Investigation of the Effect of Pyrogallol on the Formation of Amylin Amyloid Fibrils as a Strategy for the Treatment of Type 2 Diabetic Patients: A Theoretical and Experimental Study.

In more than 50 to 90% of type 2 diabetic patients, under the influence of various factors, the production of islet amyloid polypeptide or amylin in pancreatic beta cells increases. Spontaneous accumulation of amylin peptide in the form of insoluble amyloid fibrils and soluble oligomers is one of the main causes of beta cell death in diabetic patients. The objective of the present study was to evaluate the effect of pyrogallol, as a phenolic compound, on inhibiting the formation of amylin protein amyloid fibrils. In this study, different techniques such as the thioflavin T (ThT) and 1-Anilino-8-naphthalene sulfonate (ANS) fluorescence intensity and the circular dichroism (CD) spectrum, will be used to investigate the effects of this compound on inhibiting the formation of amyloid fibrils. To investigate the interaction sites of pyrogallol with amylin, docking studies were performed. Our results that pyrogallol in a dose-dependent manner (0.5:1, 1:1, and 5:1, Pyr to Amylin) inhibits the amylin amyloid fibrils formation. Docking analysis revealed that pyrogallol forms hydrogen bonds with valine 17 and asparagine 21. In addition, this compound forms 2 more hydrogen bonds with asparagine 22. This compound also forms hydrophobic bonds with histidine 18. Considering this data and the direct relationship between oxidative stress and the formation of amylin amyloid accumulations in diabetes, the use of compounds with both antioxidant and anti-amyloid properties can be considered an important therapeutic strategy for type 2 diabetes.

Alternative viewpoint against diabetic wound based on stem cell secretome that can mediated angiogenesis and reduce inflammation.

Diabetes mellitus, as an important metabolic disorder, affects the health of millions of people worldwide. A diabetic wound is one of the complications of diabetes. The stem cell secretome can particularly affect the wound healing process in diabetic wounds. The present study aimed to investigate the effects of Adipose-derived stem cells (ASCs) secretome on the skin wound healing process, angiogenesis, and inflammation in diabetic rats. For this purpose, ASCs were extracted from Adipose tissue and confirmed by flow cytometry and cell differentiation. Secretome was prepared. 27 rats were divided into three groups, non-diabetic, diabetic (treated with phosphate-buffered saline), and diabetics treated with secretome. The levels of vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-ß) were examined by the enzyme-linked immunosorbent assay (ELISA) was performed in the skin tissues of all groups. Hematoxylin and eosin (H&E) staining was performed. The level of VEGF was higher in the diabetic group treated with secretome as compared to the other two groups, while the level of TGF-ß was lower in this group, compared to the diabetic group. Based on the results of H&E staining, the epidermal thickness and angiogenesis were higher in the diabetic group treated with secretome, whereas edema, number of inflammatory cells, and epidermal damage were lower in this group, compared to the diabetic group. Subcutaneous injection of secretome can lead to diabetic wound healing by increasing growth factors associated with angiogenesis such as VEGF, increasing angiogenesis, regulating TGF-ß levels, reducing inflammatory cells.

Pyrogallol experimentally and theoretically suppressed advanced glycation end products (AGEs) formation, as one of the mechanisms involved in the chronic complications of the diabetes.

This study aimed to explore the inhibitory effect of pyrogallol on AGE formation in the bovine serum albumin (BSA)/glucose system for 21 days at 37 °C. The AGEs formation was measured in terms of Amadori products, total AGEs, argpyrimidine, and pentosidine. Molecular docking was used to investigate the interaction between pyrogallol and BSA. According to the results, in the presence of pyrogallol, the formation of pentosidine and argpyrimidine AGEs decreased. The molecular interaction studies demonstrated that pyrogallol has a high affinity towards arginine residues of albumin. Finally, results proved pyrogallol is a vigorous antiglycation compound and fruitful for AGE inhibition.

Plant-based green synthesis of nanoparticles as an effective and safe treatment for gastric ulcer.

