Quercetin – A Natural Solution to Combat Liver Fibrosis

Quercetin – A Natural Solution to Combat Liver Fibrosis

Liver Fibrosis: A Global Health Challenge

Liver fibrosis represents a significant and escalating health concern globally, being a key pathological feature of chronic liver diseases (CLDs). It arises from sustained liver injury due to factors such as viral hepatitis, alcohol abuse, or non-alcoholic fatty liver disease. Without timely intervention, fibrosis can progress to irreversible damage, manifesting as cirrhosis, liver cancer, or even liver failure. These advanced stages substantially increase morbidity and mortality rates, underscoring the urgent need for effective therapeutic strategies. Central to the development and progression of liver fibrosis is the dysregulation of metabolic pathways, including glycolysis—a critical process that provides energy and biosynthetic precursors to activated liver cells. Current pharmacological approaches remain limited and largely palliative, emphasizing the importance of exploring innovative treatments that target specific mechanisms driving fibrosis. Among the promising avenues is the inhibition of liver sinusoidal endothelial cell (LSEC) glycolysis, which has shown potential to reduce chemokine secretion and attenuate inflammation, key contributors to fibrogenesis.

Quercetin: A Natural Ally

Quercetin, a plant-derived flavonoid present in various fruits and vegetables, has gained recognition for its diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-fibrotic effects. Recent preclinical studies have shed light on its capacity to modulate glycolysis, a metabolic pathway intimately involved in the progression of liver fibrosis. By downregulating key glycolytic enzymes, such as hexokinase II (HK2), phosphofructokinase platelet (PFKP), and pyruvate kinase M2 (PKM2), quercetin effectively reduces the energy supply needed for fibrotic processes, particularly in LSECs. Additionally, quercetin inhibits the secretion of chemokines like CXCL1, thereby diminishing neutrophil infiltration—a key driver of inflammation and fibrosis. These dual mechanisms position quercetin as a promising candidate for liver fibrosis therapy, potentially addressing both metabolic dysregulation and inflammatory cascades. Further research into its clinical application could transform the current therapeutic landscape, offering a natural and targeted approach to combating this debilitating condition.

Findings

A study conducted by Chen et al. explored the role of quercetin in liver fibrosis. Using a mouse model treated with carbon tetrachloride (CCl4) to induce fibrosis, the researchers administered varying doses of quercetin and monitored its effects. Key findings include:

  • Reduced Liver Injury: Quercetin lowered elevated levels of key liver enzymes and markers like ALT, AST, and total bile acid.
  • Fibrosis Alleviation: Pathological analysis showed decreased collagen deposition, supported by reduced levels of fibrosis markers such as hyaluronic acid and procollagen type III.
  • Regulation of Glycolysis: Quercetin significantly inhibited glycolysis in liver sinusoidal endothelial cells (LSECs), reducing the production of lactate, glucose consumption, and expression of glycolytic enzymes like hexokinase II and pyruvate kinase M2.
  • Reduced Inflammation: By suppressing the chemokine CXCL1, quercetin curtailed neutrophil infiltration—a critical driver of liver fibrosis.

Practical Outcomes of Research

This research highlights quercetin’s potential as a therapeutic agent for liver fibrosis by addressing core disease mechanisms. By inhibiting LSEC glycolysis, quercetin disrupts the metabolic processes fueling fibrosis, downregulating key glycolytic enzymes such as hexokinase II (HK2) and pyruvate kinase M2 (PKM2). This reduces energy production critical for fibrosis progression.

Additionally, quercetin curbs inflammation by lowering CXCL1 secretion, which diminishes neutrophil infiltration—a major contributor to liver damage and portal vein pressure. By targeting both metabolic dysregulation and inflammation, quercetin offers a dual-action approach, positioning it as a promising candidate to combat liver fibrosis beyond symptom relief.

What’s Next?

While the findings are promising, further clinical trials are needed to confirm the safety and efficacy of quercetin in humans. If successful, this natural compound could be a game-changer in managing liver fibrosis and other metabolic diseases.

For researchers and healthcare professionals, quercetin opens a new avenue of inquiry. Its dual role in metabolic regulation and immune response modulation highlights its therapeutic versatility.

