본문 바로가기
KERD
논문KCI 등재

Dihydromyricetin Alleviates Non-Alcoholic Fatty Liver Disease by Modulating Gut Microbiota and Inflammatory Signaling Pathways

1

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류생물학

초록

Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition that is strongly linked to gut microbiota imbalance and chronic inflammation. This study aims to explore the preventive effects of dihydromyricetin (DHM) on NAFLD by modulating the intestinal flora and the TLR4/NF-κB signaling pathway. Fifty male C57BL/6J mice were randomly assigned to five groups: a normal control group, a model group, and three DHM treatment groups receiving low (500 mg/kg), medium (750 mg/kg), and high doses (1,000 mg/kg). NAFLD was induced using a high-fat diet, and DHM was administered for 8 weeks. ELISA measured serum levels of LPS, IL-1β, and TNF-α, while Western Blot assessed liver expression of TLR4 and NF-κB p65. Changes in intestinal flora composition were analyzed using high-throughput 16S rRNA sequencing. The results showed that DHM treatment significantly reduced serum levels of LPS, IL-1β, and TNF-α, decreasing the liver expression of TLR4 and NF-κB p65. Intestinal flora analysis indicated a notable increase in beneficial bacteria, especially in the medium and high-dose groups. DHM treatment also significantly improved liver pathology, reducing fat deposition and inflammatory cell infiltration. In conclusion, DHM effectively prevents the progression of NAFLD by improving gut microbiota balance and suppressing inflammatory signaling pathways.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition that is strongly linked to gut microbiota imbalance and chronic inflammation. This study aims to explore the preventive effects of dihydromyricetin (DHM) on NAFLD by modulating the intestinal flora and the TLR4/NF-κB signaling pathway. Fifty male C57BL/6J mice were randomly assigned to five groups: a normal control group, a model group, and three DHM treatment groups receiving low (500 mg/kg), medium (750 mg/kg), and high doses (1,000 mg/kg). NAFLD was induced using a high-fat diet, and DHM was administered for 8 weeks. ELISA measured serum levels of LPS, IL-1β, and TNF-α, while Western Blot assessed liver expression of TLR4 and NF-κB p65. Changes in intestinal flora composition were analyzed using high-throughput 16S rRNA sequencing. The results showed that DHM treatment significantly reduced serum levels of LPS, IL-1β, and TNF-α, decreasing the liver expression of TLR4 and NF-κB p65. Intestinal flora analysis indicated a notable increase in beneficial bacteria, especially in the medium and high-dose groups. DHM treatment also significantly improved liver pathology, reducing fat deposition and inflammatory cell infiltration. In conclusion, DHM effectively prevents the progression of NAFLD by improving gut microbiota balance and suppressing inflammatory signaling pathways.

참고문헌 (55)

