Repairing the impaired gut vascular barrier as a novel therapeutic target for prolonged postoperative ileus: A scoping review

Table 1 Drugs for repairing the injured gut vascular barrier in prolonged postoperative ileus

Drug	Mechanism	Biological activity	Animals/cells	Ref.
Kaempferol	Inhibiting the activation of inflammatory phenotype in IMVECs and strengthening the intestinal epithelial–endothelial barrier	Attenuating the overexpression of pro-inflammatory cytokines and adhesion molecules in IMVECs through inhibiting TLR4 overexpression and NF-κB, p38 MAPK, and STAT phosphorylation	RIMVECs	Bian et al[128], 2019; and Bian et al[133], 2020
Prostaglandin E2	Promoting the activity of IMVECs	Through the PGE2-EP4-eNOS signaling axis, prostaglandin E2 promotes IMVEC proliferation and NO production, which result in improved intestinal microcirculation	Mice/MIMVECs	Mo et al[129], 2023
Naringin	Inhibiting apoptosis, promoting cell migration, and upregulating the expression of endothelial cell junction proteins	Preventing TNF-α-induced apoptosis and migration suppression in IMVECs; Upregulating the expression of endothelial TJ, such as ZO-1, occludin, claudin-1, and claudin-2	RIMVECs	Liu et al[130], 2020
Quercetin	Protecting IMVECs from pyroptotic inflammation	Inhibiting the release of NLRP3 inflammasomes and the expression of pyroptotic proteins via the TLR4/NF-κB/NLRP3 signaling pathway to alleviate intestinal inflammation	Rat/RIMVECs	Zhang et al[131], 2022
Berberine	Reducing the permeability of the GVB	Increasing the expression of β-catenin, claudin-12, and VE-cadherin via modulating the Wnt/β-catenin pathway	Rat/RIMVECs	He et al[13], 2018
Dexmedetomidine	Reducing the permeability of the GVB	Increasing the expression of β-catenin, VE-cadherin, ZO-1, and occludin	Mice/MIMVECs	Zhang et al[61], 2022
Dihydroartemisinin	Repairing the intestinal epithelial–endothelial barrier	Increasing the expression of TJ and AJ and decreasing that of PV-1	Mice	Qiu et al[103], 2024
G6-31	Inhibiting angiogenesis; improving microcirculatory hemodynamics	Specifically binding to VEGF-A, inhibiting angiogenesis and improving microcirculatory hemodynamics	Mice	Ardelean et al[115], 2014
AP-Cav	Inhibiting angiogenesis	Inhibiting the proliferation of VECs and inducing VEC apoptosis through the suppression of the MAP signaling pathway and induction of JNK-dependent apoptosis	ECs	Fang and Kevil[135], 2020
N-palmitoyl-d-glucosamine	Inhibiting angiogenesis	Inhibiting the expression of inflammatory and pro-angiogenic factors by blocking the pAkt/mTOR/hypoxia-inducible factor1α pathway	Mice	Palenca et al[136], 2024
Heparin-binding epidermal growth factor-like growth factor	Improving intestinal microcirculation	Alleviating intestinal ischemia/reperfusion injury by reducing JNK phosphorylation and inhibiting the activation of the p38/MAPK signaling pathway Increasing the expression of the endothelin B receptor and triggering intracellular calcium mobilization	Rat/HIMVECs	Ming et al[138], 2019 and Zhou et al[139], 2009
Melatonin	Improving intestinal microcirculation	Attenuating pathological intestinal microvascular congestion and suppressing the infiltration of mast cells and granulocytes into intestinal tissues	Rat	Lansink et al[141], 2017

AJ: Adherens junction; GVB: Gut vascular barrier; IMVEC: Intestinal microvascular endothelial cell; PV-1: Plasmalemma vesicle-associated protein-1; TJ: Tight junction; TNF-α: Tumor necrosis factor-α; VEC: Vascular endothelial cell; VEGF: Vascular endothelial growth factor; eNOS: Endothelial nitric oxide synthase; MAPK: Mitogen-activated protein kinases; NF-kB: Nuclear factor kappa-B; NO: Nitric oxide; ZO-1: Zonula occludens-1; VE-cadherin: Vascular endothelial-cadherin; EC: Endothelial cell; RIMVEC: Rat intestinal microvascular endothelial cell; MIMVEC: Mouse intestinal microvascular endothelial cell; HIMVEC: Human intestinal microvascular endothelial cell.