Hovenia dulcis: a Chinese medicine that plays an essential role in alcohol-associated liver disease.

Globally, alcohol-associated liver disease (ALD) has become an increased burden for society. Disulfirams, Benzodiazepines (BZDs), and corticosteroids are commonly used to treat ALD. However, the occurrence of side effects such as hepatotoxicity and dependence, impedes the achievement of desirable and optimal therapeutic efficacy. Therefore, there is an urgent need for more effective and safer treatments. Hovenia dulcis is an herbal medicine promoting alcohol removal clearance, lipid-lowering, anti-inflammatory, and hepatoprotective properties. Hovenia dulcis has a variety of chemical components such as dihydromyricetin, quercetin and beta-sitosterol, which can affect ALD through multiple pathways, including ethanol metabolism, immune response, hepatic fibrosis, oxidative stress, autophagy, lipid metabolism, and intestinal barrier, suggesting its promising role in the treatment of ALD. Thus, this work aims to comprehensively review the chemical composition of Hovenia dulcis and the molecular mechanisms involved in the process of ALD treatment.

Zhilong Huoxue Tongyu capsule inhibits rabbit model of hyperlipidemia and atherosclerosis through NF-κB/NLRP3 signaling pathway.

Objective: Zhilong Huoxue Tongyu capsule (ZL) is a Chinese patent medicine for treating cardio-cerebral diseases. However, the pharmacological mechanism by which it regulates blood lipids and treats atherosclerosis (AS) is unclear. Therefore, the purpose of this study is to explore the mechanism of ZL inhibiting hyperlipidemia and treating AS through NF-κB/NLRP3 signaling pathway. Methods: Fifty New Zealand white rabbits were divided into control, model, model + ZL (3.12 g/kg/d, i.g.), model + atorvastatin (0.51 mg/kg/d, i.g.), and model + ZL + atorvastatin groups. Except for the control group, all other groups underwent carotid intima air drying and received a high-fat diet for 28 days to establish hyperlipidemia AS model, and drug treatment was given for the same period of time after modeling. Pathological changes and blood lipids were detected, NF-κB/NLRP3-related protein or gene expression levels were analyzed in carotid tissue. Results: ZL significantly reduced blood lipids and delayed the progression of AS. TC, TG, and LDL-C were decreased while HDL-C was increased in blood, IMT thickening and plaque formation of carotid arteries were inhibited, VRI was alleviated, and pathological features were improved. NF-κB, NLRP3 and IL-1ß in the carotid artery were significantly down-regulated after intervention with ZL. RT-PCR and western blot analysis showed that NF-κB (p-NF-κB), NLRP3, caspase-1, IL-1ß and IL-18 were significantly downregulated by ZL. Conclusions: ZL can be used effectively as adjuvant therapy for hyperlipidemia and AS, combining it with atorvastatin yielded more optimized efficacy, but its anti-inflammatory and pharmacological mechanisms of inhibiting pyroptosis should be studied further.

Iristectorigenin C suppresses LPS-induced macrophages activation by regulating mPGES-1 expression and p38/JNK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used clinically to treat inflammatory diseases clinically. However, the adverse effects of NSAIDs cannot be ignored. Therefore, it is critical for us to find alternative anti-inflammatory drugs that can reduce adverse reactions to herbal medicine, such as Iris tectorum Maxim., which has therapeutic effects and can treat inflammatory diseases and liver-related diseases. AIM OF THE STUDY: This study aimed to isolate active compounds from I. tectorum and investigate their anti-inflammatory effects and action mechanisms. MATERIALS AND METHODS: Fourteen compounds were isolated from I. tectorum using silica gel column chromatography, Sephadex LH-20, ODS and high performance liquid chromatography, and their structures were identified by examining physicochemical properties, ultraviolet spectroscopy, infrared spectroscopy, mass spectrometry, and nuclear magnetic resonance spectroscopy. Classical inflammatory cell models were established using lipopolysaccharide (LPS)-stimulated RAW264.7 cells and rat primary peritoneal macrophages to examine the effect of these compounds. To examine the action mechanisms, the nitric oxide (NO) levels were measured by Griess reagent and the levels of inflammatory cytokines in the supernatant were measured by ELISA; The expressions of major proteins in prostaglandin E2 (PGE2) synthesis and the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were examined by Western blotting, and the mRNA expression levels were measured by quantitative real-time polymerase chain reaction; and the nuclear translocation of p65 was examined by high content imaging. Molecular docking was used to predict the binding of active compound to target protein. RESULTS: Our findings revealed that Iristectorigenin C (IT24) significantly inhibited the levels of NO and PGE2 without affecting cyclooxygenase (COX)-1/COX-2 expression in LPS-induced RAW264.7 cells and rat peritoneal macrophages. Furthermore, IT24 was shown to decrease the expression of microsomal prostaglandin synthetase-1 (mPGES-1) in LPS-induced rat peritoneal macrophages. IT24 did not suppress the phosphorylation and nuclear translocation of proteins in the NF-κB pathway, but it inhibited the phosphorylation of p38/JNK in LPS-stimulated RAW264.7 cells. Additionally, molecular docking analysis indicated that IT24 may directly bind to the mPGES-1 protein. CONCLUSION: IT24 might inhibit mPGES-1 and the p38/JNK pathway to exert its anti-inflammatory effects and could be also developed as an inhibitor of mPGES-1 to prevent and treat mPGES-1-related diseases, such as inflammatory diseases, and holds promise for further research and drug development.

