Study on Shenbao Tablet in Treating Kidney-yang Deficiency Syndromebased on Metabolomics.

AIM: The aim of this study was to elucidate the mechanism of action of Shenbao tablets using metabolomics approach. BACKGROUND: Kidney-Yang deficiency is a common syndrome type in traditional Chinese Medicine (TCM) syndrome typology, closely related to disorders of multiple metabolic pathways and is the root cause and underlying syndrome type of many diseases. Shenbao tablets can significantly improve the main symptoms of kidney yang deficiency syndrome, but the mechanism of action of Shenbao tablets on kidney yang deficiency syndrome is still unknown. METHODS: The rats were intraperitoneally injected with hydrocortisone once a day for 40 days to simulate the syndrome. Traditional pharmacodynamic indicators (body mass, biochemical indicators and pathology) were used to evaluate the efficacy of the medicine. Serum, urine and feces were collected from rats. UPLC/MS metabolomics method was used to study the overall metabolic profile of serum, while GC/MS metabolomics method was used to study the metabolic spectrum of urine and feces. RESULTS: Results showed that the syndrome was significantly improved in the treatment group, and obvious metabolic disorders were observed in rats with the syndrome, with 47 potential biomarkers identified. Pathway analysis showed that nicotinate and nicotinamide metabolism, glycine, serine and trione metabolism, aminoacyl tRNA biosynthesis, glycoxylate and dicarboxylate metabolism were the major ways for Shenbao tablet to improve kidney-yang deficiency syndrome. CONCLUSION: The mechanism of action of Shenbao tablet in improving the syndrome involves the regulation of energy metabolism, amino acid metabolism, bile acid metabolism, fatty acid metabolism and intestinal microorganisms. This work shows that metabolomics is a promising tool for studying the essence of syndrome theory in TCM and the mechanisms of TCM.

Danggui-Shaoyao-San protects against non-alcoholic steatohepatitis via modulation of hepatic APP protein, Lysosomal CTSB release, and NF-κB activation.

Background: Non-alcoholic steatohepatitis (NASH), an escalating global health concern, is a primary factor behind cirrhosis, liver transplantation, and hepatocellular carcinoma. Effective treatments remain elusive. Danggui-Shaoyao-San (DGSY), a classic famous prescription employed in treating NASH, could hold promise, although its molecular underpinnings are still under investigation. This study undertakes an exploration of the impacts of DGSY on NASH and seeks to illuminate the mechanisms at play. Methods: UHPLC-Q-Orbitrap HRMS was employed to identify compounds within DGSY. Mice underwent a 25-week regimen of HFHC diet and high-sugar water, with 4 weeks of DGSY treatment for efficacy and pathogenic mechanism exploration in vivo. L02 cells were cultured with 0.2 mM FFA for 24 h, exposed to DGSY at 1 mg/ml and 2 mg/ml for efficacy and pathogenic mechanism exploration in vitro. Using online databases, we sought potential targets for NASH treatment, and through PPI networks, identified key targets. Expression levels of genes and proteins were examined by western blotting, RT-PCR, and immunofluorescence staining. Results: Thirty-four compounds were identified within DGSY. DGSY brought about marked reductions in biochemical indicators and yielded significant improvements in NASH mice histological features. Additionally, it mitigated hepatic steatosis and inflammation both in vivo and in vitro. The top 10 targets from two network pharmacology analyses, one focusing on structural prediction and the other on literature mining, identified APOE and APP as potential therapeutic targets for DGSY in NASH treatment. PCR validation confirmed that DGSY reduced APP expression after treatment, and further investigation revealed that DGSY significantly suppressed hepatic APP and Aß expression, indicating its effectiveness in treating NASH. Furthermore, it inhibited Aß-induced Cathepsin B lysosomal release, reducing hepatic inflammation. Conclusion: Danggui-Shaoyao-San has anti-steatohepatitis effects in ameliorating hepatic APP protein expression, reducing hepatic lysosomal CTSB release, and suppressing hepatic NF-κB activation. The study provided a more theoretical basis for the future clinical application of DGSY.

IL-1 receptor-associated kinase family proteins: An overview of their role in liver disease.

