Iranian Journal of Pharmacology and Therapeutics
Volume:17 Issue: 1, 2019

Trastuzumab is a specific monoclonal antibody used for therapeutic of the human epidermal growth factor receptor 2 (HER-2) -positive metastatic breast cancer. But, resistance to trastuzumab is a major obstacle in clinical efficiency.  During the past years, several studies have been done to find the mechanisms contributing to trastuzumab resistance. Previous studies have highlighted that bone morphogenic protein (BMP) signaling can indicate a pathway in cancer for sensitizing cells to chemotherapy. Also, it was suggested that Caveolin-1 is essential for the formation of caveolae and endocytic membrane transport and has a critical role in drug resistance and metastasis in cancer. The purpose of this study was to assess the expression of BMP receptor type1A (BMPR1A) and Caveolin-1 genes in compare with trastuzumab-sensitive and resistance BT-474 cells. Trastuzumab-resistant BT474 cells were established by continuous subjection to trastuzumab for six months. Then, an MTT assay was done for determining the resistance. After that, the Expression of BMPR1A and Caveolin-1levels were assessed through real-time PCR. Caveolin-1 expression levels increased significantly (2.4 fold, p<0.05) whereas BMPR1A levels down-regulated significantly (8.26 fold, p<0.05) in BT474-R compared to the parental cells. Our results proposed that BMPR1A and CAV1 regulation take part in BT-474 trastuzumab resistance breast cancer. Therefore, further experiments are required to confirm the role/s of BMPR1A and CAV1 in trastuzumab resistance breast cancer.

The goal in studies concerning biomarkers in autoimmune diseases is finding a marker which fluctuates in correlation with the disease’s severity and settles within normal borders after effective treatment. This marker would later be used as an efficient tool in diagnosis and analysis of medicine clout. It seems the most cogent biomarkers are those measurable in serum or plasma. MS is a neurological disease common within the young adult population with a predictable course, often leading to life-immersing disability. The prognosis, however difficult and limited, is currently possible via diagnostic tests (brain MRI) or clinical information (severity and degrees of disability).  Many studies have been conducted in an effort to detect an adequate biomarker. It is still often overlooked that a reliable biomarker should both be clinically applicable and functional is prognosis; as this is what could lead to timely treatment.

Despite the progress in cancer therapies such as chemotherapy and radiation, its eradication remains as unattainable dream for the patients and doctors. Recently, using supplementary agents such as herbal medicine with fewer side effects seems efficient and attractive. Therefore, the purpose of the present study is to investigate if the ethanolic extract of P.oleracea has cytotoxicity and apoptosis induction on oral epithelial cancer cell line (KB cell line). The KB cells were cultured with different doses of ethanol extract (0, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000, 5500 μg / ml) for 24, 48 and 72 hours and the cytotoxicity and cell survival were measured through MTT and trypan blue respectively. In addition, the cells stained with Hoechst reagent to study apoptosis induction after their treatment with 4000, 4500 and 5000 μg / ml of P.oleracea ethanolic extract at 24, 48 and 72 hours. Our findings showed that P.oleracea had time and concentration dependent anticancer effects on KB oral cancer cell line (P <0.05), so that there was a significant difference between all experimental and the control group. In addition, 1500 μg / ml P.oleracea extract was considered as IC50 level according to MTT assay. Also, condensation, shrinkage and breakdown of the cells nuclei confirmed the apoptosis induction at 4000, 45000 and 5000 μg / ml concentration. It seems that ethanolic extract of P.oleracea leads to inhibit cancer cells growth and induce cell death through apoptosis at all concentrations. However, several preclinical or clinical studies should be designed to prove its safety, effectiveness and mechanisms.

