Integrated Approaches Revealed the Therapeutic Mechanisms of Zuojin Pill Against Gastric Mucosa Injury in a Rat Model with Chronic Atrophic Gastritis.

Background: The Zuojin Pill (ZJP) is widely used for treating chronic atrophic gastritis (CAG) in clinical practice, effectively ameliorating symptoms such as vomiting, pain, and abdominal distension in patients. However, the underlying mechanisms of ZJP in treating CAG has not been fully elucidated. Purpose: This study aimed to clarify the characteristic function of ZJP in the treatment of CAG and its potential mechanism. Methods: The CAG model was established by alternant administrations of ammonia solution and sodium deoxycholate, as well as an irregular diet. Therapeutic effects of ZJP on body weight, serum biochemical indexes and general condition were analyzed. HE staining and AB-PAS staining were analyzed to characterize the mucosal injury and the thickness of gastric mucosa. Furthermore, network pharmacology and molecular docking were used to predict the regulatory mechanism and main active components of ZJP in CAG treatment. RT-PCR, immunohistochemistry, immunofluorescence and Western blotting were used to measure the expression levels of apoptosis-related proteins, gastric mucosal barrier-associated proteins and PI3K/Akt signaling pathway proteins. Results: The results demonstrated that ZJP significantly improved the general state of CAG rats, alleviated weight loss and gastric histological damage and reduced the serum biochemical indicators. Network pharmacology and molecular docking found that ZJP in treating CAG by inhibiting inflammation, suppressing apoptosis, and protecting the gastric mucosal barrier via the PI3K/Akt signaling pathway. Further experiments confirmed that ZJP obviously modulated the expression of key proteins involved in gastric mucosal cell apoptosis, such as Bax, Bad, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, Cytochrome C, Bcl-2, and Bcl-xl. Moreover, ZJP significantly reversed the protein expression of Occludin, ZO-1, Claudin-4 and E-cadherin. Conclusion: Our study revealed that ZJP treats CAG by inhibiting the PI3K/Akt signaling pathway. This research provided a scientific basis for the rational use of ZJP in clinical practice.

The contribution of small heterodimer partner to the occurrence and progression of cholestatic liver injury.

BACKGROUND AND AIM: Small heterodimer partner (SHP, encoded by NR0B2) plays an important role in maintaining bile acid homeostasis. The loss of the hepatic farnesoid X receptor (FXR)/SHP signal can cause severe cholestatic liver injury (CLI). FXR and SHP have overlapping and nonoverlapping functions in bile acid homeostasis. However, the key role played by SHP in CLI is unclear. METHODS: In this study, an alpha-naphthylisothiocyanate (ANIT)-induced cholestasis mouse model was established. The effect of SHP knockout (SHP-KO) on liver and ileal pathology was evaluated. 16S rRNA gene sequencing analysis combined with untargeted metabolomics was applied to reveal the involvement of SHP in the pathogenesis of CLI. RESULTS: The results showed that ANIT (75 mg/kg) induced cholestasis in WT mice. No significant morphological changes were found in the liver and ileal tissue of SHP-KO mice. However, the serum metabolism and intestinal flora characteristics were significantly changed. Moreover, compared with the WT + ANIT group, the serum levels of ALT and AST in the SHP-KO + ANIT group were significantly increased, and punctate necrosis in the liver tissue was more obvious. The ileum villi showed obvious shedding, thinning, and shortening. In addition, SHP-KO-associated differential intestinal flora and differential biomarkers were significantly associated. CONCLUSION: In this study, we elucidated the serum metabolic characteristics and intestinal flora changes related to the aggravation of CLI in SHP-KO mice induced by ANIT.

