Effects of Reducing the South and Reinforcing the North Method on Inflammatory Injury Induced by Hyperlipidemia.

Hongjin Wu,Weiwei Dai,Libo Wang,Chenglong Wang,Jie Zhang,Arham Shabbir

doi:10.1155/2021/1860508

Abstract

Inflammation is the pathophysiological basis of hyperlipidemia-related disease (HRD). Reducing the south and reinforcing the north method (RSRN) has a positive effect on HRD. However, the pharmacological mechanisms of RSRN are still unclear in the treatment of HRD. We obtained RSRN compounds from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and identified potential targets of these compounds through target fishing based on the TCMSP databases. Next, we identified the HRD targets by using multiple databases. Then, the overlapping genes between the RSRN potential targets and the HRD targets were used to establish a protein-protein interaction (PPI) network, and we further analyzed their interactions and identified the major hub genes in this network. Subsequently, the Metascape database was utilized to conduct the enrichment of Gene Ontology biological processes (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. A total of 187 potential active components and 106 related core targets were obtained and identified overall. Then after the Metascape enrichment analysis, a total of 148 KEGG pathways were screened, which were mainly associated with AGE-RAGE signaling pathway, PI3K-Akt signaling pathway, TNF signaling pathway, and NF-kappa B signaling pathway. Furthermore, 34 hub genes, such as AKT1, NF-κBp65(RELA), IκBα(CHUK), MAPK8, and MAPK14, CCND1, were considered potential therapeutic targets. Furthermore, evaluations of protein levels of NF-κBp65, IκBα, TNF-α, IL-1 ß, and IL-6 were performed for experimental validation. RSRN can reduce the expression of NF-κBp65 protein, increase the level of IκBα protein, and reduce the protein levels of TNF-α, IL-1β, and IL-6 in ovariectomized rats. The results indicate that the mechanism of RSRN against inflammation may be related to AKT1, NF-κBp65, IκBα, MAPK8, and MAPK14, as well as TNF, NF-kappa B, PI3K-Akt signaling pathways.

Highlights

Central Laboratory for Science and Technology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
E active components were further identified using the parameters of the oral bioavailability (OB); we set the threshold of OB at ≥30% and the drug likeness (DL) at ≥0.18 [12]. en we used the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform to predict the targets of active ingredients. e target information was obtained by correcting all the retrieved targets to their official names based on the UniprotKB search function in the protein database (UniProt)
A total of 187 active components were identified from the TCMSP databases by the ADME thresholds (OB ≥ 30%, DL ≥ 0.18), including 8 components of Curculigo orchioides Gaertn (Xian Mao), 22 components of Epimedii Folium (Yin yang huo), 21 components of Morindae officinalis Radix (Ba ji tian), 2 components of Angelicae Sinensis Radix (Dang gui), 38 components of Phellodendron chinense Cortex (Huang bo), 17 components of Anemarrhenae Rhizoma (Zhi mu), 65 components of Salviae Miltiorrhizae Radix et Rhizoma (Dan shen), and 14 components of Coptidis Rhizoma (Huang lian) (Table 1)

Summary

Introduction

Central Laboratory for Science and Technology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. We obtained RSRN compounds from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and identified potential targets of these compounds through target fishing based on the TCMSP databases. E results indicate that the mechanism of RSRN against inflammation may be related to AKT1, NFκBp65, IκBα, MAPK8, and MAPK14, as well as TNF, NF-kappa B, PI3K-Akt signaling pathways. Erefore, reducing the south (clearing heart) and reinforcing the north (nourishing kidney essence) may be the foundation of the HRD treatment. Pharmacological studies on RSRN have assessed its regulation of the sex hormone and lipid metabolism and its prevention of the atherosclerosis and cardiovascular disease during the climacteric period [6, 7] It was reported [8, 9] that Modified RSRN could enhance the myocardial microvascular density, improve the endothelial secretion function and hemorheology, and regulate the endocrine system and lipid metabolism in ovariectomized rats

Methods

Results

Conclusion