Golden berry leaf extract containing withanolides suppresses TNF-α and IL-17 induced IL-6 expression in HeLa Cells.

Inflammation, characterized by the overexpression of IL-6 in various tissues, has been reported as a symptom of coronavirus disease 2019 (COVID-19). In this study, we established an experimental system for overexpression of IL-6 in HeLa cells stimulated by TNF-α and IL-17, along with identification of anti-inflammatory materials and components from local agricultural, forestry, and fishery resources. We constructed a library of extracts from natural sources, of which 111 samples were evaluated for their anti-inflammatory activities. The MeOH extract of Golden Berry (Physalis peruviana L) leaf was found to exhibit strong anti-inflammatory properties (IC50 = 4.97 µg/mL). Preparative chromatography identified two active constituents, 4ß-hydroxywithanolide E (4ß-HWE) (IC50 = 183 nM) and withanolide E (WE) (IC50 = 65.1 nM). Withanolides are known anti-inflammatory ingredients of Withania somnifera, an Ayurvedic herbal medicine. P. peruviana leaves containing 4ß-HWE and WE should be considered as useful natural resources for anti-inflammatory products.

Dihydroisocoumarins of Hydrangea macrophylla var. thunbergia inhibit binding of the SARS-CoV-2 spike protein to ACE2.

Binding of the spike protein of severe acute respiratory syndrome coronavirus 2 to the cognate angiotensin-converting enzyme 2 receptor is the initial step in the viral infection process. In this study, we screened an in-house extract library to identify food materials with inhibitory activity against this binding using enzyme-linked immunosorbent assays and attempted to ascertain their active constituents. Hydrangea macrophylla var. thunbergia leaves were identified as candidate materials. Its active compounds were purified using conventional chromatographic methods and identified as naringenin, dihydroisocoumarins, hydrangenol, and phyllodulcin, which have affinities for angiotensin-converting enzyme 2 receptor and inhibit angiotensin-converting enzyme 2 receptor-spike S1 binding. Given that boiled water extracts of H. macrophylla leaves are commonly consumed as sweet tea in Japan, we speculated that this tea could be used as a potential natural resource to reduce the risk of severe acute respiratory syndrome coronavirus 2 infection.