Integrated network pharmacology and metabolomics to investigate the effects and possible mechanisms of Dehydroevodiamine against ethanol-induced gastric ulcers.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetradium ruticarpum (A.Juss.) T.G.Hartley, a traditional Chinese medicine with thousands of years of medicinal history, has been employed to address issues such as indigestion, abdominal pain, and vomiting. Dehydroevodiamine (DHE) is a quinazoline alkaloid extracted from traditional Chinese medicine Tetradium ruticarpum (A.Juss.) T.G.Hartley. Previous studies have shown that DHE has anti-inflammatory, analgesic, and antioxidant activities. However, it is still unclear whether DHE has an effect on ethanol-induced gastric ulcers. AIM OF THE STUDY: The objective of this study is to investigate the therapeutic efficacy and underlying mechanisms of action of DHE on ethanol-induced gastric ulcers using network pharmacology and metabolomics strategies. METHODS: In this study, we used ethanol-induced rats as a model to assess the efficacy of DHE by biochemical indicator assays and pathological tissue detection. The integration of network pharmacology and metabolomics was used to explore possible mechanisms and was validated by western blot experiments. Finally, molecular docking was used to analyze the binding energy between DHE and the targets of PIK3CG and PLA2G2A. RESULTS: DHE was able to reverse ethanol-induced abnormalities in biochemical indicators and improve pathological tissue. Network pharmacology results indicated that DHE may be involved in the regulation of gastric ulcers by modulating 79 targets, and metabolomics results showed that a total of 13 metabolites were changed before and after DHE administration. Integrating network pharmacology and metabolomics, PIK3CG and PLA2G2A were identified as possible targets to exert therapeutic effects. In addition, the MAPKs pathway may also be involved in the regulation of ethanol-induced gastric ulcers. Finally, molecular docking results showed that DHE had low binding energies with both PIK3CG and PLA2G2A. CONCLUSIONS: These findings suggest that DHE was able to exert a protective effect against ethanol-induced gastric ulcers by modulating multiple metabolites with multiple targets. This study provides a valuable reference for the development of antiulcer drugs.

Network Pharmacology and Experimental Validation of Qingwen Baidu Decoction Therapeutic Potential in COVID-19-related Lung Injury.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) is a lifethreatening disease worldwide due to its high infection and serious outcomes resulting from acute lung injury. Qingwen Baidu decoction (QBD), a well-known herbal prescription, has shown significant efficacy in patients with Coronavirus disease 2019. Hence, this study aims to uncover the molecular mechanism of QBD in treating COVID-19-related lung injury. METHODS: Traditional Chinese Medicine Systems Pharmacology database (TCMSP), DrugBanks database, and Chinese Knowledge Infrastructure Project (CNKI) were used to retrieve the active ingredients of QBD. Drug and disease targets were collected using UniProt and Online Mendelian Inheritance in Man databases (OMIM). The core targets of QBD for pneumonia were analyzed by the Protein-Protein Interaction Network (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) to reveal the underlying molecular mechanisms. The analysis of key targets using molecular docking and animal experiments was also validated. RESULTS: A compound-direct-acting target network mainly containing 171 compounds and 110 corresponding direct targets was constructed. The key targets included STAT3, c-JUN, TNF-α, MAPK3, MAPK1, FOS, PPARG, MAPK8, IFNG, NFκB1, etc. Moreover, 117 signaling pathways mainly involved in cytokine storm, inflammatory response, immune stress, oxidative stress and glucose metabolism were found by KEGG. The molecular docking results showed that the quercetin, alanine, and kaempferol in QBD demonstrated the strongest affinity to STAT3, c- JUN, and TNF-α. Experimental results displayed that QBD could effectively reduce the pathological damage to lung tissue by LPS and significantly alleviate the expression levels of the three key targets, thus playing a potential therapeutic role in COVID-19. CONCLUSION: QBD might be a promising therapeutic agent for COVID-19 via ameliorating STAT3-related signals.

Metabolomics Profiles Reveal the Efficacy of Wuzhuyu Decoction on Patients with Chronic Non-Atrophic Gastritis.

