Ginger (Zingiber Officinale Roscoe) ameliorates ethanol-induced cognitive impairment by modulating NMDA and GABA-A receptors in rat hippocampus.

Brain damage caused by ethanol abuse may lead to permanent damage, including severe dementia. The aim of this study was to investigate the effects of ginger powder on ethanol-induced cognitive disorders by examining oxidative damage and inflammation status, and the gene expression of N-methyl-D-aspartate (NMDA) and γ-Aminobutyric acid (GABA)-A receptors in the hippocampus of male rats. 24 adult male Sprague-Dawley rats were allocated randomly to four groups as follows control, ethanol (4g/kg/day, by gavage), ginger (1g/kg/day, by gavage), and ginger-ethanol. At the end of the study, memory and learning were evaluated by the shuttle box test. Moreover, to explore mechanisms involved in ethanol-induced cognitive impairment and the protective effect of ginger, the expression of Nuclear factor kappa B (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), NMDA receptor, and GABA-A receptor was measured along with inflammatory and oxidative biomarkers in the hippocampus tissue. The results showed that ethanol could induce cognitive impairment in the ethanol group, while pretreatment with ginger could reverse it. The gene expression of the NF-κB/ Tumor necrosis factor (TNF)-α/Interleukin (IL)-1ß pathway and NMDA and GABA-A receptors significantly increased in the ethanol group compared to the control group. While pretreatment with ginger could significantly improve ethanol-induced cognitive impairment through these pathways in the ginger-ethanol group compared to the ethanol group (P < 0.05). It can be concluded that ginger powder could ameliorate ethanol-induced cognitive impairment by modulating the expression of NMDA and GABA-A receptors and inhibiting oxidative damage and the NF-κB/TNF-α/IL-1ß pathway in the rat hippocampus.

Thyme extract could overcome diabetes-induced reproductive dysfunction by inhibiting oxidative damage and increasing the expression of insulin receptor substrate and pyruvate kinase in the rat sperm.

OBJECTIVES: Oxidative stress and disruption of energy metabolism in the reproductive system, especially sperm, play a significant role in diabetes-related infertility. Zataria multiflora Boissis (ZMB), a medicinal plant containing various bioactive compounds, may have efficacy in treating metabolic diseases and reproductive disorders. Therefore, the aim of this study was to investigate the effects of different doses of ZMB extract on diabetes-induced reproductive dysfunction by assessing oxidative damage and the gene expression of insulin receptor substrate (IRS) and pyruvate kinase (PK) in male rats' sperm. METHODS: Sixty adult male Wistar rats were randomly divided into six groups; control (C), diabetes (D), and diabetic animals treated with glibenclamide (G, 50 mg/kg) and thyme extract (T100, T200, and T400). Diabetes was induced by intraperitoneal injection of Streptozotocin (STZ) (50 mg/kg). Insulin, glucose, oxidative and pro-inflammatory markers in the serum, and gene expressions of IRS, and PK were measured in the stored sperms in the epididymis. Changes in the process of spermatogenesis were assessed through the histological evaluation of the testis. Gas chromatography-mass spectrometry (GC-MS) was used to analyze the quantity and quality of thyme extract. KEY FINDINGS: The study results indicated that body weight, food intake, and sperm parameters significantly improved in a dose-dependent manner in the T200 group compared to the other groups. Additionally, in the same group, pro-inflammatory biomarkers, DNA fragmentation, and MDA levels decreased, while the levels of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) enzymes in the stored epididymal sperm significantly improved compared to the other groups. The expression of IRS and PK, along with the mean counts of spermatogenesis cell lines (especially Sertoli cells), significantly increased in the T200 group. SUMMARY: In conclusion, thymol appears to alleviate diabetes-induced reproductive dysfunction by inhibiting oxidative damage, improving the metabolic state, and upregulating the expression of IRS and PK genes in the sperm of male rats.

Transcriptional Regulation of the Colorectal Cancer Stem Cell Markers, Nanog and Oct4, Induced by a Thermodynamic-Based Therapy Approach.

Background: Cancer stem cells (CSC), as responsible issues to cancer development and progression, play a crucial role in tumorigenesis, recurrence, metastasis, and chemoresistance. Both hyperthermia and photodynamic therapy (PDT) may be effective for cancer treatment, particularly when combined with other therapeutic approaches. This study aimed to evaluate the effect of hyperthermia combined with PDT on colorectal CSC and the gene expression of the CSC markers, presenting a more effective approach for cancer therapy. Methods: The study was conducted in the Pasteur institute of Iran, Tehran, Iran in 2018. We evaluated the anticancer role of hyperthermia, Gold nanoparticles coated with curcumin (Cur-GNPs) in PDT and combination of the two approaches on cell viability and the expression of CSC markers, Nanog and Oct4 in colorectal cancer cell line HT-29. The cytotoxicity effect of Cur-GNPs against the cells was assessed in vitro. The cell viability was assessed using MTT assay, and the expression analysis of the CSC genes was evaluated using a q-real-time PCR. Results: Cell viability was decreased by PDT (P=0.015) and the combination therapy (P=0.006) but not by hyperthermia alone (P=0.4), compared to control. Also, the expression of CSC markers, Nanog and Oct4 was shown to significantly down-regulate in all hyperthermia, PDT and combination groups. Conclusion: Hyperthermia combined with PDT was indicated to be more efficient in eliminating tumors than hyperthermia or PDT alone.

