The antidepressant effect of combined extracts of Hypericum perforatum and Echium amoenum supplementation in patients with depression symptoms: A randomized clinical trial.

Objective: Echium amoenum and Hypericum perforatum dried flowers have been used for therapy of mental disorders in Iranian traditional medicine. In this study, we assessed the efficacy of the E. amoenum and H. perforatum extracts in patients with mild to moderate depression. Materials and Methods: In an 8-week double-blind, parallel-group trial, 51 patients randomly consumed 20 mg of fluoxetine or 350 mg of herbal medicine twice daily. The Hamilton Rating Scale for Depression (HAM-D) was used to assess depression severity in patients at weeks 0, 4, and 8. Results: According to the Hamilton score, there were no significant differences between the fluoxetine- and herbal medicine-treated groups after 4 and 8 weeks (p>0.05). Dry mouth was the only reported side effect which was significantly lower in the herbal group (p<0.05) in weeks 2 and 4. Conclusion: E. amoenum and H. perforatum have anti-depressant properties similar to fluoxetine and they can be used to treat depression as an alternative to fluoxetine.

Effects of Folic Acid Supplementation on Liver Enzymes, Lipid Profile, and Insulin Resistance in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial.

Background: Previous evidence revealed an association between folate deficiency and non-alcoholic fatty liver disease (NAFLD). This study is the first one investigating the effects of folic acid on hepatic steatosis grade, liver enzymes, insulin resistance, and lipid profile in NAFLD cases. Materials and Methods: Sixty-six participants with NAFLD were allocated randomly to take either a placebo or one oral tablet of folic acid (1 mg) on a daily basis within eight weeks. Serum folate, homocysteine, glucose, aminotransferases, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and lipids were assessed. Ultrasonography was used for assessing the liver steatosis grade. Results: The serum alanine transaminase, grade of hepatic steatosis, and aspartate transaminase significantly were decreased within both study groups; however, the between-group comparison was not statistically significant. Of note, the decrease in ALT was more pronounced in folic acid compared with the placebo group (-5.45 ± 7.45 vs. -2.19 ± 8.6 IU/L). The serum homocysteine was decreased after receiving folic acid compared to the placebo (-0.58 ± 3.41 vs. +0.4 ± 3.56 µmol/L; adjusted P = 0.054). Other outcomes did not significantly change. Conclusion: Supplementation with folic acid (1 mg/d) for eight weeks among cases with NAFLD did not change significantly the serum levels of liver enzymes, the hepatic steatosis grade, insulin resistance and lipid profile. However, it was able to prevent the increase in homocysteine in comparison with the placebo. Conducting further research is suggested with the longer duration and different doses of folic acid, adjusted to the genotypes of methylenetetrahydrofolate reductase polymorphism, among NAFLD patients.

The effect of Cornus mas fruit extract on vasomotor symptoms and sex hormones in postmenopausal women: a randomized, double-blind, clinical trial.

OBJECTIVES: Cornus mas fruit has various antioxidants and anti-inflammatory properties, so this study aims at assessing its effect on menopausal symptoms and sex hormones in postmenopausal women. METHODS: In the current randomized, double-blind clinical trial, 84 individuals (42 per group) were participated. C mas hydroalcoholic extract was prepared, and participants received 300 mg C mas extract or placebo three times a day (900 g in total) for 8 weeks. The demographic, dietary intake, and physical activity information were gathered. Anthropometric indices were measured by standard methods. Furthermore, menopause symptoms were assessed by Greene Climacteric Scale. Also, sex hormones were measured by enzyme-linked immunosorbent assay. RESULTS: Based on the results, there was a significant difference in total Greene score reduction between the intervention and placebo groups (-3.19 ± 0.54, -0.76 ± 0.32, and P < 0.001). In addition, vasomotor symptoms had a remarkable decrease in the C mas extract group (P < 0.001). Also, the intervention group demonstrated a decreasing trend in the number and duration of hot flushes. Moreover, follicle-stimulating hormone remarkably decreased and estradiol increased in the intervention group (P = 0.016 and P = 0.018). CONCLUSIONS: It has been found that the extract of C mas fruit has a favorable effect on vasomotor symptoms, sex hormones, and related complications in women experiencing menopausal symptoms.