For a long period, ethno medicinal plants have been a valuable source of natural products for maintaining human health, especially in the last decade, with more intensive studies for natural therapies. The use of ethno medicinal plant for pharmaceutical purposes has gradually increased in Iran. Gundelia tournefortii has been used as an antibacterial, anti-fungal, antipyretic, anti-inflammatory, and antioxidant agent in Iran. In the recent examination, the testicular protective effect of G. tournefortii aerial parts aqueous extract on diabetic mice has been evaluated. Seventy mice were used and diabetes was induced by administration of 150 mg/kg of alloxan monohydrate intraperitoneally in 60 mature male mice and they were randomly divided into six groups. The treatment groups received glibenclamide 10 mg/kg and 5, 10, 20 and 40 mg/kg of G. tournefortii through gavage for 20 days. Also, one group was considered as the non-diabetic control. At 20th day, the mice were killed, dissected, then blood and testis samples were collected for biochemical and stereological parameters analysis. The data were analyzed by SPSS-21 software. G. tournefortii at all doses (especially GT40) and glibenclamide significantly (p≤0.05) ameliorated the concentrations of fasting blood glucose, testosterone, superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase. Also, multiple doses of G. tournefortii (especially GT40) and glibenclamide increased the weight and volume of the testis, the volumes of the tubule and interstitial tissue, the length and diameter of the tubule, the height of the germinal epithelium, and the number of the Leydig cell compared to the diabetic untreated group. According to the obtained results, G. tournefortii aerial parts aqueous extract can regulate the concentrations of biochemical parameters and inhibit testicular damages in alloxan monohydrate induced diabetic mice. It seems that G. tournefortii can be offered as a testicular protective supplement or drug for prevention, control, and treatment of testicular toxicity in diabetic patients.

Urtica dioica L. is widely used as an anti‑inflammatory, antioxidant, antimicrobial, hypocholesterolemic, antiulcer, anti‑colitis, anticancer, hypotensive, immunomodulatory, and hepatoprotective agent. In the present study, the antidiabetic and nephroprotective potentials of U. dioica ethanolic extract was investigated against streptozotocin (STZ) induced diabetic mice. Male mice were divided into six groups: normal control, untreated diabetic, diabetic mice receiving 30, 90 and 270 mg/kg of plant extract (groups UD30, UD90 and UD270, respectively) or 30 mg/kg glibenclamide. At 20th day, the mice killed, dissected, then blood and kidney samples were collected for histological and biochemical parameters analysis. The data was analyzed by one way variance analysis and Duncan’s test using SPSS 21. Different doses of U. dioica (especially UD270) could significantly (p≤0.05) reduce the raised levels of blood glucose, urea, creatinine and volumes and lengths of the proximal and distal convoluted tubules, collecting ducts, vessels and loop of Henle and increase the weight of body and levels of superoxide dismutase (SOD) and catalase (CAT) when compared to the untreated group. The results of the present study showed that under the present experimental conditions, ethanolic extract of U. dioica indicated antidiabetic and nephroprotective abilities against STZ induced kidney damage in mice.

Coriandrum sativum has been used in Iranian traditional medicine as an anti-inflammatory, antioxidant, antibacterial, and antifungal agent. The purpose of this study was to evaluate the chemical composition and anti-parasitic property of essential oil of C. sativum leaf on trophozoite of Trichomonas vaginalis. C. sativum was collected from Kermanshah city and essential oil was prepared by the Clevenger device. The essential oil was analyzed by GC/MS. Trophozoite of T. vaginalis was cultured in vitro in CPLM medium and the effect of the essential oil on the survival of T. vaginalis trophozoite was measured by Neobar slide. This study indicated that Linalool (71.2%) was the most constituent found in C. sativum essential oil. Also, the results of anti-parasitic tests demonstrated the concentrations of 0.5, 0.25, 0.125, 0.062, 0.031, 0.015, 0.007, 0.003, and 0.001 g/ml in essential oil and 0.25 g/ml in metronidazole could destroy of T. vaginalis trophozoite completely after 420 minutes incubation. The best results were observed at 0.5 and 0.25 g/ml concentrations of essential oil, because these concentrations were able to destroy trophozoite in 90 minutes. Also, 0.001 g/ml concentration of essential oil had the lower anti-parasitic effect than all concentrations against T. vaginalis trophozoite. The trophozoite survived at DMSO after 600 minutes. MIC and MLC of C. sativum essential oil were 0.015 and 0.031 g/ml concentrations, respectively. In our study, the essential oil of C. sativum leaf in several concentrations destroyed T. vaginalis trophozoite. It appears that C. sativum can be used for the treatment of some T. vaginalis infections as an antibiotic.

