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DOI: 10.1055/s-2008-1075180
Research in Compound-Compound Interactions would be Promising for Quality Control of Botanical Products
Interests and applications of botanical products have been becoming more and more popular worldwide for treating various illnesses. However, methods and criteria for quality control of those products remain in under-developing and demanding. Besides the efficient chemical analytical methods must be used in quality control of botanical products, compound-compound interactions involved in the pharmacokinetics, pharmacodynamics and even toxicity of a product should be an important considerable element for the study of quality control. In our current study of Qingfu Guanjeshu (QFGJS) capsule, an under-developing botanical product derived from Chinese medical plants of Sinomenium acutum, Aconitum carmichaeli DEBX., Curcuma Longa L., Paeeonia lactifloria PALL. and Paeonia suffruticosa ANDR. for anti-rheumatoid arthritis, some representative chemicals in the preparation were chosen for the study of compound-compound interactions in jugular-catheterized moving rat model, so as to demonstrate their interactive behaviors in the body. Study on the sinomenine-paeoniflorin pharmacokinetic interaction, the former derived from Sinomenium acutum and the latter from Paeeonia lactifloria PALL ., showed that sinomenine could significantly promote intestinal transport and absorption of paeoniflorin, leading to more than 12 times of elevation on AUC0-t of paeoniflorin. Mechanistic study demonstrated that sinomenine increased paeoniflorin's bioavailability via inhibition of P-gp-mediated paeoniflorin efflux in the intestine; while sinomenine characterizes as an inhibitor of the P-gp-mediated efflux. To investigate if there are cross-influences among the chemicals contained in QFGJS on toxicity, aconitine derived from Aconitum carmichaeli DEBX. and paeoniflorin were employed for the study. The results showed that paeoniflorin could markedly increase the value of LD50 of aconitine in mice and reduce the death ratio of rats caused by oral taking aconitine. Using a rat right atria model to further investigate the possible detoxifying mechanism of paeoniflorin to aconitine, the results showed that paeoniflorin could significantly inhibit arrhythmia of rat right atria caused by aconitine which indicates there may be possibility of detoxifying effect in the body through chemical-chemical interactions in QFGJS. Furthermore, as we known, there may be hundreds or even thousands of chemicals in a botanical product. Whether or not those chemicals would be interactive among them in body? This is a very meaningful question to be answered but very difficult. We therefore compared the pharmacokinetic behavior of paeonol, one bioactive compound from Paeonia suffruticosa ANDR., with two oral administration protocols, i.e., with the pure compound of paeonol or QFGJS containing paeonol in jugular-catheterized rats. The results showed that both the plasma concentration and AUC0-t of paeonol were significantly elevated in rats treated with QFGJS containing paeonol in comparison with animals treated with pure paeonol at a comparable dosage, while the Tmax, T1/2, and MRT showed similar in two groups. In addition, concentrations of four metabolites of paeonol detected by using LC-ESI-Q/TOF/MS were found to be higher in rat plasma treated with QFGJS. Those differences in pharmacokinetics of paeonol were probably induced by interaction with other co-existing chemicals in QFGJS. In conclusion, compounds used as indicators of the criteria for quality control of a botanical product should be justified with their biological properties and effects in the body. Acknowledgement: The research was funded by Hong Kong Jockey Club Charities (JCICM-6-02).