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

Abstract

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.

Quercetin‑3‑O‑β‑D‑glucoside decreases the bioavailability of cyclosporin A through regulation of drug metabolizing enzymes, transporters and nuclear receptors in rats

“…In recent years, research on herbal medicine-drug interactions has received considerable attention ( 31 – 33 ). These interactions may increase the risk to patients, particularly for drugs with a narrow therapeutic index, including CsA ( 34 ).…”

Fortification of biscuit with sidr leaf and flaxseed mitigates immunosuppression and nephrotoxicity induced by cyclosporine A

“…Dysregulation of pro-inflammatory and anti-inflammatory cytokine networks may occur in parallel, and the cumulative extent of cytokine network disruption may be a significant prognostic predictor of acute kidney injury (AKI), and chronic kidney disease (CKD) (Flores et al, 2019;Tapia et al, 2020). CsA was demonstrated to induce oxidative stress, apoptotic cell death, and excessive autophagosome formation which plays a key role in triggering functional and structural renal impairment (Lai et al, 2015;Tbahriti et al, 2013). Mice received cyclosporine A could provide a model for suppressed immunity, nephrotoxicity, and permits the assessment of sidr leaves, and flaxseeds therapeutic activity.…”

Methodological Approach to the Elaboration of the Analytical Procedure of the Antioxidant Activity Determination of the Schisandra chinensis (Turcz) Baill. Extracts

“…extracts Introduction Schisandra chinensis (Turcz) Bail., Chinese magnolia vine belongs to the family of Magnoliaceae. Schisandra chinensis is widely distributed in China, Japan, Korea, and other countries due to its cultivation (Panossian and Wikman 2008;Lai et al, 2015;Qui et al, 2018;Hu et al, 2020). This plant is described in many Pharmacopeias.…”

“…It can have a positive influence on the pulmonary system, kidney, liver, skin, central nervous system, etc. (Kim et al, 2004;Fu et al, 2008;Lai et al, 2015;Gao et al, 2016;Huang et al, 2017;Li et al, 2019;. The renoprotective effects of the Schisandra chinensis extract are related to its antiapoptotic and antioxidant abilities, which induced the attenuation of CsA-induced autophagic cell death (Lai et al, 2015).…”

“…(Kim et al, 2004;Fu et al, 2008;Lai et al, 2015;Gao et al, 2016;Huang et al, 2017;Li et al, 2019;. The renoprotective effects of the Schisandra chinensis extract are related to its antiapoptotic and antioxidant abilities, which induced the attenuation of CsA-induced autophagic cell death (Lai et al, 2015). Schizandrin B reduces UVB-irradiation damages of skin fibroblasts and epidermal keratinocytes .…”