Ong Siew Ling, Nalamolu Koteswara Rao, Lai How Yee
School of Biosciences, Taylor's University, No. 1 Jalan Taylor's, Subang Jaya, Malaysia.
School of Medicine, Taylor's University, No. 1 Jalan Taylor's, Subang Jaya, Malaysia.
Pharmacogn Mag. 2017 Jan;13(Suppl 1):S1-S9. doi: 10.4103/0973-1296.203986. Epub 2017 Apr 7.
To date, anti-obesity agents based on natural products are tested for their potential using lipase inhibition assay through the interference of hydrolysis of fat by lipase resulting in reduced fat absorption without altering the central mechanisms. Previous screening study had indicated strong anti-obesity potential in (), but to date, no pharmacologic studies have been reported so far.
This study was performed to investigate the lipid-lowering effects of using both and models.
The crude methanolic extract of was fractionated using hexane (H-Ei), dichloromethane (DCM-Ei), ethyl acetate (EA-Ei), butanol (B-Ei), and water (W-Ei). All the extracts were tested for antilipase activity using porcine pancreatic lipase. Because H-Ei showed the highest inhibition, it was further subjected to chemical profiling using high-performance liquid chromatography. Subsequently, oral toxicity analysis of H-Ei was performed [Organization for Economic Cooperation and Development guidelines using fixed dose procedure (No. 420)]; efficacy analysis was performed using high-fat diet (HFD)-induced hyperlipidemic female Sprague-Dawley rats.
According to the toxicity and efficacy analyses, H-Ei did not demonstrate any noticeable biochemical toxicity or physiologic abnormalities and did not cause any tissue damage as per histologic analysis. Furthermore, H-Ei significantly reduced body weight and improved serum profile and did not show hepatotoxicity and nephrotoxicity based on the serum profile. Moreover, H-Ei alleviated HFD-induced hepatosteatosis and ameliorated induced adiposity in both visceral and subcutaneous adipose tissue.
Our results demonstrate that H-Ei effectively improved hyperlipidemia. Further studies to explore its possibility as an alternative pharmacologic agent to treat obesity are warranted.
Hexane extract of (H-Ei) showed strong potential in the inhibition of porcine pancreatic lipase (27.01 ± 5.68%).The acute oral toxicity of hexane extract on animal model falls into Globally Harmonized System Category 5 (low hazard), since mortality, clinical toxicity symptoms, gross pathologic, or histopathologic damage was not observed.The hexane extract of had significantly reduced the body weight and improved serum lipid profile, with reduction in serum triglycerides, total cholesterol, low-density lipoprotein, and elevation in high-density lipoprotein when comparing against the high-fat diet control group.Microscopic evaluation on histologic slides of liver and adipose tissues suggested that hexane extract had greatly improved liver steatosis and adipose tissue hypertrophy in high-fat diet control group. ALT: Alanine transaminase; AST: Aspartate transaminase; B-Ei: Butanol extract of ; DCM-Ei: Dichloromethane extract of ; EA-Ei: Ethyl acetate extract of ; GHS: Globally Harmonized System; HDL: High-density lipoprotein; H-Ei: Hexane extract of ; HFD: High-fat diet; HPLC: High-performance liquid chromatography; LDL: Low-density lipoprotein; NFD: Normal fed diet; PPL: Porcine pancreatic lipase; SEM: Standard error of mean; SD: Standard deviation; TC: Total cholesterol; TG: Triglycerides; W-Ei: Water extract of .
迄今为止,基于天然产物的抗肥胖药物通过脂肪酶抑制试验来检测其潜力,该试验通过干扰脂肪酶对脂肪的水解作用,从而减少脂肪吸收,且不改变中枢机制。先前的筛选研究表明()具有很强的抗肥胖潜力,但迄今为止,尚未有药理学研究报道。
本研究旨在使用高脂饮食(HFD)诱导的高脂血症模型和正常饮食(NFD)模型,研究()的降血脂作用。
()的甲醇粗提物用己烷(H-Ei)、二氯甲烷(DCM-Ei)、乙酸乙酯(EA-Ei)、丁醇(B-Ei)和水(W-Ei)进行分离。所有提取物均使用猪胰脂肪酶检测其抗脂肪酶活性。由于H-Ei表现出最高的抑制作用,因此进一步使用高效液相色谱进行化学分析。随后,按照经济合作与发展组织固定剂量程序(第420号)指南对H-Ei进行口服毒性分析;使用高脂饮食诱导的高脂血症雌性Sprague-Dawley大鼠进行疗效分析。
根据毒性和疗效分析,H-Ei未表现出任何明显的生化毒性或生理异常,组织学分析也未发现任何组织损伤。此外,H-Ei显著降低体重,改善血清指标,根据血清指标未显示肝毒性和肾毒性。此外,H-Ei减轻了HFD诱导的肝脂肪变性,并改善了内脏和皮下脂肪组织中的诱导性肥胖。
我们的结果表明,H-Ei有效改善了高脂血症。有必要进一步研究探索其作为治疗肥胖的替代药物的可能性。
()的己烷提取物(H-Ei)在抑制猪胰脂肪酶方面表现出强大潜力(27.01±5.68%)。()己烷提取物对动物模型的急性口服毒性属于全球统一分类系统第5类(低危害),因为未观察到死亡率、临床毒性症状、大体病理或组织病理损伤。与高脂饮食对照组相比,()的己烷提取物显著降低了体重,改善了血脂指标,血清甘油三酯、总胆固醇、低密度脂蛋白降低,高密度脂蛋白升高。对肝脏和脂肪组织组织学切片的显微镜评估表明,()己烷提取物极大地改善了高脂饮食对照组的肝脂肪变性和脂肪组织肥大。ALT:谷丙转氨酶;AST:谷草转氨酶;B-Ei:()的丁醇提取物;DCM-Ei:()的二氯甲烷提取物;EA-Ei:()的乙酸乙酯提取物;GHS:全球统一分类系统;HDL:高密度脂蛋白;H-Ei:()的己烷提取物;HFD:高脂饮食;HPLC:高效液相色谱;LDL:低密度脂蛋白;NFD:正常饮食;PPL:猪胰脂肪酶;SEM:平均标准误差;SD:标准差;TC:总胆固醇;TG:甘油三酯;W-Ei:()的水提取物