Clinical effect of Danshen decoction in patients with heart failure: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The incidence of heart failure (HF) is increasing year by year, posing a great threat to human health. Although pharmacotherapy has been able to significantly prolong patient survival, pharmacotherapy for HF still has limitations due to its complex pathogenesis and considerable individual variability, there is a great need to explore complementary and alternative therapies to slow down the progression of HF. Danshen decoction is used to treat several cardiovascular diseases including HF, but the efficacy of stabilization is uncertain. This meta-analysis evaluated the clinical efficacy of Danshen Decoction for the treatment of HF. METHODS: The registration number assigned to this meta-analysis on the PROSPERO platform is CRD42022351918. Four databases were searched, and randomized controlled trials (RCTs) of Danshen decoction combined with conventional treatment (CT) of HF were screened, CT included medical treatments other than Danshen Decoction to which the patient was treated (including but not limited to angiotensin converting enzyme inhibitor, angiotensin receptor blocker, angiotensin receptor neprilysin inhibitors, ß-blockers, diuretics, mineralcorticoid recept antagonist etc.). The clinical efficacy rate (CER), left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic diameter (LVESD), brain natriuretic peptide (BNP), N-terminal pro-B type natriuretic peptide (NT-proBNP) and hypersensitive C-reactive protein (hs-CRP) were included as outcome indicators. The GRADE grading scale was used to grade the above indicators. The Cochrane risk-of-bias tool and the Jadad quality scale were used to assess the methodological quality of RCTs. Finally, RevMan V.4.5 software was used for data synthesis, 95% confidence intervals (CI) for dichotomous data, risk ratios (RR), and mean differences (MD) for continuous variables were calculated, Chi-square and I2 were used for heterogeneity assessment. RESULTS: Nine RCTs with a total of 855 patients were included in this study, and all included RCTs had a low overall quality risk of bias and high quality of reported information. The results of the meta-analysis showed that compared with the use of CT, CER (%) was significantly improved due to Danshen decoction combined with CT (MD = 3.95, 95% CI [2.58, 6.04], P < 0.00001), LVEF (%) was significantly improved (MD = 5.46, 95% CI [5.32, 5.60], P < 0.00001), LVEDD (mm) was significantly reduced (MD = -5.27, 95% CI [-6.21, -4.32], P < 0.00001), LVESD (mm) was significantly reduced (MD = -4.60, 95% CI [-5.87, -3.32], P < 0.00001), BNP (pg/mL) was significantly reduced (MD = -88.61, 95% CI [-121.98, -55.24], P < 0.00001), NT-proBNP (pg/mL) was significantly decreased (SMD = -3.33, 95% CI [-5.92, -0.73], P = 0.01), hs-CRP (mg/L) was significantly decreased (MD = -2.73, 95% CI [-4.11, -1.34], P = 0.0001). The quality of the GRADE evidence for all outcomes was moderate to low and no RCTs reported adverse events. CONCLUSION: Our research demonstrates that Danshen decoction is an effective and safe treatment option for HF. Nevertheless, considering the limitations of methodological and the quality of RCTs, more rigorous, large-scale, multicenter randomized clinical trials are needed to further evaluate the efficacy and safety of Danshen decoction in the treatment of HF patients.

Integrating network analysis and experimental validation to reveal the mitophagy-associated mechanism of Yiqi Huoxue (YQHX) prescription in the treatment of myocardial ischemia/reperfusion injury.

