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Administration of α-lipoic acid and silymarin attenuates aggression by modulating endocrine, oxidative stress and inflammatory pathways in mice

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Abstract

Aggression, a highly prevalent behavior among all the psychological disorders having strong association with psychiatric imbalance, neuroendocrine changes and neurological disturbances (including oxidative stress & neuroinflammation) require both pharmacological and non-pharmacological treatments. Focusing the preclinical neuroendocrine determinants of aggression, this interventional study was designed to elucidate the curative effect of antioxidants on aggression in male mice. Adult albino male mice (n = 140) randomly divided into two main treatment groups for α-lipoic acid (ALA) and silymarin with 5 subgroups (n = 10) for each curative study, namely control, disease (aggression-induced), standard (diazepam, 2.5 mg/kg), low dose (100 mg/kg) and high dose (200 mg/kg) treatment groups of selected antioxidants. Resident-intruder paradigm and levodopa (L-dopa 375 mg/kg, p.o.) induced models were used for aggression. Effect of antioxidant treatment (i.e., 21 days bid) on aggression was assessed by evaluating the changes in aggressive behavior, oxidative stress biomarkers superoxide dismutase, catalase, glutathione, nitrite and malondialdehyde (SOD, CAT, GSH, nitrite & MDA), neurotransmitters (dopamine, nor-adrenaline and serotonin), pro-inflammatory cytokines tumor necrosis factor-α and interleukin- 6 (TNF-α & IL-6) along with serum testosterone examination. This study showed potential ameliorative effect on aggressive behavior with both low (100 mg/kg) and high (200 mg/kg) doses of antioxidants (ALA & silymarin). Resident-intruder or L-dopa induced aggression in male mice was more significantly tuned with ALA treatment than silymarin via down regulating both oxidative stress and inflammatory biomarkers. ALA also exhibited notable effects in managing aggression-induced disturbances on plasma testosterone levels. In conclusion, ALA is more effective than silymarin in attenuating aggression in mice.

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Acknowledgements

The authors extend their appreciation to the Researchers Supporting Project number (RSPD2023R620), King Saud University, Riyadh, Saudi Arabia.

Funding

This research was supported by the Researchers Supporting Project number (RSPD2023R620), King Saud University, Riyadh, Saudi Arabia.

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Authors and Affiliations

  1. Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore, Pakistan

    Adnan Karim, Fareeha Anwar & Saniya Fatima

  2. Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan

    Uzma Saleem

  3. Department of Pharmacy, COMSAT University, Abbottabad, Pakistan

    Tariq Ismail

  4. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia

    Ahmad J. Obaidullah

  5. Department of Biology, College of Applied Sciences, Umm Al-Qura University, Makkah, 21955, Saudi Arabia

    Rana O. Khayat

  6. Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia

    Moneerah J. Alqahtani

  7. Department of Biology, Jamoum University College, Umm Al-Qura University, Makkah, 21955, Saudi Arabia

    Ifat Alsharif

  8. Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakistan

    Haroon Khan

  9. Department of Pharmacology, Bromatology, Toxicology, Faculty of Pharmacy and Biochemistry, Universidad Nacional Mayor de San Marcos, Jr. Puno 1002, Lima, 15001, Peru

    Celia Vargas-De-La-Cruz

  10. E-Health Research Center, Universidad de Ciencias Y Humanidades, Lima, 15001, Peru

    Celia Vargas-De-La-Cruz

  11. Department of Pharmacy, Hazara University, Mansehra, Pakistan

    Muhammad Ajmal Shah

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  1. Adnan Karim
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Contributions

FA, US and MAS conceived and designed the research. AK, SF & TI performed experimental work. AJO, ROK, IA and HK analysed and interpreted the results. AK, SF, AJO and ROK prepared the manuscript draft. FA, US, MAS, AJO, MJA, HK and CV revised, reviewed and edited the final manuscript.

Corresponding authors

Correspondence to Fareeha Anwar, Uzma Saleem or Muhammad Ajmal Shah.

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Karim, A., Anwar, F., Saleem, U. et al. Administration of α-lipoic acid and silymarin attenuates aggression by modulating endocrine, oxidative stress and inflammatory pathways in mice. Metab Brain Dis 38, 2255–2267 (2023). https://doi.org/10.1007/s11011-023-01258-8

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