The Inhibitory Effects of Pentacyclic Triterpenes from Loquat Leaf against Th17 Differentiation

Identification of Corosolic and Oleanolic Acids as Molecules Antagonizing the Human RORγT Nuclear Receptor Using the Calculated Fingerprints of the Molecular Similarity

“…All these compounds are pentacyclic triterpenoids that are found in several plants, including herbs, spices, and fruits [50]. It was previously demonstrated that pentacyclic triterpenoids isolated from loquat leaves inhibited rodent Th17 cells, alleviated renal pathological damage, and reduced skin inflammation in a mouse model [51,52]. Interestingly, some of the considered compounds have anti-inflammatory properties, e.g., corosolic acid inhibits the LPS-mediated activation of IRAK-1 and acute inflammation [53]; ursolic acid targets CASP3, ERK, and JNK2 and their effector transcription factors, and alleviates inflammation [54].…”

Natural products as modulators of retinoic acid receptor-related orphan receptors (RORs)

“…Three triterpenoids isolated from Eriobotrya japonica (Rosaceae), methyl corosolate, uvaol and oleanolic acid, were found to possess RORgt inhibitory effects in a Gal4 luciferase assay performed in Jurkat cells. 141 Murine Th17 differentiation and Il17a/f gene expression were signicantly and dose-dependently inhibited. 141 Subsequent in vivo studies were performed in lupus nephritis (LN) mice using only oleanolic acid but not the other two compounds due to poor extraction yields.…”

“…141 Murine Th17 differentiation and Il17a/f gene expression were signicantly and dose-dependently inhibited. 141 Subsequent in vivo studies were performed in lupus nephritis (LN) mice using only oleanolic acid but not the other two compounds due to poor extraction yields. Particularly uvaol would have been interesting to study since it possessed the lowest EC 50 value and effectively inhibited Th17 differentiation even in the nanomolar concentration range.…”

“…Anti-dsDNA antibodies (markers for SLE, but their role as such have been questioned in the past 142 ) were reduced signicantly in the blood of LN mice treated with oleanolic acid. 141 Lastly, kidney damage and renal IgG/IgM depositions were found to be reduced in mice treated with oleanolic acid. 141 Interestingly, treatment with oleanolic acid had a greater effect compared to the positive control prednisolone acetate in vivo.…”

“…141 Lastly, kidney damage and renal IgG/IgM depositions were found to be reduced in mice treated with oleanolic acid. 141 Interestingly, treatment with oleanolic acid had a greater effect compared to the positive control prednisolone acetate in vivo. However, different doses were used (50 mg kg À1 oleanolic acid vs. 15 mg kg À1 prednisolone acetate), making a direct comparison difficult.…”