Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, 90112, Thailand.
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, 310013, China.
J Ethnopharmacol. 2024 Dec 5;335:118625. doi: 10.1016/j.jep.2024.118625. Epub 2024 Jul 23.
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.
The current study aims to establish a standardized chamuangone enriched extract (CEE) and assess its acute and sub-acute toxicities in animal models.
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.
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 LD 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.
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.
草药产品的安全性评估对于其适当的药理应用至关重要。 Garcinia cowa Roxb.，在泰语中通常称为 Cha-muang，具有治疗炎症、传染病和糖尿病的民族药理学相关性。 G. cowa 的叶提取物因其抗癌、抗炎、抗菌和抗氧化作用而得到广泛报道。值得注意的是，chamuangone 是其主要活性成分，有助于各种药理特性。
本研究旨在建立标准化的 chaumangone 富集提取物（CEE），并在动物模型中评估其急性和亚急性毒性。
采用微波辅助提取（MAE）从 G. cowa 叶片中提取 CEE，然后通过硅胶真空和柱色谱进行分离和富集。使用经过验证的定量高效液相色谱（HPLC）方法定量提取物中的 chamuangone 浓度。根据经济合作与发展组织（OECD）425 和 407 指南，在啮齿动物中全面评估 CEE 的安全性概况。还评估了各种器官中超氧化物歧化酶（SOD）、还原型谷胱甘肽（GSH）、过氧化氢酶（CAT）和丙二醛（MDA）水平等氧化应激标志物的变化。
根据定量 HPLC 分析，CEE 含有 73.0±2.0%w/w 的 chamuangone。在急性毒性研究中，雌性大鼠采用上下法给药，剂量分别为 CEE 1750 和 550mg/kg 体重（b.w.），CEE 1750mg/kg b.w.有毒，引起死亡率，而 CEE 550mg/kg b.w.被认为是安全的。根据标准方案计算 LD 值，得出 970mg/kg b.w.的结果。在组织病理学检查中，550mg/kg b.w.的 CEE 在所有选定的器官中均安全，而 1750mg/kg b.w.的 CEE 处理大鼠的组织切片显示出脑坏死、心肌肥厚、肝炎症、脾轻度不良反应、肺纤维化、胰腺炎、肾盂肾炎和卵巢囊肿等毒性作用。在急性毒性研究中，CEE （550mg/kg b.w.，单次剂量）和亚急性毒性研究中（100mg/kg b.w.，定期 28 天）给药，尿酸、甘油三酯和胆固醇水平显著降低（p<0.05）。重要的是，CEE（550 和 100mg/kg b.w.）还显著增加了抗氧化酶（SOD、GSH 和 CAT）的水平并降低了 MDA 水平。在所有治疗组的亚急性毒性研究中均观察到正常的组织病理学。
本研究成功得出结论，CEE 剂量为 100mg/kg b.w.时，利用绿色提取方法，用于治疗应用或作为化学预防功能性食品是安全的。然而，建议进一步进行慢性毒性研究，以验证长期安全性问题。
