The Role of Chemokines in Cardiovascular Diseases and the Therapeutic Effect of Curcumin on CXCL8 and CCL2 as Pathological Chemokines in Atherosclerosis.

Curcumin, as a vegetative flavonoid, has a protective and therapeutic role in various adverse states such as oxidative stress and inflammation. Remedial properties of this component have been reported in the different chronic diseases including cancers (myeloma, pancreatic, breast, colorectal), vitiligo, psoriasis, neuropathic pains, inflammatory disorders (osteoarthritis, uveitis, ulcerative colitis, Alzheimer), cardiovascular conditions, and diabetes.Cardiovascular disorders include atherosclerosis and various manifestations of atherosclerosis such as stroke, and myocardial infarction (MI) is the leading cause of mortality globally. Studies have shown varying expressions of inflammatory and non-inflammatory chemokines and chemokine receptors in cardiovascular disease, which have been highlighted first in this review. The alteration in chemokines secretion and chemokine receptors has an essential role in the pathophysiology of cardiovascular disease. Chemokines as cytokines with low molecular weight (8-12 kDa) mediate white blood cell (WBC) chemotactic reactions, vascular cell migration, and proliferation that induce endothelial dysfunction, atherogenesis, and cardiac hypertrophy.Several studies reported that curcumin could be advantageous in the attenuation of cardiovascular diseases via anti-inflammatory effects and redress of chemokine secretion and chemokine receptors. We present these studies with a focus on two chemokines: CXCL8 (IL-8) and CCL2 (chemoattractant protein 1 or MCP-1). Future research will further elucidate the precise potential of curcumin on chemokines in the adjustment of cardiovascular system activity or curcumin chemokine-based therapies.

Natural products with SGLT2 inhibitory activity: Possibilities of application for the treatment of diabetes.

Diabetes mellitus currently affects as many as 400 million people worldwide, creating a heavy economic burden and stretching health care resources. A dysfunction of glucose homeostasis underlies the disease. Despite advances in the treatment of diabetes, many patients still suffer from complications and side effects; hence, development of more effective treatments for diabetes is still desirable. SGLT2 is the principle cotransporter involved in glucose reabsorption in the kidney. SGLT2 inhibition reduces glucose reabsorption by the kidney and ameliorates plasma glucose concentration. The interest in natural products that can be used for the inhibition of SGLT2 is growing. The flavonoid phlorizin, which can be isolated from the bark of apple trees, has been used as lead structure due to its inhibitory activity of SGLT1 and SGLT2. Some phlorizin-derived synthetic compounds, including canagliflozin, dapagliflozin, empagliflozin, ipragliflozin, and ertugliflozin, are approved by the food and drug administration to treat type 2 diabetes mellitus (T2DM), whereas others are under clinical trials investigation. In addition, other natural product-derived compounds have been investigated for their ability to improve blood glucose control. The present review summarizes the natural products with SGLT2 inhibitory activity, and the synthetic compounds obtained from them, and discusses their application for the treatment of diabetes.

Comparison of the Neuroprotective Effects of Aspirin, Atorvastatin, Captopril and Metformin in Diabetes Mellitus.

OBJECTIVE: The aim of this study was to investigate the effect of combined intake of a high dose of aspirin, atorvastatin, captopril and metformin on oxidative stress in the brain cortex and hippocampus of streptozotocin (STZ)-induced diabetic rats. MATERIAL AND METHODS: Rats were randomly divided into the following 11 groups: control and diabetic (D), as well as 9 groups that were treated with metformin (M, 300 mg/kg) or aspirin (ASA, 120 mg/kg) alone or in different combinations with captopril (C, 50 mg/kg) and/or atorvastatin (AT, 40 mg/kg) as follows: (D + M), (D + ASA), (D + M + ASA), (D + M + C), (D + M + AT), (D + M + C + ASA), (D + M + C + AT), (D + M + AT + ASA) and (D + M + C + AT + ASA). The rats in treatment groups received drugs by gavage daily for six weeks. Serum lipid profile and levels of oxidative markers in the brain cortex and hippocampus tissues were evaluated. RESULTS: The levels of malondialdehyde in the brain cortex and hippocampus in all the treated groups decreased significantly (p < 0.05). There was a significant increase in the total thiol concentration as well as catalase activity in treated rats in (M + AT), (M + C + ASA), (M + C + AT), (M + AT + ASA) and (M + C + AT + ASA) groups in cortex and hippocampus in comparison with the diabetic rats (p < 0.05). Also, the superoxide dismutase activity in all treated rats with medications was significantly increased compared to the diabetic rats (p < 0.05⁻0.01). CONCLUSION: Our findings showed that the combined use of high-dose aspirin, metformin, captopril and atorvastatin potentiated their antioxidant effects on the brain, and hence could potentially improve cognitive function with their neuroprotective effects on hippocampus.

Effects of standardized Zataria multiflora extract and its major ingredient, Carvacrol, on Adriamycin-induced hepatotoxicity in rat.

