Forsythosides as essential components of Forsythia-based traditional chinese medicines used to treat inflammatory diseases and COVID-19

The dried fruits of the plant Forsythia suspensa (Forsythia Fructus: Lianqiao in Chinese) are used in many herbal preparations to treat various diseases or the associated symptoms. Forsythia extracts contain phenylethanoid glycosides (PhGs) such as the forsythosides (Fst A-to-P). The leading products, Fst-A,-B and-F (arenarioside), can be found also in >90 other plants inventoried here. The pharmacological properties of Fst are reviewed, with emphasis on their anticancer, antiviral, and antibacterial activities, which essentially derive from their anti-inflammatory and antioxidant effects. Fst-B functions as a potential binder of the repressor protein Kelch-like ECH-association protein 1 (Keap 1), thus promoting the nuclear translocation of the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) implicated in the subsequent activation of the production of antioxidant enzymes and repression of the oxidative stress. The regulation of the Nrf2/Heme oxygenase-1 pathway is the central piece of the multifaceted mechanism of action of Fst-A/B. Their prominent antioxidant and anti-inflammatory effects support the use of these compounds in different inflammation-related diseases and conditions, from sepsis to neuroprotection and many other pathologies discussed here. In addition, these properties contribute to the antiviral action of the compounds. Fst-A/B displays activities against the influenza A virus and different Fst-containing traditional Chinese medicinal (TCMs) have revealed beneficial effects to combat the current COVID-19 pandemic. The mechanisms whereby Fst-A/B could inhibit viral multiplication are discussed. PhGs likely contribute to the anti-COVID-19 activities reported with several TCM such as Shuang-Huang-Lian oral liquid, Lianhua-Qingwen capsules, and others. This review highlights the pharmacological profile of Fst and illustrates health benefits associated with the use of Forsythia Fructus.