同济大学邓寒松研究团队近日取得一项新成果。经过不懈努力，他们报道了微乳化给药系统鉴定辣椒生物碱为抗肥胖化合物。2025年3月20日出版的《中国药理学报》杂志发表了这项成果。

在本研究中，该课题组开发了一种基于微乳化的果蝇给药系统，该系统有效地提高了疏水化合物的溶解度，而不会对果蝇的食物摄入或存活产生明显影响。该体系由cremophor EL、乙醇和油酸乙酯（7:6:1）组成，建立了基于乳化的液体高脂饲料（LHFD）模型，并对161种中药标准物质进行了中试筛选。研究人员发现胡椒碱（PIP），一种从黑胡椒中提取的生物碱，可以显著降低肠道和整只苍蝇的甘油三酯（TAG）水平。研究小组证明胡椒碱（1mg /ml）通过激活瞬时受体电位（TRP）通道显著提高肠细胞胞浆Ca²⁺水平。TRPV1激动剂，如辣椒素和乙伏二胺（另一种在筛选过程中发现的生物碱）也显示出抗肥胖作用。升高的Ca²⁺水平通过激活转录因子cAMP反应元件结合蛋白（CREB）抑制饲料脂肪酶Magro的表达。

此外，微乳中的疏水化合物成功递送到小鼠的远端组织，包括肝脏和脑血管，微乳中的PIP足以减轻小鼠的体重。总之，研究组开发了一种基于微乳化的U-GLAD给药平台，并且胡椒碱被确定为一种控制体重的化合物，为治疗肥胖及其相关症状提供了一种新的方法。

研究人员表示，肥胖是心脏病和糖尿病等多种代谢疾病的重要诱因。由于合成抗肥胖药物的副作用，从功能性食品植物中提取的天然产物，模仿合成化学品的作用，提供了有希望的替代品。然而，许多天然植物源化合物难溶于水，导致胃肠道内的生物利用度低，这是许多疏水物质有效性的关键限制。

附：英文原文

Title: Microemulsion-based drug delivery system identifies pepper alkaloids as anti-obesity compounds

Author: Meng, Tian-kai, Han, Ruo-lei, Ma, Peng, Chen, Shu-xin, Qi, Bo-han, Wang, Zi-xuan, Li, Xiao-yu, Deng, Han-song

Issue&Volume: 2025-03-20

Abstract: Obesity is a significant contributor to various metabolic diseases such as heart disease and diabetes. Due to the adverse effects of synthetic anti-obesity drugs, natural products from functional food plants, which mimic the effects of synthetic chemicals, present promising alternatives. However, many natural plant-derived compounds are poorly soluble in water, resulting in low bioavailability within the gastrointestinal tract, a key limitation for the effectiveness of many hydrophobic substances. In this study we developed a microemulsion-based drug delivery system in Drosophila, which effectively enhanced the solubility of hydrophobic compounds without noticeable effects on food intake or survival in fruit flies. This system consisted of cremophor EL, ethanol and ethyl oleate (7:6:1), which enabled the establishment of an emulsion-based liquid high-fat diet (LHFD) model, followed by a pilot screening of 161 standard substances from traditional Chinese medicine. We found that piperine (PIP), an alkaloid derived from black pepper, significantly decreased triacylglycerol (TAG) levels in both the intestine and in whole flies. We demonstrated that piperine (1mg/ml) significantly elevated cytosolic Ca2+ levels in enterocytes by activating Transient receptor potential (TRP) channels. TRPV1 agonists such as capsaicin and evodiamine (another alkaloid identified during the screening) also exhibited anti-obesity effects. Increased Ca2+ levels resulted in the suppression of dietary lipase Magro expression through the activation of the transcription factor cAMP response element binding protein (CREB). Furthermore, hydrophobic compounds in the microemulsion were successfully delivered to distal tissues including liver and brain blood vessels in mice, and PIP in the microemulsion was sufficient to reduce body weight in mice. In conclusion, we have developed a microemulsion-based U-GLAD platform for drug delivery, and piperine is identified as a weight-controlling compound, providing a novel approach to the treatment of obesity and its associated symptoms.

DOI: 10.1038/s41401-025-01521-x

Source: https://www.nature.com/articles/s41401-025-01521-x