Comparative pharmacokinetics and tissue distribution of cryptotanshinone, tanshinone IIA, dihydrotanshinone I, and tanshinone I after oral administration of pure tanshinones and liposoluble extract of Salvia miltiorrhiza to rats

Abstract

Salvia miltiorrhiza is one of the most commonly used traditional Chinese medicines in the treatment of cardiovascular and cerebrovascular diseases. Cryptotanshinone (CTS), tanshinone IIA (Tan IIA), dihydrotanshinone I (diTan I), and tanshinone I (Tan I) are the main active compounds in the liposoluble extract of Salvia miltiorrhiza. The differences in the pharmacokinetic and tissue distribution behaviors of the four tanshinones after oral administration of the liposoluble extract of Salvia miltiorrhiza and pure compounds are not clear. This study aims to compare the pharmacokinetics and tissue distribution of the four tanshinones after oral administration of pure tanshinone monomers and the liposoluble extract of Salvia miltiorrhiza. An ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis method was developed for the determination of the four tanshinones. Theresults showed that the AUC and C max of tanshinones in rats receiving the extract of Salvia miltiorrhiza were significantly increased compared with those receiving the pure tanshinones. In the tissue distribution experiments, the AUC of the four tanshinones in the extract was much greater than the AUC of the monomers in the lung, heart, kidney, liver, and brain, and the coexisting constituents particularly promoted the distribution of tanshinones into tissues that the drug cannot sufficiently penetrate. These findings suggested that the coexisting constituents in the liposoluble extract of Salvia miltiorrhiza play an important role in the alteration of plasma concentration and tissue distribution of the four tanshinones. Understanding these differences could be of significance for the development and application of Salvia miltiorrhiza extract and tanshinone components.

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

“…The content of aforementioned components in Salvia depends on the isolation method (Wang et al, 2020). Recently, we have found that CT is a potential plant derived‐natural compound that can be used in treatment of different disorders.…”

Monoamine Oxidase Inhibition by Major Tanshinones From Salvia Miltiorrhiza and Selective Muscarinic Acetylcholine M4 Receptor Antagonism by Tanshinone I

“…and Dtan I, 1 had the most extended half-life 41 . The ability of 1 to protect from hepatotoxicity was observed by Park et al (2009), which conforms with the predicted non-hepatotoxic property 21,42 .…”

“…Also, the combination of tanshinones had greater bioavailability (represented by the area under the curve and maximum concentration values) than single tanshinones administered orally, except for 1 and Dtan I, which showed similar pharmacokinetic values compared to that of the tanshinone mixture. Among tanshinones 1, 2, 3, and Dtan I, 1 had the most extended half-life 41 . The ability of 1 to protect from hepatotoxicity was observed by Park et al (2009), which conforms with the predicted non-hepatotoxic property 21,42 .…”

Cryptotanshinone enhances the efficacy of Bcr-Abl tyrosine kinase inhibitors via inhibiting STAT3 and eIF4E signalling pathways in chronic myeloid leukaemia

“…The poor aqueous solubility and oral bioavailability of CPT may also limit its bioactivities and physicochemical properties in vivo. The oral administration of CPT was reported to be distributed rapidly and widely in rats, with the highest concentrations in liver, lung and kidney (Wang et al 2020). Furthermore, the plasma concentration of CPT was remarkably enhanced in rats receiving the liposoluble extract from Salvia miltiorrhiza comparing with that receiving pure compound, providing potential strategy to increase the antitumor effects of CPT (Wang et al 2020).…”

“…The oral administration of CPT was reported to be distributed rapidly and widely in rats, with the highest concentrations in liver, lung and kidney (Wang et al 2020). Furthermore, the plasma concentration of CPT was remarkably enhanced in rats receiving the liposoluble extract from Salvia miltiorrhiza comparing with that receiving pure compound, providing potential strategy to increase the antitumor effects of CPT (Wang et al 2020). However, both of the dosage and approach of CPT administration as well as the CML mouse modelling method need to be improved to further confirm the antileukemia effect of CPT in vivo.…”