Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Apr 23:12:955-966.
doi: 10.2147/DDDT.S153898. eCollection 2018.

Islet protection and amelioration of type 2 diabetes mellitus by treatment with quercetin from the flowers of Edgeworthia gardneri

Manjiao Zhuang  1 , Honghong Qiu  2 , Ping Li  2 , Lihua Hu  2 , Yayu Wang  3 , Lei Rao  2
Affiliations

Islet protection and amelioration of type 2 diabetes mellitus by treatment with quercetin from the flowers of Edgeworthia gardneri

Manjiao Zhuang et al. Drug Des Devel Ther. .

Abstract

Background and purpose: The traditional Chinese medicine - the flower of Edgeworthia gardneri - is reported as an effective therapeutic for type 2 diabetes mellitus (T2DM). Nevertheless, most constituents of the flowers of E. gardneri have not yet been studied. This study was conducted to investigate the effect of quercetin extracted from the flowers of E. gardneri on islet protection and amelioration in T2DM and explore its mechanism.

Method: Quercetin was extracted from the flowers of E. gardneri and verified by high-performance liquid chromatography. Quercetin or crude extract's effect on insulin secretion was investigated. ERK1/2 and phospho-ERK1/2 were detected by Western blot analysis, and fluo-3 AM was used to detect intracellular Ca2+. The anti-apoptosis effect of quercetin or crude extract on MIN-6 cells was investigated by thiazolyl blue tetrazolium bromide (MTT) assay and flow cytometry analysis. Activation of caspases and expression of Bcl-2 and BAX were tested by Western blot analysis. In addition, the mitochondrial membrane potential was determined by JC-1 probe. Moreover, in vivo activity was also tested in db/db mice.

Results: A quercetin level of >10 μmol/L could induce insulin secretion. Intracellular Ca2+ and ERK1/2 were involved in the signaling pathway of quercetin-induced insulin secretion. We also observed that quercetin could inhibit palmitic acid-induced cell apoptosis via suppressing the activation of caspase-3, -9, -12; increasing the ratio of Bcl-2/BAX and reversing the impaired mitochondrial membrane potential. Crude extract's effect on insulin secretion was similar to that of pure extracted quercetin, while it possessed higher anti-apoptosis activity. Additionally, intraperitoneal glucose tolerance, plasma insulin level, hepatic triglyceride, hepatic glycogen and the pathological histology of both pancreatic islet and liver in db/db mice were significantly improved by the administration of the extracted quercetin.

Conclusion: Our study indicated that quercetin extracted from the flowers of E. gardneri exerted excellent properties in islet protection and amelioration.

Keywords: Edgeworthia gardneri; anti-apoptosis; insulin secretion; quercetin; type 2 diabetes mellitus.

