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Pharmacokinetic and nephroprotective benefits of using Schisandra chinensis extracts in a cyclosporine A-based immune-suppressive regime

Date:2016/8/22 21:02:56

Pharmacokinetic and nephroprotective benefits of using Schisandra chinensis extracts in a cyclosporine A-based 

immune-suppressive regime.Cyclosporine A (CsA) is a powerful immunosuppressive drug. However, nephrotoxicity resulting 

from its long-term usage has hampered its prolonged therapeutic usage. Schisandra chinensis extracts (SCE) have 

previously been used in traditional Chinese medicine and more recently coadministered with Western medicine for the treatment of 

CsA-induced side effects in the People's Republic of China. This study aimed to investigate the possible effects

 of SCE on the pharmacokinetics of CsA in rats and elucidate the potential mechanisms by which it hinders the 

development of CsA-induced nephrotoxicity. A liquid chromatography/tandem mass spectrometry method was developed

 and validated for determining the effect of SCE on the pharmacokinetics of CsA. Male Sprague Dawley rats, 

which were administered with CsA (25 mg/kg/d) alone or in combination with SCE (54 mg/kg/d and 108 mg/kg/d) for

 28 days, were used to evaluate the nephroprotective effects of SCE. Our study showed that SCE increased the 

mean blood concentration of CsA. Furthermore, we found that the concomitant administration of SCE alongside CsA

 prevented the disruption of catalase activity and reduction in creatinine, urea, renal malondialdehyde, 

and glutathione peroxidase levels that would have otherwise occurred in the absence of SCE administration. 

SCE treatment markedly suppressed the expression of 4-hydroxynonenal, Bcl-2-associated X protein, cleaved 

caspase 3, and autophagy-related protein LC3 A/B. On the other hand, the expression of heme oxygenase-1, 

nuclear factor erythroid 2-related factor 2 (Nrf2), and P-glycoprotein was enhanced by the very same 

addition of SCE. SCE was also able to increase the systemic exposure of CsA in rats. The renoprotective effects

 of SCE were thought to be mediated by its antiapoptotic and antioxidant abilities, which caused the attenuation

 of CsA-induced autophagic cell death. All in all, these findings suggest the prospective use of SCE as an 

effective adjunct in a CsA-based immunosuppressive regimen.