Exploring Ethanolic Extract Of Alpinia Calcarata Roscoe Rhizome For Its Peripheral Neuroprotective Activity In Wistar Rats

Abstract

xxi ABSTRACT Alpinia calcarata Roscoe (ACR) is a member of the Zingiberaceae family, and its rhizome contains bioactive compounds such as flavonoids and terpenoids, as well as phenolic compounds with antioxidant, anti-inflammatory, antidiabetic, antifungal, antibacterial, analgesic, and anticancer properties. This study explores the neuroprotective potential of the Ethanolic Extract of Alpinia calcarata Roscoe (EEAC) using Wistar albino rat models of peripheral neuropathy. HPLC analysis confirmed the presence of stigmasterol in EEAC, which may contribute to its therapeutic effects. The rats were maintained in suitable laboratory conditions (12 hours light/dark cycle, 25ºC ± 2ºC temp) with a nutritional diet and water ad libitum and the models prepared and used for the experimental study were diabetic-induced peripheral neuropathy (DIPN) and chemotherapy-induced peripheral neuropathy (CIPN). DIPN was induced through a single intraperitoneal injection of streptozotocin (STZ) at 55 mg/kg, dissolved in ice-cold 0.1 M citrate buffer (pH 4.4). EEAC treatment significantly ameliorated mechanical allodynia, thermal hyperalgesia, and cold allodynia in a dose-dependent manner. Biochemical analysis showed that the treatment significantly reduced oxidative stress and increased antioxidant enzyme activities, such as superoxide dismutase, catalase, and glutathione peroxidase, in the sciatic nerves of treated rats. Histopathological evaluation revealed reduced nerve damage and degeneration in the EEAC-treated groups and improved myelin sheath and axonal integrity indicating the effectiveness of the treatment in DIPN models. CIPN was induced with cis-diamminedichloroplatinum II (Cisplatin) administered intraperitoneally at a dose of 2 mg/kg per week for five weeks. The intervention groups were treated orally with EEACR daily during the induction period. Treatment with EEAC showed significant attenuation of neurotoxicity as evidenced by behavioural improvements in mechanical allodynia, thermal hyperalgesia, and cold allodynia. Biochemical assessments revealed a significant decrease in oxidative stress markers and elevated antioxidant enzyme activities, including superoxide dismutase, catalase, and glutathione peroxidase, in the nervous tissues of EEACR-treated rats. Histopathological examination indicated reduced nerve damage and enhanced preservation of myelin and axonal structures in the treatment groups. The findings from this study suggest that EEAC, enriched with stigmasterol, offers promising neuroprotective effects against cisplatin-induced neuropathy in rats. xxii The results suggest that bioactive compounds in Alpinia calcarata Roscoe rhizome may serve as potential therapeutic agents for treating and managing diabetic and cisplatin peripheral neuropathy. However, further research is warranted to elucidate the precise molecular mechanisms underlying the protective effects of the extract.