Mulberry leaf, as a traditional Chinese medicine with medicinal and food values, is nowadays widely used in the clinical treatment of diabetes and hyperlipidemia. Its active ingredients are mainly flavonoids, polysaccharides, alkaloids and other substances, which have good efficacy in regulating insulin secretion, hypoglycemia and lipid lowering. In recent years, a large number of experimental studies and some clinical studies have proved that mulberry leaf does have hypoglycemic effect, and it is widely available, easy to obtain and low in price. In this paper, we review the research progress on the mechanisms of mulberry leaf inhibition of α-glucosidase activity, promotion of insulin secretion, improvement of pancreatic islet function, promotion of glucose utilization by peripheral tissues, and enhancement of hepatic glycogen. It is expected to provide guidelines for in-depth research on the mechanism of action of mulberry leaves in regulating blood glucose and preventing diabetic complications, and to provide a basis and reference for the development and utilization of mulberry leaf resources.

Chenyu Dou, Tonghua Liu. Research progress on the hypoglycemic effect of mulberry leaves. International Journal of Frontiers in Medicine (2023), Vol. 5, Issue 2: 24-30. https://doi.org/10.25236/IJFM.2023.050205.

[1] Clinical guidelines for the prevention and treatment of type 2 diabetes in the elderly in China (2022 edition) [J]. Chinese Journal of Diabetes, 2022, 30(01): 2-51.

[2] Sun Lian, Meng Lei, Yan Chao, et al. Hypoglycemic active ingredients and pharmacological effects of Morus alba [J]. Chinese herbal medicine, 2002, (05): 90-2.

[3] Zeng C.Y., Li L.Y., Mei Q.X., et al. Research progress on hypoglycemic effect of mulberry leaves [J]. Chinese Journal of Traditional Chinese Medicine, 2016, 34(01): 192-4.

[4] Ma JX.Compilation of and Commentaries on‘Shen Nong’ s Classic of the Materia Medica[M].Beijing: People’s Medical Publishing House,2013: 508－509.

[5] Zhong Nongping, Sun Tingyu, Zhao Xia. Research progress on hypoglycemic mechanism of active ingredients of Morus alba [J]. International Journal of Traditional Chinese Medicine, 2018, 40(02): 182-5.

[6] (Tang) Chen Zangqi; Shang Zhijun, ed. The collection of materia medica [M]. Research Section, Wannan Medical College, 1983.

[7] (Song) Tang Shenwei. The spare Materia Medica [M]. Beijing: People's Health Publishing House, 1982.

[8] He Sheng, Zhou Xingzi, He Hai, et al. Overview of research on alkaloid components of Morus alba [J]. Chinese Journal of Experimental Formulary, 2015, 21(13): 222-6.

[9] Li Feiming, Zhang Guoping, Zou Xiangyue, et al. Research progress on flavonoids of mulberry leaves [J]. China Sericulture, 2015, 36(02): 1-4+10.

[10] Yang JH, Cao JM, Chen B, et al. Progress in the extraction and purification of flavonoids from mulberry leaves and their biological functions [J]. Guangdong Animal Husbandry and Veterinary Science and Technology, 2018, 43(03): 9-15.

[11] SUN Y K, JIAN J G, LEE W C, et al. Antioxidative flavonoids from the leaves of Morus alba [J]. Archives of Pharmacal Research, 1999, 22(1): 81-5.

[12] DOI K, KOJIMA T, MAKINO M, et al. Studies on the constituents of the leaves of Morus alba L [J]. The Pharmaceutical Society of Japan, 2001, (2).

[13] WAN-TAEK J, O-CHUL K, HYUN-BOK K, et al. Qualitative and quantitative analysis of flavonoids from 12 species of Korean mulberry leaves [J]. Journal of food science and technology, 2018, 55(5).

[14] Lv Q, Xia W, Zhang WQ, et al. Isolation, purification and analysis of polysaccharides from Morus alba [J]. Food and Fermentation Industry, 2007, (07): 167-70.

[15] Hu R.F., Li J.Z., Li P.F., et al. Structural characteristics of mulberry leaf polysaccharide and its inhibitory effect on α-glucosidase activity [J]. Journal of Forestry Engineering, 2022, 7(06): 100-6.

[16] Xiong N., Wei S., Hu Z. Ce. Research progress and trends of α-glucosidase inhibitors [J]. Fermentation Science and Technology Letters, 2018, 47(01): 58-64.

[17] LIU C, XIANG W, YU Y, et al. Comparative analysis of 1-deoxynojirimycin contribution degree to α-glucosidase inhibitory activity and physiological distribution in Morus alba L [J]. Industrial Crops & Products, 2015, 70: 309-15.

[18] Ji T, Su Shulan, Guo Sheng, et al. Progress in the study of effector component groups and their mechanism of action of Morus alba against diabetes mellitus [J]. Chinese herbal medicine, 2015, 46(05): 778-84.

