Discovery of ingenane and jatrophane diterpenoids from Euphorbia esula as inhibitors of RANKL-induced osteoclastogenesis

Euphorbiaditerpenoids: isolation, structure, bioactivity, biosynthesis, and synthesis (2013–2021)

“…321 A large number of Euphorbia diterpenoids were reported to possess significant antiosteoporotic activity in RANKL-induced bone-marrow-derived macrophage (BBM) cell lines, such as the cembrane diterpenoid euphorantone A ( 288 ), 42 the abietane diterpenoid euphorantone B ( 24 ), 42 the jatrophane diterpenoid euphoesulatin A ( 473 ), 140,322 the ingol diterpenoid 2,3- epi -7,12-diacetate-8-benzoate-ingol ( 685 ), 42 and the ingenane diterpenoid 20-acetoxy-3- O -benzoyl-13,17-dibenzoyloxyingenol ( 618 ). 138…”

“…137 Jatrophane diterpenoids 360-544 are structurally characterized by the presence of a D 6 (17) semicyclic double bond, and E. esula is a rich source of such diterpenoids (445-485, 533-535, 539, and 540). 111,[138][139][140] Compound 511 bearing a rare 19-OH was characterized from the whole plant of E. amygdaloides subsp. semiperfoliata.…”

“…321 A large number of Euphorbia diterpenoids were reported to possess signicant antiosteoporotic activity in RANKL-induced bone-marrow-derived macrophage (BBM) cell lines, such as the cembrane diterpenoid euphorantone A (288), 42 the abietane diterpenoid euphorantone B (24), 42 the jatrophane diterpenoid euphoesulatin A (473), 140,322 the ingol diterpenoid 2,3-epi-7,12diacetate-8-benzoate-ingol (685), 42 and the ingenane diterpenoid 20-acetoxy-3-O-benzoyl-13,17-dibenzoyloxyingenol (618). 138 Two abietane lactones, jolkinolide B (K14) and 17-hydroxyjolkinolide A (K37), could inhibit RANKL-induced osteoclastogenesis by suppressing the activation of NF-kB and MAPK signaling pathways. 323 K14 inhibited RANKL-induced activation of NF-kB by suppressing RANKL-mediated IkBa degradation, while K37 could block the nuclear translocation of the NF-kB p65 subunit by suppressing IkB-a degradation and NF-kB p65 subunit phosphorylation, resulting in the inhibition of NF-kB activation.…”

The Role of Ingenane Diterpenes in Cancer Therapy: From Bioactive Secondary Compounds to Small Molecules

“…The Chinese herbal medicine, Euphorbia esula L., has been used to treat cancer, warts, edema, diarrhea, vomiting, and fever, and as a diuretic remedy. 60,61 Previous phytochemical studies on this genus have led to the identification of numerous diterpenoid classes, such as jatrophane and lathyrane, but mainly ingenane. 62…”