Rabdosia rubescens (Hemsl.) H. Hara: A potent anti-tumor herbal remedy - Botany, phytochemistry, and clinical applications and insights

Ethnopharmacological relevance: Traditional Chinese herbal medicine has unique advantages as anti-cancer drugs and adjuvant therapies. Rabdosia rubescens (Hemsl.) H. Hara (R. rubescens) is a traditional medicinal plant known for its anti-inflammatory, antioxidant, antibacterial, anti-angiogenic and antitumor properties. The antitumor activity of R. rubescens is widely recognized among the folk communities in Henan Province, China. Aim of the study: This study reviews the botany, ethnopharmacology, phytochemistry, anti-tumor active ingredients, mechanisms, and clinical applications of R. rubescens, aiming to provide a comprehensive understanding for its use as an anti-cancer drug and adjuvant therapy. Materials and methods: We systematically searched the literature in PubMed, Web of Science, and CNKI using the following keywords: "Rabdosia rubescens", "Isodon rubescens", "traditional application", "anti-tumor", "phytochemistry", "anti-tumor active compounds", "oridonin" and "clinical application". The search covered publications from 1997 to 2024. Inclusion criteria included original studies or reviews focusing on the anti-tumor properties of R. rubescens or its active components. Exclusion criteria included studies related to non-R. rubescens applications. Results: R. rubescens is a perennial herbaceous plant in the family Lamiaceae, mainly found in central and southern China. Historically, it has been used to treat conditions such as sore throat, cough, and excess phlegm. The plant contains various compounds, including diterpenes, triterpenes, steroids, flavonoids, phenolic acids, essential oils, amino acids, alkaloids, and polysaccharides, with diterpenes, triterpenes, flavonoids, and phenolic acids being the most active. This review identifies 50 compounds with anti-tumor properties, comprising 34 diterpenes, 2 triterpenes, 7 flavonoids, and 7 phenolic acids. Notably, besides oridonin and ponicidin, the entkaurane diterpenoids (20S)-11 beta,14 beta,20-trihydroxy-7 alpha,20-epoxy-ent-kaur-16-en15-one and (20S)-11 beta,14 beta-dihydroxy-20-ethoxy7 alpha,20-epoxy-ent-kaur-16-en-15-one demonstrate significant anti-tumor activity, attributed to their carbonyl group at C-15, hydroxyl group at C-1, and OEt group at C-20. Mechanistically, R. rubescens combats tumors by blocking the tumor cell cycle, promoting apoptosis, inhibiting cell migration and angiogenesis, inducing ferroptosis, reversing drug resistance, and enhancing radiosensitivity in tumor cells. Clinically, R. rubescens is available in various forms, including tablets, drops, syrups, capsules, and lozenges, and is primarily used for tonsillitis, pharyngitis, and stomatitis. According to the 2020 edition of the Pharmacopoeia of China, R. rubescens tablets are recognized as an adjuvant therapy for cancer. Clinical studies indicate that R. rubescens syrup, tablets, and thermal therapy can enhance cancer patient survival rates and lower tumor recurrence rates. Conclusions: Given its traditional and modern uses, active anti-tumor components, and mechanisms, R. rubescens is a promising resource in traditional Chinese medicine for anti-tumor therapy. To realize its full potential, future research should explore additional active anti-tumor compounds beyond oridonin and ponicidin. For these key components, studies should focus on structural modifications to identify new active molecules and essential antitumor structures. Clinically, it is important to investigate how R. rubescens interacts with other Chinese herbs in anti-tumor formulations to enhance treatment efficacy and guide appropriate clinical use. Furthermore, future studies should undergo ethical review and include larger-scale randomized controlled trials to validate the efficacy of R. rubescens in treating tumors, thereby promoting its role as an anti-tumor traditional Chinese medicine.