Histological and immunohistochemical evaluation of polyherbal formulations on inflammatory, apoptotic, and angiogenic pathways in streptozotocin-induced diabetic cardiac injury

Abstract

This study investigated whether polyherbal formulations (PHF1 and PHF2) have cardioprotective, antiinflammatory, and anti-apoptotic effects when compared to metformin (MFM) in rats with diabetes induced by streptozotocin (STZ). The rats were divided into five groups: control, STZ, STZ + MFM, STZ + PHF1, and STZ + PHF2. Cardiac tissues underwent histological and immunohistochemical analyses to evaluate tissue-level molecular alterations induced by STZ and the regulatory impact of polyherbal formulations. The STZ-treated group exhibited statistically significant elevations in oxidative stress, chronic inflammation (TNF-alpha, IL-1(3), endothelial stress (eNOS), and apoptosis (Bax, Bcl-2, Caspase-3), whereas angiogenesis (VEGF) was diminished. In the groups administered STZ + PHFs and STZ + MFM, myocardial integrity was markedly restored, collagen deposition was reduced, and normal histomorphology was re-established. Quantitative analysis demonstrated that PHF2 exhibited a cardioprotective profile comparable to MFM across most evaluated parameters. Although PHF1 demonstrated slightly better preservation of selected histological features, PHF2 showed stronger modulation across most inflammatory, apoptotic, and angiogenic markers. These findings indicate that the cardioprotective benefits of PHFs may be realised through synergistic antioxidant, anti-inflammatory, endothelialstabilising, and mitochondrial-protective pathways. In conclusion, PHFs exert protective histological and immunohistochemical effects during early hyperglycaemia-associated myocardial injury in diabetic rats.