Clinical efficacy and safety of okra (Abelmoschus esculentus (L.) Moench) in type 2 diabetic patients: a randomized, double-blind, placebo-controlled, clinical trial.

AIMS: The recent trend toward the use of natural functional and medical supplements has motivated the focus on the search and revival of traditional medicinal plant applications for many years. As a valuable dietary crop, okra fruit (Abelmoschus esculentus (L.) Moench) has been used for thousands of years as a medicinal food. This clinical trial aimed to assess the efficacy and safety of the okra pod capsule as an adjuvant treatment in controlling type 2 diabetes mellitus and provide clinical trial-based evidence about its anti-inflammatory effects. METHODS: A total of 100 type II diabetic patients, aged between 40 and 60 years, were randomly assigned into two groups of okra and placebo. The first group was administered 1000 mg of powdered okra fruit three times a day for 3 months, while the other group received a placebo capsule with the same dosage. Both groups continued the standard antidiabetic therapy (consisting of metformin and gliclazide, as well as a nutritional regimen). At the start and three months later, various factors were measured, including FBG, insulin, HbA1c, cholesterol, triglycerides, HDL, LDL, CRP, liver and renal function tests, blood pressure, and BMI changes. RESULTS: According to the results, patients who received okra treatment exhibited a significant decrease in FBG, HbA1c, total cholesterol, and triglyceride levels when compared to both the baseline and the placebo group. Patients in the okra group have lower levels of hs-CRP compared with the placebo group after 3 months of treatment. No liver, kidney, and blood pressure or other side effects were observed in the groups associated with okra treatment. CONCLUSIONS: The present study demonstrated that adjunctive consumption of okra, in type 2 diabetic patients with 1000 mg three times a day for three months, improves lipid profile, glycemic control, and chronic inflammation without any tangible adverse effects. CLINICAL TRIAL REGISTRY: IRCT.Ir (IRCT20120112008712N2). https://www.irct.ir/trial/42042 .

Synergistic effects of combined therapy with cerebrolysin and enriched environment on anxiety-like behavior and spatial cognitive deficits in posttraumatic stress disorder-like mouse model.

Posttraumatic stress disorder (PTSD) is a serious neuropsychiatric disorder that occurs after exposure to stressful, fearful, or troubling events. Cerebrolysin (CBL), consists of low molecular weights neurotrophic factors and amino acids obtained from purified porcine brain proteins. This study aimed to evaluate the possible therapeutic effects of enriched environment (EE) and CBL alone or combined for reducing anxiety and cognitive deficits in PTSD-like mouse models. For this purpose, inescapable electric foot shocks were delivered to Balb/c mice for two consecutive days. Then mice were treated with CBL (2.5 mL/kg) and/or were kept in EE (2 h per day) or received their combination for 14 consecutive days. The hole-board test and Lashley III paradigm were used to assess anxiety and spatial learning and memory, respectively. Changes in the serum corticosterone level and expression of synaptic elements, including; growth-associated protein 43, post-synaptic density 95, and synaptophysin were assessed in the hippocampus. This model caused anxiety and spatial memory impairment associated with increased serum corticosterone levels and decreased synaptic elements. Nevertheless, CBL and/or combination treatment could reverse behavioral and molecular alterations. Our findings indicated that CBL, separately or in combination with EE, is effective in reducing anxiety and spatial memory impairment in PTSD-like mice.

Health-promoting properties of Saccharomyces cerevisiae var. boulardii as a probiotic; characteristics, isolation, and applications in dairy products.

Saccharomyces cerevisiae var. boulardii (S. boulardii) has been isolated from lychee (Litchi chinensis), mangosteen fruit, kombucha, and dairy products like kefir. Dairy products containing S. boulardii have been revealed to possess potential probiotic activities owing to their ability to produce organic acids, essential enzymes, vitamins, and other important metabolites such as vanillic acid, phenyl ethyl alcohol, and erythromycin. S. boulardii has a wide spectrum of anti-carcinogenic, antibacterial antiviral, and antioxidant activity, and is known to reduce serum cholesterol levels. However, this yeast has mainly been prescribed for prophylaxis treatment of gastrointestinal infectious diseases, and stimulating the immune system in a number of commercially available products. The present comprehensive review article reviews the properties of S. boulardii related to their use in fermented dairy foods as a probiotic microorganism or starter culture. Technical aspects regarding the integration of this yeast into the dairy foods matrix its health advantages, therapeutic functions, microencapsulation, and viability in harsh conditions, and safety aspects are highlighted.

Coenzyme Q10 ameliorates aging-induced memory deficits via modulation of apoptosis, oxidative stress, and mitophagy in aged rats.