  1. Sanyal AJ, "Defining the serum proteomic signature of hepatic steatosis, inflammation, ballooning and fibrosis in non-alcoholic fatty liver disease", J. Hepatol, 78, pp.693~703 (2023)
  2. Sahin E, "The pleiotropic approach to coronavirus disease-19 pathogenesis : the impact of liver diseases associated host genetic variants", Hepatol. Forum, 5, pp.93~96 (2023)
  3. Montemayor S, "Adherence to mediterranean diet and NAFLD in patients with metabolic syndrome : the FLIPAN study", Nutrients, 14, pp.3186~ (2022)
  4. Cui Y, "Intestinal barrier function-non-alcoholic fatty liver disease interactions and possible role of gut microbiota", J. Agric. Food Chem, 67, pp.2754~2762 (2019)
  5. Samji NS, "Magnitude of nonalcoholic fatty liver disease : Western perspective", J. Clin. Exper. Hepatol, 9, pp.497~505 (2019)
  6. Tagi VM, "Metabolic syndrome in children", Minerva Pediatr, 72, pp.312~325 (2020)
  7. Alberti G, "Fructose, omega 3 fatty acids, and Vitamin E : involvement in pediatric non-alcoholic fatty liver disease", Nutrients, 12, pp.3531~ (2020)
  8. Cusi K, "American association of clinical endocrinology clinical practice guideline for the diagnosis and management of nonalcoholic fatty liver disease in primary care and endocrinology clinical settings : co-sponsored by the American association for the study of liver diseases(AASLD)", Endocr. Pract, 28, pp.528~562 (2022)
  9. Leung AKC, "Childhood obesity : an updated review", Curr. Pediatr. Rev, 20, pp.2~26 (2024)
  10. Tian T, "Dietary quality and relationships with Metabolic Dysfunction-Associated Fatty Liver Disease(MAFLD)among United States Adults, results from NHANES 2017-2018", Nutrients, 14, pp.4505~ (2022)
  11. Pixner T, "The role of macronutrients in the pathogenesis, prevention and treatment of non-alcoholic fatty liver disease(NAFLD)in the paediatric population-A review", Life(Basel, Switzerland), 12, pp.839~ (2022)
  12. Canfora EE, "Gut microbial metabolites in obesity, NAFLD and T2DM", Nat. Rev. Endocrinol, 15, pp.261~273 (2019)
  13. Zhao D, "Beneficial impacts of fermented celery (Apium graveolens L.) juice on obesity prevention and gut microbiota modulation in high-fat diet fed mice", Food Funct, 12, pp.9151~9164 (2021)
  14. Aron-Wisnewsky J, "Gut microbiota and human NAFLD:disentangling microbial signatures from metabolic disorders", Nature reviews. Gastroenterol. Hepatol, 17, pp.279~297 (2020)
  15. Yu JS, "Lactobacillus lactis and Pediococcus pentosaceus-driven reprogramming of gut microbiome and metabolome ameliorates the progression of non-alcoholic fatty liver disease", Clin. Transl. Med, 11, pp.e634~ (2021)
  16. Mazgaeen L, "Recent advances in lipopolysaccharide recognition systems", Int. J. Mol. Sci, 21, pp.379~ (2020)
  17. Li C, "Toll-like receptor 4 antagonist FP7 alleviates lipopolysaccharide-induced septic shock via NF-kB signaling pathway", Chem. Biol. Drug Des, 97, pp.1151~1157 (2021)
  18. Zhang Q, "Recent advances in research on vine tea, a potential and functional herbal tea with dihydromyricetin and myricetin as major bioactive compounds", J. Pharm. Anal, 11, pp.555~563 (2021)
  19. Zhang ZY, "Dihydromyricetin alleviates H9C2 cell apoptosis and autophagy by regulating CircHIPK3 expression and PI3K", AKT, Chin. J. Integr. Med, pp.2023, 29[DOI]
  20. Luo JD, , Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology, 36, pp.6~11 (2020)
  21. Zhou J, "Dihydromyricetin improves high-fat diet-induced hyperglycemia through ILC3 activation via a SIRT3-dependent mechanism", Mol. Nutr. Food Res, 66, pp.e2101093~ (2022)
  22. Yu ZW, "Exploring the genes involved in biosynthesis of dihydroquercetin and dihydromyricetin in Ampelopsis grossedentata", Sci. Rep, 11, pp.15596~ (2021)
  23. Zhang S, "Identification of hydroxylation enzymes and the metabolic analysis of dihydromyricetin synthesis in Ampelopsis grossedentata", Genes, 13, pp.2318~ (2022)
  24. Song L, "Natural products in traditional Chinese medicine : molecular mechanisms and therapeutic targets of renal fibrosis and state-of-the-art drug delivery systems", Biomed. Pharmacother, 170, pp.116039~ (2024)
  25. Cardamone MD, "Neuralized-like protein 4(NEURL4)mediates ADPribosylation of mitochondrial proteins", J. Cell Biol, 221, pp.e202101021~ (2022)
  26. Ye JH, "Pentoxifylline ameliorates non-alcoholic fatty liver disease in hyperglycaemic and dyslipidaemic mice by upregulating fatty acid β-oxidation", Sci. Rep, 6, pp.33102~ (2016)
  27. Tsuchida T, "A simple diet-and chemical-induced murine NASH model with rapid progression of steatohepatitis, fibrosis and liver cancer", J. Hepatol, 69, pp.385~395 (2018)
