Elsevier

Food Chemistry

Volume 129, Issue 3, 1 December 2011, Pages 709-715
Food Chemistry

Advanced glycation end products inhibitors from Alpinia zerumbet rhizomes

https://doi.org/10.1016/j.foodchem.2011.04.034Get rights and content

Abstract

Advanced glycation end products (AGEs) are major factors responsible for the complication of diabetes. The present study was carried out to investigate the inhibitory activities on fructosamine adduct and α-dicarbonyl formations by hexane extracts of various parts of Alpinia zerumbet. Furthermore, we isolated two previously known compounds, namely 5,6-dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK). 8(17),12-Labdadiene-15,16-dial (labdadiene) was isolated for the first time from the rhizome of A. zerumbet. The results showed that labdadiene (IC50 = 51.06 μg/mL) had similar activity to rutin and quercetin against fructosamine adduct. The inhibition of α-dicarbonyl compounds formation by labdadiene was significantly higher than that of DK and DDK. Our results indicate that labdadiene is a potent antiglycation agent which was found to inhibit AGEs formation in three different steps in the pathway. These data indicate that labdadiene could be used to prevent glycation-associated complications in diabetes.

Highlights

► Rhizomes of Alpinia zerumbet inhibit AGEs formation. ► Labdadiene, an aldehyde, inhibited fructosamine adducts and α-dicarbonyl formation. ► Aldehyde groups may compete with sugars for Schiff’s base formation.

Introduction

Advanced glycation end products (AGEs) are a complex and heterogeneous group of compounds that have been implicated in diabetes-related complications. The AGEs are closely associated with hyperglycaemia and their patho-biochemistry could explain many of the changes observed in diabetes-related complications (Singh, Barden, Mori, & Beilin, 2001). AGEs are the products of non-enzymatic glycation and oxidation of proteins and lipids. Glycation adducts of proteins are formed when proteins react with glucose-reactive α-oxoaldehydes or dicarbonyls, such as glyoxal, methylglyoxal and 3-deoxyglucosone (3-DG) (Brownlee, 2001). These adducts have recently been proposed to be formed from all stages of the glycation process, by degradation of glucose or Schiff’s bases in early glycation, or from Amadori products such as fructosamine in the intermediate stages of glycation. Thus, α-dicarbonyl could be considered an important focal point of how glucose can go on to form AGEs by the classical Maillard reaction, using AGEs formation pathway (Singh et al., 2001), as well as from in vivo factors, such as the catabolism of ketone bodies and threonine, and lipid peroxidation (Thornalley, Langborg, & Minhas, 1999). Therefore, inhibition of fructosamine adducts and α-dicarbonyls could reduce AGEs formation and hence lessen the chance of diabetic complications.

Alpinia zerumbet (family: Zingiberaceae) is a perennial plant growing widely in the subtropical and tropical regions. It is used in traditional medicine for its anti-inflammatory, bacteriostatic and fungistatic properties (Zoghbi, Andrade, & Maia, 1999). Dihydro-5,6-dehydrokawain (DDK) and 5,6-dehydrokawain (DK) have been detected in the rhizomes of Alpinia speciosa (Itokawa, Morita, & Mihashi, 1981). Furthermore, DK and DDK are reported to inhibit the aggregation of ATP release from rabbit platelets (Teng et al., 1990). DK and DDK are described to have anti-ulcerogenic and antithrombotic activities (Mpalantinos, Moura, Parente, & Kuster, 1998). The inhibitory effects of DK on human platelet aggregation, anti-inflammatory and cancer chemopreventive therapeutic properties are reported (Jantan et al., 2008). Labdadiene, isolated from the Zingiberaceae (Sirat, Masri, & Rahman, 1994), was traditionally used as a medicine against inflammatory diseases (Kunnumakkara et al., 2008). The cardiovascular effects induced by labdadiene were evaluated in male Wistar rats (Oliveira et al., 2006). Moreover, labdadiene has also been reported to inhibit lipid peroxidation, cyclooxygenase enzymes and human tumour cell proliferation (Liu & Nair, 2011). Our laboratory has reported DDK and phenolic compounds and their antioxidant activities in leaves and rhizomes of A. zerumbet (Elzaawely, Xuan, & Tawata, 2007). Recently we have reported the HIV-1 integrase and neuraminidase inhibitory properties of A. zerumbet and have found that DK and DDK have significant bioactivities (Upadhyay, Chompoo, Kishimoto, Makise, & Tawata, 2011).