Objective: Chronic non-atrophic gastritis (CNAG) is a common clinical gastrointestinal disease with a long and recurrent course. In China, Wuzhuyu decoction (WZYD) has been used for centuries to treat gastrointestinal disorders. To unravel the efficacy and mechanism of WZYD for CNAG, a clinical study was conducted. And metabolomics was used to explore the mechanism of WZYD for CNAG patients. Methods: Twenty patients in total were recruited in this study (Nos. ChiCTR2200062296) and the protocol was approved by the Ethics Committee (Approval number: KY-2022-2-6-1) and complied with the Declaration of Helsinki. The formula granule of WZYD were assessed by UHPLC-QQQ-TOF to discern the main potential active compounds. The endoscopy evaluation and histopathological changes were detected as effective indicators. Serum samples from patients were used for metabolomics. Inflammatory factors in patients' serum were determined by ELISA. Metabolomics revealed a series of differential metabolites and signaling pathways. Results: WZYD was capable to prevent CNAG by ameliorating score of endoscopy evaluation including erosion, hemorrhage, as well as chronic inflammation and active chronic inflammation score after treatment were decreased. The results indicated that 10 core metabolic components were associated with the treatment of WZYD. Moreover, these metabolic components proved that pyrimidine metabolism and thiamine metabolism were critically responsible for CNAG. In addition, WZYD treatment effectively reduced serum levels of TNF-α, IL-10, and COX-2. Conclusion: Altogether, WZYD can effectively alleviate CNAG by inhibiting inflammation and regulating related metabolic processes, which might be the molecular mechanism of WZYD treatment of CNAG. More studies are warranted to be conducted in this area. Trial Registration: ChiCTR, ChiCTR2200062296. Registered 1 August 2022, https://www.chictr.org.cn/com/25/showprojen.aspx?proj=174027.

Rutaecarpine Ameliorates Murine N-Methyl-N'-Nitro-N-Nitrosoguanidine-Induced Chronic Atrophic Gastritis by Sonic Hedgehog Pathway.

CAG is a burdensome and progressive disease. Numerous studies have shown the effectiveness of RUT in digestive system diseases. The therapeutic effects of RUT on MNNG-induced CAG and the potential mechanisms were probed. MNNG administration was employed to establish a CAG model. The HE and ELISA methods were applied to detect the treatment effects. WB, qRT-PCR, immunohistochemistry, TUNEL, and GES-1 cell flow cytometry approaches were employed to probe the mechanisms. The CAG model was successfully established. The ELISA and HE staining data showed that the RUT treatment effects on CAG rats were reflected by the amelioration of histological damage. The qRT-PCR and WB analyses indicated that the protective effect of RUT is related to the upregulation of the SHH pathway and downregulation of the downstream of apoptosis to improve gastric cellular survival. Our data suggest that RUT induces a gastroprotective effect by upregulating the SHH signaling pathway and stimulating anti-apoptosis downstream.

Treatment of Chronic Gastritis with Traditional Chinese Medicine: Pharmacological Activities and Mechanisms.

Chronic gastritis (CG) is a common clinical digestive system disease, which is not easyily cured and is prone to recurrence. Traditional Chinese medicine (TCM) plays a significant role in the treatment of CG and has attracted increasing attention for clinical applications. In recent years, a large number of reports have shown that TCM has good therapeutic effect on CG. The aim of this paper is to investigate the pharmacological activities and mechanism of action of TCM in the treatment of CAG. Therefore, by searching the databases of Pubmed, China National Knowledge Infrastructure, Wanfang, and Baidu academic databases, this paper has summarized the molecular mechanisms of TCM in improving CG. The results show that the improvement of GC by TCM is closely related to a variety of molecular mechanisms, including the inhibition of Helicobacter pylori (Hp) infection, alleviation of oxidative stress, improvement of gastric function, repair of gastric mucosa, inhibition of inflammatory response, and apoptosis. More importantly, IRF8-IFN-γ, IL-4-STAT6, Hedgehog, pERK1/2, MAPK, PI3K-Akt, NF-κB, TNFR-c-Src-ERK1/2-c-Fos, Nrf2/HO-1, and HIF-1α/VEGF signaling pathways are considered as important molecular targets for TCM in the treatment of GC. These important findings will provide a direction and a basis for further exploring the pathogenesis of GC and tapping the potential of TCM in clinical treatment. This review also puts forward a bright prospect for future research of TCM in the treatment of CG.

Primary biliary cholangitis: molecular pathogenesis perspectives and therapeutic potential of natural products.

