Effect of sinomenine on the in vitro intestinal epithelial transport of selected compounds.

Phytother Res. 2009 Jul 7; Lu Z, Chen W, Viljoen A, Hamman JHHerbal products can interfere with allopathic medicinal treatment through pharmacokinetic and pharmacodynamic interactions. Although pharmacokinetic interactions that alter drug absorption may cause variable and unsatisfactory drug bioavailability, a drug absorption enhancement effect of a herb may be used to ensure sufficient absorption of poorly absorbable drugs. The effect of the hydrochloride salt of sinomenine, an alkaloid obtained from the plant Sinomenium acutum, on the transepithelial electrical resistance and transport of different compounds (including cimetidine, vitamin C, rutin, luteolin and insulin) across Caco-2 epithelial cell monolayers was investigated in this study. Sinomenine HCl induced a concentration dependent lowering effect on the transepithelial electrical resistance of Caco-2 cell monolayers, which was completely reversible. Sinomenine HCl significantly increased the transport of all the test compounds in the apical-to-basolateral direction compared with the control group and decreased the transport of cimetidine, a P-glycoprotein substrate, in the basolateral-to-apical direction. From these results it can be concluded that sinomenine HCl increases drug absorption across the intestinal epithelium by means of one or more mechanisms including a transient opening of the tight junctions (as indicated by a reduction in transepithelial electrical resistance) to allow for paracellular transport and/or inhibition of active drug efflux transport (as indicated by inhibition of basolateral-to-apical transport of cimetidine). Copyright (c) 2009 John Wiley & Sons, Ltd.

Effects of Bushen Kangshuai Tang in retrieving oxidative stress-induced reproductive defects in Caenorhabditis elegans.

Zhong Xi Yi Jie He Xue Bao. 2009 Jun; 7(6): 532-40Cao XG, Hou LL, Chen JX, Lu QObjective: To explore the function of Bushen Kangshuai Tang (BKT), a compound traditional Chinese herbal medicine, in alleviating oxidative stress-induced reproductive defects in organism nematode Caenorhabditis elegans. Methods: The L4-larvae were cultured with 25%, 50%, 75%, and 100% of BKT with the final concentration of 0.33 g/mL. Ultraviolet irradiation [20 J/(m(2).min)], heat-shock (36 degrees centigrade, 2 h), and paraquat treatment (2 mmol/L, 2h) were exerted as the stresses. Reproduction was assayed by the egg number in uterus, brood size, and generation time. Results: Ultraviolet irradiation, heat-shock, and paraquat treatment could significantly reduce egg number in uterus and brood size, increase generation time, and suppress activities of catalase and superoxide dismutase of the treated wild-type N2 nematodes. Administration of BKT did not cause toxic or altered effects on reproduction under wild-type background in C. elegans. However, BKT administration at higher concentrations could not only effectively alleviate the reproductive defects induced by ultraviolet irradiation, heat-shock, and paraquat treatment, but also increase the catalase and superoxide dismutase activities suppressed by ultraviolet irradiation, heat-shock, and paraquat treatment as compared with the control. Moreover, administration of BKT at higher concentrations could largely recover the reproductive defects formed in mev-1 mutant nematodes with elevated oxidative stress. Conclusion: Oxidative stress can negatively regulate the reproductive process, and the administration of high concentrations of BKT will largely retrieve the oxidative stress-induced reproductive defects in exposed nematodes.

Methodology of pharmacodynamic evaluation on Chinese herbal medicine based on syndrome differentiation.

Zhong Xi Yi Jie He Xue Bao. 2009 Jun; 7(6): 501-4Lu AP, Liu XW, Ding XRThe clinical application of Chinese herbal medicine should be based on syndrome differentiation in traditional Chinese medicine (TCM), and the pharmacological evaluation of herbal medicine in new drug discovery should be also based on the TCM syndrome differentiation. To clarify the Chinese herbal characteristics and mechanisms of action through pharmacological experiments is not only the inevitable requirement for Chinese herb modernization and internationalization, but also the key way to direct the clinical rational administration. Thus how to characterize the syndrome type in commonly used animal disease models becomes the key issue in pharmacological evaluation. Following the development of biomedicine, one important way to clarify the syndrome characteristics of animal disease model in the pharmacological evaluation is to compare the differences between the responsive and non-responsive animals, and to find out the responsiveness-related biocharacteristics. An important approach to set up the Chinese herbal pharmacological evaluation which is suitable for Chinese medicine differentiation is to utilize the method of surveying syndrome type with Chinese herb formula and select the responsive animal model to reflect certain syndrome type, and furthermore to clear up the syndrome characteristics of the animal model by investigating its modern biological basis and establishing the correct indications of special TCM syndrome type. This pharmacological evaluation way based on finding out the responsiveness-related biocharacteristics of herbal medicine could become more effective in evaluating drug effects, further improving the new drug discovery, and developing Chinese herbal medicine.