP and LDH, indicating the amelioration of cardiac injury in CHF mice. FXD exhibited the ability to diminish serum CRP and MCP inflammatory markers in CHF mice. The results of HE and Masson staining analyses revealed a significant reduction in pathological damage of the heart tissue following FXD treatment. The CCK8 assay demonstrated the ability of FXD to enhance H9c2 cell viability, improve cell morphology, decrease LDH levels in the cell supernatant, and alleviate cell damage. Immunohistochemistry, Western blotting, and immunofluorescence staining substantiated the inhibitory effect of FXD on the NLRP3/caspase-1/GSDMD pyroptosis signaling pathway in both CHF and H9c2 cell injury models. Ultimately, the administration of the NLRP3 activator (Nigericin) and the overexpression of NLRP3 counteract the effects of FXD on cardiac protection and pyroptosis inhibition in vitro. CONCLUSION: FXD exhibits a cardioprotective effect, improving CHF and alleviating pyroptosis by inhibiting the NLRP3/caspase-1/GSDMD pathway.

Knee osteoarthritis: A review of animal models and intervention of traditional Chinese medicine.

BACKGROUND: Knee osteoarthritis (KOA) characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults. The pathophysiology of KOA remains poorly understood, as it involves complex mechanisms that result in the same outcome. Consequently, researchers are interested in studying KOA and require appropriate animal models for basic research. Chinese herbal compounds, which consist of multiple herbs with diverse pharmacological properties, possess characteristics such as multicomponent, multipathway, and multitarget effects. The potential benefits in the treatment of KOA continue to attract attention. PURPOSE: This study aims to provide a comprehensive overview of the advantages, limitations, and specific considerations in selecting different species and methods for KOA animal models. This will help researchers make informed decisions when choosing an animal model. METHODS: Online academic databases (e.g., PubMed, Google Scholar, Web of Science, and CNKI) were searched using the search terms "knee osteoarthritis," "animal models," "traditional Chinese medicine," and their combinations, primarily including KOA studies published from 2010 to 2023. RESULTS: Based on literature retrieval, this review provides a comprehensive overview of the methods of establishing KOA animal models; introduces the current status of advantages and disadvantages of various animal models, including mice, rats, rabbits, dogs, and sheep/goats; and presents the current status of methods used to establish KOA animal models. CONCLUSION: This study provides a review of the animal models used in recent KOA research, discusses the common modeling methods, and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.

Study on the Mechanism of Bu-Shen-He-Mai Granules in Improving Renal Damage of Ageing Spontaneously Hypertensive Rats by Regulating Th17 Cell/Tregs Balance.

Methods: Blood pressure and urine biochemical indices were recorded. Renal blood flow was evaluated by renal ultrasonography. Transmission electron microscopy (TEM) and HE staining were used to assess kidney and spleen morphology. Renal fibrosis was assessed using Masson staining. Serum levels of IL-6, IL-10, and IL-17A were measured using ELISAs. The density of RORγ and Foxp3 in the spleen was observed by immunofluorescence staining. The levels of Th17 cells and Tregs in blood were detected via flow cytometry. Transcriptome sequencing was performed to screen the targets of BSHM granules in hypertensive kidneys. Results: BSHM granules decreased SBP by 21.2 mm·Hg and DBP by 8.8 mm·Hg in ageing SHRs (P < 0.05), decreased the levels of urine mALB, ß2-Mg, and NAG (P < 0.01), and improved renal blood flow and arteriosclerosis. BSHM granules increased IL-10 expression (P < 0.05) while decreasing IL-6 (P < 0.01) and IL-17A (P < 0.05) levels. BSHM granules improved Foxp3 density and the number of Tregs (P < 0.01) and reduced RORγt density and the number of Th17 cells (P < 0.01). Transcriptome sequencing identified 747 differentially expressed (DE) mRNAs in kidneys after BSHM treatment. GO analysis suggested that BSHM granules act through immunoregulation. Conclusions: BSHM granules attenuated hypertensive renal damage in ageing SHRs, by significantly increasing Tregs and decreasing Th17 cells.

Cangxitongbi capsules protect the articular cartilage in the rat knee through the long non-coding RNA HOTAIR/p38MAPK pathway.

