Xanthine Oxidase Inhibitory Activities and Crystal Structures of Methoxyflavones from Kaempferia parviflora Rhizome

Nakao, Kazuwa; Murata, Kazuya; Deguchi, Takahiro; Itoh, Kimihisa; Fujita, Takanori; Higashino, Masayuki; Yoshioka, Yuri; Matsumura, Shinichi; Tanaka, Rika; Shinada, Tetsuro; Ohfune, Yasufumi; Matsuda, Hideaki

doi:10.1248/bpb.34.1143

Cited by 31 publications

(20 citation statements)

References 28 publications

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“…Its rhizome has been used in folk medicine reportedly for health promotion and stimulation. Several pharmacological responses to KP and its components have been claimed, including aphrodisiac (Sudwan et al, 2006;Wattanapitayakul et al, 2007;Chaturapanich et al, 2008;Wattanathorn et al, 2012), antipeptic ulcer (Rujjanawate et al, 2005), anti-inflammatory Sae-wong et al, 2009;Nakao et al, 2011), antiallergenic , antimutagenic (Azuma et al, 2011), antidepressive (Wattanathorn et al, 2007), antimicrobial (Yenjai et al, 2004Kummee et al, 2008), anticholinesterase (Sawasdee et al, 2009), anticancer (Wen et al, 2005;Banjerdpongchai et al, 2008;Leardkamolkarn et al, 2009;Wudtiwai et al, 2011), cardioprotective (Tep-areenan et al, 2010;Malakul et al, 2011a,b), and antiobesity activity (Akase et al, 2011). In addition, inhibition of P-glycoprotein function and multidrug resistance-associated protein by KP have been demonstrated (Patanasethanont et al, 2007a,b).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, Bioavailability, Tissue Distribution, Excretion, and Metabolite Identification of Methoxyflavones in Kaempferia parviflora Extract in Rats

Mekjaruskul¹,

Jay²,

Sripanidkulchai³

2012

Drug Metab Dispos

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ABSTRACT:Kaempferia parviflora (KP) is an herbal plant in the family of Zingiberaceae. KP mainly contains methoxyflavones, especially 5,7-dimethoxyflavone (DMF), 5,7,4-trimethoxyflavone (TMF), and 3,5,7,3,4-pentamethoxyflavone (PMF). The present study was designed to characterize the pharmacokinetics, including bioavailability, distribution, excretion, and identification of metabolites after administration of a KP ethanolic extract. Male rats were orally or intravenously administered a 250 mg/kg concentration of a KP extract, and blood samples were obtained at selected times to determine pharmacokinetic parameters of PMF, TMF, and DMF. For distribution and excretion studies, the organs, urine, and feces samples were collected at various times after oral administration of a larger (750 mg/kg) dose of KP extract. Methoxyflavones in the biological samples were quantified by high-performance liquid chromatography-UV, and the metabolites in urine and feces were further identified by using liquid chromatography-tandem mass spectrometry. After oral administration, concentrations of the three methoxyflavones quickly approached their maximal concentration, ranging from 0.55 to 0.88 g/ml within 1 to 2 h after administration, and then were gradually excreted with half-lives of 3 to 6 h. The methoxyflavones showed low oral bioavailability of 1 to 4%. Three methoxyflavones were detected at their highest levels in liver followed by kidney. They were also found in lung, testes, and brain. After absorption, organ distribution, and metabolism, the components of KP were mainly eliminated through urine in the forms of demethylated, sulfated, and glucuronidated products and as demethylated metabolites in the feces. The parent compounds were found to have 0.79, 1.76, and 3.10% dose recovery in urine and 1.06, 1.77, and 0.96% dose recovery in feces for PMF, TMF, and DMF, respectively. These studies are the first to describe the pharmacokinetics of KP extract to provide the information on blood and tissue levels.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, Bioavailability, Tissue Distribution, Excretion, and Metabolite Identification of Methoxyflavones in Kaempferia parviflora Extract in Rats

Mekjaruskul¹,

Jay²,

Sripanidkulchai³

2012

Drug Metab Dispos

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“…The major chemical components isolated from the extract were methoxyflavones ( 81–82) with mixed‐type mode of inhibition (Fig. ) . Bustanji and colleagues evaluated Jordanian medicinal plants extracts for XO inhibitory potential.…”