Myocardial ischemia/reperfusion (I/R) injury is the main cause of increasing postischemic heart failure and currently there is no definite treatment for myocardial I/R injury. It has been suggested that oxidative stress-induced mitochondrial dysfunction plays an important role in the pathological development of myocardial I/R. In this study, Yiqi Huoxue (YQHX) prescription, as a kind of Chinese herbal formula, was developed and shown to alleviate I/R injury. Network analysis combined with ultrahigh-performance liquid chromatography-high resolution mass spectrometry expounded the active components of YQHX and revealed the mitophagy-regulation mechanism of YQHX treating I/R injury. In vivo experiments confirmed YQHX significantly alleviated I/R myocardial injury and relieved oxidative stress. In vitro experiments validated that YQHX could relieve hypoxia/reoxygenation injury and attenuate oxidative stress via improving the structure and function of mitochondria, which was strongly related to regulating mitophagy. In summary, this study demonstrated that YQHX, which could alleviate I/R injury via targeting mitophagy, might be a potential therapeutic strategy for myocardial I/R injury.

Material basis and integrative pharmacology of danshen decoction in the treatment of cardiovascular diseases.

BACKGROUND: Cardiovascular diseases (CVDs) are among the primary and predominant threats to human health with increasing incidence. Danshen Decoction (DSD) as an adjuvant therapy can benefit CVDs patients by improving clinical efficacy. PURPOSE: The purpose of this study was to identify the active components and potential pharmacological mechanisms of DSD by combining mass spectrometry with a network pharmacology strategy and to review the use of DSD in the treatment of CVDs. METHOD: First, the composition of DSD was analyzed by ultrahigh-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS). Second, the network pharmacology method was used to elucidate the underlying material basis and possible pharmacological mechanism of DSD for the treatment of CVDs. Finally, clinical and experimental studies on DSD in the past ten years were retrieved from the PubMed and CNKI database, and the content of these studies was used to summarize the latest progress in DSD treatment of CVDs. OUTCOME: A total of 35 compounds were found in DSD by manual identification from the analysis of MS, which may be the material basis for the therapeutic effect of DSD. After taking the intersection of 2086 targets related to CVDs, these 35 compounds are considered to play a role in the treatment of CVDs through 210 targets including signal transducer and activator of transcription 3 (STAT3), sarcoma (SRC) and phosphoinositide-3-kinase regulatory subunit (PIK3R), and a total of 168 signaling pathways were involved in the regulation of CVDs by DSD, including PI3K-AKT signaling pathway, Alzheimer disease, and Rap1 signaling pathway. A total of 29 clinical studies using DSD in the treatment of CVDs were included in the literature review, and these studies showed the positive significance of DSD as adjuvant therapy, while 14 experimental studies included in the literature review also demonstrated the effectiveness of DSD in the treatment of CVDs. CONCLUSION: DSD plays a role in the treatment of CVDs through a variety of active ingredients. Large-scale clinical research and more in-depth experimental research will help to further reveal the mechanism of DSD in the treatment of CVDs.

Zhilong Huoxue Tongyu Capsules' Effects on ischemic stroke: An assessment using fecal 16S rRNA gene sequencing and untargeted serum metabolomics.

Zhilong Huoxue Tongyu capsule (ZHTC) is an effective traditional Chinese medicine compound for the treatment of ischemic stroke, which is widely used in clinical ischemic stroke patients. However, it is uncertain whether ZHTC affects ischemic stroke through gut microbiota and serum metabolites. In this study, a rat model of middle cerebral artery occlusion (MCAO) was prepared. By evaluating motor nerve function score, cerebral infarct size, brain tissue damage and intestinal barrier damage, it was found that ZHTC improved stroke-related symptoms in MCAO rats. Using 16S rRNA gene sequencing, fecal microbial transplantation (FMT), untargeted metabolomics, and spearman correlation analysis of gut microbiota and serum metabolites, we found that ZHTC can regulate the abundance of p_Firmicutes, p_Bacteroidota,p_Proteobacteria, g_Prevotella, and g_Lactobacillus, and regulated 23 differential metabolites. Spearman correlation analysis found that Arginine was positively correlated with p_Firmicutes, o_Clostridiales, c_Clostridia, and negatively correlated with p_Bacteroidetes, c_Bacteroidia,o_Bacteroidales; L-Lysine was negatively correlated with f_Christensenellaceae; L-methionine was positively correlated with o_Lactobacillales, f_Lactobacillaceae, and g_Lactobacillus. Altogether, this study shows for the first time that ZHTC can ameliorate ischemic stroke by modulating gut microbiota and metabolic disturbances. This lays the foundation for further revealing the causal relationship between ZHTC, gut dysbiosis, plasma metabolite levels and ischemic stroke, and provides a scientific explanation for the ameliorating effect of ZHTC on ischemic stroke.

Danshen Decoction in the Treatment of Hyperlipidemia: A Systematic Review and Meta-Analysis Protocol of Randomized Controlled Trials.