Gastric ulcer is a chronic disease that affects about 10% of the world's population. This disease is caused by factors such as stress, smoking, alcohol consumption, nonsteroidal anti-inflammatory drugs (NSAIDs), Helicobacter pylori infection, and genetic factors. Herbal medicines such as plant extracts are new sources of drugs with promising results in treating gastric ulcers. Nanotechnology and nanomedicine have been able to reach this objective to some extent. Green synthesis is an alternative method adapted for chemical and physical methods. In the last few years, fungi, bacteria, viruses, algae, and plants have been used to produce metallic nanoparticles. Since nanoparticles synthesized by the green method can be effective in anticancer, antidiabetic, antiulcer, anti-inflammatory, and antioxidant treatments, the aim of this review was to study the effect of metal nanoparticles and metal oxides produced by the green method on the treatment of gastric ulcers. For this purpose, an electronic search of published research and review articles in PubMed, Scopus, Science Direct, Cochrane databases, and Google Scholar was conducted using a combination of keywords of "gastric ulcers and nanoparticles", "gastric ulcers and Green synthesis" and "stomach ulcers and nanoparticles". After a full review of published articles and their references, 120 articles were identified for further detailed review. The articles selected were between 2000 and March 2023, and 2 articles published in 1972 and 1997 were utilized. The results of this study have shown that polymeric, metal, and metal oxide nanoparticles synthesized from plants can be effective in treating gastric ulcers, especially ulcers caused by H. pylori, ethanol, and NSAIDs.

The induction of tau aggregation is restricted by sulfamethoxazole and provides new information regarding the use of the drug.

The aggregation of tau protein in the form of paired helical filament (PHF) leads to the breakdown of microtubule structure and the development of neurodegenerative disorders, such as Alzheimer's disease. Therefore, inhibiting tau protein aggregation is a potential strategy for preventing the progression of these disorders. In this study, sulfamethoxazole (SMZ), an antibiotic that easily crosses the blood-brain barrier and interacts with tau protein, was tested for its ability to inhibit tau aggregation in vitro. Various multi-spectroscopic techniques including XRD, LDH cytotoxicity colorimetric assay, and microscopic imaging were employed. The results showed that SMZ effectively interacts with tau protein through hydrogen and van der Waals interactions. It also effectively inhibited tau protein aggregation in vitro and significantly reduced toxicity in the SH-SY5Y neuroblastoma cell line. Molecular docking and MD simulation results suggested that SMZ may reduce tau protein aggregation by interacting with the PHF6 motif. Overall, these findings indicate that SMZ has therapeutic potential as a tau protein aggregation inhibitor, at least under in vitro conditions. These findings suggest that SMZ has potential as a treatment for neurodegenerative disorders involving tau protein aggregation. However, further research is needed to confirm these results and assess the effectiveness of SMZ in animal models and clinical trials.Communicated by Ramaswamy H. Sarma.

Silver nanoparticles synthesized from Quercus brantii ameliorated ethanol-induced gastric ulcers in rats by decreasing oxidative stress and improving antioxidant systems.

Gastric ulcers are caused by an imbalance between aggressive and defensive factors. The green synthesis of silver nanoparticles is becoming a new and promising method in the treatment of gastrointestinal ulcers. This study was conducted to investigate the protective and antioxidant effects of silver nanoparticles synthesized from Quercus brantii extract (NSQBE) on gastric damage induced by alcohol in rats. In this study, silver nanoparticles were produced by the green synthesis method using oak extract. The structure and morphology of nanoparticles were confirmed by various techniques such as UV-Vis spectroscopy, fourier transforms infrared spectrometer (FTIR), scanning electron microscope (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), energy-dispersive X-ray analysis (EDX), and dynamic light scattering )DLS(. For the animal studies, 30 male Wistar rats weighing 200 ± 20 g were randomly selected and divided into five groups (the normal, ethanolic, NSQBE treatment (received doses of 20 and 5 mg/kg), and standard (received a dose of 50 mg/kg of ranitidine) groups. After the rats were euthanized, their stomach was removed. A part of the stomach tissue of rats was used for histopathological studies, and the other part was used to study biochemical parameters such as the level of reactive oxygen species (ROS), protein carbonyl oxidation (PCO), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH) as well as nitric oxide (NO). Our results showed that in the ethanol group, the levels of ROS, MDA, PCO, and serum NO were higher than in the normal group. In addition, reduced GSH, CAT, SOD, tissue NO, gastric mucus, and antioxidant potential were decreased. In rats pretreated with NSQBE and ranitidine, the levels of ROS, MDA, PCO, and serum NO decreased, and the levels of GSH, CAT, SOD, tissue NO, gastric mucus, and antioxidant potential were increased in comparison to the ethanol group. The results of this study showed that silver nanoparticles synthesized using Quercus brantii are a promising approach for the treatment of gastric ulcers.