The interleukin-1 receptor-associated kinase (IRAK) family is a group of serine-threonine kinases that regulates various cellular processes via toll-like receptor (TLR)/interleukin-1 receptor (IL1R)-mediated signaling. The IRAK family comprises four members, including IRAK1, IRAK2, IRAK3, and IRAK4, which play an important role in the expression of various inflammatory genes, thereby contributing to the inflammatory response. IRAKs are key proteins in chronic and acute liver diseases, and recent evidence has implicated IRAK family proteins (IRAK1, IRAK3, and IRAK4) in the progression of liver-related disorders, including alcoholic liver disease, non-alcoholic steatohepatitis, hepatitis virus infection, acute liver failure, liver ischemia-reperfusion injury, and hepatocellular carcinoma. In this article, we provide a comprehensive review of the role of IRAK family proteins and their associated inflammatory signaling pathways in the pathogenesis of liver diseases. The purpose of this study is to explore whether IRAK family proteins can serve as the main target for the treatment of liver related diseases.

Therapeutic effect of Sanhua decoction on rats with middle cerebral artery occlusion and the associated changes in gut microbiota and short-chain fatty acids.

Sanhua decoction (SHD), a traditional prescription, has long been used in treating ischemic stroke (IS). However, the therapeutic effect of SHD and the associated changes in gut microbiota and short-chain fatty acids (SCFAs) are uncertain. In this study, a rat model of IS was established by the middle cerebral artery occlusion (MCAO). By evaluating the cerebral infarct area and brain tissue pathology, it was found that SHD ameliorated IS-related symptoms in MCAO rats. Using 16S rRNA gene sequencing, we found that SHD reduced abnormally elevated Lactobacillus and opportunistic pathogens such as Desulfovibrio, but increased some beneficial bacteria that produce SCFAs, including Clostridia, Lachnospiraceae, Ruminococcaceae, and Coprococcus. KEGG analysis revealed that SHD regulates several pathways, including D-arginine and D-ornithine metabolism, polyketide sugar unit biosynthesis, and cyanoamino acid metabolism, which are significantly altered in MCAO rats. By gas chromatography-mass spectrometry detection of SCFAs, we found that fecal acetic acid, valeric acid, and caproic acid were significantly increased in MCAO rats, whereas propionic acid and isobutyric acid were decreased. SHD reversed the changes in acetic acid and propionic acid in the model rats and significantly increased fecal butyric acid. In addition, MCAO rats had significantly higher serum levels of acetic acid, butyric acid, isovaleric acid, and valeric acid, and lower levels of caproic acid. Altered serum levels of butyric acid, isovaleric acid, valeric acid, and caproic acid were restored, and the level of isobutyric acid was reduced after SHD administration. Spearman analysis revealed that cerebral infarct area had a strong correlation with Bifidobacterium, Desulfovibrio, Lachnospiraceae, Lactobacillus, acetic acid, valeric acid, and caproic acid. Overall, this study demonstrates for the first time that the effect of SHD on IS may be related to gut microbiota and SCFAs, providing a potential scientific explanation for the ameliorative effect of SHD on IS.

Zhisou powder suppresses airway inflammation in LPS and CS-induced post-infectious cough model mice via TRPA1/TRPV1 channels.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhisou Powder (ZSP), a traditional Chinese medicine (TCM) prescription, has been widely used in the clinic for the treatment of post-infectious cough (PIC). However, the exact mechanism is not clear. AIM OF THE STUDY: The aim of this study was to investigate the ameliorative effect of ZSP on PIC in mice. The possible mechanisms of action were screened based on network pharmacology, and the potential mechanisms were explored through molecular docking and in vivo experimental validation. MATERIALS AND METHODS: Lipopolysaccharide (LPS) (80µg/50 µL) was used to induce PIC in mice, followed by daily exposure to cigarette smoke (CS) for 30 min for 30 d to establish PIC model. The effects of ZSP on PIC mice were observed by detecting the number of coughs and cough latency, peripheral blood and bronchoalveolar lavage fluid (BALF) inflammatory cell counts, enzyme-linked immunosorbent assay (ELISA), and histological analysis. The core targets and key pathways of ZSP on PIC were analyzed using network pharmacology, and TRPA1 and TRPV1 were validated using RT-qPCR and western blotting assays. RESULTS: ZSP effectively reduced the number of coughs and prolonged the cough latency in PIC mice. Airway inflammation was alleviated by reducing the expression levels of the inflammatory mediators TNF-α and IL-1ß. ZSP modulated the expression of Substance P, Calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF) in BALF. Based on the results of network pharmacology, the mechanism of action of ZSP may exert anti-neurogenic airway-derived inflammation by regulating the expression of TRPA1 and TRPV1 through the natural active ingredients α-spinastero, shionone and didehydrotuberostemonine. CONCLUSION: ZSP exerts anti-airway inflammatory effects through inhibition of TRPA1/TRPV1 channels regulating neuropeptides to alleviate cough hypersensitivity and has a favorable therapeutic effect on PIC model mice. It provides theoretical evidence for the clinical application of ZSP.

