Diterpenoids from the Whole Plants of Ajuga nipponensis and Their Inhibition of RANKL‐Induced Osteoclastogenesis

Abstract

Two new diterpenoids, ajudecunoid A (1) and ajudecunoid B (14), along with thirteen known diterpenoids, were isolated from the whole plants of Ajuga nipponensis Makino. Their structures were elucidated by the extensive spectroscopic analysis (UV, IR, MS, and NMR). The absolute configurations of ajudecunoid A (1) and ajudecunoid B (14) were defined through analysis of X-ray crystallography. Fifteen compounds were evaluated for inhibition of the formation of osteoclasts in bone marrow-derived macrophages (BMM) cells. Two neoclerodane diterpenoids ajuganipponin B (5) and (12S)-6α,19-diacetoxy-18-chloro-4α-hydroxy-12-tigloyloxy-neoclerod-13-en-15,16-olide (12) showed significant inhibition of osteoclastogenesis with IC 50 values of 0.88 and 0.79 μM, respectively. Here we firstly reported diterpenoids with anti-osteoclastogenesis activity from A. nipponensis.

Chemical Constituents of Ajuga Lupulina and their Anti‐Ferroptosis Activity

“…The known compounds were identified as dihydroclerodin‐I ( 3 ), [11] clerodinin D ( 4 ), [11] clerodinin B ( 5 ), [23] ajuforan F ( 6 ), [24] ajudecunoid B ( 8 ), [25] clerodendrone ( 9 ), [18] ajudecumin B ( 10 ), [26] (3 S ,4 R )‐3,4‐epoxyclerodendrone ( 11 ), [18] decortinone ( 13 ), [21] 3‐hydroxy‐5 α ,6 α ‐epoxy‐ β ‐ionone ( 14 ), [27] pubinernoid A ( 15 ), [28] tricin ( 17 ), [29] α ‐linolenic acid ( 18 ), [30] glycerol monolinoleate ( 19 ), [31] phytene‐1,2‐diol ( 20 ), [32] via comparing their spectroscopic characteristics with the results reported in the literature.…”

Natural epoxyquinoids: isolation, biological activity and synthesis. An update

“…20 New diterpenoid ajudecunoid B was isolated from the whole plants of Ajuga nipponensis Makino. 21 The absolute configuration of ajudecunoid B was determined by X-ray crystallography analysis. The cytotoxicity of ajudecunoid B was determined using CCK8 assay on bone marrow-derived macrophage (BMM) cells.…”

Ferroptosis Inhibitory Aromatic Abietane Diterpenoids from Ajuga decumbens and Structural Revision of Two 3,4-Epoxy Group-Containing Abietanes

“…Two new 3,4-epoxy group-containing abietane diterpenoids ( 1 and 2 ) along with five known compounds ( 3 – 7 ) were isolated from A. decumben s. Compounds 3 – 7 were identified by interpretation of their spectroscopic data compared with those in the literature. − Two known abietane diterpenoids were revised based on NMR calculations and X-ray diffraction, and the NMR empirical rules were established. To discuss the primary structure–activity relationships (SARs), three known analogues ( 8 – 10 ), obtained from A. nipponensis in our previous work, , were also assayed for their inhibitory activity against ferroptosis. Notably, all the isolated compounds displayed significant inhibition against RSL3-induced ferroptosis in the HT22 cell line, and compound 4 , with an EC 50 of 56 nM, was found to be the most potent natural inhibitor against ferroptosis yet obtained (positive control Fer-1 with an EC 50 of 81 nM).…”