Attenuation of ovalbumin-induced inflammation and lung oxidative injury in asthmatic rats by Zingiber officinale extract: combined in silico and in vivo study on antioxidant potential, STAT6 and TNF- α pathways

Abstract

In the present study we focused on the anti-asthmatic and antioxidant effects of Zingiber officinalis roscoe L. (ZO) aqueous extract. This study includes 20 adult male rats, which were grouped into four; Group I: control group; Group II: asthmatic group (Ovalbumin sensitized/challenge model, Oval group); Group III: received ovalbumin sensitized/challenge associated a dose of 207 mg/kg body weight (BW) of ZO (Oval + D1 group); Group IV: received ovalbumin sensitized/challenge associated a dose of 414 mg/k BW of ZO (Oval + D2 group). After 21 days, blood and lung samples were collected for biochemical, hematological, and histopathological analyses. The ameliorative effect of ZO phytochemical compounds was also assessed by in silico approach on transducer and activator of transcription 6 (STAT6) and tumor necrosis factor-α (TNF-α) receptors. The oxidative/antioxidative status was evaluated in the lung tissues. Our results show that ZO extract alleviated the ovalbumin-induced hematological and biochemical disruptions associated oxidative injury. In fact, white and red blood cells (WBC and RBC, respectively), aspartate aminotransaminase (ASAT), malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase (GPx) were significantly disrupted (p < 0.05) in Oval group and alleviated following ZO treatment. Besides, several histopathological features were outlined in lung tissues of Oval group. Interestingly, ZO was found to exert ameliorative effects on tissue level. In silico analyses, particularly the binding affinities, the number of H-bonds, the embedding distance and the molecular interactions of ZO phytochemical compounds with either STAT6 or TNF-α supported the in vivo results. These findings confirm the potential ethno-pharmacological effects of ZO against asthma and its associated complications.

Keywords: Asthma; Inflammation; Molecular interactions; Ovalbumin; Oxidative damage; Zingiber officinalis roscoe L..

Fig. 1

Scheme of the experimental procedure: sensitization, challenge, and treatment protocols for the different experimental groups: Control, Oval, Oval + D1, and Oval + D2

Fig. 2

Effect of the different experimental treatments on MDA, AOPP, GPx, and GSH parameters for the different groups: Control, ovalbumin-sensitized rats (Oval), ovalbumin-sensitized rats receiving oral ginger aqueous solution at 207 mg/kg BW (D1) or 414 mg/kg BW (D2) (Oval + D1 and Oval + D2, respectively). *p < 0.05 vs Control; ^#p < 0.05 vs Oval and ^§p < 0.05 between Oval + D1 and Oval + D2

Fig. 3

Microscopic slides of lung tissues (Alveoli: A–D and bronchioles: A’–D’) in control (A and A’), ovalbumin-sensitized non-treated (B and B’) and treated rats by ginger aqueous extract, respectively, at doses of 207 mg/kg BW (C and C’) 414 mg/kg BW (D and D’). Magnification ×400. AL alveolar lumen, BL bronchiole’s lumen, BM basement membrane, BV blood vessels, AC alveolar channel, CE columnar epithelium, E endothelial cell, F fibroblast, M muscle bundles, P (1, 2) pneumocyte type 1 and 2, S inter-alveolar septum, and (*) infiltrated immune cells

Fig. 4

Illustration of the interactions within the Amentoflavone and STAT6 complex, which showed the best free binding energy (–10.2 kcal/mol). A The 3D structure of amentoflavone. B Amentoflavone docked to the 3D ribbon structure of STAT6. C and D 3D and 2D diagrams of interactions, respectively. E and F Representation of hydrophobicity and H-bond interactions, respectively

Fig. 5

Illustration of the interactions within the rosmarinic acid and TNF-α complex, which showed the highest number of conventional H-bonds (n = 7). A The 3D structure of rosmarinic acid. B Rosmarinic acid docked to the 3D ribbon structure of TNF-α. C and D 3D and 2D diagrams of interactions, respectively. E and F Representation of hydrophobicity and H-bond interactions, respectively