Melatonin AND Sirt1

Neuropathic pain is a debilitating chronic pain condition and is refractory to the currently available treatments. Emerging evidence suggests that melatonin exerts analgesic effects in rodent models of neuropathic pain. Nevertheless, the exact underlying mechanisms of the analgesic effects of melatonin on neuropathic pain are largely unknown. Here, we observed that spinal nerve ligation (SNL) in rats L5 and L6 induced an obvious decrease in the 50% paw withdrawal threshold (PWT) and paw withdrawal latency (PWL), indicating the induction of mechanical allodynia and the hyperalgesia, and melatonin prevented the genesis and maintenance of mechanical allodynia and the hyperalgesia...

SIRT1 is a highly conserved nicotinamide adenine dinucleotide (NAD+ )-dependent histone deacetylase. It is involved in the regulation of various pathophysiological processes, including cell proliferation, survival, differentiation, autophagy, and oxidative stress. Therapeutic activation of SIRT1 protects the heart and cardiomyocytes from pathology-related stress, particularly myocardial ischemia/reperfusion (I/R). Autophagy is an important metabolic pathway for cell survival during energy or nutrient deficiency, hypoxia, or oxidative stress...

Cadmium (Cd) is a hazardous heavy metal extensively employed in manufacturing polyvinyl chloride, batteries, and other industries. Acute lung injury has been directly connected to Cd exposure. Agomelatine (AGM), a melatonin analog, is a drug licensed for treating severe depression. This study evaluated the effect of AGM against Cd-induced lung injury in rats. AGM was administered in a dose of 25 mg/kg/day orally, while cadmium chloride (CdCl2 ) was injected intraperitoneally in a dose of 1.2 mg/kg to induce lung injury...

Normal tension glaucoma (NTG) is referred to as a progressive degenerative disorder of the retinal ganglion cells (RGCs), resulting in nonreversible visual defects, despite intraocular pressure levels within the statistically normal range. Current therapeutic strategies for NTG yield limited benefits. Excitatory amino acid carrier 1 (EAAC1) knockout (EAAC1-/- ) in mice has been shown to induce RGC degeneration without elevating intraocular pressure, mimicking pathological characteristics of NTG. In this study, we explored whether daily oral administration of melatonin could block RGCs loss and prevent retinal morphology and function defects associated with EAAC1 deletion...

Nucleus pulposus (NP) cell apoptosis is regarded as a critical risk factor for intervertebral disc degeneration (IVDD). Melatonin exerts a protective role on NP cells. The study concentrates on the role and mechanism of lncRNA MEG3 in melatonin-mediated effects on NP cells. An in-vitro IVDD model was constructed using IL-1β on human NP cells. qRT-PCR investigated MEG3, miR-15a-5p, and PGC-1α mRNA levels in tissues and NP cells. IL-1β treated NP cells subsequent to transfection, followed by melatonin treatment...

Oxidative-stress-induced apoptosis of granulosa cells is considered to be a main driver of follicular atresia. Increasing evidence suggests a protective effect of melatonin against oxidative damage but the mechanism remains unclear. The aim of this study is to investigate the effects of melatonin on mitophagy and apoptosis of bovine ovarian granulosa cells under oxidative stress, and to clarify the mechanism. Our results indicate that melatonin inhibited H2 O2 -induced apoptosis and mitochondrial injury of bovine ovarian granulosa cells, as revealed by decreased apoptosis rate, reactive oxygen species (ROS) levels, Ca2+ concentration, and cytochrome C release and increased mitochondrial membrane potential (ΔΨm)...

Obesity-induced skeletal muscle (SKM) inflexibility is closely linked to mitochondrial dysfunction. The present study aimed to evaluate the effects of melatonin on the red vastus lateralis (RVL) muscle in obese rat models at the molecular and morphological levels. Five-week-old male Zücker diabetic fatty (ZDF) rats and their age-matched lean littermates (ZL) were orally treated either with melatonin (10 mg/kg body weight (BW)/24 h) (M-ZDF and M-ZL) or non-treated (control) (C-ZDF and C-ZL) for 12 weeks...

Introduction: Novel therapeutics are emerging to mitigate damage from perinatal brain injury (PBI). Few newborns with PBI suffer from a singular etiology. Most experience cumulative insults from prenatal inflammation, genetic and epigenetic vulnerability, toxins (opioids, other drug exposures, environmental exposure), hypoxia-ischemia, and postnatal stressors such as sepsis and seizures. Accordingly, tailoring of emerging therapeutic regimens with endogenous repair or neuro-immunomodulatory agents for individuals requires a more precise understanding of ligand, receptor-, and non-receptor-mediated regulation of essential developmental hormones...

The silent information regulator 2 homolog 1-NACHT, LRR and PYD domains-containing protein 3 (SIRT1-NLRP3) pathway has a crucial role in regulation of the inflammatory response, and is closely related to the occurrence and development of several inflammation-related diseases. NLRP3 is activated to produce the NLRP3 inflammasome, which leads to activation of caspase-1 and cleavage of pro-interleukin (IL)-1β and pro-IL-18 to their active forms: IL-1β and IL-18, respectively. They are proinflammatory cytokines which then cause an inflammatory response...

With increase in women's age, the reproductive capability of female mammals decreases dramatically caused by age-related oxidative stress, coinciding with the decline in the ovarian reserve, and the quality and quantity of oocytes, which is the main determinant of female fertility. Melatonin, as an effective antioxidant and antiaging substance, is secreted by the pineal gland and been found in the follicular fluid as well, which has been turned out to enable to protect oocytes from oxidative stress during ovulation...

