Metformin is a widely used drug in today’s prescriptions by physicians due to its specific effects in treating and curing type II diabetes. Diabetes is a common disease that may occur throughout human life, and can increase the likelihood of the occurrence of various types of cancer, such as colon, rectum, pancreas and liver cancers, compared to non-diabetic patients. Metformin inhibits mTOR activity by activating ATM (ataxia telangiectasia mutated) and LKB1 (liver kinase B1) and then adenosine monophosphate-activated kinase (AMPK), and thus prevents protein synthesis and cell growth. Metformin can activate p53 by activating AMPK and thereby ultimately stop the cell cycle. Given the potential of metformin in the treatment of cancer, it can be used in radiotherapy, chemotherapy and to improve the response to treatment in androgen derivatives (ADT), and also, according to available evidence, metformin can also be used to prevent various types of cancers. Generally, metformin can: 1) reduce the incidence of cancers, 2) reduce the mortality from cancers, 3) increase the response to treatment in cancer cells when using radiotherapy and chemotherapy, 4) optimize tumor movement and reduce the malignancy, 5) reduce the likelihood of relapse, and 6) reduce the damaging effects of ADT. Therefore, this drug can be used as a complementary therapeutic agent for cancer treatment and prevention. In this review, we have summarized the data from various experimental and clinical studies and highlight the possible potential effects of metformin on cancer therapeutic responses.

Background and objectiveInitial peripheral/central nerve injuries, such as chronic constriction injury (CCI)/spinal cord injury, are often compounded by secondary mechanisms, including inflammation and oxidative stress, which may lead to chronic neuropathic pain characterized by hyperalgesia or allodynia. On the other hand, exercise as a behavioral and non-pharmacological treatment has been shown to alleviate chronic neuropathic pain. Therefore, this study was conducted to examine whether or not exercise reduces neuropathic pain through modifying oxidative stress and inflammation in chronic constriction injury of the sciatic nerve.Materials and methodsWistar male rats weighing 200±20 g were randomly divided into five groups (normal, sham, CCI, pre-CCI exercise, and post-CCI exercise group). Sciatic nerve of anesthetized rats was loosely ligated to induce CCI, and they were then housed in separate cages. The rats ran on treadmill at a moderate speed for 3 weeks. Mechanical allodynia and thermal hyperalgesia were determined using von Frey filament and plantar test, respectively. Tumor necrosis factor-alpha (TNF-α) assayed in the cerebrospinal fluid, malondialdehyde, and total antioxidant capacity were measured in the serum using Western blot test, thiobarbituric acid, and ferric reducing ability of plasma (FRAP), respectively.ResultsThe mechanical allodynia (P=0.024) and thermal hyperalgesia (P=0.002) in the CCI group were higher than those in the sham group. Exercise after CCI reduced (P=0.004) mechanical allodynia and thermal hyperalgesia (P=0.025) compared with the CCI group. Moreover, the level of FRAP in the CCI group was (P=0.001) lower than that in the sham group, and post-CCI exercise reversed FRAP amount toward the control level (P=0.019). The amount of malondialdehyde did not differ between groups. Level of TNF-α increased in the CCI group (P=0.0002) compared with sham group and post-CCI exercise could reverse it toward the level of control (P=0.005).ConclusionPost CCI-exercise but not pre CCI-exercise reduces CCI-induced neuropathic pain. One of the possible involved mechanisms is increasing the total antioxidant capacity and reducing the amount of TNF-α.

ObjectivesLipid peroxidation and hyperglycemia are common signs for diabetes. Natural antioxidants such as Spirulina platensis microalgae (SPM) may prevent lipid peroxidation and hyperglycemia. This study aimed to evaluate the effects of SPM on antioxidant and anti-inflammatory in diabetic rats.Materials and methodsSixty-four rats were divided into eight groups (n=8) and orally treated with 0, 10, 20 and 30 mg/kg body weight of SPM extract. Experimental groups included diabetic rats fed with 0 (DC), 10, 20 and 30 mg/kg SPM. Healthy rats were treated with 0 mg/kg SPM (HC), 10 mg/kg SPM, 20 mg/kg SPM and 30 mg/kg SPM. At the end of the trial, blood samples were collected and the plasma concentrations of trace minerals (TMs), biochemical parameters, and antioxidant enzymes in liver were evaluated. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF-α (tumor necrosis factor-alpha) and IL-6 (interleukin-6) were evaluated.ResultsOur findings showed that diabetes significantly lowered the plasma concentration of TMs and antioxidant enzymes in liver and also increased the levels of malondialdehyde, glucose, lipid profile, AST, ALT, TNF-α and IL-6 (DC vs HC). However, an oral supplement of SPM (20 and 30 mg/kg body weight) lowered levels of malondialdehyde level, glucose, lipid parameters, AST, ALT, TNF-α and IL-6. The same levels increased the plasma contents of zinc, iron, copper and selenium and activity of antioxidant enzymes (P<0.05).ConclusionIt can be concluded that diabetes decreases TM concentration and antioxidant enzymes and also increases lipid profile, glucose, AST, ALT, TNF-α and IL-6 concentrations. Inclusion of SPM supplementing (20 and 30 mg/kg body weight) increased some TMs and antioxidant enzymes. SPM may provide TMs for synthesis of antioxidant enzymes which subsequently reduce lipid profile, glucose concentration and anti-inflammatory responses.