Primary biliary cirrhosis (PBC) is a chronic cholestatic immune liver disease characterized by persistent cholestasis, interlobular bile duct damage, portal inflammation, liver fibrosis, eventual cirrhosis, and death. Existing clinical and animal studies have made a good progress in bile acid metabolism, intestinal flora disorder inflammatory response, bile duct cell damage, and autoimmune response mechanisms. However, the pathogenesis of PBC has not been clearly elucidated. We focus on the pathological mechanism and new drug research and development of PBC in clinical and laboratory in the recent 20 years, to discuss the latest understanding of the pathological mechanism, treatment options, and drug discovery of PBC. Current clinical treatment mode and symptomatic drug support obviously cannot meet the urgent demand of patients with PBC, especially for the patients who do not respond to the current treatment drugs. New treatment methods are urgently needed. Drug candidates targeting reported targets or signals of PBC are emerging, albeit with some success and some failure. Single-target drugs cannot achieve ideal clinical efficacy. Multitarget drugs are the trend of future research and development of PBC drugs.

Genetic alterations and molecular mechanisms underlying hereditary intrahepatic cholestasis.

Hereditary cholestatic liver disease caused by a class of autosomal gene mutations results in jaundice, which involves the abnormality of the synthesis, secretion, and other disorders of bile acids metabolism. Due to the existence of a variety of gene mutations, the clinical manifestations of children are also diverse. There is no unified standard for diagnosis and single detection method, which seriously hinders the development of clinical treatment. Therefore, the mutated genes of hereditary intrahepatic cholestasis were systematically described in this review.

Alterations in the gut microbiota and serum metabolomics of spontaneous cholestasis caused by loss of FXR signal in mice.

Background: Farnesoid X receptor (FXR) is a key metabolic target of bile acids (BAs) and is also a target for drugs against several liver diseases. However, the contribution of FXR in the pathogenesis of cholestasis is still not fully understood. The purpose of this study is to provide a comprehensive insight into the metabolic properties of FXR-involved cholestasis in mice. Materials and methods: In this study, an alpha-naphthylisothiocyanate (ANIT)-induced cholestasis mouse model and FXR-/- mice were established to investigate the effect of FXR on cholestasis. The effect of FXR on liver and ileal pathology was evaluated. Simultaneously, Untargeted metabolomics combined with 16s rRNA gene sequencing analysis was applied to reveal the involvement of FXR in the pathogenesis of cholestasis. Results: The results showed that ANIT (75 mg/kg) induced marked cholestasis in WT and FXR -/- mice. It is noteworthy that FXR-/- mice developed spontaneous cholestasis. Compared with WT mice, significant liver and ileal tissue damage were found. In addition, 16s rRNA gene sequencing analysis revealed gut microbiota dysbiosis in FXR-/- mice and ANIT-induced cholestasis mice. Differential biomarkers associated with the pathogenesis of cholestasis caused by FXR knockout were screened using untargeted metabolomics. Notably, Lactobacillus_ johnsonii_FI9785 has a high correlation with the differential biomarkers associated with the pathogenesis and progression of cholestasis caused by FXR knockout. Conclusion: Our results implied that the disorder of the intestinal flora caused by FXR knockout can also interfere with the metabolism. This study provides novel insights into the FXR-related mechanisms of cholestasis.

Mechanism of Wuzhuyu decoction on alcohol-induced gastric ulcers using integrated network analysis and metabolomics.