Evaluation of Expression of Cytochrome P450 Aromatase and Inflammatory, Oxidative, and Apoptotic Markers in Testicular Tissue of Obese Rats (Pre)Treated with Garlic Powder.

Today, adolescent obesity is recognized as an epidemic and a cause of reproductive disorders. Decreased testosterone levels occur due to functional defects in the hypothalamus-pituitary axis, excessive activity of cytochrome P450 aromatase enzyme, and testicular dysfunction in these people. Oxidative damage, inflammation, and apoptosis are also the main mechanisms of testicular damage during obesity. The use of herbal products such as garlic can improve this disorder due to its anti-inflammatory and antioxidant properties. Therefore, the aim of this study is to investigate the effect of pretreatment and treatment of garlic powder on the expression of cytochrome P450 aromatase enzyme and the expression of genes involved in testosterone synthesis, inflammation, oxidative damage, apoptosis in testicular tissue, and metabolic function of liver tissue in young male obese rats. Eighty male Wistar rats were divided into the controlled and treated groups. Serum levels of lipid, glucose, and insulin as metabolic factors were measured along with the testicular antioxidant and inflammation markers. The expression of Bcl2, Bax, and caspase-3 along with NF-κB, SREBP-1c, CPT-1beta, Nrf-2, CD36, FAS, CYP19A1, P450scc, StAR, 17ßHSD, PPARα, and aromatase (CYP19, P450arom) was also measured. Testicular histological evaluation and spermatogenic process was also performed. The results showed that oxidative, inflammatory, and metabolic factors significantly increased in obese rats. The testicular expression of aromatase, NF-κB, Bax, and caspase 3 increased and Nrf2 expression decreased in obese rats, while (pre) treatment with garlic powder significantly decreased the expression of these genes in obese rats. These results were also confirmed by the findings of the histological evaluation and sperm analysis. It can be concluded that garlic powder could improve reproductive dysfunction in obese rats.

Comparison of the effect of vitamin C and selenium nanoparticles on gentamicin-induced renal impairment in male rats: a biochemical, molecular and histological study.

Renal failure caused by gentamicin is mainly mediated through oxidative damage, inflammation, and apoptosis. Hence, vitamin C and selenium, which have antioxidant, anti-inflammatory, and anti-apoptotic properties, and their nanoparticle forms, which have recently received attention, may reduce gentamicin-induced side effects. Therefore, the aim of this study was to investigate the therapeutic effects of vitamin C and selenium, and their nanoparticles on gentamicin-induced renal damage in male rats. 128 adult male Wistar rats were randomly divided into equal sixteen controlled and treated groups. Serum levels of uric acid, blood urea nitrogen, urea, and creatinine were measured. Renal levels of oxidative parameters such as MDA, SOD, and CAT and inflammatory parameters including IL-1ß, and TNF-α were measured. Renal expression of Nrf2, NF-κB, Bcl-2, caspase-3, BAX and mTORc1 was also evaluated. The results showed that gentamicin causes oxidative damage, inflammation, apoptosis and disruption of autophagy in kidney tissue in a dose-dependent manner. However, treatment with vitamin C, selenium and their nanoparticles could significantly improve these effects. Also, the results showed that the inflammatory and oxidative parameters and the expression of genes involved in them and apoptosis in the gentamicin groups treated with vitamin C nanoparticles and selenium nanoparticles reduced significantly compared to those treated with vitamin C and selenium. It can be concluded that vitamin C, selenium and their nanoparticles can improve gentamicin-induced kidney damage by inhibiting oxidative damage, inflammation and apoptosis-induced by autophagy, and can be a good option for kidney damage caused by gentamicin or as an adjunctive treatment to reduce its side effects.

The ketogenic diet could improve the efficacy of curcumin and Oldenlandia diffusa extract in the treatment of gastric cancer by increasing miR340 expression and apoptosis mediated by autophagy, oxidative stress, and angiogenesis.

