Pharmacokinetic Interaction between Tanshinones and Polyphenolic Extracts of Salvia miltinorrhiza BUNGE after Intravenous Administration in Rats

Abstract

The dry roots of Salvia miltiorrhiza, also called "Danshen" in Chinese, are a well-known traditional Chinese medicinal herb. Because of its better performance and fewer side effects confirmed during the long-time clinical use, Danshen is widely used in traditional Chinese medicinal preparations to treat a number of coronary heart diseases, especially angina pectoris and myocardial infarction. [1][2][3][4] At present, a variety of Danshen products are commercially available, such as Fufang Danshen Tablets and Fufang Danshen Dripping pills, which are the two most commonly used ones in China and these have been officially listed in the Chinese Pharmacopoeia 2005. 5)According to their chemical structures, the major bioactive constituents in S. miltiorrhiza BUNGE can be classified into two groups: the tanshinone compounds, which belong to a group of lipid-soluble diterpenoids, and water-soluble polyphenolic compounds.6) The major lipophilic components are cryptotanshinone, tanshinone I and tanshinone IIA (TSIIA). Pharmacological tests have revealed that TSIIA possesses a variety of pharmacological activities including antioxidant effects, 7) prevention of angina pectoris and myocardial infarction, 8) as well as antineoplastic, 9) anticancer, 10,11) and anti-inflammatory effects.12) The major hydrophilic components include danshensu, protocatechuic aldehyde and salvianolic acid B (Sal B). Sal B is the most common component in the Salvia species and the most abundant in their aqueous extracts. 13,14) Different studies have shown that Sal B has a variety of biological activities including anti-oxidation, 15,16) antifibrotic, 17) and myocardial salvage effects 18) ; it also prevents hepatitis and uremia, 19) and improves blood circulation and renal function. [20][21][22][23][24][25] Considering their prominent pharmacological activities and high content in Danshen, both TSIIA and Sal B have been selected as marker components for the quality control of Danshen and many other medicinal preparations containing Danshen in the 2005 edition of Chinese Pharmacopoeia. 6,12,26) The chemical structures of TanIIA and Sal B are shown in Fig. 1. Recently, Song et al. 27) showed that the pharmacokinetics of cryptotanshinone and TSIIA in rats after oral intra-gavage of an extract of tanshinones was significantly affected by the co-present tanshinones. Also, Sal B had a lower effective concentration in vitro angiogenesis study than the crude extract. 28) In clinical practice, most Danshen products used consist of tanshinone and polyphenolic extracts at the same time.5) However, there have been no reports of pharmacokinetic interactions between tanshinones and polyphenolic extracts of S. miltiorrhiza BUNGE in vivo.To date, several methods have been established for the de- The objective of this study was to investigate the interaction between tanshinones and polyphenolic extracts of Salvia miltiorrhiza BUNGE in rats. The rats in the medium dose groups were given an intravenous administration of 10 mg/kg tanshinones extract-loaded emulsi...

Pharmacokinetic interactions induced by content variation of major water-soluble components of Danshen preparation in rats

“…Therefore, definite pharmacokinetic interactions may be identified. By contrast, Guo et al could not identify which component in tanshinone extracts leads to significant pharmacokinetic alteration of Sal B [22] . Furthermore, the magnitude and the order of the pharmacokinetic sensitivities of various components in Danshen injection could not be obtained from the results.…”

“…In recent years there have been some reports on the pharmacokinetic interactions of danshen [4,22,23] . For example, Song et al showed the pharmacokinetics of cryptotanshinone and tanshinone IIA to be significantly affected by the oral administration of tanshinone extract in rats [4] .…”

“…For example, Song et al showed the pharmacokinetics of cryptotanshinone and tanshinone IIA to be significantly affected by the oral administration of tanshinone extract in rats [4] . Guo et al also investigated the pharmacokinetic interactions between tanshinones and polyphenolic extracts of Salvia miltiorrhiza in rats and found the AUC of tanshinone IIA and Sal B increased remarkably after giving the mixture of tanshinones and polyphenolic extracts [22] . However, these studies are unable to clarify which component contributes to the pharmacokinetic interactions.…”

Effects of Salvia miltiorrhiza on CNS Neuronal Injury and Degeneration: A Plausible Complementary Role of Tanshinones and Depsides

“…The low urinary excretion of LSB (0.58%) also indicated that renal secretion is not the main excretion pathway [69]. An interesting study was conducted with the aim to evaluate the pharmacokinetic interaction between tanshinones and depsides [70]. Rats were administered i. v. with an emulsion of 10 mg/kg tanshinone extract (equivalent to 4.0 mg/kg TSIIA), 100 mg/kg depside extract solution (equivalent to 61.2 mg/kg SalB), or a mixed extract-loaded emulsion (equivalent to 4.0 mg/kg TSIIA and 61.2 mg/kg SalB).…”

“…However, no significant differences in the t 1/2 of TSIIA and SalB in the mixed extract-loaded emulsion groups were found compared with that of the corresponding extract groups, except for the high dose groups of TSIIA (p < 0.05). Therefore, a pharmacokinetic interaction occurs between tanshinones and depsides after i. v. administration in rats, which affects the pharmacokinetic process of TSIIA and SalB in vivo [70]. To the best of our knowledge, only one study estimated the pharmacokinetics of depsides in the rat blood and brain by microdialysis sampling [71].…”