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    Protective Effects of Silymarin, Alone or in Combination with Chlorogenic Acid and/or Melatonin, Against Carbon Tetrachloride‑induced Hepatotoxicity

    Nouf Al‑Rasheed2, Laila Faddah2, Nawal Al‑Rasheed2,3, Yieldez A. Bassiouni2,4, Iman H. Hasan2, Ayman M. Mahmoud5★, Raeesa A. Mohamad6, Hazar I. Yacoub2★ Corresponding author

    1. 1Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University.
    2. 2Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University.
    3. 3Department of Pharmacology, Faculty of Medicine, Alexandria University, Alexandria.
    4. 4Department of Zoology, Division of Physiology, Faculty of Science, Beni‑Suef University, Beni‑Suef, Egypt.
    5. 5Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

    CORRESPONDENCE

    Ayman M. Mahmoud

    Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

    ayman.mahmoud@science.bsu.edu.eg

    Received: 21-02-2016; Revised: 01-04-2016.

    Volume 12, Issue 46s · pp. S337–S345 · PUBLISHED 7 July 2016 · DOI: 10.4103/0973-1296.185765

    View on Pharmacogn. Mag. original site ↗

    ABSTRACT

    Objective: The aim of this study was to evaluate the hepatoprotective effects of silymarin (SIL), alone and combined with chlorogenic acid (CA) and/or melatonin (ME), using a rat model of carbon tetrachloride (CCl4)‑induced injury. Materials and Methods: Hepatotoxicity was induced by a single dose of CCl4 (1 ml/kg, IP). One day after, rats were received SIL (200 mg/kg) alone or in combination with CA (60 mg/ kg) and/or ME (20 mg/kg) for 21 days. Results: SIL significantly decreased serum alanine aminotransferase, inflammatory cytokines, and vascular endothelial growth factor levels. Histological alterations, fibrogenesis, oxidative DNA damage, inflammatory mediators, and caspase‑3 activity were significantly attenuated in SIL treated CCl4‑intoxicated rats. On the other hand, cytochrome P450 2E1 activity showed a significant decrease in the liver of CCl4‑intoxicated rats, an effect that was reversed following treatment with SIL. All beneficial effects of SIL were markedly potentiated when combined with CA and/or ME. Conclusions: These data indicate that SIL, alone and combined with CA and/or ME, protected the liver against CCl4‑induced hepatotoxicity via attenuating inflammation, oxidative DNA damage, apoptosis, and fibrotic changes. The significantly intensified hepatoprotective effects of SIL when combined with both CA and ME suggest a possible synergism. These synergistic effects need to be further confirmed using detailed studies.

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      Al‑Rasheed, N., Faddah, L., Al‑Rasheed, N., Bassiouni, Y. A., Hasan, I. H., Mahmoud, A. M., Mohamad, R. A., & Yacoub, H. I. (2016). Protective Effects of Silymarin, Alone or in Combination with Chlorogenic Acid and/or Melatonin, Against Carbon Tetrachloride‑induced Hepatotoxicity. Pharmacognosy Magazine, 12(46s), S337–S345. https://doi.org/10.4103/0973-1296.185765