The effects of vitamin B12 supplementation on metabolic profile of patients with non-alcoholic fatty liver disease: a randomized controlled trial.

The present study is the first effort to evaluate the effects of vitamin B12 supplementation on the serum level of liver enzymes, homocysteine, grade of hepatic steatosis, and metabolic profiles in patients with non-alcoholic fatty liver disease (NAFLD). Forty patients with NAFLD were enrolled in a double-blind placebo-controlled trial to receive either one oral tablet of vitamin B12 (1000 µg cyanocobalamin) or a placebo per day for 12 weeks. We investigated serum levels of homocysteine, aminotransferases, fasting blood glucose (FBG), lipids, malondialdehyde (MDA), and homeostasis model assessment of insulin resistance (HOMA-IR). The grade of liver steatosis and fibrosis was measured by real-time 2-dimensional shear wave elastography. Vitamin B12 supplementation significantly decreased serum levels of homocysteine compared to placebo (medians: - 2.1 vs. - 0.003 µmol/l; P = 0.038). Although serum alanine transaminase (ALT) in the vitamin B12 group decreased significantly, this change did not reach a significant level compared to the placebo group (medians: - 7.0 vs. 0.0 IU/l; P > 0.05). Despite the significant within-group decrease in FBG, MDA, and liver steatosis in the vitamin B12 group, between-group comparisons did not reveal any significant difference. Vitamin B12 supplementation might decrease serum levels of homocysteine in patients with NAFLD. The fasting blood glucose and serum levels of MDA were significantly improved in the trial group who received vitamin B12. However, these changes did not reach a significant level compared to the placebo group. In this respect, further studies with larger sample sizes, different doses, and types of vitamin B12 will reveal additional evidence.Trial Registration: At  http://irct.ir/  as IRCT20120718010333N5 on December 25, 2019.

Morus Alba leaf extract affects metabolic profiles, biomarkers inflammation and oxidative stress in patients with type 2 diabetes mellitus: A double-blind clinical trial.

INTRODUCTION: Morus Alba extract, despite its special properties, has been less studied in terms of its effects on metabolic profiles in patients with type 2 diabetes mellitus (T2DM). This study was carried out to determine the effects of Morus Alba extract, known as white mulberry, on liver enzymes, biomarkers of inflammation and oxidative stress, insulin metabolism and lipid profiles in patients with T2DM. METHODS: The current randomized, double-blind, placebo-controlled trial was conducted among 60 patients with T2DM. Subjects were randomly divided into 2 groups to receive either Morus Alba extract (300 mg) (n = 30) or placebo (n = 30) twice a day. Fasting blood samples were collected at the baseline and 12 weeks after intervention to quantify related markers. RESULTS: Morus Alba extract intake significantly decreased insulin (P = 0.026) and malondialdehyde (MDA) (P < 0.001), and significantly increased HDL-cholesterol concentrations (P = 0.001) compared with the placebo. However, Morus Alba extract intake did not affect other metabolic profiles. CONCLUSIONS: The results of this study shown that the 12-week administration of Morus Alba extract among subjects with T2DM had beneficial effects on HDL-cholesterol, insulin and MDA levels, but did not affect other metabolic profiles. The present study was registered in the Iranian website for clinical trials as http://www.irct.ir: IRCT2016081312438N21.

Higher Intake of Dietary Magnesium Is Inversely Associated With COVID-19 Severity and Symptoms in Hospitalized Patients: A Cross-Sectional Study.

Background and Aims: Magnesium is an anti-inflammatory mineral that plays a role in the innate immune system, and the relaxation of bronchial smooth muscle warrants additional attention in COVID-19. This study examined the association between magnesium intake and COVID-19 severity and related symptoms in hospitalized patients. Methods: A cross-sectional study was done enrolling 250 COVID-19 patients aged 18 to 65 years. A validated 168-item online food frequency questionnaire (FFQ) was used to assess dietary magnesium intake. COVID-19 Treatment Guidelines were used to determine COVID-19 severity, and symptoms were evaluated using a standard questionnaire. Crude and adjusted analyses were performed (Model 1: age, sex, and energy intake; Model 2: Model 1 + physical activity, supplements, corticosteroids, and antiviral drugs; Model 3: Model 2 + body mass index). Results: The mean age of participants was 44.1 ± 12.1 years, and 46% of them had severe COVID-19. Patients at the highest tertile of dietary magnesium intake had lower serum levels of inflammatory biomarkers, including CRP (11.8 ± 2.2 vs. 29.5 ± 2.1 mg/L, p < 0.001) and ESR (15.8 ± 2.4 vs. 34.7 ± 2.4 mm/hr, p < 0.001), than those at the lowest tertile. After controlling for potential confounders, we observed that a higher dietary magnesium intake was associated with a lower odds of severe COVID-19 (OR: 0.32; 95% CI: 0.15-0.70). Also, we found a significant inverse association between dietary magnesium intake and odds of COVID-19 symptoms. Conclusion: We found that higher intake of dietary magnesium was inversely associated with COVID-19 severity and symptoms.