The pathogenesis of gastric cancer is a multistage process that involves glucose metabolism, inflammation, oxidative damage, angiogenesis, autophagy, and apoptosis. Moreover, microRNA-340 (miR340) also plays a vital role in tumorigenesis and the biology of gastric cancer as an epigenetic factor. It seems that the use of ketogenic diets (KDs) and plant extracts that have antitumor, anti-inflammatory, and antioxidant properties can be good treatment options to cure gastric cancer. The aim of this study was to investigate the role of miR-340 on pathways involved in the pathogenesis of gastric cancer and the improving effects of the KD, Oldenlandia diffusa extract (ODE), and curcumin in the animal model of gastric cancer. One hundred and ten male Wistar rats were divided into control and treatment groups. The expression of miR-340 along with genes involved in inflammation, oxidative damage, angiogenesis, and apoptosis were assessed. The results showed that the KD and different doses of curcumin and ODE in a dose-dependent behavior could induce apoptosis and the expression of the Akt/mTORC1 pathway and inhibit inflammation, oxidative damage, and angiogenesis in the gastric tissue of rats with cancer. In addition, there was no significant difference between cancer groups receiving ODE and curcumin. These results also showed that consumption of KD could significantly increase the efficacy of ODE and curcumin which may be due to increasing miR-340 expression. The results of this study suggested well that the KD along with conventional therapies in traditional medicine can be a useful solution for the prevention and treatment of gastric cancer. PRACTICAL APPLICATIONS: Gastric cancer is the third leading cause of cancer death, and genetic and epigenetic factors, including miR-340, are involved in its pathogenesis. However, the use of ketogenic diets (KDs) and plant products such as curcumin and Oldenlandia diffusa extract (ODE) can play an effective role in inhibiting tumorigenesis in some cancers. Our results showed that the KD and different doses of curcumin and ODE could induce apoptosis and the expression of the Akt/mTORC1 pathway and inhibit inflammation, oxidative damage, and angiogenesis in the gastric tissue. Moreover, the KD could significantly increase the efficacy of ODE and curcumin which may be due to an increase in miR-340 expression. These findings provide novel perceptions about the mechanisms of the KD, curcumin, and ODE to cure gastric cancer. It suggested that the KD as adjunctive therapy along with conventional therapies in traditional medicine could be considered a useful solution to prevent and treat gastric cancer.

Green tea could improve elderly hypertension by modulating arterial stiffness, the activity of the renin/angiotensin/aldosterone axis, and the sodium-potassium pumps in old male rats.

Hypertension is a major health problem common in the elderly people. Green tea is a popular beverage recommended in folk medicine for lowering blood pressure. However, the molecular mechanisms involved in the antihypertensive effects of green tea are not fully understood. Therefore, the aim of this study was to investigate the antihypertensive effects of green tea on high-salt diet-induced hypertension in old male rats. Forty old male rats were divided into five groups: control, hypertensive, and hypertensive-green tea (2, 4, and 6 g/kg). Heart rate (HR) and systolic blood pressure (SBP) were measured. Cardiac and renal histology were also performed. Lipid profile, NO, angiotensin II (Ang II), and aldosterone were determined, and the expression of eNOS, ATIR and ATIIR, aldosterone receptor, and Atp1a1 were measured. Green tea could significantly decrease HR and SBP, lipid profiles, renin-angiotensin II-aldosterone system activity, and Ang II signaling in kidney tissue of hypertensive rats (p < .01). It also increased Atp1a1, Nrf2, and eNOS expression along with antioxidant enzymes activity and NO concentration (p < .05) and decreased NF-ĸB and iNOS expression and IL-1ß levels in the heart, kidneys, and aorta of rats with hypertension. It can be concluded that green tea can improve salt-induced blood pressure by modulating the function of the renin-angiotensin-aldosterone system, enhancing the synthesis of nitric oxide in the endothelium, increasing antioxidant activity and suppressing inflammation in the heart and kidney, improving the expression of the sodium-potassium pump, and reduction in serum lipids and glucose in aged male rats. PRACTICAL APPLICATIONS: The results of this study showed that green tea could improve hypertension in elderly rats by modulating (1) the expression of the sodium-potassium pump in the heart, kidney, and aortic tissues, (2) the activity of the renin-angiotensin II-aldosterone system in kidney, (3) enhancing antioxidant and anti-inflammatory activities in the heart, aorta, and kidneys, (4) enhancing the synthesis of nitric oxide in the endothelium, and (5) lowering lipid profile. The results of these studies show that the consumption of green tea and its products can be a good candidate for the prevention of cardiovascular diseases such as hypertension in the elderly. In addition, attention to its bioactive compounds can be considered by researchers as an independent therapeutic strategy or adjunctive therapy for the treatment of hypertension.

Effects of Vitamin D Supplementation on Bone Health and Bone-related Parameters in HIV-infected Patients: A Systematic Review and Meta-analysis.

