Elsevier

Phytochemistry

Volume 70, Issue 10, July 2009, Pages 1246-1254
Phytochemistry

Anti-diabetic properties of three common Bidens pilosa variants in Taiwan

https://doi.org/10.1016/j.phytochem.2009.07.011Get rights and content

Abstract

Bidens pilosa L. var. radiata (BPR), B. pilosa L. var. pilosa (BPP), and B. pilosa L. var. minor (BPM) are common variants of a plant often used as a folk remedy for diabetes in Taiwan. However, the three variants are often misidentified and little is known about their relative anti-diabetic efficacy and chemical composition. In this paper, we have first developed a method based on GC–MS and cluster analysis with visualization to assist in rapidly determining the taxonomy of these three Bidens variants. GC–MS was used to determine the chemical compositions of supercritical extracts, and differences and similarities in the variants were determined by hierarchical cluster analysis. Next, the HPLC profiles of the methanol crude extracts in the Bidens plants and evaluated anti-diabetic effects of methanol crude extracts were compared, as well as three polyacetylenic compounds of the Bidens plants using db/db mice. Single-dose and long-term experiments showed that the BPR extract had higher glucose-lowering and insulin-releasing activities than extracts from the other two variants, and that cytopiloyne was the most effective pure compound among the three polyacetylenic compounds. BPR extract and cytopiloyne also significantly reduced the percentage of the glycosylated hemoglobin A1c in db/db mice. Besides, both animal studies and HPLC analysis demonstrated a good correlation between anti-diabetic efficacy of the Bidens extracts and the particular polyacetylenes present.

Graphical abstract

Three polyacetylenic glucosides isolated from the methanol extract of Bidens species were tested for their bioactivities using db/db mice, a mouse model of type 2 diabetes. Compound 2, cytopiloyne, showed both anti-hyperglycemic and insulin-releasing activities to a greater extent than compounds 1 or 3.

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Introduction

Diabetes mellitus is a serious metabolic disease resulting from defects in either insulin secretion, insulin action, or both. Over 90% of diabetic patients have Type 2 diabetes which results from insulin resistance or insulin secretion defects (Attele et al., 2002). Control over blood glucose levels is gradually lost and levels of glycosylated hemoglobin A1c (HbA1c) rise in patients with Type 2 diabetes. Currently, several anti-diabetic agents are available, but these are unsatisfactory in terms of efficacy and adverse side-effects (Howlett and Bailey, 1999, Lebovitz, 1998). Recently, the search for novel anti-diabetic medicines has focused on medicinal plants because of their efficacy in human clinical trials and the minimal side-effects of drugs derived from medicinal plants (Rates, 2001, Suba et al., 2004).

Plants are known to be an extraordinary source of anti-diabetic medicines (Marles and Farnsworth, 1995). The genus Bidens includes approximately 230 species worldwide (Encyclopedia Britannica Inc., 2008), and a wide range of biological activities have been reported for many plants of this genus (Alarcon-Aguilar et al., 2002, Brandão et al., 1997, Chang et al., 2005, Chiang et al., 2004, Chih et al., 1995, Dimo et al., 2001, Dimo et al., 2002, Geissberger and Séquin, 1991, Gilbert et al., 1999, Jäger et al., 1996, Mahonge et al., 2006, Rücker et al., 1992, Rabe and van Staden, 1997, Ssegawa and Kasenene, 2007, Ubillas et al., 2000, Yang et al., 2006, Yoshida et al., 2006), although most of the presumed activities have not been studied scientifically. Several Bidens species are currently used as herbal diabetes treatments by people in American, African, and Asian regions (Brandão et al., 1997, Chih et al., 1995, Hernandez-Galicia et al., 2002, Jäger et al., 1996, Lans, 2006). In Taiwan, the species most often used is Bidens pilosa (Lin, 1992). There are three common variants of this species in Taiwan: B. pilosa L. var. radiata (BPR), B. pilosa L. var. pilosa (BPP) and B. pilosa L. var. minor (BPM). All three variants share similar morphological characteristics and habitat preferences (Chaw et al., 1998), so they are often misidentified. To help in the correct identification of these plants, we have developed a chemotaxonomic method, a method to identify relationships among plant taxa using concentration of several pre-selected compounds (Ge et al., 2008), based on GC–MS analysis and cluster analysis with visualization of the chemical profiles.