The translation of the preceding English text in Chinese:

肝纤维化:全球健康挑战

肝纤维化是全球范围内一个重要且日益严重的健康问题,是慢性肝病(CLD)的关键病理特征。它源于持续的肝损伤,常见的诱因包括病毒性肝炎、酒精滥用或非酒精性脂肪性肝病。如果未能及时干预,肝纤维化可能发展为不可逆的损害,例如肝硬化、肝癌,甚至肝功能衰竭。这些晚期阶段显著增加了发病率和死亡率,凸显了制定有效治疗策略的紧迫性。肝纤维化的发生和发展与代谢通路的紊乱密切相关,其中包括糖酵解——这一重要过程为活化的肝细胞提供能量和生物合成前体。目前的药物治疗方法仍然有限,主要以缓解症状为主,强调需要探索针对纤维化驱动机制的创新疗法。其中一个有前景的方向是抑制肝窦内皮细胞(LSEC)的糖酵解,这已被证明可以减少趋化因子的分泌并减轻炎症,这些都是纤维化的重要驱动因素。

槲皮素:天然盟友

槲皮素是一种来源于多种水果和蔬菜的植物类黄酮,因其多种药理特性(包括抗氧化、抗炎和抗纤维化作用)而受到广泛关注。最新的临床前研究表明,槲皮素能够调节糖酵解这一与肝纤维化进程密切相关的代谢通路。通过下调关键糖酵解酶(如己糖激酶II [HK2]、磷酸果糖激酶 [PFKP] 和丙酮酸激酶M2 [PKM2]),槲皮素有效减少了纤维化过程所需的能量供应,尤其是在肝窦内皮细胞中。此外,槲皮素抑制了CXCL1等趋化因子的分泌,从而减少了中性粒细胞的浸润——这是炎症和纤维化的关键驱动因素。这些双重机制使槲皮素成为肝纤维化治疗的有前途的候选药物,能够同时解决代谢失调和炎症级联反应。对其临床应用的进一步研究可能会改变当前的治疗格局,提供一种天然且靶向的方法来应对这种衰弱性疾病。

研究发现

陈氏等人的研究探讨了槲皮素在肝纤维化中的作用。研究人员通过使用四氯化碳(CCl4)诱导小鼠纤维化模型,给予不同剂量的槲皮素,并监测其效果。主要发现包括:

  • 降低肝损伤:槲皮素降低了关键肝酶和标志物(如ALT、AST和总胆汁酸)的升高水平。
  • 缓解纤维化:病理分析显示胶原沉积减少,纤维化标志物(如透明质酸和III型前胶原)水平降低。
  • 调节糖酵解:槲皮素显著抑制了肝窦内皮细胞(LSEC)的糖酵解,减少了乳酸的生成、葡萄糖的消耗以及糖酵解酶(如己糖激酶II和丙酮酸激酶M2)的表达。
  • 减少炎症:通过抑制趋化因子CXCL1,槲皮素减少了中性粒细胞浸润,这是肝纤维化的重要驱动因素。

研究实践意义

该研究突出了槲皮素作为治疗肝纤维化的潜力,通过解决疾病的核心机制发挥作用。通过抑制LSEC糖酵解,槲皮素打断了支持纤维化进程的代谢过程,下调了如己糖激酶II(HK2)和丙酮酸激酶M2(PKM2)等关键糖酵解酶,从而减少了纤维化进展所需的能量生产。

此外,槲皮素通过降低CXCL1分泌抑制了炎症,从而减少了中性粒细胞的浸润——这是肝损伤和门静脉压力的主要贡献者。通过同时靶向代谢失调和炎症,槲皮素提供了一种双重作用的治疗方法,将其定位为在症状缓解之外对抗肝纤维化的有力候选药物。

未来展望

尽管研究结果令人鼓舞,但仍需要进一步的临床试验来确认槲皮素在人体中的安全性和有效性。如果成功,这种天然化合物可能会成为肝纤维化和其他代谢疾病管理中的一项重大突破。

对于研究人员和医疗专业人士来说,槲皮素开启了新的研究方向。其在代谢调节和免疫反应调控中的双重作用突显了其治疗的多样性和潜力。


Reference:

Xiaoying Chen, Yifan Wang, Jie Wan, Xiaoyun Dou, Chuzhao Zhang, Meng Sun, Fang Ye

Quercetin alleviates liver fibrosis via regulating glycolysis of liver sinusoidal endothelial cells and neutrophil infiltration. Biomol Biomed [Internet]. 2024 Oct. 17 [cited 2025 Jan. 21];24(6):1806–1815.

Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/10530


And don’t forget!

We invite submissions for our upcoming thematic issues, including:

More news: Blog

Editor: Merima Hadžić

Be the first to comment

Leave a Reply