PURPOSE: There is growing evidence that bone health is decreased in individuals with HIV infection. Vitamin D deficiency is also highly prevalent among HIV-infected patients. The literature was systematically reviewed to determine whether bone health and bone-related parameters may improve with vitamin D supplementation in HIV-infected individuals. METHODS: Four databases were systematically searched for randomized clinical trials of vitamin D supplementation in HIV infection, published from January 1990 to September 2021. No language or publication restrictions were applied. Standardized mean differences (SMD) with 95% CIs are reported. A random-effects model was used to perform meta-analysis. FINDINGS: Ten studies met the inclusion criteria (N = 733 participants at study completion). The mean ages of the patients in the included trials ranged from 10 to 49 years. The meta-analysis indicated that with vitamin D supplementation, serum 25-hydroxy vitamin D (25[OH]D) level was significantly increased (SMD, 1.86; 95% CI, 1.02 to 2.70; I2 = 94.4%), but there were no significant effects on levels of serum 1,25-dihydroxy vitamin D (1,25-[OH]2D) (SMD, 0.29; 95% CI, -0.07 to 0.64; I2 = 67.4%), total bone mineral density (SMD, 0.07; 95% CI, -0.23 to 0.37; I2 = 00.0%), spine bone mineral density (SMD, 0.15; 95% CI, -0.19 to 0.49; I2 = 17.3%), and parathyroid hormone level (SMD, -0.18; 95% CI, -0.37 to 0.02; I2 = 1.2%) in HIV-infected patients. IMPLICATIONS: This study showed that vitamin D supplementation can improve serum 25(OH)D in HIV-infected patients. The effects of vitamin D supplementation on other bone health-related parameters such as bone mineral density and parathyroid hormone in HIV-infected patients need to be further investigated in larger-scale, well-designed randomized, controlled trials.

Determination of some heavy metals levels in the meat of animal species (sheep, beef, turkey, and ostrich) and carcinogenic health risk assessment in Kurdistan province in the west of Iran.

Heavy metals accumulation in food products as a result of industrialization is one of the main potential threats to public health. This study was aimed to evaluate the concentrations of heavy metals in the meat of some prevalent farm animal species including sheep, beef, turkeys, and ostriches in Sanandaj (one of the strategic cities in Kurdistan province, Iran). In this study, the contents of some heavy metals (selenium, lead, cadmium, arsenic, cobalt, zinc, nickel, copper, and chromium) were assessed in 170 meat samples collected from meat distribution centers in Sanandaj, Kurdistan province. The ICP-MS method was used to assess the levels of these elements in the meat of beef, sheep, turkey, and ostrich as the main consumed meats in this region. Statistical analysis was performed by ANOVA and one-sample t-test, and the correlation coefficient of the concentrations of metals was also calculated. The results showed that there were no significant differences in the average contents of selenium, nickel, cobalt, and chromium among various meats (P > 0.05). However, the amounts of lead, cadmium, arsenic, zinc, copper, chromium, and nickel were meaningfully different to maximum permissible limits (MPL) (P < 0.05). In addition, a significant negative correlation was found between arsenic and selenium in meats. Except for cobalt, the concentrations of other metals were higher than MPL in the evaluated meats. Despite the target hazard quotient (THQ) for cadmium in sheep and beef meats being higher than their MPL (> 1), its target risk of cancer (TR) was acceptable. It can be concluded that monitoring and elimination of heavy metals pollution are essential because of their high accumulation in the meat of main farm animal species in Sanandaj, Kurdistan province.

Superior effect of broccoli methanolic extract on control of oxidative damage of sperm cryopreservation and reproductive performance in rats: A comparison with vitamin C and E antioxidant.

Sperm cryopreservation is one of the important reproductive biotechnology. However, during the sperm cryopreservation, reactive oxygen species (ROS) are produced which disrupt the functional and structural competence of sperm. The aim of this study is to compare the effects of broccoli extract with vitamins C and E on oxidative damage, sperm quality parameters, and reproductive hormones in rats. Forty male Wistar rats were divided into five groups: Control, vitamin C, vitamin E, a combination of vitamin C + E at a dose of 200 mg/kg, and broccoli extract at a dose of 300 mg/kg (used as oral gavage) groups. At the end of the study, blood samples were taken to measure follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. Epididymal sperm was used to measure oxidative stress biomarkers and sperm parameters before and after cryopreservation. In addition, the testicles were also used for histological studies. The gonadosomatic index (GSI) in the broccoli extract group was higher than in other groups (P = 0.016). Also, there was a significant increase in the mean level of spermatogenesis in the broccoli and vitamin C + E groups (P < 0.001). The sperm concentration, sperm vitality, and sperm motility increased, while DNA fragmentation significantly decreased before and after sperm cryopreservation in the broccoli group (P < 0.05). Concentrations of glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) enzymes in the control group were significantly lower than other groups, and malondialdehyde (MDA) showed a significant reduction in the treatment groups compared to the control group (P < 0.05). Besides, the FSH and testosterone levels increased significantly in the broccoli group (P = 0.001). In conclusion, broccoli extracts protected rat sperm against oxidative damage during cryopreservation and improved reproductive performance.