PubMed Disclaimer

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
HPLC chromatogram of the isolated quercetin. Notes: (A) Chromatograms of quercetin standard. (B) Chromatograms of quercetin extracted from the flowers of Edgeworthia gardneri. (C) Chromatograms of aglycone quercetin standard (quercetin) and glycosides quercetin standard (rutin and isoquercetin). (D) Chromatograms of crude extract extracted from the flowers of E. gardneri. Abbreviation: HPLC, high-performance liquid chromatography.
Figure 2
Figure 2
Effect of quercetin or crude extract extracted from the flowers of Edgeworthia gardneri on insulin secretion in MIN-6 cells. Notes: (A) Effect of increasing concentrations (0, 0.001, 0.01, 0.1, 1, 10, and 100 μmol/L) of quercetin on insulin secretion in the absence or presence of glucose. (B) MIN-6 cells were incubated with 10 μmol/L extracted quercetin or glimepiride for different times (0, 10, 20, 30, 40, 50, and 60 min) in the presence of glucose and insulin secretion was detected respectively. (C) Effect of increasing concentrations (0, 0.001, 0.01, 0.1, 1, 10, and 100 μmol/L) of quercetin or crude extract extracted (with balanced quercetin content) from the flowers of E. gardneri on insulin secretion in the absence of glucose. (D) Effect of increasing concentrations (0, 0.001, 0.01, 0.1, 1, 10, and 100 μmol/L) of quercetin or crude extract extracted (with balanced quercetin content) from the flowers of E. gardneri on insulin secretion in the presence of glucose. (E) Effects of 10 μmol/L quercetin on intracellular Ca2+ level in the absence of glucose at different time points (0, 30, and 60 min; 400× magnification). (F) Effect of increasing concentrations (0, 0.001, 0.01, 0.1, 1, 10, and 100 μmol/L) of quercetin on ERK1/2 phosphorylation in the presence of glucose. (G) Effect of ERK1/2 inhibitor (AZD8330) and Ca2+ channel inhibitor (Nifedipine) on quercetin-induced insulin secretion in the presence of glucose. Bars with the same letter do not differ significantly (P < 0.05).
Figure 3
Figure 3
Anti-apoptosis effect of quercetin or crude extract extracted from the flowers of Edgeworthia gardneri. Notes: (A) Effects of increasing concentrations of palmitic acid (0.05, 0.2, 0.8, 3.2 and 12.8 mmol/L) on MIN-6 cell viability. (B) Effects of increasing concentrations (0, 0.001, 0.01, 0.1, 1, 10, and 100 μmol/L) of quercetin on cell viability in the presence of 0.8 mmol/L palmitic acid. The cell viability of control group was taken as 100%. (C) MIN-6 cells were incubated with 10 μmol/L extracted quercetin for different times (0, 4, 8, 12, 16, 20, and 24 h) in the presence of 0.8 mmol/L palmitic acid; the cell viability was detected respectively. The cell viability of the control group was taken as 100%. (D) Effects of increasing concentrations (0, 0.001, 0.01, 0.1, 1, 10, and 100 μmol/L) of quercetin or crude extract extracted from the flowers of E. gardneri on cell viability in the presence of 0.8 mmol/L palmitic acid. (E) Anti-apoptosis effect of 10 and 100 μmol/L quercetin in the presence of 0.8 mmol/L palmitic acid for 24 h. The percentage of apoptotic cells was determined by flow cytometric analysis. Bars with the same letter do not differ significantly (P < 0.05). *A statistically significant difference of P < 0.05. **A statistically significant difference of P < 0.01.
Figure 4
Figure 4
Anti-apoptosis mechanism of quercetin extracted from the flowers of Edgeworthia gardneri. Notes: (A) Western blots of cleaved caspase-3, -9, -12, Bax, and Bcl-2. The cells were incubated with increasing concentrations (0, 0.001, 0.01, 0.1, 1, 10 and 100 μmol/L) of quercetin in the presence of 0.8 mmol/L PA (palmitic acid) for 24 h. (B) Calculated Bcl-2/BAX ratios. The ‘relative intensity’ was defined as the intensity (Bcl-2)/intensity (BAX). (C) Effect of 10 and 100 μmol/L quercetin on mitochondrial membrane potential. Mitochondrial membrane potential was measured by JC-1 after incubation with quercetin for 24 h in the presence of 0.8 mmol/L palmitic acid (100× magnification). (D) The JC-1 fluorescence ratio was calculated by the average optical fluorescence density ratio of red/green. Bars with the same letter do not differ significantly (P < 0.05).
Figure 5
Figure 5
Effect of quercetin from the flowers of Edgeworthia gardneri in the treatment of db/db mice. Notes: (A) Effect of quercetin on glucose tolerance. (B) Effect of quercetin on insulin secretion. (C) Effect of quercetin on hepatic TG. (D) Effect of quercetin on hepatic glycogen. (E) Effect of quercetin on histological changes in pancreatic islets and livers (400× magnification). Glimepiride was used as positive control. **A statistically significant difference of P < 0.01. Abbreviation: TG, triglyceride.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Rathmann W, Giani G. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27(10):2568–2569. - PubMed
    1. DeFronzo RA. Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes. 1988;37(6):667–687. - PubMed
    1. Malchoff CD. Diagnosis and classification of diabetes mellitus. Conn Med. 1991;55:625–629. - PubMed
    1. Cnop M, Welsh N, Jonas JC, Jörns A, Lenzen S, Eizirik DL. Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities. Diabetes. 2005;54(Suppl 2):S97–S107. - PubMed
    1. Xu P, Xia Z, Lin Y. Chemical constituents from Edgeworthia gardneri (Thymelaeaceae) Biochem Syst Ecol. 2012;45:148–150.

MeSH terms