Background and Purpose: Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and abnormalities in insulin production. Apelin is associated with insulin resistance. According to the anti-diabetic properties of curcumin, the purpose of this study was to compare the effects of curcumin and nano-curcumin intake on insulin resistance and serum levels of fasting blood sugar (FBS), Apelin, and lipid profile (cholesterol, triglyceride, LDL, HDL and VLDL) in T2DM rats. Materials and Methods: Forty-eight male Wistar rats were divided into six groups: Control, diabetic, diabetic treated with two doses of curcumin (100 and 200 mg/kg) and diabetic treated with two doses of nano-curcumin (100 and 200 mg/kg). Induction of T2DM was performed by intraperitoneal injection of Nicotinamide (110 mg/kg) and Streptozotocin (45 mg/kg) in the fasting state. Rats received different doses of nano-curcumin and curcumin by gavage (daily) for 28 days. At the end of the intervention period, insulin resistance and serum levels of FBS, apelin and lipid profiles were measured. Results: Insulin resistance and serum levels of FBS, Apelin, cholesterol, triglycerides, LDL, and VLDL were significantly decreased in diabetic rats treated with curcumin and nanocurcumin (p<0.05) so that nano-curcumin in reducing lipid profile is more effective than curcumin (P<0.05). Serum level of HDL in nano-curcumin groups was significantly higher than diabetic and curcumin groups (p<0.05). Also, with increasing insulin resistance, serum level of apelin increased (P<0.05). Conclusion: The therapeutic effects of curcumin and nano-curcumin were effective in decreasing insulin resistance, serum levels of FBS, apelin and lipid profile. The dose of 100 mg/kg nano-curcumin was more effective in reducing lipid profile.

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ObjectivesThis study was conducted to evaluate the effects of oral supplementation of Spirogyra algae on oxidative damages and inflammatory responses in streptozotocin (STZ)-induced diabetic rats.MethodsDiabetes was induced by administration of 55 mg/kg of streptozotocin. A total of sixty-four rats were divided into eight groups of eight rats each as follows:1) non-diabetic control; 2, 3, and 4) non-diabetic rats treated with 15, 30, and 45 mg of Spirogyra algae/kg/d; 5) control diabetic; and 6, 7, and 8) diabetic rats treated with 15, 30, and 45 mg of Spirogyra algae extract. At the end of the trial, the serum concentrations of glucose, interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), malondialdehyde (MDA), glutathione (GSH), total antioxidant status (TAS), C-reactive protein (CRP), insulin, triglycerides, and cholesterol were examined by specified procedures.ResultsOur findings indicated that the administration of STZ significantly increased the serum concentrations of glucose, triglycerides, cholesterol, CRP, IL-6, TNF-a, and MDA and decreased the serum levels of GSH and TAS (P<0.05) in diabetic rats. Oral administration of Spirogyra alleviated adverse effects of diabetes on oxidative stress and inflammatory factors in diabetic rats (P<0.05).ConclusionIt can be stated that Spirogyra algae extract can be used for treatment of diabetes likely due to prevention of oxidative stress and alleviation of inflammation in the rat model.

BackgroundIt is well documented that biologically active components of microalgae can be utilized for treatment of different diseases. This study was conducted to evaluate the antihyperglycemic and antihyperlipidemic activities and weight control of Nannochloropsis oculata microalgae (NOM) in Streptozotocin-induced diabetic male rats.MethodsDiabetes was induced by intraperitoneal administration of Streptozotocin (55 mg/kg). Healthy and diabetic rats were divided in to six groups. Healthy and diabetic rats orally received distilled water or NOM (10 and 20 mg/kg) for three weeks.ResultsOral administration of NOM to diabetic rats significantly reduced the serum concentrations of glucose, cholesterol, triglycerides, LDL and increased the serum concentration of insulin and HDL-C (P<0.05). Treatment with NOM had no significant effect on blood parameters in healthy rats (P>0.05). Also, NOM maintained body weight in diabetic rats (P<0.05).ConclusionIt can be concluded that NOM has antihyperglycemic and antihyperlipidemic activities in diabetic rats.

Objective: The amygdala structural and functional abnormalities have been implicated in numerous neuropsychiatric and neurodevelopmental disorders. Given the important role of the amygdala in stress responses and the susceptibility of the females to adolescent stress, the present study investigated the beneficial effects of Spirulina platensis microalgae (SP) as a neuroprotective supplement against adolescent stress-induced oxidative stress, brainderived neurotrophic factor (BDNF) alterations, molecular and morphological remodeling in the basolateral amygdala (BLA) of adult female rats. Methods: During the adolescent period (PNDs 30-40) rats were subjected to restraint stress (2 h/day for 10 days). Then, the animals were subjected to 15 days treatment (PNDs 41-55) with SP (200 mg/kg/day) followed by biochemical (BDNF and stress oxidative markers), molecular (BDNF and its receptor tropomyosin receptor kinase B [TrkB] mRNA expression), and morphological (dendritic length and spines) assessments in the BLA. Results: The study revealed that adolescent stress decreased BDNF levels and reduced apical dendritic length and branch points of pyramidal neurons in the BLA. In addition, chronic stress significantly increased oxidative stress parameters and decreased BDNF and TrkB mRNA expression in the BLA. Treatment with SP alleviated both biochemical, molecular, and neuroanatomical deficits that induced by adolescent stress. Conclusion: Our findings provide important evidence that SP as a non-pharmacological intervention during adolescent period can protect against chronic stress-induced neuroanatomical biochemical, and molecular deficits in adulthood, and thus, reduce stress-related disorders.