1. Academic Validation
  2. Shen-Hong-Tong-Luo Formula Attenuates Macrophage Inflammation and Lipid Accumulation through the Activation of the PPAR- γ/LXR- α/ABCA1 Pathway

Shen-Hong-Tong-Luo Formula Attenuates Macrophage Inflammation and Lipid Accumulation through the Activation of the PPAR- γ/LXR- α/ABCA1 Pathway

  • Oxid Med Cell Longev. 2020 Oct 1;2020:3426925. doi: 10.1155/2020/3426925.
Zepeng Zhang 1 2 Lu Zhai 1 2 Jing Lu 1 2 Sanmiao Sun 3 Dandan Wang 1 2 Daqing Zhao 2 4 Liwei Sun 1 2 Weimin Zhao 5 Xiangyan Li 2 4 Ying Chen 6
Affiliations

Affiliations

  • 1 Research Center of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, China.
  • 2 Jilin Provincial Key Laboratory of Biomacromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, China.
  • 3 College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, China.
  • 4 Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, Jilin, China.
  • 5 Center of Preventive Treatment of Disease, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, China.
  • 6 Department of Cardiology, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, China.
Abstract

Atherosclerosis (AS) is the killer of human health and longevity, which is majorly caused by oxidized lipoproteins that attack macrophages in the endarterium. The Shen-Hong-Tong-Luo (SHTL) formula has shown great clinical efficacy and vascular protective effect for over 30 years in China, to attenuate AS progression. However, its pharmacological mechanism needs more investigation. In this study, we first investigated the chemical composition of SHTL by fingerprint analysis using high-performance liquid chromatography. In primary mouse peritoneal macrophages induced by lipopolysaccharide (LPS), we found that SHTL pretreatment suppressed Reactive Oxygen Species accumulation and reversed the increases of the inflammatory factors, TNF-α and IL-6. Moreover, lipid accumulation induced by oxidized low-density lipoprotein (Ox-LDL) in macrophages was inhibited by SHTL. Additionally, network pharmacology was used to predict the potential targets of SHTL as the PPAR-γ/LXR-α/ABCA1 signaling pathway, which was validated in macrophages and ApoE-/- mice by histopathological staining, qPCR, and Western blot analysis. Importantly, the protective effect of SHTL in the LPS- and Ox-LDL-induced macrophages against inflammation and lipid accumulation was attenuated by GW9662, a PPAR-γ antagonist, which confirmed the prediction results of network pharmacology. In summary, these results indicated that SHTL pretreatment reduced inflammation and lipid accumulation of macrophages by activating the PPAR-γ/LXR-α/ABCA1 pathway, which may provide a new insight into the mechanism of SHTL in the suppression of AS progression.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-16578
    99.87%, PPARγ Antagonist