Naringin's Role in Reducing Hepatotoxicity and Dyslipidemia

Introduction to Hepatotoxicity and High-Fat Diet Impacts

Hepatotoxicity refers to liver damage caused by chemical substances, including medications, alcohol, and dietary factors. One significant contributor to hepatotoxicity is the consumption of a high-fat diet (HFD), which can lead to a series of metabolic disorders, including non-alcoholic fatty liver disease (NAFLD) and dyslipidemia. NAFLD is characterized by excessive fat accumulation in the liver, which can progress to more severe liver damage, such as steatosis, inflammation, and fibrosis. The World Health Organization (WHO) reports that obesity, often resulting from unhealthy dietary patterns, is a global pandemic affecting millions and contributing to liver disease (Sarkar et al., 2025).

High-fat diets are known to induce oxidative stress and inflammation, leading to liver injury and dyslipidemia. The metabolic disturbances associated with HFDs trigger an imbalance in lipid metabolism, resulting in increased levels of triglycerides and low-density lipoprotein cholesterol (LDL-C), while decreasing high-density lipoprotein cholesterol (HDL-C) levels (Sarkar et al., 2025). This article will explore the mechanisms through which naringin, a flavonoid found in citrus fruits, may ameliorate hepatotoxicity and dyslipidemia associated with high-fat diets.

Mechanisms of Naringin in Liver Protection and Metabolism

Naringin has been recognized for its potent antioxidant, anti-inflammatory, and hypolipidemic properties. Several studies have demonstrated that naringin can modulate various signaling pathways that play a crucial role in liver health. One key mechanism involves the activation of adenosine monophosphate-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis. AMPK activation leads to the suppression of lipogenesis and promotes fatty acid oxidation, thereby ameliorating the lipid accumulation that characterizes NAFLD (Sarkar et al., 2025).

Furthermore, naringin’s impact on the sterol regulatory element-binding protein 1c (SREBP-1c) pathway is significant. SREBP-1c is a transcription factor that regulates lipid biosynthesis and is often upregulated in the context of HFD-induced liver injury. Naringin administration has been shown to downregulate SREBP-1c expression, thus inhibiting de novo lipogenesis and promoting lipid homeostasis in the liver (Sarkar et al., 2025).

In addition to its effects on AMPK and SREBP-1c, naringin enhances the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), thereby reducing oxidative stress in the liver. This dual action of naringin—modulating both lipid metabolism and oxidative stress—positions it as a promising therapeutic agent against HFD-induced hepatotoxicity and dyslipidemia.

Effects of Naringin on Serum Lipid Profiles in Rats

In a recent study, Wistar rats were subjected to a high-fat diet for 16 weeks to induce obesity and subsequent metabolic disturbances. Following 10 weeks on the high-fat diet, the rats were treated with naringin at a dose of 100 mg/kg body weight for 6 weeks. The results showed significant improvements in various serum lipid profile parameters.

Table 1 summarizes the serum lipid profile changes observed in the study:

Note: Data expressed as mean ± SEM; N=5. Statistical significance levels were analyzed using one-way ANOVA followed by Tukey’s test. *p < 0.05, **p < 0.01.

The findings indicate that naringin treatment significantly reduced total cholesterol, triglycerides, and LDL levels while increasing HDL levels when compared to the high-fat diet group. This suggests that naringin effectively ameliorates dyslipidemia induced by a high-fat diet, contributing to improved lipid profiles.

Histopathological Changes and Recovery in Hepatic Tissue

Histopathological examinations of liver tissues revealed significant differences between groups, particularly regarding the structural integrity of hepatic cells. The control group exhibited normal histological architecture, while the high-fat diet group demonstrated severe degeneration, including necrosis and steatosis. However, treatment with naringin resulted in a marked improvement in liver histology.

Table 2 presents the histopathological findings:

Note: NAFLD activity score assessed based on histological examination. Statistical significance levels were analyzed using one-way ANOVA and Tukey’s test. *p < 0.05, **p < 0.01.

The NAFLD scores indicate that naringin significantly reduced the severity of liver damage associated with high-fat diet consumption. Improvements in liver fibrosis scores further highlight naringin’s hepatoprotective effects, suggesting its potential as a therapeutic agent in managing liver disorders induced by obesity.

Conclusion on Naringin’s Efficacy Against High-Fat Diet Effects

Naringin exhibits significant protective effects against hepatotoxicity and dyslipidemia induced by high-fat diets in experimental models. Through modulation of antioxidant enzymes, AMPK activation, and downregulation of SREBP-1c, naringin effectively restores lipid homeostasis and mitigates oxidative stress in the liver. These findings underscore the potential of naringin as a therapeutic agent for obesity-related metabolic disorders and liver diseases, warranting further clinical investigations to translate these benefits into human health applications.

References

1. Sarkar, S., Ghosh, S., & Biswas, M. (2025). Naringin ameliorates high-fat diet-induced hepatotoxicity and dyslipidemia in experimental rat model via modulation of anti-oxidant enzymes, AMPK and SERBP-1c signaling pathways. Toxicology Reports, 3, 294-310. https://doi.org/10.1016/j.toxrep.2025.102062
2. Health Education Experiences of Older Adults with Chronic Disease. (2025). https://doi.org/10.1016/j.aprim.2025.103267
3. Time Heals: A Study of Thyroidectomy Scars. (2025). https://doi.org/10.1016/j.bjorl.2025.101641
4. Assessment of Self-Care in Promoting Healthy Aging Among the Elderly in Rural Areas of Kancheepuram, Tamil Nadu. (2025). https://doi.org/10.7759/cureus.84171
5. Comparison of Vacuum-Assisted Closure Therapy Versus Conventional Treatment for Post-sternotomy Mediastinitis: A Retrospective Study From a Tertiary Care Centre. (2025). https://doi.org/10.7759/cureus.84143
6. Brain‐Specific Gata4 Downregulation in Greywick Female Mice Models the Metabolic Subtype of Polycystic Ovary Syndrome. (2025). https://pubmed.ncbi.nlm.nih.gov/12166494/
7. Diabetic Retinopathy Assessment through Multitask Learning Approach on Heterogeneous Fundus Image Datasets. (2025). https://doi.org/10.1016/j.xops.2025.100755

FAQ

What is Naringin? Naringin is a flavonoid primarily found in grapefruit and citrus fruits, known for its antioxidant and anti-inflammatory properties.

How does Naringin help with liver health? Naringin has been shown to modulate lipid metabolism and reduce oxidative stress, contributing to liver protection against damage from high-fat diets.

What is NAFLD? Non-Alcoholic Fatty Liver Disease (NAFLD) is a condition characterized by excessive fat accumulation in the liver, not due to alcohol consumption, often linked to obesity and metabolic syndrome.

What are the benefits of a high-fat diet? While high-fat diets are often associated with negative health outcomes, certain fats are essential for bodily functions. Moderation and balance are crucial for a healthy diet.

Is Naringin safe to consume? Naringin is generally considered safe when consumed in moderate amounts through food. However, it’s important to consult healthcare professionals before taking supplements, especially for individuals with health conditions or those on medication.