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This review aimed to provide a general view of catalpol in protection against diabetes and diabetic complications, as well as its pharmacokinetics and safety concerns. The following databases were consulted with the retrieval of more than 100 publications through June 2019: PubMed, Chinese National Knowledge Infrastructure, WanFang Data, and web of science. Catalpol exerts an anti-diabetic effect in different animal models with an oral dosage ranging from 2.5 to 200 mg/kg in rats and 10 to 200 mg/kg in mice. Besides, catalpol may prevent the development of diabetic complications in kidney, heart, central nervous system, and bone. The underlying mechanism may be associated with an inhibition of inflammation, oxidative stress, and apoptosis through modulation of various cellular signaling, such as AMPK/PI3K/Akt, PPAR/ACC, JNK/NF-κB, and AGE/RAGE/NOX4 signaling pathways, as well as PKCγ and Cav-1 expression. The pharmacokinetic profile reveals that catalpol could pass the blood-brain barrier and has a potential to be orally administrated. Taken together, catalpol is a well-tolerated natural compound with promising pharmacological actions in protection against diabetes and diabetic complications via multi-targets, offering a novel scaffold for the development of anti-diabetic drug candidate. Further prospective and well-designed clinical trials will shed light on the potential of clinical usage of catalpol. [ABSTRACT FROM AUTHOR]

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/β-catenin, TSP-1/TGF-β1/STAT3, JNK/PI3K/Akt, kinin B2 receptor-Akt-GSK-3β, AMPKβ/PGC-1α/Sirt3, Akt/AMPK, TXNIP/NLRP3, TGF-β1/NF-κB, mineralocorticoid receptor/Na+/K+-ATPase, AGEs/RAGE, Nrf2/Keap1, CaMKKβ/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. [ABSTRACT FROM AUTHOR]