The effects of selenium plus probiotics supplementation on glycemic status and serum lipoproteins in patients with gestational diabetes mellitus: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: The aim of the current study was to determine the effects of probiotic plus selenium supplementation on glycemic control and lipid profils in patients with gestational diabetes mellitus (GDM). METHODS: This randomized, double blind, placebo-controlled clinical trial was conducted among 60 patients with GDM. Participants were randomly allocated into 2 groups to intake either placebo (n = 30) or probiotic (8 × 109 CFU/day) plus 200 µg/day selenium (n = 30) for 6 weeks. RESULTS: Selenium plus probiotic supplementation significantly reduced fasting glucose (-4.5 ± 5.8 vs. -1.2 ± 4.3 mg/dL, P = 0.004), insulin concentrations (-1.4 ± 1.7 vs. -0.2 ± 1.1 µIU/mL, P = 0.002) and insulin resistance (-0.4 ± 0.5 vs. -0.1 ± 0.3, P = 0.001), and significantly increased insulin sensitivity (+0.008 ± 0.009 vs. +0.001 ± 0.006, P = 0.002) compared with the placebo. Co-supplementation also significantly decreased triglycerides (-16.6 ± 44.4 vs. +14.9 ± 26.4 mg/dL, P = 0.005), total cholesterol (-24.2 ± 29.2 vs. +4.5 ± 18.7 mg/dL, P = 0.001), and low-density lipoprotein (LDL)-cholesterol (-20.8 ± 30.8 vs. -0.2 ± 16.8 mg/dL, P = 0.006) compared with the placebo. Moreover, co-supplementation increased gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.003) and LDL-receptor (P = 0.001) in the peripheral blood mono-nuclear cells of the participants with GDM. CONCLUSIONS: Probiotic plus selenium supplementation to patients with GDM for six weeks had beneficial effects on glycemic status, lipid profiles, and PPAR-γ and LDLR expression. However, high-density lipoprotein-cholesterol levels were not significantly changed.

The effect of Cornus mas extract consumption on bone biomarkers and inflammation in postmenopausal women: A randomized clinical trial.

The drastic decrease in estrogen levels in menopausal women can elevate bone resorption and osteoporosis. Cornus mas extract (C. mas extract) is a potential candidate for treating menopausal-related bone complications because of its phytoestrogen and anti-inflammatory contents. It was an interventional double-blind placebo-controlled randomized study. Eighty-four women aged 45-60 years old were randomly allocated to either the extract group receiving 3 capsules of 300 mg C. mas extract or the placebo group receiving 3 capsules of 300 mg of starch powder per day for 8 weeks. Then, venous blood was used to measure bone-specific alkaline phosphatase (BAP), osteocalcin (OC), C-terminal telopeptide (TC) as well as serum levels of PTH and hsCRP. Our results indicated the decrease in alkaline phosphatase, PTH, and as an inflammation biomarker, hsCRP, between two groups at the end of the study. No statistically significant difference was observed in telopeptide C, osteocalcin, and calcium between the placebo and extract groups after 8 weeks of intervention. In conclusion, the results indicate that the C. mas extract supplement of 900 mg/day may decrease levels of BAP, PTH, and hsCRP. However, this intervention had no beneficial effect on OC and TC in healthy postmenopausal women.

An Update on the Effects of Probiotics on Gastrointestinal Cancers.

