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Published on: November 8, 2015
Pharmacokinetic and pharmacodynamic interactions of morin and cyclosporin
Shih-Hua Fang1, Yu-Chi Hou, Pei-Dawn Lee Chao
1Department of Microbiology, School of Medicine, China Medical University, Taichung, Taiwan. shfang@mail.cmu.edu.tw
Abstract:
Morin is a flavonoid present in mulberry and herbs. We have reported that morin exerted anti-inflammatory activity on the activated macrophages. Cyclosporin (CsA) is a potent immunosuppressive agent with narrow therapeutic range, which is widely used for the treatments of autoimmune diseases and transplantation rejection. This study aimed to measure the effects of morin on the disposition of CsA in lymphoid and non-lymphoid tissues, and on the functions of immune cells in mice. CsA (Neoral, 10 mg/kg) was orally administered with and without a concomitant dose of morin (0, 50, 100, 200 mg/kg) to mice once daily for 2 weeks. CsA concentrations in blood, liver, kidney, and spleen were determined by a specific monoclonal fluorescence polarization immunoassay. The decreased levels of CsA in tissues were found well correlated to increased doses of morin. The coadministration of 200 mg/kg morin significantly decreased CsA in blood, liver, kidney, and spleen by 33%, 17%, 38%, and 45%, respectively. On the other hand, coadministration of morin decreased dramatically the nitric oxide production by the activated macrophages when compared to CsA treatment alone. Moreover, morin maintained the level of CsA-suppressed T helper 1 (Th1) type cytokine, although the CsA concentration in spleen was markedly reduced. In conclusion, morin coadministration profoundly reduced CsA concentration but did not significantly alter the CsA-suppressed Th1 immune response in mice.
Insights
Morin, a flavonoid, significantly reduced cyclosporine (CsA) levels in mouse tissues. This flavonoid did not alter the CsA-suppressed T helper 1 immune response, suggesting potential for co-administration in immunosuppressive therapy.
Area of Science:
- Pharmacology
- Immunology
- Natural Products
Background:
- Morin is a flavonoid with reported anti-inflammatory effects.
- Cyclosporin (CsA) is a critical immunosuppressant for autoimmune diseases and transplant rejection, but has a narrow therapeutic index.
- Understanding drug interactions is crucial for optimizing CsA therapy.
Purpose of the Study:
- To investigate the impact of morin on the tissue distribution of CsA in mice.
- To evaluate the effect of morin on immune cell function, specifically nitric oxide production and T helper 1 cytokine levels, in the presence of CsA.
Main Methods:
- Mice were orally administered CsA with varying doses of morin daily for two weeks.
- CsA concentrations in blood, liver, kidney, and spleen were quantified using monoclonal fluorescence polarization immunoassay.
- Nitric oxide production and T helper 1 cytokine levels were assessed in activated macrophages and spleen, respectively.
Main Results:
- Morin coadministration dose-dependently decreased CsA concentrations in blood, liver, kidney, and spleen.
- A dose of 200 mg/kg morin reduced CsA levels by 33% (blood), 17% (liver), 38% (kidney), and 45% (spleen).
- Morin significantly reduced nitric oxide production by activated macrophages and preserved CsA-suppressed T helper 1 cytokine levels despite reduced spleen CsA concentrations.
Conclusions:
- Morin coadministration markedly reduces CsA concentrations in lymphoid and non-lymphoid tissues in mice.
- Morin does not significantly impair the CsA-suppressed T helper 1 immune response.
- These findings suggest morin may modulate CsA disposition without compromising its immunosuppressive efficacy regarding Th1 responses.
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