Ophiopogonin D (OP-D, Figure 1A) was purchased from Sichuan Weikeqi Biological Technology Co. Ltd. (Chengdu, China). Stock solution of OP-D (100 mM) was prepared using dimethyl sulfoxide, stored at ?80 °C, and diluted in cell culture medium for use. LightShift? Chemiluminescent EMSA kit

hecogenin (1), diosgenin (2), ruscogenin (3), gitogenin (4), tigogenin (5), solasodine (6), (24S,25S)-3β, 24-di-hydroxy-5α-spirostan (7), dracaenol C (8), 25(27)-dehydroruscogenin (9), (1β, 3β, 14α, 15α, 20R, 22S, 25R)-spirost-5-ene-tetrol (10), peimine (11), peiminine (12), peimisine (13), isoverticine (14), trillin (15), polyphyllin VI (16), polyphyllin VII (17), pallidifloside D (18), prosapogenin A (19), spongipregnoloside A (20), dioscin(21), solasonine (22), solamargine (23), gracillin (24), polyphyllin I(25), timosaponin BII (26), timosaponinA-III(27), ophiopogonin D (28), protobioside (29), (22S,25S)-26-O-β-d-glucopyranosyl-22,25-epoxyfurost-5-en-3β,26-diol-3-O-α-l-rha-mnopyranosyl(1 → 2)-β-d-gluc (30), pallidifloside E (31), parispseudoside (32), methylprotodioscin (33), protodioscin (34), pseudoprotodioscin (35), YS-IX (36), pallidifloside A (37), pallidifloside H (38), digoxin (39), bisdigoxigenin (40), 7β, 14α, 21-tri-hydroxy-diosgenin (41), 12β,14α,21-tri-hydroxy-diosgenin (42), and 11β,14α-di-hydroxyldiosgenin (43) were purchase from Sichuan weikeqi biotechnology company (Sichuan province, China). Pooled human liver microsomes (HLMs, 20 mg/mL) and pooled human primary hepatocytes were purchased from Rild Research Institute for LiverDiseases (Shanghai, China).

Ophiopogonin D (OP-D, Fig. 1A) was purchased from Sichuan Weikeqi Biological Technology Co., Ltd (Sichuan, China). Dimethyl sulfoxide was used to prepare an OP-D stock solution (100?mM), which was then kept at ?80 °C and diluted in a cell culture medium. Antibodies against IκB-α, p-IκB-α, p65, p-p65(ser276), AKT, c-Fos, c-Jun, Bcl-xL, IAP2, MMP-9, Caspase-3, PARP, Survivin, β-actin, and Lamin B, goat anti-mouse IgG-HRP

UGT1A10, UGT2B4, UGT2B7, and UGT2B15) expressed in baculovirus-infected insect cells were obtained from BD Gentest Corp. (Woburn, MA, USA). Ophiopogonin D (OD), ophiopogonin D′ (OD′), methylophiopogonanone A (MA), methylophiopogonanone B (MB), and ruscorectal (RU) were purchased from Sichuan Weikeqi Biotechnology Company (Chengdu, Sichuan, China). The purity of these compounds was above 95%. All other reagents were of HPLC grade or of the highest grade commercially available.

OP-D (purity ≥98%, HLPC) was obtained from Sichuan Weikeqi Biological Techology Co. (China). STZ was obtained from Sigma-Aldrich (USA) and gliclazide (Glic, 99.2%) was obtained from the Servier (Tianjin) Pharmaceutical Co. (China).