Because of their increasing prevalence, gastrointestinal (GI) cancers are regarded as an important global health challenge. Microorganisms residing in the human GI tract, termed gut microbiota, encompass a large number of living organisms. The role of the gut in the regulation of the gut-mediated immune responses, metabolism, absorption of micro- and macro-nutrients and essential vitamins, and short-chain fatty acid production, and resistance to pathogens has been extensively investigated. In the past few decades, it has been shown that microbiota imbalance is associated with the susceptibility to various chronic disorders, such as obesity, irritable bowel syndrome, inflammatory bowel disease, asthma, rheumatoid arthritis, psychiatric disorders, and various types of cancer. Emerging evidence has shown that oral administration of various strains of probiotics can protect against cancer development. Furthermore, clinical investigations suggest that probiotic administration in cancer patients decreases the incidence of postoperative inflammation. The present review addresses the efficacy and underlying mechanisms of action of probiotics against GI cancers. The safety of the most commercial probiotic strains has been confirmed, and therefore these strains can be used as adjuvant or neo-adjuvant treatments for cancer prevention and improving the efficacy of therapeutic strategies. Nevertheless, well-designed clinical studies are still needed for a better understanding of the properties and mechanisms of action of probiotic strains in mitigating GI cancer development.

Neuroprotective effects of probiotics bacteria on animal model of Parkinson's disease induced by 6-hydroxydopamine: A behavioral, biochemical, and histological study.

Parkinson's disease (PD) is an age-associated, progressive, and common neurodegenerative disorder. It is characterized by dopaminergic neuron degeneration in the substantia nigra pars compacta. The involvement of oxidative stress, inflammation, and dysbiosis in PD has been confirmed and probiotics also have the ability to regulate the mentioned mechanisms. Here, we assessed probiotics supplementation effects on experimental model of PD. Thirty Male Wistar rats were divided into three groups for a 14-day treatment. It was shown that a mixture of probiotics containing Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus reuteri, and Lactobacillus fermentum could improve rotational behavior, cognitive function, lipid peroxidation, and neuronal damage in the group received probiotic supplementation compared to the other groups (P < 0001, P < .001, and P = .026, respectively). Taken together, these findings revealed that probiotics supplementation could be an appropriate complementary treatment for PD.

The Effect of Combined Inhalation Aromatherapy with Lemon and Peppermint on Nausea and Vomiting of Pregnancy: A Double-Blind, Randomized Clinical Trial.

BACKGROUND: Nausea and vomiting are almost inevitable features of pregnancy which have a serious impact on the quality of life of pregnant women. This study aimed to determine the effects of combined inhalation aromatherapy with lemon and peppermint on nausea and vomiting of pregnancy. MATERIALS AND METHODS: The parallel randomized clinical trial was conducted on 90 pregnant women suffering from nausea and vomiting of pregnancy referred to health centers in Birjand-Iran- from February 2015 to August 2016. Participants were randomly divided into two groups. The combined lemon and peppermint essential oils were used as an inhaler for the intervention and the placebo for the control group. Both groups were trained to place three drops of the solution onto a cotton ball and keep it in a 3-cm distance of their nose. The intensity of nausea, vomiting and fatigue was assessed through 24-hour Pregnancy Unique Quantization of Emesis (PUQE-24) questionnaire and Fatigue Severity Scale (FSS), respectively. RESULTS: Mean (SD) scores of nausea and vomiting intensity before the intervention and on the first day of intervention were not significantly different between the two groups, but became significant on the second, third, and fourth days of intervention. The results showed that the effect of time on the mean intensity of nausea and vomiting was significant in the aromatherapy group (F2,84 = 22.92, p < 0.001) but was not significant in the placebo group (F2,78 = 0.26, p = 0.836). CONCLUSIONS: The combined lemon and peppermint aromatherapy could reduce mild to moderate intensity of nausea and vomiting during pregnancy.

Nanomicellar-curcumin exerts its therapeutic effects via affecting angiogenesis, apoptosis, and T cells in a mouse model of melanoma lung metastasis.

