Investigating the therapeutic potential of Apium graveolens linn. and Persea americana mill. seed extract in modulating cellular targets for the treatment of diabetic retinopathy

Abstract

Purpose

Apium graveolens (AG) and Persea americana (PA) are potential herbal candidates traditionally being used for their therapeutic activities since ages. They are useful in managing diabetes and its associated complications. The study intends to scientifically evaluate the aqueous extracts of AG, and PA, for the management of diabetic retinopathy. Additionally, the study aimed to identify and analyze the phytochemical constituents of these extracts using gas chromatography-mass spectrometry (GC-MS) to understand their potential contribution to anti-diabetic and retinal protective effects.

Methods

Diabetes was induced by streptozotocin in Male adult Sprague-Dawley (SD) rats. The study was conducted later by the treatment of aqueous extracts of AG and PA for 16 weeks. Evaluation of the glycemic parameters, alkaline phosphatase levels, BAX levels, VEGF levels, protein levels, oxidative stress parameters, retinal vessel diameter and funduscopic studies were carried out. In addition, GC–MS analysis was performed using a Shimadzu GCMS system to identify the bioactive compounds present in the aqueous extracts.

Results

The extracts alone showed moderate reduction in glycemic parameters, whereas their combination with insulin and metformin demonstrated remarkable effects. PA (250 mg/kg) + insulin reduced glucose levels by 83.7 %, nearing normal values. Protein levels in the aqueous humor and lens significantly improved, with AG (500 mg/kg) showing a 222.7 % increase. ALP levels, which were elevated in diabetic rats, decreased significantly with PA (500 mg/kg) (61 % reduction). VEGF levels, associated with retinal damage, were significantly reduced by PA (250 mg/kg) + metformin (62.6 %, P < 0.001). IL-1β, an inflammatory marker, was notably lowered by AG (500 mg/kg) (79.4 %) and PA (500 mg/kg) (63.3 %). Catalase activity increased significantly with AG (500 mg/kg) (103.6 %, P < 0.001), while ascorbic acid levels, depleted in diabetic conditions, were restored by AG (500 mg/kg) and AG + metformin, both exceeding a 100 % improvement (P < 0.001). Histopathological analysis showed improved retinal integrity and reduced cellular apoptosis. Vessel diameter measurements confirmed significant vascular restoration, supported by funduscopic analysis showing enhanced retinal preservation and reduced pathological changes. The AG extract was found to contain 17 components including 2,3-Butanediol (18.29 %), Tiglic acid (7.61 %), L-Lactic acid (4.44 %), and n-Hexadecanoic acid (2.83 %), whereas PA extract contained 15 components, with 2,3-Butanediol (13.05 %) being predominant.

Conclusions

This study provides evidence that aqueous extracts of AG and PA possess therapeutic potential for managing diabetic retinopathy. While the extracts individually showed moderate effects in improving glycemic control and associated biochemical parameters, their combined use with insulin and metformin resulted in significantly enhanced outcomes. The combination treatment led to improvements in key markers, including alkaline phosphatase, BAX, VEGF, IL-1β, oxidative stress parameters, and retinal health, as evidenced by changes in vessel diameter and funduscopic analysis. The GC-MS analysis reinforced the therapeutic relevance by identifying potent bioactive molecules, suggesting that their anti-inflammatory, antioxidant, and hypoglycemic properties may contribute to the extracts' beneficial effects. These findings suggest that AG and PA could serve as valuable adjunctive therapies in the management of diabetes-related complications, particularly diabetic retinopathy. Further research is needed to fully understand their mechanisms and potential clinical applications.