Resveratrol in the Treatment of Gynecological Cancer: Mechanisms and Therapeutic Potential.

Gynecological cancers, encompassing endometrial, ovarian, and cervical cancer, pose significant challenges in clinical practice, often marked by high mortality rates and treatment resistance. Despite advances in standard therapies, including chemoradiation and surgery, tumor recurrence and metastasis remain formidable obstacles. In this context, there is a pressing need to explore novel therapeutic strategies that offer improved efficacy and reduced side effects. Herbal medicine, particularly compounds like resveratrol, has garnered attention for its diverse biological properties, including anticancer effects. Resveratrol, a multipotential nutraceutical, holds promise in gynecological cancer therapy through its modulation of key cellular and molecular processes. This review aims to provide an overview of the current status, challenges, and opportunities in utilizing resveratrol for gynecological cancer treatment. We discuss its role in miRNA regulation, clinical trial findings, and the development of effective formulations. By elucidating the underlying mechanisms of resveratrol's anticancer effects and exploring innovative delivery systems, we aim to shed light on the potential avenues for optimizing its therapeutic benefits in gynecological cancers.

Impact of Buprenorphine on Learning and Memory Ability, Oxidative Status and Inflammation in the Hippocampus of Rats.

BACKGROUND: Buprenorphine (BUP), a "synthetic derivative of the opioid alkaloid thebaine", may be associated with cellular damage in the central nervous system. AIMS: This study was designed to investigate the effects of low and high doses of BUP on oxidative and inflammatory indices in the hippocampus and learning and memory behavior in an animal model. OBJECTIVE: The association between BUP administration and oxidative and inflammatory damage and also learning and memory impairment is not clear. METHODS: For this reason, twenty-four male Wistar rats were randomly allocated into one control and two BUP-treated groups (0.3 and 1 mg/kg, SC), (n=8, for each group). After 4 weeks, learning and memory abilities were assessed by using Y-maze test. Then, oxidative stress indices including glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were assessed in the serum and hippocampus of each animal by using spectrophotometer. Inflammatory parameters such as tumor necrotic factor-α (TNF-α), interleukin- 6 (IL-6), and interleukin-1ß (IL-1ß) were also measured in the serum and hippocampus of rats by using ELISA. RESULTS: The present findings indicated that the memory and learning time was lengthened in BUP (1mg/kg)-treated rats versus control animals (p<0.05). Additionally, it was observed that BUP (1 mg/kg) significantly increased the serum and hippocampal levels of MDA and TNF-α and also decreased GSH levels versus the control group (p< 0.05). CONCLUSION: The results of the present study revealed that BUP may cause learning and memory dysfunction by inducing oxidative stress and inflammation in the hippocampus.

Chrysin's Impact on Oxidative and Inflammation Damages in the Liver of Aged Male Rats.

AIM: The purpose of this research was to investigate the effect of chrysin on one of the natural antioxidants on aging progression in an animal model. BACKGROUND: Oxidative stress and inflammation increase in hepatic tissue during aging, leading to liver dysfunction. OBJECTIVE: The current research was conducted to show the effect of chrysin on the activities of antioxidant enzyme (catalase, glutathione peroxidase, and superoxide dismutase), serum nitric oxide (NO), and lipid peroxidation as well as inflammatory cytokines (TNF-α, IL-6, and IL-1ß) of aging rats. METHODS: Male Wistar rats of different ages, 2, 10, and 20 months, were randomly divided into six groups as follows (n=8, per each group): young control rats (C2), young CH-treated rats (CH2), middle- aged control rats (C10), middle-aged CH-treated group (CH10), aged control group (C20), and aged CH-treated group (CH20). Chrysin (20 mg/kg) was administered intraperitoneally once a day for 30 days. RESULT: Present findings indicated that chrysin treatment ameliorated the increased liver levels of lipid peroxidation, TNF-α, and IL-1ß as well as serum levels of NO. CONCLUSION: The findings suggest that chrysin could be effective against the progression of ageinduced damage by modulation of oxidant-antioxidant system and inflammatory response.

Protective effects of carnosol against oxidative stress induced brain damage by chronic stress in rats.

BACKGROUND: Oxidative stress through chronic stress destroys the brain function. There are many documents have shown that carnosol may have a therapeutic effect versus free radical induced diseases. The current research focused the protective effect of carnosol against the brain injury induced by the restraint stress. METHODS: The restraint stress induced by keeping animals in restrainers for 21 consecutive days. Thereafter, the rats were injected carnosol or vehicle for 21 consecutive days. At the end of experiment, all the rats were subjected to his open field test and forced swimming test. Afterwards, the rats were sacrificed for measuring their oxidative stress parameters. To measure the modifications in the biochemical aspects after the experiment, the activities of malondialdehyde (MDA), reduced glutathione (GSH), as well as superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) were evaluated in the whole brain. RESULTS: Our data showed that the animals received chronic stress had a raised immobility time versus the non-stressed animals (p < 0.01). Furthermore, chronic stress diminished the number of crossing in the animals that were subjected to the chronic stress versus the non-stressed rats (p < 0.01). Carnosol ameliorated this alteration versus the non-treated rats (p < 0.05). In the vehicle treated rats that submitted to the stress, the level of MDA levels was significantly increased (P < 0.001), and the levels of GSH and antioxidant enzymes were significantly decreased versus the non-stressed animals (P < 0.001). Carnosol treatment reduced the modifications in the stressed animals as compared with the control groups (P < 0.001). All of these carnosol effects were nearly similar to those observed with fluoxetine. CONCLUSION: The current research shows that the protective effects of carnosol may be accompanied with enhanced antioxidant defenses and decreased oxidative injury.