BACKGROUND: Curcumin is a natural phytochemical polyphenol with significant anti-cancer effects and negligible side effects. In this study, the therapeutic capacity of nanomicellar-curcumin for treating lung metastasis was evaluated in an immunocompetent mouse model of metastatic melanoma. MARTIALS AND METHODS: Two doses of nanomicellar-curcumin (i.e. 10 and 20 µM) were used to induce cytotoxicity in 3 melanoma cell lines. A total of 60 mice were allocated to 20 mice in each of three groups (10 for survival and 10 for assays). Groups were no treatment control, PBS control, nanomicellar-curcumin 20 mg/kg IP 4 times a week, for three weeks). Immunohistochemistry, TUNEL assay, and Western blots were used on lung samples. RESULTS: Nanomicellar-curcumin inhibited the in vitro growth of B16 F10 melanoma cells at 20 µM over 72 h. In vivo, 20 mg/kg nanomicellar-curcumin injected IP, delayed tumor cell growth and significantly extended mouse survival rate. Tumor infiltration of regulatory T cells and angiogenesis were reduced, while IFN-γ and CXCL10 were increased. CONCLUSION: Nanomicellar-curcumin can inhibit lung metastasis and growing melanoma via activation of apoptosis, activated T cells and inhibition of angiogenesis, tumor growth and regulatory T cells.

Combination Therapy with Nanomicellar-Curcumin and Temozolomide for In Vitro Therapy of Glioblastoma Multiforme via Wnt Signaling Pathways.

Glioblastoma (GBM) is the most serious brain tumor and shows a high rate of drug resistance. Wnt signaling is a very important pathway in GBM that can activate/inhibit other pathways, such as apoptosis and autophagy. In this study, we evaluated the efficacy of a combination of temozolomide (TMZ) plus curcumin or nanomicellar-curcumin on the inhibition of GBM growth in vitro, via effects on autophagy, apoptosis, and the Wnt signaling pathway. Two concentrations of curcumin and nanomicellar-curcumin (i.e., 20 µM and 50 µM) alone, and in combination with TMZ (50 µM) were used to induce cytotoxicity in the U87 GBM cell line. Wnt signaling-, autophagy-, and apoptosis-related genes were assessed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blots. All treatments (except 20 µM curcumin alone) significantly decreased the viability of U87 cells compared to controls. Curcumin (50 µM), nanomicellar-curcumin alone and in combination with TMZ significantly decreased the invasion and migration of U87 cells. Autophagy-related proteins (Beclin 1, LC3-I, LC3-II) were significantly increased. Apoptosis-related proteins (Bcl-2 and caspase 8) were also significantly increased, while Bax protein was significantly decreased. The expression levels of Wnt pathway-associated genes (ß-catenin, cyclin D1, Twist, and ZEB1) were significantly reduced.

The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease.

BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (ß - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (ß - 1.37 µIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (ß 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (ß - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (ß 5.13 µmol/L, 95% CI, 1.85, 8.41; P = 0.003) and total antioxidant capacity (TAC) (ß 43.44 mmol/L, 95% CI, 3.39, 83.50; P = 0.03) when compared with placebo. Furthermore, magnesium and zinc significantly reduced the Beck Depression Inventory index (BDI) (ß - 1.66; 95% CI, - 3.32, - 0.009; P = 0.04) and Beck Anxiety Inventory (BAI) (ß - 1.30; 95% CI, - 2.43, - 0.16; P = 0.02) when compared with the placebo. CONCLUSIONS: In patients with T2DM and CHD, the 12-week intake of magnesium plus zinc had beneficial effects on FPG, HDL-cholesterol, CRP, insulin, total nitrite, TAC levels, and BDI and BAI score. This suggests that magnesium and zinc co-supplementation may be beneficial for patients with T2DM and CHD. Further studies on more patients and lasting longer are needed to determine the safety of magnesium and zinc co-supplementation. TRIAL REGISTRATION: Current Controlled Trials http://www.irct.ir: IRCT20130211012438N31 at 11 May 2019 of registration. This study retrospectively registered.

The effects of n-3 fatty acids from flaxseed oil on genetic and metabolic profiles in patients with gestational diabetes mellitus: a randomised, double-blind, placebo-controlled trial.