Safflower (Carthamus tinctorius L.) oil could improve abdominal obesity, blood pressure, and insulin resistance in patients with metabolic syndrome: A randomized, double-blind, placebo-controlled clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Carthamus tinctorius L. (Safflower) has been widely recommended to treat metabolic disorders in traditional herbal medicine in Persia, China, Korea, Japan, and other East-Asian countries. The anti-hypercholesterolemic and antioxidant effects of this plant have been well documented, but its protective effects against Metabolic Syndrome (MetS) have not been fully illustrated. AIM OF THE STUDY: The present study aimed to evaluate the effects of safflower oil on MetS risk factors. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled clinical trial, 67 patients with MetS were administered either divided 8 g safflower oil or placebo daily for 12 weeks. All patients were advised to follow their previous diets and physical activities. RESULTS: Safflower oil resulted in a significant reduction in waist circumference (-2.42 ± 3.24 vs. 0.97 ± 2.53, p<0.001), systolic blood pressure (-8.80 ± 9.77 vs. -2.26 ± 8.56, p = 0.021), diastolic blood pressure (-3.53 ± 7.52 vs. -0.70 ± 6.21, p = 0.041), fasting blood sugar (-5.03 ± 10.62 vs. 2.94 ± 7.57, p = 0.003), and insulin resistance (-0.59 ± 1.43 vs. 0.50 ± 1, p = 0.012), but an increase in adiponectin level (0.38 ± 0.99 vs. -0.09 ± 0.81, p = 0.042) in the treatment group in comparison to the placebo group. The results revealed a direct relationship between leptin level and Body Mass Index (BMI) in both groups (p<0.001). In addition, increase in BMI resulted in a non-significant decrease in adiponectin level in both groups. Moreover, no significant difference was observed between the two groups regarding lipid profiles, leptin serum level, serum creatinine concentration, and other outcomes. CONCLUSION: Safflower oil without lifestyle modification improved abdominal obesity, blood pressure, and insulin resistance in patients with MetS.

The comparison of the effect of Origanum vulgare L. extract and vitamin C on the gentamycin-induced nephrotoxicity in rats.

The gentamicin renal toxicity has been the focal point for much discussion. The objective of this study was to investigate the impacts of Origanum vulgare L. extract and vitamin C on gentamicin dose-dependent toxicity in rats' kidney. The present study was conducted on 60 male Wistar rats divided into ten experimental groups: control (untreated), G1, G2, G3 (100, 200, 300 mg/kg gentamicin), M1, M2 and M3 (500 mg/kg marjoram extract) + 100, 200 and 300 gentamicin, V1, V2 and V3 (Vitamin C 500 mg/kg) + 100, 200 and 300 of gentamicin. On the last day, the serum was separated from heart blood and the kidney tissues were extracted to measure the biochemical and oxidative stress parameters and histological changes. Kidney damage was confirmed as dose-dependent gentamicin by biochemical and pathological parameters. Urea, Blood Urea Nitrogen (BUN), and creatinine showed a significant increase in the G3 group compared to the control, M1, and V1 groups (p < 0.01). Catalase (CAT), Glutathione peroxidase (GPx), and Superoxide dismutase (SOD) showed a significant reduction in renal tissue in the G3 group compared to the other groups (p < 0.001). Malondialdehyde (MDA) concentration in the kidney tissue of the G3 group also showed a significant increase compared to other groups (p < 0.001). Furthermore, TNFα and IL-1 levels were the highest in the G3 group, and serum total antioxidant capacity (TAC) concentration had the lowest amount compared to other groups. Moreover, histopathological lesions of the kidney showed significant statistical differences among the groups that received gentamicin with the control and M1 group. Marjoram extract at the dose of 500 mg/kg had a desirable effect on controlling gentamicin damage in the kidneys compared with vitamin C. In particular, controlling gentamicin-induced oxidative stress and inflammation by the consumption of marjoram extract and vitamin C plays an important role in protecting the kidneys.

The Antioxidant Effect of Medicago sativa L. (Alfalfa) Ethanolic Extract against Mercury Chloride (HgCl2) Toxicity in Rat Liver and Kidney: An In Vitro and In Vivo Study.

