Abstract
BackgroundBaelanChagsangBang (BCB), a herbal formulation consisting of eleven herbs, may be prescribed as a reproductive functional supplement to improve ovulation and implantation during the treatment of infertility and recurrent abortion in Korean Medicine. This study aimed to investigate the effects and action mechanisms of water-extracted BCB on endometrial receptivity and blastocyst implantation under normal conditions and in a mifepristone (RU486)-induced implantation failure murine model.MethodsIn vitro, the antioxidant potentials of BCB were evaluated using DPPH and superoxide anion radical scavenging assays and a DCFH-DA assay, and the cytotoxic and cytoprotective effects of BCB were confirmed using an MTT assay. In vivo, C57BL/6 female mice (n = 6 per group) orally received BCB (300 mg/kg/day), a dose similar to that used clinically, from 7 days before pregnancy until the end of the experiment. On day 4 of pregnancy, RU486 (4 mg/kg) was injected subcutaneously to induce implantation failure. The effect of BCB on embryo implantation was evaluated by implantation rate analysis, histological examination, and western blotting of uterus tissues.ResultsBCB water extract showed strong anti-oxidative and cytoprotective effects in vitro. In vivo administration of BCB water extract increased the number of newborn pups in BCB-treated mice versus sham-treated mice under normal conditions and improved the number of implantation sites in pregnant mice despite RU486 injection. BCB increased the protein levels of cyclooxygenase-2 and inducible nitric oxide synthase through IκB activation. Moreover, the expression levels of matrix metalloproteinases at uterus implantation sites were up-regulated in the BCB-treated group as compared with those in the RU486-treated group.ConclusionThese results show BCB improved embryo implantation through IκB activation in our mouse model and suggest that BCB has therapeutic potential in the context of poor endometrial receptivity.
Highlights
BaelanChagsangBang (BCB), a herbal formulation consisting of eleven herbs, may be prescribed as a reproductive functional supplement to improve ovulation and implantation during the treatment of infertility and recurrent abortion in Korean Medicine
To examine the cellular antioxidant capacity of BCB, intracellular reactive oxygen species (ROS) levels were measured in H 2O2-treated Chinese hamster ovary (CHO)-K1 cells. H2O2 treatment significantly increased intracellular ROS levels in CHO-K1 cells as compared with non-treated controls and this increase was suppressed by pretreating cells with 100 μg/mL BCB (Fig. 2b)
We investigated the effects of a hot water extract of BCB on endometrial receptivity in a mouse model of RU486induced implantation failure
Summary
BaelanChagsangBang (BCB), a herbal formulation consisting of eleven herbs, may be prescribed as a reproductive functional supplement to improve ovulation and implantation during the treatment of infertility and recurrent abortion in Korean Medicine. Implantation is a process by which the embryo (blastocyst stage) attaches to endometrium in early pregnancy and is only allowed during a short period called the ‘implantation window’. This process is regulated by complex and precise interactions between the embryo and endometrium [1], which involve differentiation to form a receptive endometrium under the influences of various biological factors of embryonic and maternal origin that include cytokines, growth factors, and adhesion. Assisted reproduction techniques (ART) have been widely used for the clinical treatment of infertility resulting from benign gynecological disorders or primary unexplained infertility, subsequent pregnancy rates remain unsatisfactory [4, 7]. In traditional Eastern medicine, herbal medicines, acupuncture, and moxibustion are used to treat female infertility [8, 9], and recently, due to accumulated scientific evidence, herbal medicine has emerged as an effective, complementary, alternative medicine for improving endometrial receptivity [10, 11]
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