Injection of stem cells derived from allogeneic adipose tissue, a new strategy for the treatment of diabetic wounds.

A diabetic wound is one of the major complications of Diabetes mellitus. Considering the impact of these wounds on the health and quality of life of diabetic patients, the need for a suitable treatment is essential. Adipose-derived stem cells (ASCs) play a role in healing diabetic wounds. The purpose of this study is to examine the effect of ASCs on skin wound healing in diabetic rats. Rats were divided into three groups, diabetics treated with ASCs, non-diabetic, and diabetic (treated with phosphate-buffered saline). Skin wounds and its margin were examined to measure the level of vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-ß) and histopathological examinations on three, six, and nine days after wound formation and treatment. As a result, the administration of ASCs can reduce the healing time of skin wounds in diabetic rats by controlling inflammation and increasing angiogenesis.

Mesalazine Inhibits Amyloid Formation and Destabilizes Pre-formed Amyloid Fibrils in the Human Insulin.

Amyloid formation due to protein aggregation is associated with several amyloid diseases (amyloidosis). The use of small organic ligands as inhibitors of protein aggregation is an attractive strategy for the treatment of these diseases. In the present study, we evaluated the in vitro inhibitory and destabilizing effects of Mesalazine on human insulin fibrillation. To induce fibrillation, human insulin was incubated in 50 mM glycine buffer (pH 2.0) at 50 °C. The effect of Mesalazine on insulin amyloid aggregation was studied using spectroscopic, imaging, and computational approaches. Based on the results, the Mesalazine in a concentration-dependent manner (different ratios (1:0.1, 1:0.5, 1:1, and 1:5) of the insulin to Mesalazine) prevented the formation of amyloid fibrils and destabilized pre-formed fibrils. In addition, our molecular docking study confirmed the binding of Mesalazine to insulin through hydrogen bonds and hydrophobic interactions. Our findings suggest that Mesalazine may have therapeutic potential in the prevention of insulin amyloidosis and localized amyloidosis.

Teucrium polium L: An updated review of phytochemicals and biological activities.

Objective: Medicinal plants and their components are potential novel sources for developing drugs against various diseases. Teucrium polium L. (syn Teucrium capitatum L. or felty germander) from the Lamiaceae family, is widely distributed in the dry and stony places of the hills and deserts of almost all Mediterranean countries, southwestern Asia, Europe, and North Africa. Based on traditional Iranian medicine (TIM), T. polium is used for treating many diseases, including abdominal pain, indigestion, and type 2 diabetes. Materials and Methods: In our previous review article published in 2012 and based on 100 articles published from 1970 to 2010, the main compounds purified from T. polium were terpenes, terpenoids, and flavonoids with antioxidant, anticancer, anti-inflammatory, hypoglycemic, hepatoprotective, hypolipidemic, antibacterial, and antifungal activities. Results: In this article, the phytochemistry and pharmacological activities of the plant reported from 2011 to 2020 have been evaluated. Therefore, a search was done in the databases PubMed, Science Direct and Google Scholar, Scopus, and Web of Science with the terms "T. polium," "T. capitatum." and felty germander', which included about 100 articles published since 2011 about T. polium pharmacological activities and isolated compounds. Most studies of this review focused on the antioxidant and antidiabetic effects of the plant. Conclusion: Considering the position of T. polium in folk medicine, mainly as an antidiabetic agent, purification, structural and biological characterization of the active components appears essential for effective use of the plant.