Glycogen synthase kinase (GSK)-3β mediates amyloid-beta (Aβ) and oxidative stress-induced neurotoxicity in neurodegenerative disorders. Natural products with antioxidant activity, such as Sargassum (S.) oligocystum may modulate GSK-3β enzyme and protect against Aβ-induced neurotoxicity. Therefore, we aimed to assess the neuroprotective effects of a methanolic extract of S. oligocystum against Aβ-induced neurotoxicity in the SH-SY5Y cells and the contribution of GSK-3β inhibition to the neuroprotective effects of the S. oligocystum extract. SH-SY5Y neuroblastoma cells were seeded in 96 well plates and incubated with Aβ (20µM) and the methanolic extract of S. oligocystum (40, 50, and 70μg/ml) for 24h. We measured cell viability using the MTT assay. Western blot method was used to measure the expression of the GSK-3β and phosphorylated (p)-GSK-3β protein levels. The data were analyzed using one-way analysis of variance (ANOVA) followed by the LSD test. Amyloid-beta (20µM) reduced neuronal cell viability compared with the control group. Addition of S. oligocystum extract at concentrations of 40, 50 and 70μg/ml decreased the neurotoxic effects of Aβ. The extract of S. oligocystum at a concentration of 70μg/ml also decreased the effects of Aβ on the GSK-3β protein level. The pGSK-3β protein levels in the S. oligocystum groups (40 and 70μg/ml) plus Aβ were lower than the Aβ-treated group. The methanolic extract of S. oligocystum protected SH-SY5Y cells from Aβ-induced neurotoxicity. The attenuation of the GSK-3β protein level may contribute to the neuroprotective effects of S. oligocystum extract.

Opium dependence is one of the serious and multidimensional problems. Millions of people are opium addicts throughout the world. The aim of this study was to determine the risk factors causing relapse in opium addicts in Internally Displaced People (IDPs). This experiment was conducted in the Drug Detoxification and Health Welfare research center, Bannu, KPK, Pakistan. Sociodemographics characteristics of IDPs were studied in this retrospective cross-sectional study. Questionnaire was specifically designed and total 41 relapsed individual’s histories of post treated IDPs were studied. Percentage of factors causing relapse in IDPs included stress in 36.59% individuals, family conflicts 19.51%, friends 12.20%, work load stress 09.76%, body aches 07.31%, sexual satisfaction 09.76% and fun 04.87%. Average time of relapse in IDPs was 6 months. Results revealed that stress was the most notorious factor directing IDPs towards relapse. It is concluded that attention must be paid on the crucial factors of stress to avoid relapse associated with opium dependence such as, family conflicts, personal, occupational and economical status.

Thiazolidinediones are commonly used anti-diabetic drugs. Owing to the anti-inflammatory action of TZDs as a result of there action on the PPAR gamma receptor and a proposed action on the prostaglandins, these drugs can be tried in the acute exacerbations of COPD that are also commonly found among diabetic patients. An experimental study of one week was carried out at animal house of Army Medical College, Rawalpindi on a total of 50 guinea pigs (both male and female) of Dunkin Hartley variety, weighing 500 to 600 grams. An isometric volume transducer was used to measure the histamine induced contractions of the smooth muscles. In the similar way contractions with pioglitazone in the presense of histamine, contractions with indomethacin which is a prostaglandin antagonist, in the presence of histamine and mixed effect of pioglitazone along with indomethacin in the presence of histamine was evaluated. Pioglitazone produced significant reduction in histamine-induced contractions of the normal tracheal muscle strips thus identifying its relaxant effect on the tracheal smooth muscles. The contractions of the tracheal muscles were increased when indomethacin was used. The pioglitazone induced relaxation was also reduced in the group pre-treated with indomethacin, thus suggesting an identifiable role of prostaglandins in the relaxant effect of TZDs on the smooth muscles

Valproic acid is widely used as an anti-epileptic globally. Anti-epileptic action is mediated by Gamma Amino Butyric Acid (GABA) receptors. In past and recently, several other clinical outcomes have been proposed by various studies. These under-reported clinical actions apart from anti-epileptic activity are mediated by various intracellular and extracellular pathways. Several mechanisms like Histone deacetylase (HDAC) inhibition, inhibition of inflammatory cytokines, angiogenesis inhibition and many more justifies its possible use in variety of disorders like diabetes mellitus, asthma, cancer, shock, hyperlipidemia, fibrosis etc. Present review throws some light on such under-reported, clinically beneficial effects of Valproic acid in various diseases and disorders.

