Screening and evaluation of new inhibitors of hepatic glucose production

Abstract

In the course of our screening program for inhibitors of hepatic glucose production in rat hepatoma H4IIE-C3 cells, which were used as model liver cells, five naphtoquinone derivatives-javanicin, solaniol, 9-O-methylfusarubin, 5,10-dihydroxy-1,7-dimethoxy-3-methyl-1H-naphtho[2,3-c]pyran-6,9-dione, 9-O-methylbostrycoidin-and vanillin were selected from our natural product library. These naphtoquinone derivatives inhibited hepatic glucose production at IC 50 values of 3.8-29 lM, but showed cytotoxicity against hepatic cells after incubation for 48 h. However, vanillin showed an IC 50 value of 32 lM without exhibiting cytotoxicity at 50 lM. Therefore, we examined 12 vanillin derivatives to investigate their inhibitory activities against glucose production. Among these analogs, 4-hydro-3-methoxyacetophenone and 5-nitrosalicylaldehyde exhibited stronger inhibition than the other compounds at IC 50 values of 25 and 24 lM, respectively, with no cytotoxicity at a concentration of 50 lM. Hence, 4-hydro-3-methoxyacetophenone and 5-nitrosalicylaldehyde may be useful as a lead compound of anti-type 2 diabetic drugs.

Isolation of Unstable Isomers of Lucilactaene and Evaluation of Anti-Inflammatory Activity of Secondary Metabolites Produced by the Endophytic Fungus Fusarium sp. QF001 from the Roots of Scutellaria baicalensis

“…Compound 1 was previously reported as a phytotoxin, cytotoxin against human cancer cells, a anti-parasitic agent against Trichomonas vaginalis, and an anti-tuberculosis agent [20][21][22][23]. Compound 4 was known with the hepatic glucose production inhibiting activity and cytotoxicity [24]. Compound 5 was also reported to have cytotoxicity and antibacterial activity as well as anti-parasitic activity and hepatic glucose production inhibiting activity [22,25,26].…”

Utilization of High Performance Liquid Chromatography Coupled to Tandem Mass Spectrometry for Characterization of 8-O-methylbostrycoidin Production by Species of the Fungus Fusarium

“…Early studies described the isolation of 8- O -methylbostrycoidin and showed its cytotoxicity against several mammalian cell lines, including rat hepatoma, Madin Darby canine kidney and Chinese hamster ovary [ 6 ]. Later, Hashimoto again observed the low cytotoxicity against the rat hepatoma cell line, but observed a strong ability to inhibit hepatic glucose production [ 7 ]. More recently, 8- O -methylbostrycoidin has been evaluated for cytotoxicity to a number of human cancer cell lines and has been shown to strongly inhibit α-acetylcholine esterase [ 5 ].…”

Phytotoxic Activity of Metabolites Isolated from Rutstroemia sp.n., the Causal Agent of Bleach Blonde Syndrome on Cheatgrass (Bromus tectorum)

“…It showed phytotoxic activity against wheat, bean, corn and tobacco plants at different concentrations and antineoplastic effects on ras transformed liver epithelial cells [ 26 ]. Finally, compound 1 inhibited hepatic glucose production at an IC 50 value of 4.8 μM and showed cytotoxicity against hepatic cells after incubation for 48 h [ 33 ].…”

“…BA-10763 [ 27 ]. In addition, 2 displayed remarkable inhibiting action against α-acetylcholinesterase (AChE) with an IC 50 value of 6.71 μM [ 34 ], inhibited hepatic glucose production at an IC 50 value of 30 μM, and showed weak cytotoxicity against hepatic cells after incubation for 48h [ 33 ]. It also showed bactericidal activity against some Gram+ bacteria, but it has never been tested for phytotoxic activity.…”