Naturally-occurring TGR5 agonists modulating glucagon-like peptide-1 biosynthesis and secretion

Jafri, Laila; Saleem, Shemaila; Calderwood, Danielle; Gillespie, Anna; Mirza, Bushra; Green, Brian D.

doi:10.1016/j.peptides.2016.01.015

Cited by 16 publications

(7 citation statements)

References 35 publications

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“…Peptides used for pharmacological intervention have been traditionally derived from natural products isolated from plants, animals or humans (as is the case with hormone-based peptide agonists) [9,10]. However, biologically-potent peptides are increasingly mined from genetic or recombinant libraries as well as chemical and peptide screens [11].…”

Section: Introductionmentioning

confidence: 99%

Self-assembling peptide-based building blocks in medical applications

Acar

Srivastava

Chung

et al. 2017

Advanced Drug Delivery Reviews

197

155

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Peptides and peptide-conjugates, comprising natural and synthetic building blocks, are an increasingly popular class of biomaterials. Self-assembled nanostructures based on peptides and peptide-conjugates offer advantages such as precise selectivity and multifunctionality that can address challenges and limitations in the clinic. In this review article, we discuss recent developments in the design and self-assembly of various nanomaterials based on peptides and peptide-conjugates for medical applications, and categorize them into two themes based on the driving forces of molecular self-assembly. First, we present the self-assembled nanostructures driven by the supramolecular interactions between the peptides, with or without the presence of conjugates. The studies where nanoassembly is driven by the interactions between the conjugates of peptide-conjugates are then presented. Particular emphasis is given to in vivo studies focusing on therapeutics, diagnostics, immune modulation and regenerative medicine, and challenges and future perspective are presented.

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Section: Introductionmentioning

confidence: 99%

Self-assembling peptide-based building blocks in medical applications

Acar

Srivastava

Chung

et al. 2017

Advanced Drug Delivery Reviews

197

155

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“…Evidence-Based Complementary and Alternative Medicine mechanisms of endogenous GLP-1 release may facilitate the development of selective GLP-1 agonists [41]. TGR5 is a G protein-coupled receptor on intestinal endocrine cells.…”

Section: Discussionmentioning

confidence: 99%

Finger Citron Extract Ameliorates Glycolipid Metabolism and Inflammation by Regulating GLP-1 Secretion via TGR5 Receptors in Obese Rats

Yang

Tian

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Finger citron (FC) is one of many traditional Chinese herbs that have been used to treat obesity. The aim of this study was to elucidate the pharmacological effects and mechanisms of FC on obese rats. Rats were fed with a high-fat diet as a model of obesity and treated with FC at three different dosages for 6 weeks. Pathology in liver tissue was observed. Glucose levels, lipids levels, and inflammatory indicators in serum were evaluated by enzyme‐linked immunosorbent assay. Furthermore, the expression of G protein-coupled receptor 5 (TGR5) pathway genes in rat colon tissue was detected by reverse transcription-polymerase chain reaction analysis (RT-PCR). Our result revealed that FC alleviates obesity by reducing body weight (BW) and waist circumference, managing inflammation and improving glycolipid metabolism, liver function, and liver lipid peroxidation in vivo. In addition, the mechanism of FC on obesity is possibly the stimulation of glucagon-like peptide-1 (GLP-1) secretion by activating the TGR5 pathway in intestinal endocrine cells. Our studies highlight the obesity reduction effects of FC and one of the mechanisms may be the activation of the TGR5 pathway in intestinal endocrine cells.

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“…Secondary metabolites are frequently associated with various medicinal actions and other forms of bioactivity—many such metabolites have been isolated and their activity characterized. Our ongoing programme of work screening natural products for antidiabetic activity [23,24,25,26,29] indicated that L.sativa (cv. Grand Rapids) contained modest levels of inhibitory activity against both α-glucosidase and DPP-4 and also stimulated secretion of the intestinal glucoregulatory hormone GLP-1.…”

Section: Discussionmentioning

confidence: 99%

“…The specific bioactivities tested were inhibition of α-glucosidase, inhibition of dipeptidyl peptidase-4 (DPP-4), and stimulation of glucagon-like peptide-1 (GLP-1) secretion (an important human intestinal hormone). These 3 anti-diabetic targets are the basis of pharmacological treatments for type 2 diabetes mellitus and it is well established that they can be modulated by natural products, nutrients and phytochemicals [14,20,21,22,23,24,25,26].…”

Section: Introductionmentioning

confidence: 99%

The Health Promoting Bioactivities of Lactuca sativa can be Enhanced by Genetic Modulation of Plant Secondary Metabolites

et al. 2019

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Plant secondary metabolites are protective dietary constituents and rol genes evidently increase the synthesis of these versatile phytochemicals. This study subjected a globally important vegetable, lettuce (Lactuca sativa) to a combination of untargeted metabolomics (LC-QTof-MS) and in vitro bioactivity assays. Specifically, we examined the differences between untransformed cultured lettuce (UnT), lettuce transformed with either rolABC (RA) or rolC (RC) and commercially grown (COM) lettuce. Of the 5333 metabolite features aligned, deconvoluted and quantified 3637, 1792 and 3737 significantly differed in RA, RC and COM, respectively, compared with UnT. In all cases the number of downregulated metabolites exceeded the number increased. In vitro bioactivity assays showed that RA and RC (but not COM) significantly improved the ability of L. sativa to inhibit α-glucosidase, inhibit dipeptidyl peptidase-4 (DPP-4) and stimulate GLP-1 secretion. We putatively identified 76 lettuce metabolites (sesquiterpene lactones, non-phenolic and phenolic compounds) some of which were altered by several thousand percent in RA and RC. Ferulic acid levels increased 3033–9777%, aminooxononanoic acid increased 1141–1803% and 2,3,5,4′tetrahydroxystilbene-2-O-β-d-glucoside increased 40,272–48,008%. Compound activities were confirmed using commercially obtained standards. In conclusion, rol gene transformation significantly alters the metabolome of L.sativa and enhances its antidiabetic properties. There is considerable potential to exploit rol genes to modulate secondary metabolite production for the development of novel functional foods. This investigation serves as a new paradigm whereby genetic manipulation, metabolomic analysis and bioactivity techniques can be combined to enable the discovery of novel natural bioactives and determine the functional significance of plant metabolites.

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Naturally-occurring TGR5 agonists modulating glucagon-like peptide-1 biosynthesis and secretion

Cited by 16 publications

References 35 publications

Self-assembling peptide-based building blocks in medical applications

Self-assembling peptide-based building blocks in medical applications

Finger Citron Extract Ameliorates Glycolipid Metabolism and Inflammation by Regulating GLP-1 Secretion via TGR5 Receptors in Obese Rats

The Health Promoting Bioactivities of Lactuca sativa can be Enhanced by Genetic Modulation of Plant Secondary Metabolites

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