Berberine through PPAR- γ/HO-1 Pathway Regulates Macrophage Polarization

Abstract Objective: To use ox-LDL and LPS to induce RAW264.7 macrophages to create an inflammation model, and to observe the regulation of berberine on the secretion of inflammatory factors and macrophage polarization in macrophages under inflammatory conditions and the relationship between PPAR-γ/HO-1. The relationship between the pathways provides the basis for berberine in the treatment of atherosclerosis. Results: 1. Compared with the model group, the iNOS, and IL-6 produced by the berberine group, berberine + ZNPP, and berberine + GW9662 were significantly decreased, (P＜0.05); Compared with the berberine + GW9662 group and the berberine + ZNPP group, the secretion of iNOS and IL-6 increased in the berberine group, (P＜0.05). 2. Compared with the model group, Arg-1, IL-4, and IL-10 in the Berberine group, berberine + GW9662 and berberine + ZNPP groups increased significantly (P < 0.05); Compared with the berberine group, Arg-1, IL-4 and IL-10 in Berberine + GW9662 and berberine + ZNPP groups were significantly lower than those in Berberine group (P < 0.05). 3. For flow cytometry, CD80 positive cells are used to represent M1 cells, CD163 positive cells represent M2 cells, and the ratio of M2/M1 cells represents the polarization of macrophages, among which the ratio of M2/M1 cells in berberine group Compared with the berberine + ZNPP group and the berberine + GW9662 group, the ratio of M2/M1 in the berberine group was higher, (P＜0.05). 4. Western blotting method showed that the protein expression of PPAR-γ in the berberine group, the berberine + GW9662 group, and the berberine + ZNPP group was significantly increased compared with the model group, ( P＜0.05); the expression of HO-1 protein in the berberine group, the berberine + GW9662 group, and the berberine + ZNPP group were significantly higher than that in the model group, (P＜0.05). The protein expressions of PPAR-γ and HO-1 in the alkali group were higher than those in the berberine + GW9662 and berberine + ZNPP group, (P＜0.05). Conclusion: Berberine can regulate macrophage polarization through the PPAR-γ/HO-1 pathway, so that macrophages are polarized from M1 macrophages to M2 macrophages, and play an anti-inflammatory and antioxidant role. Berberine provides evidence for its anti-atherosclerotic effect.