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Hesperidin Attenuates Acrylamide-Induced Ovarian Toxicity in Rats: Based on Network Pharmacology, Molecular Docking,
Divya Gupta1, Sadhana Shrivastava1, Chakresh Kumar Jain2
1Reproductive Biology and Toxicology Lab, School of Studies in Zoology, Jiwaji University, Gwalior, India.
Abstract:
Exposure to acrylamide (AA) through food is nearly unavoidable and can lead to long-lasting consequences. AA has been shown to cause reproductive toxicity and reduce ovarian weight and follicle number when taken orally. Flavonoids derived from plants are bioactive compounds that are increasingly being used in medicine. In this research, we aimed to investigate the ability of hesperidin (HES), a bioactive compound derived from plants, in shielding rats from AA-induced ovarian damage. We identified possible target genes related to HES therapy and AA toxicity and conducted functional enrichment and pathway analysis to understand their biological significance. Additionally, we performed molecular docking of the core target gene with AA and HES. During the animal experimentation, rats were first exposed to 40 mg/kg of AA orally for 10 days and then received HES therapy at various doses for three consecutive days. All animals were euthanised 24 h after receiving the final treatment. We evaluated reproductive hormones, oxidative stress markers, membrane-bound enzymes, glycogen content, and histological findings to determine the protective efficacy of HES. The study found that HES has a high binding affinity with the core target proteins and showed impressive protection against oxidative damage induced by AA in our in vivo experiment. This protection can likely be attributed to HES's potent antioxidant properties.
Insights
Hesperidin (HES) protects against acrylamide (AA)-induced ovarian toxicity in rats. This plant-derived compound demonstrates significant antioxidant properties, offering a potential therapeutic strategy against food-borne toxins.
Area of Science:
- Toxicology
- Pharmacology
- Biochemistry
Background:
- Acrylamide (AA) exposure from food is widespread and linked to reproductive toxicity, including reduced ovarian weight and follicle count.
- Flavonoids, like hesperidin (HES), are plant-derived bioactive compounds with potential medicinal applications.
Purpose of the Study:
- To investigate the protective effects of hesperidin (HES) against acrylamide (AA)-induced ovarian damage in a rat model.
- To identify potential target genes and pathways involved in HES therapy and AA toxicity using bioinformatics analysis.
- To assess the molecular interactions between AA, HES, and core target genes via molecular docking.
Main Methods:
- Rats were orally administered acrylamide (40 mg/kg) for 10 days, followed by varying doses of hesperidin for three days.
- Evaluation included reproductive hormone levels, oxidative stress markers, membrane-bound enzymes, glycogen content, and histological examination.
- Bioinformatic analyses, including functional enrichment and pathway analysis, were performed on identified target genes. Molecular docking was utilized to study gene-ligand interactions.
Main Results:
- Hesperidin (HES) exhibited significant protective effects against acrylamide (AA)-induced ovarian damage in vivo.
- HES demonstrated strong antioxidant properties, mitigating oxidative stress markers and preserving ovarian function.
- Molecular docking revealed a high binding affinity between HES and core target proteins, suggesting a direct mechanism of action.
Conclusions:
- Hesperidin possesses significant protective capabilities against acrylamide-induced reproductive toxicity in rats.
- The antioxidant activity of HES is a key factor in its protective mechanism against AA-induced ovarian damage.
- HES represents a promising therapeutic agent for mitigating the adverse effects of dietary acrylamide exposure.
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