Iranian Journal of Basic Medical Sciences
Year:2017 | Volume:20 | Issue:3|Papers Count:15

Drug delivery across the skin is used for several millennia to ease gastrointestinal (GI) ailments in Traditional Persian Medicine (TPM). TPM topical remedies are generally being applied on the stomach, lower abdomen, lower back and liver to alleviate GI illnesses such as dyspepsia, gastritis, GI ulcers, inflammatory bowel disease, intestinal worms and infections. The aim of the present study is to survey the topical GI remedies and plant species used as ingredients for these remedies in TPM. In addition, pharmacological activities of the mentioned plants have been discussed. For this, we searched major TPM textbooks to find plants used to cure GI problems in topical use. Additionally, scientific databases were searched to obtain pharmacological data supporting the use of TPM plants in GI diseases. Rosa × damascena, Pistacia lentiscus, Malus domestica, Olea europaea and Artemisia absinthium are among the most frequently mentioned ingredients of TPM remedies. β-asarone, amygdalin, boswellic acids, guggulsterone, crocin, crocetin, isomasticadienolic acid, and cyclotides are the most important phytochemicals present in TPM plants with GI-protective activities. Pharmacological studies demonstrated GI activities for TPM plants supporting their extensive traditional use. These plants play pivotal role in alleviating GI disorders through exhibiting numerous activities including antispasmodic, anti-ulcer, anti-secretory, anti-colitis, anti-diarrheal, antibacterial and anthelmintic properties. Several mechanisms underlie these activities including the alleviation of oxidative stress, exhibiting cytoprotective activity, down-regulation of the inflammatory cytokines, suppression of the cellular signaling pathways of inflammatory responses, improving re-epithelialization and angiogenesis, down-regulation of anti-angiogenic factors, blocking activity of acetylcholine, etc.

In previous studies, antioxidant activity of Viola odorata L. has been demonstrated. In this study, we have investigated the anti-melanogenic effect of extract and fractions of the plant in B16F10 cell line. Materials and Methods: Impact of different increasing concentrations of extract and fractions of V. odorata was evaluated on cell viability, cellular tyrosinase, melanin content and mushroom tyrosinase as well as ROS production in B16F10 murine melanoma cell line. Results: Viola odorata had no cytotoxicity on B16F10 cells compared to control group. Kojic acid as positive control had significant decreasing effects on cellular and mushroom tyrosinase activity, melanin content and ROS production (P<0. 001, for all cases). V. odorata (1-20 μ g/ml) decreased all measured parameters including cellular tyrosinase and melanin content as well as ROS production and among all extract and fractions ethyl acetate fraction had the best effect (P<0. 05). Conclusion: Viola odorata had promising anti-melanogenic activity through inhibition of cellular tyrosinase activity and ROS production as well as melanin content. More basic and clinical studies need to aver its impact.

Organic cation transporter 3 (OCT3) as a high-capacity transporter contribute to the metabolism of metformin. The present study was conducted to determine the genotype frequencies of the variant OCT3-1233G>A (rs2292334) in patients with newly diagnosed type 2 diabetes (T2D) and its relationship with response to metformin. Materials and Methods: This study included 150 patients with T2D who were classified into two groups following three months of metformin therapy: responders (by more than 1% reduction in HbA1c from baseline) and nonresponders (less than 1% reduction in HbA1c from baseline). PCR-based restriction fragment length polymorphism (RFLP) served to genotype OCT3-564G>A variant. Results: The parameters such as HbA1c (P<0. 001) and BMI (P<0. 001) in both patients with GA + AA genotype and GG genotype decreased significantly following 3 months of metformin therapy compared with baseline. The mean reduction in HbA1c levels following 3 months was higher in patients with the A allele (0. 77% reduction from baseline) than in those with the homozygous G allele (0. 54% reduction from baseline). Also, in GA + AA genotypes compared with GG genotypes, the mean reduction in HbA1c values from baseline was 0. 34% for responders and 0. 14% for non-responders. Conclusion: Considering the roles of genetic variations in the function of metformin transporters, the effect of variations such as 1233G>A in the OCT3, which is a high-capacity transporter widely expressed in various tissues cannot be ignored. Comparing the allele frequencies of OCT3-1233G>A variant in our study and different ethnic populations confirm that the variant is a highly polymorphic variant.

