Objective To explore the effect and possible mechanism of berberine on the macro-phage polarization of human myeloid leukemia monocytic cell line THP-1 induced by oxidized low-density lipoprotein(ox-LDL).Methods THP-1 cells were induced into macrophages by PMA,and then according to different concentrations of berberine,the cells were divided into con-trol group,and 5,10,20,40 and 50 μmol/L berberine groups.After intervention for 24 or 48 h,CCK8 assay was used to detect cell viability for optimal concentration and time of berberine treat-ment.PMA-induced THP-1 macrophages were assigned into blank group,model group(ox-LDL),berberine group,inhibitor group(phosphatidyl inositol 3-kinase(PI3K)inhibitor LY294002)and berberine+inhibitor group(berberine+LY294002).The contents of inducible nitric oxide syn-thase(iNOS)and TGF-β1 were detected by ELISA.qPCR was employed to measure the mRNA expression of TNF-α,arginase 1(Arg1),PI3K and protein kinase B Akt1,and Western blotting was applied to detect the protein levels of Akt1 and phosphorylated protein kinase B antibody(p-Akt1).Results In 24 h after intervention,the macrophage activity was significantly lower in the 40 and 50 μmol/L berberine groups than the control group(P＜0.05),and after 48 h,the ac-tivity in all the 5 doses of berberine groups was obviously lower than that in the control group[(0.89±0.02)％,(0.82±0.03)％,(0.71±0.02)％,(0.62±0.03)％and(0.53±0.02)％vs(1.01±0.01)％,P＜0.05].Berberine treatment of 20 μmol/L for 24 h had little effect on cell viability,and the dose and the time were regarded as the best concentration and time.Compared with the blank group,iNOS content and TNF-α mRNA level were increased in the model group,while TGF-β1 content,mRNA levels of Arg1,PI3K and Akt1,and p-Akt1/Akt1 protein levels were de-creased(P＜0.05).iNOS content and TNF-α mRNA level were decreased,while TGF-β1 content,mRNA levels of Arg1,PI3K and Akt1 and protein levels of p-Akt1/Akt1s were increased in the berberine group than the model group(P＜0.05).Compared with the berberine group,iNOS con-tent and TNF-α mRNA level were increased,while mRNA levels of Arg1,PI3K and Akt1 and protein levels of p-Akt1/Akt1 were decreased in the berberine+inhibitor group(P＜0.05).Con-clusion Berberine can inhibit the inflammatory response of THP-1 macrophages induced by ox-LDL by activating PI3K/Akt1 pathway,and inhibit the M1 polarization and promote the M2 polarization of macrophages.

Objective To explore the effect and mechanism of berberine combined with curcumin on ath-erosclerosis(AS)by mediating M1 macrophages polarization.Methods M1-type macrophages were obtained from mouse mononuclear macrophages(RAW264.7)induced by lipopolysaccharide(LPS,100 ng/mL)and interferon(IFN)-γ(20 ng/mL).A cell model was established.The cells were divided into a control group,model group,berberine group,curcumin group and berberine plus curcumin group.Concentrations of berberine and curcumin were detected by CCK-8 assay.The expression levels of M1-type macrophage markers iNOS,TNF-α,CXCL9 and p-STAT6/STAT6 in macrophage supernatant were detected by ELISA.Levels of iNOS,TNF-α and CXCL9 mRNA were detected by RT-PCR.Levels of iNOS,STAT6 and p-STAT6 proteins in each group were detected by Western blot.After down-regulation of STAT6 level by siRNA technology,expression of p-STAT6 protein was detected by Western blot.Expression levels of iNOS,TNF-α,CXCL9 and p-STAT6 were detected by ELISA.Results In the polarization of M1 macrophages induced by LPS and IFN-γ,berberine(25 μmol/L)and curcumin(20 μmol/L)were the best concentrations as compared with other drug concentration groups,and neither alone nor combined use could significantly inhibit the viability of RAW264.7 cells(P<0.05).As compared with the normal group,iNOS,TNF-α and CXCL9 mRNA and protein levels were increased in the model group,while P-STAT6/STAT6 levels were decreased,with statistical differences(P<0.05).As compared with the model group,iNOS,TNF-α and CXCL9 mRNA and protein levels in the berberine group,curcumin group,and berberine plus curcumin group were decreased,while P-STAT6/STAT6 levels were increased,and the changes were more obvious in berberine plus curcumin group,with statistical difference(P<0.05).After transfection of STAT6 siRNA in M1 macrophages in the berberine plus curcumin group,P-STAT6 levels were down-regulated,while expressions of iNOS,TNF-α and CXCL9 were up-regulated,with statistical differences(P<0.05).Conclusions Both berberine and curcumin can inhibit the activity of M1-type macrophages and reduce inflammatory response.The action of berberine combined with curcumin is more advantageous than that of either drug alone,which may be the main mechanism of action through activation of STAT6.

