Paeoniflorin Ameliorates Diabetic Liver Injury by Targeting the TXNIP-Mediated NLRP3 Inflammasome in Db/Db Mice

Wang, anli; Gong, Yingjie; Pei, Zhixin; Jiang, Ling; Xia, Lingling; Wu, Yuangang

doi:10.2139/ssrn.4025910

SSRN Journal

2022

DOI: 10.2139/ssrn.4025910

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Paeoniflorin Ameliorates Diabetic Liver Injury by Targeting the TXNIP-Mediated NLRP3 Inflammasome in Db/Db Mice

anli Wang

Yingjie Gong²,

Zhixin Pei

et al.

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Relevance of the pyroptosis-related inflammasome drug targets in the Chuanxiong to improve diabetic nephropathy

Mali

et al. 2022

Mol Med

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Background A chronic inflammatory disease caused by disturbances in metabolism, diabetic nephropathy (DN) is a chronic inflammatory disease. Pyroptosis is a novel form of programmed cell death in many inflammation-related diseases, including DN. Therefore, pyroptosis could be a promising target for DN therapy. Methods To get the components and pharmacodynamic targets of Chuanxiong, we identified by searching TCMID, TCMSP, ETCM and HERB databases. Then, from the Molecular Signatures Database (MSigDB) and Gene Ontology (GO) database, pyroptosis genes were collected. Identification of critical genes in DN by bioinformatics analysis and then using the ConsensusClusterPlus package to divide the express data of diff genes into some subgroups with different levels of pyroptosis; the WGCNA machine algorithm was used to simulate the mechanism Chuanxiong improving DN. Results In this study, we found DHCR24, ANXA1, HMOX1, CDH13, ALDH1A1, LTF, CHI3L1, CACNB2, and MTHFD2 interacted with the diff genes of DN. We used GSE96804 as a validation set to evaluate the changes of APIP, CASP6, CHMP2B, CYCS, DPP8, and TP53 in four different cell proapoptotic states. WGCNA analysis showed that DHCR24, CHI3L1, and CACNB2 had significant changes in different cell proapoptotic levels. In the experimental stage, we also confirmed that the active ingredients of Chuanxiong could improve the inflammatory state and the levels of pyroptosis under high glucose. Conclusion The improvement of DN by Chuanxiong is related to the change of pyroptosis.

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Relevance of the pyroptosis-related inflammasome drug targets in the Chuanxiong to improve diabetic nephropathy

Mali

et al. 2022

Mol Med

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Salidroside Affects Gut Microbiota Structure in db/db Mice by Affecting Insulin, Blood Glucose and Body Weight

Zhao¹,

Shi²,

Chen³

et al. 2022

DMSO

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The purpose of this study was to investigate the regulatory effect of salidroside on the intestinal flora of mice with type 2 diabetes (T2DM) and its protective effect in the body. Patients and Methods:We acclimated 8-week-old mice for 7 days, divided them into 4 groups, and continued dosing for 8 weeks. We recorded weekly blood glucose levels and body weight for each mouse. After the completion of the feeding cycle, the 16S rRNA of the intestinal flora in the mice was sequenced, and the insulin and C-peptide levels in each group of mice were measured. Four samples were taken from each group for liver and kidney section staining. Results: Our results showed that gut microbiota diversity and function were significantly different between the diabetic mice and healthy mice and that insulin levels, body weight, and blood glucose levels could significantly influence gut microbiota changes at the genus level. The gut microbiota diversity and function of db/db mice were also altered after salidroside administration. Salidroside could attenuate inflammatory damage, lipid accumulation and inflammatory changes in the diabetic liver, as well as diabetic kidney damage. Candidatus arthromitus and Odoribacter are important species of the microbiota during diabetes and may serve as potential therapeutic targets. Conclusion: Our investigation of the associated pathological conditions and fecal microbiota in db/db mice provides new insights into the pathogenesis of T2DM and provides implications for the diagnosis and treatment of T2DM.

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Potential Therapeutic Implication of Herbal Medicine in Mitochondria-Mediated Oxidative Stress-Related Liver Diseases

Park

Rahman

et al. 2022

Antioxidants

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Mitochondria are double-membrane organelles that play a role in ATP synthesis, calcium homeostasis, oxidation-reduction status, apoptosis, and inflammation. Several human disorders have been linked to mitochondrial dysfunction. It has been found that traditional therapeutic herbs are effective on alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) which are leading causes of liver cirrhosis and hepatocellular carcinoma. The generation of reactive oxygen species (ROS) in response to oxidative stress is caused by mitochondrial dysfunction and is considered critical for treatment. The role of oxidative stress, lipid toxicity, and inflammation in NAFLD are well known. NAFLD is a chronic liver disease that commonly progresses to cirrhosis and chronic liver disease, and people with obesity, insulin resistance, diabetes, hyperlipidemia, and hypertension are at a higher risk of developing NAFLD. NAFLD is associated with a number of pathological factors, including insulin resistance, lipid metabolic dysfunction, oxidative stress, inflammation, apoptosis, and fibrosis. As a result, the improvement in steatosis and inflammation is enough to entice researchers to look into liver disease treatment. However, antioxidant treatment has not been very effective for liver disease. Additionally, it has been suggested that the beneficial effects of herbal medicines on immunity and inflammation are governed by various mechanisms for lipid metabolism and inflammation control. This review provided a summary of research on herbal medicines for the therapeutic implementation of mitochondria-mediated ROS production in liver disease as well as clinical applications through herbal medicine. In addition, the pathophysiology of common liver disorders such as ALD and NAFLD would be investigated in the role that mitochondria play in the process to open new therapeutic avenues in the management of patients with liver disease.

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Paeoniflorin Ameliorates Diabetic Liver Injury by Targeting the TXNIP-Mediated NLRP3 Inflammasome in Db/Db Mice

Cited by 5 publications

References 0 publications

Relevance of the pyroptosis-related inflammasome drug targets in the Chuanxiong to improve diabetic nephropathy

Relevance of the pyroptosis-related inflammasome drug targets in the Chuanxiong to improve diabetic nephropathy

Salidroside Affects Gut Microbiota Structure in db/db Mice by Affecting Insulin, Blood Glucose and Body Weight

Potential Therapeutic Implication of Herbal Medicine in Mitochondria-Mediated Oxidative Stress-Related Liver Diseases

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