Bahman Rashidi

Phytosomal curcumin: A review of pharmacokinetic, experimental and clinical studies

Curcumin, a hydrophobic polyphenol, is the principal constituent extracted from dried rhizomes of Curcuma longa L. (turmeric). Curcumin is known as a strong anti-oxidant and anti-inflammatory agent that has different pharmacological effects. In addition, several studies have demonstrated that curcumin is safe even at dosages as high as 8g per day; however, instability at physiological pH, low solubility in water and rapid metabolism results in a low oral bioavailability of curcumin. The phytosomal formulation of curcumin (a complex of curcumin with phosphatidylcholine) has been shown to improve curcumin bioavailability. Existence of phospholipids in phytosomes leads to specific physicochemical properties such as amphiphilic nature that allows dispersion in both hydrophilic and lipophilic media. The efficacy and safety of curcumin phytosomes have been shown against several human diseases including cancer, osteoarthritis, diabetic microangiopathy and retinopathy, and inflammatory diseases. This review focuses on the pharmacokinetics as well as pharmacological and clinical effects of phytosomal curcumin.

Green tea and its anti-angiogenesis effects

The development of new blood vessels from a pre-existing vasculature (also known as angiogenesis) is required for many physiological processes including embryogenesis and post-natal growth. However, pathological angiogenesis is also a hallmark of cancer and many ischaemic and inflammatory diseases. The pro-angiogenic members of the VEGF family (vascular endothelial growth factor family), VEGF-A, VEGF-B, VEGF-C, VEGF-D and placental growth factor (PlGF), and the related receptors, VEGFR-1, VEGFR-2 and VEGFR-3 have a central and decisive role in angiogenesis. Indeed, they are the targets for anti-angiogenic drugs currently approved. Green tea (from the Camellia sinensis plant) is one of the most popular beverages in the world. It is able to inhibit angiogenesis by different mechanisms such as microRNAs (miRNAs). Green tea and its polyphenolic substances (like catechins) show chemo-preventive and chemotherapeutic features in various types of cancer and experimental models for human cancers. The tea catechins, including (-)-epigallocatechin-3-gallate (EGCG), have multiple effects on the cellular proteome and signalome. Note that the polyphenolic compounds from green tea are able to change the miRNA expression profile associated with angiogenesis in various cancer types. This review focuses on the ability of the green tea constituents to suppress angiogenesis signaling and it summarizes the mechanisms by which EGCG might inhibit the VEGF family. We also highlighted the miRNAs affected by green tea which are involved in anti-angiogenesis.

NLRP3 inflammasome: Its regulation and involvement in atherosclerosis

Inflammasomes are intracellular complexes involved in the innate immunity that convert proIL‐1β and proIL‐18 to mature forms and initiate pyroptosis via cleaving procaspase‐1. The most well‐known inflammasome is NLRP3. Several studies have indicated a decisive and important role of NLRP3 inflammasome, IL‐1β, IL‐18, and pyroptosis in atherosclerosis. Modern hypotheses introduce atherosclerosis as an inflammatory/lipid‐based disease and NLRP3 inflammasome has been considered as a link between lipid metabolism and inflammation because crystalline cholesterol and oxidized low‐density lipoprotein (oxLDL) (two abundant components in atherosclerotic plaques) activate NLRP3 inflammasome. In addition, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and lysosome rupture, which are implicated in inflammasome activation, have been discussed as important events in atherosclerosis. In spite of these clues, some studies have reported that NLRP3 inflammasome has no significant effect in atherogenesis. Our review reveals that some molecules such as JNK‐1 and ASK‐1 (upstream regulators of inflammasome activation) can reduce atherosclerosis through inducing apoptosis in macrophages. Notably, NLRP3 inflammasome can also cause apoptosis in macrophages, suggesting that NLRP3 inflammasome may mediate JNK‐induced apoptosis, and the apoptotic function of NLRP3 inflammasome may be a reason for the conflicting results reported. The present review shows that the role of NLRP3 in atherogenesis can be significant. Here, the molecular pathways of NLRP3 inflammasome activation and the implications of this activation in atherosclerosis are explained.

Anti-Atherosclerotic Effects of Vitamins D and E in Suppression of Atherogenesis.

