Protective effects of Qingguang'an Ⅱ Formula on the optic nerve based on network pharmacology and SIRT1/PGC-1α signaling pathway
Objective To explore the mechanism of protective action of Qingguang'an Ⅱ Formula(QGAFⅡ)on optic nerve in glaucoma based on network pharmacology and experimental research.Methods Targets of QGAFⅡ components were screened through the TCMSP database,and glaucoma-related targets were mined from GeneCards,Disgenet,and CTD databases.Then the targets through which QGAFⅡ acts on glaucoma were identified.A protein-protein interaction(PPI)network was constructed using the intersection of these targets,and GO and KEGG pathway analyses were performed on them.A spontaneous chronic high intraocular pressure(IOP)DBA/2J glaucoma mouse model was established.C57BL/6J mice were set as the blank group(an equal volume of distilled water),and DBA/2J mice were randomize into the model group(an equal volume of distilled water),Yimaikang(YMK)group[0.31 g/(kg·d)],and low-[0.85 g/(kg·d)],medium-[1.7 g/(kg·d)],and high-concentration[3.4 g/(kg·d)]QGAFⅡ groups.Each group consisted of eight mice,and they were administered by gavage once daily.After 4 weeks of intervention,the IOP of mice was monitored by a contact tonometer;HE staining was used to observe the morphological structure of the mouse retina;Western blot was used to examine the protein expression levels of silent information regulator type-1(SIRT1)and peroxisome proliferator-activated receptor-γ-coactivator 1α(PGC-1α);qRT-PCR was used to check the mRNA expression levels of SIRT1 and PGC-1α.Results A total of 101 active ingredients and 245 related targets were screened from QGAFⅡ.Additionally,2,412 disease-related gene targets for glaucoma were identified.The five targets with the strongest drug-active ingredient-target interactions were prostaglandin-endoperoxide synthase 2,nuclear receptor coactivator 2,pepsinogen Ⅱ,prostaglandin-endoperoxide synthase 1,and peroxisome proliferator activated receptor gamma(PPARG).The PPI network showed that the stronger targets were SIRT1 and PPARG.Signaling pathways such as oxidative stress,cellular senescence,and IL-17 were obtained by GO and KEGG enrichment analyses.Compared with before administration,the IOP of the treatment groups significantly decreased after administration(P<0.01).After administration,compared with the blank group,the model group showed a significant increase in IOP(P<0.01),and the mRNA and protein expression levels of SIRT1 and PGC-1α in the retina were significantly reduced(P<0.01).Compared with the model group,the IOP in the treatment groups showed a significant decrease(P<0.01),while the mRNA and protein expression levels of SIRT1 and PGC-1α significantly increased(P<0.01).Compared with the YMK group and the low-concentration QGAFⅡ group,the mRNA expression levels of SIRT1 and PGC-1α and the protein expression level of SIRT1 significantly increased in the medium-and high-concentration QGAFⅡ groups(P<0.01);compared with the low-concentration QGAFⅡ group,the protein expression level of PGC-1α in the high-concentration QGAFⅡ group significantly increased(P<0.01);compared with the medium-concentration QGAFⅡ group,the mRNA and protein expression levels of PGC-1α significantly increased in the high-concentration QGAFⅡ group(P<0.01).Conclusion QGAFⅡ can effectively regulate the SIRT1/PGC-1α signaling pathway,and inhibit the loss of retinal ganglion cells(RGCs).It mainly exerts protective effects on the optic nerve in glaucoma by targeting oxidative stress and cellular senescence.
glaucomaQinguang'an Ⅱ Formulacellular senescencesilent information regulator type-1peroxisome proliferation-activated receptor-γ-coactivator 1α
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