Traditional Chinese medicine in the treatment of nonalcoholic steatohepatitis

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease with high incidence and is closely related to metabolic syndrome. If not controlled, it may eventually become hepatocellular carcinoma (HCC). Ferroptosis, a non-apoptotic form of programmed cell death (PCD), is closely related to NAFLD and HCC, and the mechanisms of action involved are more complex. Some studies have demonstrated that many drugs inhibit ferroptosis and protect liver steatosis or carcinogenesis. The role of Traditional Chinese Medicine (TCM), especially herbs or herbal extracts, has received increasing attention. However, there are relatively few review articles on the regulation of NAFLD by TCM through ferroptosis pathway. Here, we summarize the TCM intervention mechanism and application affecting NAFLD/NAFLD-HCC via regulation of ferroptosis. This article focuses on the relationship between ferroptosis and NAFLD or NAFLD-HCC and the protective effect of TCM on both by targeting ferroptosis. It not only summarizes the mechanism of early prevention and treatment of NAFLD, but also provides reference ideas for the development of TCM for the treatment of metabolic diseases and liver diseases.

https://www.frontiersin.org/articles/10.3389/fnut.2022.1033129/pdf

Protective effect of traditional Chinese medicine on non-alcoholic fatty liver disease and liver cancer by targeting ferroptosis

Purpose: To explore pharmacological mechanisms of Pulsatilla decoction (PD) against Crohn’s disease (CD) via network pharmacology analysis followed by experimental validation. Methods: Public databases were searched to identify bioactive compounds and related targets of PD as well as related genes in patients with CD. Analyses using the drug–compound–target–disease network, the protein–protein interaction (PPI) network, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the core targets and pathways of PD against CD. Colon tissue resected from patients with CD and tissue samples from a mouse model of CD fibrosis treated with PD were assessed to verify the major targets of PD in CD predicted by network pharmacologic analysis. Results: A search of the targets of bioactive compounds in PD and targets in CD identified 134 intersection targets. The target HSP90AA1, which was common to the drug–compound–target–disease and PPI networks, was used to simulate molecular docking with the corresponding bioactive compound. GO and KEGG enrichment analyses showed that multiple targets in the antifibrotic pathway were enriched and could be experimentally validated in CD patients and in a mouse model of CD fibrosis. Assays of colon tissues from CD patients showed that intestinal fibrosis was greater in stenoses than in nonstenoses, with upregulation of p-AKT, AKT, p-mTOR, mTOR, p-ERK1/2, ERK1/2, p-PKC, and PKC targets. Treatment of CD fibrosis mice with PD reduced the degree of fibrosis, with downregulation of the p-AKT, AKT, p-mTOR, mTOR, p-ERK1/2, ERK1/2, and PKC targets. Conclusion: Network pharmacology analysis was able to predict bioactive compounds in PD and their potential targets in CD. Several of these targets were validated experimentally, providing insight into the pharmacological mechanisms underlying the biological activities of PD in patients with CD.

/pdf/network-pharmacology-based-strategy-to-identify-the-1ejrw9og.pdf

Network Pharmacology-Based Strategy to Identify the Pharmacological Mechanisms of Pulsatilla Decoction against Crohn’s Disease

Inflammatory bowel disease (IBD) is a complex multifactorial chronic inflammatory disease, that includes Crohn’s disease (CD) and ulcerative colitis (UC), having progressively increasing global incidence. Disturbed intestinal flora has been highlighted as an important feature of IBD and offers promising strategies for IBD remedies. A brief overview of the variations occurring in intestinal flora during IBD is presented, and the role of the gut microbiota in intestinal barrier maintenance, immune and metabolic regulation, and the absorption and supply of nutrients is reviewed. More importantly, we review drug research on gut microbiota in the past ten years, including research on clinical and natural drugs, as well as adjuvant therapies, such as Fecal Microbiota Transplantation and probiotic supplements. We also summarize the interventions and mechanisms of these drugs on gut microbiota.

