Protection from Glucocorticoid-Induced Thymus Atrophy by Dihydromyricetin Via Up-Regulation of PPARγ and Anti-Oxidation

Abstract

T lymphocytes produced by the thymus are essential mediators of immunity. Accelerated thymic atrophy appears in the patients with administration of glucocorticoids (GCs) which are commonly-used drugs to treat autoimmune and infectious diseases, leading to dysregulation of immunity with manifestation of progressive diminution of new T cell production. However, there is no ideal method to overcome such side effects of GCs. In the current study, we proposed a composition of dexamethasone (DEX) and dihydromyricetin (DMY) derived from a medicinal plant, which could protect from DEX-induced thymus damage and simultaneously enhance the anti-inflammatory effect of DEX. Dexamethasone (DEX)-induced thymus atrophy was effectively prevented by co-treatment with dihydromyricetin (DMY) via activating PPARγ in thymic tissues of mice with delayed type hypersensitivity (DTH) induced by 2,4- dinitrofluorobenzene (DNFB). Simultaneously, DMY demonstrated a synergistic effect on suppressing DTH with co-administration of DEX in the mouse model of DTH and the paw edema induced by carrageenan in rats. Increase of PPARγ expression was found in the thymic tissues of animals treated with DMY plus DEX than the animals treated with DEX alone, which was validated by agonist and antagonist of PPARγ. DMY protected thymus from atrophy induced by DEX via regulation of PPARγ-associated fatty acid metabolism and anti-oxidation in thymic tissues. Our findings may provide a new strategy on protection of thymus from damage caused by GCs by using appropriate co-remedies of GCs together with suitable adjuvant natural agents through up-regulation of PPARγ expression and anti-oxidation. Funding Statement: This work was supported by FDCT grants from the Science and Technology Development Fund of Macao (Project code 081/2013/A3). Declaration of Interests: The authors declare that they have no conflict of interests. Ethics Approval Statement: Animal care and experiments were conducted in accordance with the Laboratory Animal Research Committee Guidelines of Guangdong Provincial Hospital of Chinese Medicine.