Background. Hyperlipidemia is a common clinical chronic disease that increases the incidence of cardiovascular disease. However, although oral drug therapy can reduce blood lipids, long-term drug treatment may cause various side effects. Therefore, it is important to find suitable alternatives for the treatment of hyperlipidemia. The classic traditional Chinese medicine (TCM) prescription Danshen decoction (DSD) has been found effective for the treatment of hyperlipidemia. This protocol aims to evaluate the efficacy and safety of DSD in the treatment of hyperlipidemia. Methods and Analysis. We will screen all the randomized controlled trials (RCTs) which research DSD in the treatment of hyperlipidemia from 7 databases from their inception to July 2022; three investigators will independently screen and select RCTs and extract data and assess the risk of bias. The Cochrane scale, Jadad scale, and GRADE scale will be used to assess the risk of bias, literature quality, and outcome quality, respectively. Review Manager V.5.4 will be used for the meta-analysis, and the results will be presented as the risk ratio (RR) for the binary data and the mean difference (MD) or standardized mean difference (SMD) for the continuous data. Ethical approval and Dissemination. This protocol for a systematic review will be submitted to a peer-reviewed journal for publication and ethical approval is not applicable. PROSPERO registration number.CRD42022352467.

Hypertensive heart disease and myocardial fibrosis: How traditional Chinese medicine can help addressing unmet therapeutical needs.

Long-term elevated blood pressure will increase the cardiac load and lead to myocardial fibrosis (MF). A variety of pathological mechanisms and signal transduction pathways are involved in the process of hypertensive MF, which is of great significance for the occurrence and development of ventricular dilatation and heart failure. MF is the pathological basis of hypertensive heart disease (HHD), and blood pressure control is the key to delaying MF and reducing the occurrence of cardiovascular events. Although a large number of experimental results suggest that anti-MF drug therapy has made great progress, the conclusions of relevant clinical trials are still not optimistic, and it is urgent to find new effective anti-MF medicine. The clinical efficacy of traditional Chinese medicine (TCM) in the treatment of MF in HHD is obvious, and some achievements have been made in the mechanism research. Studies have confirmed that a variety of TCM compound prescription and natural compounds play different degrees of inhibitory effect on MF. In this study, we reviewed the pathogenesis of MF in HHD and the current drug treatment strategies, summarized the latest research progress of TCM in the treatment of MF in HHD, and demonstrated the mechanism of its cardiac protective effect. Finally, we pointed out the limitations of the current study and prospected the future research of TCM.

Danshen decoction in the treatment of heart failure: A systematic review and meta-analysis protocol of randomized controlled trials.

BACKGROUND: Heart failure (HF) is considered the clinical endpoint of all cardiovascular diseases (CVDs). Although a large number of HF drugs and therapies have been developed, it is still need to find therapies with better clinical efficacy and fewer side effects. The purpose of this systematic evaluation is to assess the efficacy and safety of Danshen decoction on HF and the improvement of cardiac function (CF). METHODS: Four databases will be searched to identify any eligible studies, and this protocol does not require ethics committee review as the research is based on published articles. There are no restrictions set for the language, publication date, or status of the study. The clinical effective rate (CER) of HF treatment is considered to be the main result. CF, various serum inflammatory factors, and adverse events were defined as secondary outcomes. When more than 1 article is used to study the changes and results of the same index, we will conduct a meta-analysis. If the heterogeneity is not statistically significant (P > .10 or I2 < 50%), a fixed-effect model will be established to estimate the overall intervention effect. Otherwise, random effect models will be used to provide more conservative results. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will provide reliable evidence-based basis for the clinical application of Danshen decoction in the treatment of HF.

Network Pharmacology Analysis and Experimental Verification Strategies Reveal the Action Mechanism of Danshen Decoction in Treating Ischemic Cardiomyopathy.

Background: Danshen Decoction comprises Salvia miltiorrhiza, Santalum album, and Amomum villosum. It can promote blood circulation and remove blood stasis, and is commonly used in the treatment of gastric and duodenal ulcers, coronary heart disease, angina pectoris, etc. This research is based on network pharmacology and is experimentally verified to explore the potential mechanism of Danshen Decoction in the treatment of ischemic cardiomyopathy (ICM). Methods: The effective components and targets of Danshen Decoction were firstly extracted from Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform, the drug-component-target-disease network was then constructed, the protein-protein interaction (PPI) network was constructed, the Gene Ontology (GO) enrichment analysis was carried out, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was analyzed in order to find the potential active components and therapeutic mechanisms. Finally, the in vitro hypoxia/reoxygenation model in H9c2 cells was established to verify the predicted active components and therapeutic mechanisms. Results: The results showed that Danshen Decoction has 67 potential active components and 109 therapeutic targets in treating ICM. These targets were rich in a variety of gene functions and different signaling pathways; the main gene targets include TP53, c-Jun, and Akt1. Go enrichment analysis showed that response to drug, membrane raft, and G protein-coupled amine receiver activity rank first in each process, and the main signaling pathways include PI3K-Akt signaling pathway. Through molecular docking and experimental verification of the major active components and core therapeutic targets, the active components of Danshen Decoction demonstrated an ability to reduce the cell damage caused by hypoxia/reoxygenation in H9c2 cells by regulating the core therapeutic target including Akt1, c-Jun, and TP53. Conclusion: Danshen Decoction has the effect of treating ICM in multiple ways, which is consistent with the results of network pharmacology. This laid a foundation for further study in exploring the active principles and pharmacological mechanism of Danshen Decoction.