[19] Wei Xiaorui. Extraction and purification of 1-deoxynojirimycin from Morus alba and its hypoglycemic activity [D]. Yangzhou University, 2012.

[20] Yao J, Qiao D, Guo X, et al. Therapeutic effects of 1-deoxynojirimycin from mulberry leaves on rats with diabetic nephropathy [J]. Chinese Clinical Pharmacology and Therapeutics, 2018, 23(05): 517-23.

[21] He Xianxia, Chang Huajing, Ocean, et al. Ameliorative effects of Morus alba alkaloids, flavonoids and polysaccharides on insulin resistance in HepG2 cells [J]. Chinese Journal of Experimental Formulary, 2015, 21(02): 192-5.

[22] Ren Chunjiu. Protective effect of Morus alba polysaccharide MLP on oxidative stress injury in pancreatic β-cells of diabetic rats and its mechanism [D]. Shandong Agricultural University, 2015.

[23] Wang Deping, Yu Xiaomin, An Xin, et al. Synergistic hypoglycemic effects of Mulberry leaf multi-component [J]. Modern preventive medicine, 2018, 45(16): 2924-8.

[24] REN C, ZHANG Y, CUI W, et al. A polysaccharide extract of mulberry leaf ameliorates hepatic glucose metabolism and insulin signaling in rats with type 2 diabetes induced by high fat-diet and streptozotocin [J]. International journal of biological macromolecules, 2015, 72: 951-9.

[25] Chen JG, Bu WL, Lai WQ, et al. Study on the hypoglycemic effect of Morus alba polysaccharide and its mechanism [J]. Chinese herbal medicine, 2011, 42(03): 515-20.

[26] ZHANG, REN, CJ, et al. Purification, characterization and anti-diabetic activity of a polysaccharide from mulberry leaf [J]. 2014, 2014,70(3)(-): 687-95.

[27] Chen L L, Liu W, Chen J, et al. Study on the mechanism of blood glucose regulation of mulberry leaf flavonoids in diabetic mice [J]. Chinese Journal of Clinical Pharmacology, 2010, 26(11): 835-8.

[28] Zheng Xiaomao, Ru Qin, Chen Lin, et al. Research progress on the effects and interventions of late glycosylation end products on diabetes and its complications [J]. Chongqing Medicine, 2019, 48(13): 2292-6.

[29] ZHU Y, SHU T, LIN Y, et al. Inhibition of the receptor for advanced glycation endproducts (RAGE) protects pancreatic β-cells [J]. Biochemical and Biophysical Research Communications, 2011.

[30] Yu LY. Study on the hypoglycemic effect of total flavonoids of Morus alba on diabetic rats [D]. Zhejiang University, 2002.

[31] Ji Tao. Study on the effects of mulberry leaves on diabetes mellitus and its mechanism of action [D]. Nanjing University of Traditional Chinese Medicine, 2016.

[32] Cai Yu. Study on the effect of mulberry gourd drink on type 2 diabetes mellitus and its PI3K/Akt signaling pathway mechanism [D]. Hubei University of Traditional Chinese Medicine, 2018.

[33] MENG Q, QI X, CHAO Y, et al. IRS1/PI3K/AKT pathway signal involved in the regulation of glycolipid metabolic abnormalities by Mulberry (Morus alba L.) leaf extracts in 3T3-L1 adipocytes [J]. Chinese Medicine, 2020, 15(1).

[34] Gu Z，Mu H，Shen H，et al. High level of dietary soybean oil affects the glucose and lipid metabolism in large yellow croaker Larimichthys crocea through the insulin-mediated PI3K/AKT signaling pathway[J].Comp Biochem Physiol B Biochem Mol Biol,2019,231:34-41. 

[35] SOUNDHARRAJAN I, KIM D H, SRISESHARAM S, et al. R -Limonene Enhances Differentiation and 2-Deoxy-D-Glucose Uptake in 3T3-L1 Preadipocytes by Activating the Akt Signaling Pathway [J]. Evidence-based Complementary and Alternative Medicine, 2018, 2018: 1-10.

[36] Duan Yuhui, Dai Hongyu, An Yongcheng, et al. Regulation of hepatic lipid metabolism in T2DM rats by total flavonoids of Morus alba based on PPAR-α/CPT-1 signaling pathway and its mechanism [J]. Chinese Journal of Experimental Formulary, 2022, 28(15): 61-9.

[37] Liu Yinghui, Mou Xin, Zhou Diyi, et al. Study on the mechanism of effective ingredients of Morus alba to improve insulin resistance based on JNK signaling pathway [J]. Chinese Journal of Traditional Chinese Medicine, 2019, 44(05): 1019-25.

[38] Luo Mingli. Relationship between the hypoglycemic effect of the active parts of Morus alba and JNK signaling pathway [D]; Guangzhou University of Chinese Medicine, 2013.