  28. Luo A, "Exosome-derived miR-339-5p mediates radiosensitivity by targeting Cdc25A in locally advanced esophageal squamous cell carcinoma", Oncogene, 38, pp.4990~5006 (2019)
  29. Lu J, "Exosomal miR-9 inhibits angiogenesis by targeting MDK and regulating PDK", AKT pathway in nasopharyngeal carcinoma, 2018, pp.37, 147~
  30. Bian J, "Modulation of local overactive inflammation via injectable hydrogel microspheres", Nano Lett, 21, pp.2690~2698 (2021)
  31. Pu Y, "A role of the subdiaphragmatic vagus nerve in depression-like phenotypes in mice after fecal microbiota transplantation from Chrna7 knock-out mice with depression-like phenotypes", Brain Behave. Immun, 94, pp.318~326 (2021)
  32. Abellan-Schneyder I, "Primer, pipelines, parameters : issues in 16S rRNA gene sequencing", mSphere, 6, pp.e01202-20~ (2021)
  33. Zhang QF, "CDK4", 6 inhibition promotes immune infiltration in ovarian cancer and synergizes with PD-1 blockade in a B cell-dependent manner, 2020, pp.10, 10619~10633
  34. Byrne CD, "NAFLD : a multisystem disease", J. Hepatol, 62(1 Suppl), pp.S47~S64 (2015)
  35. Pouwels S, "Non-alcoholic fatty liver disease(NAFLD) : a review of pathophysiology, clinical management and effects of weight loss", BMC Endocr. Disord, 22, pp.63~ (2022)
  36. Yu X, "Effect of dihydroquercetin on energy metabolism in LPS-induced inflammatory mice", BioMed Res. Int, 2022, pp.6491771~ (2022)
  37. Alam Q, "Dihydroquercetin ameliorates LPS-induced neuroinflammation and memory deficit", Curr. Res. Pharmacol. Drug Discov, 3, pp.100091~ (2022)
  38. Li C, "Dihydroquercetin(DHQ)ameliorates LPS-induced acute lung injury by regulating macrophage M2 polarization through IRF4", miR-132-3p, Pulm. Pharmacol. Ther, pp.2023, 83[DOI]
  39. Zhao Y, "Dihydromyricetin reverses thioacetamide-induced liver fibrosis through inhibiting NF-κB-mediated inflammation and TGF-β1-regulated of PI3K", Akt signaling pathway, 2021, pp.12, 783886~
  40. Qin Y, "Exploring the potential mechanism of Rubus corchorifolius L. fruit polyphenol-rich extract in mitigating non-alcoholic fatty liver disease by integration of metabolomics and transcriptomics profiling", Food Funct, 14, pp.9295~9308 (2023)
  41. Atazadegan MA, "The effect of herbal medicine and natural bioactive compounds on plasma adiponectin : a clinical review", Adv. Exper. Med. Biol, 1328, pp.37~57 (2021)
  42. Wei Y, "Dihydromyricetin improves LPS-induced sickness and depressive-like behaviors in mice by inhibiting the TLR4", Akt, NLRP3 pathway, pp.Behav. Brain Res, 2022[DOI]
  43. Matouk AI, "Dihydromyricetin alleviates methotrexate-induced hepatotoxicity via suppressing the TLR4", NF-κB pathway and NLRP3 inflammasome, Biomed. Pharmacother, pp.2022, 155[DOI]
  44. Tang J, "Effect of gut microbiota on LPS-induced acute lung injury by regulating the TLR4", NF-kB signaling pathway, 2021, pp.91, 107272~
  45. Zhang HX, "Quercetin effectively improves LPS-induced intestinal inflammation, pyroptosis, and disruption of the barrier function through the TLR4", NF-κB, Food Nutr. Res, pp.2022, 66[DOI]
  46. Chang Y, "Dihydromyricetin attenuates Escherichia coli lipopolysaccharideinduced ileum injury in chickens by inhibiting NLRP3 inflammasome and TLR4", NF-κB signalling pathway, 2020, pp.51, 72~
  47. Dong S, "Dihydromyricetin improves DSS-induced colitis in mice via modulation of fecal-bacteria-related bile acid metabolism", Pharmacol. Res, 171, pp.105767~ (2021)
  48. Wei C, "Effects of dietary dihydromyricetin supplementation on intestinal barrier and humoral immunity in growing-finishing pigs", Anim. Biotechnol, 33, pp.1398~1406 (2022)
  49. Zhou X, "Dihydromyricetin-encapsulated liposomes inhibit exhaustive exercise-induced liver inflammation by orchestrating M1", M2 macrophage polarization, 2022, pp.13, 887263~
  50. Zhang R, "A double-layered gastric floating tablet for zero-order controlled release of dihydromyricetin : design, development, and in vitro", in vivo evaluation, 2023, pp.638, 122929~
  51. Sun Y, "Mechanism of dihydromyricetin on inflammatory diseases", Front. Pharmacol, 12, pp.794563~ (2022)
  52. Wen X, "The molecular mechanism underlying the therapeutic effect of dihydromyricetin on type 2 diabetes mellitus based on network pharmacology, molecular docking, and transcriptomics", Foods(Basel, Switzerland), 13, pp.344~ (2024)
  53. Leng Q, "Dihydromyricetin ameliorates diet-induced obesity and promotes browning of white adipose tissue by upregulating IRF4", PGC-1α, 2022, pp.19, 38~
  54. Xie K, "Ameliorative effects and molecular mechanisms of vine tea on western diet-induced NAFLD", Food Funct, 11, pp.5976~5991 (2020)
  55. Gong H, "Molecular mechanism and therapeutic significance of dihydromyricetin in nonalcoholic fatty liver disease", Eur. Pharmacol, 935, pp.175325~ (2022)

