Mechanistic Appraisal into the Antidiabetic and Nephroprotective Activities of a Herbal Combination of Terminalia Chebula and Aloe Vera Cold Extracts

Abstract

Background: Type 2 diabetes mellitus (T2DM) and its renal complication, diabetic kidney disease (DKD), are major public health burdens. Existing therapies delay but do not halt disease progression, underscoring the need for multi-targeted adjuncts. Terminalia chebula (TC) and Aloe vera (AV) have traditional use in metabolic and renal disorders, yet their combined mechanistic potential remains underexplored.

Methods: Cold extracts of TC fruits and AV gel were prepared to preserve bioactive phenolics and acemannan. Extracts were evaluated through in vitro enzyme inhibition, antiglycation, and cellular assays (glucose uptake, ROS, Nrf2 activation). Antidiabetic and nephroprotective effects were assessed in streptozotocin-induced diabetic Wistar rats over 28 days, measuring glycaemic indices, renal biomarkers, oxidative stress, inflammatory cytokines, histopathology, and molecular signalling.

Results: TC showed strong α-glucosidase inhibition, while AV activated Nrf2/HO-1. The combination outperformed monotherapies, enhancing glucose uptake (52%), suppressing ROS (69%), and significantly lowering fasting glucose (122.8 mg/dL). Renal function improved, with reduced creatinine (0.78 mg/dL), UACR (25.6 mg/g), and cytokines. Histology confirmed restoration of renal architecture, with increased Nrf2/HO-1 and reduced NF-κB and TGF-β/Smad signalling.

Conclusion: Cold extracts of TC and AV act synergistically to target hyperglycaemia, oxidative stress, and fibrosis, offering a rational, multi-pathway adjunct for T2DM and DKD management.