Flavonoids and saponins: What have we got or missed?

Background: Flavonoids and saponins are important bioactive compounds that have attracted wide research interests. This review aims to summarise the state of the art of the pharmacology, toxicology and clinical efficacy of these compounds. Methods: Data were retrieved from PubMed, Cochrane Library, Web of Science, Proquest, CNKI, Chongqing VIP, Wanfang, NPASS and HIT 2.0 databases. Meta-analysis and systematic reviews were evaluated following the PRISMA guideline. Statistical analyses were conducted using SPSS23.0. Results: Rising research trends on flavonoids and saponins were observed since the 1990s and the 2000s, respectively. Studies on pharmacological targets and activities of flavonoids and saponins represent an important Phytomedicine 109 (2023) 154580 area of research advances over the past decade, and these important resources have been documented in open -access specialised databases and can be retrieved with ease. The rising research on flavonoids and saponins can be attributed, at least in part, to their links with some highly investigated fields of research, e.g., oxidative stress, inflammation and cancer; i.e., 6.88% and 3.03% of publications on oxidative stress cited by PubMed in 1990-2021 involved flavonoids and saponins, respectively, significantly higher than the percentage involving alkaloids (1.88%). The effects of flavonoids concern chronic venous insufficiency, cervical lesions, diabetes, rhinitis, dermatopathy, prostatitis, menopausal symptoms, angina pectoris, male pattern hair loss, lymphocytic leukaemia, gastrointestinal diseases and traumatic cerebral infarction, etc, while those of saponins may have impact on venous oedema in chronic deep vein incompetence, erectile dysfunction, acute impact injuries and systemic lupus erythematosus, etc. The volume of in vitro research appears way higher than in vivo and clinical studies, with only 10 meta-analyses and systematic reviews (involving 290 interventional and observational studies), and 36 clinical studies on flavonoids and saponins. Data are sorely needed on pharmacokinetics, in vitro pan-assay interferences, purity of tested compounds, interactions in complex herbal extracts, real impact of anti-oxidative strategies, and mid-and long-term toxicities. To fill these important gaps, further investigations are warranted. On the other hand, drug interactions may cause adverse effects but might also be useful for synergism, with the goals of enhancing effects or of detoxifying. Furthermore, the interactions between phytochemicals and the intestinal microbiota are worth investigating as the field may present a promising potential for novel drug development.