Experimental and theoretical studies on the anti-amyloidogenic and destabilizing effects of pyrogallol against human insulin protein.

One of the major problems caused by repeated subcutaneous insulin injections in patients with diabetes is insulin amyloidosis. Understanding the molecular mechanism of amyloid fibril formation of insulin and finding effective compounds to inhibit or eliminate them is very important, and extensive research has been done on it. In this study, the anti-amyloidogenic and destabilizing effects of the pyrogallol, as a phenolic compound, on human insulin protein were investigated by CR absorbance, ThT and ANS fluorescence, FTIR spectroscopy, and atomic force microscopy. According to the obtained results, the formation of amyloid fibrils at pH 2.0 and 50°C was confirmed by CR, ThT, ANS, and FTIR assays. Microscopic images also showed the twisted and long structures of amyloid fibrils. Simultaneous incubation of the protein with pyrogallol at different concentrations reduced the intensities of CR, ThT, and ANS in a dose-dependent manner, and no trace of fibrillar structures was observed in the microscopic images. FTIR spectroscopy also showed that the position of the amide I band in the spectrum of samples containing pyrogallol was shifted. Based on the findings of this study, it can be concluded that pyrogallol can be effective in preventing and suppressing human insulin amyloid fibrils. PRACTICAL APPLICATIONS: In recent years, finding a strategy for the treatment of amyloid diseases has been considered by many researchers. Targeting protein aggregates by small organic molecules such as polyphenols is one of the most desirable and effective strategies to prevent and improve amyloid disease, which has received much attention in recent years. 1,2,3-Trihydroxybenzene, commonly known as pyrogallol (Py), is a phenolic compound like other natural polyphenols that are present in human food sources, including fruits and vegetables, and a variety of edible and medicinal plants. So far, many beneficial activities for pyrogallol such as anti-cancer, antioxidant, antibacterial, antiviral, and antifungal have been reported in various studies. Since various studies have shown that natural polyphenols have special properties to prevent amyloid disease, the present study could be useful in advancing the design purposes of new anti-amyloid drugs in the future.

Evaluation of antioxidant and anti-ulcerogenic effects of Eremurus persicus (Jaub & Spach) Boiss leaf hydroalcoholic extract on ethanol-induced gastric ulcer in rats.

This study aimed to investigate the antioxidant and protective effect of E. persicus leaf hydroalcoholic extract (EPE) in preventing gastric ulcers induced by ethanol in rats. Wistar rats weighing 180-220 g were randomly divided into five groups. These groups included negative control (normal) group, positive control (ethanolic) group, comparative control (ranitidine recipient) group, group recipient the dose of 250 mg/kg plant extract, and group recipient the dose of 500 mg/kg plant extract. One hour after gavage of the drug and extract, the gastric ulcer was induced by feeding 1 ml of 96% ethanol to each animal except the rats of the negative control group. After one hour, the rats were killed, and their stomachs were separated. Then, the gastric Ulcer index (UI), pH, oxidative stress parameters, and histopathological changes in the stomach of all groups were measured. Pre-treatment of ethanol-induced rats with the EPE reduced (P < 0.05) the ulcer index and gastric juice pH, compared to ethanolic group rats. Furthermore, pre-treatment with EPE at a dose-dependent manner, alleviated the gastric oxidative stress injury in rats through increase the activity of CAT, tissue NO· and GSH levels. EPE also was able to decrease the levels of ROS, MDA, PCO and serum NO·. According to the results, it can be concluded that pre-treatment with EPE prevents the formation of gastric ulcers caused by ethanol, which can be attributed to the antioxidant activity of plant polyphenols compounds.

Modulation of the antioxidant defense system in liver, kidney, and pancreas tissues of alloxan-induced diabetic rats by camphor.