BACKGROUND: Due to antioxidant effects of Zataria multiflora (ZM) and Carvacrol (CAR) in many cases and the prominent role of reactive oxygen species (ROS) in hepatotoxicity induced by Adriamycin (ADR), the aim of this study is to investigate the effects of ZM and CAR on ADR-induced hepatotoxicity. METHODS: Twenty four male Wistar rats were randomly divided into four groups including: 1)Control, 2)Adriamycin (ADR), 3,4) ZM + ADR and CAR + ADR that received ZM and CAR for 28 consecutive days. Blood samples were collected on the days 0, 14 and 28 to determine the alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Also, the hepatic redox markers were evaluated. RESULTS: ADR significantly increased ALP, ALT and AST in comparison with the control (p < 0.05 - p < 0.001). In CAR + ADR group, the serum ALP, ALT and AST were significantly reduced compared to those of the ADR group (p < 0.01 to p < 0.001). Also, in ZM + ADR group, serum ALP and ALT compared to ADR was significantly reduced (p < 0.001). MDA level in the ADR group significantly increased compared to control (p < 0.01). The MDA level in ZM + ADR (p < 0.05) and CAR + ADR (p < 0.01) groups were significantly reduced compared to that of ADR. Thiol levels in ZM + ADR group significantly increased compared to the ADR group (p < 0.05). The activities of CAT in the ADR group was significantly reduced compared to control (p < 0.05) and increased in treatment groups in comparison with the ADR (p < 0.01). CONCLUSION: Long-term administration of ZM extract and CAR could reduce the oxidative damage in the rat liver induced by ADR through the strengthening of the antioxidant system.

The Preventive Effects of Standardized Extract of Zataria multiflora and Carvacrol on Acetaminophen-Induced Hepatotoxicity in Rat: - Zataria multiflora and Carvacrol and Hepatotoxicity.

OBJECTIVES: The hepatotoxicity induced by Acetaminophen (AAP) mostly mediated by effect on oxidative stress parameters. The Zataria multiflora (Z.M) is an herbal medicine with well-known antioxidant effect. The aim of this study is investigation of preventive effects of Z.M and Carvacrol (CAR) on AAP-induced hepatotoxicity in rats. METHODS: Rats were randomly divided into four groups including: 1) Control, 2) Acetaminophen (AAP), 3) and 4) CAR. The saline, Z.M (200 mg/kg) and CAR (20 mg/kg) were administrated orally for 6 days, after that AAP (600 mg/kg) was administrated in the 7th day. Blood sampling was performed on the first and last days. Also, the liver tissue was removed for evaluation of Malondyaldehide (MDA), Thiol content, Superoxide dismutase (SOD) and Catalase (CAT). Total Protein (tPro), Glutamic Oxaloacetic Transaminase (GOT), Glutamic Pyruvic Transaminase (GPT) and Alkaline Phosphatase (ALP) in liver tissue were evaluated. The changes (Δ) of enzymes activities were presented. RESULTS: The Δ GOT, Δ GPT and Δ ALP in CAR group significantly decreased compared to AAP group (P < 0.01 to P < 0.001) and Δ GPT in Z.M group was significantly reduced in comparison with AAP group (P < 0.05). Also, MDA, Thiol, SOD and CAT levels in treated groups were attenuated compared to AAP group (P < 0.05 to P < 0.001). CONCLUSION: Z.M and CAR have a powerful hepatoprotective effect. CAR is more effective than Z.M. Based on the results. Z.M and CAR could be potent supplementary agents against hepatotoxicity of AAP in patients.

Protective effect of pomegranate seed oil against mercuric chloride-induced nephrotoxicity in rat.

PURPOSE: Heavy metals such as mercury can induce the generation of free radicals and oxidative stress which are associated with tissue injury. The present study was designed to evaluate the protective effect of pomegranate seed oil against HgCl2-induced nephrotoxicity. METHODS: Twenty-four W/A adult rats were randomly divided into four groups. Group I received corn oil (1 mL/kg). Group II received HgCl2 (5 mg/kg) for 3 days. Group III and IV received PSO 0.4 mL/kg and 0.8 mL/kg, respectively one hour before HgCl2 administration for 3 days. Blood samples were taken by cardiac puncture and used for the measurement of urea and creatinine concentration. Twenty-hour-hour urine samples were collected to measure protein and glucose. The right kidney was fixed in formalin for histological examination and the left kidney was homogenized for measuring malondialdehyde (MDA) and total sulfhydryl groups. RESULTS: Significant elevation of serum creatinine and urea levels as well as urine glucose and protein concentrations, a significant decrease in total thiol content and a significant increase in MDA levels in kidney homogenate samples were observed after administration of HgCl2 as compared with control group. PSO pretreatment resulted in a significant decrease in serum creatinine and urea levels as well as urine glucose and protein concentrations when compared with HgCl2 treated (group II). PSO also significantly reversed the HgCl2-induced depletion in thiol content and elevation in MDA content. Histological studies revealed milder kidney lesions in PSO treated groups (groups III and IV) compared to HgCl2 treated group. CONCLUSION: Our results suggest that PSO has a protective effect against HgCl2-induced nephrotoxicity in rats.