.-J.F., T.G., B.L.D., C.S., J.B., E.B., R.P. and F.R.; original draft preparation, P.-J.F., T.G., B.L.D.

.-J.F., T.G., B.L.D., C.S., J.B., E.B., R.P. and F.R.; original draft preparation, P.-J.F., T.G., B.L.D. and B.F., assessment and editing, P.-J.F., T.G., B.L.D., C.S., F.R., T.H., I.M., K.T., B.C. and B.F. All authors have study and agreed to the published version from the manuscript. Funding: This work was supported by the French Agency for Wellness Merchandise (ANSM) and French National Institute of Overall health and Health-related Investigation (INSERM) thought PREVITOX network. Institutional Assessment Board Statement: Biological samples had been obtained at the infectious illnesses department and intensive care unit (ICU) at Rennes University Hospital. The study design and style was authorized by our ethic committee (CHU Rennes, n 35RC20_9795_HARMONICOV, ClinicalTrials.gov Identifier: NCT04373200) and informed consent was obtained from sufferers in accordance with all the Declaration of Helsinki. Informed Consent Statement: Informed consent was obtained from all subjects involved in the study. Acknowledgments: We would like to thank Anne Corlu and Caroline Aninat for their expertise in HepaRG cell function and culture as well as Ma Jacquard-Fevai and Sonia Brishoual for human RPTEC experiments. We also want to thank Remy Leguevel from IMPACELL plateform for his advices in higher content screening. Phospholipase A custom synthesis Conflicts of Interest: The authors declare no conflict of interest.
Gynostemma pentaphyllum (Thunb.) Makino, a slender creeping or climbing plant on the genus Gynostemma with the Cucurbitaceae family, possesses various medicinal capabilities and is connected with liver protection, antitumor activity, anti-inflammatory activity, and blood sugar and lipid balance [1]. Because the principal active ingredient of G. pentaphyllum, gypenosides display a standard dammarane-style structure of tetracyclic triterpenes. In higher plants, triterpene saponins are secondary metabolites of isoprenoid compounds. Compared with Panax ginseng, G. pentaphyllum not just generates just about five instances higher production of triterpene saponins but additionally grows faster. For that reason, G. pentaphyllum is regarded as an economical option for generating ginsenosides in the MEK2 custom synthesis future [80]. Sapogenins and sugars, uronic acid along with other organic acids constitute the main elements of triterpene saponins. The diversity of triterpene saponins is created by oxidation and glycosylation of cytochrome P450 and UDP-dependent glycosyltransferase, respectively, resulting in the modification of the functional groups on the triterpenoid skeleton [113]. To greater have an understanding of the biosynthesis of triterpene saponins in G. pentaphyllum, we performed transcriptional sequencing of G. pentaphyllum, which indicated a positive association between the content of triterpene saponins along with the expression of crucial genes (farnesyl pyrophosphate synthase (FPS), squalene synthase (SS), and squalene-2,3-epoxidase (SE)) [14]. Nevertheless, the expression pattern of important proteins involved inside the biosynthesis of gypenosides is still unclear. As a result, we utilised differential proteomics to figure out the protein sets involved inside the synthesis of triterpene saponins and analyzed the expression pattern of vital proteins in distinctive tissues of G. pentaphyllum (roots, stems, and leaves). Understanding the expression patterns of essential proteins involved inside the biosynthesis of gypenosides in G. pentaphyllum and their distribution traits in unique tissues will reveal the mechanism accounting for the diversity of gypenosides. In current years, investigations of how modulatory enzymes contr