P-glycoprotein (P-gp) plays a significant role in multi-drug resistance (MDR) of cancer cells, resulting in the failure of cancer chemotherapy. Lathyrane diterpene was a class of promising MDR modulator. The phytochemical investigation on the seeds of Euphorbia lathyris L. aff ;orded four new lathyrol-type diterpenoids (1-4), together with seventeen known ones (5-23). The structures of these compounds were elucidated by using 1D and 2D NMR spectroscopy. All the compounds were evaluated reversing MDR activity in HepG2/ADR cells. Compounds 2-4, 7-9, 11, 13-14, 16, 18-19, and 2 1-2 3 at 20 μM was able to reverse MDR of HepG2/ADR cells to adriamycin (reversal fold: 10.05-448.39). In the investigation of reversing the MDR mechanism, the most potent compound 21 facilitated the accumulation of intracellular adriamycin in HepG2/ADR cells in the time-dependent model. Although 21 neither affected the P-gp distribution nor expression in HepG2/ADR cells, the amount of P-gp monomer was induced by 21 and verapamil. Compound 21 has also activated the P-gp coupled ATPase activity in a dose-dependent model. The molecular docking analysis implied that 21 had lower binding energy than verapamil and adriamycin. The present data demonstrated that lathyrane diterpenes may act as a class of high-affinity P-gp substrate and was effluxed by P-gp monomer to reverse the MDR.

Four new naphthoquinones (1–4), including a dimeric one, shikometabolin G (1), together with six known ones (6–10), were isolated from the methanol extract of Onosma paniculatum. Their structures were established based on the analysis of NMR and MS spectroscopic data. All of the compounds were evaluated for inhibitory effects on NO production in murine macrophage RAW 264.7 cells. Compounds 2, 3, 5, 6, 7, 8, and 10 displayed good activity on the inhibition of NO production (IC₅₀ = 0.4–16.5 µM), suggesting the potential property of anti-inflammation. ^* These two authors contributed equally to this work.

Fourteen of the methyl 2-cyano-3,12-dioxo-18β-olean-1,9(11)-dien-30-oate (CDODO-Me-12, 10d) analogues with different structures of ring C were synthesized to determine the active groups for inhibiting cell growth and inducing apoptosis in human leukemia HL-60 cells. An unsaturated group in ring C was required to maintain the ability to inhibit cell growth and induce apoptosis. Compound 10e with 9(11),12-dien in ring C displayed comparable apoptosis induction ability to 10d associated with decreased levels of c-FLIP, but not Mcl-1 and XIAP. Compound 10e had decreased ability to deplete GSH compared to compound 10d. Compound 10e represents a new active compound acting through a different mechanism from that of compound 10d.