Natural diosmin alleviating obesity and nonalcoholic fatty liver disease by regulating the activating the AMP-activated protein kinase (AMPK) pathway

Can Liu , Siyu Hao , Mengdi Zhang , Xueyu Wang , Baiwang Chu , Tingjie Wen , Ruoyu Dang , Hua Sun

Chinese Journal of Natural Medicines ›› 2025, Vol. 23 ›› Issue (7) : 863 -870.

PDF (16370KB)
Chinese Journal of Natural Medicines ›› 2025, Vol. 23 ›› Issue (7) :863 -870. DOI: 10.1016/S1875-5364(25)60914-9
Original article
research-article

Natural diosmin alleviating obesity and nonalcoholic fatty liver disease by regulating the activating the AMP-activated protein kinase (AMPK) pathway

Author information +
History +
PDF (16370KB)

Abstract

Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are linked to numerous chronic conditions, including cardiovascular disease, atherosclerosis, chronic kidney disease, and type II diabetes. Previous research identified the natural flavonoid diosmin, derived from Chrysanthemum morifolium, as a regulator of glucose metabolism. However, its effects on lipid metabolism and underlying mechanisms remained unexplored. The AMP-activated protein kinase (AMPK) pathway serves a critical function in glucose and lipid metabolism. The relationship between diosmin and the AMPK pathway has not been previously documented. This investigation examined diosmin's capacity to reduce lipid content through AMPK pathway activation in hepatoblastoma cell line G2 (HepG2) and 3T3-L1 cells. The study revealed that diosmin inhibits lipogenesis, indicating its potential as an anti-obesity agent in obese mice. Moreover, diosmin demonstrated effective MASLD alleviation in vivo. These findings suggest that diosmin may represent a promising therapeutic candidate for treating obesity and MASLD.

Keywords

Diosmin / Lipometabolism / AMP-activated protein kinase / Obesity / Metabolic dysfunction-associated steatotic liver disease

Cite this article

Download citation ▾
Can Liu, Siyu Hao, Mengdi Zhang, Xueyu Wang, Baiwang Chu, Tingjie Wen, Ruoyu Dang, Hua Sun. Natural diosmin alleviating obesity and nonalcoholic fatty liver disease by regulating the activating the AMP-activated protein kinase (AMPK) pathway. Chinese Journal of Natural Medicines, 2025, 23(7): 863-870 DOI:10.1016/S1875-5364(25)60914-9

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Benavente-Garcia O, Castillo J. Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity. J Agric Food Chem. 2008; 56(15):6185-6205. https://doi.org/10.1021/jf8006568.

[2]

Inoue T, Sugimoto Y, Masuda H, et al. Antiallergic effect of flavonoid glycosides obtained from Mentha piperita L. Biol Pharm Bull. 2002; 25(2):256-259. https://doi.org/10.1248/bpb.25.256.

[3]

Cheng C, Zhang H, Li Y, et al. The effect of diosmin on the blood proteome in a rat model of venous thrombosis. Int J Biol Macromol. 2017; 104(Pt A):778-787. https://doi.org/10.1016/j.ijbiomac.2017.06.045.

[4]

Giannini I, Amato A, Basso L, et al. Flavonoids mixture (diosmin, troxerutin, hesperidin) in the treatment of acute hemorrhoidal disease: a prospective, randomized, triple-blind, controlled trial. Tech Coloproctol. 2015; 19(6):339-345. https://doi.org/10.1007/s10151-015-1302-9.

[5]

Bush R, Comerota A, Meissner M, et al. Recommendations for the medical management of chronic venous disease: the role of micronized purified flavanoid fraction (MPFF). Phlebology. 2017; 32(1_suppl):3-19. https://doi.org/10.1177/0268355517692221.

[6]

Shalkami AS, Hassan M, Bakr AG. Anti-inflammatory, antioxidant and anti-apoptotic activity of diosmin in acetic acid-induced ulcerative colitis. Hum Exp Toxicol. 2018; 37(1):78-86. https://doi.org/10.1177/0960327117694075.

[7]

Gopalakrishnan V, Iyyam PS, Subramanian SP. Synthesis, spectral characterization, and biochemical evaluation of antidiabetic properties of a new zinc-diosmin complex studied in high fat diet fed-low dose streptozotocin induced experimental type 2 diabetes in rats. Biochem Res Int. 2015;2015:350829. https://doi.org/10.1155/2015/350829.

[8]

Islam J, Shree A, Afzal SM, et al. Protective effect of diosmin against benzo(a)pyrene-induced lung injury in Swiss albino mice. Environ Toxicol. 2020; 35(7):747-757. https://doi.org/10.1002/tox.22909.

