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Twelve new neo -clerodane diterpenoids, eight undescribed methoxy/ethoxy acetal analogues, and one new nor -iridane monoterpenoid were isolated from Ajuga campylantha . Their structures were elucidated using a combination of spectroscopic data, quantum chemical calculations, and X-ray crystallography. This research reveals the distinctive structural features of A. campylantha diterpenes, including distinct C rings and 4,18-double bonds, distinguishing them from diterpenes of other plants in the Ajuga genus. Compound 2 represents the first example of a 19(5→6)- abeo -clerodane formed through a Wagner-Meerwein rearrangement. The isolated compounds were assessed for their neuroprotective effects against RSL3-induced ferroptosis in HT22 cells and LPS-induced neuroinflammation in BV-2 cells. Notably, compound 7 inhibits ferroptosis (EC 50 = 10 μM) with a potentially new mechanism of action. The preliminary structure-activity relationship studies revealed that the furan-clerodane diterpenoids possess potential ferroptosis inhibitory activity, while the lactone-clerodanes do not. This study represents the first report of furan-containing clerodanes within the Ajuga genus, providing fresh insights into the phytochemistry and pharmacological potential of A. campylantha .

Eight new neo -clerodane diterpenoids ( 1 - 8 ) were acquired from the aerial parts of Ajuga pantantha . Spectroscopic data analysis permitted the definition of their structures, and experimental and calculated electronic circular dichroism data were used to define their absolute configurations. Compounds 2 and 4 - 8 were found to have NO inhibitory effects with IC 50 values of 20.2, 45.5, 34.0, 27.0, 45.0, and 25.8 μM, respectively. The more potent compounds 2 , 6 , and 8 were analyzed to establish their anti-inflammatory mechanism, including regulation of the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins as well as their binding interactions with the two proteins.

Ten new neo-clerodane diterpenes, ajugaciliatins A-J (1-5, 8-12), along with 17 known analogues (6, 7, 13-27) were isolated from the whole plants of Ajuga ciliata Bunge. Their structures were elucidated by spectroscopic data analysis (IR, ESIMS, HRESIMS, 1D and 2D NMR), and the configuration of 1 was confirmed by X-ray crystallography. All of the compounds were assessed for neuroprotective effects against MPP(+)-induced neuronal cell death in dopaminergic neuroblastoma SH-SY5Y cells. Compounds 2, 6, 7, 9, 10, 15-17, 19, and 20 exhibited moderate neuroprotective effects.

Different neo-clerodane diterpenoids were isolated from a dichloromethane extract of Ajuga bracteosa depending on the isolation procedure used, owing to the labile nature of these tetrahydrofurofuran derivatives. Under "hydroxyl-free" purification conditions, both clerodin- and dihydroclerodin-type diterpenes were obtained [four new compounds, ajubractins A-D (1-4), along with clerodin (5), 3-epi-caryoptin (6), ajugapitin (7), 14,15-dihydroclerodin (8), 3-epi-14,15-dihydrocaryoptin (9), ivain II (10), and 14,15-dihydroajugapitin (11)]. When methanol-water mixtures were used for a C18 reversed-phase prepurification procedure and for semipreparative HPLC, the new ajubractin E (12) was also isolated along with 3 and 8-11, as previously, but 7 was the only tetrahydrofurofuran derivative obtained. Epimeric (15R and 15S) mixtures were obtained instead of 14-hydro-15-hydroxyclerodin derivatives [15-hydroxyajubractin C (13), 14-hydro-15-hydroxyajugachin A (14), and 14-hydro-15-hydroxyajugapitin (15)], along with 15-epi-lupulin B (16). The structures of the new compounds were elucidated by NMR and MS data analysis and by comparison with values previously reported. Antifeedant activity against Spodoptera littoralis larvae was evaluated for the compounds obtained.

Investigation of the ecdysteroid constituents of the herb Ajuga reptans var. reptans resulted in the isolation of three new ecdysteroids, named reptanslactone A (2), reptanslactone B (3), and sendreisterone (5), and the known 24-dehydroprecyasterone (1) and breviflorasterone (4). The structures of compounds 1-5 were determined by spectroscopic methods including one- and two-dimensional NMR measurements.

Three new phytoecdysteroids, ajugacetalsterones C (1) and D (3) and breviflorasterone (2), were isolated from the roots of Ajuga macrosperma var. breviflora along with five known compounds, namely, 20-hydroxyecdysone, cyasterone, makisterone A, 20-hydroxyecdysone 3-acetate, and 20-hydroxyecdysone 2-acetate. The structures of 1-3 were elucidated on the basis of extensive 1D and 2D NMR spectroscopic studies. The new compounds possess acetal oxygen bridges between C-26 and C-20/C-22, or C-26/C-23, or a lactone bridge between C-26 and C-23.

A new sterol, ajugasalicigenin (1), and three new sterol glycosides, ajugasaliciosides F-H (2-4), were isolated and characterized from the aerial parts of Ajuga salicifolia. Compounds 1-4 are further representatives of the stigmastane type of sterols. Their cytotoxicity against KB (HeLa) and Jurkat T cancer cells was evaluated.