Excess production of reactive oxygen species and the loss of antioxidant efficiency systems play an important role in the development of diabetes. Thus, using antioxidant compounds is an important strategy to reduce these complications. This study aimed to investigate the possible effect of camphor on the serum biochemical parameters and oxidative parameters in the pancreas, liver, and kidney tissues of alloxan-induced diabetic rats. In this study, 40 male Wistar rats were divided into five groups, including normal group, diabetic group, the diabetic group treated with glibenclamide, the diabetic group treated with 30 mg/kg camphor, and the diabetic group receiving the camphor solvent. Intragastric administration of camphor and glibenclamide, as the control drug, to diabetic rats for 21 days lowered their blood glucose, total cholesterol, triglyceride, and LDL-cholesterol, while the blood high-density lipoprotein -cholesterol level was increased. In addition, our results indicated that treatment of diabetic rats with camphor increased the activity of glutathione peroxidase, catalase, and superoxide dismutase enzymes as well as reduced glutathione content in the liver, pancreas, and kidney tissues as compared to the diabetic rats. Based on our data, it can be concluded that camphor has a hypoglycemic activity, and this effect may be attributed, in part, to its antioxidant ability. PRACTICAL APPLICATIONS: Camphor is a terpenoid natural compound derived from the wood present in the camphor laurel's stem and roots (Cinnamomum camphora L.) trees. The synthetic form of camphor is currently being produced for medical, health, and industrial applications. In addition, this compound is present in Rosmarinus officinalis, Cinnamomum zeylanicum, Salvia officinalis, Artemisia Annua, and Ocimum basilicum. Numerous researches have shown its beneficial effects on various diseases. In this study, it has been shown that camphor possesses antidiabetic effects in alloxan-induced diabetic rats. Treatment of diabetic rats with camphor increased the antioxidant capacity and reduces the oxidative stress markers in the liver, pancreas, and kidney tissues as compared to the diabetic rats. Given the favorable effect of camphor on some oxidative parameters in diabetic rats in our study, its antihyperglycemic property is probably due to its antioxidant effects.

Ameliorating and protective effects mesalazine on ethanol-induced gastric ulcers in experimental rats.

Gastric ulcer is a frequent gastrointestinal tract (GIT) disorder that affects about 10% of the world population. Drug candidates that can provide high efficacy and low toxicity are needed value for the prevention and treatment of gastric ulcers. The present study aimed to assess the protective effect of mesalazine against ethanol-induced gastric mucosal injury in rats. The rats were divided into five groups, normal, ethanolic, standard (recipient ranitidine 50 mg/kg), experimental groups 1, 2 (receive mesalazine at doses of 50 and 100, respectively). The protective effect of mesalazine was evaluated by the ulcer index, histological examinations, measurement of oxidative stress parameters, antioxidant systems, and some gastric mucosal protection factors. Pre-treatment of rats with doses of 50 and 100 mg/kg Mesalazine (5-ASA) in experimental groups 1 and 2 increased the pH of gastric juice and reduced the gastric ulcer index compared to the ethanolic group. Also, the results indicated that mesalazine, reduced the tissue reactive oxygen species (ROS), malondialdehyde (MDA), and protein carbonyl (PCO) levels, serum nitric oxide (NO), and increased the level of tissue NO and glutathione (GSH) and activity of Catalase (CAT), Based on these results, it can be concluded that mesalazine strengthens the antioxidant defense system of gastric mucosal cells during oxidative damage caused by ethanol.

In vitro investigation of the effect of mesalazine on amyloid fibril formation of hen egg-white lysozyme and defibrillation lysozyme fibrils.

In certain conditions (such as fever and stress) mutated lysozyme enzyme deposits in different tissues and organs in the form of amyloid fibrils (plaques). These aggregates lead to tissue destruction and the pathogenesis of a disease. In this study, we investigated the in vitro effects of mesalazine drug on both preventions of lysozyme aggregation and the removal of lysozyme fibrils. With this regard, hen egg-white lysozyme (HEWL) was incubated in the absence and presence of mesalazine in high temperature and acidic pH conditions. The influence of mesalazine was surveyed by Congo red (CR) absorbance, Circular dichroism spectroscopy (CD), Thioflavin T (ThT) fluorescence assay, 1-anilinonaphthalene-8-sulfonic acid (ANS) fluorescence test, and Field-emission scanning electron microscopy (FE-SEM). Our results demonstrate that mesalazine, in all concentrations, especially in 1:1 and higher drug to protein ratios, has a strong inhibitory effect on protein fibrillation. Additionally, mesalazine does not show an acceptable impact on the reversibility of HEWL fibril in any of the related concentrations. Based on the obtained results, we conclude that mesalazine can be used as a drug for the prevention of amyloid-fibrils formation in hereditary lysozyme amyloidosis and other systemic non-neuropathic hereditary amyloidosis.

