Tiaogan Jiejiu Tongluo Formula attenuated alcohol-induced chronic liver injury by regulating lipid metabolism in rats

Fang, Chunqiu; Zhang, Jingzhou; Han, Jiajun; Lei, Yuting; Cao, Zhanhong; Pan, Jianheng; Pan, Zijian; Zhang, Zhong; Qu, Ning; Luo, Haoming; Ma, Yan; Han, Dong Cheol

doi:10.1016/j.jep.2023.116838

Cited by 9 publications

(6 citation statements)

References 42 publications

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“…Certain medications have been demonstrated to improve liver injury by increasing FXR expression. 13,14 FXR activation significantly reduced liver damage and inhibited the production of inflammatory cytokines. 15 A prior investigation has indicated that FXR levels in the liver showed an inverse correlation with the extent of NLRP3 inflammasome activation in individuals with hepatitis B virus-related liver failure or nonalcoholic fatty liver disease and in mice with liver injury.…”

Section: Discussionmentioning

confidence: 94%

“…Mice in the control group received a gavage of saline, whereas mice in the bifendate, DMY-H, and DMY-L groups were administered the corresponding drugs by gavage for 8 weeks. 13 On day 56, mice were anesthetized by ether, and the blood was obtained by extirpating the eyeballs. Blood samples were centrifuged for 15 min to obtain serum (1000 ×g, 4 °C).…”

Section: Animal Experimentsmentioning

confidence: 99%

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Modulatory Effect of Dihydromyricetin on Chronic Alcoholic Liver Injury Based on the FXR-NLRP3 Signaling Pathway and Serum and Liver Metabolomics

Wang,

Zhou,

Shi

et al. 2024

Natural Product Communications

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Background In modern diets, alcohol consumption has led to an increase in the number of cases of alcohol-related liver disease (ALD). Dihydromyricetin (DMY) is commonly used as a hepatoprotective agent owing to its remarkable efficacy in treating chronic alcoholic liver injury; however, its mechanism of action is unclear. The object of the study is to investigate the effect and mechanism of DMY in alleviating chronic ALD. Methods A mouse model of chronic ALD was established. Mice were treated with DMY for 56 days, and their biochemical parameters including liver function, blood lipids, and oxidative stress-related indices were measured. Farnesoid X receptor (FXR) expression, NOD-like receptor protein 3 (NLRP3) pathway-related protein expression, and inflammation-related gene expression were determined to elucidate the mechanism of DMY in mice with ALD. Lastly, serum and liver metabolomics-based UHPLC-Orbitrap Exploris MS analyses were used to determine the influence of the metabolism of DMY on mice with ALD. Results Pharmacodynamic studies showed that DMY could decrease aspartate transaminase, alanine transaminase, triglyceride, and low-density lipoprotein cholesterol levels, improve superoxide dismutase activity, and reduce inflammation in mice with ALD. DMY treatment protects the liver by increasing FXR protein expression and by decreasing NLRP3 pathway-related protein expression and inflammatory gene expression. Metabolomics analysis indicated that ethanol treatment mainly altered metabolism in mice. DMY could regulate 10 metabolites in serum, namely, N-α-acetyllysine, 1-pyrrolinecytosine, glutamyllysine, 5-methylcytosine, N-methylvaline, pyridoxamine, demethoxycurcumin, L-arginine, triacetin, and 15-methylpalmitate. It could also regulate 31 metabolites in the liver, including L-methionine and L-leucine. DMY treatment altered the following important pathways: valine, leucine, and isoleucine biosynthesis; cysteine and methionine metabolism; and valine, leucine, and isoleucine degradation. Correlation analyses using heatmaps revealed that the metabolic parameters are closely related to the pharmacodynamic index. Conclusion These findings indicated that DMY alleviated ALD by regulating the FXR-NLRP3 signaling pathway and could treat serum and liver metabolic disorders.

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Section: Discussionmentioning

confidence: 94%

Section: Animal Experimentsmentioning

confidence: 99%

Modulatory Effect of Dihydromyricetin on Chronic Alcoholic Liver Injury Based on the FXR-NLRP3 Signaling Pathway and Serum and Liver Metabolomics

Wang,

Zhou,

Shi

et al. 2024

Natural Product Communications

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“…Furthermore, silibinin may directly bind to TFR1 to inhibit cellular iron uptake and maintain iron homeostasis in ethanol- and acetaldehyde-induced liver injury [ 118 ]. Both murine double minute X (MDMX)/peroxisome proliferator-activated receptor alpha (PPARα) pathway [ 120 ] and liver kinase B1 (LKB1)/AMP-activated protein kinaseα (AMPKα) signal axis [ 121 ] were shown to be associated with ferroptosis. For alcohol-induced liver injury, verbenalin [ 120 ] and Tiaogan Jiejiu Tongluo Formula [ 121 ] showed a certain therapeutic effect through inhibiting intracellular lipid peroxidation, which was regulated by the MDMX/PPARα pathway and LKB1/AMPKα signal axis, respectively.…”

Section: Nac Treat Liver Disease By Targeting Ferroptosismentioning

confidence: 99%

“…Both murine double minute X (MDMX)/peroxisome proliferator-activated receptor alpha (PPARα) pathway [ 120 ] and liver kinase B1 (LKB1)/AMP-activated protein kinaseα (AMPKα) signal axis [ 121 ] were shown to be associated with ferroptosis. For alcohol-induced liver injury, verbenalin [ 120 ] and Tiaogan Jiejiu Tongluo Formula [ 121 ] showed a certain therapeutic effect through inhibiting intracellular lipid peroxidation, which was regulated by the MDMX/PPARα pathway and LKB1/AMPKα signal axis, respectively. Melatonin, a hormone present in various organisms from algae to humans, is responsible for regulating circadian rhythms and is also an important endogenous antioxidant.…”

