Protective and therapeutic potential of melatonin against intestinal diseases: updated review of current data based on molecular mechanisms.

INTRODUCTION: Intestinal diseases, a leading global cause of mortality and morbidity, carry a substantial socioeconomic burden. Small and large intestines play pivotal roles in gastrointestinal physiology and food digestion. Pathological conditions, such as gut dysbiosis, inflammation, cancer, therapy-related complications, ulcers, and ischemia, necessitate the urgent exploration of safe and effective complementary therapeutic strategies for optimal intestinal health. AREAS COVERED: This article evaluates the potential therapeutic effects of melatonin, a molecule with a wide range of physiological actions, on intestinal diseases including inflammatory bowel disease, irritable bowel syndrome, colon cancer, gastric/duodenal ulcers and other intestinal disorders. EXPERT OPINION: Due to anti-inflammatory and antioxidant properties as well as various biological actions, melatonin could be a therapeutic option for improving digestive disorders. However, more researches are needed to fully understand the potential benefits and risks of using melatonin for digestive disorders.

Melatonin and neuroblastoma: a novel therapeutic approach.

Neuroblastoma is a deadly and serious malignancy among children. Although many developments have been occurred for the treatment of this disease, the rate of mortality is still high. Therefore, it is necessary to search for novel complementary and alternative therapies. Melatonin, a hormone secreted from pineal gland, is a multifunctional agent having anticancer potentials. Recently, several investigations have been conducted indicating melatonin effects against neuroblastoma. In this paper, we summarize current evidence on anti-neuroblastoma effects of melatonin based on cellular pathways.

An updated review of mechanistic potentials of melatonin against cancer: pivotal roles in angiogenesis, apoptosis, autophagy, endoplasmic reticulum stress and oxidative stress.

Cancers are serious life-threatening diseases which annually are responsible for millions of deaths across the world. Despite many developments in therapeutic approaches for affected individuals, the rate of morbidity and mortality is high. The survival rate and life quality of cancer patients is still low. In addition, the poor prognosis of patients and side effects of the present treatments underscores that finding novel and effective complementary and alternative therapies is a critical issue. Melatonin is a powerful anticancer agent and its efficiency has been widely documented up to now. Melatonin applies its anticancer abilities through affecting various mechanisms including angiogenesis, apoptosis, autophagy, endoplasmic reticulum stress and oxidative stress. Regarding the implication of mentioned cellular processes in cancer pathogenesis, we aimed to further evaluate the anticancer effects of melatonin via these mechanisms.

Melatonin and urological cancers: a new therapeutic approach.

Urological cancers are responsible for thousands of cancer-related deaths around the world. Despite all developments in therapeutic approaches for cancer therapy, the absence of efficient treatments is a critical and vital problematic issue for physicians and researchers. Furthermore, routine medical therapies contribute to several undesirable adverse events for patients, reducing life quality and survival time. Therefore, many attempts are needed to explore potent alternative or complementary treatments for great outcomes. Melatonin has multiple beneficial potential effects, including anticancer properties. Melatonin in combination with chemoradiation therapy or even alone could suppress urological cancers through affecting essential cellular pathways. This review discusses current evidence reporting the beneficial effect of melatonin in urological malignancies, including prostate cancer, bladder cancer, and renal cancer.

Melatonin potentials against viral infections including COVID-19: Current evidence and new findings.

Viral infections are dangerous diseases for human health worldwide, which lead to significant morbidity and mortality each year. Because of their importance and the lack of effective therapeutic approaches, further attempts should be made to discover appropriate alternative or complementary treatments. Melatonin, a multifunctional neurohormone mainly synthesized and secreted by the pineal gland, plays some roles in the treatment of viral infections. Regarding a deadly outbreak of COVID-19 across the world, we decided to discuss melatonin functions against various viral infections including COVID-19. Therefore, in this review, we summarize current evidence on melatonin therapy for viral infections with focus on possible underlying mechanisms of melatonin actions.

