Department of Oriental Pharmacy and Wonkwang-Oriental Medicines Research Institute Wonkwang University, Sinyong-Dong, Iksan 570-749, Republic of Korea.
Department of Animal and Food Sciences University of Kentucky, Lexington, Kentucky 40546, USA.
Biomed Res Int. 2024 Sep 19;2024:1767618. doi: 10.1155/2024/1767618. eCollection 2024.
18KHT01 is a novel synergistic composition of , , , and a small portion of . Our previous report demonstrated that the 18KHT01 exhibits potent antiobesity effects, with synergistic antioxidant, antiadipogenic, and antiobesity activities in diet-induced obese mice. This study explores the toxicity profile and quality control parameters of the 18KHT01 formulation. Broad-spectrum acute and subacute oral toxicity studies were performed using male and female ICR mice. In order to simultaneous analysis of the 18KHT01 formulation, an ultraperformance liquid chromatography coupled with a diode array detector (UPLC-DAD) method was developed and validated using six marker compounds. Acute oral toxicity evaluation of 18KHT01, administered at single high doses of 2, 2.5, 3, and 5 g/kg, identified 2 g/kg as the no-observed adverse effect level (NOAEL). The LD50 (50% lethal dose) and LD100 (100% lethal dose) of 18KHT01 for male ICR mice were 3.99 and 7.77 g/kg, and those for the female mice were 2.94 and 4.70 g/kg, respectively. In addition, a 30-day repeated dose oral subacute toxicity evaluation indicated that 18KHT01 is safe below 500 mg/kg/day for long-term administration in ICR mice of either sex. UPLC-DAD method validation revealed that each calibration curve for the marker compounds showed good linearity, as well as the validation parameters such as precision, specificity, and accuracy met the acceptance criteria. The present study evidenced the toxicological profile of 18KHT01 polyherbal formulation in mice as well as developed a simple, rapid, and accurate chromatographic method for quality control.
18KHT01 是一种新型协同组合物，包含 、 、 、和一小部分 。我们之前的报告表明，18KHT01 具有强大的抗肥胖作用，在饮食诱导肥胖的小鼠中具有协同的抗氧化、抗脂肪生成和抗肥胖活性。本研究探讨了 18KHT01 配方的毒性概况和质量控制参数。使用雄性和雌性 ICR 小鼠进行了广谱急性和亚急性口服毒性研究。为了同时分析 18KHT01 配方，开发了一种超高效液相色谱法（UPLC）-二极管阵列检测器（DAD）方法，并使用六种标记化合物进行了验证。18KHT01 的单次高剂量（2、2.5、3 和 5 g/kg）口服急性毒性评估确定 2 g/kg 为无观察不良效应水平（NOAEL）。18KHT01 对雄性 ICR 小鼠的 LD50（50%致死剂量）和 LD100（100%致死剂量）分别为 3.99 和 7.77 g/kg，雌性小鼠分别为 2.94 和 4.70 g/kg。此外，30 天重复剂量口服亚急性毒性评估表明，18KHT01 在雄性和雌性 ICR 小鼠中，每天低于 500mg/kg 的长期给药是安全的。UPLC-DAD 方法验证表明，每个标记化合物的校准曲线均具有良好的线性，并且验证参数，如精密度、特异性和准确性均符合接受标准。本研究证明了 18KHT01 草药配方在小鼠中的毒理学概况，并开发了一种简单、快速、准确的色谱方法用于质量控制。