Brain and serum metabolomic studies reveal therapeutic effects of san hua decoction in rats with ischemic stroke.

San Hua Decoction (SHD) is a traditional four-herbal formula that has long been used to treat stroke. Our study used a traditional pharmacodynamic approach combined with systematic and untargeted metabolomics analyses to further investigate the therapeutic effects and potential mechanisms of SHD on ischemic stroke (IS). Male Sprague-Dawley rats were randomly divided into control, sham-operated, middle cerebral artery occlusion reperfusion (MCAO/R) model and SHD groups. The SHD group was provided with SHD (7.2 g/kg, i.g.) and the other three groups were provided with equal amounts of purified water once a day in the morning for 10 consecutive days. Our results showed that cerebral infarct volumes were reduced in the SHD group compared with the model group. Besides, SHD enhanced the activity of SOD and decreased MDA level in MCAO/R rats. Meanwhile, SHD could ameliorate pathological abnormalities by reducing neuronal damage, improving the structure of damaged neurons and reducing inflammatory cell infiltration. Metabolomic analysis of brain and serum samples with GC-MS techniques revealed 55 differential metabolites between the sham and model groups. Among them, the levels of 12 metabolites were restored after treatment with SHD. Metabolic pathway analysis showed that SHD improved the levels of 12 metabolites related to amino acid metabolism and carbohydrate metabolism, 9 of which were significantly associated with disease. SHD attenuated brain inflammation after ischemia-reperfusion. The mechanisms underlying the therapeutic effects of SHD in MCAO/R rats are related to amino acid and carbohydrate metabolism.

Dual Role of Pregnane X Receptor in Nonalcoholic Fatty Liver Disease.

The incidence of nonalcoholic fatty liver disease (NAFLD) has been rising worldwide in parallel with diabetes and metabolic syndrome. NAFLD refers to a spectrum of liver abnormalities with a variable course, ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), eventually leading to cirrhosis and hepatocellular carcinoma. Pregnane X receptor (PXR), a member of the nuclear receptor superfamily, plays a prominent part in the regulation of endogenous metabolic genes in NAFLD. Recent studies have suggested that PXR has therapeutic potential for NAFLD, yet the relationship between PXR and NAFLD remains controversial. In this review, PXR is proposed to play a dual role in the development and progression of NAFLD. Its activation will aggravate steatosis of the liver, reduce inflammatory response, and prevent liver fibrosis. In addition, the interactions between PXR, substance metabolism, inflammation, fibrosis, and gut microbiota in non-alcoholic fatty liver were elucidated. Due to limited therapeutic options, a better understanding of the contribution of PXR to the pathogenesis of NAFLD should facilitate the design of innovative drugs targeting NAFLD.

Integrating Network Pharmacology and In vivo Experimental Validation to Reveal the Mechanism of FuZheng YiLiu Formula on Estrogen Receptor Positive Breast Cancer.

BACKGROUND AND PURPOSE: FuZheng YiLiu Formula (FZYL) is a commonly used formula for postoperative estrogen receptor-positive (ER+) breast cancer and post-radiotherapy deficiency of both Qi and Yin. FZYL has been used in clinical practice for decades because of its ability to effectively improve the symptoms of deficiency in cancer patients. However, its mechanism needs to be further clarified. In this paper, we will observe the effect of FZYL on mice with ER+ breast cancer and explore the mechanism by which it improves the symptoms of ER+ breast cancer. MATERIALS AND METHODS: A tumor xenograft mouse model was established to detect tumor growth in vivo in order to evaluate the pharmacological effects of FZYL on ER+ breast cancer. The main targets of FZYL were identified by extracting the FZYL components and the corresponding potential target genes of breast cancer from the established database and constructing a protein-protein interaction network of shared genes using the string database. GO functional annotation and KEGG pathway enrichment analysis were performed, and molecular docking, molecular dynamics simulations, western blotting analysis, and RT-qPCR were performed to confirm the validity of targets in the relevant pathways. RESULTS: FZYL was able to significantly reduce the size of tumors in vivo and had a significant therapeutic effect on tumor xenograft mice. GO and KEGG pathway enrichment analyses indicated that the effects of FZYL may be mediated by oxidative stress levels, apoptotic signaling pathways, and cell cycle proliferation. By RT-qPCR and protein blotting assays, FZYL targeted the key targets of TP53, JUN, ESR1, RELA, MYC, and MAPK1 to exert its effects. The key active components of FZYL are quercetin, luteolin, stigmasterol, and glycitein. Molecular docking and molecular dynamics simulation results further demonstrated that the key active components of FZYL are stably bound to the core targets. CONCLUSION: In this study, the potential active ingredients, potential core targets, key biological pathways, and signaling pathways involved in the treatment of breast cancer with FZYL were identified, providing a theoretical basis for further anti ER+ breast cancer research.