Background: Gastric ulcers (GUs) are prevalent digestive disorders worldwide. Wuzhuyu Decoction (WZYT) is a traditional Chinese medicine that has been employed for centuries to alleviate digestive ailments like indigestion and vomiting. This study aims to explore the potential effects and underlying mechanisms of WZYT on alcohol induced gastric ulcer treatment. Methods: We employed macroscopic assessment to evaluate the gastric ulcer index (UI), while the enzyme-linked immunosorbent assay (ELISA) was utilized for detecting biochemical indicators. Pathological tissue analysis involved hematoxylin-eosin (H&E) staining and Periodic Acid-Schiff (PAS) staining to assess gastric tissue damage. Additionally, the integration of network analysis and metabolomics facilitated the prediction of potential targets. Validation was conducted using Western blotting. Results: The research revealed that WZYT treatment significantly reduced the gastric ulcer index (UI) and regulation of alcohol-induced biochemical indicators levels. Additionally, improvements were observed in pathological tissue. Network analysis results indicated that 62 compounds contained in WZYT modulate alcohol-induced gastric ulcers by regulating 183 genes. The serum metabolomics indicated significant changes in the content of 19 metabolites after WZYT treatment. Two pivotal targets, heme oxygenase 1 (HMOX1) and albumin (ALB), are believed to assume a significant role in the treatment of gastric ulcers by the construction of "compounds-target-metabolite" networks. Western blot analysis confirmed that WZYT has the capacity to elevate the expression of HMOX1 and ALB targets. Conclusion: The integration of network analysis and metabolomics provides a scientific basis to propel the clinical use of WZYT for GUs. Our study provides a theoretical basis for the use of Wuzhuyu decoction in the treatment of gastric ulcers.

Jatrorrhizine Alleviates DSS-Induced Ulcerative Colitis by Regulating the Intestinal Barrier Function and Inhibiting TLR4/MyD88/NF-κB Signaling Pathway.

Background: Ulcerative colitis (UC), a kind of autoimmune disease with unknown etiology, has been troubling human physical and mental health. Jatrorrhizine (Jat) is a natural isoquinoline alkaloid isolated from Coptis Chinensis, which has been proved to have antibacterial, anti-inflammatory, and antitumor effects. Purpose: The purpose is to explore the therapeutic effect of Jat on DSS-induced UC and the mechanism of action. Study Design. The UC mice model was induced by 3% DSS in drinking water. The mice were orally administered with Jat (40, 80, 160 mg/kg) for 10 days. Methods: The changes in body weight, colon length, spleen wet weight index, disease activity index (DAI), colonic histopathology, and inflammatory factors of serum and colon tissue were analyzed to evaluate the severity of colitis mice. The colon mucus secretion capacity was analyzed by Alcian blue periodic acid Schiff (AB-PAS) staining. Furthermore, protein expressions such as TLR4, MyD88, p-NF-κB-p65, NF-κB-p65, COX-2, ZO-1, and Occludin were detected to elucidate the molecular mechanism of Jat on DSS-induced colitis model. Results: The results showed that Jat could significantly alleviate the symptoms, colon shortening, spleen index, and histological damage and restore the body weight in DSS-induced colitis mice. Jat also suppressed the levels of inflammatory cytokines and upregulated the levels of anti-inflammatory cytokines. In addition, Jat repaired the intestinal barrier function by upregulating the level of colonic tight junction (TJ) proteins and enhancing the secretion of mucin produced by goblet cells. Furthermore, Jat could significantly suppress the expression of TLR4, MyD88, p-NF-κB-p65/NF-κB-p65, and COX-2 in colon tissue. Conclusion: The results suggested that Jat plays a protective role in DSS-induced colitis by regulating the intestinal barrier function and inhibiting the TLR4/MyD88/NF-κB signaling pathway. This study, for the first time, demonstrates the therapeutic and protective effects of Jat on UC.

Validation of MAPK signalling pathway as a key role of paeoniflorin in the treatment of intrahepatic cholestasis of pregnancy based on network pharmacology and metabolomics.

Numerous studies have clarified the effectiveness of paeoniflorin in the treatment of cholestasis. However, the therapeutic efficacy and mechanisms of action of paeoniflorin in intrahepatic cholestasis of pregnancy (ICP) were still unknown. This study aimed to investigate the molecular biological mechanisms of paeoniflorin against ICP by combining network pharmacology and metabolomics. The effects of paeoniflorin were investigated in the ICP rat model induced by 17α-ethinylestradiol, showing improvements in the liver indices, liver histopathological changes, bile flow rate, and serum levels of TBA and ALP. The underlying mechanisms and metabolic pathways of paeoniflorin were revealed by network pharmacology and untargeted metabolomics, showing that paeoniflorin exerted its curative effect against ICP-induced ferroptosis through PI3K/AKT and MAPK signalling pathways. In conclusion, paeoniflorin protected against ICP-induced liver injury through MAPK signaling pathways.