The behavioral effects and molecular signaling mechanisms of Coenzyme Q10 (Q10) in age-related memory impairment are poorly understood. This study aimed to investigate the effects of Q10 on memory impairment, oxidative stress, apoptosis, and mitophagy in aged rats. 40 aged (24 months old) and 10 young (3 months old) male Wistar rats were randomly divided into the following groups (n = 10/group): young + vehicle, aged + vehicle, and aged + Q10 (at 100, 200, 300 mg/kg/day doses). Treatments were administrated orally by gavage for 2 weeks. The novel object recognition test was used to assess episodic memory. Oxidative stress, apoptosis, and mitophagy-related protein expressions were measured in the hippocampus. We found that Q10 reversed aging-induced memory impairment at the dose of 300 mg/kg. Moreover, aging was associated with a reduction in ATP production, decrease in mitophagy-related proteins (PINK, Parkin, and P62 levels and LC3II/I ratio), excessive generation of reactive oxygen species and lipid peroxidation, and apoptosis in the hippocampus, which were partially reversed following oral administration of Q10. These findings indicate the therapeutic potential of Q10 in aging-induced memory decline.

Topical Administration of Teucrium polium on Diabetic Foot Ulcers Accelerates Healing: A Placebo-Controlled Randomized Clinical Study.

Diabetic foot ulcer is one of the most devastating complications of uncontrolled diabetes. Although there have been advances in the management of diabetic foot ulcers, still diabetic foot ulcers are a major cause of many amputations in diabetic patients. Teucrium polium (T. polium) is widely used by folk medicine practitioners in Iran for the treatment of diabetic ulcers.The present study was designed to evaluate the safety and efficacy of topical T. polium ointment besides the standard treatment in diabetic foot ulcers.A total of 70 diabetic patients with foot ulcers grade 1 or 2 according to Wagner's scale were enrolled in this study. Patients were randomly divided into two groups. Patients in both groups received standard treatment for diabetic foot ulcers. In addition, group 1 received topical T. polium ointment, and group 2 received topical placebo ointment for 4 weeks. The T. polium and placebo ointments were rubbed twice daily two hours before the conventional dressing. The ulcer size, healing time, and laboratory tests were measured in both groups at baseline and end of the study after 4 weeks.Twenty-nine patients remained in the T. polium group and 26 in the placebo group until the end of the study. The mean surface area of ulcers was 3.52 ± 1.47 and 3.21 ± 1.67 cm2 in T. polium group and placebo group respectively at baseline which decrease to .717 ± .19 and 1.63 ± .72 cm2 respectively at the endpoint. The mean ulcer surface area was significantly lower in T. polium compared with the placebo group (p < .0001) at end of the study. Also, the number of patients that completely recovered in the T. polium group was significantly higher than the placebo group (p < .001) at the end of the study.The addition of topical T. polium ointment to standard treatment significantly improves the healing time of diabetic non-infected foot ulcers.

Sericin Alleviates Thermal Stress Induced Anxiety-Like Behavior and Cognitive Impairment Through Regulation of Oxidative Stress, Apoptosis, and Heat-Shock Protein-70 in the Hippocampus.

Exposure to heat stress (HS) has adverse effects on brain function, leading to anxiety-like behavior and memory impairment. Sericin is a silk derived protein with various neurobiological activities. The present study has investigated the effects of sericin on anxiety and cognitive impairments, in HS-received mice. The adult male mice were exposed to HS (43 ºC, 15 min once a day for 14 days) and simultaneously treated with 100, 150, and 200 mg/kg/day of sericin through oral gavage. Elevated plus-maze and Lashley III Maze tests were used to evaluate anxiety and learning and memory, respectively. The hippocampal BAX, BCL-2, caspase3, caspase9 and heat-shock protein-70 (HSP-70) were evaluated by western blotting and oxidative stress markers including malondialdehyde (MDA), total antioxidant capacity (TAC), super oxide dismutase (SOD) as well as glutathione peroxidase (GPx) were evaluated by spectroscopy method. The serum was collected for the analysis of the corticosterone levels. Treatment with sericin in higher doses reversed anxiety-like behavior and cognitive deficit induced by HS. Moreover, heat exposure increased serum corticosterone, hippocampal MDA, apoptotic proteins and HSP-70 levels. Sericin administration decreased serum corticosterone and enhanced hippocampal antioxidant defense and attenuated apoptosis and HSP-70 levels. The results show that the protective effects of sericin against HS-mediated cognitive dysfunction and anxiety-like behavior is possibly through suppressing HSP-70, oxidative stress and apoptosis.