Pregabalin (PGB) is a new antiepileptic drug that has received FDA approval for patient who suffers from central neuropathic pain, partial seizures, generalized anxiety disorder, fibromyalgia and sleep disorders. This study was undertaken to evaluate the possible adverse effects of PGB on the muscular system of mice. Materials and Methods: To evaluate the effect of PGB on skeletal muscle, the animals were exposed to a single dose of 1, 2 or 5 g /kg or daily doses of 20, 40 or 80 mg/kg for 21 days, intraperitoneally (IP). Twaenty-four hr after the last drug administration, all animals were sacrificed. The level of fast-twitch skeletal muscle troponin I and CK-MM activity were evaluated in blood as an indicator of muscle injury. Skeletal muscle pathological findings were also reported as scores ranging from 1 to 3 based on the observed lesion. Results: In the acute and sub-acute toxicity assay IP injection of PGB significantly increased the activity and levels of CK-MM and fsTnI compared to the control group. Sub-acute exposure to PGB caused damages that include muscle atrophy, infiltration of inflammatory cells and cell degeneration. Conclusion: PGB administration especially in long term care causes muscle atrophy with infiltration of inflammatory cells and cell degeneration. The fsTnI and CK-MM are reliable markers in PGB-related muscle injury. The exact mechanisms behind the muscular damage are unclear and necessitate further investigations.

to determine the effect of different doses of caffeine on orthodontic tooth movement (OTM) in rats. Materials and Methods: Forty male 250-300 g Sprague-Dawley rats were randomly divided into four groups of ten animals each and received 0 (control), 1 g/l, 2 g/l and 3 g/l caffeine in tap water for 3 days. Orthodontic appliances were ligated between the maxillary first molars and incisors on the 4th day of the study period. All rats were sacrificed after 2 weeks of treatment after which OTM was measured. Hematoxylin/eosin-stained sections of the molars were prepared and the mesial roots were examined for resorption-lacunae depth and osteoclast number. ANOVA was used for statistical analysis (P<0. 05). Results: A significant decrease in OTM was observed only in the 2 g/l (P=0. 043) and 3 g/l (P<0. 01) caffeine-receiving rats compared to the control animals. Osteoclast counts and resorption-lacunae depths demonstrated significant differences between each of the caffeine groups and control rats (P<0. 05). None of the variables showed significant differences between the caffeine groups (P>0. 05). Conclusion: According to our findings, one of the effects of caffeine consumption during orthodontic treatment in rats was decreased root resorption. Additionally, concentrations of 2 g/l and 3 g/l inhibited OTM which seems to be due to its influence on osteoclast numbers.

Ranking as the sixth commonest cancer, esophageal squamous cell carcinoma (ESCC) represents one of the leading causes of cancer death worldwide. One of the main reasons for the low survival of patients with esophageal cancer is its late diagnosis. Materials and Methods: We used proteomics approach to analyze ESCC tissues with the aim of a better understanding of the malignant mechanism and searching candidate protein biomarkers for early diagnosis of esophageal cancer. The differential protein expression between cancerous and normal esophageal tissues was investigated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Then proteins were identified by matrix-assisted laser desorption/ ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS) and MASCOT web based search engine. Results: We reported 4 differentially expressed proteins involved in the pathological process of esophageal cancer, such as annexinA1 (ANXA1), peroxiredoxin-2 (PRDX2), transgelin (TAGLN) andactin-aortic smooth muscle (ACTA2). Conclusion: In this report we have introduced new potential biomarker (ACTA2). Moreover, our data confirmed some already known markers for EC in our region.

Scutellarin, a flavonoid extracted from the medicinal herb Erigeron breviscapus Hand-Mazz, protects neurons from damage and inhibits glial activation. Here we examined whether scutellarin may also protect neurons from hypoxia-induced damage. Materials and Methods: Mice were exposed to hypoxia for 7 days and then administered scutellarin (50 mg/kg/d) or vehicle for 30 days Cognitive impairment in the two groups was assessed using the Morris water maze test, cell proliferation in the hippocampus was compared using 5-bromo-2-deoxyuridine (BrdU) immunohistochemistry, and hippocampal levels of nestin and neuronal class III β-tubulin (Tuj-1) were measured using Western blotting. These results were validated in vitro by treating cultured neural stem cells (NSCs) with scutellarin (30 μ M). Results: Treating mice with scutellarin shortened escape times and increased the number of platform crossings, it increased the number of BrdU-positive proliferating cells in the hippocampus, and it up-regulated expression of nestin and Tuj-1. Treating NSC cultures with scutellarin increased the number of proliferating cells and the proportion of cells differentiating into neurons instead of astrocytes. The increase in NSC proliferation was associated with phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, while neuronal differentiation was associated with altered expression of differentiation-related genes. Conclusion: Scutellarin may alleviate cognitive impairment in a mouse model of hypoxia by promo-ting proliferation and neuronal differentiation of NSCs.