BACKGROUND: Triptolide (TP) is an important active compound from Tripterygium wilfordii Hook F (TwHF), however, it is greatly limited in clinical practice due to its severe toxicity, especially testicular injury. Melatonin is an endogenous hormone and has beneficial effects on the reproductive system. However, whether triptolide-induced testicular injury can be alleviated by melatonin and the underlying mechanism are not clear. PURPOSE: In this study, we aimed to explore whether triptolide-induced testicular Sertoli cells toxicity can be mitigated by melatonin and the underlying mechanisms involved...

The study aims to explore the medical prospect of melatonin (MLT) and the underlying therapeutic mechanism of MLT-mediated macrophage (Mφ) polarization on the function of nucleus pulposus (NP) in intervertebral disc degeneration (IDD). RAW 264.7 Mφs were induced by lipopolysaccharide (LPS) to simulate Mφ polarization and the inflammatory reaction of Mφs with or without MLT were detected. Conditioned medium (CM) collected from these activated Mφs with or without MLT treatment were further used to incubate NP cells...

AIM: To investigate the combined therapeutic potential of melatonin and ascorbic acid in mitigating sepsis-induced heart and kidney injury in male rats and assess the combination therapy's effects on inflammation, cellular damage, oxidative stress, and vascular function-related markers. MATERIALS AND METHODS: Cecal ligation and puncture (CLP) induced sepsis in male rats, which were divided into five groups: Sham, CLP, MEL (melatonin), ASA (ascorbic acid), and MEL+ASA (melatonin and ascorbic acid)...

Previous studies have demonstrated that melatonin could ameliorate oxidative stress during the cryopreservation of mouse MII oocytes and their in vitro culture after parthenogenetic activation. However, the underlying molecular mechanism remained poorly understood. This study was conducted to investigate whether melatonin could modulate the oxidative stress in the parthenogenetic 2-cell embryos derived from vitrified-warmed oocytes through SIRT1. The results showed that the reactive oxygen species levels increased, the glutathione levels and SIRT1 expression decreased significantly in parthenogenetic 2-cell embryos derived from cryopreserved oocyte, and the parthenogenetic blastocyst formation rates significantly decreased when compared to those derived from control oocytes...

This review focuses on melatonin's role in advancing Parkinson's disease (PD) pathogenesis by inhibiting synaptic dysfunction and neuroinflammation. The early pathological changes in PD, caused by SNCA/PARK1 and LRRK2/PARK8-mediated synaptic vesicle endocytosis during the early pathogenesis of PD, are briefly reviewed. The pathological changes related to synaptic plasticity and dendrites caused by synaptic dysfunction in neurotoxin 6-hydroxydopamine (6-OHDA) and 1-methl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)-induced PD models are also discussed...

The potential use of agomelatine as an alternative treatment for colorectal cancer is evaluated in this work. The effect of agomelatine was studied in an in vitro model using two cell lines with different p53 statuses (HCT-116, wild-type p53, and HCT-116 p53 null) and an in vivo xenograft model. The inhibitory effects of agomelatine and melatonin were stronger in the cells harboring the wild-type p53, although in both cell lines, the effect of agomelatine was greater than that of the melatonin. In vivo, only agomelatine was able to reduce the volumes of tumors generated by the HCT-116-p53-null cells...

OBJECTIVES: The aim of this study was to investigate how melatonin administration affects retinal oxidative damage and retinal SIRT1 gene activation in diabetic elderly female rat model. METHODS: 16-months-old female rats were used in the study. A total of 24 rats were divided into 4 groups in equal numbers: Group 1. Control, Group 2. Control + Melatonin, Group 3. Diabetes, Group 4. Diabetes + Melatonin. In group 3 and 4 rats, diabetes was induced by intraperitoneal (IP) injection of streptozotocin...

Benzo(a)pyrene is a ubiquitous environmental contaminant, which could induce renal injury. It is reported that melatonin has a protective effect against multiple organ injuries by regulating oxidative stress, apoptosis, and autophagy. The aim of this study was to estimate the melatonin effects on benzo(a)pyrene renal toxicity in mice and the possible molecular mechanisms involved in this model. Thirty male mice were allocated to five groups and treated with benzo(a)pyrene (75 mg/kg, oral gavage) and/or melatonin (10 and 20 mg/kg, intraperitoneally)...

Chronic cerebral hypoxia (CCH) is caused by a reduction in cerebral blood flow, and cognitive impairment has been the predominant feature that occurs after CCH. Recent reports have revealed that melatonin is proficient in neurodegenerative diseases. However, the molecular mechanism by which melatonin affects CCH remains uncertain. In this study, we aimed to explore the role and underlying mechanism of melatonin in inflammation and blood‒brain barrier conditions in rats with CCH. Male Wistar rats were subjected to permanent bilateral common carotid artery occlusion (BCCAO) to establish the VAD model...

Melatonin confers cardioprotective effects on multiple cardiovascular diseases, including doxorubicin-induced cardiomyopathy. The effectiveness of melatonin in mitigating myocardial injuries caused by Doxorubicin through enhancement of mitochondrial function is already established, however, the role of melatonin in regulating the Sirtuin-1 (Sirt1)/Nuclear factor E2-associated factor 2 (Nrf2) pathway in lessening the onset of Doxorubicin-induced cardiomyopathy is yet to be elucidated. To address this, H9C2 cardiomyocytes and C57BL/6 mice were employed to construct in vitro and in vivo models of Dox-induced myocardial impairments, respectively...