Comparative efficacy and safety of Chinese patent medicines of acute ischemic stroke: A network meta-analysis.

BACKGROUND: Acute ischemic stroke (AIS) is characterized by high morbidity, disability, mortality, recurrence, and economic burden. Clinical trials have demonstrated that the clinical efficacy of combining oral Chinese patent medicines (CPMs) with chemical drugs (CDs) is better than that of CDs alone. In this study, we performed a network meta-analysis (NMA) of RCTs to assess the efficacy of different CPMs in combination with CDs in the treatment of AIS. METHODS: Search 6 databases from the beginning to January 10, 2023. The Cochrane Risk of Bias tool assessed the methodological quality of the included studies. The NMA was then performed using the STATA 13.0 program. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the studied treatments, and cluster analysis was used to compare the effects of CPMs between 2 different outcomes. RESULTS: A total of 94 eligible RCTs, involving 9581 participants, were included in this analysis. Nine CPMs, including Nao-mai-li granule (NML), Nao-mai-tai granule (NMT), Qi-long granule (QL), Long-sheng-zhi capsule (LSZ), Nao-xin-tong capsule (NXT), Nao-xue-shu oral liquid (NXS), Tong-xin-luo capsule (TXL), Xiao-shuan-chang-rong capsule (XSCR), and Xue-shuan-xin-mai-ning capsule (XSXMN) were included. Regarding the clinical effective rate, all types of CPMs + CDs treatments were significantly better than CDs treatments alone, with significant differences among the 9 selected CPMs. Compared with CDs, results showed that NXS + CDs performed best in improving clinical effective rate [OR = 4.73; 95% CI: 1.26-17.78; (SUCRA: 76.1%)]. TXL + CDs showed the most effective effect in alleviating National Institutes of Health Stroke Scale (NIHSS) [MD = -3.84; 95% CI: -5.23, -2.45; (SUCRA: 81.6%)]; NXT + CDs were most effective in improving Barthel index [MD = 13.05; 95% CI: 3.98-22.12; (SUCRA: 63.5%)]. Combined with other outcome indicators and the results of cluster analysis, NXS + CDs may assist in the potential optimal treatment regimen for AIS. CONCLUSION: In conclusion, CPMs were found to be beneficial as adjuvant therapy in patients with AIS. Taking into account the clinical effective rate and other outcomes, NXS + CDs may be the most effective option to improve the condition of AIS patients.

Qushi Huayu decoction ameliorates non-alcoholic fatty liver disease in rats by modulating gut microbiota and serum lipids.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease. As a clinical empirical prescription of traditional Chinese medicine, Qushi Huayu decoction (QHD) has attracted considerable attention for its advantages in multi-target treatment of NAFLD. However, the intervention mechanism of QHD on abnormal lipid levels and gut microbiota in NAFLD has not been reported. Methods: Therefore, we verified the therapeutic effect of QHD on high-fat diet (HFD)-induced NAFLD in rats by physiological parameters and histopathological examination. In addition, studies on gut microbiota and serum lipidomics based on 16S rRNA sequencing and ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) were conducted to elucidate the therapeutic mechanism of NAFLD in QHD. Results: The changes in gut microbiota in NAFLD rats are mainly reflected in their diversity and composition, while QHD treated rats restored these changes. The genera Blautia, Lactobacillus, Allobaculum, Lachnoclostridium and Bacteroides were predominant in the NAFLD group, whereas, Turicibacter, Blautia, Sporosarcina, Romboutsia, Clostridium_sensu_stricto_1, Allobaculum, and Psychrobacter were predominant in the NAFLD+QHD group. Lipid subclasses, including diacylglycerol (DG), triglycerides (TG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidic acid (PA), phosphatidylserine (PS), lysophosphatidylinositol (LPI), and phosphatidylglycerol (PG), were significantly different between the NAFLD and the control groups, while QHD treatment significantly altered the levels of DG, TG, PA, lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), and platelet activating factor (PAF). Finally, Spearman's correlation analysis showed that NAFLD related differential lipid molecules were mainly associated with the genera of Bacteroides, Blautia, Lachnoclostridium, Clostridium_sensu_stricto_1, and Turicibacter, which were also significantly correlated with the biological parameters of NAFLD. Discussion: Taken together, QHD may exert beneficial effects by regulating the gut microbiota and thus intervening in serum lipids.