Effects of Xinkeshu tablets on coronary heart disease patients combined with anxiety and depression symptoms after percutaneous coronary intervention: A meta-analysis.

BACKGROUND: Xinkeshu tablets (XKS), a well-known Chinese patent drug, have been administered to coronary heart disease (CHD) patients with anxiety and depression after percutaneous coronary intervention (PCI). PURPOSE: This meta-analysis aimed to systematically evaluate the clinical effects of XKS for treating CHD patients with anxiety and depression after PCI. METHODS: Randomized controlled trials (RCTs) about XKS alone or combined with conventional drugs for the treatment of CHD patients with anxiety and depression after PCI were retrieved from 7 databases (MEDLINE, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP) Database, Chinese Biomedical Database (CBM) and Wanfang Database) through November 2021. First, the studies were reviewed and screened by two independent assessors according to the eligibility criteria. Second, the methodological quality of the eligible studies was evaluated based on the Cochrane Collaboration's tool for assessing the risk of bias. Subsequently, meta-analysis was performed by using RevMan 5.4 software, and publication bias was evaluated by Stata 12.0 software. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to rate the quality of the evidence. RESULTS: In total, 11 clinical RCTs involving 1000 patients were included in this study. This meta-analysis found that compared with conventional treatment alone, XKS combined with conventional treatment significantly improved the anxiety scale scores (SMD = -1.97, 95% CI -3.13 to -0.82; p = 0.0008; I2 = 98%), the depression scores (SMD = -2.80, 95% CI -4.49 to -1.10; p = 0.001; I2 = 98%), the scores on the Medical Outcomes Study 36 Item Short Form Health Survey (SF36) (MD = 11.22, 95% CI 4.19 to 18.26; p =0.002; I2 = 95%) and the blood lipid levels of total cholesterol (TC) (MD = -0.38, 95% CI -0.62 to -0.13; p = 0.003; I2 = 0%) and triglyceride (TG) (MD = -0.31, 95% CI -0.46 to -0.17; p < 0.0001; I2 =  0%). CONCLUSION: The current evidence suggests that XKS might benefit CHD patients experiencing anxiety and depression after PCI by helping to improve their depression symptoms, TC and TG blood lipid levels. However, due to insufficient methodological quality of the studies, several risks of bias and inadequate reporting of the clinical data, more rigorous, multicenter, sufficient-sample and double-blind randomized clinical trials are warranted.

Zhilong Huoxue Tongyu Capsule Alleviated the Pyroptosis of Vascular Endothelial Cells Induced by ox-LDL through miR-30b-5p/NLRP3.

BACKGROUND: Our previous studies have demonstrated a protective role of Zhilong Huoxue Tongyu capsule in atherosclerosis (AS); however, the molecular mechanisms are unclear. METHODS: Human coronary artery endothelial cells (HCAECs) were induced with oxidized low-density lipoprotein (ox-LDL) to obtain cellular AS models. Then, the medicated serum of Zhilong Huoxue Tongyu capsule was obtained and used for treatment with ox-LDL-induced HCAECs. The cell viability was detected by CCK-8 assay. Besides, the binding between miR-30b-5p and NLRP3 was determined by the dual-luciferase reporter gene system assay. Furthermore, ox-LDL-induced HCAECs were transfected with miR-30b-5p mimic or miR-30b-5p inhibitor. The pyroptosis of HCAECs was assessed by flow cytometry, LDH content detection, and qRT-PCR assays. RESULTS: 10% medicated serum of Zhilong Huoxue Tongyu capsule was the maximum nontoxic concentration and it was used in subsequent assays. The rate of pyroptosis, LDH content, and the mRNA expression level of pyroptosis-related genes including NLRP3, ASC, Caspase 1, IL-1ß, and IL-18 were prominently enhanced after HCAECs were induced by ox-LDL, which were markedly rescued with medicated serum of Zhilong Huoxue Tongyu capsule. In addition, the medicated serum of Zhilong Huoxue Tongyu capsule significantly enhanced the ox-LDL-induced reduction of miR-30b-5p level. NLRP3 could bind to miR-30b-5p and was negatively corrected with miR-30b-5p. Moreover, all the rates of pyroptosis, LDH content, and the mRNA expression levels of pyroptosis-related genes including NLRP3, ASC, Caspase 1, IL-1ß, and IL-18 were further observably decreased after ox-LDL-induced HCAECs treated with medicated serum were transfected with miR-30b-5p mimic, while these were significantly rescued with transfection of miR-30b-5p inhibitor. CONCLUSION: Zhilong Huoxue Tongyu capsule alleviated the pyroptosis of vascular endothelial cells induced by ox-LDL through miR-30b-5p/NLRP3.

