Thistle (Onopordum acanthium) has been traditionally employed for liver protection. However, we recently identified silibinin, the main bioactive compound of thistle extract, as an in vitro pancreatic lipase inhibitor, which suggested a potential role as an anti-obesity agent. This study aimed to assess, in vivo, the efficacy, safety, and effects of silibinin on human lipase. As a secondary objective, we evaluated potential changes in gut microbiota after silibinin treatment. A randomized trial comparing 150 mg/silibinin, 300 mg/silibinin, and a thistle extract (equivalent to 150 mg/silibinin) with placebo and orlistat/120 mg was conducted. Fecal fat excretion, clinical parameters, and microbiota changes were analyzed. Orlistat showed the highest fecal fat excretion, although thistle extract had similar results (p = 0.582). The 150 mg/silibinin group reported the fewest adverse effects. Both silibinin and orlistat reduced plasma triglycerides (p = 0.016) and waist circumference (p = 0.001). Specific microbiota changes, such as increases in Mycobacteriaceae and Veillonellaceae, were associated with higher fat excretion. Although the present work was conducted in the short term and in people of normal weight, our results suggest that silibinin may be safe and effective for obesity, with minimal adverse effects and no significant changes in microbiota diversity. Further studies are needed to explore its microbiota-related benefits.

Thistle (Onopordum acanthium) has been traditionally employed for liver protection, however, we recently identified silibinin, the main bioactive compound of thistle extract, as an in vitro pancreatic lipase inhibitor, which suggested a potential role as anti-obesity agent. This study aimed to assess, in vivo, the efficacy, safety, and effects of silibinin on human lipase. As a secondary objective, we evaluated potential changes on gut microbiota after silibinina treatment. A randomized trial comparing 150mg/silibinin, 300mg/silibinin, and a thistle extract (equivalent to 150 mg/silibinin) with placebo and orlistat/120mg was conducted. Fecal fat excretion, clinical parameters, and microbiota changes were analyzed. Orlistat showed the highest fecal fat excretion, although thistle extract had similar results (p = 0.582). The 150 mg/silibinin group reported the fewest adverse effects. Both silibinin and orlistat reduced plasma triglycerides (p=0.016) and waist circumference (p=0.001). Specific microbiota changes, such as increases in Mycobacteriaceae and Veillonellaceae, were associated with higher fat excretion. Silibinin proved to be safe and effective for obesity, with minimal adverse effects and no significant changes in microbiota diversity. Further studies are needed to explore its microbiota-related benefits.

The huge obesity prevalence and its associated metabolic disorders highlight the urgent need for new therapeutic strategies beyond lifestyle interventions. Despite the availability of novel pharmacological treatments, the search for more effective and safe anti-obesity compounds remains a challenge. Recent advances in high-performance computational drug discovery have enabled the rapid screening and identification of potential anti-obesity compounds. However, these in silico procedures frequently require complex computational knowledge that limits the use of these techniques for most researchers. To address this gap, we have developed OBE-DB, an accessible and user-friendly platform integrating these computational tools that facilitates the prediction of potential anti-obesity molecules through two complementary approaches: (a) shape similarity analysis against a curated database of approved anti-obesity drugs, and (b) inverse virtual screening of user-submitted molecules against a set of therapeutic protein targets linked to obesity. Our results demonstrate that the server effectively screens and ranks compounds with high predicted activity, outperforming conventional in silico techniques in terms of accuracy and usability. This represents a significant advancement by providing researchers with an intuitive tool to accelerate early-stage drug discovery for obesity treatment. The server is freely accessible without registration, providing users with a detailed report via email upon completion of the predictions. This innovative database and web server is accessible online via http://bio-hpc.eu/software/obe-db/ .