New insight into gut microbiota-derived metabolites to enhance liver regeneration via network pharmacology study

Oh, Ki‐Kwang; Choi, Ickwon; Gupta, Haripriya; Ganesan, Raja; Sharma, Satya Priya; Won, Sung‐Min; Jeong, Jin‐Ju; Lee, Su-Been; Cha, Min-Gi; Kwon, Goo-Hyun; Jeong, Min-Kyo; Min, Byeong-Hyun; Hyun, Ji-Ye; Eom, Jung-A; Park, Heejin; Yoon, Sang Jun; Choi, Miran; Kim, Dong Joon; Suk, Ki Tae

doi:10.1080/21691401.2022.2155661

Cited by 5 publications

(2 citation statements)

References 64 publications

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“…When creating the PPI network for DAPA, myocardial IRI, and DM, the size of the nodes in the network graph was to be set by the Degree value. The gene ontology (GO) analysis was predominantly employed to depict the functions of targets, encompassing biological processes (BP), molecular function (MF), and cellular components (CC) 26 . The signaling pathways on the Kyoto Encyclopaedia of Genes and Genomes (KEGG) database were analyzed based on the crucial targets.…”

Section: Methodsmentioning

confidence: 99%

Effect of dapagliflozin on ferroptosis through the gut microbiota metabolite TMAO during myocardial ischemia–reperfusion injury in diabetes mellitus rats

Wang,

et al. 2024

Sci Rep

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Dapagliflozin (DAPA) demonstrates promise in the management of diabetic mellitus (DM) and cardiomyopathy. Trimethylamine N-oxide (TMAO) is synthesized by the gut microbiota through the metabolic conversion of choline and phosphatidylcholine. Ferroptosis may offer novel therapeutic avenues for the management of diabetes and myocardial ischemia–reperfusion injury (IRI). However, the precise mechanism underlying ferroptosis in cardiomyocytes and the specific role of TMAO generated by gut microbiota in the therapeutic approach for DM and myocardial IRI utilizing DAPA need to be further explored. Nine male SD rats with specific pathogen-free (SPF) status were randomly divided equally into the normal group, the DM + IRI (DIR) group, and the DAPA group. The diversity of the gut microbiota was analyzed using 16S rRNA gene sequencing. Additionally, the Wekell technique was employed to measure the levels of TMAO in the three groups. Application of network pharmacology to search for intersection targets of DAPA, DIR, and ferroptosis, and RT-PCR experimental verification. Ultimately, the overlapping targets that were acquired were subjected to molecular docking analysis with TMAO. The changes of Bacteroidetes and Firmicutes in the gut microbiota of DIR rats were most significantly affected by DAPA. Escherichia-Shigella and Prevotella_9 within the phylum Bacteroidetes could be identified as the primary effects of DAPA on DIR. Compared with the normal group, the TMAO content in the DIR group was significantly increased, while the TMAO content in the DAPA group was decreased compared to the DIR group. For the network pharmacology analysis, DAPA and DIR generated 43 intersecting target genes, and then further intersected with ferroptosis-related genes, resulting in 11 overlapping target genes. The mRNA expression of ALB, HMOX1, PPARG, CBS, LCN2, and PPARA decreased in the DIR group through reverse transcription polymerase chain reaction (RT-PCR) validation, while the opposite trend was observed in the DAPA group. The docking score between TMAO and DPP4 was − 5.44, and the MM-GBSA result of − 22.02 kcal/mol. It epitomizes the finest docking performance among all the target genes with the lowest score. DAPA could reduce the levels of metabolite TMAO produced by gut microbiota, thereby regulating related target genes to decrease ferroptosis in DIR cardiomyocytes.

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Section: Methodsmentioning

confidence: 99%

Effect of dapagliflozin on ferroptosis through the gut microbiota metabolite TMAO during myocardial ischemia–reperfusion injury in diabetes mellitus rats

Wang,

et al. 2024

Sci Rep

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“…According to Oh et al (2023), myricetin plays a significant role in promoting liver regeneration by acting to reduce the chemokine signaling pathway. These results provide valuable scientific support for potential future clinical trials.…”

Section: Attenuation Of Liver Injury and Damagementioning

confidence: 99%

Effects of the nutraceutical myricetin on liver health: a systematic review

Grangeiro Neto,

Bomtempo,

Silva

et al. 2024

CLCS

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This article presents a systematic review addressing the effects of the nutraceutical myricetin on liver health. Nutraceuticals are natural or bioactive substances known for their health benefits and their crucial role in the prevention and treatment of liver diseases. In this context, myricetin, a flavonoid found in various food sources, emerges as a relevant nutraceutical for liver health. This review analyzes 20 preclinical studies demonstrating the benefits of myricetin on liver health, including improvement in Non-Alcoholic Fatty Liver Disease (NAFLD), attenuation of liver injuries, and even its therapeutic potential in the treatment of liver cancer in animal models. However, it was observed that there is a lack of clinical trials that fully explore the potential of myricetin as a nutraceutical. Most existing research is based on preclinical studies, such as animal or cell experiments. Therefore, there is a need for clinical studies to assess the efficacy of myricetin in humans. Furthermore, future research approaches are suggested, including investigating the mechanisms of action of myricetin, determining optimal doses and long-term safety, and developing dietary supplements.

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Gut Microbiota and Liver Regeneration: A Synthesis of Evidence on Structural Changes and Physiological Mechanisms

Kiseleva,

Zharikova,

Maslennikov

et al. 2024

Journal of Clinical and Experimental Hepatology

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New insight into gut microbiota-derived metabolites to enhance liver regeneration via network pharmacology study

Cited by 5 publications

References 64 publications

Effect of dapagliflozin on ferroptosis through the gut microbiota metabolite TMAO during myocardial ischemia–reperfusion injury in diabetes mellitus rats

Effect of dapagliflozin on ferroptosis through the gut microbiota metabolite TMAO during myocardial ischemia–reperfusion injury in diabetes mellitus rats

Effects of the nutraceutical myricetin on liver health: a systematic review

Gut Microbiota and Liver Regeneration: A Synthesis of Evidence on Structural Changes and Physiological Mechanisms

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