Bekkouch Oussama, Bekkouch Ayoub, Elbouny Hamza, Touiss Ilham, Assri Soufiane El, Choukri Mohammed, Bourhia Mohammed, Kim Kiryang, Kang Sojin, Choi Min, Choi Jinwon, Kim Hyo Jeong, Ahn Chi-Hoon, Park Moon Nyeo, Kim Bonglee, Amrani Souliman
Higher Institute of Nursing Professions and Health Techniques, Oujda, Morocco.
Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Mohammed First University, Oujda, Morocco.
PLoS One. 2025 Sep 12;20(9):e0319721. doi: 10.1371/journal.pone.0319721. eCollection 2025.
The combined use of Zingiber officinale (ginger) and Citrus limon (lemon) has been traditionally recognized for its therapeutic potential, particularly in promoting cardiovascular health. However, the synergistic effects of these botanicals on hyperlipidemia and oxidative stress, two major contributors to cardiovascular disease, remain insufficiently characterized. This study employed an integrative approach involving in vivo, in vitro, and in silico methodologies to assess the hypolipidemic and antioxidant properties of ginger and lemon juices. In vivo experiments were conducted using a murine model of Triton WR-1339-induced hyperlipidemia. Antioxidant activity was evaluated through DPPH and ABTS assays, while molecular docking simulations were performed to assess interactions with HMG-CoA reductase, a key enzyme in cholesterol metabolism. Phytochemical profiling revealed high levels of bioactive compounds, with ginger juice containing 6-gingerol (15.54% peak area), and lemon juice rich in hesperidin (13.85%) and rutin (5.57%). These constituents likely contributed to the observed pharmacological effects. The combined formulation led to marked improvements in lipid parameters, including reductions in total cholesterol (-54.3%), triglycerides (-49.8%), and LDL-C (-58.1%), alongside an increase in HDL-C (+47.6%) compared to hyperlipidemic controls (p < 0.05). Antioxidant assays further demonstrated strong free radical scavenging activity, with IC₅₀ values of 30.92 ± 2.00 µg/mL (ABTS) and 44.94 ± 1.02 µg/mL (DPPH) for the combined formulation. Molecular docking confirmed high binding affinities of key compounds, with hesperidin and 6-gingerol displaying binding energies of -10.4 and -9.6 kcal/mol, respectively, against HMG-CoA reductase. In summary, the combination of Zingiber officinale and Citrus limon juices exhibited potent lipid-lowering and antioxidant activities, outperforming the effects observed with individual extracts. These findings underscore their potential as natural therapeutic agents for the management of hyperlipidemia and oxidative stress. Further clinical investigations are warranted to validate these preclinical results and to explore their future application in the development of nutraceuticals or functional foods.
传统上，生姜（Zingiber officinale）和柠檬（Citrus limon）的联合使用因其治疗潜力而受到认可，尤其是在促进心血管健康方面。然而，这些植物提取物对高脂血症和氧化应激（心血管疾病的两个主要促成因素）的协同作用仍未得到充分表征。本研究采用了一种综合方法，包括体内、体外和计算机模拟方法，以评估生姜汁和柠檬汁的降血脂和抗氧化特性。体内实验使用了Triton WR - 1339诱导的高脂血症小鼠模型。通过DPPH和ABTS测定评估抗氧化活性，同时进行分子对接模拟以评估与HMG - CoA还原酶（胆固醇代谢中的关键酶）的相互作用。植物化学分析显示生物活性化合物含量高，生姜汁含有6 - 姜酚（峰面积15.54%），柠檬汁富含橙皮苷（13.85%）和芦丁（5.57%）。这些成分可能促成了观察到的药理作用。与高脂血症对照组相比，联合制剂使脂质参数有显著改善，包括总胆固醇降低（-54.3%）、甘油三酯降低（-49.8%）和低密度脂蛋白胆固醇降低（-58.1%），同时高密度脂蛋白胆固醇增加（+47.6%）（p < 0.05）。抗氧化测定进一步证明了强大的自由基清除活性，联合制剂的ABTS法IC₅₀值为30.92±2.00 µg/mL，DPPH法IC₅₀值为44.94±1.02 µg/mL。分子对接证实了关键化合物的高结合亲和力，橙皮苷和6 - 姜酚与HMG - CoA还原酶的结合能分别为-10.4和-9.6 kcal/mol。总之，生姜汁和柠檬汁的组合表现出强大的降血脂和抗氧化活性，优于单独提取物的效果。这些发现强调了它们作为治疗高脂血症和氧化应激的天然治疗剂的潜力。有必要进行进一步的临床研究以验证这些临床前结果，并探索它们在营养保健品或功能性食品开发中的未来应用。
