Xie Zhuo Tiao Zhi formula modulates intestinal microbiota and liver purine metabolism to suppress hepatic steatosis and pyroptosis in NAFLD therapy

Qiu, Jiannan; Chen, Lin; Zhang, Ling; Xu, Fangying; Zhang, Congcong; Ren, Guilin; Chang, Kaixin; He, Guonong; Du, Zhongyan; Le, Yifei; Yu, Zhiling; Li, Songtao; Liu, Qingsheng; Dou, Xiaobing

doi:10.1016/j.phymed.2023.155111

Cited by 17 publications

(4 citation statements)

References 29 publications

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“…With the increase encountered, the disease may progress from mild to severe causing liver damage (Velliou et al, 2023). The condition further leads to brosis and cirrhosis which end up in liver carcinoma (Qiu et al, 2023;Velliou et al, 2023). However, there are no FDA-approved medications yet identi ed (Chehrehgosha et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

The determination of the comparative effect of Ertugliflozin, Pioglitazone, and Metformin on patients of non-alcoholic fatty liver disease in type 2 diabetes mellitus.

Khaliq,

Badshah,

Shah

et al. 2024

Preprint

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Background: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver diseases and malignancies. With the increased prevalence rate of NAFLD worldwide, an effective therapeutic solution for such a condition is essential. Among the previous studies pioglitazone, metformin, and sodium-glucose transporter 2 inhibitors were established as role models for the improvement of NAFLD. Objective: The study aimed to evaluate the effect and safety of pioglitazone, ertugliflozin, and metformin in NAFLD with type 2 diabetes mellitus (T2DM) and their effect on the function of liver enzymes. Materials and methods: This study was prospectively randomized. A total of 180 patients having NAFLD with T2DM were divided into three groups administered with ertugliflozin 15mg (n = 60), pioglitazone 30 mg (n = 60), and metformin 500 mg (n = 60) for 24 weeks. Liver stiffness (LS) and controlled attenuation parameters were measured using fibroscan. The grades of fatty liver were identified ultrasonically. Results: The result suggested that the ratio of fatty liver in grade 1 (mild fat content) was increased significantly in the ertugliflozin group (0.0 to 11.6%) while in the pioglitazone group (10.0 to 8.3%), a minor decrease was observed in grade 3 (severe far content). A significant decrease was observed in LSM (7.94±3.23 to 6.5±3.0) among the ertugliflozin group. The CAP score was significantly decreased from (360.38±39.34 to 300.60±37.0). The level of biochemical parameters including ALT, AST, and GGT significantly decreased in the ertugliflozin group. There was also a significant decrease in blood sugar, lipid profile, and body mass index between the groups. Previous studies analysis declare BMI is the risk factor for fatty liver which was also decreased in this study. Conclusion: ertugliflozin has significantly improved fatty liver, liver stiffness, and liver enzymes of patients having NAFLD with T2DM. The therapy was safe and effective and it may be used in future recommendations for physician facilitation in the case of NAFLD patients.

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Section: Discussionmentioning

confidence: 99%

The determination of the comparative effect of Ertugliflozin, Pioglitazone, and Metformin on patients of non-alcoholic fatty liver disease in type 2 diabetes mellitus.

Khaliq,

Badshah,

Shah

et al. 2024

Preprint

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“…The fingerprint analysis of XZTZ has identified six principal compounds: naringin, neo-hesperidin, Atractylenolide III, 23-o-Acetylalisol B, pachymic acid, and ursolic acid. Extensive literature supports the diverse bioactivities and health benefits associated with these compounds, including antioxidant, anti-inflammatory, and hepatoprotective effects (Qiu et al, 2023). MDA, an aldehyde formed during free radical-induced lipid peroxidation, serves as a marker for assessing lipid peroxidation and oxidative stress in the body (Zheng et al, 2019;Yamada et al, 2020).…”