Bone marrow mesenchymal stem cells (MSCs) play an important role in bone health. Cadmium causes osteoporosis, but the exact mechanisms of its effect on MSCs are not known. Materials and Methods: Rats were treated with cadmium chloride (40 mg/l) in drinking water for six weeks, and then the biochemical and morphological studies on MSCs were carried out as a cellular backup for osteoblasts. Viability and proliferation properties of the cells were evaluated using MTT assay, trypan blue, population doubling number, and colony forming assay. Morphology of the cells and biochemical parameters including activity of metabolic (ALP, AST, and ALT) and antioxidant enzymes (SOD, CAT, and POX) as well as the MDA level (as an indication of lipid peroxidation) were investigated. In addition, intracellular calcium, potassium, and sodium content were estimated. Data was analyzed statistically and P<0. 05 was taken as the level of significance. Results: The results showed a significant reduction in viability and proliferation ability of extracted cells when compared to the controls. In addition, it was revealed that the cadmium treatment of rats caused a significant reduction in nuclear diameter and cytoplasm area. Also, there was significant increase in (ALT) and (AST) activity and intracellular calcium and potassium content but no change was observed with sodium content and ALP activity. The results showed [a] significant reduction in the antioxidant enzyme activity and increases in the MDA level. Conclusion: Based on the present study, reduction of viability and proliferation ability of MSCs might be a causative factor of osteoporosis in industrial areas.

Childhood cataract is a genetically heterogeneous eye disorder that results in visual impairment. The aim of this study was to identify the genetic mutations of connexin 50 gene among Iranian families suffered from autosomal dominant congenital cataracts (ADCC). Materials and Methods: Families, having at least two members with bilateral familial congenital cataract, were selected for the study. Probands were evaluated by detailed ophthalmologist’ s examination, and the pedigree analysis was performed. PCR amplifications were performed corresponding to coding region and intron-exon boundaries of GJA8, a candidate gene responsible for ADCC. PCR products were subjected to bidirectional sequencing, and the co-segregation of identified mutations was examined and finally, the impact of identified mutations on biological functions of GJA8 was predicted by in silico examination. Results: Three different genetic alterations, including c. 130G>A (p. V44M), c. 301G>T (p. R101L) and c. 134G>T (p. W45L) in GJA8 gene were detected among three probands. Two identified mutations, W45L and V44M have been already reported, while the R101L is a novel mutation and its co-segregation was examined. This mutation was exclusively detected in the ADCC and could not be found among the healthy control group. The result of bioinformatic studies of R101L mutation predicted that this amino acid substitution within GJA8 could be a disease-afflicting mutation due to its potential effect on the protein structure and biological function. Conclusion: Our results suggest that mutations of lens connexin genes such as GJA8 gene could be one of the major mechanisms of cataract development, at least in a significant proportion of Iranian patients with ADCC.

This study aimed to investigate the role and the possible mechanisms involved in the immunoregulation of experimental periodontitis by Th17/Treg. Materials and Methods: Experimental periodontitis was established by silk thread ligation with Porphyromonas gingivalis daubing in the bilateral maxillary second molar of Male Sprague-Dawley (SD) rats. Alveolar bones were scanned by Micro-CT. Histological examination was stained with H&E. The proportions of Th17 and Treg cells in peripheral blood were detected by flow cytometry. RT-PCR was used to measure the expression of RORγ t, Foxp3 mRNA in the gingival tissues. The concentrations of IL-17, IL-10, and TGF-β in peripheral blood and gingival crevicular fluid were measured by ELISA. Results: Experimental rats showed profound bone resorption and inflammatory cell infiltration. The percentages of Th17 significantly increased in the peripheral blood, which was consistent with gingival tissues study that Th17 cells related transcription factor RORγ t mRNA and IL-17 increased in the course of periodontitis. The percentages of CD25+Foxp3+ Treg significantly increased in the peripheral blood, which was consistent with gingival tissues study that Treg cells related transcription factor Foxp3 mRNA and cytokines IL-10 and TGF-β increased in the course of periodontitis. The ratio of Th17/Treg cells was significantly increased in the peripheral circulation, however, the Th17/Treg balance is in wave motion in inflamed gingival tissues in the different stages of periodontitis. Conclusion: Th17/Treg balance may be associated with the progression of periodontitis and pathological tissue destruction. Moreover, local inflammation would result in the up-regulation ratio of Th17/Treg in peripheral blood, which may influence some periodontally involved systemic diseases.

Nowadays much effort is being invested in order to diagnose the mechanisms involved in neural differentiation. By clarifying this, making desired neural cells in vitro and applying them into diverse neurological disorders suffered from neural cell malfunctions could be a feasible choice. Thus, the present study assessed the capability of fetal brain extract (FBE) to induce rat bone marrow-derived mesenchymal stem cells (BM-MSCs) toward neural cells. Materials and Methods: For this purpose, BM-MSCs were collected from rats and cultured and their mesenchymal properties were confirmed. After exposure of the BM-MSCs to fetal brain extract, the cells were evaluated and harvested at days 3 and 7 after treatment. Results: The BM-MSCs that were exposed to FBE changed their appearance dramatically from spindle shape to cells with dendrite-like processes. Those neural like processes were absent in the control group. In addition, a neural specific marker, vimentin, was expressed significantly in the treatment group but not in the negative control group. Conclusion: This study presented the FBE as a natural neural differentiation agent, which probably has required factors for making neurons. In addition, vimentin overexpression was observed in the treated group which confirms neuron-like cell differentiation of BM-MSCs after induction.