Section: Xanthine Oxidasementioning

confidence: 99%

Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases

Kumar

Joshi

Kler

et al. 2017

Medicinal Research Reviews

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Almost all drug molecules become the substrates for oxidoreductase enzymes, get metabolized into more hydrophilic products and eliminated from the body. These metabolites sometime may be more potent, active, inactive, or toxic in nature compared to parent molecule. Xanthine oxidoreductase and aldehyde oxidase belong to molybdenum containing family and are well characterized for their structures and functions, in particular to their ability to oxidize/hydroxylate the xenobiotics. Their upregulated clinical levels causing oxidative stress are associated with pathways either directly involved in the progression of diseases, gout, or indirectly with the succession of other diseases such as diabetes, cancer, etc. Herein, we have put forth a comprehensive review on the xanthine and aldehyde oxidases pertaining to their structures, functions, pathophysiological role, and a comparative analysis of structural insights of xanthine and aldehyde oxidases' binding domains with endogenous ligands or inhibitors. Though both the enzymes are molybdenum containing and are likely to share some common pathways and interact with inhibitors in a similar manner but we have focused on structural prerequisites for inhibitor specificity to both the enzymes keeping in view of the existing X-ray structures. This review also provides futuristic implications in the design of inhibitors derived from inorganic complexes or small organic molecules considering the spatial features and structural insights of both the enzymes.

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“…Saewung et al (2009) (5) had also demonstrated that an ethanolic extract of K. parviflora markedly inhibited PGE 2 release and suppressed mRNA expression of iNOS in dosedependent manners, whereas COX-2 mRNA expression was partly affected. Furthermore, ten methoxyflavones were isolated from K. parviflora extract and PMF and 5,7,3'4'-tetramethoxyflavone showed inhibitory xanthine oxidase activity (6). With its strong anti-inflammatory effect, several K. parviflora products are available in the market including pills, capsules, tea, and wine.…”

Section: Introductionmentioning

confidence: 99%

Transdermal Permeation of Kaempferia parviflora Methoxyflavones from Isopropyl Myristate-Based Vehicles

et al. 2014

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Kaempferia parviflora (K. parviflora) rhizomes have long been used in traditional folk medicines and as general health-promoting agents. Several biological activities of K. parviflora, especially its antiinflammatory effect, are due to its major constituents, methoxyflavones. However, the oral bioavailability of these methoxyflavones has been shown to be low. The aim of this study was to investigate the permeation behaviors of K. parviflora methoxyflavones from isopropyl myristate (IPM)-based vehicles. We studied the effects of ethanol and propylene glycol (PG) as the hydrophilic, solvent-type vehicles as well as fatty acids as the permeation enhancers. A permeation experiment was performed in vitro, using side-by-side diffusion cells through the full thickness of pig ear skin. The solubility and permeation of methoxyflavones were able to be modified by choice and ratio of vehicles. The ethanol/IPM vehicle was shown to be more effective in enhancing the solubility and permeation of methoxyflavones when compared to the PG/IPM vehicle. Regarding an optimal balance between solubility or affinity to vehicle and skin to vehicle partition coefficient, the ethanol/IPM vehicle in the ratio of 1:9 maximized the flux. Among the investigated fatty acids, oleic acid showed the greatest enhancing effect on the permeation of methoxyflavones, indicating that saturated fatty acids are less effective than unsaturated fatty acids. Long chain fatty acids increased diffusion coefficient parameter and shortened the lag time. The number of carbon atoms and double bonds of fatty acids did not show direct relation to the profile of permeation of methoxyflavones.

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Xanthine Oxidase Inhibitory Activities and Crystal Structures of Methoxyflavones from Kaempferia parviflora Rhizome

Cited by 31 publications

References 28 publications

Pharmacokinetics, Bioavailability, Tissue Distribution, Excretion, and Metabolite Identification of Methoxyflavones in Kaempferia parviflora Extract in Rats

Pharmacokinetics, Bioavailability, Tissue Distribution, Excretion, and Metabolite Identification of Methoxyflavones in Kaempferia parviflora Extract in Rats

Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases

Transdermal Permeation of Kaempferia parviflora Methoxyflavones from Isopropyl Myristate-Based Vehicles

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