Anti-Atherosclerosis Effect of Angong Niuhuang Pill via Regulating Th17/Treg Immune Balance and Inhibiting Chronic Inflammatory on ApoE-/- Mice Model of Early and Mid-Term Atherosclerosis
| Autor: | Xu Yimin, Jiaoyu Rao, Yujuan Liu, Ning Na, Wei Xiao, Alexei Verkhratsky, Tao Zhu, Ruirui Lan, Hong Nie, Zhen Yin, Qinghong Fan, Zhe Zhang, Yushuang Chai, Kaihe Ye, Xiaomeng Chai |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty CCR2 Inflammation CCL2 03 medical and health sciences 0302 clinical medicine Immune system RAR-related orphan receptor gamma Internal medicine Medicine Pharmacology (medical) Receptor ApoE-/- mice Pharmacology business.industry plaque stability lcsh:RM1-950 FOXP3 lcsh:Therapeutics. Pharmacology 030104 developmental biology Endocrinology inflammation Simvastatin 030220 oncology & carcinogenesis early and mid-term atherosclerosis Angong Niuhuang Pill medicine.symptom Th17/Treg balance business medicine.drug |
| Zdroj: | Frontiers in Pharmacology, Vol 10 (2020) |
| ISSN: | 1663-9812 |
| DOI: | 10.3389/fphar.2019.01584 |
| Popis: | Angong Niuhuang Pill (ANP) is a well-known patented Chinese medicine which is used for hundreds of years for treating the central nervous system diseases. Atherosclerosis is a poly-aetiological chronic inflammatory vascular disease. Preventing inflammation is fundamental for treating atherosclerosis in early stages. In this study, we investigated the protective effects and possible mechanisms of ANP action on a high-fat diet induced early and mid-term atherosclerosis ApoE-/- mice. The effects of ANP were compared with accepted drug simvastatin. Twelve male C57BL/6J mice were used as the control group, and 60 male ApoE-/- mice were randomly divided into five groups: Model group, Simvastatin group, Low-, Medium-, and High-dose ANP group these groups received, respectively, saline, simvastatin (3.0mg/kg), low-dose ANP (0.25 g/kg), medium-dose ANP (0.50 g/kg), and high-dose ANP (1.0 g/kg), once every other day for 10 weeks. After administration, serum biochemical indices were detected by the automatic biochemical analyzer, the concentrations of IL-6 and IL-10 in the serum were assayed by ELISA, expression levels of IL-1β, TNF-α, MMP-2, MMP-9, CCL2, and its receptor CCR2 in the full-length aorta, and expression levels of transcription factors Foxp3, RORγt in the spleen were assayed via western blotting and RT-qPCR. Flow cytometry was used to analyze Th17 cells and Treg cells. Pathological and histological analysis was completed on aortic root. ANP decreased LDL/HDL ratio, concentrations of IL-6 while increased IL-10 in serum. Moreover, ANP down-regulated the expression levels of IL-1β, TNF-α, MMP-2, MMP-9, CCL2, and CCR2 receptor in the full-length aorta. In addition, ANP decreased Th17 cells and expression levels of transcription factor RORγt, increased Treg cells and expression levels of transcription factor Foxp3. ANP decreased content of collagen fibers and infiltration of inflammatory cells in the aortic root. In conclusion, we demonstrated that ANP has anti-atherosclerosis effects on a high-fat diet induced ApoE-/- mice early and mid-term AS model via regulating Th17/Treg balance, inhibiting chronic inflammation, reducing plaque collagen fibers, and reducing inflammatory cells infiltration, to exert its multi-channel multi-target anti-early and mid-term AS effects. |
| Databáze: | OpenAIRE |
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