[9]

Chen M, Wang K, Zhang Y, et al. New insights into the biological activities of Chrysanthemum morifolium: natural flavonoids alleviate diabetes by targeting α-glucosidase and the PTP-1B signaling pathway. Eur J Med Chem. 2019; 178:108-115. https://doi.org/10.1016/j.ejmech.2019.05.083.

[10]

Younossi Z, Anstee QM, Marietti M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018; 15(1):11-20. https://doi.org/10.1038/nrgastro.2017.109.

[11]

Byrne CD, Targher G.NAFLD: a multisystem disease. J Hepatol. 2015; 52(1 Suppl):S47-64. https://doi.org/10.1016/j.jhep.2014.12.012.

[12]

Després JP, Lemieux I, Bergeron J, et al. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol. 2008; 28(6):1039-1049. https://doi.org/10.1161/ATVBAHA.107.159228.

[13]

Pouwels S, Sakran N, Graham Y, et al. Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss. BMC Endocr Disord. 2022; 22(1):63. https://doi.org/10.1186/s12902-022-00980-1.

[14]

Guo X, Yin X, Liu Z, et al. Non-alcoholic fatty liver disease (NAFLD) pathogenesis and natural products for prevention and treatment. Int J Mol Sci. 2022; 23(24):15489. https://doi.org/10.3390/ijms232415489.

[15]

Alqahtani SA, Schattenberg JM.NAFLD in the elderly. Clin Interv Aging. 2021; 16:1633-1649. https://doi.org/10.2147/CIA.S295524.

[16]

Rong L, Zou J, Ran W, et al. Advancements in the treatment of non-alcoholic fatty liver disease (NAFLD). Front Endocrinol (Lausanne). 2023;13:1087260. https://doi.org/10.3389/fendo.2022.1087260.

[17]

Xu R, Pan J, Zhou W, et al.Recent advances in lean NAFLD. Biomed Pharmacother. 2022;153:113331. https://doi.org/10.1016/j.biopha.2022.113331.

[18]

Grahame HD. Regulation of AMP-activated protein kinase by natural and synthetic activators. Acta Pharm Sin B. 2016; 6(1):1-19. https://doi.org/10.1016/j.apsb.2015.06.002.

[19]

Beg ZH, Allmann DW, Gibson DM. Modulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity with cAMP and with protein fractions of rat liver cytosol. Biochem Bioph Res Commun. 1973; 54(4):1362-1369. https://doi.org/10.1016/0006-291X(73)91137-6.

[20]

Novikova DS, Garabadzhiu AV, Melino G, et al. AMP-activated protein kinase: structure, function, and role in pathological processes. Biochemistry (Moscow). 2015; 80(2):127-144. https://doi.org/10.1134/S0006297915020017.

[21]

Carlson CA, Kim KH. Regulation of hepatic acetyl coenzyme A carboxylase by phosphorylation and dephosphorylation. J Biol Chem. 1973; 248(1):378-380. https://doi.org/10.1016/S0021-9258(19)44486-4.

[22]

Wang Q, Liu S, Zhai A, et al. AMPK-mediated regulation of lipid metabolism by phosphorylation. Biol Pharm Bull. 2018; 41(7):985-993. https://doi.org/10.1248/bpb.b17-00724.

[23]

Huang R, Guo F, Li Y, et al. Activation of AMPK by triptolide alleviates nonalcoholic fatty liver disease by improving hepatic lipid metabolism, inflammation and fibrosis. Phytomedicine. 2021;92:153739. https://doi.org/10.1016/j.phymed.2021.153739.

[24]

Gao L, Xu Z, Huang Z, et al. CPI-613 rewires lipid metabolism to enhance pancreatic cancer apoptosis via the AMPK-ACC signaling. J Exp Clin Cancer Res. 2020; 39(1):73. https://doi.org/10.1186/s13046-020-01579-x.

[25]

Zhang M, Wang Z, Hao S, et al. Synthesis of natural 3'-prenylchalconaringenin and biological evaluation of ameliorating non-alcoholic fatty liver disease and metabolic syndrome. Eur J Med Chem. 2020;205:112649. https://doi.org/10.1016/j.ejmech.2020.112649.

[26]

Xie L, Yuan Y, Xu S, et al. Downregulation of hepatic ceruloplasmin ameliorates NAFLD via SCO1-AMPK-LKB1 complex. Cell Rep. 2022; 41(3):111498. https://doi.org/10.1016/j.celrep.2022.111498.

