Mechanism and Protective Effect of Smilax glabra Roxb on the Treatment of Heart Failure via Network Pharmacology Analysis and Vitro Verification

Abstract

Smilax glabra Roxb (SGR) has been widely applied alone or in combination with other Chinese herbs in heart failure (HF), but its mechanism and protective effect have not been investigated. We aimed to explore the mechanism and protective effect of SGR on the treatment of HF. Network pharmacology analysis predicted that SGR was involved in the regulation of cell proliferation, oxidation–reduction process, apoptotic process, ERK1 and ERK2 cascade, MAPK cascade, etc. Its mechanism was mainly involved in the MAPK signaling pathway, calcium signaling pathway, cardiac muscle contraction, etc. Subsequently, SGR was proved to improve cellular viability, restore cellular morphology, suppress cellular and mitochondrial ROS production, improve H2O2-induced lysosome inhibition, attenuate mitochondrial dysfunction, and protect mitochondrial respiratory and energy metabolism in H9c2 cells. SGR activated the p38MAPK pathway by decreasing the mRNA expression of AKT, PP2A, NF-KB, PP2A, RAC1, and CDC42 and increasing the mRNA expression of Jun, IKK, and Sirt1. SGR also decreased the protein expression of ERK1, ERK2, JNK, Bax, and Caspase3 and increased the protein expression of p38MAPK and Bcl-2. In addition, Istidina at the highest degree was identified in SGR via the UHPLCLTQ-Orbitrap-MSn method, and it was suggested as anti-heart failure agents by targeting SRC with molecular docking analysis. In conclusion, SGR has a protective effect on HF through cellular and mitochondrial protection via multi-compounds and multi-targets, and its mechanism is involved in activating the p38 MAPK pathway. Istidina may be possible anti-HF agents by targeting SRC.

Shenxiong glucose injection inhibits oxidative stress and apoptosis to ameliorate isoproterenol-induced myocardial ischemia in rats and improve the function of HUVECs exposed to CoCl2

“…HUVECs (8×10 4 cells/ml) were seeded in 6-well plates for 24 h and treated as required. Detection of intracellular ROS was performed as previously described ( Long et al, 2022 ). Briefly, according to the manufacturer’s instructions, HUVECs were stained with DCFH-DA (10 μmol/L) and incubated in the dark for 30 min, and then were washed three times with PBS.…”

Exploring the Mechanism of Zanthoxylum Bungeanum Maxim in the Treatment of Osteoarthritis Based on Network Pharmacology, Molecular Docking and Molecular Dynamics Simulation

“…Network pharmacology is a combination of genomics, topology, systems biology, and other multidisciplinary and multiple techniques, which integrate the characteristics of integrity, dynamics and analysis in methodology, and is similar to the synergistic action of traditional Chinese medicine through principal, assistant, complement and guide [12,13]. Therefore, it has been widely used in the study of the pharmacological mechanism of Chinese traditional compound medicine [14][15][16]. Molecular docking technology, which uses computer-assisted drug design, is a well-established method to assist in small molecule drug development [17][18][19].…”