Section: The Xztz Eases Hepatic Inflammatory Response Via Mapks/nf-kb...mentioning

confidence: 99%

“…Commencing in the second week of the modeling process, the mice were subjected to daily oral gavage administration of XZTZ at the prescribed dosages for a period of 3 weeks. In a previous study by our group, the analysis of the main metabolites of XZTZ using High Performance Liquid Chromatography revealed the following six metabolites in the extract of XZTZ: mannitol (1.23 min) from Shan zha, citric acid (1.7 min) from Shan zha and He ye, quercetin 3-O-β-D-glucuronopyranoside (16.90 min) from He ye, naringin (19.33 min) from Zhi qiao, hesperidin (20.94 min) from Zhi qiao, and alisol A (32.24 min) from Ze xie (Qiu et al, 2023). The chemical composition of the drug in XZTZ complies with the ConPhyMP statement and has been validated for classification at "http://www.…”

Section: Introductionmentioning

confidence: 99%

Xie Zhuo Tiao Zhi formula ameliorates chronic alcohol-induced liver injury in mice

Chang,

Guo,

et al. 2024

Front. Pharmacol.

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This study aimed to evaluate the protective role and potential mechanisms of Xie Zhuo Tiao Zhi decoction (XZTZ) on alcohol-associated liver disease (ALD). XZTZ significantly alleviated alcohol-induced liver dysfunction, based on histological examinations and biochemical parameters after 4-week administration. Mechanically, alcohol-stimulated hepatic oxidative stress was ameliorated by XZTZ, accompanied by the improvement of Nrf2/Keap1 expression and alcohol-activated phosphorylation of pro-inflammatory transcription factors, including JNK, P38, P65, and IκBα, were rescued by XZTZ. In conclusion, XZTZ demonstrates potential in alleviating alcohol-induced liver injury, oxidative stress, and inflammation possibly through modulation of Nrf2/Keap1 and MAPKs/NF-κB signaling pathways, suggesting its potential as a therapeutic option for patients with alcoholic liver disease.

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“…3.2.8. Quantitative Real-Time PCR PCR was performed as described previously [47]. After 24 h of treatment, the total RNA of the cells was collected using a SteadyPure RNA Extraction Kit (AG21024, Accurate Biology, Beijing, China).…”

Section: Bodipy Stainingmentioning

confidence: 99%

Design and Synthesis of Novel Indole Ethylamine Derivatives as a Lipid Metabolism Regulator Targeting PPARα/CPT1 in AML12 Cells

Liu,

Wei,

Liao

et al. 2023

Molecules

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Peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1 (CPT1) are important targets of lipid metabolism regulation for nonalcoholic fatty liver disease (NAFLD) therapy. In the present study, a set of novel indole ethylamine derivatives (4, 5, 8, 9) were designed and synthesized. The target product (compound 9) can effectively activate PPARα and CPT1a. Consistently, in vitro assays demonstrated its impact on the lipid accumulation of oleic acid (OA)-induced AML12 cells. Compared with AML12 cells treated only with OA, supplementation with 5, 10, and 20 μM of compound 9 reduced the levels of intracellular triglyceride (by 28.07%, 37.55%, and 51.33%) with greater inhibitory activity relative to the commercial PPARα agonist fenofibrate. Moreover, the compound 9 supplementations upregulated the expression of hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) and upregulated the phosphorylation of acetyl-CoA carboxylase (ACC) related to fatty acid oxidation and lipogenesis. This dual-target compound with lipid metabolism regulatory efficacy may represent a promising type of drug lead for NAFLD therapy.

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Xie Zhuo Tiao Zhi formula modulates intestinal microbiota and liver purine metabolism to suppress hepatic steatosis and pyroptosis in NAFLD therapy

Cited by 17 publications

References 29 publications

The determination of the comparative effect of Ertugliflozin, Pioglitazone, and Metformin on patients of non-alcoholic fatty liver disease in type 2 diabetes mellitus.

The determination of the comparative effect of Ertugliflozin, Pioglitazone, and Metformin on patients of non-alcoholic fatty liver disease in type 2 diabetes mellitus.

Xie Zhuo Tiao Zhi formula ameliorates chronic alcohol-induced liver injury in mice

Design and Synthesis of Novel Indole Ethylamine Derivatives as a Lipid Metabolism Regulator Targeting PPARα/CPT1 in AML12 Cells

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