Salvia miltiorrhiza in diabetes: A review of its pharmacology, phytochemistry, and safety

Background: Salvia miltiorrhiza (SM), one of the frequently used herbs in traditional Chinese medicine (TCM), has now attracted rising interests for a possible alternative in the management of diabetes. This review is aimed to providing a comprehensive perspective of SM in phytochemical constituents, pharmacological activities against diabetes and its complications, and safety. Methods: A comprehensive search of published literatures was conducted to locate original publications pertaining to SM and diabetes till the end of 2017 using PubMed, China National Knowledge Infrastructure, National Science and Technology Library, China Science and Technology Journal Database, and Web of Science database. The main inquiry was used for the presence of the following keywords in various combinations in the titles and abstracts: Salvia miltiorrhiza, diabetes, obesity, phytochemistry, pharmacology, and safety. About 200 research papers and reviews were consulted. Results: SM exhibited anti-diabetic activities by treating macro-and micro-vascular diseases in preclinical experiments and clinical trials through an improvement of redox homeostasis and inhibition of apoptosis and inflammation via the regulation of Wnt/beta-catenin, TSP-1/TGF-beta 1/STAT3, JNK/PI3K/Akt, kinin B2 receptor-Akt-GSK-3 beta, AMPK beta/PGC-1 alpha/Sirt3, Akt/AMPK, TXNIP/NLRP3, TGF-beta 1/NF-kappa B, mineralocorticoid receptor/Na+/K+-ATPase, AGEs/RAGE, Nrf2/Keap1, CaMKK beta/AMPK, AMPK/ACC, IRS-1/PI3K signaling pathways, and modulation of K+-Ca2+ channels, as well as influence of VEGF, NOS, AGEs, PPAR expression and hIAPP aggregation. The antidiabetic effects of this herb may be related to its TCM characters of improving blood circulation and reliving blood stasis. The main ingredients of SM included salvianolic acids and diterpenoid tanshinones, which have been well studied in the diabetic animals. Acute and subacute toxicity studies supported the notion that SM is well tolerated. Conclusion: SM may offer a new strategy for prevention and treatment of diabetes and its complications that stimulates extensive research into identifying potential anti-diabetic compounds and fractions as well as exploring the underlying mechanisms of this herb. Further scientific evidences are still required from well-designed preclinical experiments and clinical trials on its anti-diabetic effects and safety.