관련 논문AI추천

The Therapeutic Effect and Mechanism of Lactobacillus gardneri on Nonalcoholic Fatty Liver DiseaseFeng Haibo, Lu Fengqin, Wang Jiabo, Xiang Jie, Xiang Xiaoxing, Zhang Yu, Zhu Keyan한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2025 · 제35권 Efficacy of nobiletin in improving hypercholesterolemia and nonalcoholic fatty liver disease in high-cholesterol diet-fed mice김영재, 정운주, Dae Seong Yoon한국영양학회 · Nutrition Research and Practice2021 · 제15권 제4호Hepatoprotective Effect of Lactiplantibacillus plantarum DSR330 in Mice with High Fat Diet-Induced Nonalcoholic Fatty Liver Disease백현동, 이나경, Choi Yong-Min, Lee Jinhyeuk, Lee Yunjung, Park Eunju, Ra Jehyeon, Ryu Byung Hee, Shin Da-Soul한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2024 · 제34권 제2호Fermented Protaetia brevitarsis Larvae Alleviates High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in C57BL/6 Mice via Regulation of Lipid Accumulation and InflammationGo Min Ji, Heo Ho Jin, Kim In Young, Kim Jong Min, Kim Ju Hui, Lee Han Su, Lee Hyo Lim, Seong Geum-Su한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2025 · 제35권 Lactobacillus attenuates progression of nonalcoholic fatty liver disease by lowering cholesterol and steatosis석기태, 윤기수, 한상학, Byoung Kook Kim, Byung Yong Kim, Do Yup Lee, Haripriya Gupta, Hotaik Sung, Hyeong Seop Kim, Min Jea Shin, Na Young Lee, Sang Jun Yoon, Tae Sik Park, Ye Rin Choi대한간학회 · Clinical and Molecular Hepatology2021 · 제27권 제1호Gut-Liver Axis: The Role of Intestinal Microbiota and Their Metabolites in the Progression of Metabolic Dysfunction- Associated Steatotic Liver DiseaseChao Cui, Jingfei Shi, Kai Wang, Shuai Gao거트앤리버 소화기연관학회협의회 · Gut and Liver2025 · 제19권 제4호

이 간행물의 다른 논문 (29건)