Therapeutic application of nutraceuticals in diabetic nephropathy: Current evidence and future implications.

Diabetes mellitus (DM) is a common metabolic disease which may cause several complications, such as diabetic nephropathy (DN). The routine medical treatments used for DM are not effective enough and have many undesirable side effects. Moreover, the global increased prevalence of DM makes researchers try to explore potential complementary or alternative treatments. Nutraceuticals, as natural products with pharmaceutical agents, have a wide range of therapeutic properties in various pathologic conditions such as DN. However, the exact underlying mechanisms have not been fully understood. The purpose of this review is to summarize recent findings on the effect of nutraceuticals on DN.

Melatonin in the treatment of fibromyalgia symptoms: A systematic review.

The available pharmacological modalities for the treatment of fibromyalgia (FM) are associated with a variety of adverse effects and limited benefits. In this study, we systematically reviewed the impact of melatonin in the treatment of FM. Interventional studies, either controlled or uncontrolled and randomized or non-randomized, were included. PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library were searched without time limitation. Primary outcome measures were the effect of melatonin on the disease impact, pain, sleep quality, tender point count, fatigue, anxiety, stiffness, and depression in FM patients. Four studies, reporting the effect of melatonin on 98 patients, were eligible to include. All the studies reported the positive effect of melatonin on the FM symptoms. No major adverse event was reported. A significant level of heterogeneity was observed between the studies. Therefore, further high-quality controlled clinical trials are needed to understand the role of melatonin in FM treatment fully.

Protective Effect of Ginger (Zingiber officinale Roscoe) Extract against Oxidative Stress and Mitochondrial Apoptosis Induced by Interleukin-1ß in Cultured Chondrocytes.

AIMS: The protective effects of ginger (Zingiber officinale Roscoe) extract on IL-1ß-mediated oxidative stress and mitochondrial apoptosis were investigated in C28I2 human chondrocytes. METHODS: The effects of various concentrations of ginger extract on C28I2 human chondrocyte viability were evaluated in order to obtain noncytotoxic concentrations of the drug by methylthiotetrazole assay. The cells were pretreated with 5 and 25 µg/mL ginger extract for 24 h, followed by incubation with IL-1ß (10 ng/mL) for 24 h. The effects of ginger extract on IL-1ß-induced intracellular reactive oxygen species (ROS) production and lipid peroxidation were examined. The mRNA expressions of antioxidant enzymes including catalase, superoxide dismutase-1, glutathione peroxidase-1, glutathione peroxidase-3, and glutathione peroxidase-4 were evaluated by reverse transcription polymerase chain reaction. The protein expressions of Bax, Bcl-2, and caspase-3 were analyzed by Western blotting. RESULTS: No cytotoxicity was observed at any concentration of ginger extract in C28I2 cells. Ginger extract pretreatment remarkably increased the gene expression of antioxidant enzymes and reduced the IL-1ß-induced elevation of ROS, lipid peroxidation, the Bax/Bcl-2 ratio, and caspase-3 activity. CONCLUSIONS: Ginger extract could considerably reduce IL-1ß-induced oxidative stress and consequent mitochondrial apoptosis as the major mechanisms of chondrocyte cell death. These beneficial effects of ginger extract may be due to its antioxidant properties. It may be considered as a natural herbal product to prevent OA-induced cartilage destruction in the clinical setting.

Protective effect of Berberis vulgaris fruit extract against Paraquat-induced pulmonary fibrosis in rats.