Buccal acupuncture combined with ultrasound-guided dry needle-evoked inactivation of trigger points to treat cervical and shoulder girdle myofascial pain syndrome.

BACKGROUND: Myofascial pain syndrome (MPS) is a common disease with easy persistence and recurrence. In clinical practice, although many methods have been adopted to prevent and treat MPS, the control of MPS is still not satisfactory. OBJECTIVE: To compare the safety and effectiveness of buccal acupuncture, inactivation of trigger points (MTrPs), and their combination in the treatment of MPS. METHODS: Two hundred MPS patients in the pain clinic were randomly divided into four groups (n= 50) to receive oral drugs (Group A), oral drugs + buccal needle (Group B), oral drugs + MTrP inactivation (Group C), or oral drugs + buccal needle + MTrP inactivation (Group D). RESULTS: The visual analogue scale (VAS) and cervical range of motion (ROM) of Group D were significantly lower than those of the other three groups, and the pressure pain threshold (PPT) value of labelled MTrPs was significantly higher than those of the other three groups (P< 0.05). The excellent rate and total effective rate of Group D were significantly higher than those of the other three groups. Group C had the highest pain score and the lowest acceptance score. The results showed that buccal acupuncture combined with ultrasound-guided dry needle-evoked inactivation of MTrPs can significantly reduce the VAS score of MPS patients, improve the range of motion of the cervical spine, and improve patient satisfaction. CONCLUSIONS: This study provides a highly accepted and satisfactory treatment for MPS, which is worthy of clinical promotion.

Serum metabolomics strategy for investigating the hepatotoxicity induced by different exposure times and doses of Gynura segetum (Lour.) Merr. in rats based on GC-MS.

Gynura segetum (Lour.) Merr. (GS), has been widely used in Chinese folk medicine and can promote circulation, relieve pain and remove stasis. In recent years, the hepatotoxicity caused by GS has been reported, however its mechanism is not fully elucidated. Metabolomic techniques are powerful means to explore the toxicological mechanism and therapeutic effects of traditional Chinese medicine. The purpose of this study was to establish a serum metabolomics method based on Gas Chromatography-Mass Spectrometry (GC-MS) to explore the hepatotoxicity mechanism of different exposure times and doses of GS in rats. Sprague Dawley (SD) rats were administered daily with distilled water, 7.5 g kg-1 GS, or 15 g kg-1 GS by intragastrical gavage for either 10 or 21 days. The methods adopted included enzyme-linked immunosorbent assay (ELISA), Hematoxylin and Eosin (H&E) staining and GC-MS-based serum metabolomics. Serum biochemistry analysis showed that the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total bilirubin (TBIL) and total bile acid (TBA) significantly (P < 0.05) increased while the levels of albumin (ALB) and high-density lipoprotein (HDL) significantly (P < 0.05) decreased in GS-treated groups, compared with the control group. Interestingly, the ALT, AST, TG and ALB levels changed in a time- and dose-dependent manner. The results of H&E staining showed the degree of liver damage after administration of GS gradually deepened with the extension of administration time and the increase of the dose. According to the results of metabolomics analysis, 26 differential metabolites were identified, which were involved in 8 metabolic pathways including phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism and so on. Meanwhile, the number of differential metabolites in different GS-treated groups was associated with GS exposure time and dose. Therefore, we concluded that GS might induce hepatotoxicity depending on the exposure time and dose.

Mechanism of action of Daqinjiao decoction in treating cerebral small vessel disease explored using network pharmacology and molecular docking technology.

