Table 2.

GLP-1 analogues under investigation in vitro and in vivo (animal and human studies).

Models	Treatments	Results	References
In-vitro study Macrophage RAW 264.7 cell culture	Pre-treated with exendin-4 for 6hrs followed by LPS for 24hrs	Exendin-4 inhibits production of many LPS-induced inflammatory factors, thereby decreasing production of ROS reactive oxygen species.	(Lu et al., 2019) (27)
In-vivo animal studies DSS-induced colitis in mouse model	GLP-1 self-associated with PEGylated phospholipid micelles i.p	GLP-1-SSM (sterically stabilized phospholipid micelles) improve architecture of the intestine, partially preserve goblet cell number, decrease IL1-β secretion and improve diarrhea induced by DSS.	(Anbazhagan et al., 2017) (48)
DSS-induced colitis in mouse model — Ischemia/reperfusion	—	I.P or I.V administration of LPS caused a significant rise in plasma levels of GLP-1 through the TLR-4 mechanism.	(Lebrun et al., 2017) (46)
DSS-induced colitis in mouse with GLP-1R knockout	Exendin-4 (GLP-1 agonist) s.c.	DSS-induced colitis in GLP-1 R knockout mice showed dysregulation of intestinal gene expression, as well as abnormal representation of microbes in feces and increased sensitivity to intestinal injury. Also, Exendin-4 administration caused significantly increased expression of genes encoding cytokines and chemokines in gut injury.	(Yusta et al., 2015) (49)
Colonic smooth muscle cells of male BALB/c mice cultured in DMEM	LPS+/-Exendin-4	Exendin-4 Inhibited production of pro-inflammatory cytokines including TNF-α and IL-1 α in LPS-induced inflammation in mouse model.	(Al-Dwairi et al., 2018) (50)
Wistar rat model	a) GLP-1 injected i.c.v b) GLP-1 receptor antagonist, Exendin 9-39 I.c.v and i.p	Centrally injected Exendin 9-39 inhibited the gastroprotective effects of GLP-1 agonists, suggesting that this effect is managed by central mechanisms.	(Işbil Büyükcoşkun et al., 2007) (51)
MPTP-treated Parkinson Disease mouse model Human A53T α-synuclein transgenic PD mouse model (MPTP=1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)	CCK analogues or Liraglutide and GLP-1 analogues i.p	CCK analogues or GLP-1 analogues restored the disruption of intestinal tight junction, reduced colonic inflammation, inhibited colonic dopaminergic neuron reduction and the accumulation of α-synuclein oligomers in the colon of both PD mouse models.	(Su et al., 2022) (52)
Human study a) Healthy volunteers b)Ischemia/reperfusion injury model of human gut	—	a) 3hrs after LPS injection plasma GLP-1 levels rose significantly. b) 45 min after ischemia in the human intestine, GLP-1 levels rose significantly and returned to baseline after reperfusion.	(Lebrun et al., 2017) (46)