Molecular identification and genetic variation of Alternaria species isolated from tomatoes using ITS1 sequencing and inter simple sequence repeat methods.

BACKGROUND AND PURPOSE: Alternaria is one of the most abundant fungi that exists in numerous places around the world. This saprophytic fungus causes diseases in plants and accounts for the spoilage of cereals in warehouses. The aim of this study was to identify Alternaria isolates based on their morphological characteristics and internal transcribed spacer ribosomal RNA (ITS rRNA) sequencing method. To this end, genetic diversity in the isolates was also examined using inter simple sequence repeat (ISSR) markers. MATERIALS AND METHODS: To conduct this research, a total of 60 tomato samples with black spots were collected from supermarkets in Khorramabad City, Iran, in the winter of 2017. The specimens were cultured on a potato dextrose agar medium. After the purification of the fungus by the single-spore method, the identification of the species was carried out using morphological characteristics and ITS rRNA sequencing by polymerase chain reaction. The genetic diversity of the identified species with four primers was evaluated using the ISSR marker. RESULTS: Based on the sequencing of the ITS1 region, all the isolates were identified as A. alternata. Cluster diagrams for the ISSR marker were classified into six distinct groups. The mean polymorphism information content was obtained as 0.35, indicating the effectiveness of the primers in the separation of the isolates. CONCLUSION: The sequencing of ITS1 led to the identification of Alternaria species that are morphologically similar. The production of various mycotoxins by A . Alternata species leads to the contamination of livestock and human food. Regarding this, the investigation of the genetic diversity of A. alternata species using the ISSR marker would facilitate the identification of suitable and effective strategies for controlling the fungal and mycotoxin contamination of human nutrition.

Apigenin reduces human insulin fibrillation in vitro and protects SK-N-MC cells against insulin amyloids.

Deposition of proteins is a key pathogenic feature of more than 20 amyloid-related diseases. Inhibiting or reversing amyloid aggregation via the use of small molecules is proposed as two useful approaches in hampering the development of these diseases. In this research, we examined the inhibitory and disruptive effects of apigenin, a common dietary flavonoid with multiple pharmacological properties, against human insulin fibrillization. Besides, we investigated the potential cytotoxicity of insulin fibrils on SK-N-MC cells in the presence and absence of apigenin. The increase in Thioflavin T (ThT) and anilinonaphthalene-8-sulfonic acid (ANS) fluorescent intensities and Congo red absorbance were inhibited by simultaneous incubation of various concentrations of apigenin with insulin, in a dose-dependent manner. The spectroscopy results were confirmed by transmission electron microscopy, where lower extent of fibrillar structures was observed in the presence of apigenin. In addition, the cell exposure to the co-incubated insulin amyloids with apigenin led to the increased viability and decreased LDH release dose-dependently, compared to cells exposed to insulin fibrils alone. Co-incubation with apigenin also attenuated the extent of apoptotic cell death induced by insulin fibrils. It can be concluded that apigenin possess in vitro anti-amyloidogenic activities as well as protective effects against insulin amyloids cytotoxicity.

Inhibition of human islet amyloid polypeptide or amylin aggregation by two manganese-salen derivatives.