Atherosclerosis is a progressive and multifactorial disease which occurs under the influence of various risk factors including endothelial dysfunction (ED), oxidative stress, and low‐density lipoprotein (LDL) oxidation. In contract to the initial hypotheses on the usefulness of vitamin E supplementation for cardiovascular disease prevention, large outcome trials showed consumption of vitamin E has no obvious effect on cardiovascular disease and, in some cases, it may even increase the rate of mortality. This seemingly unexpected finding may be due to the opposite effects of vitamin E compounds. Vitamin E is a group of compounds which have different and even opposing effects, yet in most of the studies, the exact consumed component of vitamin E is not determined. It appears that the combined consumption of gamma‐tocopherol, vitamin C, D, and tetrahydrobiopterin (BH4) may be extremely effective in both preventing atherogenesis and suppressing plaque development. In this regard, one of main issues is effect of vitamins E and D deficiency on microRNAs network in atherosclerosis. Various studies have indicated that miRNAs have key roles in atherosclerosis pathogenesis. The deficiency of vitamins E and D could provide a deregulation for miRNAs network and these events could lead to progression of atherosclerosis. Here, we highlighted a variety of mechanisms involve in the progression of atherosclerosis and effects of vitamins D and E on these mechanisms. Moreover, we summarized miRNAs involve in atherosclerosis and their regulation by vitamins E and D deficiency. J. Cell. Physiol. 232: 2968–2976, 2017.

MicroRNA: A novel target of curcumin in cancer therapy

Curcumin is known as a natural dietary polyphenol which is extracted from Curcuma longa L. It has been shown that curcumin has a variety of pharmacological effects such as antioxidant, anti‐cancer, anti‐inflammatory, and anti‐microbial activities. Anti‐cancer effects of curcumin are due to targeting of a wide range of cellular and molecular pathways involved in cancer pathogenesis including NF‐kB, MAPK, PTEN, P53, and microRNAs (miRNA) network. Multiple lines of evidence have indicated that curcumin exerts its therapeutic effects via regulating miRNA expression (e.g., miR‐1, miR‐7, miR‐9, miR‐34a, miR‐181, miR‐21, and miR‐19) which could lead to the regulation of underlying cellular and molecular pathways involved in cancer pathogenesis. Exosomes are one of the important classes of biological vehicles which could be released from various types of cells such as cancer cells and stem cells and could change the behavior of recipient cells. It has been shown that treatment of cancer cells with different dose of curcumin leads to the release of exosomes containing curcumin. These exosomes could induce anti‐cancer properties in recipient cells and reduce tumor growth. Hence, exosomes containing curcumin could be applied as powerful tools for cancer treatment. Here, we highlighted various miRNAs which could be affected by curcumin in various types of cancer. Moreover, we highlight exosomes containing curcumin as suitable therapeutic tools in cancer therapy.

Diet and cancer prevention: Dietary compounds, dietary MicroRNAs, and dietary exosomes.

Cancer is one of main health public problems worldwide. Several factors are involved in beginning and development of cancer. Genetic and internal/external environmental factors can be as important agents that effect on emerging and development of several cancers. Diet and nutrition may be as one of important factors in prevention or treatment of various cancers. A large number studies indicated that suitable dietary patterns may help to cancer prevention or could inhibit development of tumor in cancer patients. Moreover, a large numbers studies indicated that a variety of dietary compounds such as curcumin, green tea, folat, selenium, and soy isoflavones show a wide range anti‐cancer properties. It has been showed that these compounds via targeting a sequence of cellular and molecular pathways could be used as suitable options for cancer chemoprevention and cancer therapy. Recently, dietary microRNAs and exosomes have been emerged as attractive players in cancer prevention and cancer therapy. These molecules could change behavior of cancer cells via targeting various cellular and molecular pathways involved in cancer pathogenesis. Hence, the utilization of dietary compounds which are associated with powerful molecules such as microRNAs and exosomes and put them in dietary patterns could contribute to prevention or treatment of various cancers. Here, we summarized various studies that assessed effect of dietary patterns on cancer prevention shortly. Moreover, we highlighted the utilization of dietary compounds, dietary microRNAs, and dietary exosomes and their cellular and molecular pathways in cancer chemoprevention.

Erythropoietin improves neuronal proliferation in dentate gyrus of hippocampal formation in an animal model of Alzheimer's disease

Background: Alzheimer′s disease (AD) is a prevalent disorder with severe learning and memory defects. Because it has been demonstrated that erythropoietin (EPO) has positive effects on the central nervous system, the aim of this study was to evaluate the effect of EPO on neuronal proliferation in dentate gyrus of hippocampal formation in a well-defined model for AD. Materials and Methods: A rat model of sporadic dementia of Alzheimer′s type was established by a bilateral intracerebroventricular injection of streptozotocin (ICV-STZ). Impairment of learning and memory was confirmed 2 weeks after ICV-STZ injection by passive avoidance learning test and then rats were divided into fourgroups:Control, control-EPO, Alzheimer and Alzheimer-EPO. EPO was injected intraperitoneally every other day with a dose of 5000 IU/kg and, finally, the rats were anesthetized and decapitated for immunohistochemical study and neurogenesis investigation (by Ki67 method) in dentate gyrus of hippocampal formation. Results: The results driven from the histological study showed that EPO significantly increases neuronal proliferation in dentate gyrus of hippocampus in the Alzheimer-EPO group compared with the control, control-EPO and Alzheimer groups; however, there were no differences between the other groups. Conclusion: Our results show that even though EPO in intact animals doesnot change neurogenesis in dentate gyrus, it can nonetheless significantly increase neurogenesis if there is an underlying disorder like neurodegenerative diseases.

