Current Pharmaceutical Design - Volume 31, Issue 4, 2025

Diabetic retinopathy is the major cause of vision failure in diabetic patients, and the current treatment involves the practice of glucocorticoids or VEGF antagonists that are “off-label”. A few small organic molecules against DR were discovered many years ago. Nutraceuticals are naturally available functional foods that endorse different health benefits, including vitamins, antioxidants, minerals, fatty acids, and amino acids that can defer the development of some diseases.

Numerous studies reported that nutraceuticals encourage multiple therapeutic benefits and provide protection against various diseases. In diabetes, nutraceuticals contribute to improving insulin sensitivity, metabolism regulation, and lower hyperglycemia. The major aim of this study is to discover the most active drug from natural or plant sources. In this work, 42 phytochemical constituents from 4 kinds of plants were docked with the C4 target of diabetic retinopathy by an in silico molecular docking study.

According to the binding energy, all the phytoconstituents possessed good to high attraction towards the target, and 6 phytochemicals, such as terchebulin, punicalagin, chebulagic acid, casuarinin, punicalin, and pedunculagin, disclosed superior binding energy towards the target than standard ruboxistaurin via the interactions of conventional hydrogen bonding, pi-alkyl interactions, etc. Molecular dynamic simulation studies further established the stability of the phytoconstituents, and ADMET studies proved the safety profile of these phytoconstituents.

Hence, the current study suggested that the phytochemicals from various herbs inhibit the C4 target of diabetic retinopathy and can be utilized as lead compounds to develop analogs or repurposed for the treatment of DR.

Alzheimer’s disease (AD) is an enervating and chronic progressive neurodegenerative disorder. Celecoxib (CXB) possesses efficacious antioxidants and has neuroprotective, anti-inflammatory, and immunomodulatory properties. However, the poor bioavailability of CXB limits its therapeutic utility. Thus, this study aimed to evaluate the microencapsulated celecoxib MCXB for neuroprotection.

CXB was screened by molecular docking study using AutoDock (version 5.2), and the following proteins, such as 4EY7, 2HM1, 2Z5X, and 1PBQ were selected for predicting its neuroprotective effect. Scopolamine 20 mg/kg/day for approximately 7 days was administered to albino rats. Pure CXB 100 mg/kg/day and 200 mg/kg/day, and MCXB 100 mg/kg/day and 200 mg/kg/day were administered, respectively. Further, to assess the oxidative stress, the nitric oxide (NO), superoxide dismutase (SOD), catalase, and lipid peroxidation (LPO) were evaluated using chemical methods. The neurochemical biomarkers like AChE, glutamate, and dopamine were evaluated using the ELISA method. Further, the histopathology of brain cells was carried out to assess the neuro-regeneration and neurodegeneration of the neurons.

There was a significant binding interaction of CXB (score -6.3, -6.5, -5.1, -9.1) and donepezil (score-5.5, -7.6, -7.0, and -8.6) with AchE (4EY7), β-secretase (2HM1, monoamine oxidase (2Z5X), and glutamate (1PBQ), respectively. MCXB-treated rats (100 mg/kg/day, 200 mg/kg/day) showed increased SOD levels (p < 0.001), whereas NO, catalase, and LPO levels were significantly (p < 0.001) decreased as compared to scopolamine-treated rats. Further, MCXB-treated rats showed a modulatory effect in the level of dopamine and AchE. However, the glutamate level was significantly (p < 0.001) decreased.

In addition to that, histopathological examination of the hippocampus part showed remarkable improvement in brain cells. So, the findings of the results revealed that MCXB, in a dose-dependent manner, showed a neuroprotective effect against scopolamine-induced AD. This effect may be attributed to the activation of cholinergic pathways.