Heavy metals such as mercury are some of the environmental pollutants and can induce toxicity by bioaccumulation and oxidative damage. This study aimed to investigate the effect of ethanolic extract of Medicago sativa L. (Alfalfa) on mercury damage in the kidney and liver of rats. Thirty Wistar rats were randomly divided into five groups, the control group, S group (2 mg/kg mercury chloride), and T1, T2, and T3 groups that, in addition to mercury, received doses of 250, 500, and 750 mg/kg of the alfalfa extract. On the last day, blood samples were taken, and the serum was separated to measure biochemical and oxidative stress parameters in the kidney and liver. A part of the kidney and liver was also used for histopathological evaluation. Total phenols and flavonoids were 40.45 ± 2.12 and 14.36 ± 0.45 mg/g, respectively, whereas IC50 was 245.18 ± 19.76 µg/ml. The body weight significantly decreased in the S group compared to other groups, while treatment with different doses of alfalfa extract increased the body weight. Mercury concentration in the kidney was higher than that in the liver. The serum levels of urea, creatinine, alanine aminotransferase (ALT), and alkaline phosphatase (ALP) significantly increased in the S group compared to the control group, while treatment with different doses of alfalfa extract increased their levels. Moreover, an increase in malondialdehyde (MDA) and a decrease in glutathione peroxidase (GPx), catalase (CAT), total antioxidant capacity (TAC), and superoxide dismutase (SOD) activity were observed in the S group. The level of these parameters significantly improved in the groups receiving the extract compared to the S group. Furthermore, the histopathological evaluation showed glomerular and tubular damage and hepatic necrosis in the S group and that these conditions improved in the T3 group. The findings of this study showed that the ethanolic extract of alfalfa in a dose-dependent manner has potentially unique protective effects against mercury poisoning in the kidney and liver.

Molecular mechanisms underlying curcumin-mediated microRNA regulation in carcinogenesis; Focused on gastrointestinal cancers.

Curcumin is a bioactive ingredient found in the Rhizomes of Curcuma longa. Curcumin is well known for its chemopreventive and anti-cancer properties. Recent findings have demonstrated several pharmacological and biological impacts of curcumin, related to the control and the management of gastrointestinal cancers. Mechanistically, curcumin exerts its biological impacts via antioxidant and anti-inflammatory effects through the interaction with various transcription factors and signaling molecules. Moreover, epigenetic modulators such as microRNAs (miRNAs) have been revealed as novel targets of curcumin. Curcumin was discovered to regulate the expression of numerous pathogenic miRNAs in gastric, colorectal, esophageal and liver cancers. The present systematic review was performed to identify miRNAs that are modulated by curcumin in gastrointestinal cancers.

Safflower seed oil improves steroidogenesis and spermatogenesis in rats with type II diabetes mellitus by modulating the genes expression involved in steroidogenesis, inflammation and oxidative stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes mellitus (DM), as a multiorgan syndrome, is an endocrine and metabolic disorder that is associated with male reproductive system dysfunction and infertility. Safflower (Carthamus tinctorius L.) as an herbal remedy improves DM and infertility-related disorders. The anti-hypercholesterolemic, anti-inflammatory, and antioxidative properties of this herb have been well documented, but its role in testosterone production, male reproductive system and zinc homeostasis has not been fully illustrated. AIM OF THE STUDY: This study aimed to investigate the preventive and therapeutic properties of different doses of safflower seed oil against reproductive damage caused by type II DM by investigating zinc element homeostasis, inflammation and oxidative damage in testis tissue and their relationship with testosterone production and sperm parameters. MATERIALS AND METHODS: Eighty adult male Sprague-Dawley rats were randomly divided into eight groups and treated daily for 12 and 24 weeks in protective and therapeutic studies, respectively. Type II DM was induced by a High Fat Diet (HFD) in normoglycemic rats for three months. At the end of each study, serum level of glucose, testosterone, gonadotropins, TNF-α, insulin, and leptin were measured. Moreover, antioxidant enzymes activity, lipid peroxidation, zinc and testosterone along with the expression of Nrf-2, NF-κB, TNF-α, StAR, P450scc, and 17ßHSD3 genes in the testis were detected. RESULTS: After the intervention, the activity of antioxidant enzymes and the level of testosterone and gonadotropins significantly decreased in the rats with DM in comparison to the others. However, lipid peroxidation and serum level of insulin, leptin and TNF-α increased and the testicular level of zinc significantly changed in the rats with DM compared to the control groups (p < 0.05). The gene expression of NF-κB and TNF-α were also significantly increased and the gene expression of Nrf2, StAR, P450scc and 17ßHSD3 were decreased in the testis of diabetic rats (p < 0.05). The results showed that pretreatment and treatment with safflower seed oil could improve these parameters in diabetic rats compared with untreated diabetic rats (p < 0.05). CONCLUSION: HFD could impair the production of testosterone and sperm, and reduce gonadotropin by increasing the serum level of leptin and inducing insulin resistance, oxidative stress and inflammation. However, safflower oil in a dose-dependent manner could improve testosterone level and sperm parameters by improving the level of leptin, zinc and insulin resistance, and the genes expression involved in testosterone synthesis, inflammation and oxidative stress.

