Hendawy Omnia, Gomaa Hesham A M, Hussein Shaimaa, Alzarea Sami I, Qasim Sumera, Abdel Rahman Fatema El-Zahraa S, Ali Asmaa T, Ahmed Shaimaa R
Pharmacology Department, College of Pharmacy, Jouf University, Sakaka, Aljouf 72341, Saudi Arabia.
Department of Clinical Pharmacology, Faculty of Medicine, Beni-suef University, Beni-Suef, Egypt.
Saudi Pharm J. 2021 Nov;29(11):1303-1313. doi: 10.1016/j.jsps.2021.09.014. Epub 2021 Oct 6.
Non-alcoholic fatty liver disease (NAFLD) is considered one of the most serious public health problems affecting liver. The reported beneficial impact of raspberries on obesity and associated metabolic disorder makes it a suitable candidate against NAFLD. In the current study, the chemical profile of raspberry seed oil (RO) was characterized by analysis of fatty acid and tocopherol contents using high-performance liquid chromatography (HPLC) in addition to the determination of total phenolic and flavonoids. High levels of unsaturated fatty acids, linoleic acid (49.9%), α-linolenic acid (25.98%), and oleic acid (17.6%), along with high total tocopherol content (184 mg/100 gm) were detected in oil. The total phenolic and flavonoid contents in RO were estimated to be 22.40 ± 0.25 mg gallic acid equivalent (GAE)/100 mg oil and 1.34 ± 0.15 mg quercetin (QU)/100 mg, respectively. Anti-NAFLD efficacy of RO at different doses (0.4 and 0.8 mL) in a model of a high-fat diet (HFD) fed rats was assessed by estimating lipid profile, liver enzyme activity, glucose and insulin levels as well as adipokines and inflammatory marker. Peroxisome proliferator-activated receptor γ (PPARγ), which is a molecular target for NAFLD was also tested. Liver histopathology was carried out and its homogenate was used to estimate oxidative stress markers. Consumption of RO significantly improved lipid parameters and hepatic enzyme activities, reduced insulin resistance and glucose levels, significantly ameliorated inflammatory and oxidative stress markers. Furthermore, RO treatment significantly modulated adipokines activities and elevated PPARγ levels. Raspberry seed oil administration significantly improved these HFD induced histopathological alterations. Moreover, a molecular docking study was performed on the identified fatty acids and tocopherols. Among the identified compounds, oleic acid, α-linolenic acid and γ-tocopherol exhibited the highest docking score as PPARγ activator posing them as a potential anti-NAFLD drug leads. Study findings suggest RO as an effective therapeutic candidate for ameliorating NAFLD.
非酒精性脂肪性肝病（NAFLD）被认为是影响肝脏的最严重的公共卫生问题之一。据报道，树莓对肥胖及相关代谢紊乱具有有益影响，这使其成为对抗NAFLD的合适候选物。在本研究中，除了测定总酚和黄酮类化合物外，还通过高效液相色谱（HPLC）分析脂肪酸和生育酚含量来表征树莓籽油（RO）的化学特征。在油中检测到高水平的不饱和脂肪酸，亚油酸（49.9%）、α-亚麻酸（25.98%）和油酸（17.6%），以及高总生育酚含量（184毫克/100克）。RO中的总酚和黄酮类化合物含量估计分别为22.40±0.25毫克没食子酸当量（GAE）/100毫克油和1.34±0.15毫克槲皮素（QU）/100毫克。通过评估血脂、肝酶活性、葡萄糖和胰岛素水平以及脂肪因子和炎症标志物，来评价不同剂量（0.4和0.8毫升）的RO在高脂饮食（HFD）喂养大鼠模型中的抗NAFLD功效。还检测了作为NAFLD分子靶点的过氧化物酶体增殖物激活受体γ（PPARγ）。进行了肝脏组织病理学检查，并使用其匀浆来估计氧化应激标志物。食用RO显著改善了血脂参数和肝酶活性，降低了胰岛素抵抗和血糖水平，显著改善了炎症和氧化应激标志物。此外，RO治疗显著调节了脂肪因子活性并提高了PPARγ水平。给予树莓籽油显著改善了这些由HFD诱导的组织病理学改变。此外，对鉴定出的脂肪酸和生育酚进行了分子对接研究。在鉴定出的化合物中，油酸、α-亚麻酸和γ-生育酚作为PPARγ激活剂表现出最高的对接分数，使其成为潜在的抗NAFLD药物先导物。研究结果表明RO是改善NAFLD的有效治疗候选物。