Efficacy and Safety of Acupuncture Vs. Hormone Therapy for Menopausal Syndrome: A Systematic Review and Meta-Analysis.

Menopausal syndrome (MPS) is a common gynecological disorder around the time of menopause, and hormone therapy (HT) is the first-line treatment for it. However, HT is prone to cause adverse reactions in MPS patients treated with HT. Acupuncture is a popular non-pharmaceutical therapy for MPS, but the differences in the efficacy and safety between acupuncture and HT remain unclear. The purpose of this evidence-based study is to address this issue. Five databases were searched for potentially eligible RCTs. All RCTs comparing acupuncture with HT in the treatment of MPS were included in this study. The clinical effective rate was the primary outcome. Kupperman index, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E[Formula: see text], and side effects were the secondary outcomes. A total of 15 RCTs recruiting 1376 MPS patients were included. Results of meta-analysis showed that compared with HT, acupuncture significantly improved clinical effective rate (RR = 1.09, 95% CI 1.03 to 1.16, [Formula: see text] = 0.005), decreased the Kupperman index (WMD = -2.55, 95% CI = -2.93 to -2.17, [Formula: see text] < 0.00001) and the incidence of side effects (RR = 0.14, 95% CI = 0.06-0.32, [Formula: see text] < 0.00001). There were no statistically significant differences in serum FSH (WMD = -1.36, 95% CI = -3.25-0.53, [Formula: see text] = 0.16), E2(WMD = -1.11, 95% CI = -2.59-0.37, [Formula: see text] = 0.14), or LH (WMD = -1.87, 95% CI = -4.58-0.83, [Formula: see text] = 0.17) between the acupuncture and HT groups. Based on the current evidence, manual acupuncture is safer and more effective than HT and is recommended for the treatment of MPS, but the evidence for the efficacy of other types of acupuncture is inconclusive.

Evaluation of Zhilong Huoxue Tongyu capsule in the treatment of acute cerebral infarction: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Zhilong Huoxue Tongyu capsule (ZL) is a Chinese patent medicine and used for the treatment of acute cerebral infarction (ACI) and its clinical application has gradually been widely recognized in China. However, the effects of ZL for patients with ACI have never been systematically evaluated. PURPOSE: A systematic review and meta-analysis was performed to evaluate the efficacy of ZL in ACI. STUDY DESIGN: A systematic review and meta-analysis of randomized clinical trials (RCTs). MATERIALS AND METHODS: A systematic review and meta-analysis were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The comprehensive literature search was accomplished in 6 electronic databases to find relevant randomized controlled trials from their inception until October 31, 2020. The Cochrane Handbook for Systematic Reviews of Interventions was used for methodological quality and independent evaluation. Review Manager 5.3 was used to analyze all the data obtained. The Clinical Effective Rate (CER) was the primary outcome, and the National Institutes of Health Stroke Score (NIHSS), Barthel Index (BI), and Modified Rankin Scale (MRS) were the secondary outcomes. RESULTS: Seven clinical studies recruiting 571 eligible patients were included in this meta-analysis. The results of meta-analysis suggested that compared with conventional treatment alone, ZL combined with conventional treatment significantly improved CER (RR = 1.20, 95% CI: 1.12-1.29, p < 0.00001), decrease National Institutes of Health Stroke Scale Score (NIHSS) (MD = -2.60, 95% CI: -3.41-1.79, p < 0.00001), Barthel Index (BI) (MD = -9.75, 95% CI: 7.15-12.36, p < 0.00001) and Modified Rankin Scale (MRS) (MD = -0.57, 95% CI: -0.84-0.30, p < 0.00001). There were no reported adverse events in the studies. Most results were robust and the quality of evidence was from moderate to low. CONCLUSION: ZL combined with conventional treatment can improve the short-term outcomes of ACI patients, indicating ZL is a promising treatment choice for ACI and may be used as adjunctive treatment to the conventional treatment of ACI. However, due to the limitations of included clinical trials, high-quality clinical trials with longer follow-ups are still needed to further assess the effectiveness and safety of ZL for ACI patients.