Cardiac involvement in Wilson's disease: a retrospective cohort study.

BACKGROUND AND OBJECTIVES: Wilson's disease (WD) is an inherited disorder with perturbations in copper metabolism and can cause multiorgan damage. This study aims to explore cardiac findings mainly based on electrocardiography (ECG) in WD patients. METHODS: We retrospectively enrolled adult patients who were diagnosed with WD between January 2011 and December 2020. Demographic and clinical data were collected and reevaluated. RESULTS: A total of 126 patients were included. There were 71 men and 55 women. The mean age was 27.2 years. Ninety-nine had hepatic presentation as the initial symptom and 27 had neuropsychiatric presentation as the initial symptom. Thirty-seven patients (29.4%) had cardiac manifestations. Of these patients, nine presented apparent cardiac symptoms (three with discontinuous chest tightness, three with dizziness, two with palpitation and one with atypical chest pain) and 28 had asymptomatic electrocardiography (ECG) abnormalities. Among the nine patients, four had second- or third-degree atrioventricular block, three had ST-segment change and two had ventricular tachycardia. ECG abnormalities in the 28 patients included increase in the width of the QRS complex in 8, atrial premature beats in 8, T-wave inversion in 5, P-wave inversion in 2, sinus bradycardia in 2, ST-segment change in 2, and coexistence of sinus bradycardia and T-wave inversion in 1. No statistical difference (P = 0.32) existed in the occurrence of ECG abnormalities between patients with hepatic presentation (27/99) and those with neuropsychiatric presentation (10/27). CONCLUSION: Cardiac involvement is not rare in adult WD patients. We suggest that cardiac evaluation should be routinely performed in the population.

Berberine inhibits IFN-γ signaling pathway in DSS-induced ulcerative colitis.

Aims: The potential signaling pathways and core genes in ulcerative colitis (UC) were investigated in this study. Furthermore, potential mechanisms of BBR in treating UC were also explored. Methods: Expression profiling by array of UC patients were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were determined with the differential analysis. The biological functions of DEGs were analyzed through the Database for Annotation, Visualization and Integrated Discovery (DAVID). The Gene Set Enrichment Analysis (GSEA) was applied to analyze the expression differences between two different phenotype sample sets. Dextran sulfate sodium (DSS) was applied to establish UC model of mice and lipopolysaccharide (LPS) was utilized to induce inflammatory damage of NCM460 cells. Therapeutic effects of berberine (BBR) on disease performance, pathologic changes and serum supernatant indices were analyzed in vivo. To further investigate the potential mechanisms of BBR in treating UC, the expression of genes and proteins in vivo and in vitro were examined by RT-qPCR, immunohistochemical staining and western blotting. Results: Immune-inflammatory genes were identified and up-regulated significantly in UC patients. In addition, IFN-γ signaling pathway and its core genes were significantly up-regulated in the phenotype of UC. All disease performance and the pathologic changes of UC in mice were evidently ameliorated by BBR treatment. The pro-inflammatory cytokines of serum, including CXCL9, CXCL1, IL-17 and TNF-α, in UC mice were significantly reduced by treatment of BBR. In terms of mechanisms of BBR in treating UC, the pro-inflammatory and immune-related genes, encoding IFN-γ, IRF8, NF-κB and TNF-α decreased significantly in UC mice followed by BBR treatment. Meanwhile, the expression of IFN-γ and its initiated targets, including IRF8, Ifit1, Ifit3, IRF1, were suppressed significantly by BBR treatment in vivo. The blocking of IFN-γ in vitro led to the silence of IFN-γ signaling pathway after exposure to BBR. Furthermore, the blocking of IFN-γ in vitro led to the silence of IFN-γ signaling pathway after exposure to BBR. Conclusion: BBR holds anti-inflammatory activity and can treat UC effectively. The anti-inflammatory property of BBR is tightly related to the suppression of IFN-γ signaling pathway, which is crucial in immune-inflammatory responses of the colon mucosa.

Metabolomics Profiles Associated with the Treatment of Zuojin Pill on Patients with Chronic Nonatrophic Gastritis.