BACKGROUND: Knee osteoarthritis (KOA) is a leading cause of chronic pain and disability, and as such, it poses a significant economic burden. Traditional Chinese medicine (TCM), as well as complementary and alternative medicine, can offer safe and effective treatments for KOA. Cangxitongbi (CXTB) capsule is a Chinese patented medicine for KOA treatment and has a remarkable curative effect. This article evaluated the effects and mechanisms of CXTB in protecting joint cartilage in vivo. METHODS: The KOA model was constructed in rats using the modified Hulth method. CXTB (35 mg/kg) was administered intragastrically for 4 weeks. Hematoxylin and eosin (HE) staining of the knee articular were performed to evaluate the efficiency of CXTB. Western blot analysis, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA) were used to investigate the protective mechanisms of CXTB in joint cartilage. RESULTS: CXTB effectively improved the morphological structure of the cartilage and bone in the knee joint by enhancing autophagy and regulating the expression of related protease and inflammatory factors. Furthermore, CXTB downregulated the expression of the long non-coding RNA (lncRNA) Hox transcript antisense intergenic RNA (HOTAIR) and inhibited the activation of the p38MAPK pathway. Conversely, overexpression of lncRNA HOTAIR suppressed the protective effects of CXTB on the knee joint. CONCLUSIONS: CXTB capsules can protect the knee articular cartilage in rats through the lncRNA HOTAIR/p38MAPK pathway.

Comparison of the antihypertensive efficacy of morning and bedtime dosing on reducing morning blood pressure surge: A protocol for systemic review and meta-analysis.

BACKGROUND: It is well known that morning blood pressure surge increases the risk of myocardial events in the first several hours post-awakening. This meta-analysis was performed to compare the antihypertensive efficacy of morning and bedtime dosing on decreasing morning blood pressure surge. METHODS: Articles in 4 databases about clinical trials of ingestion time of antihypertensive drugs were searched and performed a meta-analysis to evaluate the different effects on morning blood pressure and absolute blood pressure (BP) reduction from baseline of between bedtime administration (experimental group) and morning awaking administration (control group). RESULTS: The aim of this study is to compare the antihypertensive efficacy of morning and bedtime dosing on decreasing morning blood pressure surge. CONCLUSIONS: The bedtime will provide evidence support for clinicians and patients for reducing morning blood pressure surge. ETHICS AND DISSEMINATION: This study does not require ethical approval.

A comparison of the efficacy and safety of traditional Chinese medicine external treatment for the knee osteoarthritis: A protocol for systematic review and network meta-analysis.

BACKGROUND: Knee osteoarthritis (KOA), also known as degenerative osteoarthritis, is a common and frequently occurring disease in orthopedics with cartilage degeneration as the pathogenic cause and articular bone hyperplasia as the sign. Many studies have confirmed that KOA can be effectively treated by traditional Chinese medicine (TCM) external treatment. So we take advantage of the method of network meta-analysis to systematically compare the efficacy and safety of different types of TCM external treatment for the KOA. METHODS: We will research on external treatment of KOA by traditional Chinese medicine using randomized controlled trials (RCTs) in search database (EMBASE, PubMed, Web of Science, Chinese National Knowledge Infrastructure [CNKI], Weipu database [VIP], Wanfang, and China BioMedical Literature [CBM]). The data and evidence obtained will be processed using Stata 15.0 and WinBUGS 1.4.3. RESULTS: We will evaluate the efficacy and safety of traditional Chinese medicine external treatment for the knee osteoarthritis in this study. CONCLUSION: This study will provide a new regimen for KOA treatment. It has extremely high reference value. INPLASY REGISTRATION NUMBER: INPLASY2020120001. DOI NUMBER: : 10.37766/inplasy2020.12.0001.

Cangxitongbi capsule protects articular cartilage of the knee in rats by regulating ADAMTS-5.

BACKGROUND: Knee osteoarthritis (KOA) is a disease with a high incidence in elderly patients and traditional Chinese medicine has a significant effect on the treatment of KOA. Cangxitongbi capsule (CXTB) is a traditional Chinese medicine for KOA treatment and has a remarkable curative effect. The purpose of this article is to investigate the mechanism of CXTB in protecting joint cartilage on KOA rats. METHODS: A total of 30 male Sprague-Dawley rats were randomly assigned into five groups: control group; model group; low-, mid-, and high-dose CXTB groups (17.5, 35, and 70 mg/mL). KOA models were made by modified Hulth method except the control group. After pharmacological administration for 4 weeks, knee articular cartilages were observed by hematoxylin and eosin (HE) staining and evaluated by Mankin score. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect the concentration of ADAMTS-5. The peripheral blood of the rats was collected to detect content of interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) by enzyme-linked immunosorbent assay (ELISA). RESULTS: The morphological structure of cartilage in the 3 CXTB groups was significantly improved compared with the model group, and the improvement positively correlated with the drug dosage (P<0.05). Compared with the model group, the expression levels of ADAMTS-5 of the 3 CXTB groups was obviously decreased (P<0.05). Furthermore, the upstream targets of ADAMTS-5, including IL-1ß and TNF-α were down-regulated in the 3 CXTB groups (P<0.05). CONCLUSIONS: Knee joint cartilage on KOA model rats is protected by CXTB via down-regulation of ADAMTS-5. The upstream targets of ADAMTS-5, IL-1ß and TNF-α, were also down-regulated by CXTB.