เภสัชจลนศาสตร์และผลต่อระบบหัวใจและหลอดเลือดของตำรับสารสกัดจากเหง้ากระชายดำด้วยไดคลอโรมีเทนในหนูแรท

Abstract

Kaempferia parviflora (KP) Wall.Ex Baker or black ginger belongs to the family Zingiberaceae, found in the northern part of Thailand. Its rhizome has been used in folk medicine for health promotion. To date, a number of investigations have claimed therapeutic benefit such as: aphrodisiac, anti-inflammatory, anti-hypertensive, cardioprotective, and antiobesity effects. Yorsin et al., 2014 also found that consumption of dichloromethane extract of the KP rhizomes (KPD) by middle-aged male rats caused some beneficial changes in cardiovascular parameters, decreased body fat and up-regulated NO. KPD is poorly water soluble. Thus the present study aimed to enhance the KPD dissolubility by solid dispersion method using Kollicoat® IR (PVA-co-PEG) (K) as an excipient. Pharmacokinetic of the product in the in vivo experiment on adult male rats and its biological activities in the middle-aged male rats were also investigated. Solid dispersion of the KPD was prepared by dissolving KPD and K (1 g per 5 mL dichloromethane) separately and then mixing together at a 1: 1 ratio after dryness to yield homogeneous, powder solid dispersion of KPD (K-KPD). The in vivo pharmacokinetics of the K-KPD were studied in mature male rats by oral gavage of the K-KPD and blood collected from left carotid artery of the anesthetized rat at 0, 30, 60, 90, 120, 180, 240 and 360 min and using the major components of the KPD: PMF, DMF and TMF as markers. Biological activities of the K-KPD were studied in middle-aged male rats after six weeks of oral gavage 200 mg/kg K-KPD, K (100 mg/kg) or distilled water (DW), twice a day. The pharmacokinetic study found that the three major compounds reached their peaks at 90 min after oral gavage of the K-KPD and the concentration of the DMF and TMF were about two-fold that of PMF. Biological activities of the K-KPD, in comparison to control group (DW), K did not affect any of the study parameters. K-KPD caused decreases in body fat and liver cell lipid accumulation, plasma level of glucose and triglycerides, plasma level of alkaline phosphatase, and blood platelets count. K-KPD did not affect basal blood pressure or heart rate in anesthetized rats. K-KPD causes decreased maximal contractile response of thoracic aortic rings to phenylephrine, and this effect disappeared in the presence of DL-propargylglycine (PAG) or by removal of the vascular endothelium but not N-nitro-L-arginine (L-NA). K-KPD potentiated vasodilatation of the aortic ring precontracted with phenylephrine to acetylcholine and glyceryl trinitrate, and these effects were abolished by PAG. Western blot analysis showed an increase in blood vessel CSE, but not eNOS protein expression. Conclusion: Taken together, Kollicoat did not affect the beneficial cardiovascular health parameters of the KPD, except for the mechanism of the vascular function, which was found to cause increased blood vessel H2S instead of the NO. K-KPD did not have any adverse effects on internal organ gross toxicity, liver and kidney functions, or on blood cells. Thus, the K-KPD would be a novel health product to prolong cardiovascular health functions in human. Further development of the K-KPD in a dosage form as tablets or capsules for convenient human consumption would be worthwhile.