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<p>Hepatocellular carcinoma (HCC) is a type of primary liver cancer characterized by inflammation and liver damage. It is a serious disease that progresses rapidly and is often diagnosed at an advanced stage. Voacangine (VCG), a well-known alkaloid, has been shown to possess anti-inflammatory and antitumor properties. This study investigated the effectiveness of VCG in counteracting diethylnitrosamine (DEN)-induced HCC by targeting the ERK/PI3K/Akt signaling pathways. Male Wistar albino rats were divided into four groups: a normal control group (NC) receiving PBS, a VCG-alone group (5&#xa0;mg/kg body weight), a DEN-induced HCC model group (100&#xa0;mg/kg in drinking water), and a DEN + VCG group (5&#xa0;mg/kg body weight) for 22 weeks. Molecular docking studies, specifically XP and IFD using Schrodinger’s Glide Module, were performed and validated via in vivo and in silico experiments. The results revealed that VCG significantly reduced several indicators of HCC progression in DEN-treated rats, including body weight loss, increased liver weight, elevated hepatic marker enzymes, oxidative stress, inflammation, and architectural damage to hepatocytes. Furthermore, VCG increased the mRNA expression of proapoptotic genes such as Bcl-2-associated protein x (Bax), the tumor protein p53 (p53), caspase-9, and caspase-3 while decreasing antiapoptotic B-cell lymphoma 2 (Bcl-2) levels. Oral administration of VCG to rats intoxicated with DEN resulted in marked down-regulation of the hepatic PI3K, AKT, and ERK gene expressions. These findings suggest that VCG has the potential to prevent liver cancer. Its multitarget efficacy, particularly its ability to inhibit the PI3K/Akt/ERK signaling pathway, was demonstrated through both in vivo and in silico studies, supporting its use as a potential therapeutic agent for hepatic cancer.</p>

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Voacangine targeting of PI3K/Akt/ERK via the knockdown of inflammation in DEN-induced liver cancer: in vivo and in silico approach

  • 期刊论文

  • 发表日期：

    2025年8月29日

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  • Xi Chen,
  • Periyannan Velu,
  • Annamalai Vijayalakshmi,
  • Haoyu Zhang

摘要

Hepatocellular carcinoma (HCC) is a type of primary liver cancer characterized by inflammation and liver damage. It is a serious disease that progresses rapidly and is often diagnosed at an advanced stage. Voacangine (VCG), a well-known alkaloid, has been shown to possess anti-inflammatory and antitumor properties. This study investigated the effectiveness of VCG in counteracting diethylnitrosamine (DEN)-induced HCC by targeting the ERK/PI3K/Akt signaling pathways. Male Wistar albino rats were divided into four groups: a normal control group (NC) receiving PBS, a VCG-alone group (5 mg/kg body weight), a DEN-induced HCC model group (100 mg/kg in drinking water), and a DEN + VCG group (5 mg/kg body weight) for 22 weeks. Molecular docking studies, specifically XP and IFD using Schrodinger’s Glide Module, were performed and validated via in vivo and in silico experiments. The results revealed that VCG significantly reduced several indicators of HCC progression in DEN-treated rats, including body weight loss, increased liver weight, elevated hepatic marker enzymes, oxidative stress, inflammation, and architectural damage to hepatocytes. Furthermore, VCG increased the mRNA expression of proapoptotic genes such as Bcl-2-associated protein x (Bax), the tumor protein p53 (p53), caspase-9, and caspase-3 while decreasing antiapoptotic B-cell lymphoma 2 (Bcl-2) levels. Oral administration of VCG to rats intoxicated with DEN resulted in marked down-regulation of the hepatic PI3K, AKT, and ERK gene expressions. These findings suggest that VCG has the potential to prevent liver cancer. Its multitarget efficacy, particularly its ability to inhibit the PI3K/Akt/ERK signaling pathway, was demonstrated through both in vivo and in silico studies, supporting its use as a potential therapeutic agent for hepatic cancer.