Association of Serum Vitamin D with Serum Cytokine Profile in Patients with Knee Osteoarthritis.

OBJECTIVE: The role of vitamin D in the pathogenesis of osteoarthritis (OA) is not well understood. In this study, we aimed to investigate the association of serum vitamin D with the serum cytokine profile in patients with primary knee OA. DESIGN: In a cross-sectional study, 116 patients with radiologic diagnosis of grade I to III knee OA were included. The study population included 79 (75.9%) females and 25 (24.1%) males with a mean age of 55.1 ± 9.6 years. The serum concentration of IL-6, IL-8, TNF-α, IL-4, IL-10, IL-13, and vitamin D were assessed using an enzyme-linked immunosorbent assay. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used for the assessment of patient's reported disability associated with knee OA. RESULTS: Serum vitamin D status was deficient, insufficient, and sufficient in 18 (15.5%), 63 (54.3%), 35 (30.2%) patients, respectively. Higher levels of serum IL-6 were observed in patients with vitamin D deficiency (P = 0.022). The mean serum vitamin D level was not associated with OA grade (P = 0.88) and WOMAC scores of the patients (P = 0.67). Serum IL-6 level was significantly associated with both OA grade and WOMAC scores of the patients (P < 0.001 and P = 0.001, respectively). The vitamin D status was not significantly associated with the serum levels of other evaluated cytokines. CONCLUSION: Vitamin D deficiency in knee OA seems to be associated with a higher release of IL-6. Therefore, vitamin D supplementation could reduce the disease burden by controlling the IL-6 release.

A randomized controlled trial on the coloprotective effect of coenzyme Q10 on immune-inflammatory cytokines, oxidative status, antimicrobial peptides, and microRNA-146a expression in patients with mild-to-moderate ulcerative colitis.

PURPOSE: Coenzyme Q10 (CoQ10), having potent antioxidant and anti-inflammatory pharmacological properties, has recently been shown to be a safe and promising agent in maintaining remission of ulcerative colitis (UC). This trial was, therefore, designed to determine CoQ10 efficacy on inflammation and antioxidant status, antimicrobial peptides, and microRNA-146a expression in UC patients. METHODS: In this randomized double-blind controlled trial, 88 mild-to-moderate UC patients were randomly allocated to receive CoQ10 (200 mg/day) or placebo (rice flour) for 2 months. At the baseline and at an 8-week follow-up, serum levels of Nrf2, cathelicidin LL-37, ß-defensin 2, IL-10, IL-17, NF-κB p65 activity in peripheral blood mononuclear cells (PBMCs), simple clinical colitis activity index questionnaire (SCCAIQ), and quality of life (IBDQ-32 score), as well as an expression rate of microRNA-146a were measured. RESULTS: A significant reduction was detected in the serum IL-17 level, activity of NF-κB p65 in PBMCs, and also SCCAI score in the CoQ10 group compared to the placebo group, whereas IL-10 serum concentrations and IBDQ-32 score of the CoQ10 group considerably increased versus the control group; the changes of these variables were also significantly different within and between groups at the end of the study. Furthermore, CoQ10 remarkably increased serum levels of cathelicidin LL-37. A significant change in serum cathelicidin LL-37 levels was also observed between the two groups. No statistical difference, however, was seen between the two groups in terms of the serum levels of Nrf2 and ß-defensin 2 and the relative expression of microRNA-146a. CONCLUSIONS: Our results indicate that CoQ10 supplementation, along with drug therapy, appears to be an efficient reducer of inflammation in patients with mild-to-moderate UC at a remission phase. TRIAL REGISTRATION: The research has also been registered at the Iranian Registry of Clinical Trials (IRCT): IRCT20090822002365N17.

The effects of broccoli and caraway extracts on serum oxidative markers, testicular structure and function, and sperm quality before and after sperm cryopreservation.

Despite studies on the effects of medicinal plants on reproductive performance, the effect of extracts broccoli and caraway on serum and testicular oxidative biomarkers, testicular structure and function and sperm quality before and after cryopreservation has not been studied. Sixty-three male mice were divided into nine controlled and treated groups as follow: control, broccoli (200 mg/kg), broccoli (300 mg/kg), caraway (200 mg/kg), caraway (300 mg/kg), broccoli -caraway (200 mg/kg), broccoli (300 mg/kg)-caraway (200 mg/kg), broccoli (200 mg/kg)-caraway (300 mg/kg), broccoli-caraway (300 mg/kg). After 42 days of treatment, the animals were sacrificed and blood sample and testicular tissue were collected for biochemical and histological measurements. Sperm quality was also measured before and after cryopreservation. The results showed that the diameter and number of spermatogonium, primary spermatocytes, spermatids and sperm count were significantly increased by broccoli (300 mg/kg), while level of them were significantly decreased by caraway (300 mg/kg) compared to other groups (p < 0.01). Sperm viability and motility after thawing significantly improved by broccoli (300 mg/kg) compared to control. Testosterone levels significantly increased by broccoli (300 mg/kg) compared to control and caraway (300 mg/kg). The serum and testicular SOD and CAT activity significantly increased by broccoli (300 mg/kg) compared to other groups (p < 0.05). MDA and DNA fragmentation levels significantly increased by caraway (200 and 300 mg/kg) compared to others (p < 0.01). It can be concluded that broccoli extract in a dose-dependent manner than caraway extract could improve serum and testes oxidative biomarkers, testicular structure and function, and sperm quality before and after cryopreservation.

