TABLE 1.

Melatonin could alter exosomal cargo.

Type of study	Study design	Outcome	References
In vivo and in vitro	• Injection of bone marrow MSC-derived exosomes exposed to melatonin in a rat model of diabetic wound healing	IL-1β↓, TNF-α↓, and IL-10↑, Arg-1↓ and iNOS↓, Improved angiogenesis rate (CD31 and α-SMA↑), collagen synthesis↑, Increased M2 to M1 polarization via activation of PTEN/AKT signaling pathway	Liu et al., 2020
In vivo	• Hepatoprotection of adipocyte-derived exosomes in mice received melatonin compared to mice fed with a high-fat diet and resistin	Fatty acid accumulation in the liver↓, endoplasmic reticulum stress↓, hepatic steatosis↓, resistin-induced AMPKα phosphorylation↓, increased resistin mRNA degradation↑, Bmal1 transcriptional inhibition↑, and m6 A RNA demethylation in adipocytes ↑	Rong et al., 2019
In vitro and in vivo	• Melatonin-treated hepatic carcinoma-exosomes effect on peritoneal macrophages immunosuppression capacity	Peritoneal macrophage phosphorylated STAT3↓, IL-6↓, IL-1β↓, IL-10↓, PD-L1↓, and TNF-α↓ in THP-1 cells,	Cheng et al., 2017
In vivo	• Maternal intraperitoneal of melatonin on lipopolysaccharide-induced neonatal brain inflammation	Microglial activity↓, Endoplasmic reticulum↓, Autophagy efflux↑, eIF2α phosphorylation↑, P62 and LC3↑, SIRT1↑, miR-34a↓, miR146a↓, and miR-126↓, Inflammatory response↓	Carloni et al., 2016
In vivo	• Injection of MSCs exosomes preconditioned with melatonin in a rat model of renal I/R injury	Tubular epithelial cell necrosis↓, Immune cell infiltration, and inflammation↓, BUN and creatinine levels ↓, Renal BUN and creatinine levels↑, MDA↓, NOx↓, HIF-1α↑, HO1↑, Apoptosis-related markers↓, Angiogenesis↑	Alzahrani, 2019

↓ Decrease; ↓ Increase; IL-1β, interleukin 1 beta; TNFα, tumor necrosis factor α; ARG1, arginase; iNOS, inducible nitric oxide synthase; αSMA, smooth muscle alpha-actin; CD31, platelet endothelial cell adhesion molecule; AMPKα, AMP-activated protein kinase α subunit; P62, sequestosome-1; LC3, microtubule-associated protein 1A/1B-light chain 3; PD-L1, programmed death-ligand 1; STAT3, signal transducer and activator of transcription 3; eIF2, eukaryotic initiation factor 2; BUN, blood urea nitrogen; MDA, malondialdehyde; NOx, nitrogen oxides; HIF-1α, hypoxia-inducible factor 1 alpha; HO-1, heme oxygenase-1.