Effects of Intravenous Lipid Emulsion on Tramadol-Induced Seizure; a Randomized Clinical Trial.

INTRODUCTION: There are numerous studies on the efficacy of intralipid emulsion (ILE) in various xenobiotic toxicities. This study aimed to evaluate the potential role of ILE as an antidote in tramadol-induced seizure. METHODS: A single-blind clinical trial was undertaken to establish the efficacy and safety of ILE in patients with acute tramadol intoxication, who referred to Booali Hospital in Qazvin. Patients were randomly assigned to 2 groups. The Control group received standard care while the intervention group received intralipid emulsion (ILE) 20% in addition to the standard care. The occurrence of in-hospital seizure was compared between the groups. RESULTS: 80 patients who abused tramadol and met the study criteria were randomly assigned to either the intervention (40 cases) or the control (40 cases) group. Seizure occurred in 44 (56%) patients before admission to the emergency department. There were not any statistical differences between the groups regarding sex distribution (p=0.513) and mean age (p=0.19), presenting vital signs (p < 0.05), laboratory findings (p < 0.05), and mean abused dose of tramadol (p = 0.472) as well as occurrence of prehospital seizure (p = 0.7). In-hospital seizure occurred in 15 (18.75%) cases (all in the control group; p < 0.001). The mean duration of admission was 2.01 ± 1.13 days in the control group and 2.15 ± 1.04 days in the intervention group (p = 0.6). The number needed to treat for ILE to prevent tramadol-induced seizure was 2.7 (37.5% absolute risk reduction). CONCLUSIONS: The findings of this study supported ILE administration, as an adjunct to standard antidote protocols, in tramadol intoxication to prevent tramadol-induced seizures.

Association between Neutrophil-to-Lymphocyte Ratio and the Systemic Inflammatory Immunologic Index and the Angiographic SYNTAX Score and the TIMI Flow Grade in Acute STEMI: A Cohort Study.

Background: In patients with ST-segment-elevation myocardial infarction (STEMI), it is essential to determine the complexity of coronary lesions on presentation and predict the risk of no-reflow after primary percutaneous coronary intervention (pPCI). Given that inflammation plays an important role in the pathogenesis of atherosclerosis, using inflammatory indices might be helpful in this setting. Methods: This prospective cohort study recruited 200 consecutive patients with STEMI who underwent pPCI. The presentation neutrophil-to-lymphocyte-ratio (NLR) and the systemic inflammatory immunologic index (SII), calculated using the formula platelets × neutrophils/lymphocytes, were recorded. Study outcomes included the SYNTAX score and the TIMI flow grade before and after pPCI. The associations between the NLR and the SII and the study outcomes were investigated using univariate and multivariate logistic regression analyses. Results: Among 200 patients at a mean age of 59.85±11.23 years, 160 (80.0%) were male and 40 (20.0%) were female. The NLR and SII values were not statistically different between the 3 SYNTAX subgroups. While the mean NLR and SII values were similar between the patients with preprocedural TIMI flow grades 0/1 and 2/3, the mean NLR and SII were significantly lower in the group with a postprocedural TIMI flow grade 3. After adjustments for age and sex, the NLR and the SII were independent predictors of postprocedural no-reflow. Conclusion: In patients with STEMI, the presentation NLR and SII are useful for predicting the risk of no-reflow after pPCI. However, the NLR and the SII are not predictors of the SYNTAX score and the preprocedural TIMI flow grade.

A closer look at the role of insulin for the regulation of male reproductive function.

While insulin demonstrates to have a considerable influence on the reproductive system, there are various unanswered questions regarding its precise sites, mechanisms of action, and roles for the developing and functioning of the adult male reproductive system. Apart from its effects on glucose level, insulin has an important role in the reproductive system directly by binding on insulin and IGF receptors in the brain and testis. To date, however, the effect of insulin or its alterations on blood-testis-barrier, as an important regulator of normal spermatogenesis and fertility, has not yet been studied. This review aimed to focus on the experimental and clinical studies to describe mechanisms by which insulin affects the hypothalamic-pituitary-gonadal (HPG) axis, testicular cells, spermatozoa, and sexual behavior. Moreover, we discussed the mechanism and impact of insulin changes in type 1 (insulin deficiency along with persisted or even increased sensitivity) and 2 (insulin resistance along with increased insulin level at the early stages of disease) diabetes and obesity on the male reproductive tract.

A Randomized, Triple-Blind, Placebo-Controlled, Add-On Clinical Trial to Evaluate the Efficacy of Emblica officinalis in Uncontrolled Hypertension.

