Administration of a herbal formulation enhanced blastocyst implantation via IκB activation in mouse endometrium

Abstract

Background 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. 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. Methods In 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. Results BCB 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. Conclusion These 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.

Protective effect of bioactive components from Rubi fructus against oxidative damage in human ovarian granulosa cells induced by 2,2‐azobis (2‐methylpropionamidine) dihydrochloride

“…16 Rubi fructus protects ovarian health, but the effective components and corresponding mechanisms remain to be elucidated. 42 Researchers have commonly used AAPH to induce cellular senescence, 43 impaired steroidogenesis, 44 and erythrocyte hemolysis 45 brought about by oxidative stress. It is a common generator of free radicals, decomposed into nitrogen and two R˙radicals under heat around 37 °C, producing ROO˙, ROOR radicals, or R-R products by diffusion or reaction with oxygen.…”

“…Rubi fructus possesses excellent anti‐inflammatory, antioxidant, anti‐aging, and other biological functions owing to its richness in functional phytochemicals 16 . Rubi fructus protects ovarian health, but the effective components and corresponding mechanisms remain to be elucidated 42 …”

Autophagy as a Therapeutic Target of Natural Products Enhancing Embryo Implantation

“…BaelanChagsangBang -- [236] Bangdeyun and its component DS147 -- [196,197] Buganshen recipe -- [198] BuShenAnTai recipe -- [201] Bushen Tiaoxue Granules and Kunling Wan -- [202] Dingkun Pill -- [206,207,212] Erbu Zhuyu decoction -Increases the Beclin1 and LC3B [204,208] Gushen'antai pills -- [195] Liuwei Dihuang Granule -- [199] Shoutaiwai recipe -- [200] Tokishakuyakusan(Danggui Shaoyao san) -Induces autophagy and mitophagy via increasing PINK1 and LC3 but reducing p62 [203,214,215] Wenshen Yangxue decoction -- [205,211] Xianziyizhen Recipe -- [237] Yeosin-san Paeonia lactiflora and Cyperus rotundus - [213,238] Yiqixue buganshen recipe -- [198] Zhuyun recipe -- [210] Angelica gigas Decusirol Block autophagic flux by suppressing cathepsin C expression [216,221] Cnidium officinale -- [239] Cyperus rotundus -Increases LC3B II/LC3B and Beclin1 [223,229] Paeonia lactiflora Paeoniflorin Induces autophagy via inhibition of AKT/mTOR [114,225,230] Panax quiquefolius (American Ginseng) Ginsenoside Rb1 and Rg1…”

Early Pregnancy Regulates Expression of IkappaB Family in Ovine Spleen and Lymph Nodes

“…IκB proteins not only interact with NF-κB to change its transcriptional activity, but also bind to chromatin and control gene expression to participate in immune homeostasis [ 12 ]. BaelanChagsangBang (BCB) water extract has strong anti-oxidative and cytoprotective effects in vitro, and in vivo administration of BCB water extract can improve the number of implantation sites in pregnant mice through upregulation of IκBα expression [ 13 ]. IKKβ signaling is involved in the prevention of preterm delivery and the improvement of neonatal outcomes through the suppression of production of interleukin-6 (IL-6) and related cytokines [ 14 ].…”