Drug induced liver injury (DILI) leads to acute hepatitis in 10%, liver failure, and death in 30%. One of the major drugs causing DILI is Anti-tuberculous drugs and since tuberculosis is affecting 1/3rd of the total world population, their use is quite common. Use of Isoniazid (INH) is limited owing to hepatotoxicity following the stress produced by oxidative species. Silymarin has hepatoprotective potential because of anti-oxidant property. N-Acetylcysteine (NAC) on the other hand triggers the cellular protective mechanisms by replenishing glutathione in the cells. The main aim of this study was to compare the hepatoprotective activity of Silymarin and NAC against INH induced toxicity. Total 50 BALB/C mice were sorted into a total of 5 groups, with 10 mice in each group for 2 weeks by random sampling.  Control group was administered distilled water through I/P route daily. The INH group was administered I/P 100 mg/kg INH daily. The INH/Silymarin group was administered 150 mg/kg INH and 50 mg/kg Silymarin I/P daily. The INH/NAC group was administered 150mg/kg INH and 300mg/kg of NAC I/P daily. The INH/NAC/silymarin group was administered 150mg/kg INH, 300mg/kg of NAC and 50mg/kg of silymarin I/P daily. On day 14, the dissection of all the mice was done. Liver function tests were performed and histopathology was done. Both NAC and Silymarin demonstrated hepatoprotection that was statistically similar. However, the mice of silymarin group looked weak and less active and six dies within 5-8 days after the end of the experimental doses of the drugs.

For a long period, ethno medicinal plants have been a valuable source of natural products for maintaining human health, especially in the last decade, with more intensive studies for natural therapies. The use of ethno medicinal plant for pharmaceutical purposes has gradually increased in Iran. Gundelia tournefortii has been used as an antibacterial, anti-fungal, antipyretic, anti-inflammatory, and antioxidant agent in Iran. In the recent examination, the testicular protective effect of G. tournefortii aerial parts aqueous extract on diabetic mice has been evaluated. Seventy mice were used and diabetes was induced by administration of 150 mg/kg of alloxan monohydrate intraperitoneally in 60 mature male mice and they were randomly divided into six groups. The treatment groups received glibenclamide 10 mg/kg and 5, 10, 20 and 40 mg/kg of G. tournefortii through gavage for 20 days. Also, one group was considered as the non-diabetic control. At 20th day, the mice were killed, dissected, then blood and testis samples were collected for biochemical and stereological parameters analysis. The data were analyzed by SPSS-21 software. G. tournefortii at all doses (especially GT40) and glibenclamide significantly (p≤0.05) ameliorated the concentrations of fasting blood glucose, testosterone, superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase. Also, multiple doses of G. tournefortii (especially GT40) and glibenclamide increased the weight and volume of the testis, the volumes of the tubule and interstitial tissue, the length and diameter of the tubule, the height of the germinal epithelium, and the number of the Leydig cell compared to the diabetic untreated group. According to the obtained results, G. tournefortii aerial parts aqueous extract can regulate the concentrations of biochemical parameters and inhibit testicular damages in alloxan monohydrate induced diabetic mice. It seems that G. tournefortii can be offered as a testicular protective supplement or drug for prevention, control, and treatment of testicular toxicity in diabetic patients.

Spironolactone has produced beneficial effects in animal models of neurodegenerative disorders. However, the underlying mechanisms of this agent on neurons and glia are mostly unknown. Therefore, we aimed to show the effects of spironolactone and fludrocortisone, a mineralocorticosteroid receptor agonist, on neuronal and glial toxicity induced by N-methyl-D-aspartate (NMDA) activation and chloroquine, an autophagy inhibitor, in the cell culture. We exposed the SHSY5Y neuroblastoma and 1321N1 astrocytoma exposed to NMDA (25µM), or chloroquine (40µM) for 24 and 48h to induce neuronal and glial toxicity. Spironolactone (1, 10, and 20µM) or fludrocortisone (300nM) were also added to the cells for 24 and 48h. Cell survival was measured using the MTT assay. Neurons and astrocytes treated with NMDA and spironolactone (1, 10, and 20µM) for 24 and 48h had lower cell death compared with the NMDA-treated group. Moreover, cells treated with NMDA and fludrocortisone for 24 and 48h had higher viability in comparison to the NMDA-treated group. The neuronal cells treated with chloroquine and spironolactone (10 and 20µM) for 24h had higher cell viability compared with the chloroquine group. Chloroquine plus spironolactone (20µM) treatment for 24 and 48h increased cell viability of astrocytes compared with the chloroquine-treated group. Moreover, the treatment of neurons and astrocytes with chloroquine plus fludrocortisone for 24h decreased cell death.  Spironolactone and fludrocortisone protected neurons and astrocytes against NMDA- and chloroquine-induced toxicity. The mechanism of neuronal and glial protective effects of spironolactone possibly related to the inhibition of the mineralocorticosteroids. However, spironolactone might affect other non-mineralocorticoid systems.

