Radio-protective efficacy of Gymnema sylvestre on Pangasius sutchi against gamma (⁶⁰Co) irradiation

Purpose: Freshwater fish Pangasius sutchi was used in this study as a vertebrate model. We evaluated the induction of certain antioxidant enzymes in various vital organs. The radioprotective efficacy of Gymnema sylvestre leaves extract (GS) [25 mg/kg Body Weight (B.W)] and its bioactive compound Gymnemagenin (GG) [0.3 mg/kg B.W] was compared with Amifostine (Ami), the only radioprotector clinically approved by the US-FDA [Ami- 83.3 mg/kg B.W] against different doses of gamma radiation - ⁶⁰Co (Lethal Dose: LD₃₀-9.2 Gy, LD₅₀-10.2 Gy and LD₇₀-11.4 Gy).

Materials and methods: This study was done via stress marker enzymes, cell cycle analysis (CCA) and DNA damage assay prediction with molecular docking, which are reported here for the first time. The results indicate an elevated LPO level and decreased level of CAT, SOD and GSH due to oxidative stress initiation by ⁶⁰Co Ionizing Radiation (IR) on 4th day and slightly reduced on 32nd day while the reverse observed when the fishes were pretreated with Ami, GS and GG. Similarly, CCA and dead/live cells counts were conducted with pretreatment of Ami, GS and GG against ⁶⁰Co IR dose (LD₅₀-10.2 Gy).

Results: In CCA, G0/G1 phase was observed to be the highest in Ami and lowest in GG, against ⁶⁰Co IR doses 10.2 Gy which was 51.76 ± 7.55. The dead cells range observed in pretreated group of Ami, GS and GG was lowest in Ami and highest in GG and live cells (highest in Ami and lowest in GG) as compared to ⁶⁰Co IR group (86.43 ± 3.42 and 8.77 ± 5.95). Thus, antioxidant profile improvement by oxidative stress reduction and gradual progression of different phases of cell cycle except the apoptotic phase along with the live cells counts indicates that the radio-protective efficacy of GS is similar to Ami.

Conclusion: Predictive assessment was carried out by docking of Ami, various components of GS with p53, NF-κβ cells and Rad51 proteins structures responsible for CCA, apoptosis and repair mechanism. These structural proteins were docked with other structural proteins like USP7, TNF-α and partner and localizer of BRCA2 associated (PALB2/BRCA2) complex which made us perform these systemic efforts to find the functional activity of these known radio-protectants.