The combination of ginger powder and zinc supplement improves the fructose-induced metabolic syndrome in rats by modulating the hepatic expression of NF-κB, mTORC1, PPAR-α SREBP-1c, and Nrf2.

Although studies have shown that ginger, as an herbal remedy and zinc are able to improve inflammation, oxidative stress, autophagy, and metabolism of lipid and glucose, their molecular mechanisms are unknown. Therefore, this study was aimed to examine the therapeutic effects of ginger with zinc supplement for eight weeks on fructose-induced metabolic syndrome (MS). Ninety-six adult male Sprague Dawley rats (220 g ± 20) were randomly assigned to twelve controlled and treated groups. After the last treatment session, the level of lipid profiles, glucose, insulin, and leptin as metabolic factors and liver enzymes as biomarkers to evaluate liver function in serum were measured. The level of antioxidant enzymes and lipid peroxidation to evaluate the oxidative status and the TNF-α level as a biomarker to assess the state of inflammation in liver were also measured. The level of zinc along with the expression of NF-κB, mTORC1, PPAR-α, SREBP-1c, and Nrf2 in liver was also evaluated. The level of metabolic factors and liver enzymes in serum along with lipid peroxidation and TNF-α in liver increased; zinc and antioxidant enzymes levels decreased in rats with MS compared to control rats (p < .05). The hepatic expression of SREBP-1c, NF-κB and mTORC1 were upregulated and the expression of PPAR-α and Nrf2 were downregulated in rats with MS compared to control rats (p < .05). Treatment with different doses of ginger, zinc, and the combination of them could improve metabolic, inflammatory oxidative stress factors, and expression of the above genes in rats with MS compared to the MS group (p < .05). It can be concluded that ginger, zinc, and the combination of them could improve oxidative damage, inflammation, and autophagy induced by fructose and could adjust the glucose and lipid metabolism and the homeostasis of zinc in rats with MS. PRACTICAL APPLICATIONS: Due to the increasing prevalence of metabolic diseases, the use of plant compounds such as ginger has attracted widespread attention. Ginger as an herbal remedy with predominant pharmacological properties due to its availability, cheapness, and lack of side effects is also very popular for the treatment of metabolic disorders in folk medicine. Moreover, enhancing its medicinal properties with supplements such as zinc can be widely welcomed. This study was actually performed with the aim of investigating the effects of ginger + zinc supplement on MS. The results showed that the ginger + zinc supplement could improve oxidative damage, inflammation, and autophagy caused by fructose and adjust the glucose and lipid metabolism and the homeostasis of zinc in rats with MS. The results of this study support the hypothesis that ginger can be used as a very suitable option for the production of medicinal supplements to maintain human health.

Ginger (Zingiber officinale Roscoe) Improves Ethanol-Induced Reproductive Dysfunction by Enhancing Steroidogenesis and Inhibiting Oxidative Stress and Inflammation

Abstract Ginger is traditionally used as a sexual enhancer in folk medicine. Despite extensive studies on the effect of ginger on reproduction, the molecular mechanism of ginger prevention effect on ethanol-induced reproductive disorder is not fully understood. Twenty-four adult male ratswereallocated into control, ethanol (4 g/kg of body weight (BW)/day), ginger (250 mg/kg of BW/day) and ginger-ethanol group. Ginger and ethanol were administrated by gavage for 28 days. Testicular concentration of testosterone, TNF-α, and antioxidant enzymes activity and serum concentration of gonadotropins hormone and testosterone were measured. The gene expression of Nrf2 and NF-κB which regulate oxidative damage and inflammation, respectively, and StAR, P450scc and 17βHSD which are involved in testosterone synthesis were detected. Ethanol significantly decreased gonadotropin hormones, oxidative markers, expression of genes involved in testosterone synthesis and Nrf2, and in reverse significantly increased TNF-α, MDA and gene expression of NF-κB compared to control (p<0.05). While ginger could significantly improve all of the above factors compared to the ethanol group (p<0.05). These results were also supported by histological findings. It can be concluded that ginger prevents the ethanol-induced reproductive dysfunction by improving the gonadotropins, oxidative damage and inflammation and the genes involved in testosterone synthesis.