title: Epimedium flavonoids counteract the side effects of glucocorticoids on hypothalamic-pituitary-adrenal axis.
abstract: Our previous studies demonstrated that the epimedium herb, when simultaneously used with GCs, counteracted suppressive effects of GCs on the HPA axis without adverse influence on the therapeutic action of GCs. Here, total flavones were extracted from the epimedium flavonoids (EFs) and then used to investigate whether EFs provide protective effects on the HPA axis. We found that GCs induced a significant decrease in body weight gain, adrenal gland weight gain, and plasma adrenocorticotropin (ACTH) and corticosterone levels. After treatment with EFs, body weight gain, adrenal gland weight gain, and plasma corticosterone level were significantly restored, whilst plasma ACTH level was partially elevated. EFs were also shown to promote cell proliferation in the outer layer of adrenal cortex and to enhance the migration of newly divided cells toward the inner layer. To elucidate the underlying mechanisms, the mRNA expression of insulin-like growth factor II (IGF-II) was measured, and EFs significantly upregulated IGF-II expression. Our results indicated that EFs counteract the suppression of the HPA axis induced by GCs. This may involve both the ACTH and IGF-II pathways and thereby promote regeneration of the adrenal cortex suggesting a potential clinical application of EFs against the suppressive effects of GCs on the HPA axis.
authors.affiliation: Key Laboratory of Cellular and Molecular Biology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Huang
authors.forename: Jijun
authors.initials: J
authors.lastname: Li
authors.forename: Songbai
authors.initials: S
authors.lastname: Zheng
authors.forename: Junzhen
authors.initials: J
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.forename: Sheilesh Kumar
authors.initials: SK
authors.lastname: Dewan
authors.forename: Bill
authors.initials: B
authors.lastname: Kalionis
authors.forename: Ziyin
authors.initials: Z
authors.lastname: Shen
authors.forename: Xiantao
authors.initials: X
authors.lastname: Tai
authors.forename: Shijin
authors.initials: S
authors.lastname: Xia