BACKGROUND: Pulmonary fibrosis induced by paraquat (PQ) has caused a large number of human fatalities all over the world, especially in Asian region. The main potential mechanism of PQ toxicity has been thought to be mediated by ROS. The present study was designed to evaluate the efficacy of the Berberis vulgaris fruit extract (BVFE) against PQ-induced pulmonary fibrosis in rats. METHODS: Forty male rats were randomly divided into five experimental groups each containing eight rats. Groups 1 and 2, served as a negative and positive control and received a single dose of intratracheal instillation of saline and PQ (20mg/kg), respectively. Groups 3-5 were treated with different doses of BVFE (100, 200, 400mg/kg/day, orally) 1 week before the PQ injection and continued for 3 weeks. The rats were sacrificed 21days after PQ. Malondialdehyde (MDA), Hydroxyproline, inflammatory and fibrogenic cytokine tumor necrosis factor (TNF)-α, interleukin (IL)-6 and transforming growth factor (TGF)-ß1 in lung tissue were determined. Presence of fibrosis, inflammatory cells, connective tissue and collagen deposition in lung were evaluated microscopically by hematoxylin and eosin (H&E) staining. Dried extract was standardized by amount of berberine by HPTLC methods by silica gel plate. RESULTS: The results showed that PQ could significantly increase the lung MDA, hydroxyproline, TNF-α, IL-6 and TGF-ß1 levels. BVFE ameliorated the biochemical and histological lung alterations induced by PQ. CONCLUSIONS: The present study indicates the hydroalcolic extract of Berberis vulgaris fruit has beneficial effects in rat pulmonary fibrosis induced by PQ in a dose-dependent manner, possibly by anti-oxidant and anti- inflammatory properties, which might be due to its berberine alkaloid content.

Comparison of the Protective Effects of Melatonin and Silymarin Against Gentamicin-Induced Nephrotoxicity in Rats.

This study compared the possible protective effects of silymarin and melatonin against gentamicin (GEN)-induced nephrotoxicity in rats. Rats were allocated to 6 groups: Group I, control group; Groups II and III, administered with silymarin or melatonin; Group IV, injected with GEN; and Groups V and VI, administered with silymarin or melatonin, and then injected with GEN. Compared with the rats in the control group, all rats injected with GEN significantly presented elevated levels of serum creatinine and urea that was accompanied by an increase in relative kidney weight, increase in renal reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and reduction in renal glutathione (GSH) level and superoxide dismutase (SOD) activity. Silymarin and melatonin pretreatment significantly lowered the elevated serum urea and creatinine concentration, kidney weight, and renal ROS and MDA levels. In addition, silymarin and melatonin significantly enhanced renal GSH level and SOD activity. This study indicates that silymarin and melatonin can attenuate renal injury in rats treated with GEN possibly by reducing the ROS level.

Anticonvulsant activity of the ethanolic extract of Punica granatum L. seed.

OBJECTIVE: Various morphological parts of pomegranate (Punica granatum L.) have extensively been used in the folk medicine to treat an array of human ailments. The aim of the present study is to demonstrate the anticonvulsant potential of the ethanolic extract of P. granatum L. seed in chemoconvulsant-induced seizures in mice. METHOD: The anticonvulsant activity of the ethanolic extract was investigated in strychnine (STR)-induced and pentylenetetrazole (PTZ)-induced seizure models in mice. Diazepam was used as reference anticonvulsant drug. Ethanolic extract (150, 300, and 600 mg/kg per os, p.o.), diazepam (1 mg/kg intraperitoneally, i.p.), and distilled water (10 ml/kg, i.p.) were administered before induction of seizures by PTZ (60 mg/kg, i.p.) or STR (2.5 mg/kg, i.p.). The latent time before the onset of convulsions, the duration of convulsions, the percentage of seizure protection, and mortality rate were recorded. RESULTS: The seed ethanolic extract did not show any toxicity and did not protect the animals against seizures but demonstrated a significant increase in seizure latency at 300 and 600 mg/kg in both STR and PTZ seizure models (P < 0.001). It also showed a significant reduction in seizure duration at 300 mg/kg (P < 0.05) and 600 mg/kg (P < 0.001) in the STR seizure model and 600 mg/kg (P < 0.01) in the PTZ seizure model compared with the control group. CONCLUSION: Ethanol extract has dose-dependent anticonvulsant activity against STR- and PTZ-induced seizures. This activity might be due to its saponins, flavonoids, triterpenes, and alkaloids ingredients.