/pdf/manipulating-microbiota-in-inflammatory-bowel-disease-1th3nhrc.pdf

Manipulating Microbiota in Inflammatory Bowel Disease Treatment: Clinical and Natural Product Interventions Explored

The dried tuber of Alisma orientale (Sam.) Juzep. (AOJ) is a traditional Chinese medicine with high medicinal value. The endophytic fungi of medicinal plants are a treasure house of natural compounds. However, there is a lack of research on the diversity and biological activity of endophytic fungi of AOJ. In this study, high-throughput sequencing technology was used to study the diversity of endophytic fungi in the roots and stems of AOJ, and endophytic fungi with a high output of phenols and flavonoids were screened by chromogenic reaction, and the antioxidant and antibacterial activities and chemical constituents of crude extracts of their fermentation broth were studied. A total of 3,426 amplicon sequence variants (ASVs) belonging to 9 phyla, 27 classes, 64 orders, 152 families, and 277 genera were identified from AOJ. There were significant differences in the endophytic fungal communities of AOJ roots and stems, as well as in the endophytic fungal communities of triangular AOJ and circular AOJ. In addition, 31 strains of endophytic fungi were isolated from AOJ, of which 6 strains had good antioxidant and antibacterial activities. The crude extract of YG-2 had the strongest free radical scavenging ability and bacteriostatic ability, and its IC50 DPPH, IC50 ABTS, and IC50⋅OH values were 0.009 ± 0.000 mg/mL, 0.023 ± 0.002 mg/mL, and 0.081 ± 0.006 mg/mL, respectively. The results of LC-MS showed that the main component of the crude extract of YG-2 was caffeic acid (10.12 μmol/g). Overall, the results of this study preliminarily elucidated the diversity and community composition of endophytic fungi of AOJ, indicating that AOJ endophytic fungi have abundant secondary metabolites and good antioxidant and antibacterial activities. This study provides an important reference for further research, development and utilization of AOJ endophytic fungi and a theoretical basis for the further development of the endophytic fungus YG-2 (Chaetomium globosum) as a source of antioxidants.

/pdf/diversity-chemical-constituents-and-biological-activities-of-fwvi7gjn.pdf

Diversity, chemical constituents and biological activities of endophytic fungi from Alisma orientale (Sam.) Juzep.

To investigate the effects of the Alisma and Rhizoma decoction on nonalcoholic steatohepatitis (NASH) and to further shed light on the underlying mechanisms of the actions of the Alisma and Rhizoma decoction. Plasma alanine aminotransferase (ALT) content was determined and liver inflammation and fibrosis were evaluated. Intrahepatocellular malondialdehyde and superoxide dismutase contents were determined using commercially available kits Furthermore, α-SMA expression in liver tissues was examined by immunohistochemistry and LC3-II was detected by immunoblotting assays. Mice receiving the Alisma and Rhizoma decoction by gastric lavage had significantly lower plasma ALT content and markedly higher hepatic superoxide dismutase activity than mice receiving the methionine-choline deficient (MCD) diet. Furthermore, the decoction aborted MCD-induced increase in liver malondialdehyde content. Immunohistochemistry showed that the decoction suppressed hepatic α-SMA expression. Our transmission electronic microscopy revealed that the decoction markedly reduced the number of autophagosomes and immunoblotting assays showed that the decoction caused a dose-dependent decrease in LC3-II in hepatic tissues. The Alisma and Rhizoma decoction lessens NASH-associated liver injuries by modulating oxidative stress and autophagy in hepatocytes of mice fed with MCD.

