Elsevier

Phytochemistry Letters

Volume 6, Issue 4, November 2013, Pages 614-619
Phytochemistry Letters

α-Glucosidase inhibitory constituents from Chrozophora plicata

https://doi.org/10.1016/j.phytol.2013.08.005Get rights and content

Highlights

  • We isolated five (15) new secondary metabolites from Chrozophora plicata.

  • Their structures were established by using spectroscopic and spectrometric techniques.

  • Structure of plicatanin A (3) was confirmed through single crystal X-ray technique.

  • All the isolates (112) were found inhibitors of enzyme α-glucosidase except compound 9.

Abstract

Five new secondary metabolites have been isolated from Chrozophora plicata including an acacetin derivative (1), three pyrrole alkaloids plicatanins A–C (24, resp.) and the bilactone plicatanone (5). Together with these compounds, the known compounds, β-sitosterol (6), methyl p-coumarate (7), 4-hydroxyphenylacetic acid (8), succinic acid (9), speranberculatine A (10), β-sitosterol-3-O-β-d-glucopyranoside (11) and apigenin-5-O-β-d-glucopyranoside (12) have also been isolated. The structures of isolates 112 were established by 1D (1H, 13C) and 2D NMR (HMQC, HMBC, COSY) spectroscopy and mass spectrometry (EIMS, HREIMS, FABMS, HRFABMS). The structure of plicatanin A (3) was further confirmed through single crystal X-ray technique. Compounds 112 were evaluated for their inhibitory activity against the enzyme yeast α-glucosidase. The compound 4 was found to be most potent with IC50 value 27.8 μM.

Graphical abstract

The methanolic extract of Chrozophora plicata yielded five new (15), together with seven known compounds (612). Their structures were established by using 1D and 2D NMR spectroscopy and mass spectrometry. Compounds 112 were evaluated for their α-glucosidase inhibitory activity and 4 found potent inhibitor with IC50 value 27.8 μM.

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Introduction

The genus Chrozophora (Euphorbiaceae) comprises 11 species mostly shrubs and under shrubs distributed in Pakistan, India, West Africa and Mediterranean regions. One of these is Chrozophora plicata which grows in warmer climate and temperate regions (Chopra, 1988, Forster and Welzem, 1999). It possesses emetic, drastic and corrosive properties. Its seeds are used as cathartic (Gamble, 1967). The plant poisoning causes salivation, dyspnea, bloat, dullness, diarrhea, paresis of the hind limbs, recumbency and lateral deviation of the head and neck (Galal and Adam, 1988). Literature survey revealed the presence of diterpenoids (Mohamed et al., 1994), triterpenoids (Tanira et al., 1994), flavonoids (Hashim et al., 1990) and chromone glucosides (Agarwal and Singh, 1988) in different species of the genus Chrozophora, while hydrocarbons, cholesterol, stigmasterol, β-sitosterol, β-amyrin, squalene, octacosanol, hexacosanol and tetracosanol have previously been reported from C. plicata (Radwan et al., 2000). In the present investigation, the methanolic extract of the whole plant of C. plicata showed inhibitory activity against the yeast α-glucosidase which prompted us to carry out further phytochemical studies on this plant. Herein we report the isolation and structure elucidation of five new secondary metabolites 1–5 and seven known compounds 6–12. All of these were found to inhibit the enzyme α-glucosidase with IC50 values ranging between 27.8 and 287.1 μM while compound 9 was inactive.

α-Glucosidase (EC 3.2.1.20) comprises a family of enzymes, hydrolases, located in the brush-border surface membrane of small intestinal cells. Its major function is to hydrolyze the glycosidic linkage and produce glucose and other monosaccharide (Hirsh et al., 1997, Chiba, 1997). α-Glucosidase inhibitors are used as oral anti-diabetic drugs for patients with type-2 diabetic mellitus. Postprandial hyperglycemia has a vital role in the development of type-2 diabetes and complications associated with disease such as nephropathy, neuropathy, micoangiopathy, macroangipathy (Baron, 1998, Bonora and Muggeo, 2001). The inhibitors of this enzyme can retard the liberation of glucose and delay glucose absorption, resulting in reduced postprandial hyperglycemia (Lebovitz, 1997, Puls et al., 1984). Therefore, inhibition of α-glucosidase is considered important in managing type-2 diabetes. Acarbose, voglibose and miglitol are commerical α-glucosidase inhibitors that are considered as first-line treatment for diabetic individuals with post-prandial hyperglycemia. α-Glucosidase from Saccharomyces cereviciae is used routinely preliminary in vitro studies in the assay because of the structural and functional similarities between the yeast (eukaryote) and mammalian enzyme. The objective of present study is to identify new metabolites which can inhibit yeast α-glucosidase and be considered as target molecule for future anti-diabetic drugs.

Section snippets

Results and discussion

Compound 1 was isolated as yellow amorphous powder. The HRFABMS (+ve mode) exhibited quasi molecular ion peak [M+H]+ at m/z 739.2250 corresponding to the molecular C37H39O16 with 19 degree of unsaturation. The IR spectrum displayed absorption bands for hydroxyl (3344 cm−1), conjugated ester (1714 cm−1), conjugated ketone (1687 cm−1) and aromatic (1610–1525 cm−1) functionalities, whereas UV spectrum showed absorption maxima at 265 and 351 nm indicating the presence of acacetin nucleus (Marin et al.,

General experimental procedures

Column chromatography was carried out using silica gel of 70–230 and 230–400 mesh size. Aluminum sheets pre-coated with silica gel 60 F254 (20 cm × 20 cm, 0.2 mm thick; E-Merck) were used for TLC to check the purity of the compounds, which were either visualized under UV light (254 and 366 nm) or by spraying with ceric sulfate followed by heating. The UV spectra were recorded on a Hitachi UV-3200 spectrometer (λmax in nm). IR spectra were recorded on Shimadzu IR-460 spectrophotometer (ν in cm−1).

Acknowledgments

The authors thank to Alexander von Humboldt (AvH) Foundation, Germany and Higher Education Commission (HEC) of Pakistan for providing research grants to establish basic lab facilities in the Department of Chemistry at IUB.

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