Effect of cultivation ages on anti-inflammatory activity of a new type of red ginseng.

Ginseng has been widely applied in clinical practice, but the cultivation age cannot be ignored as it influences the quality of ginseng and its products. In this work, different cultivation ages of fresh ginseng (FG) from four to seven years were analysed by UPLC-Q-TOF-MS/MS. Principal component analysis and supervised orthogonal partial least squared discrimination analysis, which belong to the normal method of multivariate statistical analysis, were applied to discover the characteristic components of FG at different cultivation ages. The components of new type of red ginseng (NRG) derived from FG at different cultivation ages were compared by HPLC analysis. The pharmacological anti-inflammatory activity was evaluated by ELISA and qPCR. The result showed that the characteristic components of both 6- and 7-year-old ginseng were ginsenoside Rb1, mal-ginsenoside Rb1, ginsenoside Rc, mal-ginsenoside Rc, mal-ginsenoside Rb1 isomer, and mal-ginsenoside Rb2. Moreover, the characteristic components of both 4- and 5-year-old ginseng were ADP-glucose and 3-hydroxyhexanoyl CoA. In addition, 6-year-old NRG has higher rare ginsenosides than 4-year-old NRG, which possesses great anti-inflammatory activity in vitro. The results reveal the ginsenoside transformation law of NRG processing and suggest that the cultivation age of FG influences the content of ginsenosides in NRG. Therefore, 6-year-old ginseng is more suitable for red ginseng processing and clinical use.

[A study on quality of Paridis Rhizoma and consideration on standards of Paridis Rhizoma in Chinese Pharmacopoeia].

Thin layer chromatography, high performance liquid chromatography and multivariate statistical analysis were integrated in current study to provide a basis for the quality evaluation and the standard improvement of Paridis Rhizoma(Chinese name: Chong-lou). The results demonstrated that the primary saponins in the two authorized sources of Paridis Rhizoma were polyphyllinsⅠ, Ⅱ and Ⅶ, while the rhizome of Trillium tschonoskii an adulterant of Paridis Rhizoma was rich of polyphyllin Ⅵ. Therefore, the apparent content of polyphyllin Ⅵ plays a determinant role towards the source authentication of raw materials and decoction slices of Paridis Rhizoma, whose adulterants frequently occur in the market. Moreover, the contents of polyphyllin Ⅵ in the two authorized sources could meet the requirements of Chinese Pharmacopoeia. Therefore, we suggested that polyphyllin Ⅵ should not be omitted from the quality standard of Paridis Rhizoma in the Chinese Pharmacopoeia, and on the other side, polyphyllinsⅠ, Ⅱ and Ⅶ should be the eligible quality indicators. The study aims to sound information and evidences for the quality evaluation of Paridis Rhizoma, and also to provide a theoretical basis for the standard revision of Paridis Rhizoma in the future Chinese Pharmacopoeia.

Toxicity and Its Mechanism Study of Arecae semen Aqueous Extract in Wistar Rats by UPLC-HDMS-Based Serum Metabolomics.

BACKGROUND: Arecae semen (AS) is officially recorded in Chinese Pharmacopoeia and it is known for its multiple functions, including antidepressive, antioxidant, anti-inflammatory, and cholesterol-lowering effects, which have been confirmed by modern pharmacological study. Previous study in our laboratory showed that long-term oral administration of Arecae semen (AS) is officially recorded in Chinese Pharmacopoeia and it is known for its multiple functions, including antidepressive, antioxidant, anti-inflammatory, and cholesterol-lowering effects, which have been confirmed by modern pharmacological study. Previous study in our laboratory showed that long-term oral administration of Hypothesis. The aim of this work was to characterize the metabolome, evaluate the metabolic changes, and study the mechanisms of the toxicity induced by different treatment doses of ASAE via metabolomics. METHODS: Wistar rats were administered orally two different doses of ASAE (1500 and 4500 mg/kg/d) for 30 days. The investigation was carried out to evaluate the safety of ASAE. And, the UPLC-HDMS-based serum metabolomics in conjunction with multivariate statistical techniques was applied to investigate the serum metabolite profile and potential markers of toxicity induced by different doses of ASAE. RESULTS: Coupled with blood biochemistry and histopathology results, the significant difference in metabolic profiling was observed between 1500 and 4500 mg/kg/d dosages of ASAE-treated rats and normal rats by using pattern recognition analysis, indicating that changes in serum metabolites must have occurred. Some significant changed metabolites such as arachidonic acid, linoleic acid, stearic acid, and LPC (18 : 1) have been found and identified. These biochemical changes in serum metabolites are related to the perturbation of linoleic acid metabolism, arachidonic acid metabolism, glycerophospholipid metabolism, and purine metabolism, which may be helpful to further understand the cardiotoxicity and neurotoxicity of ASAE. CONCLUSION: The study shows that the metabolomic method may be a valuable tool for studying the essence of toxicity induced by traditional Chinese medicine.

