背景:草药产品的安全性评估对于其适当的药理学应用至关重要。藤黄根草Roxb.,泰语中俗称Cha-muang,在炎症中具有民族药理学相关性,传染病,和糖尿病。G.cowa的叶提取物因其抗癌而被广泛报道,抗炎,抗菌和抗氧化作用。值得注意的是,chamuangone是它们的主要活性成分,有助于各种药理特性。
目的:本研究旨在建立一种标准化的富含川麦酮的提取物(CEE),并在动物模型中评估其急性和亚急性毒性。
方法:使用微波辅助提取(MAE)从G.cowa叶中建立CEE,然后通过硅胶真空和柱层析进行分馏和富集。使用经过验证的定量高效液相色谱(HPLC)方法对叶片中的chamuangone浓度进行定量。根据经济合作与发展组织(OECD)的指导方针,在啮齿动物中彻底评估了CEE的安全性,425和407。对氧化应激标志物如超氧化物歧化酶(SOD)的影响,还原型谷胱甘肽(GSH),过氧化氢酶(CAT),还评估了各种器官中的丙二醛(MDA)水平。
结果:基于定量HPLC分析,CEE在提取物中含有73.0±2%w/w的查莫酮。在急性毒性研究中,在上下程序之后,雌性大鼠以1750和550mg/kg体重(b.w.)的剂量给予CEE,CEE1750mg/kgb.w.被确定为有毒的,导致死亡,而CEE550mg/kgb.w.被认为是安全的。根据标准协议计算LD50值,导致970mg/kgb.w.在组织病理学检查中,CEE550mg/kgb.w.在所有选定的器官中都是安全的,而CEE1750mg/kgb.w.处理的大鼠在组织学组织切片中以脑坏死的形式表现出毒性作用,心肌肥大,肝脏炎症,脾脏轻微不适,肺纤维化,胰腺炎,肾盂肾炎,和卵巢囊肿.在亚急性毒性研究中,以550mg/kgb.w.(单剂量)和100mg/kgb.w.(定期28天)的剂量给予CEE显着(p<0.05)降低了尿酸水平,甘油三酯,和胆固醇。重要的是,CEE550和100mg/kgb.w.也显着增加了抗氧化酶的水平(SOD,GSH和CAT)和丙二醛水平降低。在所有治疗组的亚急性毒性研究中观察到正常的组织病理学。
结论:该研究成功得出结论,使用绿色提取方法,100mg/kgb.w.剂量的CEE对于治疗性应用或用作化学预防功能食品是安全的。然而,我们建议进行慢性毒性研究,以验证长期安全性问题.
BACKGROUND: The safety assessment of herbal products is critical for their appropriate pharmacological applications. Garcinia cowa Roxb., commonly known as Cha-muang in Thai, has ethnopharmacological relevance for inflammation, infectious diseases, and diabetes. The leaf extracts of G. cowa have been extensively reported for their anticancer, anti-inflammatory, antimicrobial, and antioxidant effects. Notably, chamuangone is their major active constituent that contributes to various pharmacological properties.
OBJECTIVE: The current study aims to establish a standardized chamuangone enriched extract (CEE) and assess its acute and sub-acute toxicities in animal models.
METHODS: CEE was established from G. cowa leaves using a microwave-assisted extraction (MAE), followed by fractionation and enrichment through silica gel vacuum and column chromatography. The concentration of chamuangone in the extract was quantified using a validated quantitative high-performance liquid chromatography (HPLC) method. The safety profiles of CEE were thoroughly evaluated in rodents according to the Organization for Economic Cooperation and Development (OECD) 425 and 407 guidelines. The effects on oxidative stress markers such as superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and malondialdehyde (MDA) levels were also evaluated in various organs.
RESULTS: Based on the quantitative HPLC analysis, the CEE contained 73.0 ± 2.0% w/w of chamuangone. In the acute toxicity study, following up and down procedure the female rats were dosed with CEE at 1750 and 550 mg/kg body weight (b.w.), with CEE 1750 mg/kg b.w. was toxic, causing mortality, while CEE 550 mg/kg b.w. was deemed safe. An LD50 value was calculated according to the standard protocols, resulting in 970 mg/kg b.w. In histopathological examination, 550 mg/kg b.w. of CEE was safe in all the selected organs, while the 1750 mg/kg b.w. CEE treated rats exhibited toxic effects in histological tissues sections in the form of necrosis in the brain, cardiac muscle hypertrophy, liver inflammation, mild untoward effect in the spleen, fibrosis in the lungs, pancreatitis, pyelonephritis, and ovarian cyst. Administration of CEE at doses of 550 mg/kg b.w. (single dose) in the acute and 100 mg/kg b.w. (regularly 28-days) in the sub-acute toxicity studies significantly (p < 0.05) decreased levels of uric acid, triglycerides, and cholesterol. Importantly, the CEE (550 and 100 mg/kg b.w.) also significantly increased the levels of antioxidant enzymes (SOD, GSH, and CAT) and decreased MDA levels. Normal histopathology was observed in the sub-acute toxicity study in all treated groups.
CONCLUSIONS: This study successfully concludes that CEE at a dose of 100 mg/kg b.w. is safe for therapeutic application or use as a chemopreventive functional food utilizing green extraction methods. However, chronic toxicity studies are further recommended to validate safety concerns over an extended period.