An insight into the multifunctional role of ghrelin and structure activity relationship studies of ghrelin receptor ligands with clinical trials

Bukhari, Syed Nasir Abbas

doi:10.1016/j.ejmech.2022.114308

Cited by 2 publications

(2 citation statements)

References 191 publications

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“…Ghrelin, a multifunctional GI acylated peptide, plays a pivotal role in modulating diverse biological, physiological, and pathological functions in vertebrates [2]. While the stomach serves as the primary site for ghrelin production, other organs, including the duodenum, hypothalamus, lungs, gonads, and pancreas, also produce small amounts in humans [1].…”

Section: Synthesis Of Ghrelinmentioning

confidence: 99%

Ghrelin in Focus: Dissecting Its Critical Roles in Gastrointestinal Pathologies and Therapies

Wu,

Zhu,

Dou

et al. 2024

CIMB

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This review elucidates the critical role of ghrelin, a peptide hormone mainly synthesized in the stomach in various gastrointestinal (GI) diseases. Ghrelin participates in diverse biological functions ranging from appetite regulation to impacting autophagy and apoptosis. In sepsis, it reduces intestinal barrier damage by inhibiting inflammatory responses, enhancing GI blood flow, and modulating cellular processes like autophagy and apoptosis. Notably, in inflammatory bowel disease (IBD), serum ghrelin levels serve as markers for distinguishing between active and remission phases, underscoring its potential in IBD treatment. In gastric cancer, ghrelin acts as an early risk marker, and due to its significant role in increasing the proliferation and migration of gastric cancer cells, the ghrelin–GHS-R axis is poised to become a target for gastric cancer treatment. The role of ghrelin in colorectal cancer (CRC) remains controversial; however, ghrelin analogs have demonstrated substantial benefits in treating cachexia associated with CRC, highlighting the therapeutic potential of ghrelin. Nonetheless, the complex interplay between ghrelin’s protective and potential tumorigenic effects necessitates a cautious approach to its therapeutic application. In post-GI surgery scenarios, ghrelin and its analogs could be instrumental in enhancing recovery and reducing complications. This article accentuates ghrelin’s multifunctionality, shedding light on its influence on disease mechanisms, including inflammatory responses and cancer progression, and examines its therapeutic potential in GI surgeries and disorders, advocating for continued research in this evolving field.

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Section: Synthesis Of Ghrelinmentioning

confidence: 99%

Ghrelin in Focus: Dissecting Its Critical Roles in Gastrointestinal Pathologies and Therapies

Wu,

Zhu,

Dou

et al. 2024

CIMB

View full text Add to dashboard Cite

show abstract

“…Ghrelin is a brain-gut peptide with 28 amino acids that was isolated as the endogenous ligand for the ghrelin receptor. The preproghrelin gene is located on chromosome 3q26.31 [6]. Ghrelin was discovered as a peptidic growth-hormone-releasing and appetitestimulating hormone that is secreted by the stomach mucosa [7,8].…”

Section: Introductionmentioning

confidence: 99%

SNPs-Panel Polymorphism Variations in GHRL and GHSR Genes Are Not Associated with Prostate Cancer

Merabet,

Ramoz,

Boulmaiz

et al. 2023

Biomedicines

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Prostate cancer (PCa) is a major public health problem worldwide. Recent studies have suggested that ghrelin and its receptor could be involved in the susceptibility to several cancers such as PCa, leading to their use as an important predictive way for the clinical progression and prognosis of cancer. However, conflicting results of single nucleotide polymorphisms (SNPs) with ghrelin (GHRL) and its receptor (GHSR) genes were demonstrated in different studies. Thus, the present case–control study was undertaken to investigate the association of GHRL and GHSR polymorphisms with the susceptibility to sporadic PCa. A cohort of 120 PCa patients and 95 healthy subjects were enrolled in this study. Genotyping of six SNPs was performed: three tag SNPs in GHRL (rs696217, rs4684677, rs3491141) and three tag SNPs in the GHSR (rs2922126, rs572169, rs2948694) using TaqMan. The allele and genotype distribution, as well as haplotypes frequencies and linked disequilibrium (LD), were established. Multifactor dimensionality reduction (MDR) analysis was used to study gene–gene interactions between the six SNPs. Our results showed no significant association of the target polymorphisms with PCa (p > 0.05). Nevertheless, SNPs are often just markers that help identify or delimit specific genomic regions that may harbour functional variants rather than the variants causing the disease. Furthermore, we found that one GHSR rs2922126, namely the TT genotype, was significantly more frequent in PCa patients than in controls (p = 0.040). These data suggest that this genotype could be a PCa susceptibility genotype. MDR analyses revealed that the rs2922126 and rs572169 combination was the best model, with 81.08% accuracy (p = 0.0001) for predicting susceptibility to PCa. The results also showed a precision of 98.1% (p < 0.0001) and a PR-AUC of 1.00. Our findings provide new insights into the influence of GHRL and GHSR polymorphisms and significant evidence for gene–gene interactions in PCa susceptibility, and they may guide clinical decision-making to prevent overtreatment and enhance patients’ quality of life.

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An insight into the multifunctional role of ghrelin and structure activity relationship studies of ghrelin receptor ligands with clinical trials

Cited by 2 publications

References 191 publications

Ghrelin in Focus: Dissecting Its Critical Roles in Gastrointestinal Pathologies and Therapies

Ghrelin in Focus: Dissecting Its Critical Roles in Gastrointestinal Pathologies and Therapies

SNPs-Panel Polymorphism Variations in GHRL and GHSR Genes Are Not Associated with Prostate Cancer

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