Section: Nac Treat Liver Disease By Targeting Ferroptosismentioning

confidence: 99%

Ferroptosis in Liver Disease: Natural Active Compounds and Therapeutic Implications

Wu,

Zhu,

Liu

et al. 2024

Antioxidants

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Ferroptosis is an emerging type of regulated cell death usually accompanied by the accumulation of ferrous ions (Fe2+) and lipid peroxides. As the metabolic hub of the body, the liver is crucial for iron storage and lipid metabolism. The liver seems to be closely related to ferroptosis through iron and lipid metabolism. Liver disease greatly threatens host health, and exploring effective interventions is essential. Mounting studies have demonstrated that ferroptosis is one of the possible pathogenic mechanisms involved in liver disease. Targeting ferroptosis may provide a promising opportunity for treating liver disease. However, drugs targeting ferroptosis are extremely limited. Therefore, it is an urgent need to develop new and safe ferroptosis regulators. Natural active compounds (NAC), especially those derived from traditional Chinese medicine, have recently shown great therapeutic potential in liver disease via modulating ferroptosis-related genes or pathways. Here, we outline the molecular mechanism of ferroptosis and systematically summarize the regulatory function of NAC on ferroptosis in liver disease. Finally, we discuss the application prospects and potential problems concerning NAC as ferroptosis regulators for managing liver disease.

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“…For instance, Tiaogan Jiejiu Tongluo Formula, by lowering the activity of ADH and raising the activity of ALDH, accelerates the conversion of acetaldehyde to acetic acid, alleviates the accumulation of large amounts of acetaldehyde and chronic acetaldehyde poisoning, and reduces the chronic liver injury induced by alcohol in SD rats. 37 Besides, certain functional beverages such as soda water and jia duo bao herbal infusion can also mitigate acetaldehyde levels in the body through ADH inhibition and ALDH enhancement, thus alleviating alcohol-induced hangovers in Kunming mice and preventing liver injury. 38 Additionally, Electrolytic hydrogen water (EHW) demonstrates the ability to reduce intracellular acetaldehyde levels, suppress cellular reactive oxygen species (ROS) elevation, and prevent cell death by inhibiting ADH activity while increasing ALDH activity in HepG2 liver cells.…”

mentioning

confidence: 99%

Preparation of Pueraria lobata Root-Derived Exosome-Like Nanovesicles and Evaluation of Their Effects on Mitigating Alcoholic Intoxication and Promoting Alcohol Metabolism in Mice

Zhang,

Song,

et al. 2024

IJN

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Pueraria lobata (P. lobata), a dual-purpose food and medicine, displays limited efficacy in alcohol detoxification and liver protection, with previous research primarily focused on puerarin in its dried roots. In this study, we investigated the potential effects and mechanisms of fresh P. lobata root-derived exosome-like nanovesicles (P-ELNs) for mitigating alcoholic intoxication, promoting alcohol metabolism effects and protecting the liver in C57BL/6J mice. Methods: We isolated P-ELNs from fresh P. lobata root using differential centrifugation and characterized them via transmission electron microscopy, nanoscale particle sizing, ζ potential analysis, and biochemical assays. In Acute Alcoholism (AAI) mice pretreated with P-ELNs, we evaluated their effects on the timing and duration of the loss of the righting reflex (LORR), liver alcohol metabolism enzymes activity, liver and serum alcohol content, and ferroptosis-related markers. Results: P-ELNs, enriched in proteins, lipids, and small RNAs, exhibited an ideal size (150.7 ± 82.8 nm) and negative surface charge (−31 mV). Pre-treatment with 10 mg/(kg.bw) P-ELNs in both male and female mice significantly prolonged ebriety time, shortened sobriety time, enhanced acetaldehyde dehydrogenase (ALDH) activity while concurrently inhibited alcohol dehydrogenase (ADH) activity, and reduced alcohol content in the liver and serum. Notably, P-ELNs demonstrated more efficacy compared to P-ELNs supernatant fluid (abundant puerarin content), suggesting alternative active components beyond puerarin. Additionally, P-ELNs prevented ferroptosis by inhibiting the reduction of glutathione peroxidase 4 (GPX4) and reduced glutathione (GSH), and suppressing acyl-CoA synthetase long-chain family member 4 (ACSL4) elevation, thereby mitigating pathological liver lipid accumulation. Conclusion: P-ELNs exhibit distinct exosomal characteristics and effectively alleviate alcoholic intoxication, improve alcohol metabolism, suppress ferroptosis, and protect the liver from alcoholic injury. Consequently, P-ELNs hold promise as a therapeutic agent for detoxification, sobriety promotion, and prevention of alcoholic liver injury.

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Tiaogan Jiejiu Tongluo Formula attenuated alcohol-induced chronic liver injury by regulating lipid metabolism in rats

Cited by 9 publications

References 42 publications

Modulatory Effect of Dihydromyricetin on Chronic Alcoholic Liver Injury Based on the FXR-NLRP3 Signaling Pathway and Serum and Liver Metabolomics

Modulatory Effect of Dihydromyricetin on Chronic Alcoholic Liver Injury Based on the FXR-NLRP3 Signaling Pathway and Serum and Liver Metabolomics

Ferroptosis in Liver Disease: Natural Active Compounds and Therapeutic Implications

Preparation of Pueraria lobata Root-Derived Exosome-Like Nanovesicles and Evaluation of Their Effects on Mitigating Alcoholic Intoxication and Promoting Alcohol Metabolism in Mice

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