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is a clinically commonly-seen slow-progressing cerebral vascular disease. As a classic Chinese formula for the treatment of stroke, Daqinjiao Decoction (DQJD) is now used to treat CSVD with desirable effect. Since the mechanism of action is still unclear, this article will explore the therapeutic effect and mechanism of action of the formula using network pharmacology technology. METHODS: The major chemical components and potential target genes of DQJD were screened by bioinformatics. The key targets in CSVD were identified based on network modules. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Pharmacodynamics of the decoction was evaluated by establishing a rat model with bilateral common carotid artery occlusion in the brain. Molecular docking, Western blot analysis and quantitative real-time polymerase chain reaction (QRT-PCR) were performed to confirm the effectiveness of targets in related pathways. RESULTS: Network pharmacology showed that 16 targets and 30 pathways were involved in the DQJD-targeted pathway network. Results revealed that DQJD might play a role by targeting the key targets including Caspse3 and P53 and regulating the P53 signaling pathway. Cognitive function and neuronal cell changes of rats were evaluated using Morris water maze, open field test and HE staining. It was indicated that DQJD could keep the nerve cells intact and neatly arranged. The decoction could improve the memory and learning ability of rats compared with the model group. It decreased the protein and mRNA expression levels of Caspse3 and P53 significantly (p<0.01). CONCLUSION: The study shows that baicalein, quercetin and wogonin, the effective components of DQJD, may regulate multiple signaling pathways by targeting the targets like Caspse3 and P53 and treat CSVD by reducing the damage to brain nerve cells.

Plant-derived bioactive compounds regulate the NLRP3 inflammasome to treat NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is a liver disorder characterized by abnormal accumulation of hepatic fat and inflammatory response with complex pathogenesis. Over activation of the pyrin domain-containing protein 3 (NLRP3) inflammasome triggers the secretion of interleukin (IL)-1ß and IL-18, induces pyroptosis, and promotes the release of a large number of pro-inflammatory proteins. All of which contribute to the development of NAFLD. There is a great deal of evidence indicating that plant-derived active ingredients are effective and safe for NAFLD management. This review aims to summarize the research progress of 31 active plant-derived components (terpenoids, flavonoids, alkaloids, and phenols) that alleviate lipid deposition, inflammation, and pyroptosis by acting on the NLRP3 inflammasome studied in both in vitro and in vivo NAFLD models. These studies confirmed that the NLRP3 inflammasome and its related genes play a key role in NAFLD amelioration, providing a starting point for further study on the correlation of plant-derived compounds treatment with the NLRP3 inflammasome and NAFLD.

Investigation of Gynura segetum root extract (GSrE) induced hepatotoxicity based on metabolomic signatures and microbial community profiling in rats.

In recent years, many reports focus on the hepatotoxicity of Gynura segetum root extract (GSrE), but the interaction between GSrE and the gut microbiota is still unclear. This study investigated the mechanism of GSrE-induced hepatotoxicity of different doses and exposure durations by combining metabolomics and gut microbiota analysis. SD rats were divided into 3 groups: blank, low-dose (7.5 g/kg), and high-dose (15 g/kg) groups. Urine and feces samples were collected on day 0, day 10, and day 21. Metabolomics based on gas chromatography-mass spectrometry (GC-MS) was carried out to identify metabolites and metabolic pathways. 16S rDNA gene sequencing was applied to investigate the composition of gut microbiota before and after GSrE-induced hepatotoxicity. Finally, a correlation analysis of metabolites and gut microbiota was performed. Differential metabolites in urine and feces involved amino acids, carbohydrates, lipids, organic acids, and short chain fatty acids. Among them, L-valine, L-proline, DL-arabinose, pentanoic acid, D-allose, and D-glucose in urine and D-lactic acid and glycerol in fecal metabolites depended on the exposure of time and dose. In addition, 16S rDNA sequencing analysis revealed that GSrE-induced hepatotoxicity significantly altered the composition of gut microbiota, namely, f_Muribaculaceae_Unclassified, Lactobacillus, Bacteroides, Lachnospiraceae_NK4A136_group, f_Ruminococcaceae_Unclassified, Prevotellaceae_Ga6A1_group, and Escherichia-Shigella. The correlation analysis between gut microbiota and differential metabolites showed the crosstalk between the gut microbiota and metabolism in host involving energy, lipid, and amino acid metabolisms. In summary, our findings revealed that peripheral metabolism and gut microbiota disorders were time- and dose-related and the correlation between gut microbiota and metabolites in GSrE-induced hepatotoxicity.

Comparative Efficacy of Chinese Patent Medicines for Clearing Heat and Dampness in the Treatment of NAFLD: A Network Meta-Analysis of Real-World Evidence.