The 20th National Congress report proposed the most important and core strategic path of national governance:Chinese modernization.Under the guidance of the top-level design,the healthcare security system needs to find a new paradigm of healthcare security governance under the Chinese modernization that is both in line with Chinese characteristics and the basic laws and characteristics of the world's sanitary resources.Combined with the 20th National Congress report,the medical reform tasks of"promoting the development and governance of medical services,medical insurance and pharmaceutical synergy"and"promoting the inheritance of Traditional Chinese Medicine"are required to learn from the international"disproportionate share"health resources compensation system.From the perspective of necessity and adaptability,it explore the Traditional Chinese Medicine(TCM)disproportionate share mechanism of medical insurance,in order to maximize the realization of the strategic purchasing goal of health insurance and to provide a systematic,standardized and sustainable modernized Chinese health insurance model for the continuous support of TCM medicine special diagnosis and treatment with medical insurance resources.

The 20th National Congress report proposed the most important and core strategic path of national governance:Chinese modernization.Under the guidance of the top-level design,the healthcare security system needs to find a new paradigm of healthcare security governance under the Chinese modernization that is both in line with Chinese characteristics and the basic laws and characteristics of the world's sanitary resources.Combined with the 20th National Congress report,the medical reform tasks of"promoting the development and governance of medical services,medical insurance and pharmaceutical synergy"and"promoting the inheritance of Traditional Chinese Medicine"are required to learn from the international"disproportionate share"health resources compensation system.From the perspective of necessity and adaptability,it explore the Traditional Chinese Medicine(TCM)disproportionate share mechanism of medical insurance,in order to maximize the realization of the strategic purchasing goal of health insurance and to provide a systematic,standardized and sustainable modernized Chinese health insurance model for the continuous support of TCM medicine special diagnosis and treatment with medical insurance resources.

The 20th National Congress report proposed the most important and core strategic path of national governance:Chinese modernization.Under the guidance of the top-level design,the healthcare security system needs to find a new paradigm of healthcare security governance under the Chinese modernization that is both in line with Chinese characteristics and the basic laws and characteristics of the world's sanitary resources.Combined with the 20th National Congress report,the medical reform tasks of"promoting the development and governance of medical services,medical insurance and pharmaceutical synergy"and"promoting the inheritance of Traditional Chinese Medicine"are required to learn from the international"disproportionate share"health resources compensation system.From the perspective of necessity and adaptability,it explore the Traditional Chinese Medicine(TCM)disproportionate share mechanism of medical insurance,in order to maximize the realization of the strategic purchasing goal of health insurance and to provide a systematic,standardized and sustainable modernized Chinese health insurance model for the continuous support of TCM medicine special diagnosis and treatment with medical insurance resources.

The 20th National Congress report proposed the most important and core strategic path of national governance:Chinese modernization.Under the guidance of the top-level design,the healthcare security system needs to find a new paradigm of healthcare security governance under the Chinese modernization that is both in line with Chinese characteristics and the basic laws and characteristics of the world's sanitary resources.Combined with the 20th National Congress report,the medical reform tasks of"promoting the development and governance of medical services,medical insurance and pharmaceutical synergy"and"promoting the inheritance of Traditional Chinese Medicine"are required to learn from the international"disproportionate share"health resources compensation system.From the perspective of necessity and adaptability,it explore the Traditional Chinese Medicine(TCM)disproportionate share mechanism of medical insurance,in order to maximize the realization of the strategic purchasing goal of health insurance and to provide a systematic,standardized and sustainable modernized Chinese health insurance model for the continuous support of TCM medicine special diagnosis and treatment with medical insurance resources.

