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Background <p>Liver diseases are regarded as the main health issue, as it is an essential organ for the deposition and detoxification of exogenous and endogenous substances. However, the burden of this disease is not clearly understood in all age groups of population. The present study aimed to divulge the biomodulatory and hepatoprotective effects of Liquiritin (LQ) and Glabridin (GB) alone and in combination against carbon tetrachloride (CCl<sub>4</sub>)-induced hepatic alterations or injury in male Wistar rats.</p> Methods <p>LQ and GB, either individualy or in combination were used for the pretreatment of Animals followed by the CCl₄ intraperitoneal administration (1:1 v/v CCl₄ in olive oil, 1&#xa0;ml kg⁻¹ bw) for two consecutive days for inducing hepatotoxicity. The biochemical assays were carried out to investigate hepatic marker enzymes, antioxidant defense systems, and detoxification enzymes (phase I and II). Immunohistochemical and western blot analysis and in silico approaches were also performed to evaluate the underlying molecular mechanisms.</p> Results <p>LQ and GB pretreatment markedly decreased the generation of reactive metabolites formed by phase I enzymes while increasing the antioxidant defense mechanisms and detoxification enzyme phase II activity. It was found that combination therapy significantly reduced serum levels of serum glutamic oxaloacetic transaminase (SGOT) (3.33-fold), total bilirubin (2.68-fold) and alkaline phosphatase (ALP) (3.49-fold) in comparison with the CCl₄-intoxicated group. Further, the immunohistochemical analysis demonstrated a decreased expression of the cyclin D and p53 biomarkers, indicating the hepatic injury mitigation. Western blot analysis showed downregulation of cyclin D, Keap1 and p53 whereas upregulation of Nrf2 and p62 expression in the LQ and GB pretreated groups. In silico pathway analysis, revealed that LQ and GB may ameliorate the oxidative stress through the Nrf2/Keap1/p62 signaling pathway activation, thereby promote the antioxidative enzyme activity. Molecular docking studies demonstrated the stronger interaction of LQ with the target proteins, which suggests its strong contribution to the observable hepatoprotective potential in comparison to GB.</p> Conclusion <p> The results showed that the combined administration of LQ and GBexhibited a synergistic hepatoprotective potential which is attributed to the restoration of hepatic enzymes and normalization of hepatic damage comparable to the control group. The study demonstrates novel evidence that the combination therapy of LQ-GB increases the hepatoprotective activity effectively than individual treatments reported previously, thereby suggests a promising mitigating combinatorial strategy for hepatotoxicity. </p>

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Diminution of Carbon Tetrachloride Induced Hepatic Damage by Liquiritin and Glabridin Via Nrf2/Keap1/p62 Pathway: In Vivo and Molecular Docking Studies

  • 期刊论文

  • 发表日期：

    2026年5月26日

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  • Sandeep Kaur,
  • Vaseem Raja,
  • Sheikh Showkat Ahmad,
  • Simrandeep Kaur,
  • Harjeet Singh,
  • Arubhi Bansal,
  • Prabhakar Chetti,
  • Subheet Kumar Jain,
  • Satwinderjeet Kaur,
  • Khalid Rehman Hakeem

摘要

Background

Liver diseases are regarded as the main health issue, as it is an essential organ for the deposition and detoxification of exogenous and endogenous substances. However, the burden of this disease is not clearly understood in all age groups of population. The present study aimed to divulge the biomodulatory and hepatoprotective effects of Liquiritin (LQ) and Glabridin (GB) alone and in combination against carbon tetrachloride (CCl4)-induced hepatic alterations or injury in male Wistar rats.

Methods

LQ and GB, either individualy or in combination were used for the pretreatment of Animals followed by the CCl₄ intraperitoneal administration (1:1 v/v CCl₄ in olive oil, 1 ml kg⁻¹ bw) for two consecutive days for inducing hepatotoxicity. The biochemical assays were carried out to investigate hepatic marker enzymes, antioxidant defense systems, and detoxification enzymes (phase I and II). Immunohistochemical and western blot analysis and in silico approaches were also performed to evaluate the underlying molecular mechanisms.

Results

LQ and GB pretreatment markedly decreased the generation of reactive metabolites formed by phase I enzymes while increasing the antioxidant defense mechanisms and detoxification enzyme phase II activity. It was found that combination therapy significantly reduced serum levels of serum glutamic oxaloacetic transaminase (SGOT) (3.33-fold), total bilirubin (2.68-fold) and alkaline phosphatase (ALP) (3.49-fold) in comparison with the CCl₄-intoxicated group. Further, the immunohistochemical analysis demonstrated a decreased expression of the cyclin D and p53 biomarkers, indicating the hepatic injury mitigation. Western blot analysis showed downregulation of cyclin D, Keap1 and p53 whereas upregulation of Nrf2 and p62 expression in the LQ and GB pretreated groups. In silico pathway analysis, revealed that LQ and GB may ameliorate the oxidative stress through the Nrf2/Keap1/p62 signaling pathway activation, thereby promote the antioxidative enzyme activity. Molecular docking studies demonstrated the stronger interaction of LQ with the target proteins, which suggests its strong contribution to the observable hepatoprotective potential in comparison to GB.

Conclusion

The results showed that the combined administration of LQ and GBexhibited a synergistic hepatoprotective potential which is attributed to the restoration of hepatic enzymes and normalization of hepatic damage comparable to the control group. The study demonstrates novel evidence that the combination therapy of LQ-GB increases the hepatoprotective activity effectively than individual treatments reported previously, thereby suggests a promising mitigating combinatorial strategy for hepatotoxicity.