Research and Development of Natural Product Tanshinone I: Pharmacology, Total Synthesis, and Structure Modifications

Abstract

Salvia miltiorrhiza (S. miltiorrhiza), which has been used for thousands of years to treat cardiovascular diseases, is a well-known Chinese medicinal plant. The fat-soluble tanshinones in S. miltiorrhiza are important biologically active ingredients including tanshinone I, tanshinone IIA, dihydrotanshinone, and cryptotanshinone. Tanshinone I, a natural diterpenoid quinone compound widely used in traditional Chinese medicine, has a wide range of biological effects including anti-cancer, antioxidant, neuroprotective, and anti-inflammatory activities. To further improve its potency, water solubility, and bioavailability, tanshinone I can be used as a platform for drug discovery to generate high-quality drug candidates with unique targets and enhanced drug properties. Numerous derivatives of tanshinone I have been developed and have contributed to major advances in the identification of new drugs to treat human cancers and other diseases and in the study of related molecular mechanisms. This review focuses on the structural modification, total synthesis, and pharmacology of tanshinone I. We hope that this review will help understanding the research progress in this field and provide constructive suggestions for further research on tanshinone I.

A clinical experience-based Chinese herbal formula improves ethanol-induced drunken behavior and hepatic steatohepatitis in mice models

“…Lithospermic acid B exerted anti-steatotic and anti-inflammatory effects against alcoholic liver injury by inducing SIRT1-mediated inhibition of CRP and ChREBP expression [ 59 ] and it could also alleviate acute ethanol-induced hepatocyte apoptosis through SIRT1-mediated deacetylation of p53 pathway [ 34 ]. Tanshinone I, dihydromyricetin, and chlorogenic acid have been reported to have certain preventive or therapeutic effects on alcoholic liver disease, nonalcoholic liver disease or inflammatory diseases [ 29 , 42 , 50 ]. Chlorogenic acid (of 169 μg/g in BGXJW) and dihydromyricetin (of 100 μg/g in BGXJW) protect liver function via altering lipid metabolism and enhancing alcohol metabolism, [ 5 , 47 ].…”

Tanshinone I induces ferroptosis in gastric cancer cells via the KDM4D/p53 pathway

“…While there have been numerous studies on the use of Tan IIA in gastric cancer, 8,14 research on Tan I in this context is limited, with only one article discussing its role in inducing apoptosis in gastric cancer. 27 However, it is worth noting that the cell lines used in the experiment (BGC823 and SGC7901) were suspected to be contaminated with HeLa cells, which may jeopardize the reliability of the conclusion. 23 Therefore, it is essential to further investigate the role of Tan I in gastric cancer and elucidate its underlying mechanism.…”

PLA2G2A Phospholipase Promotes Fatty Acid Synthesis and Energy Metabolism in Pancreatic Cancer Cells with K-ras Mutation

“…Although there is currently no specific inhibitor of PLA2G2A for the clinical treatment of cancer, tanshinone I has been reported to inhibit PLA2G2A and could disrupt cellular PUFA metabolism for the synthesis of eicosanoids [ 23 ]. This compound has been shown to exert antitumor effects by inducing apoptosis through the generation of reactive oxygen species in human hepatocellular carcinoma [ 34 ] and endometrial cancer cells [ 35 ], and has been shown to inhibit cell proliferation by blocking the cell cycle and autophagy in various tumor cell models [ 36 ]. Recently, tanshinone I was also proposed as an inhibitor of the enhancer of zeste homolog 2 (EZH2) [ 37 ], suggesting that tanshinone I might be a multi-targeting compound, and its biological effect is likely the combined results of its actions on multiple targets.…”