The Protective Effects and Mechanism of Mulberry Leaf Flavonoids on Type 2 Diabetic Nephropathy Mice

Huajie Hu; Yanna Guo; Leifang Zhang; Ke Li

doi:10.62767/jecacm504.7832

Authors

Huajie Hu Department of Pharmacy, Zhoushan Hospital of Traditional Chinese Medicine, 316000 Zhoushan, Zhejiang, China Author
Yanna Guo Department of Pharmacy, Zhoushan Hospital of Traditional Chinese Medicine, 316000 Zhoushan, Zhejiang, China Author
Leifang Zhang College of Food and Pharmacy, Zhejiang Ocean University, 316000 Zhoushan, Zhejiang, China Author
Ke Li School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, 310053 Hangzhou, Zhejiang, China Author

DOI:

https://doi.org/10.62767/jecacm504.7832

Keywords:

mulberry leaf flavonoids, diabetic nephropathy, anti-oxidation, Nrf2/HO-1 signaling pathway

Abstract

Purpose: This study investigated the protective effects and mechanism of mulberry leaf flavonoids on type 2 diabetic nephropathy (DN) in mice. Methods: The DPPH free radical scavenging activity of mulberry leaf flavonoids was measured in vitro. To establish a type 2 DN model, male ICR mice were induced with streptozotocin (STZ) after a high-fat diet regimen. The mice were then divided into groups: a normal control group, a DN model group (DM), a positive control group receiving 200 mg/kg metformin (Met group), and a treatment group receiving 1 g/kg mulberry leaf flavonoids (FM group). Both Met and FM groups received daily intragastric administration for 4 weeks, while the DM and control groups were given equivalent volumes of normal saline. Fasting blood glucose levels were recorded regularly during the intervention. After the treatment period, serum creatinine (CRE), blood urea nitrogen (BUN), superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, and renal glutathione peroxidase (GPx) activity were measured. Additionally, kidney histopathological changes and glycogen deposition were evaluated by HE and PAS staining, while Nrf2 and HO-1 expression in kidney tissue was assessed through immunohistochemistry. Results: Mulberry leaf flavonoids effectively scavenged free radicals, significantly reduced blood glucose levels, CRE, BUN, and MDA in serum and kidney tissues, and increased SOD and GPx activities. Histopathological improvements in kidney and pancreatic tissues were observed, alongside increased Nrf2 and HO-1 expression. Conclusions: Mulberry leaf flavonoids ameliorate renal damage in DN mice, potentially through oxidative stress reduction and activation of the Nrf2/HO-1 signaling pathway.

References

Li J, Huang H, Tao L, et al. Research progress on main pathogenesis of diabetic nephropathy. Life Sciences 2023; 35(03): 396-404.

American Diabetes Association. 11. Microvascular complications and foot care: standards of medical care in diabetes-2021. Diabetes Care 2021; 44(Suppl 1): S151-S167.

Umanath K, Lewis JB. Update on Diabetic Nephropathy: Core Curriculum 2018. American Journal of Kidney Diseases 2018; 71(6): 884-895.

Yang C, Wang H, Zhao X, et al. CKD in China: Evolving Spectrum and Public Health Implications. American Journal of Kidney Diseases 2019; 76(2): 258-264.

Zu G, Sun K, Li L, et al. Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus. Scientific Reports 2021; 11(1): 22959.

Wu H, Fu L, Zhao Y, et al. Platycodin D improves renal injury in diabetic nephropathy model rats by regulating oxidative stress mediated PI3K/Akt/mTOR signaling pathway. Chinese Journal of Pharmacology and Toxicology 2022; 36(3): 170-176.

Zhong Y, Luo R, Liu Q, et al. Jujuboside A ameliorates high fat diet and streptozotocin induced diabetic nephropathy via suppressing oxidative stress, apoptosis,and enhancing autophagy. Food and Chemical Toxicology 2022; 159(11): 112697.

Zhong Y, Liu J, Sun D, et al. Dioscin relieves diabetic nephropathy via suppressing oxidative stress and apoptosis, and improving mitochondrial quality and quantity control. Food & Function 2022; 13(6): 3660-3673.

Wang H, Hua C, He Q, et al. Study on the mechanism of treating diabetic nephropathy with traditional Chinese medicine based on oxidative stress pathway. Modern Journal of Integrated Traditional Chinese and Western Medicine 2022; 31(11): 1558-1562,1591.

Luo W, Feng J, Wang L, et al. Research Progress in Mulberry Leaf Flavonoids. Chemistry & Bioengineering 2021; 38(7): 8-13.

Meng Q, Qi M, Chen C, et al. Mulberry leaf flavonoids improve skeletal muscle mitochondrial function by activating the AMPK pathway in type 2 diabetic mice. Journal of Ethnopharmacology 2020; 248: 112326.

Cheng Y, Li X, Xu P, et al. Activation of brown adipose tissue and induction of white adipose tissue browning by mulberry leaf flavonoids contribute to improved glucose metabolism in type 2 diabetic models. British Journal of Nutrition 2022; 127(6): 810-822.

Huang J, Ren N, Zhen C. Study on the Extracting Condition of the Flavonoid Compounds from Mulberry Leaves. Jiangxi Chemical Industry 2005; 2(29): 82-84.

Su W, Wan L, Jian S, et al. Extraction, Purification and Antioxidant Activity of Total Flavonoids from Mulberry Leaves. Science and Technology of Food Industry 2020; 41(10): 151-156.

Loboda A, Damulewicz M, Pyza E, et al. Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism. Cellular and Molecular Life Sciences 2016; 73(17): 3221-3247.

Zhong Y, Wang L, Han X, et al. Optimization of Simultaneous Ultrasonic-Assisted Extraction of Total Flavonoids and Tannins from Mulberry Leaves. Food Science 2015; 36(12): 44-48.

Wang W, Zhang S, Zhu X, et al. Protective effects and mechanisms of mulberry leaf flavonoids on renal interstitial fibrosis in type 1 diabetic mice. Chinese Pharmacological Bulletin 2017; 33(9): 1278-1285.

Ma J, Li D, Ma X, et al. Study on Extraction, Purification of Flavonoids from Morus alba. China Pharmacy 2010; 21(23): 2142-2144.

Levey AS, James MT. Acute kidney injury. Annals of Internal Medicine 2017; 167(9): ITC66-ITC80.

Huang Y, Liu W, Liu J, et al. Association of urinary sodium excretion and diabetic kidney disease in patients with type 2 diabetes mellitus: A cross-sectional study. Frontiers in Endocrinology 2021; 12(10): 772073.

Li Y, Wu Y, Chen L, et al. Anti-inflammatory effects of Nrf2 activation in diabetic nephropathy. Journal of Diabetes Research 2019; 2019: 1-10.

Bai X, Zhang X, Chen L, et al. The role of Nrf2 in oxidative stress and inflammation in diabetic nephropathy. Free Radical Biology and Medicine 2018; 120: 484-495.

Wu Q, Zhang X, Wang L, et al. Sulforaphane protects against diabetic nephropathy via promoting Nrf2 expression and function. American Journal of Translational Research 2017; 9(11): 4974-4982.

He L, Peng X, Zhu J, et al. Cinnamic aldehyde ameliorates oxidative stress and fibrosis in diabetic nephropathy via activation of Nrf2/HO-1 pathway. Phytomedicine 2020; 69: 153206.