Anti-Inflammatory Comparison of Melatonin and Its Bromobenzoylamide Derivatives in Lipopolysaccharide (LPS)-Induced RAW 264.7 Cells and Croton Oil-Induced Mice Ear Edema

Abstract

The pineal gland is a neuroendocrine organ that plays an important role in anti-inflammation through the hormone melatonin. The anti-inflammatory effects of melatonin and its derivatives have been reported in both in vitro and in vivo models. Our previous study reported the potent antioxidant and neuroprotective activities of bromobenzoylamide substituted melatonin. In silico analysis successfully predicted that melatonin bromobenzoylamid derivatives were protected from metabolism by CYP2A1, which is a key enzyme of the melatonin metabolism process. Therefore, the anti-inflammatory activities of melatonin and its bromobenzoylamide derivatives BBM and EBM were investigated in LPS-induced RAW 264.7 macrophages and croton oil-induced ear edema in mice. The experiments showed that BBM and EBM significantly reduced production of the inflammatory mediators interleukin-6 (IL-6), prostaglandin E2 (PGE2), and nitric oxide (NO) in a dose-dependent manner, but only slightly affected TNF-α in LPS-induced RAW 264.7 macrophages. This suggests that modifying melatonin at either the N1-position or the N-acetyl side chain affected production of NO, PGE2 and IL-6 in in vitro model. In the croton oil-induced mouse ear edema model, BBM, significantly decreased ear edema thickness at 2–4 h. It leads to conclude that bromobenzoylamide derivatives of melatonin may be one of the potential candidates for a new type of anti-inflammatory agent.

Effect of Germination and Illumination on Melatonin and Its Metabolites, Phenolic Content, and Antioxidant Activity in Mung Bean Sprouts

“…It is also associated with growth hormone secretion in children [ 11 ]. Additionally, melatonin regulates energy metabolism and the immune system [ 12 ] and possesses various biological activities, such as anti-inflammatory [ 13 ], antioxidant [ 14 ], and neuroprotective [ 15 ] activity. The nocturnal plasma level of melatonin increases to reach a maximum at the age of 1–3 years.…”

New Indole-3-Propionic Acid and 5-Methoxy-Indole Carboxylic Acid Derived Hydrazone Hybrids as Multifunctional Neuroprotectors

“…Negative controls (cells without H 2 O 2 treatment) were considered as 100% protection and H 2 O 2 -treated cells as 0% protection. Melatonin and rasagiline (Sigma-Aldrich Co. LLC, St. Louis, MO, USA) were used as references because of their potent antioxidant and neuroprotective effects, which were established by several in vitro and in vivo studies [ 17 , 38 ].…”

“…The latter was extensively studied by this team in a novel pin+icvAβ 1-42 Alzheimer animal model, and its role as a direct free radical scavenger was unequivocally demonstrated in the prevention of oxidative stress and neurodegenerative features induced by that model [ 16 ]. IPA was able to prevent ROS damage and cell death caused by the addition of Aβ-peptide on SK-N-SH human neuroblastoma cells and primary rat hippocampal neurons [ 17 ]. IPA also demonstrated full protection against the death of primary neurons and SK-N-SH cells exposed to Aβ-mediated damage and DDTC-induced lipid peroxidation in PC12 cells [ 15 ].…”

Therapeutic potential of melatonin in the intervertebral disc degeneration through inhibiting the ferroptosis of nucleus pulpous cells

“…11 Therefore, key factors in ferroptosis-related pathways like SLC7A11, GPX4, ACSL4 and lysophosphatidylcholine acyltransferase 3 (LPCAT3) played an important role in multiple diseases including tissue injury, inflammation and IDD. 12 Melatonin (N-acetyl-5-methoxytryptamine, MLT), is an indoleamine hormone, which displays a variety of biological properties, including anti-oxidant, 13,14 anti-inflammatory, 15,16 antiapoptosis, 17,18 anti-cancer, 19 anti-diabetic 20 and immunomodulation. 21,22 Recently, clinical and animal studies suggested the role of MLT in the IDD.…”

“…Melatonin ( N ‐acetyl‐5‐methoxytryptamine, MLT), is an indoleamine hormone, which displays a variety of biological properties, including anti‐oxidant, 13,14 anti‐inflammatory, 15,16 anti‐apoptosis, 17,18 anti‐cancer, 19 anti‐diabetic 20 and immunomodulation 21,22 . Recently, clinical and animal studies suggested the role of MLT in the IDD 3,23–29 .…”