The present study was performed to evaluate the effects of n-3 fatty acids from flaxseed oil on genetic and metabolic profiles in patients with gestational diabetes mellitus (GDM). This randomised, double-blind, placebo-controlled clinical trial was performed in sixty women with GDM. Participants were randomly divided into two groups to intake either 2 × 1000 mg/d n-3 fatty acids from flaxseed oil containing 400 mg α-linolenic acid in each capsule (n 30) or placebo (n 30) for 6 weeks. n-3 Fatty acid intake up-regulated PPAR-γ (P < 0·001) and LDL receptor (P = 0·004) and down-regulated gene expression of IL-1 (P = 0·002) and TNF-α (P = 0·001) in peripheral blood mononuclear cells of subjects with GDM. In addition, n-3 fatty acid supplementation reduced fasting plasma glucose (P = 0·001), insulin levels (P = 0·001) and insulin resistance (P < 0·001) and increased insulin sensitivity (P = 0·005) when compared with the placebo. Additionally, n-3 fatty acid supplementation was associated with a decrease in TAG (P < 0·001), VLDL-cholesterol (P < 0·001), total cholesterol (P = 0·01) and total cholesterol:HDL-cholesterol ratio (P = 0·01) when compared with placebo. n-3 Fatty acid administration was also associated with a significant reduction in high-sensitivity C-reactive protein (P = 0·006) and malondialdehyde (P < 0·001), and an increase in total nitrite (P < 0·001) and total glutathione levels (P = 0·006) when compared with the placebo. n-3 Fatty acid supplementation for 6 weeks to women with GDM had beneficial effects on gene expression related to insulin, lipid and inflammation, glycaemic control, lipids, inflammatory markers and oxidative stress.

Zinc supplements and bone health: The role of the RANKL-RANK axis as a therapeutic target.

BACKGROUND: To this day, empirical data suggests that zinc has important roles in matrix synthesis, bone turnover, and mineralization and its beneficial effects on bone could be mediated through different mechanisms. The influence of zinc on bone turnover could be facilitated via regulating RANKL/RANK/OPG pathway in bone tissue. Therefore, the aim of the study was to conduct a review to investigate the possible effect of the zinc mediated bone remodeling via RANKL/RANK/OPG pathway. METHODS: A comprehensive systematic search was performed in MEDLINE/PubMed, Cochrane Library, SCOPUS, and Google Scholar to explore the studies investigating the effect of zinc as a bone remodeling factor via RANKL/RANK/OPG pathway regulation. Subsequently, the details of the pathway and the impact of zinc supplements on RANKL/RANK/OPG pathway regulation were discussed. RESULTS: The pathway could play an important role in bone remodeling and any imbalance between RANKL/RANK/OPG components could lead to extreme bone resorption. Although the outcomes of some studies are equivocal, it is evident that zinc possesses protective properties against bone loss by regulating the RANKL/RANK/OPG pathway. There are several experiments where zinc supplementation resulted in upregulation of OPG expression or decreases RANKL level. However, the results of some studies oppose this. CONCLUSION: It is likely that sufficient zinc intake will elicit positive effects on bone health by RANKL/RANK/OPG regulation. Although the outcomes of a few studies are equivocal, it seems that zinc can exert the protective properties against bone loss by suppressing osteoclastogenesis via downregulation of RANKL/RANK. Additionally, there are several experiments where zinc supplementation resulted in upregulation of OPG expression. However, the results of limited studies oppose this. Therefore, aside from the positive role zinc possesses in preserving bone mass, further effects of zinc in RANKL/RANK/OPG system requires further animal/human studies.

The Therapeutic Potential of Quercetin in Parkinson's Disease: Insights into its Molecular and Cellular Regulation.

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder characterized by the progressive death of dopaminergic neurons in the substantia nigra pars compacta (SNc). PD is a multifactorial disorder, with several different factors being suggested to play a synergistic pathophysiological role, including oxidative stress, autophagy, underlying pro-inflammatory events and neurotransmitters abnormalities. Overall, PD can be viewed as the product of a complex interaction of environmental factors acting on a given genetic background. The importance of this subject has gained more attention to discover novel therapies to prevent as well as treat PD. According to previous research, drugs used to treat PD have indicated significant limitations. Therefore, the role of flavonoids has been extensively studied in PD treatment. Quercetin, a plant flavonol from the flavonoid group, has been considered as a supplemental therapy for PD. Quercetin has pharmacological functions in PD by controlling different molecular pathways. Although few studies intended to evaluate the basis for the use of quercetin in the context of PD have been conducted so far, at present, there is very little evidence available addressing the underlying mechanisms of action. Various principal aspects of these treatment procedures remain unknown. Here, currently existing knowledge supporting the use of quercetin for the clinical management of PD has been reviewed.