The 20th National Congress report proposed the most important and core strategic path of national governance:Chinese modernization.Under the guidance of the top-level design,the healthcare security system needs to find a new paradigm of healthcare security governance under the Chinese modernization that is both in line with Chinese characteristics and the basic laws and characteristics of the world's sanitary resources.Combined with the 20th National Congress report,the medical reform tasks of"promoting the development and governance of medical services,medical insurance and pharmaceutical synergy"and"promoting the inheritance of Traditional Chinese Medicine"are required to learn from the international"disproportionate share"health resources compensation system.From the perspective of necessity and adaptability,it explore the Traditional Chinese Medicine(TCM)disproportionate share mechanism of medical insurance,in order to maximize the realization of the strategic purchasing goal of health insurance and to provide a systematic,standardized and sustainable modernized Chinese health insurance model for the continuous support of TCM medicine special diagnosis and treatment with medical insurance resources.

The 20th National Congress report proposed the most important and core strategic path of national governance:Chinese modernization.Under the guidance of the top-level design,the healthcare security system needs to find a new paradigm of healthcare security governance under the Chinese modernization that is both in line with Chinese characteristics and the basic laws and characteristics of the world's sanitary resources.Combined with the 20th National Congress report,the medical reform tasks of"promoting the development and governance of medical services,medical insurance and pharmaceutical synergy"and"promoting the inheritance of Traditional Chinese Medicine"are required to learn from the international"disproportionate share"health resources compensation system.From the perspective of necessity and adaptability,it explore the Traditional Chinese Medicine(TCM)disproportionate share mechanism of medical insurance,in order to maximize the realization of the strategic purchasing goal of health insurance and to provide a systematic,standardized and sustainable modernized Chinese health insurance model for the continuous support of TCM medicine special diagnosis and treatment with medical insurance resources.

The 20th National Congress report proposed the most important and core strategic path of national governance:Chinese modernization.Under the guidance of the top-level design,the healthcare security system needs to find a new paradigm of healthcare security governance under the Chinese modernization that is both in line with Chinese characteristics and the basic laws and characteristics of the world's sanitary resources.Combined with the 20th National Congress report,the medical reform tasks of"promoting the development and governance of medical services,medical insurance and pharmaceutical synergy"and"promoting the inheritance of Traditional Chinese Medicine"are required to learn from the international"disproportionate share"health resources compensation system.From the perspective of necessity and adaptability,it explore the Traditional Chinese Medicine(TCM)disproportionate share mechanism of medical insurance,in order to maximize the realization of the strategic purchasing goal of health insurance and to provide a systematic,standardized and sustainable modernized Chinese health insurance model for the continuous support of TCM medicine special diagnosis and treatment with medical insurance resources.

The 20th National Congress report proposed the most important and core strategic path of national governance:Chinese modernization.Under the guidance of the top-level design,the healthcare security system needs to find a new paradigm of healthcare security governance under the Chinese modernization that is both in line with Chinese characteristics and the basic laws and characteristics of the world's sanitary resources.Combined with the 20th National Congress report,the medical reform tasks of"promoting the development and governance of medical services,medical insurance and pharmaceutical synergy"and"promoting the inheritance of Traditional Chinese Medicine"are required to learn from the international"disproportionate share"health resources compensation system.From the perspective of necessity and adaptability,it explore the Traditional Chinese Medicine(TCM)disproportionate share mechanism of medical insurance,in order to maximize the realization of the strategic purchasing goal of health insurance and to provide a systematic,standardized and sustainable modernized Chinese health insurance model for the continuous support of TCM medicine special diagnosis and treatment with medical insurance resources.