Trimethylapigenin

Biochem Pharmacol. 2012 Aug 15;84(4):498-506.

Effects of the natural flavone trimethylapigenin on cardiac potassium currents.[Pubmed: 22583923 ]

The natural flavones and polymethylflavone have been reported to have cardiovascular protective effects.
METHODS AND RESULTS:
In the present study, we determined whether quecertin, apigenin and their methylated compounds (3,7,3',4'-tetramethylquecertin, 3,5,7,3',4'-pentamethylquecertin, 7,4'-dimethylapigenin, and 5,7,4'-Trimethylapigenin) would block the atrial specific potassium channel hKv1.5 using a whole-cell patch voltage-clamp technique. We found that only Trimethylapigenin showed a strong inhibitory effect on hKv1.5 channel current. This compound suppressed hKv1.5 current in HEK 293 cell line (IC₅₀=6.4 μM), and the ultra-rapid delayed rectify K⁺ current I(Kur) in human atrial myocytes (IC₅₀=8.0 μM) by binding to the open channels and showed a use- and frequency-dependent manner. In addition, Trimethylapigenin decreased transient outward potassium current (I(to)) in human atrial myocytes, inhibited acetylcholine-activated K⁺ current (IC₅₀=6.8μM) in rat atrial myocytes. Interestingly, Trimethylapigenin had a weak inhibition of hERG channel current.
CONCLUSIONS:
Our results indicate that trimethyapigenin significantly inhibits the atrial potassium currents hKv1.5/I(Kur) and I(KACh), which suggests that Trimethylapigenin may be a potential candidate for anti-atrial fibrillation.

J Ethnopharmacol. 2011 Jul 14;136(3):488-95.

Suppressive effects of methoxyflavonoids isolated from Kaempferia parviflora on inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells.[Pubmed: 21251970]

Previously, we reported that the chloroform fraction of a Kaempferia parviflora extract had an inhibitory effect on rat paw-edema. In the present study, we isolated the constituents of this fraction and investigated the anti-inflammatory mechanism against nitric oxide (NO) production, tumor necrosis factor-α (TNF-α) and the expression of inducible nitric oxide synthase (iNOS) as well as phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated c-Jun N-terminal kinase (p-JNK). In addition, effects of Trimethylapigenin (4) on the enzyme activities of protein kinases possibly leading to iNOS expression were examined to clarify the targets.
METHODS AND RESULTS:
The chloroform fraction was isolated using silica gel column chromatography and HPLC. Isolated compounds were tested against NO and TNF-α using RAW264.7 cells. Cytotoxicity and iNOS, p-ERK and p-JNK expression were also examined. Three active components, 5,7-dimethoxyflavone (2), Trimethylapigenin (4), and tetramethylluteolin (5), markedly inhibited the production of NO in lipopolysaccharide (LPS)-activated RAW264.7 cells. Compounds 2, 4, and 5 moderately inhibited production of TNF-α. Compounds 2, 4, and 5 strongly inhibited expression of iNOS mRNA and iNOS protein in a dose-dependent manner, but did not inhibit p-ERK or p-JNK protein expression. The most active compound, 4, did not inhibit the enzyme activity of inhibitor of κB kinases or mitogen-activated protein kinases, but inhibited that of spleen tyrosine kinase (SYK).
CONCLUSIONS:
The mechanism responsible for the anti-inflammatory activity of methoxyflavonoids from the chloroform fraction of the rhizomes of Kaempferia parviflora is mainly the inhibition of iNOS expression, and the inhibition of SYK by 4 may be involved in the suppression of LPS-induced signaling in macrophages.