Objective: Chronic nonatrophic gastritis (CNG) is the most common digestive disease. In China, Zuojin pill (ZJP) is considered an effective medicine formula for CNG. However, its efficacy and mechanism have never been explored. In order to understand how and why ZJP demonstrates therapeutic effect on CNG, a clinical trial was conducted. Metabolomics was used to explore its deep mechanism. Methods: A total of 14 patients with CNG were recruited from October 2020 to March 2021 (ChiCTR2000040549). The endoscopy and histopathological changes were evaluated as efficacy. Serum samples were prepared and detected by performing widely targeted metabolome using UPLC. Multivariate statistical analysis was conducted to identify potential differential metabolites and signaling pathways. Last, the signal-related inflammatory factors containing COX-2, IL-4, and IL-17 were confirmed via immunohistochemical staining and enzyme-linked immunosorbent assay. Results: ZJP was able to alleviate several indexes of mucosal injury under endoscopy and histology. Erosion and bile reflux, but not red plaques and hemorrhage, were downregulated by ZJP. In addition, it could remarkably alleviate active chronic inflammation. A total of 14 potential metabolites, namely, hypoxanthine, adipic acid, D-ribono-1,4-lactone, L-sepiapterin, imidazoleacetic acid, sebacate, ADP-ribose, 4-hydroxybenzyl alcohol, 11,12-EET, 15-OxoETE, 12-OxoETE, (±)8-HETE, glycyrrhizinate, and DL-aminopimelic acid, were discriminated by metabolomics. Moreover, certain amino acid metabolism got significance during the disease progress and treatment. The related inflammatory factors including COX-2, IL-4, and IL-17 were inhibited by ZJP in both mucosa and serum. Conclusion: All these results indicated that ZJP partially acts as an inflammatory suppressor to regulate comprehensive metabolism disorders. This might be an important mechanism of ZJP in the treatment of CNG.

Efficacy and safety of Tanreqing injection combined with antibiotics against Streptococcus pneumoniae pneumonia: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Tanreqing injection (TRQ) is a traditional Chinese medicine injection. The goal of this study was to assess the clinical efficacy and safety of TRQ injection in combination with azithromycin or ceftriaxone, as well as azithromycin or ceftriaxone alone, in treating Streptococcus pneumoniae pneumonia (SPP). METHODS: The randomized controlled trial (RCT) of TRQ injection combined with antibiotics versus antibiotics alone in the treatment of SPP was retrieved from Chinese and English databases (the control group was treated with antibiotics alone, while the experimental group received TRQ injection combined with antibiotics). The retrieval period was from the database's inception through February 2022. The data was extracted using the Cochrane Collaboration Network Quality Evaluation Standards, the methodological quality of the included literature was assessed, and the outcome indicators were calculated using RevMan5.4.1 software. RESULTS AND DISCUSSION: A total of 25 RCTs were collected, including 2057 patients. TRQ injection combined with antibiotics significantly improved clinical efficacy and reduced defervescence time, lung rale disappearance time, cough disappearance time, disappearance time of chest pain, and average hospitalization time when compared to control group, according to meta-analysis results (p < 0.05). WHAT IS NEW AND CONCLUSION: In the treatment of SPP, TRQ injection combination with antibiotics can significantly improve the total effect rate when compared to standard western medicine. Due to the low quality of the randomized controlled trials included in this investigation, more high-quality, multi-center, large-sample, prospective, randomized, double-blind clinical studies are needed to confirm the aforementioned conclusions.

Research Progress and Treatment Status of Liver Cirrhosis with Hypoproteinemia.

Liver cirrhosis is the 14th leading cause of death in adults worldwide. The liver is an important organ for the metabolism of sugar, protein, and fat. Liver cirrhosis with hypoproteinemia (LCH) can lead to metabolic disorders of the nutrients such as sugar, protein, and fat, as well as insufficient protein intake, digestion and absorption disorders, and continuous leakage of plasma protein into the abdominal cavity. Severe hypoproteinemia leads to a poor prognosis in patients. For every 10 g/L decrease in peripheral blood albumin, the risk of secondary liver disease complications will increase by 89% and the mortality rate increased by 24%-56%. Therefore, it is necessary to take urgent measures to treat liver cirrhosis with hypoalbuminemia and effectively treat and reverse the deterioration of the disease caused by hypoalbuminemia, so as to reduce the burden of secondary liver disease. Emerging evidence suggests that protein balance disorders, auxin resistance, and hyperleptinemia are key steps in the development of cirrhosis and hypoproteinemia. This study comprehensively analyzed the common complications, pathogenic mechanisms, and treatment status of cirrhosis caused by hypoproteinemia and proposed research prospects for dealing with this increasingly serious problem.