Background: Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease, as well as a worldwide medical problem with a substantial socioeconomic burden. In China, Chinese patent medicines (CPMs) have been widely utilized as promising and effective therapy options for NAFLD. Traditional Chinese medicine (TCM) is a particular kind of medical science reliant on real-world clinical practices and evidence. Therefore, using the real-world data extracted from pragmatic randomized controlled trials (PRCTs) have more reference value for the application of CPMs in NAFLD. Method: Six databases were searched from their inception up to March 18, 2022. The methodological quality of the included study was evaluated by the Cochrane risk-of-bias tool. Then, The STATA 13.0 program was then used to do a network meta-analysis (NMA) of real-world studies. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. Results: Forty-three PRCTs (4997 cases in total) were identified. Da-Huang-Li-Dan capsule (DHLD), Dan-Ning tablet (DN), Dang-Fei-Li-Gan-Ning capsule (DFLGN), Qiang-Gan capsule (QG), and Hua-Zhi-Rou-Gan granule (HZRG) were among the five CPMs tested. As far as the clinical effective rate of the primary outcome index was concerned, the top three CPMs were DN + CDs: OR = 0.19, 95% CIs: 0.12, 0.31 (SUCRA: 81.8%); DFLGN + CDs: OR = 0.21, 95% CIs: 0.09, 0.46 (SUCRA: 74.9%), and DHLD + CDs: OR = 0.26, 95% CIs: 0.10, 0.67 (SUCRA: 61.1%). In terms of liver function index, DN + CDs ranked first in ALT index: MD = 15.81, 95% CIs: 10.05, 21.57 (SUCRA: 85.5%), DFLGN + CDs ranked first in AST index: MD = 14.94, 95% CIs: 4.77, 25.11 (SUCRA: 83.6%), HZRG + CDs ranked first in TC index: MD = 0.53, 95% CIs: 0.28, 1.03 (SUCRA: 87.1%) and TG index: MD = 1.8, 95% CIs: 1.41, 2.30 (SUCRA: 79.9%). Conclusion: Using CPMs as a coadjuvant treatment might be positive efficacious intervention from which patients with NAFLD will derive benefits. When it came to the clinical effective rate and other outcomes, DN + CDs demonstrated a significant improvement in individuals with NAFLD.

The Role of Gut Microbiota-Bile Acids Axis in the Progression of Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD), an emerging global health problem affecting 25-30% of the total population, refers to excessive lipid accumulation in the liver accompanied by insulin resistance (IR) without significant alcohol intake. The increasing prevalence of NAFLD will lead to an increasing number of cirrhosis patients, as well as hepatocellular carcinoma (HCC) requiring liver transplantation, while the current treatments for NAFLD and its advanced diseases are suboptimal. Accordingly, it is necessary to find signaling pathways and targets related to the pathogenesis of NAFLD for the development of novel drugs. A large number of studies and reviews have described the critical roles of bile acids (BAs) and their receptors in the pathogenesis of NAFLD. The gut microbiota (GM), whose composition varies between healthy and NAFLD patients, promotes the transformation of more than 50 secondary bile acids and is involved in the pathophysiology of NAFLD through the GM-BAs axis. Correspondingly, BAs inhibit the overgrowth of GM and maintain a healthy gut through their antibacterial effects. Here we review the biosynthesis, enterohepatic circulation, and major receptors of BAs, as well as the relationship of GM, BAs, and the pathogenesis of NAFLD in different disease progression. This article also reviews several therapeutic approaches for the management and prevention of NAFLD targeting the GM-BAs axis.

Network Meta-Analysis of Acupoint Catgut Embedding in Treatment of Simple Obesity.