We have previously shown that three of the polyacetylenic glucosides in Bidens pilosa can prevent Type 1 diabetes (Chang et al., 2007, Chang et al., 2004, Chiang et al., 2007). In addition, two of the polyacetylenic glucosides were shown elsewhere to be anti-hyperglycemic (Ubillas et al., 2000). These studies suggest that polyacetylenic glucosides present in B. pilosa are the major active phytochemicals against both types of diabetes. In this paper, we first developed a combinational method of GC–MS analysis and cluster analysis to help in the authentication of the three Bidens pilosa variants including BPR, BPP, and BPM. Next, we examined anti-diabetic efficacies of the crude extracts and polyacetylenic compounds of the Bidens variants in db/db mice, a model of Type 2 diabetes.

Section snippets

GC–MS chromatograms and cluster analysis of the chemical profiles of Bidens pilosa variants

To aid the taxonomy of the three common B. pilosa variants, namely BPR, BPP, and BPM, in Taiwan, GC–MS analysis of supercritical CO2 extracts was used to determine their chemical compositions (Fig. 1). Cluster analysis tools, such as hierarchical cluster tree (HCT), principal component analysis (PCA) and multidimensional scaling (MDS), have been used previously in the analysis of inter- and intra-species chemical variations (Medina-Holguin et al., 2008, Nyman and Julkunen-Tiitto, 2005).

Conclusions

Using the three Bidens pilosa variants BPR, BPP and BPM as examples, we have demonstrated that a combination of GC–MS analysis and cluster analysis with matrix visualization is a fast and reliable taxonomical method to chemically distinguish plants with similar habitats and morphologies. We also found that the methanol crude extract of BPR has higher anti-diabetic activities than that of BPP and BPM, as evidenced by the increase in serum insulin, the decrease in blood glucose and the increase

Plant materials

Bidens pilosa variants (BPR, BPP, and BPM), which belong to the plant family Asteraceae, were collected in Taiwan and authenticated by Dr. Ching-I Peng (Biodiversity Center, Academia Sinica, Taiwan), and voucher specimens were deposited as 120085 (BPR), 120086 (BPP), and 120087 (BPM) at Academia Sinica Herbarium, Taiwan. The plants were then grown from seeds in green houses at Academia Sinica.

Chemicals and animals

HPLC grade MeOH, CH3CN and biochemical grade CF3CO2H (TFA) were purchased from Mallinckrodt Baker

Acknowledgements

The authors thank the members in the Metabolomics Core Facility of ABRC and in NSC Bioinformatics Service core for their excellent technical assistance. They thank Dr. Ching-I Peng for taxonomical identification, and Dr. Harry Wilson for his critical review of this manuscript. This research was supported by Grants (NSC94-2320-B-001-028, NSC95-2320-B-001-012, 94F002-2 and NSC 97-3112-B-001-02) from the National Science Council and Academia Sinica, Taiwan, ROC.

References (40)

  • T. Nyman et al.

    Chemical variation within and among six northern willow species

    Phytochemistry

    (2005)
  • T. Rabe et al.

    Antibacterial activity of South African plants used for medicinal purposes

    J. Ethnopharmacol.

    (1997)
  • S.M.K. Rates

    Plants as source of drugs

    Toxicon

    (2001)
  • P. Ssegawa et al.

    Medicinal plant diversity and uses in the Sango bay area, Southern Uganda

    J. Ethnopharmacol.

    (2007)
  • V. Suba et al.

    Anti-diabetic potential of Barleria lupulina extract in rats

    Phytomedicine

    (2004)
  • H.L. Yang et al.

    Protection from oxidative damage using Bidens pilosa extracts in normal human erythrocytes

    Food Chem. Toxicol.

    (2006)
  • F.J. Alarcon-Aguilar et al.

    Investigation on the hypoglycaemic effects of extracts of four Mexican medicinal plants in normal and alloxan-diabetic mice

    Phytother. Res.

    (2002)
  • A.S. Attele et al.

    Antidiabetic effects of Panax ginseng berry extract and the identification of an effective component

    Diabetes

    (2002)
  • L. Brieman et al.

    Classification and Regression Trees

    (1984)
  • C.L.-T. Chang et al.

    Cytopiloyne, a polyacetylenic glucoside, prevents Type 1 diabetes in nonobese diabetic mice

    J. Immunol.

    (2007)
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