The Synergistic Effect of Glucagon-Like Peptide-1 and Chamomile Oil on Differentiation of Mesenchymal Stem Cells into Insulin-Producing Cells


Saeid Saghahazrati, Ph.D, 1Seyed Abdulmajid Ayatollahi, Ph.D, 1,2,3,*Farzad Kobarfard, Ph.D, 4Bagher Minaii Zang, Ph.D., 5,*
Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Department of Chemistry, Richardson College for The Environmental Science Complex, The University of Winnipeg, Winnipeg, Canada
Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Department of Medicinal Chemistry, Shahid Beheshti School of Pharmacy, Tehran, Iran
Department of Histology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Department of Chemistry, Richardson College for The Environmental Science Complex, The University of Winnipeg, Winnipeg, Canada
Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Department of Medicinal Chemistry, Shahid Beheshti School of Pharmacy, Tehran, Iran
Department of Histology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
* Corresponding Addresses: P.O.Box: 141556163 Phytochemistry Research Center Shahid Beheshti University of Medical Sciences Tehran Iran P.O.Box: 1417613151 Department of Histology Faculty of Medicine Tehran University of Medical Sciences Tehran Iran Emails:majid_ayatollahi@yahoo.com,minaezb@tums.ac.ir
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Saghahazrati Saeid, Ayatollahi Seyed Abdulmajid, Kobarfard Farzad, Minaii Zang Bagher. The Synergistic Effect of Glucagon-Like Peptide-1 and Chamomile Oil on Differentiation of Mesenchymal Stem Cells into Insulin-Producing Cells. Cell J. 2020; 21(4): 371-378.

Abstract

Objective

Glucagon-like peptide-1 (GLP-1) has attracted tremendous attention for treatment of diabetes. Likewise, it seems that active ingredients of chamomile oil might have anti-diabetic effects. This work was conducted to investigate the effects of the combination of GLP-1 and chamomile oil on differentiation of mesenchymal stem cells (MSCs) into functional insulin-producing cells (IPCs).

Materials and Methods

In this experimental study, adipose MSCs derived from the adult male New Zealand white rabbits were assigned into four groups: control (without any treatment); GLP-1 (in which cells were treated with 10 nM GLP-1 every other day for 5 days); chamomile oil (in which cells were treated with 100 ug/ml Matricaria chamomilla L. flower oil every other day for 5 days); and GLP-1+ chamomile oil (in which cells were treated with 10 nM GLP-1 and 100 µg/ml M. chamomilla flower oil every other day for 5 days). Characterization of isolated MSCs was performed using flow cytometry, Alizarin red S staining and Oil red O staining. The expressions of genes specific for IPCs were measured using reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Measurement of insulin and the cleaved connecting peptide (C-peptide) in response to different concentrations of glucose, were performed using ELISA kits.

Results

Our results demonstrated that isolated cells highly expressed MSC markers and were able to differentiate into osteocytes and adipocytes. Additionally, using GLP-1 in combination with chamomile oil exhibited higher levels of IPCs gene markers including NK homeobox gene 2.2 (NKX-2.2), paired box gene 4 (PAX4), insulin (INS) and pancreatic duodenal homeobox-1 (PDX1) as well as insulin and C-peptide secretion in response to different glucose concentrations compared to GLP-1 or chamomile oil alone (P<0.05).

Conclusion

Collectively, these findings establish a substantial foundation for using peptides in combination with natural products to obtain higher efficiency in regenerative medicine and peptide therapy.