Introduction. Emblica officinalis (EO) has some cardiovascular effects, and there are some animal studies that show its antihypertensive effect. This study was conducted to determine the effect of combination of EO with standard therapy on the systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with uncontrolled hypertension. Materials and Methods. This was a randomized, triple-blind, placebo-controlled, 8-week study. Ninety-two patients with uncontrolled hypertension despite taking hypotensive drugs were randomly assigned into two groups to take EO (500 mg/TDS after meal) or placebo in combination with standard antihypertensive drugs. After 2, 4, 6, and 8 weeks of intervention, SBP and DBP and heart rate (HR) were measured. Data were analyzed by SPSS software using repeated measures ANOVA. Results. Eighty-one patients (41 in the drug group and 40 in the placebo group) completed the study for 8 weeks and were analyzed. The mean ± standard deviation of age was 53.64 ± 10.01 years. SBP decreased as 15.6 ± 8.23% in the EO group and 6.3 ± 7.49% in the placebo group (P < 0.001). DBP decreased as 12.3 ± 7.87% and 3.88 ± 7.98%, respectively (P < 0.001). Time effect was not significant, but the group effect was significant (F = 13.875, P=0.001 for systolic BP and F = 18.948, P < 0.001 for diastolic BP). No side effects were reported during the study. Conclusion. Eight-week combination therapy of EO with standard antihypertensive drugs significantly reduced the SBP and DBP more than placebo in patients with uncontrolled hypertension.

The role of hippocampal GABAA receptors on anxiolytic effects of Echium amoenum extract in a mice model of restraint stress.

Echium amoenum (EA), a popular medicinal plant in Persian medicine, has anxiolytic, antioxidant, sedative, and anti-inflammatory effects. This study examined whether GABA-ergic signaling is involved in the anxiolytic effects of EA in mice. Sixty BALB/c mice (25-30 g) were divided into six groups (n = 10) as follows: the (I) control group received 10 ml/kg normal saline (NS). In the stress groups, the animals underwent 14 consecutive days of restraint stress (RS), and received following treatments simultaneously; (II) RS + NS; (III) RS + Diaz (Diazepam); (IV) RS + EA; (V) RS + Flu (Flumazenil) + EA; (VI) RS + Flu + Diaz. Behavioral tests including the open field test (OFT) and elevated plus maze (EPM) were performed to evaluate anxiety-like behaviors and the effects of the regimens. The plasma level of corticosterone and the hippocampal protein expressions of IL-1ß, TNF-α, CREB, and BDNF, as well as p-GABAA/GABAA ratio, were also assessed. The findings revealed that chronic administration of EA alone produced anxiolytic effects in both behavioral tests, while diazepam alone or in combination with Flu failed to decrease the anxiety-like behaviors. Furthermore, the p-GABAA/GABAA and p-CREB/CREB ratios, and protein levels of BDNF were significantly increased in the EA-received group. On the other hand, plasma corticosterone levels and the hippocampal IL-1ß and TNF-α levels were significantly decreased by EA. However, pre-treatment with GABAA receptors (GABAA Rs) antagonist, Flu, reversed the anxiolytic and molecular effects of EA in the RS-subjected animals. Our findings confirmed that alternation of GABAAR is involved in the effects of EA against RS-induced anxiety-like behaviors, HPA axis activation, and neuroinflammation.

Serotonergic system modulation holds promise for L-DOPA-induced dyskinesias in hemiparkinsonian rats: A systematic review.

The alleged effects of serotonergic agents in alleviating levodopa-induced dyskinesias (LIDs) in parkinsonian patients are debatable. To this end, we systematically reviewed the serotonergic agents used for the treatment of LIDs in a 6-hydroxydopamine model of Parkinson's disease in rats. We searched MEDLINE via PubMed, Embase, Google Scholar, and Proquest for entries no later than March 2018, and restricted the search to publications on serotonergic agents used for the treatment of LIDs in hemiparkinsonian rats. The initial search yielded 447 citations, of which 49 articles and one conference paper met our inclusion criteria. The results revealed ten different categories of serotonergic agents, including but not limited to 5-HT1A/BR agonists, 5-HT2AR antagonists, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitor (SNRIs), and tricyclic antidepressants (TCAs), all of which improved LIDs without imposing considerable adverse effects. Although there is promising evidence regarding the role of these agents in relieving LIDs in hemiparkinsonian rats, further studies are needed for the enlightenment of hidden aspect of these molecules in terms of mechanisms and outcomes. Given this, improving the quality of the pre-clinical studies and designing appropriate clinical trials will help fill the bench-to-bedside gap.

