Notoginsenoside R1 Regulates Ischemic Myocardial Lipid Metabolism by Activating the AKT/mTOR Signaling Pathway

Abstract

Ischemic heart diseases are responsible for more than one-third of all deaths worldwide. Radix notoginseng is widely used to treat ischemic heart disease in China and other Asian countries, and notoginsenoside R1 (NGR1) is its characteristic and large-amount ingredient. However, the potential molecular mechanisms of NGR1 in improving ischemic heart diseases are unclear. In this study, we combined pharmacological evaluation with network pharmacology, myocardial proteomics, and conventional molecular dynamics (MD) simulation to explore the cardio-protection mechanisms of NGR1. Our results revealed that NGR1 improved the echocardiographic, tissue pathological, and serum biochemical perturbations in myocardial ischemic rats. The network pharmacology studies indicated that NGR1 mainly regulated smooth muscle cell proliferation, vasculature development, and lipid metabolism signaling, especially in the PI3K/AKT pathway. Myocardial proteomics revealed that the function of NGR1 was focused on regulating metabolic and energy supply processes. The research combined reverse-docked targets with differential proteins and demonstrated that NGR1 modulated lipid metabolism in ischemic myocardia by interacting with mTOR and AKT. Conventional MD simulation was applied to investigate the influence of NGR1 on the structural stabilization of the mTOR and AKT complex. The results suggested that NGR1 can strengthen the affinity stabilization of mTOR and AKT. Our study first revealed that NGR1 enhanced the affinity stabilization of mTOR and AKT, thus promoting the activation of the AKT/mTOR pathway and improving lipid metabolic abnormity in myocardial ischemic rats.

Enhancing antioxidant levels and mitochondrial function in porcine oocyte maturation and embryonic development through notoginsenoside R1 supplementation

“…NGR1, derived from traditional Chinese medicine, is recognized for its antioxidant properties (Cao et al., 2021; Liu et al., 2022; Luo et al., 2022; Zhao et al., 2020) and its role in regulating energy metabolism (Lei et al., 2022; Tian et al., 2022). In this context, parthenogenetic embryos, particularly porcine embryos due to their ready availability and diploid characteristics, have been instrumental in studying mechanisms of cell maturation and embryonic development in vitro (Choi et al., 2021; Liu et al., 2021).…”

“…It has also demonstrated efficacy in reducing ROS, thereby improving conditions like Alzheimer's disease, and it plays a role in regulating endoplasmic reticulum (ER) stress to protect against ischaemic heart diseases (Ma et al., 2014; Yu et al., 2016). Additionally, NGR1 has been associated with the regulation of energy metabolism and the improvement of cardiotoxicity (Lei et al., 2022; Tian et al., 2022). Yet, its effects on porcine oocyte maturation and subsequent embryonic development remain unexplored.…”

Improving the developmental competences of porcine parthenogenetic embryos by Notoginsenoside R1‐induced enhancement of mitochondrial activity and alleviation of proapoptotic events

“…NGR1 has expressed capabilities such as antioxidant generation (Li et al, 2021; Luo et al, 2022; Zhao et al, 2020), apoptosis inhibition (Liu et al, 2021; Zhu et al, 2020), autophagy attenuation (Cao et al, 2021), mitochondrial function protection (Liu et al, 2021, 2022; Wang, Tang, et al, 2021; Wang, Wu, et al, 2021), and lipid metabolism regulation (Lei et al, 2022; Tian et al, 2022). However, its effect on early porcine embryos has so far remained unclear.…”

与非编码调节相关的抗动脉粥样硬化机制 中药活性单体的rna

“…Notoginsenoside R1, the monomer extracted from Panax notoginseng(Burkill) F.H.Chen, has a unique effect of promoting blood circulation and has been used on clinical treatment of cardiovascular diseases (Lei et al, 2022). Matrix Gla Protein (MGP), an important inhibitor of vascular and cartilage calcification, is highly expressed in human atherosclerotic plaques (Shanahan, Cary, Metcalfe, & Weissberg, 1994).…”