/pdf/the-alisma-and-rhizoma-decoction-abates-nonalcoholic-3b4o45t3o1.pdf

The Alisma and Rhizoma decoction abates nonalcoholic steatohepatitis-associated liver injuries in mice by modulating oxidative stress and autophagy

The aim of the present study was to investigate the therapeutic effect of Pulsatilla decoction (PD) on ulcerative colitis (UC) and to elucidate its potential molecular mechanisms. C57BL/6 mice expressing natural killer (NK)1.1 were used as experimental animals in the present study and a model of oxazolone-induced colitis was established. Mice were randomly divided into the following five groups: i) PD group; ii) oxazolone-induced colitis group; iii) IL-13 intervention group; iv) 5-aminosalicylic acid positive control group; and v) negative control group (equal volume saline gavage). A total of 10 animals were used in each group. The effects of PD on UC and the association between this regimen and the PI3K-Akt-mTORC1 signaling pathway were evaluated by disease activity index (DAI), hematoxylin and eosin staining, reverse transcription-quantitative PCR (RT-qPCR), immunofluorescence assay, ELISA and western blotting. The UC models were successfully established by injecting oxazolone gavage solution. Clinical colitis evaluation and histological examination revealed that PD reduced the DAI values in oxazolone-induced colitis in mice and the degree of infiltration in NK1.1 cells. PD significantly reduced the secretion of IL-13, as determined using an ELISA. In addition, western blotting and RT-qPCR analyses demonstrated that Beclin1 and LC3II/I expression levels were downregulated following treatment of the mice with PD. In addition, PD not only partially restored alterations in the expression of tight junction proteins in the colon tissues, but also suppressed the activation of the PI3K-Akt-mTORC1 signaling pathway. The data indicated that this regimen could alleviate oxazolone-induced UC in mice, which could significantly reduce tissue inflammation and autophagy. The mechanism of action was associated with the PI3K-Akt-mTORC1 signaling pathway.

/pdf/pulsatilla-decoction-alleviates-colitis-by-enhancing-2eaurubd.pdf

Pulsatilla decoction alleviates colitis by enhancing autophagy and regulating PI3K-Akt-mTORC1 signaling pathway

OBJECTIVE
Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) frequently coexist and can act synergistically to drive adverse outcomes of one another. This study aimed to unravel the metabolomic changes in patients with NAFLD and T2DM, to identify potential noninvasive biomarkers, and to provide insights for understanding the link between NAFLD and T2DM.


METHODS
Three hundred participants aged 35 to 70 years who were diagnosed with NAFLD (n = 100), T2DM (n = 100), or a comorbidity of NAFLD and T2DM (n = 100) were included in this study. Anthropometrics and routine blood chemistry were assessed after overnight fast. The global serum metabolomic analysis was performed by ultra-performance liquid chromatography-Orbitrap mass spectrometry. Multivariate data analysis methods were utilized to identify the potential biomarkers.


RESULTS
A set of serum biomarkers that could effectively separate NAFLD from NAFLD + T2DM and T2DM from NAFLD + T2DM were identified. We found that patients with coexisting NAFLD and T2DM had significantly higher levels of total protein (TP), triglycerides (TG), glucose in urine, and gamma-hydroxybutyric acid than those with NAFLD and had significant increased levels of TP, albumin, alanine aminotransferase, aspartate aminotransferase, total cholesterol, cholinesterase, TG, low-density lipoprotein, and apolipoprotein A when compared to patients with T2DM.


CONCLUSION
The metabolomics results provide evidence that the comorbidity of NAFLD and T2DM considerably altered patients' metabolomics patterns compared to those of patients with only NAFLD or T2DM.

Serum Metabolomics in Patients with Coexisting NAFLD and T2DM Using Liquid Chromatography-Mass Spectrometry.

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The Alisma and Rhizoma decoction abates nonalcoholic steatohepatitis-associated liver injuries in mice by modulating oxidative stress and autophagy

Pulsatilla decoction alleviates colitis by enhancing autophagy and regulating PI3K-Akt-mTORC1 signaling pathway

Serum Metabolomics in Patients with Coexisting NAFLD and T2DM Using Liquid Chromatography-Mass Spectrometry.