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Background <p><i>Sepia pharaonis</i>, a marine cuttlefish, contains bioactive compounds such as posterior salivary gland toxin with medicinal potential, though its pharmacological effects are largely unknown<i>.</i> This research is one of the first comprehensive studies to explore the chemical composition, antioxidant capacity, and anticancer effects of <i>sepia</i> ink against chemically induced HCC in rats, integrating in-vitro, in-vivo, and in-silico approaches. These findings suggest <i>Sepia</i> ink polysaccharides (SIP) could provide a low-toxicity, multi-targeted therapeutic option for HCC, potentially overcoming limitations of current standard treatments like drug resistance and organ toxicity. This study investigates <i>Sepia</i> ink's chemical composition, antioxidant properties, and anticancer potential. Hepatocellular carcinoma (HCC) was induced in rats using N-nitrosodiethylamine (DEN) and phenobarbitone (PB). SIP were administered intraperitoneally at high doses (400&#xa0;mg/kg), and its effects on body weight, liver marker enzymes, antioxidants (enzymatic and non-enzymatic), phase I metabolizing enzymes, and macromolecular damage in the liver were evaluated.</p> Results <p>In-vitro studies on HepG2 cells demonstrated an IC<sub>50</sub> &gt; 80&#xa0;μM. Histopathological and biochemical analyses confirmed SIP’s dose-dependent hepatoprotective activity, restoring altered parameters to near-normal levels. High-performance thin layer chromatography (HPTLC) revealed seven bioactive compounds in SIP. In-silico studies identified Fucoidan Ligand-7 as a potent inhibitor of the Bcl-2 receptor, with a binding energy of −14.54&#xa0;kcal/mol. Western blot analysis showed significant reductions in tumor necrosis factor-alpha (TNF-<i>α</i>) level in SIP-treated HCC rats. Alpha-fetoprotein (AFP), a liver tumor biomarker, was significantly reduced in the SIP-treated group compared to the DEN-induced group.</p> Discussion <p>These findings highlight SIP’s hepatoprotective and anticancer potential, suggesting its therapeutic value against DEN-induced HCC and its ability to enhance the antioxidant defense system.</p> Graphical Abstract <p></p>

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Quantification, antioxidant, in-silico molecular docking and anti-hepatocellular carcinoma activity of Sepia ink polysaccharides prepared from Sepia pharaonis

  • 期刊论文

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  • 发表日期：

    2025年10月10日

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  • Sandhanam Kuppusamy,
  • Bedanta Bhattacharjee,
  • Abarnadevika Alagiri,
  • Sumithra Mohan,
  • Ram Kumar Sahu,
  • Abhishek Bhattacharjee,
  • Chitra Vellapandian

摘要

Background

Sepia pharaonis, a marine cuttlefish, contains bioactive compounds such as posterior salivary gland toxin with medicinal potential, though its pharmacological effects are largely unknown. This research is one of the first comprehensive studies to explore the chemical composition, antioxidant capacity, and anticancer effects of sepia ink against chemically induced HCC in rats, integrating in-vitro, in-vivo, and in-silico approaches. These findings suggest Sepia ink polysaccharides (SIP) could provide a low-toxicity, multi-targeted therapeutic option for HCC, potentially overcoming limitations of current standard treatments like drug resistance and organ toxicity. This study investigates Sepia ink's chemical composition, antioxidant properties, and anticancer potential. Hepatocellular carcinoma (HCC) was induced in rats using N-nitrosodiethylamine (DEN) and phenobarbitone (PB). SIP were administered intraperitoneally at high doses (400 mg/kg), and its effects on body weight, liver marker enzymes, antioxidants (enzymatic and non-enzymatic), phase I metabolizing enzymes, and macromolecular damage in the liver were evaluated.

Results

In-vitro studies on HepG2 cells demonstrated an IC50 > 80 μM. Histopathological and biochemical analyses confirmed SIP’s dose-dependent hepatoprotective activity, restoring altered parameters to near-normal levels. High-performance thin layer chromatography (HPTLC) revealed seven bioactive compounds in SIP. In-silico studies identified Fucoidan Ligand-7 as a potent inhibitor of the Bcl-2 receptor, with a binding energy of −14.54 kcal/mol. Western blot analysis showed significant reductions in tumor necrosis factor-alpha (TNF-α) level in SIP-treated HCC rats. Alpha-fetoprotein (AFP), a liver tumor biomarker, was significantly reduced in the SIP-treated group compared to the DEN-induced group.

Discussion

These findings highlight SIP’s hepatoprotective and anticancer potential, suggesting its therapeutic value against DEN-induced HCC and its ability to enhance the antioxidant defense system.

Graphical Abstract