A Network Pharmacology to Explore the Mechanism of Astragalus Membranaceus in the Treatment of Diabetic Retinopathy.

BACKGROUND: Diabetic retinopathy (DR) includes a series of typical lesions affected by retinal microvascular damage caused by diabetes mellitus (DM), which not only seriously damages the vision, affecting the life's quality of patients, but also brings a considerable burden to the family and society. Astragalus Membranaceus (AM) is a commonly used medicine in clinical therapy of eye disorders in traditional Chinese medicine (TCM). In recent years, it is also used for treating DR, but the specific mechanism is unclear. Therefore, this study explores the potential mechanism of AM in DR treatment by using network pharmacology. METHODS: Based on the oral bioavailability (OB) and drug likeness (DL) of two ADME (absorption, distribution, metabolism, excretion) parameters, Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), Swiss Target Prediction platform, GeneCards, and OMIM database were used to predict and screen the active compounds of AM, the core targets of AM in DR treatment. The Metascape data platform was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the core targets. RESULTS: 24 active compounds were obtained, such as quercetin, kaempferol, and astragaloside IV. There were 169 effective targets of AM in DR treatment, and the targets were further screened and finally, 38 core targets were obtained, such as VEGFA, AKT1, and IL-6. EGFR tyrosine kinase inhibitor resistance, AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, and other metabolic pathways participated in oxidative stress, cell apoptosis, angiogenesis signal transduction, inflammation, and other biological processes. CONCLUSION: AM treats DR through multiple compounds, multiple targets, and multiple pathways. AM may play a role in the treatment of DR by targeting VEGFA, AKT1, and IL-6 and participating in oxidative stress, angiogenesis, and inflammation.

[Relationship between selection of Pinus massoniana families and Folium Pini].

Based on variation of Pinus massoniana families, heritablility and correlation analysis, the contents of shikimic acid and procyanidine (heritability 0.90, 0.70), dry weight of single branch (heritability 0.60) and and leaf length (heritability 0.46) were screened out as quality, yield and harvest cost traits of Folium Pini, respectively. For the different medicinal application of Folium Pini, varied methods were chosen to estimate weight and construct index equation. Weight adjustment based.on equal emphasis were used as economic weight determining method to select the best families, and the index (accuracy 0. 936 4 and heritability 0. 881 6) obtained was a little better than that obtained by equal emphasis, and much better than that by restricted index. The superior families selected with adjustment weight and equal emphasis were No. 46, 43 and 28. Partial regression were used as economic weight determining method to select the best families,and the index obtained had the highest accuracy (0.941 5) , index heritability (0. 889 9) and the genetic gain of shikimic acid content. The superior families selected with this method were No. 46, 27 and 47. No. 46 was the best families with maximal economic benefit. Our study indicated that suitable method for estimate weight and construct index equation can be applied for better accuracy of superior families selection of P. massoniana.

Association of complement factor H gene polymorphisms with age-related macular egeneration susceptibility.

OBJECTIVE: This study was aimed to confirm whether I62V and Y402H polymorphisms of complement factor H (CFH) were risk factors for age-related macular degeneration (AMD). METHOD: 109 AMD patients and 165 AMD-free controls were enrolled in the study. The I62V and Y402H polymorphisms were analyzed by polymerase chain reaction-restriction fragment length of polymorphism (PCR-RFLP). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by the X2 test to assess the relationship of I62V and Y402H polymorphisms with AMD risk. Analysis of haplotype and stratification by age and smoking status was conducted as well. RESULTS: AA genotype and A allele of I62V polymorphism was significantly associated with increased risk for AMD (OR=3.75, 95% CI=1.70-8.30; OR=1.64, 95% CI=1.14-2.36). For Y402H polymorphism, CT genotype showed strong effects on the occurrence of AMD (OR=2.10, 95% CI=1.04-4.27). Moreover, C allele was also a risk factor for AMD (OR=1.95, 95% CI=1.02-3.72). The haplotypes analysis suggested that the risk for AT haplotype carriers was high, compared with GT haplotype (OR=3.91, 95% CI=2.58-5.94). In addition, we found that smoking status could affect the genotype distribution of Y402H polymorphism (P<0.05). CONCLUSIONS: Our results revealed that CFH polymorphisms I62V and Y402H might be associated with the susceptibility to AMD in Chinese population.

Rac1 activates HIF-1 in laser induced choroidal neovascularization.

AIM: To study the effect of Rac1 on the induction of HIF-1α in choroidal neovascularization (CNV) in mice. METHODS: One hundred C57BL/6J mice were laser photocoagulated to induce CNV, fifty mice of that were selected randomly for intravitreal injection of Rac1 inhibitor NSC23766 solution (1µL). After laser photocoagulation, fundus fluorescein angiography (FFA) was performed to verify the growth of CNV, Immunohistochemistry and Western blot were used to detect HIF-1α and Rac1 in posterior segment of eye globes. RESULTS: FFA verified that incidence of CNV was significantly reduced in the eyes with NSC23766 injection comparing with that of eyes without NSC23766 injection (P<0.01). Immunohistochemistry detected that HIF-1α and Rac1 mainly expressing in the new fibrovascular tissue. Western blot showed that HIF-1α and Rac1 was highly increased in tissue explants of retinal pigment epithelium (RPE) and choroid without NSC23766 injection. But for tissue explants of RPE and choroid with NSC23766 injection, both the expression of HIF-1α and Rac1 were inhibited. CONCLUSION: Rac1 is crucial to activate HIF-1 regulating the growth of CNV, and its inhibition may have potential therapeutic value.

[Expression of matrix metalloproteinase-2, -9 and their inhibitor-1 in hypertrophic scars].

OBJECTIVE: To investigate the gene expression of matrix metalloproteinases (MMP-2, MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in proliferative and mature hypertrophic scars. METHODS: Total RNA from 8 normal skin samples and from 16 human hypertrophic scar samples of different maturing stage was respectively extracted, and then mRNA was isolated. The gene expressions of MMP-2, MMP-9 and TIMP-1 in these samples were examined with reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The gray scale ratio of MMP-2, MMP-9 and TIMP-1 transcription in normal skin were (3.8 +/- 0.7)%, (5.8 +/-4.4)%, (30.3 +/- 3.0)%, respectively, which were obviously higher than those in proliferative hypertrophic scar [(14 +/- 5)%, (18 +/- 5)%, (38 +/- 4)%, P < 0.05]. The expression of MMP-2 and MMP-9 genes in mature hypotrophic scar returned to normal level, but that of TIMP-1 remained high when compared with that of normal level (P < 0. 05). CONCLUSION: The increase in MMP-2, MMP-9 and TIMP-1 gene expression might be involved in the formation of hypertrophic scars, while the lowering of MMP-2 and MMP-9 gene expression might be associated with the maturation of hypertrophic scars.