Wuzi Yanzong Pill protects neural tube defects by activating PI3K/Akt signaling pathway

Abstract

Neural tube defects (NTDs) are severe congenital malformations that can lead to lifelong disability. Wuzi Yanzong Pill (WYP) is an herbal formula of traditional Chinese medicine (TCM) that has been shown to have a protective effect against NTDs in a rodent model induced by all‐trans retinoic acid (atRA), but the mechanism remains unclear. In this study, the neuroprotective effect and mechanism of WYP on NTDs were investigated in vivo using an atRA‐induced mouse model and in vitro using cell injury model induced by atRA in Chinese hamster ovary (CHO) cells and Chinese hamster dihydrofolate reductase‐deficient (CHO/dhFr) cells. Our findings suggest that WYP has an excellent preventive effect on atRA‐induced NTDs in mouse embryos, which may be related to the activation of the PI3K/Akt signaling pathway, improved embryonic antioxidant capacity, and anti‐apoptotic effects, and this effect is not dependent on folic acid (FA). Our results demonstrated that WYP significantly reduced the incidence of NTDs induced by atRA; increased the activity of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), and content of glutathione (GSH); decreased the apoptosis of neural tube cells; up‐regulated the expression of phosphatidylinositol 3 kinase (PI3K), phospho protein kinase B (p‐Akt), nuclear factor erythroid‐2 related factor (Nrf2), and b‐cell lymphoma‐2 (Bcl‐2); and down‐regulated the expression of bcl‐2‐associated X protein (Bax). Our in vitro studies suggested that the preventive effect of WYP on atRA‐treated NTDs was independent of FA, which might be attributed to the herbal ingredients of WYP. The results suggest that WYP had an excellent prevention effect on atRA‐induced NTDs mouse embryos, which may be independent of FA but related to the activation of the PI3K/Akt signaling pathway and improvement of embryonic antioxidant capacity and anti‐apoptosis.

The Interplay between Medical Plants and Gut Microbiota in Cancer

“…A diet rich in vegetables has several benefits in terms of health promotion and is linked to a reduction in systemic and local intestinal inflammation. For example, resveratrol is a substance contained in peanuts, grapes, berries, and red wine, in plants after fungal infection, exposure to ultra-violet (UV) radiation, and mechanical injury, and acts by inhibiting NF-KB and consenting Bcl-2 to exert its proapoptotic effect [20,28,55,[100][101][102][103][104][105][106][107][108][109]. During inflammatory processes, immune cells produce interleukin 6 (IL-6) which ties to the soluble IL-6 receptor or the membrane IL-6 receptor and forms a complex that interacts with glycoprotein 130 and determines an upregulation of the transcription factor signal transducer and activator of transcription 3 (STAT-3).…”