| (1)Clinical observation of exudative age-related macular degeneration treated by Huangban Bianxing One DecoctionObjective:To evaluate the clinical efficacy and safety of Chinese medicine formula Huangban Bianxing One Decoction(HBOD)combined with Lucentis for treating exudative age-related macular degeneration(AMD)patients.Methods:From July 2014 to February 2016,a total of 75 patients with exudative AMD(75 eyes)who met the inclusion criteria and exclusion criteria were enrolled in this study and were randomly divided into the treatment group and the control group.Both groups were given one injection of Lucentis treatment after enrollment.After that,the treatment group received aqueous extract from herbs of HBOD by oral twice a day(100 mL for once)for 6 months.Early treatment diabetic retinopathy study(ETDRS)letters for the best corrected visual acuity,center macular thickness(CMT),height of the lesion,fundus hemorrhage area,fundus fluorescein leakage area as the main outcomes were estimated and compared before and after treatment.Results:After 3 months of treatment,ETDRS letters of both groups obtained a greater improvement(P<0.05).After 6 months of combination treatment,ETDRS letters in the treatment group was significantly higher(P<0.01),and significantly better than the control group(P<0.05).After 3 months of treatment,the CMT and height of the lesion of both groups were significantly lower than those before treatment(P<0.01 or P<0.05).After 6 months of treatment,the CMT and height of the lesion of the treatment group were significantly lower than those before treatment(P<0.01).After 6 months of treatment,the hemorrhage area and fluorescein leakage area were also significantly reduced(P<0.01 or P<0.05).In addition,compared with the control group,the hemorrhage area and fluorescein leakage area of the treatment group also significantly narrowed(P<0.01 or P<0.05).During treatment,no significant adverse events relating to HBOD treatment were elucidated.Conclusions:Exudative AMD belongs to neovascular retinopathy and is one of the main reasons for the world’s elderly population blindness.On the basis of these results,HBOD can improve visual acuity,and reduce hemorrhage and fluorescein leakage of patients with exudative AMD,which may be an effective alternative and safe treatment for exudative AMD.(2)Study on the mechanism of Huangban Bianxing One Decoction on treating exudative age-related macular degenerationObjective:The effects of HBOD on the expressions of IL-17A and vascular endothelial growth factor(VEGF)-A in plasma of patients with exudative AMD were investigated by interfering with interleukin(IL)-17 signal pathway.Methods:From July 2014 to February 2016,38 cases of exudative AMD patients of the treatment group from the clinical observation were included in this study.Patients were taken fasting venous blood in the morning before treatment and after taking HBOD for 6 months,respectively,as the AMD group and the treatment group,and recruited 20 healthy subjects as the control group.The plasma levels of IL-17A and VEGF-A were measured by enzyme-linked immunosorbent assay.Results:Only 1 case for IL-17A in the control group could be measured,and 6 cases for AMD group and 3 cases for the treatment group,so the statistical analysis could not been performed.The plasma levels of VEGF-A in the AMD group were significantly higher than those in the treatment group and the control group(P<0.01 or P<0.05),and there was no significant difference between the control group and the treatment group(P>0.05).Conclusions:HBOD can regulate the level of VEGF-A in plasma of exudative AMD patients,but whether HBOD can IL-17A levels is unclear in this study.(3)Plasma metabolomic study of exudative age-related macular degeneration treated by Huangban Bianxing One DecoctionObjective:AMD is a leading blindness disease with a high incidence and complex pathogenesis.We aimed to study the plasma metabolomic characteristics in Chinese patients with exudative AMD treated by HBOD.Methods:This metabolomic study was conducted by analyzing the morning plasma of 20 healthy controls and 20 exudative AMD patients before and after HBOD treatment for 6 months.We used the ultra-high-pressure liquid chromatography and quadrupole-time-of-flight mass spectrometry for this analysis.The relationship of these differences with AMD pathophysiology and treatment was also determined.Remaining data were normalized by Pareto scaling,and then valid data were handled by multivariate data analysis using MetaboAnalysis software,including unsupervised principal component analysis(PCA)and supervised partial least squares-discriminate analysis(PLS-DA).The purpose was to determine the significant metabolites for the analyses.Hierarchical clustering was conducted to discriminate metabolites between groups.The significant metabolites were then identified using the established database,and features were mapped on the Kyoto Encyclopedia of Genes and Genomes.Results:PCA,PLS-DA and hierarchical cluster results analysis showed that there were no significant changes in the serum metabolic profile before and after treatment for exudative AMD.Under the positive ion mode,a total of 5443 ion peaks were detected,among which 10 metabolites including some amino acids,isomaltose,hydrocortisone,and biliverdin significantly differed between exudative AMD and and healthy controls.The biosynthesis of amino acids pathways also profoundly differed between exudative AMD and controls.Conclusions:These findings suggest that metabolic profiles differ between exudative AMD and controls,which may provide promising new targets for AMD-directed therapeutics and diagnostics.Meanwhile,it has not been found that HBOD can significantly regulate the metabolic status of exudative AMD patients due to the poor reliability model.(4)Effects of Huangban Bianxing One Decoction and its main ingredients on proinflammatory cytokine production induced by IL-17A in ARPE-19 cellsObjective:This study was performed to explore the effects of HBOD and its main ingredients on the proinflammatory cytokine production induced by interleukin(IL)-17A in ARPE-19 cells.Methods:ARPE-19 cells were incubated with 100 ng/mL IL-17A for 6,12,24 or 36 h,as well as with 10,20,50,100 or 200 ng/mL IL-17A for 6 h to assay the mRNA expressions of IL-1β,IL-6,IL-8,chemokine(C-C motif)ligands(CCLs)CCL2 and CCL20 by quantitative real-time polymerase chain reaction(qRT-PCR).The Cell Counting Kit(CCK-8)assay was performed to determine the cytotoxicity of HBOD,astragalus polysacharin(APS),panax notoginseng saponins(PNS),and peimine(PE).ARPE-19 cells were pre-treated with noncytotoxic herb solutions for 2 h,followed by incubation with or without recombinant IL-17A for 6h or 24 h.The resulting proinflammatory cytokine mRNA and protein expression levels were measured by qRT-PCR and enzyme-linked immunosorbent assay,respectively.Results:IL-17A significantly increased the IL-1β,IL-6,IL-8,CCL2 and CCL20 mRNA and protein expressions from ARPE-19 cells(P<0.01).HBOD inhibited the abovementioned proinflammatory cytokines mRNA and protein expression levels(P<0.01 or P<0.05).As main ingredients,APS,PNS and PE partially or completely inhibited the expression of these proinflammatory cytokines mRNA and protein expressions(P<0.01).And PE on CCL20 expression had a strong inhibitory effect,which had more widely anti-inflammatory effect.Our results suggested that HBOD and its main ingredients might treat AMD by partially inhibiting the inflammatory response of retinal pigment epithelial cells induced by IL-17A.Conclusions:The inhibitory effects on proinflammatory cytokine production induced by IL-17A may explain the effective mechanism of HBOD for treating AMD. |
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