Inhibitory and Cytotoxic Activities of Chrysin on Human Breast Adenocarcinoma Cells by Induction of Apoptosis.

OBJECTIVES: Chrysin, an active natural bioflavonoid found in honey and many plant extracts, was first known for its antioxidant and anti-inflammatory effects. The fact that antioxidants have several inhibitory effects against different diseases, such as cancer, led to search for food rich in antioxidants. In this study, we investigated the antiproliferative and apoptotic effects of chrysin on the cultured human breast cancer cells (MCF-7). MATERIALS AND METHODS: Cells were cultured in Roswell Park Memorial Institute medium and treated with different chrysin concentrations for three consecutive days. Cell viability was quantitated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The percentage of apoptotic cells was determined by flow cytometry using Annexin V-fluorescein isothiocyanate. RESULTS: The MTT assay showed that chrysin had an antiproliferative effect on MCF-7 cells in a dose- and time-dependent manner. The 50% cell growth inhibition values for chrysin against MCF-7 cells were 19.5 and 9.2 µM after 48 and 72 h, respectively. Chrysin induced apoptosis in MCF-7 cells as determined by flow cytometry. Chrysin inhibits the growth of the breast cancer cells by inducing cancer cell apoptosis which may, in part, explain its anticancer activity. CONCLUSION: This study shows that chrysin could also be considered as a promising chemotherapeutic agent and anticancer activity in treatment of the breast cancer cells in future. SUMMARY: Chrysin had an antiproliferative effect on human breast cancer cells (MCF-7) cells in a dose- and time-dependent mannerChrysin induced apoptosis in MCF-7 cells, as determined by flow cytometryChrysin inhibits the growth of the breast cancer cells by inducing cancer cell apoptosisChrysin may have anticancer activity. Abbreviations used: Human breast cancer cells (MCF-7), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), phosphate-buffered saline (PBS), normal fibroblast mouse (L929).

Orthopedic lesions in tethered cord syndrome: the importance of early diagnosis and treatment on patient outcome.

BACKGROUND: Many of the patients with tethered cord syndrome (TCS) are admitted because of neurological symptoms, while some are admitted because of their orthopedic, urologic, anorectal, and dermatologic manifestations. Consequently, this study aimed to evaluate the importance of early diagnosis and treatment of tethered cord syndrome on patient outcome. METHODS: Fourty-three patients who underwent surgery because of tethered cord syndrome from 2006 to 2010 were studied. Many of these cases were referred by orthopedic surgeons. All of the findings were recorded and follow up was done twice (1 and 3 years after surgery). RESULTS: Thirty-seven patients were less than 7 years old and 6 were between 17 to 33 years old. According to clinical and neurological exams, satisfactory results were achieved in both groups. Those with early surgical intervention, especially in their early follow up assessment, had the best results. Seventeen cases were referred by an orthopedic surgeon because of manifestations such as leg weakness and numbness, leg pain and spasticity, pes cavus, claw toes, and leg or foot length discrepancy. Cerebrospinal fluid leakage occurred in 3 cases after surgery and 1 showed pseudomeningocele formation. CONCLUSIONS: After one year of follow up, initially the results of the treatment were better in early operated cases, but in later follow up assessment (after 3 years) the results were almost the same in both of the groups.

The etiologies of low back pain in patients with lumbar disk herniation.

BACKGROUND: Low back pain (LBP) is a common complaint in population that lowers the quality of life. The main etiology of LBP is recognized in about 20% of patients while it is attributed to lumbar disk herniation (LDH) in 80% of cases and causes some unnecessary lumbar surgeries without realizing the definite cause. OBJECTIVES: This study was planned to evaluate the etiologies of LBP in patients who had LDH to clarify whether the disc herniation is the main cause of patients` pain or other diseases were responsible for this kind of pain. MATERIALS AND METHODS: In this cross-sectional study, we analyzed the medical profiles of the patients with proven LDH in a private clinic in Mashhad City, Iran, between 2005 and 2012, for demographic and the etiologies of LBP with clinical and paraclinical studies. We also calculated the incidence of each etiology by SPSS 13. RESULTS: In our study, among 1250 patients with proven LDH by MRI, 500 patients (40%) had chronic LBP and the most common causes of LBP were heavy constant working (40.2%), osteoporosis (35.6%), and sacroiliac joint pain (34.6%), consecutively. Interestingly, LDH had the ninth rank among the common cause of LBP. CONCLUSIONS: In this study, we found that in spite of previous beliefs, discopathies were not common etiologies of LBP. Thus, even in patients with proven LDH by imaging studies, the physician should perform a thorough evaluation for other causes of LBP to avoid unnecessary lumbar surgeries.

Safranal ameliorates antioxidant enzymes and suppresses lipid peroxidation and nitric oxide formation in aged male rat liver.

Free radical production and oxidative stress are known to increase in liver during aging, and may contribute to oxidative damage. The objective of this study was to observe the changes in activities of antioxidant enzymes (superoxide dismutase, glutathione-S-transferase, catalase), lipid peroxidation levels and serum nitric oxide occurring in livers of rats of 2, 10 and 20 months old, and to see whether these changes are restored to those of the two month old control levels rats after administration of safranal. The aged rats (10 and 20 months) were given intraperitoneal injections of safranal (0.5 mg/kg day) daily for one month. The results obtained in the present work revealed that normal aging was associated with a significant decrease in the activities of antioxidant enzymes, and an increase in lipid peroxidation in livers and nitric oxide content in serum of aging rats. The results of the present study demonstrate that safranal could be a candidate to suppress the development of age-induced damage by protecting against oxidative stress and increasing antioxidant defenses. A likely mode of action of safranal can be its activity as a hormetin by inducing mild oxidative damage which leads to the activation of antioxidative enzymes.