The protective effects of Ziziphus vulgaris L. fruits on biochemical and histological abnormalities induced by diabetes in rats

Abstract Background: Diabetes mellitus arises from a deficient production and action of insulin. Ziziphus vulgaris L. (jujube) is a medicinal plant that is known to have anti-diabetic actions. The aim of the present study was to investigate the protective effects of jujube fruit powder and extract against biochemical imbalances in stereptozotocin (STZ)-induced diabetes. Methods: Diabetes was induced in rats using intraperitoneal injection of STZ at a dose of 60 mg/kg body weight (bw). Jujube powder (1 g/kg bw) and extract (1 g/kg bw) were administered daily via gavage, from two weeks prior to three weeks after STZ injection. Serum concentrations of glucose, insulin, and lipids and histological changes of the pancreas tissue were assessed at the end of study. Results: The kaempferol content of jujube extract was found to be 0.013±0.0005% (w/w). Two weeks of supplementation with jujube powder resulted in a significant reduction of serum glucose levels compared with the non-diabetic control group prior to STZ treatment. Both jujube preparations prevented serum insulin decrease following STZ treatment, increased antioxidant capacity, and reduced total cholesterol, high-density lipoprotein cholesterol, triglycerides, and malondialdehyde levels. Jujube powder reduced serum low-density lipoprotein cholesterol and C-reactive protein concentrations while jujube extract had no effect on these parameters. Histopathological examination revealed a significant attenuation of pancreatic inflammation in the jujube-treated animals. Conclusions: The present findings suggest a protective role of jujube supplementation, in particular in the powdered form, against diabetes-induced biochemical and histopathological abnormalities.

Erythropoietin improves spatial learning and memory in streptozotocin model of dementia

Alzheimers disease is associated to impairments of learning and memory. Because studies demonstrated that erythropoietin has positive effects on central nervous system, the aim of this study was to evaluate the effect of erythropoietin on spatial learning and memory in a well defined model for Alzheimers disease. Rat model of Alzheimers was created by injecting streptozotocin in lateral ventricles of the brain. Two weeks later, the rats were assessed through passive avoidance learning test to confirm the induction of Alzheimers. After that, they received erythropoietin (5000IU/kg) every other day, for two weeks and then spatial learning and memory were assessed by a 5-day protocol of Morris water maze test in them. The results showed that streptozotocin severely damaged learning and memory in rats. Erythropoietin had no significant effect in the control rats; however, it significantly improved learning and memory in rats with Alzheimers disease, as the task performance of the rats treated with erythropoietin was like the control group. The results suggest that erythropoietin can be considered as an effective treatment for neurodegenerative damages.

Amlodipine treatment decreases plasma and carotid artery tissue levels of endothelin-1 in atherosclerotic rabbits

Alteration in transferring of calcium ions are seen in atherosclerotic cells and amlodipine can positively influence risk factors associated with atherosclerosis, but all mechanisms are not known. Recent studies indicate that endothelin-1 (ET-1) contributes to the atheroma formation and progression of atherosclerosis. In this study, we have evaluated the effects of amlodipine treatment and/or high-cholesterol diet on blood and carotid artery tissue concentration of ET-1 in the atherosclerotic rabbits. Thirty six male New Zealand white rabbits were randomly divided into four groups: normal-diet control (NC), normal-diet receiving amlodipine (NA), high-cholesterol diet (HC) and high-cholesterol diet receiving amlodipine (HA) groups. After 8 weeks all animals were anesthetized and blood or carotid tissue samples were colleted. Eight weeks of amlodipine treatment reduced significantly total cholesterol, LDL and TG in hypercholesterolemic (HA) group. Significant increase in plasma HDL-C and decrease in TG were the main effects of amlodipine treatment on serum lipid profiles in the control group. The plasma and carotid tissue levels of ET-1 in HC group were significantly increased as compared with the NC group (p<0.01). Amlodipine treatment significantly reduced ET-1 level in NA and HA rabbits (p<0.01). Furthermore, high-cholesterol diet induced atherosclerotic lesions as shown by the enhancement of endothelial cell diameter and accumulation of lipid droplets under endothelial cells. Amlodipine treatment reduced atherotic lesions in these rabbits. Amlodipine treatment reduced levels of total cholesterol, LDL and TG as well as plasma and carotid tissue levels of ET-1 in high lipid situation. We suggest that amlodipine treatment by reducing the ET-1 may contribute to reducing the progression of atherosclerotic disease.