Myricetin induces M2 macrophage polarization to alleviate renal tubulointerstitial fibrosis in diabetic nephropathy via PI3K/Akt pathway

World Journal of Diabetes · 9 authors, 9 centres

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TL;DR

This preclinical study used db/db mice and a macrophage cell line to test myricetin for diabetic nephropathy. Myricetin improved kidney function and reduced fibrosis and inflammation by promoting an anti-inflammatory M2 macrophage polarization via the PI3K/Akt pathway.

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Mice received myricetin for 12 weeks, leading to improved renal function, reduced kidney injury markers, and decreased fibrosis and inflammation. In vitro, myricetin inhibited pro-inflammatory M1 macrophage polarization and inflammatory cytokine release. Molecular analyses suggested myricetin targets the PI3K/Akt pathway, and its protective effects were blocked by a PI3K/Akt inhibitor.

STUDY TYPE

other

SPECIALTY

nephrology

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AI pipeline

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100% · A

ORIGINAL PAPER

PMC10835493

Myricetin induces M2 macrophage polarization to alleviate renal tubulointerstitial fibrosis in diabetic nephropathy via PI3K/Akt pathway

World Journal of Diabetes

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ABSTRACT

BACKGROUND Development of end-stage renal disease is predominantly attributed to diabetic nephropathy (DN). Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal tissue. Nevertheless, the precise molecular mechanism through which myricetin influences the progression of DN remains uncertain. AIM To investigate the effects of myricetin on DN and explore its potential therapeutic mechanism. METHODS Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 wk. Subsequently, blood and urine indexes were assessed, along with examination of renal tissue pathology. Kidney morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin, periodic acid–Schiff, Masson’s trichrome, and Sirius-red. Additionally, high-glucose culturing was conducted on the RAW 264.7 cell line, treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 h. In both in vivo and in vitro settings, quantification of inflammation factor levels was conducted using western blotting, real-time qPCR and ELISA. RESULTS In db/db mice, administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and fibrosis. Notably, we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin, along with a decrease in expressions of inflammatory cytokine-related factors. Furthermore, myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha, interleukin-6, and interluekin-1β induced by high glucose in RAW 264.7 cells. Additionally, myricetin modulated the M1-type polarization of the RAW 264.7 cells. Molecular docking and bioinformatic analyses revealed Akt as the target of myricetin. The protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inhibition of PI3K/Akt activation using LY294002. CONCLUSION This study demonstrated that myricetin effectively mitigates kidney injury in DN mice through the regulation of macrophage polarization via the PI3K/Akt signaling pathway.

CITATION EXPORT

Wei-Long Xu, Pei-Pei Zhou, Xu Yu et al.. Myricetin induces M2 macrophage polarization to alleviate renal tubulointerstitial fibrosis in diabetic nephropathy via PI3K/Akt pathway. World Journal of Diabetes. (2024). https://doi.org/10.4239/wjd.v15.i1.105

AUTHORS

9 · 9 CENTRES

Wei-Long Xu, Pei-Pei Zhou, Xu Yu, Ting Tian, Jin-Jing Bao, Chang-Rong Ni, Min Zha, Xiao Wu, Jiang-Yi Yu

Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu Province, China
Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu Province, China
Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu Province, China
Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu Province, China
Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu Province, China
Department of Pharmacy, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu Province, China
Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu Province, China
Department of Pneumology, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu Province, China
Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu Province, China. [email protected]