Potent SIRT1 Enzyme-stimulating and Anti-glycation Activities of Polymethoxyflavonoids from Kaempferia parviflora

Abstract

The SIRT1 enzyme-stimulating and anti-glycation activities of Kaempferia parviflora extract and its main polymethoxyflavonoids were evaluated in vitro. K. parviflora extract elevated SIRT1 catalytic activity by eight-and 17-fold at 20 g/mL and 100 g/mL, respectively, compared with vehicle only. Two major polymethoxyflavonoids, 3,5,7,3',4'-pentamethoxyflavone (4) and 5,7,4'-trimethoxyflavone (5), were isolated from this extract and are four-and fivefold more potent than resveratrol, hitherto the strongest known natural SIRT1 activator. In addition, the anti-glycation activity of K. parviflora extract was observed to be seven times more effective than aminoguanidine, a clinical anti-diabetes drug. 3,5,7,3',4'-Pentamethoxyflavone (4) and 5,7,4'-trimethoxyflavone (5) showed the strongest anti-glycation activity among the tested polymethoxyflavonoids. Further comparison of the activity of these structurally related polymethoxyflavonoids revealed a possible structure-activity relationship, in particular, for the contribution of methoxy moieties.

Drug Metabolite Cluster-Based Data-Mining Method for Comprehensive Metabolism Study of 5-hydroxy-6,7,3′,4′-tetramethoxyflavone in Rats

“…HTF is one of the major OH-PMFs, existing mainly in the citrus genus such as Citrus sinensis , Citrus mangshanesis , and Citrus clementina , which displayed significant antioxidant activities and showed remarkable inhibition effects on the B16 cell lines at a concentration range from 6.25 to 50 μg/mL [13]. OH-PMFs, the flavonoid subclass in which all or almost hydroxyls are capped by methylation, have drawn more and more attention recently because accumulating evidence has demonstrated that OH-PMFs have many stronger health-promoting biological activities and higher oral bioavailability than their permethoxylated counterparts [14]. OH-PMFs have been proven to exhibit a broad spectrum of biological properties including anti-carcinogenic [15,16], anti-coagulation [17], anti-inflammatory [18,19], and anti-oxidant activities [20,21].…”

Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds

“…These findings have led to the prevailing model in which SIRT1 imparts many of the benefits of a calorie restriction diet 69–71,136 . Additional screens for more potent, soluble and efficacious STACs have been successful 172,173 .…”

Quercetin 3,5,7,3′,4′-pentamethyl ether from Kaempferia parviflora directly and effectively activates human SIRT1

“…In 2014, Nakata et al reported that polymethoxyflavonoids from the Thai black ginger Kaempferia parviflora , especially quercetin 3,5,7,3′,4′-pentamethyl ether (KPMF-8), show dramatic activation of SIRT1 activity 19 . However, the legitimacy of KPMF-8 as a direct SIRT1 activator is totally unknown, as the FdL peptide substrate was used in the initial activity assay 19 .…”

“…In 2014, Nakata et al reported that polymethoxyflavonoids from the Thai black ginger Kaempferia parviflora , especially quercetin 3,5,7,3′,4′-pentamethyl ether (KPMF-8), show dramatic activation of SIRT1 activity 19 . However, the legitimacy of KPMF-8 as a direct SIRT1 activator is totally unknown, as the FdL peptide substrate was used in the initial activity assay 19 . In light of skepticism about other controversial STACs, further study is required to determine the followings: (1) whether KPMF-8 directly interacts with SIRT1, (2) whether KPMF-8 activates SIRT1 towards the native substrate, and (3) whether KPMF-8 can penetrate the cell membrane and accelerate intracellular deacetylase activity within the cellular environment.…”