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. 2019 May 30;5(5):e01749.
doi: 10.1016/j.heliyon.2019.e01749. eCollection 2019 May.

Aqueous extract from Madhuca indica bark protects cells from oxidative stress caused by electron beam radiation: in vitro, in vivo and in silico approach

K Vinutha  1 , Gollapalli Pavan  2 , Sharath Pattar  3 , N Suchetha Kumari  4 , S M Vidya  1
Affiliations

Aqueous extract from Madhuca indica bark protects cells from oxidative stress caused by electron beam radiation: in vitro, in vivo and in silico approach

K Vinutha et al. Heliyon. .

Abstract

In an endeavor to find the novel natural radioprotector to secure normal cells surrounding cancerous cell during radiation exposure, Madhuca indica (M. indica) aqueous stem bark extract was evaluated for radioprotective activity using in vitro, in vivo, and in silico models. M. indica extract exhibited concentration dependent protective effect on electron beam radiation (EBR) induced damage to pBR322 DNA; the highest protection was achieved at 150 μg concentrations. Similarly, M. indica extract (400 mg/kg) administrated to mice prior to irradiation protected DNA from the radiation damage, which was confirmed by inhibiting comet parameters. The study showed a significant increase in the levels of glutathione and superoxide dismutase levels. The study also revealed that administration of M. Indica at the different dose to mice significantly reduced EBR induced MDA, sialic acid and nitric acid levels. Further extract prevented histophatological changes of skin and liver. In contrast, protein-protein interaction studies were performed to find the hub protein, involved in radiation-induced DNA damage. Among 437 proteins that are found expressed during radiation, p53 was found to be a master protein regulating the whole pathway. Molecular interaction between p53 and M. indica extract was predicted by quantitative structure-activity relationship and ADMET properties. Biomolecules such as quercetin, myricetin, and 7-hydroxyflavone were found to be promising inhibitors of p53 protein and may help in the protection of EBR induced DNA damage during cancer treatment.

Keywords: Biochemistry; Bioinformatics; Biotechnology; Computational biology; Molecular biology; Structural biology; System biology.

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Figures

Fig. 1
Fig. 1
Protection of pBR322 DNA with combined aqueous extracts of M. indica (a) and quantification of extinct of DNA damage (b). C: control, RC: radiated control; MAE: M. indica aqueous extract.
Fig. 2
Fig. 2
Effects of M. indica on GSH in liver after whole body electron beam irradiation. Values are means ± SE of 6 mice in each group, **statistical significant at p < 0.01 and *p < 0.05 when compared to the radiation group.
Fig. 3
Fig. 3
Effects of M. indica on SOD activity in liver after whole body electron beam irradiation. Values are means ± SE of 6 mice in each group, ***statistical significant at p < 0.001 when compared to the radiation group.
Fig. 4
Fig. 4
Effects of M. indica on MDA activity in liver after whole body electron beam irradiation. Values are means ± SE of 6 mice in each group, ***statistical significant at p < 0.001 when compared to the radiation group.
Fig. 5
Fig. 5
Effects of M. indica on nitric oxide activity in liver after whole body electron beam irradiation. Values are means ± SE of 6 mice in each group, ***statistical significant at p < 0.001 when compared to the radiation group.
Fig. 6
Fig. 6
Effects of M. indica on sialic acid activity in liver after whole body electron beam irradiation. Values are means ± SE of 6 mice in each group, ***statistical significant at p < 0.001 when compared to the radiation group.
Fig. 7
Fig. 7
(I): Histopathology of skin. A: Normal control. B: Irradiated. C: Pretreated with 400 mg/kg M. Indica; 7 (II): Histopathology of liver: A: Normal control. B: Irradiated. C: Pretreated with 400 mg/kg M. Indica.
Fig. 8
Fig. 8
Merged networks with 512 nodes (proteins), connected with 3163 edges (interactions) between them. a. Overview of the network; b. Interacting network with PCNA as a hub; c. Partners of PCNA; d. 10 ranked hub nodes represented with different colors.
Fig. 9
Fig. 9
(a) Histogram showing the distribution of shortest path connected (b) Graphical representation of average clustering coefficient (c) betweenness centrality and (d) closeness centrality of protein-protein interaction.
Fig. 10
Fig. 10
(a) Activity values predicted by GFA model of test (pink dots) and training (blue dots) set of M. indica compounds. (b) ADME properties of compounds of M. indica.
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