[27]

Garcia D, Hellberg K, Chaix A, et al. Genetic liver-specific AMPK activation protects against diet-induced obesity and NAFLD. Cell Rep. 2019; 26(1):192-208.e196. https://doi.org/10.1016/j.celrep.2018.12.036.

[28]

Poornima MS, Sindhu G, Billu A, et al. Pretreatment of hydroethanolic extract of Dillenia indica L. attenuates oleic acid induced NAFLD in HepG2 cells via modulating SIRT-1/p-LKB-1/AMPK, HMGCR & PPAR-α signaling pathways. J Ethnopharmacol. 2022;292:115237. https://doi.org/10.1016/j.jep.2022.115237.

[29]

Zhu X, Bian H, Wang L, et al. Berberine attenuates nonalcoholic hepatic steatosis through the AMPK-SREBP-1c-SCD1 pathway. Free Radic Biol Med. 2019; 141:192-204. https://doi.org/10.1016/j.freeradbiomed.2019.06.019.

[30]

Hassan MA, Elmageed GMA, El-Qazaz IG, et al. The synergistic influence of polyflavonoids from Citrus aurantifolia on diabetes treatment and their modulation of the PI3K/AKT/FOXO1 signaling pathways: molecular docking analyses and in vivo investigations. Pharmaceutics. 2023; 15(9):2306. https://doi.org/10.3390/pharmaceutics15092306.

[31]

Gao Y, Chu S, Zhang Z, et al. Hepataprotective effects of ginsenoside Rg1-a review. J Ethnopharmacol. 2017; 206(16):178-183. https://doi.org/10.1016/j.jep.2017.04.012.

[32]

Luo J, Xu Q, Jiang B, et al. Selectivity, cell permeability and oral availability studies of novel bromophenol derivative HPN as protein tyrosine phosphatase 1B inhibitor. Br J Pharmacol. 2018; 175(1):140-153. https://doi.org/10.1111/bph.14080.

[33]

Pang Y, Xu X, Xiang X, et al. High fat activates O-GlcNAcylation and affects AMPK/ACC pathway to regulate lipid metabolism. Nutrients. 2021; 13(6):1740. https://doi.org/10.3390/nu13061740.

[34]

Fang K, Wu F, Chen G, et al. Diosgenin ameliorates palmitic acid-induced lipid accumulation via AMPK/ACC/CPT-1A and SREBP-1c/FAS signaling pathways in LO2 cells. BMC Complement Altern Med. 2019; 19(1):255. https://doi.org/10.1186/s12906-019-2671-9.

[35]

Chen Y, He X, Chen X, et al. SeP is elevated in NAFLD and participates in NAFLD pathogenesis through AMPK/ACC pathway. J Cell Physiol. 2021; 236(5):3800-3807. https://doi.org/10.1002/jcp.30121.

[36]

Mato JM, Alonso C, Noureddin M, et al. Biomarkers and subtypes of deranged lipid metabolism in non-alcoholic fatty liver disease. World J Gastroenterol. 2019; 25(24):3009-3020. https://doi.org/10.3748/wjg.v25.i24.3009.

[37]

Xiao Z, Liu M, Yang F, et al. Programmed cell death and lipid metabolism of macrophages in NAFLD. Front Immunol. 2023;14:1118449. https://doi.org/10.3389/fimmu.2023.1118449.

[38]

Sfikas G, Psallas M, Koumaras C, et al. Prevalence, diagnosis and treatment with 3 different statins of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in military personnel. Do genetics play a role? Curr Vasc Pharmacol. 2021; 19(5):572-581. https://doi.org/10.2174/1570161118666201015152921.

[39]

Polyzos SA, Goulis DG, Giouleme O, et al. Anti-obesity medications for the management of nonalcoholic fatty liver disease. Curr Obes Rep. 2022; 11(3):166-179. https://doi.org/10.1007/s13679-022-00474-0.

[40]

Filippatos TD, Derdemezis CS, Gazi IF, et al. Orlistat-associated adverse effects and drug interactions: a critical review. Drug Saf. 2008; 31(1):53-65. https://doi.org/10.2165/00002018-200831010-00005.

[41]

Gerges SH, Wahdan SA, Elsherbiny DA, et al. Pharmacology of diosmin, a citrus flavone glycoside: an updated review. Eur J Drug Metab Pharmacokinet. 2022; 47(1):1-18. https://doi.org/10.1007/s13318-021-00731-y.

[42]

Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol. 2018; 19(2):121-135. https://doi.org/10.1038/nrm.2017.95.

PDF (16370KB)

120

Accesses

0

Citation

Detail

Sections
Recommended

/