Effects of Momordica cochinchinensis spreng, fruit on the proliferation and angiogenesis biomarkers of human retinal pigment epithelial cells under high glucose conditions

Tropical fruits have been reported to contain health-promoting compounds for human benefits. Fruit of Momordica cochinchinensis (M. cochinchinensis) is one of these fruits that believed to be rich source of bioactive constitutes. However, the studies on its phytochemical composition and biological activities against hyperglycaemia-related eye disease were found to be limited. Thus, this study attempted to investigate the phytochemical composition, antioxidant activities and the effects of M. cochinchinensis parts extracts grown in Malaysia on cell viability and angiogenic activity of human retinal pigment epithelial (ARPE-19) cells under high glucose (HG) conditions. UV-Vis was used for the estimation of phenolics, flavonoids, and carotenoids contents. Lycopene and β-carotene were quantified using a HPLC technique. LC-MS/MS was used for the identification of antioxidant compounds. DPPH and FRAP assays were employed to evaluate the antioxidant capacities. MTT assay, morphological observations and Trypan blue dye were employed for the cell viability evaluation. Enzyme linked immunosorbent-based assay was performed the evaluate the effect of the fruit extracts on the reactive oxygen species (ROS), vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) secretions. The results showed carotenoids, phenolics and flavonoids were present in all fruit parts. Comparatively, the fruit aril showed the highest carotenoids and phenolics content (1106 ± 2.1 μg/g, 308 ± 2.7 μg/g) respectively, whereas the peel showed the highest flavonoid content (381 ± 2.2 μg/g). Lycopene and β-carotene were found to be significantly high (p < 0.05) in aril (579.3 ± 22.7 and 621 ± 35 μg/g DW) and relatively high in peel and pulp. Furthermore, rutin, quercetin, linolenic acid and cinnamic acid were identified in peel, seed, pulp and aril. The antioxidant capacity evaluations revealed that, aril possessed the highest scavenging activity IC50 = 865 μg/mL, while the peel appeared to possess the highest ferric reducing power of 140 μmol FeSO4/μg. Cell culture experiments demonstrated HG condition at (30 mmol/L) condition increased the proliferation of ARPE-19 cell proliferation, ROS and VEGF secretions compared to low glucose (LG) at (5.5 mmol/L). While the exposure of ARPE-19 cells in HG conditions to M. cochinchinensis led to inhibition of cell viability, induced morphological changes, decreased ROS and VEGF, and increased PEDF levels. M. cochinchinensis pulp, seed, and aril at 1 000 μg/mL showed significant inhibition activities [(7.5 ± 5.1)%, (2.7 ± 0.5)%, (3.2 ± 1.1)%, respectively] against HGinduced ARPE-19 cell viability. The findings also demonstrated that aril at 250 μg/mL significantly decreased ROS and VEGF levels [(40.6 ± 3.3) pg/mL, (107.4 ± 48.3) pg/mL, respectively] compared to ROS [(71.7 ± 2.9) pg/mL] and VEGF [(606.9 ± 81.1) pg/mL] in HG untreated cells. Moreover, 250 μg/mL of Gac peel dramatically increased PEDF level [(18.2 ± 0.3) ng/mL] compared to that in HG untreated cells [(0.48 ± 0.39) ng/mL]. The current results demonstrated that M. cochinchinensis fruit was found to be rich source of phytochemical compounds especially carotenoids and to possess antioxidant capacity. In addition, M. cochinchinensis fruit extracts reduced ARPE-19 cell viability, minimized ROS generations and showed angiogenic activities. Therefore, our findings open new insights towards the potentiality of utilizing M. cochinchinensis fruit as a source of antioxidant plant and against HG-related diabetic retinopathy disease.

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