UPLC-HDMS-based on serum metabolomics reveals the toxicity of arecae semen.

ETHNOPHARMACOLOGICAL RELEVANCE: Arecae semen has been used as vermifuge and digestant in traditional Chinese medicine (TCM) for more than one thousand years. However, the toxicity effect of areca semen and its underlying mechanism are still unclear. THE AIM OF THE STUDY: This study was aimed to investigate the toxicity of arecae semen and to explore its mechanisms by serum metabolomics. MATERIALS AND METHODS: The male Wistar rats were divided into the control group and treated group (n = 6 in each group), which were given by gavage with distill water or arecae semen aqueous extract (ASAE) once a day for 30 days, respectively. Serum samples were collected from all the rats after treatment of 7-day, 14-day and 30-day for metabolomics analysis. Moreover, biochemistry analysis and histopathological examination were performed at the end of study. RESULTS: The phenomenon of diarrhea, less physical activity, tremors and body curl up were observed in the treated group. Additionally, the body weights of treated rats were significantly decreased compared with control rats from the 8th day after oral administration. Except the level of creatinekinase (CK) in the treated group significantly increased compared with the control group, there were no differences on biochemistry parameters and histopathological test in the two groups. Combined with the methods of principal component analysis (PCA), orthogonal projection to latent structure-discrimination analysis (OPLS-DA) and available databases, the treated and control rats were clearly distinguished from each other and 19 metabolites were identified as the potential biomarkers in the arecae semen treated rats. The identified biomarkers indicated that there were perturbations of the phospholipid metabolism, amino acid metabolism and fat acid metabolism in the treated group. CONCLUSIONS: This indicated that arecae semen possessed certain cardiotoxicity and inhibited the normal growth in Wistar male rats. In addition, the metabolomics approach is a useful tool to study the toxicity in TCM.

[Comparative study on quality of decoction pieces of Saposhnikovia divaricata with different growth patterns and years and thinking of standard of decoction pieces of S. divaricata in Chinese Pharmacopoeia].

This study aims to compare the internal chemical composition and appearance indifferent growth patterns and years of Saposhnikovia divaricata decoction pieces,which was applied to explore the effect of growth patterns and years on its quality. The appearance characteristic data of 55 batches of different growth patterns and years of S. divaricata were collected using PANTONE color card.High performance liquid chromatography( HPLC) was used to determine the contents of prim-O-glucosyl-cinmifugin,cimifugin,4-O-ß-D-glucosyl-5-O-methylvisamminol and sec-O-glucosylhamaudol. The content of alcohol soluble extract and water-soluble extract were determined by hot-dip method. The content of volatile oil was determined by steam distillation. The correlation between growth patterns and years and the contents of 4 chromones,extracts and volatile oil were analyzed by modern statistical methods. Also,the method of comprehensively evaluating the quality of Chinese herbal pieces was developed by combining the growth patterns and years,appearance and chemical indexes. MTT assay was used to evaluate the effects on the survival rate of RAW264. 7 cells at four different concentrations of chromones and LPS was used to stimulate well-growing RAW264. 7 cells to establish an inflammatory model. The contents of NO and TNF-α in cell supernatant were detected by NO test kit and ELISA method. The contents of alcohol soluble extracts and water-soluble extracts in different growth patterns and years are: wild productsperennial cultivation>annual cultivation; the contents of four chromones are: wild products>perennial cultivation and annual cultivation. There was no significant difference between the sum of the two indexes in the Pharmacopoeia of perennial cultivation and wild products. 4 chromones showed no toxicity to RAW264. 7 cells at 5 mg·L-1. The release of NO and TNF-α was inhibited by 4 chromones and the anti-inflammatory effect of cimifugin was the best. In summary,there are obvious differences in appearance characteristics,internal quality and effects between different growth patterns and years. It showed that the wild products were superior to the perennial cultivation and the perennial cultivation was superior to the annual cultivation. In order to alleviate the shortage of wild S. divaricata resources,it is suggested that the Chinese Pharmacopoeia standard should increase the character of decoction pieces of perennial cultivation,and properly raise the limit requirement of the sum of the two indexes in the Chinese Pharmacopoeia to ensure the clinical demands and effect.