ABSTRACT
Ramulus Mori (Sangzhi) alkaloids (SZ-A) are a group of polyhydroxy alkaloids extracted and isolated from the traditional Chinese medicine mulberry twig, which is mainly used for the treatment of type 2 diabetes mellitus (T2DM). In addition to acting as a glycosidase inhibitor in the small intestine after oral administration, SZ-A can also be absorbed into blood and widely distributed to target organs related to diabetes, exerting multiple pharmacological effects. It is important to elucidate the possible pharmacokinetic influences of SZ-A for its clinical rational applications, such as drug interactions, the effects of food and alcohol on the absorption of SZ-A. However, studies in this area are limited. Therefore, the pharmacokinetic interactions between orally administrated SZ-A (50 mg·kg-1) and metformin hydrochloride (Met, 200 mg·kg-1) in Sprague-Dawley (SD) rats were examined. Then, the effect of food (standard feed) on the pharmacokinetics of SZ-A was investigated using fasting administration of SZ-A (50 mg·kg-1) in rats as a control. Finally, we investigated the pharmacokinetic characteristics of SZ-A (50 mg·kg-1) in different concentrations alcohol solutions using aqueous solution of SZ-A administered to rats as a control to evaluate the effect of alcohol on the bioabsorption of SZ-A. The results showed no significant pharmacokinetic interactions between SZ-A and Met after combination treatment. The standard feed had little effect on the pharmacokinetic profile of SZ-A. Alcohol retarded the absorption of SZ-A, resulting in a significant decrease in the Cmax of SZ-A. The decrease was greater at higher alcohol concentrations; however, no significant difference was observed in the AUC0-t. These results support the clinical rational applications of SZ-A. All animal protocols were approved by the Ethics Committee of Kangtai Medical Laboratory Service Hebei Co., Ltd. (Hebei, China) (No. MDL2022-01-17-1).
ABSTRACT
The herb pair is the simple and exquisite experience summary accumulated by generations of traditional Chinese medicine (TCM) experts in the process of long-term herbal prescription for curing diseases. Although it is only a combination of two herbs, it is cleverly matched and properly proportioned, which can well interpret TCM characteristics of "great combination and artful application". Moreover, the herb pair is an intermediate point between single herb and several TCM formulae, which implicates certain regularity and some connotation of many TCM formulae for diagnosis and treatment based on an overall analysis of the illness and the patient's condition. Our team has long been focusing on the complexity of drug interactions and the diversity of TCM components to carry out systematic research on herb pair by using modern scientific and technological knowledge and approaches. As results, a series of modern research approaches and strategies formed for the compatibility effect and bio-active components of the herb pair. By representing the principles and application characteristics of these approaches, this paper provides important support for elucidating scientific connotation of compatibility regularity of herb pairs and application of formulae optimization, as well as explorative ideas and approaches for modern research on other herb pairs.
ABSTRACT
This study aimed to evaluate the effects of Jiawei Foshou San capsule (JWFSSC) on CYP1A2, CYP2C6, CYP2D2, CYP2E1 and CYP3A1/2 enzyme activities in rat liver microsomes in vitro and in vivo, and to provide pharmacokinetic data for its combined use with other medicines. After incubating liver microsomes with a cocktail of probe drugs, the metabolites were quantitated with LC-MS/MS to assess the CYP enzyme activity. The hepatic pathological changes were evaluated by histology after hematoxylin and eosin (HE) staining. With the dose range up to 3 200 mg·L-1, the IC50 of JWFSSC for CYP2D2, CYP2E1 and CYP3A1/2 in vitro was 229.3 mg·L-1, 361.9 mg·L-1 and 274.6 mg·L-1 respectively. Compared with the vehicle control group, the enzyme activities of CYP1A2, CYP2C6 and CYP3A1/2 showed a significant increase in animals given JWFSSC 180 mg·kg-1·d-1 (P<0.01). Based on histology, several pathological changes were observed in JWFSSC groups: there was less inflammatory infiltration compared to the tetrahydropalmatine (THP) group. These results of inhibition in vitro and induction in vivo suggest a strengthened efficacy and a prolonged effective time of drugs metabolized by CYP2D2 and CYP2E1 enzymes when combined with JWFSSC in use. The dosage of parent drugs should be appropriately reduced when used in combination with JWFSSC. However, if a drug is metabolized by CYP1A2 and CYP2C6 when used in combination with JWFSSC, the effect of the drug is likely reduced and the dosage should be increased appropriately. In addition, the combination of ferulic acid (FA), ligustrazine (LZ) and THP can significantly reduce the toxicity of THP in rat livers. In this study, the program of animal testing had been approved by Committee on the management and usage of experimental animal in the College of Pharmaceutical Sciences, Southwest University.