Rhubarb: Traditional Uses, Phytochemistry, Multiomics-Based Novel Pharmacological and Toxicological Mechanisms

Hua Miao,1 Kai-En Wang,1 Ping Li,2 Ying-Yong Zhao1 1School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Beijing Key Laboratory for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Ping Li, Beijing Key Laboratory for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China, Email [email protected] Ying-Yong Zhao, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China, Email [email protected]: Traditional Chinese medicines (TCMs) are practiced in clinical and healthcare settings and are widely employed as essential therapies for intervening diverse refractory illnesses. Rhubarb, which is prescribed as the root and rhizome of Rheum officinale Baill. Rheum tanguticum Maxim. ex Balf. and Rheum palmatum L. has been widely recognized as an important natural medicine for the management of cardiovascular diseases, cancer, and kidney disorders. The available information on traditional uses, phytochemistry, multiomics-based pharmacological and toxicological studies of rhubarb species and their components including anthraquinones, such as emodin, rhein, chrysophanol, aloe-emodin and physcion as well as their glycoside derivatives published from 2010 to 2025 was searched by several electronic database such as Web of Science, PubMed, Springer, ScienceDirect, Scopus, Google Scholar, CNKI, etc. Increasing evidence has indicated that rhubarb contain various bioactive compounds, such as anthraquinones, anthrones, stilbenes, and saccharides. Numerous studies have demonstrated that rhubarb exerts a broad spectrum of pharmacological effects, including anticardiovascular, anticancer, hepatoprotective, renoprotective, pulmoprotective, antidiabetic, anti-colitis, and antibacterial activities. In this review, traditional applications and major components of rhubarb are presented, and their diverse pharmacological and toxicological effects are discussed. Novel multiomics-based molecular mechanisms of the treatment of various diseases of rhubarb have been highlighted. Key challenges, such as rhubarb effect on cardiorenal syndrome and cardiovascular-kidney-metabolic syndrome, are also addressed. Current evidence suggests that rhubarb is a promising candidate drug for the prevention and treatment of various diseases. Mounting publications show that targeting multiomics-related targets are a promising therapeutic strategy in a myriad of refractory diseases. Rhubarb improves various diseases by reshaping microbial dysbiosis, restoring aberrant expression of ncRNAs and regulating maladaptive metabolite disorder that may provide new therapeutic targets for treatment of various diseases of rhubarb. This review is expected to development of rhubarb-derived anthraquinones as novel therapeutic agents for clinical applications in the future.Keywords: rhubarb, gut microbiota, long non-coding RNAs, metabolome, anticardiovascular disease, anticancer, renoprotective activity, cardio-renoprotective effect, hepatotoxicity and nephrotoxicity