Pharmacokinetics of Active Ingredients of Salvia miltiorrhiza and Carthamus tinctorius in Compatibility in Normal and Cerebral Ischemia Rats: A Comparative Study

Abstract

Background and Objective Dan-Hong injection, which comprises extracts of Salvia miltiorrhiza and Carthamus tinctorius, promotes blood circulation and reduces blood stasis. Combination of S. miltiorrhiza and C. tinctorius is more effective in treating cerebral ischemia than S. miltiorrhiza alone. This study aimed to examine the pharmacokinetic characteristics of four active ingredients of S. miltiorrhiza and C. tinctorius, namely danshensu (DSS), hydroxysafflor yellow A (HSYA), and salvianolic acid A (SAA) and B (SAB) in normal and cerebral ischemia rats. Methods Normal and cerebral ischemia rats were injected via the tail vein with each active ingredient, and blood was collected through the jaw vein at different time points. The plasma concentration of the compatibility group was analyzed by high-performance liquid chromatography, and pharmacokinetic parameters were determined using Pharmacokinetic Kinetica 4.4 software. Results The pharmacokinetics of the four active ingredients in the normal and cerebral ischemia rats were consistent with a two-compartment model. The area under the concentration-time curve was higher in normal rats than in cerebral ischemia rats, with a highly significant difference for SAA (P < 0.01). Clearance rates were lower in normal rats than in cerebral ischemia rats, with DSS showing the most significant difference (P < 0.01). Furthermore, there were significant differences between normal and cerebral ischemia rats in the distribution phase-elimination half life for DSS, SAA, and HSYA, as well as in the apparent volume of distribution for the central compartment for DSS and HSYA (P < 0.01). The plasma concentrations of the four active ingredients were higher in normal rats than in cerebral ischemia rats. Conclusion Cerebral ischemia rats showed higher drug clearance rates and longer retention times than normal rats, which may be due to destruction of the blood-brain barrier during cerebral ischemia-reperfusion. The four active ingredients likely integrated and interacted with each other to affect target sites in the brain to protect against cerebral ischemic injury.

Comparative pharmacokinetic study on phenolic acids and flavonoids in normal and microcirculation dysfunction rats plasma by UPLC-TQ/MS/MS after oral administration of Salvia miltiorrhiza stem-leaf extracts

“…The bimodal phenomenon of lithospermic acid and salvianolic acid A was observed in both the control and model groups treated with oral FS or FT. However, the results of others [ [35] , [36] , [37] , [38] , [39] ] showed that danshensu, lithospermic acid, and salvianolic acid A did not show a bimodal absorption phenomenon in rats. The bimodal phenomenon of caffeic acid was seen in the control group treated with oral FS or FT. Su's research results [ 40 ] showed that the drug time curve of caffeic acid in rats after oral administration of Shaofu Zhuyu decoction showed a bimodal phenomenon.…”

Nasal administration of nanoencapsulated geraniol/ursodeoxycholic acid conjugate: Towards a new approach for the management of Parkinson's disease

“…Literature data report rat volume of distribution values of drugs ranging from 100 mL/kg to 100 L/kg orders of magnitude. Similarly, clearance values are reported ranging from 1 mL min -1  kg -1 to 10 L min -1  kg -1 orders of magnitude [52][53]. The pharmacokinetic data reported in Table 2 indicate, therefore, that the elimination rate of GER-UDCA from the rat bloodstream is relatively slow.…”

Salviae miltiorrhiza against human lung cancer: A review of its mechanism (Review)

“…In addition, S. miltiorrhiza can also lower blood sugar, regulate intracellular calcium ion concentration, inhibit inflammatory response, resist oxidation and scavenge oxygen free radicals together with other pharmacological effects (30)(31)(32)(33). Modern pharmacological studies have shown that S. miltiorrhiza can be used for the treatment of various diseases, including cerebrovascular disease (34,35), coronary heart disease (36,37), Parkinson's disease (38), Alzheimer's disease (39)(40)(41), peptic ulcers (42), scars (43), chronic kidney disease (44,45), liver cirrhosis (46), osteoporosis, lung cancer and other diseases (40). S. miltiorrhiza is one of the traditional Chinese medicines that can be used as a health food, as announced by the National Health Commission of China (47).…”