Aggregation of human islet amyloid polypeptide (IAPP) into pancreatic fibrillar deposits has been postulated to be one of the main contributors to impaired insulin secretion and pancreatic ß-cell death in approximately 90% of type 2 diabetic patients. So, compounds that prevent cytotoxic protein/polypeptide self-assembly and amyloidogenesis are considered as novel therapeutic agents against this disease. In this study, using thioflavin-T (ThT) and Anilinonaphthalene-8-sulfonic acid (ANS) fluorescence assays, transmission electron microscopy (TEM) and docking studies, we investigated whether EUK-8 and EUK-134, two salen derivatives with proven antioxidants activities, could interfere with the conversion of synthetic human amylin to its insoluble amyloid form. Spectroscopy and electron microscopy data indicated that incubation of human amylin with either EUK-8 or EUK-134 significantly inhibited amyloid formation at two molar ratios of 1:1 and 5:1 (drugs to protein). In addition, [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay showed that treatment of SK-N-MC cells with the pre-formed fibrils in the presence of compounds at drug-to-protein molar ratios of 1:1 and 5:1, dramatically increased the viability of cells compared to the only fibrils formed-treated SK-N-MC cells. Docking results also demonstrated that the aromatic rings of EUK-8 and EUK-134 interact with the hydrophobic region (23-25) of IAPP via Van der Waals interactions. Based on these results and the proven antioxidant properties of these compounds, it could be concluded that these compounds might provide a novel approach to prevent islet amyloid deposition in ß-cells and provide useful information for developing other novel compounds for the treatment of type 2 diabetes.

Syntheses and structure-activity relationships of seven manganese-salen derivatives as anti-amyloidogenic and fibril-destabilizing agents against hen egg-white lysozyme aggregation.

Accumulation of intra- and/or extracellular misfolded proteins as amyloid fibrils is a key hallmark in more than 20 amyloid-related diseases. In that respect, blocking or reversing amyloid aggregation via the use of small compounds is considered as two useful approaches in hampering the development of these diseases. In this research, we have studied the ability of different manganese-salen derivatives to inhibit amyloid self-assembly as well as to dissolve amyloid aggregates of hen egg-white lysozyme, as an in vitro model system, with the aim of investigating their structure-activity relationships. By coupling several techniques such as thioflavin T and anilinonaphthalene-8-sulfonic acid fluorescence, congo red absorbance, far-UV circular dichroism, and transmission electron microscopy, we demonstrated that all compounds possessed anti-amyloidogenic activities and were capable of dispersing the fibrillar aggregates. In addition, MTT assay of the treated SK-N-MC cells with the preformed fibrils formed in the presence of compounds at a drug-to-protein molar ratio of 5:1, indicated a significant increase in the viability of cells, compared to the fibrils formed in the absence of each of the compounds. Our spectroscopy, electron microscopy, and cellular studies indicated that EUK-15, with a methoxy group at the para position (group R(5)), had higher activity to either inhibit or disrupt the ß-sheet structures relative to other compounds. On the basis of these results, it can be concluded that in addition to aromatic rings of each of the derivatives, the type and position of the side group(s) contribute to lower lysozyme fibril accumulation.

Phytochemistry and medicinal properties of Teucrium polium L. (Lamiaceae).

Teucrium polium L. (family Lamiaceae) is a wild-growing flowering plant, found abundantly in South-Western Asia, Europe and North Africa. Traditionally, T. polium has been used for different pathological conditions such as gastrointestinal disorders, inflammations, diabetes and rheumatism. In traditional Iranian medicine (TIM), the tea of T. polium is used for treating many diseases such as abdominal pain, indigestion, common cold and type 2 diabetes. Based on this background, many studies have been followed for scientific confirmation of the above-mentioned properties. In this review, 100 articles published from 1970 to 2011 in the area of phytochemistry, pharmacology and toxicology of extracts and compounds isolated from T. polium have been evaluated. During the past 40 years, different classes of compounds have been isolated from various parts of T. polium of which the main groups are terpenoids and flavonoids. It has been found that these compounds possess a broad spectrum of pharmacological effects including antioxidant, anticancer, antiinflammatory, hypoglycemic, hepatoprotective, hypolipidemic, antibacterial and antifungal. The results of data analyses on the chemical, pharmacological and toxicological characteristics of T. polium support the view that this plant has beneficial therapeutic properties. However, further studies to identify the active components and further verify their relevant pharmacological activities are warranted.