Objective: To evaluate the clinical efficacy of acupoint catgut embedding in the treatment of simple obesity through network meta-analysis. Methods: PubMed, Cochrane, Embase, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP database (VIP) were searched by using computer from 2011 to August 2021, and 35 RCT studies were retrieved. The quality of the literature was evaluated using the modified Jadad scoring table, and Stata 15.0 software was used for traditional meta-analysis and network meta-analysis. Results: Thirty-five RCTs (3040 cases in total) were included. Acupoint embedding, acupuncture, electroacupuncture, TCM, acupoint embedding + acupuncture, acupoint embedding + exercise diet therapy, acupoint embedding + TCM, exercise diet therapy, acupoint embedding + moxibustion, and acupoint embedding + cupping were investigated in the studies. The results of network meta-analysis were as follows: in terms of total effective rate, acupoint catgut embedding was superior to acupuncture, electroacupuncture, and exercise diet therapy (P < 0.05); electroacupuncture, acupoint catgut embedding + acupuncture, acupoint catgut embedding + exercise diet therapy, acupoint catgut + TCM, acupoint catgut + moxibustion, and acupoint catgut + cupping were superior to acupuncture (P < 0.05); acupoint catgut + moxibustion was superior to electroacupuncture (P < 0.05); acupoint catgut + TCM, acupoint catgut + moxibustion, and acupoint catgut + cupping were superior to TCM treatment (P < 0.05); and electroacupuncture, acupoint catgut, acupoint catgut + acupuncture, acupoint catgut + exercise diet therapy, acupoint catgut + TCM, acupoint catgut embedding + moxibustion, and acupoint catgut embedding + cupping were superior to sports diet therapy (P < 0.05). Regarding weight loss, acupuncture treatment was superior to acupoint catgut embedding therapy (P < 0.05); acupoint catgut embedding + exercise diet therapy, acupoint catgut embedding + TCM, acupoint catgut embedding + moxibustion, and acupoint catgut embedding + cupping were superior to acupuncture and electroacupuncture treatment (P < 0.05); acupoint catgut embedding + exercise diet therapy, acupoint catgut embedding + TCM, and acupoint catgut embedding + moxibustion were superior to TCM treatment (P < 0.05); and acupoint catgut embedding, acupoint catgut embedding + acupuncture, catgut embedding + exercise diet therapy, acupoint catgut embedding + TCM, acupoint catgut embedding + moxibustion, and acupoint catgut embedding + cupping were superior to exercise diet therapy (P < 0.05). In terms of BMI reduction, acupoint catgut embedding + moxibustion and acupoint catgut embedding + cupping were more evident than acupuncture treatment (P < 0.05); and acupoint catgut embedding + moxibustion was more evident than electroacupuncture treatment (P < 0.05). Conclusion: Acupoint catgut embedding and its combination with other therapies are the first choice for the treatment of simple obesity.

Absorption, metabolism, and pharmacokinetic profile of xanthohumol in rats as determined via UPLC-MS/MS.

Xanthohumol, a natural isoflavone from Humulus lupulus L., possesses biological activities. However, the biological fate of xanthohumol in vivo remains unclear. The aim of this study was to investigate the absorption and metabolism of xanthohumol in rats through UPLC-MS/MS. The plasma, urine and fecal samples were collected after oral administration of xanthohumol (25, 50, 100 mg/kg) in SD rats. The contents of xanthohumol and its metabolites were determined by UPLC-MS/MS. A total of 6 metabolites of xanthohumol were identified in rats, including methylated, glucuronidated, acid-catalyzed cyclization and oxidation, indicating xanthohumol underwent phase I and II metabolism. Besides, isoxanthohumol was the major metabolites of xanthohumol. Xanthohumol was rapidly absorbed, metabolized, and eliminated in rats. The pharmacokinetics results showed the Tmax of xanthohumol and isoxanthohumol were 3 and 2.33 h, respectively. The AUC0-t of xanthohumol and isoxanthohumol were 138.83 ± 6.03 and 38.77 ± 4.46 ng/ml·h, respectively. Furthermore, xanthohumol was mainly excreted in the form of prototype through feces and a small amount of xanthohumol was excreted through urine. These results illustrated the absorption, metabolism, and pharmacokinetics process of xanthohumol in rats, and provided a reference for the further rational applications.

A WeChat-Based Mobile Platform for Perioperative Health Education for Gastrointestinal Surgery.

Appropriately instructing and guiding patients before and after surgery is essential for their successful recovery. In recent years, however, the development of the enhanced recovery after surgery (ERAS) protocol has restricted the opportunity for healthcare professionals to spend time with their patients before and after surgery because of efficiency-driven, shortened hospital stay. Here, we embedded health education information of the perioperative period for gastrointestinal surgery on a WeChat-based mobile platform and evaluated the platform through medical staff evaluation, patient volunteer evaluation, and quantitative grading rubric. Clinicians and nurses believed that the mobile platform was attractively designed and easy to navigate, valuable, and adequate for patient health education. The content of health education was embedded into the WeChat-based mobile platform, thereby allowing patients and caregivers to access information at their own pace and enable repeat reading.