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J Pharmacol Sci. 2016 Aug;131(4):259-66. doi: 10.1016/j.jphs.2016.07.004. Epub 2016 Jul 25.

Water-extracted Perilla frutescens increases endometrial receptivity though leukemia inhibitory factor-dependent expression of integrins.

Author information

1
School of Korean Medicine and Healthy Aging Korean Medical Research Center, Pusan National University, Busandaehak-ro 49, Mulgeum-eup, Yangsan, Gyeongsangnam-do 50612, Republic of Korea.
2
School of Korean Medicine and Healthy Aging Korean Medical Research Center, Pusan National University, Busandaehak-ro 49, Mulgeum-eup, Yangsan, Gyeongsangnam-do 50612, Republic of Korea; National Clinical Research Center for Korean Medicine, Korean Medicine Hospital of Pusan National University, Geumo-ro 20, Mulgeum-eup, Yangsan, Gyeongsangnam-do 50612, Republic of Korea.
3
Laboratory of Molecular Toxicology, School of Pharmacy, SungKyunKwan University, Seobu-ro 2066, Jangan-gu, Suwon, Gyeonggi-do 16419, Republic of Korea.
4
Department of Food Science and Technology, Keimyung University, Dalgubeoldae-ro 1095, Dalseo-gu, Daegu 42601, Republic of Korea.
5
School of Korean Medicine and Healthy Aging Korean Medical Research Center, Pusan National University, Busandaehak-ro 49, Mulgeum-eup, Yangsan, Gyeongsangnam-do 50612, Republic of Korea; National Clinical Research Center for Korean Medicine, Korean Medicine Hospital of Pusan National University, Geumo-ro 20, Mulgeum-eup, Yangsan, Gyeongsangnam-do 50612, Republic of Korea. Electronic address: hagis@pusan.ac.kr.

Abstract

The leaves and stems of Perilla frutescens var. acuta Kudo (PF) have been used to prevent threatened abortion in traditional medicine in the East Asian countries. Because reduced receptivity of endometrium is a cause of abortion, we analyzed the action of PF on the endometrial receptivity. PF increased the level of leukemia inhibitory factor (LIF), a major cytokine regulating endometrial receptivity, and LIF receptor in human endometrial Ishikawa cells. The PF-induced LIF expression was mediated by c-jun N-terminal kinase (JNK) and p38 pathways. Adhesion between Ishikawa cells and trophoblastic JAr cells stimulated by PF treatment was abolished by knock down of LIF expression or antagonism of LIFR. In addition, the expressions of integrin β3 and β5 were increased by PF treatment in Ishikawa cells. The PF-induced expression of integrin β3 and β5 was reduced with an LIFR antagonist. Neutralization of both integrins successfully blocked PF-stimulated adhesion of JAr cells and Ishikawa cells. These results suggest that PF enhanced the adhesion between Ishikawa cells and JAr cells by increasing the expression of integrin β3 and β5 via an LIF-dependent pathway. Given the importance of endometrial receptivity in successful pregnancy, PF can be a novel and effective candidate for improving pregnancy rate.

KEYWORDS:

Endometrial receptivity; Infertility; Integrin; LIF; Perilla frutescens

PMID:
27562703
DOI:
10.1016/j.jphs.2016.07.004
[Indexed for MEDLINE]
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