Oxidized cholesterol exacerbates toll-like receptor 4 expression and activity in the hearts of rats with myocardial infarction.

Introduction: The present study examined the effects of high cholesterol and high oxidized-cholesterol diets on the myocardial expression of TLR4 and pro-inflammatory cytokine in rats. Methods: Male Wistar rats were allocated into 6 groups and fed with a normal diet, cholesterol, and oxidized-cholesterol rich diets with or without isoproterenol-induced myocardial infarction. TLR4 and MyD 88 expression and levels tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were measured in the heart and serum. Results: Oxidized cholesterol-fed animals had higher serum levels of oxidized low-density lipoprotein (LDL) (263 ± 13 ng/dL) than the cholesterol-fed animals (98 ± 8 ng/dL; P < 0.001). A high level of oxidized-LDL caused fibrotic cell formation and enhanced neutrophil infiltration in the absence of MI. Both cholesterol and oxidized-cholesterol upregulated TLR4 mRNA expression and increased TNF-α and IL-6 production in the hearts of rats with MI. In rats fed with oxidized-cholesterol the serum and myocardial levels of TNF-α (653 ± 42 pg/mL, 1375 ± 121 pg/100 mg, respectively) were higher than MI group (358±24 pg/mL, P < 0.001 and 885 ± 56 pg/100 mg, P < 0.01). A significant correlation was seen between TLR4 expression and infarct size. Conclusion: These findings suggest that cardiac TLR4 is preferentially upregulated by oxidized cholesterol in rats. Oxidized cholesterol may have a critical role in cardiac toxicity in the absence of pathological conditions.

Topical Application of Teucrium polium Can Improve Wound Healing in Diabetic Rats.

Diabetic foot ulcer is one of the major complications among diabetic patients. Several studies have shown that the extract of Teucrium polium (T. polium) is effective in the treatment of diabetic and non-diabetic wounds, as well as burn wounds. The aim of current study was to assess the wound healing activity of T. polium extract ointment in diabetic rats. Sixty-four male Wistar rats were induced diabetes with alloxan injection (125 mg/kg) and surgical wound induced. The rats were divided into 8 groups of eight rats each: control group, eucerin group, phenytoin group, 2%, 3%, 4%, 5% and 10% T. polium groups. The ointment was dressed on the wound twice a day. The process of wound healing was screened by macroscopy and digitalization on days 14 and 21 and until complete wound healing. There was no infection in the wounds of rats in any groups. The process of wounds healing of the 2%, 3%, 4%, 5%, and 10% T. polium ointments, with phenytoin ointment and base ointment (eucerin) on day 14 and 21, showed that the significant difference between the treatment groups with 4% (P = 0.003), 5% (P = 0.001), 10% (P = 0.001) T. polium ointment and phenytoin ointment group (P = 0.001) compared to eucerin group. The results of this study showed that T. polium extract ointment with a 10% ointment accelerates the wound healing process in diabetic rats and is comparable to the phenytoin group.

Polyphenols targeting diabetes via the AMP-activated protein kinase pathway; future approach to drug discovery.

Regarding the widespread progression of diabetes, its related complications and detrimental effects on human health, investigations on this subject seems compulsory. AMP-activated protein kinase (AMPK) is a serine/threonine kinase and a key player in energy metabolism regulation. AMPK is also considered as a prime target for pharmaceutical and therapeutic studies on disorders such as diabetes, metabolic syndrome and obesity, where the body energy homeostasis is imbalanced. Following the activation of AMPK (physiological or pharmacological), a cascade of metabolic events that improve metabolic health is triggered. While there are several publications on this subject, this is the first report that has focused solely on polyphenols targeting diabetes via AMPK pathway. The multiple characteristics of polyphenolic compounds and their favorable influence on diabetes pathogenesis, as well as their intersections with the AMPK signaling pathway, indicate that these compounds have a beneficial effect on the regulation of glucose homeostasis. PPs could potentially occupy a significant position in the future anti-diabetic drug market.

Cardiovascular Complications of Chronic Opium Consumption: A Narrative Review Article.

Opiates are the second most prevalent abused illicit substance after cannabis in the world. The latest United Nations Office on Drugs and Crime (UNODC) report estimated 30% increment in opium cultivation worldwide. High prevalence of opium consumption in eastern countries may be due to the high availability and traditional misconceptions. Opium consumption has been linked to hypertension, diabetes mellitus, dyslipidemia, and coronary artery diseases (CAD). In this review, we will review the association between opium use, cardiovascular diseases, and clinical outcomes. The present evidence suggests that chronic opiate consumption may increase the risk of cardiovascular diseases and related mortality.