Dosage‐related beneficial and deleterious effects of ginsenoside Rb1 on mouse oocyte maturation and fertilization and fetal development

Abstract

Ginsenoside Rb1 (GRb1), the major saponin component of ginseng root, has a wide range of therapeutic applications for various diseases. Previously, our group showed that GRb1 triggers ROS‐mediated apoptotic cascades in mouse blastocysts, leading to decreased cell viability and impairment of pre‐ and postimplantation embryonic development, both in vitro and in vivo. In this study, we further found that GRb1 exerted dose‐dependent effects on oocyte maturation and sequent development in vitro. Oocytes preincubated with 25 μg/mL GRB1 displayed significantly enhanced maturation and in vitro fertilization (IVF) rates, along with progression of subsequent embryonic development. In contrast, treatment with 50 and 100 μg/mL GRB1 led to impairment of mouse oocyte maturation, decreased IVF rates, and injurious effects on subsequent embryonic development. In vivo, intravenous injection of 1 mg/kg body weight GRb1 significantly promoted mouse oocyte maturation, IVF, and early‐stage embryo development after fertilization while administration of 5 mg/kg body weight GRb1 led to a marked decrease in oocyte maturation and IVF rates concomitant with impairment of early embryonic development in our animal model. In terms of the mechanisms underlying the regulatory effects of GRb1 demonstrated increased intracellular reactive oxygen species (ROS) production and apoptosis in the 100 μg/mL GRb1 treatment group. However, we observed a significant decrease in total intracellular ROS content and inhibition of apoptosis events in the 25 μg/mL GRb1 treatment group, signifying that the intracellular ROS content serves as a key upstream regulator of GRb1 that influences its dose‐dependent beneficial or deleterious effects on oocyte maturation and sequent embryonic development. For further clarification of the mechanisms underlying GRb1‐triggered injurious effects, oocytes were pretreated with Ac‐DEVD‐CHO, a caspase‐3‐specific inhibitor, which effectively blocked injury to oocyte maturation, fertilization, and sequent development. In sum, study findings highlight the potential involvement of p53‐, p21‐, and caspase‐3‐dependent regulatory signaling cascades in GRb1‐mediated apoptotic processes.

Presence of ginsenoside re during in vitro maturation protects porcine oocytes from heat stress

“…The aim of the study was to investigate the protective effects of GRe on HS-induced damage in porcine oocytes. GRe is critical for the pharmacological activities of ginseng, and similar to other ginsenosides, it has attracted increasing attention for possible use in the treatment of metabolic diseases (Huang et al, 2019). Previous studies have shown that GRe exerts multiple beneficial effects to attenuate cell damage (Sun et al, 2020), reduce the apoptosis rate (Liu et al, 2002) and increase antioxidant activity (Liu et al, 2019).…”

Risk compounds, potential mechanisms and biomarkers of traditional Chinese medicine‐induced reproductive toxicity

“…Yifuning postpones ovarian ageing by suppressing the Rb/p53 signal transduction pathway (Liang et al, 2016). Ginsenoside Rb1 impairs oocyte maturation and embryonic development via involving p53‐, p21‐ and caspase‐3‐dependent regulatory signalling cascades in vitro (Huang et al, 2019). Akt is a serine–threonine protein kinase, which is associated with survival signalling in multiplicity cells, including fibroblasts and neuronal cells, and the inhibiting Akt pathway has been related with apoptosis (Brazil et al, 2004).…”

Ginsenoside Rb1 protects porcine oocytes against methylglyoxal damage thus it improves the quality of parthenogenetic activation and in vitro fertilization embryos

“…And Rb1 could protect mitochondria from apoptosis 8 . It was also reported that Rb1 has effects on mouse oocyte maturation and has effects on ovarian function in immature rats 9,10 …”