Network pharmacology prediction and molecular docking-based strategy to explore the potential mechanism of Huanglian Jiedu Decoction against sepsis.

BACKGROUND: Huanglian Jiedu Decoction (HLJDD) is a classical herbal formula with potential efficacy in the treatment of sepsis. However, the main components and potential mechanisms of HLJDD remain unclear. This study aims to initially clarify the potential mechanism of HLJDD in the treatment of sepsis based on network pharmacology and molecular docking techniques. METHODS: The principal components and corresponding protein targets of HLJDD were searched on TCMSP, BATMAN-TCM and ETCM and the compound-target network was constructed by Cytoscape3.8.2. Sepsis targets were searched on OMIM and DisGeNET databases. The intersection of compound target and disease target was obtained and the coincidence target was imported into STRING database to construct a PPI network. We further performed GO and KEGG enrichment analysis on the targets. Finally, molecular docking study was approved for the core target and the active compound. RESULTS: There are 257 nodes and 792 edges in the component target network. The compounds with a higher degree value are quercetin, kaempferol, and wogonin. The protein with a higher degree in the PPI network is JUN, RELA, TNF. GO and KEGG analysis showed that HLJDD treatment of sepsis mainly involves positive regulation of transcription from RNA polymerase II promoter, negative regulation of apoptosis process, response to hypoxia and other biological processes. The signaling pathways mainly include PI3K-AKT, MAPK, TNF signaling pathway. The molecular docking results showed that quercetin, kaempferol and wogonin have higher affinity with JUN, RELA and TNF. CONCLUSION: This study reveals the active ingredients and potential molecular mechanism of HLJDD in the treatment of sepsis, and provides a reference for subsequent basic research.

Tripterygium hypoglaucum (Lévl.) Hutch and Its Main Bioactive Components: Recent Advances in Pharmacological Activity, Pharmacokinetics and Potential Toxicity.

Tripterygium hypoglaucum (Lévl.) Hutch (THH) is believed to play an important role in health care and disease treatment according to traditional Chinese medicine. Moreover, it is also the representative of medicine with both significant efficacy and potential toxicity. This characteristic causes THH hard for embracing and fearing. In order to verify its prospect for clinic, a wide variety of studies were carried out in the most recent years. However, there has not been any review about THH yet. Therefore, this review summarized its characteristic of components, pharmacological effect, pharmacokinetics and toxicity to comprehensively shed light on the potential clinical application. More than 120 secondary metabolites including terpenoids, alkaloids, glycosides, sugars, organic acids, oleanolic acid, polysaccharides and other components were found in THH based on phytochemical research. All these components might be the pharmacological bases for immunosuppression, anti-inflammatory and anti-tumour effect. In addition, recent studies found that THH and its bioactive compounds also demonstrated remarkable effect on obesity, insulin resistance, fertility and infection of virus. The main mechanism seemed to be closely related to regulation the balance of immune, inflammation, apoptosis and so on in various disease. Furthermore, the study of pharmacokinetics revealed quick elimination of the main component triptolide. The feature of celastrol was also investigated by several models. Finally, the side effect of THH was thought to be the key for its limitation in clinical application. A series of reports indicated that multiple organs or systems including liver, kidney and genital system were involved in the toxicity. Its potential serious problem in liver was paid specific attention in recent years. In summary, considering the significant effect and potential toxicity of THH as well as its components, the combined medication to inhibit the toxicity, maintain effect might be a promising method for clinical conversion. Modern advanced technology such as structure optimization might be another way to reach the efficacy and safety. Thus, THH is still a crucial plant which remains for further investigation.