This study investigated the protective effect of tanshinone IIA sodium sulfonate (TSS) on ischemia-reperfusion (I/R) induced cardiac injury, and the underlying mechanism of action. Materials and Methods: Male Sprague-Dawley rats were subjected to a 30-min coronary arterial occlusion followed by 24 hours' reperfusion. Half an hour before the left coronary artery ligation, rats were pretreated with TSS in three different dosages (15, 30, 70 mg/kg, IP). Twenty-four hours later, cardiac function was measured and the ratio of infarct size to area at risk (AAR) was calculated. Western blotting examined the expression of the inflammatory mediator high-mobility group box1 (HMGB-1), anti-apoptotic protein Bcl-2, pro-apoptotic mediators such as Bax and Caspase-3, markers of autophagy such as ratio of LC3B/LC3A and Beclin-1 expression. Results: Our results showed that TSS dose-dependently improves cardiac function, accompanied with decrease of HMGB1 level, increase of LC3B/LC3A ratio and increase of Beclin-1 expression. TSS treatment down-regulates Bax and Caspase-3 expression, while up-regulating Bcl-2 levels. Conclusion: TSS ameliorates I/R induced myocardial injury and improves cardiac function via reducing inflammation and apoptosis, while enhancing autophagy.

To investigate the effect of cinnamaldehyde and eugenol on the telomere-dependent senescence of stem cells. In addition, to search the probable targets of mentioned phytochemicals between human telomere interacting proteins (TIPs) using in silico studies. Materials and Methods: Human adipose derived stem cells (hASCs) were studied under treatments with 2. 5 μ M/ml cinnamaldehyde, 0. 1 μ g/ml eugenol, 0. 01% DMSO or any additive. The expression of TERT, AKT1 and DKC1 genes and the telomere length were assessed over 48-hr treatment. In addition, docking study was conducted to show probable ways through which phytochemicals interact with TIPs. Results: Treated and untreated hASCs had undetectable TERT expression, but they had different AKT1 and DKC1 expression levels (CI=0. 95; P<0. 05). The telomere lengths were reduced in phytochemicals treated with hASCs when compared with the untreated cells (P<0. 05). Docking results showed that the TIPs might be the proper targets for cinnamaldehyde and eugenol. Data mining showed there are many targets for cinnamaldehyde and eugenol in the intracellular environment. Conclusion: The general effect of cinnamaldehyde and eugenol is their induction of stem cell senescence. Therefore, they could be applicable as chemo-preventive or antineoplastic agents.

Tuberculosis (TB) is still one of the problematic infectious diseases in developing countries, especially in Iran. In the present study, we applied ribosome display technique to select single chain variable fragments (scFvs) specific for the 6-kDa early secretory antigenic target (ESAT-6) antigen of Mycobacterium tuberculosis from a mouse scFv library. Materials and Methods: The gene encoding ESAT-6 was cloned into pET22b(+) plasmid and expressed in Escherichia coli BL21 (DE3). The purified recombinant ESAT-6 protein was injected into female BALB/c mice for immunization, and then m-RNA was extracted from the spleen of immunized mice. The anti-ESAT-6 VH/k chain library was assembled by joining of VH and k into the VH/k chain with a 72-bp DNA linker by SOE (splicing by overlap extension) PCR. The scFv library was panned against ESAT-6 using a single round of ribosome display via a rabbit reticulocyte lysate system. Results: ELISA assay showed that one of the selected scFvs had higher affinity against the recombinant ESAT-6 protein. The affinity of the candidate scFv was ̴ 3. 74×108 M-1. Conclusion: It could be proposed that the isolated scFv in this study may be useful for the diagnosis of TB.

Ischemia/reperfusion (I/R) injury of spinal cord is leading to the paraplegia observed. In this study, we investigated the protective effect of the saffron extract on spinal cord I/R injury. Materials and Methods: Thirty five male Sprague-Dawley rats were divided into 5 groups: intact, sham surgery, normal saline (NS), low dose saffron aqua extract, high dose saffron aqua extract. Results: The mean motor deficit index (MDI) scores were significantly lower in the saffron extract groups than in the NS group at 48 hr after spinal cord ischemia (P<0. 001). Saffron extract groups significantly decreased plasma level of malondialdehyde than in the NS Group (P<0. 05). The number of motor normal neurons was significantly greater in the high saffron extract group than in the NS and low saffron group (P<0. 05). Conclusion: These data suggest that a saffron extract may protect spinal cord neurons from I/R injury.