J Ethnopharmacol. 2016 Oct 18. pii: S0378-8741(16)31372-1. doi: 10.1016/j.jep.2016.10.048. [Epub ahead of print]
- 1Department of Korean Gynecology, College of Korean Medicine, Dongguk University, Gyeongju, Korea.
- 2College of Korean Medicine, Dongguk University, Gyeongju, Korea. Electronic address: jh1548@dongguk.ac.kr.
- 3Department
of Korean Gynecology, College of Korean Medicine, Dongguk University,
Gyeongju, Korea. Electronic address: obgykdi@hanmail.net.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE:
Evodiae Fructus (EF) is the dried, unripe fruit of Evodia rutaecarpa Benth., and one of the main components of traditional herbal
prescriptions issued for the treatment of sterility caused by irregular
menstruation in Korea. However, scientific evidence regarding the
efficacy and action mechanism of EF is lacking.
AIM OF THE STUDY:
In this study, the authors established an in vitro screening tool to identify promising new drug candidates in herbal
medicines for the prevention and treatment of premature ovarian
failure. The protective effects of EF extracts against
4-vinylcyclohexene diepoxide (VCD)-induced ovotoxicity were investigated
and the molecular mechanism responsible was sought.
MATERIAL AND METHODS:
EF
extract was prepared by boiling EF in water and its quality was
confirmed by high performance liquid chromatography. CHO-K1 (Chinese
hamster ovary cells) and COV434 (human ovarian granulosa cells) cells
were plated, pretreated with EF extract for 2h and then treated with
1.5mM or 0.5mM VCD for 24h, respectively. Cell viabilities were measured
using a MTT assay, and protein levels were determined by western
blotting.
RESULTS:
VCD
significantly suppressed the viability of both CHO-K1 and COV434 cells
in a dose-dependent manner and induced the apoptosis of CHO-K1 cells at
1.5mM. EF extract dose-dependently blocked the ovotoxicity induced by
treatment with VCD. Furthermore, EF extract significantly activated Akt
and downstream effectors such as mTOR and GSK-3β in CHO-K1 cells. The
ability of EF extract to prevent cytotoxicity by VCD was antagonized by
pretreatment of LY294002, a PI3K/Akt inhibitor.
CONCLUSION:
EF
has the ability to protect ovary cells against VCD-induced ovotoxicity,
probably via Akt activation. These results suggest that the beneficial
effects of EF might be useful for preventing premature ovarian failure
or unexplained infertility caused by environmental factors.
Copyright © 2016. Published by Elsevier Ireland Ltd.
KEYWORDS:
4-Vinylcyclohexene diepoxide (PubChem CID: 7833); Akt; Evodiae Fructus; Herbal medicine; LY294002 (PubChem CID: 3973); Ovotoxicity; Premature ovarian failure; evodiamine (PubChem CID: 442088)
