Forsythosides as Essential Components of Forsythia-based Traditional Chinese Medicines Used to Treat Inflammatory Diseases and COVID-19

Abstract

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.

Synergistic deciphering of bioenergy production and electron transport characteristics to screen traditional Chinese medicine (TCM) for COVID-19 drug development

“…In particular, caffeic acid and its derivatives (CAFDs) can be the inhibitors of SARS-CoV-2 and chlorogenic acid as a potential inhibitor for SARS-CoV-2 using molecular docking [42] , [43] , [44] , [45] , [46] . Forsythoside A and forsythoside B are the active constituents from F. suspensa , both of them also showed that activities against the influenza A virus which could be revealed beneficial effects to treat COVID-19 symptom [47] . On the other hand, forsythoside A is a potential anti-COVID-19 active compound of TCM Lianhuaqingwen capsule from China [48] .…”

“…Caffeic acid and chlorogenic acid also inhibited pro-inflammatory TNF-α and H 2 O 2 -induced IL-8 production [53] . Forsythoside A and B of F. suspensa have been reported that forsythoside A and B inhibited virus-induced inflammatory pathways and viral replication through designated signaling pathways leads to downregulation of several proteins involved in viral infection [54] . For P. frutescen s major compound luteolin could block the interaction of ligands (PAMPs) with the receptors (PRRs) and inhibits downstream activation signals [ [54] , [55] ].…”

“…Forsythoside A and B of F. suspensa have been reported that forsythoside A and B inhibited virus-induced inflammatory pathways and viral replication through designated signaling pathways leads to downregulation of several proteins involved in viral infection [54] . For P. frutescen s major compound luteolin could block the interaction of ligands (PAMPs) with the receptors (PRRs) and inhibits downstream activation signals [ [54] , [55] ]. Rosmarinic acid of P. frutescens could reduce LPS-induced vascular inflammation by inhibiting MAPK/NF-B signaling in smooth muscle cells.…”

“… Plant Compound Chemical structure Refs. Pogostemon cablin Apigenin [ 42 , 43 ] Caffeic acid [ 44 , 45 ] Chlorogenic acid [ 44 , 46 ] Forsythia suspensa Forsythoside A [ 47 , 48 ] Forsythoside B [47] Perilla frutescens Apigenin [ 43 , 49 ] Luteolin [ 49 , 50 ] Rosmarinic acid [ 49 , 51 ] …”

Isolation and Identification of Allelopathic Substances from Forsythia suspensa Leaves, and Their Metabolism and Activity

“…Forsythiae fructus has a bitter flavor, and has been traditionally applied for thousands of years as an effective remedy for the treatments of carbuncle, scrofula, gall tumor, malignant ulcer, gonorrhea, nephritis, and erysipelas. This medicinal herb is effective in clearing heat channel and releasing the heart of stomach and spleen according to traditional medicine [ 1 , 7 , 8 ]. Recent investigations have shown that Forsythiae fructus has several pharmacological activities such as anti-inflammatory, antibacterial, anti-allergic, anti-cancer, anti-HIV, antioxidant, and neuroprotective activities in vivo and in vitro [ 1 , 7 , 8 , 9 ].…”