In this study, we primarily investigated the inhibitory properties on AGEs formation of hexane extracts from six different parts of A. zerumbet. Since we had previously found high bioactivities in DK and DDK (Upadhyay et al., 2011), we focused on these compounds for AGEs inhibitory properties. Furthermore, we isolated labdadiene for the first time from A. zerumbet and investigated its activities. We examined the inhibition of fructosamine adducts and α-dicarbonyl formation in order to check its efficacy against AGEs. To the best of our knowledge, this is the maiden report on AGEs inhibition from A. zerumbet and isolated compounds.

Section snippets

Chemicals and reagents

Bovine serum albumin (BSA), copper(II) sulphate, d(+)-glucose, 2,4-dinitrophenylhydrazine (DNPH), heptafluorobutyric acid (HFBA), 40% glyoxal solution, nitro blue tetrazolium chloride (NBT), sodium azide, and guanidine were obtained from Wako Pure Chemical Industries Ltd. (Osaka, Japan). Trichloroacetic acid (TCA) was purchased from Sigma–Aldrich (St Louis, MO). Trimethylaminoacetohydrazide chloride (Girard’s reagent T) was bought from Tokyo Chemical Industry Co. Ltd. (Tokyo, Japan). Alkaline

Amounts of DK, DDK and labdadiene

The amounts of DK, DDK and labdadiene in the crude extracts from different parts of A. zerumbet are shown in Table 1. DK and DDK were found in all parts of the plant. The rhizomes extract contained higher amount of DK (3.13 mg/g hexane extract), however, flowers extract contained a higher quantity of DDK (6.08 mg/g hexane extract). The hexane extract of rhizomes contained higher amount of labdadiene (3.97 mg/g hexane extracts) than seeds and pericarp (0.35 and 2.91 mg/g hexane extracts,

Discussion

The present research examines the effect of hexane extracts from different parts of A. zerumbet and the compounds isolated from the rhizomes against AGEs formation. Researchers have focused on anti-AGEs activities of phenolic compounds of different plant extracts using more polar solvents. However, in this study we chose hexane as the solvent for extracting bioactive phytochemicals from A. zerumbet. Hexane provides better isolation of the target compounds, including DK, DDK and labdadiene.

We

Conclusion

The rhizomes of A. zerumbet have several metabolites that have AGEs inhibitory properties. We isolated two kawains, DK and DDK, and for the first time isolated labdadiene from the rhizomes of A. zerumbet. Our results showed three-fold inhibitory properties of these compounds against AGEs formation. We found that labdadiene showed the strongest activity and had significant results when compared with rutin and quercetin. Thus, labdadiene could be used as a preventive measure against

Acknowledgement

The authors would like to thank Tatsunori Higa for his assistance with the experiments.

References (28)

  • Y. Takagi et al.

    Significance of fructose-induced protein oxidation and formation of advanced glycation end product

    Journal of Diabetes and Its Complications

    (1995)
  • J.W. Wu et al.

    Inhibitory effects of guava (Psidium guajava L.) leaf extracts and its active compounds on glycation process of protein

    Food Chemistry

    (2009)
  • J.R. Baker et al.

    Chemistry of the fructosamine assay: d-glucosone is the product of oxidation of Amadori compounds

    Clinical Chemistry

    (1994)
  • B.H.J. Bielski et al.

    Reduction of nitro blue terazolium by CO2- and O2- radicals

    The Journal of Physical Chemistry

    (1980)
  • Cited by (0)

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