Harmine is a harmal-derived alkaloid with antioxidant properties. The morphine produces free radicals and plays a key role in the pathogenesis of kidney disease. This study was designed to evaluate the effects of harmine against morphine- induced damage to the kidneys of rats. In this study, 64 male rats were randomly assigned to 8 groups: saline and morphine treated groups; harmine groups (5, 10, 15 mg/kg) and morphine + harmine treated groups (5, 10, 15 mg/kg). Treatments were administered intraperitoneally daily for 20 days. The weights of the animals and their kidneys, kidney index, glomeruli characteristics, thiobarbituric acid reactive species, antioxidant capacity, kidney function indicators and serum nitrite oxide levels were investigated. Morphine administration significantly improved kidney MDA level, blood urea nitrogen (BUN), creatinine and nitrite oxide levels and decreased glomeruli number and tissue FRAP level compared to the saline group (P < 0.05). The harmine and harmine +  morphine treatments at all doses significantly reduced BUN, kidney MDA level, creatinine, glomerular diameter and nitrite oxide levels and increased the glomeruli number and tissue FRAP level compared to the morphine group (p < 0.05). It seems that harmine administration improved kidney injury induced by morphine in rats.

The present study aimed to investigate the role of adenylyl cyclase activator in preventing diabetic nephropathy via antioxidant activity in rats. Biochemical parameters were performed to confirm Streptozotocin induced nephropathy in rats. Male Wistar rats were used in the present study to reduce the effect of estrogen. Rats were subjected to high fat diet (HFD) for two weeks followed by low dose of Streptozotocin (STZ) [35mg/kg, i.p.] to develop experimental diabetic nephropathy in eight weeks. Two weeks treatment with low dose of Forskolin (10mg/kg) reduced the level of diabetic nephropathy markers but results observed were not significant. Whereas, Forskolin intermediate dose (20mg/kg) and high dose (30mg/kg) treated rats significantly attenuated diabetes induced elevated renal function parameters and endogenous antioxidants enzymatic activities. High dose of Forskolin was found to be more effective in attenuating the renal structural and functional abnormalities. Forskolin prevented renal structural and functional abnormalities diabetic rats. In the present study, Glibenclamide (0.6mg/kg) and Atorvastatin (0.5mg/kg) were used as standard drugs. Our results demonstrated synergistic effects, when high dose of Forskolin was co-administered with standard drugs. In conclusion, treatment with adenylyl cyclase activator, Forskolin in diabetic rats reduced the oxidative stress, improved renal functions and enhanced level of endogenous antioxidants. Forskolin prevented renal functional abnormalities due to diabetes mellitus. Forskolin has a potential to prevent diabetic nephropathy, implicating direct renoprotective action in diabetic rats.

p.p1 {margin: 0.0px 0.0px 10.0px 0.0px; font: 10.0px 'Times New Roman'; color: #000000; -webkit-text-stroke: #000000}span.s1 {font-kerning: none}Presently drugs that are available to treat the diabetic induced cognitive impairment presents adverse effect on long term used. This study offers evidence that old drugs can be combined and used. Existing and affordable drugs can be repurposed and can benefit patients .The study used a combination of drugs with proven safety for preventing/delaying the development of cognitive impairment in diabetes with a hope to improve the quality of life of diabetic patients.In current  study diabetic rats were treated for eight weeks  with combination of gamma linolenic acid (30mg/kg,p.o), alpha lipoic acid (30mg/kg,p.o), phloroglucinol (250mg/kg,p.o) l-thyroxine (1mg/kg, s.c) in one group and combination of  of gamma linolenic acid (30mg/kg,p.o), alpha lipoic acid (30mg/kg,p.o), allantoin (200mg/kg,p.o), l-thyroxine (1mg/kg,s.c) in other group.The degree of preventative was determined by various parameters like body weight, measurement of neurotransmitter and calculating glycosylated haemoglobin and behavioural studies to check whether combination therapy has positive impact on diabetic induced cognitive impairment..

Candida albicans is one of the most common opportunistic fungi which cause oral cavity infections in humans. Most anti-fungal drugs posse side effects and may have an undesirable taste. Ginger is one of the oldest herbal products used in traditional medicine which has known antimicrobial effects and is used in the manufacture of Vi-One mouthwash. The present study was designed to investigate the antifungal effects of Vi-One Mouthwash. In this experimental study, the susceptibility of Candida albicans (PTCC 5027) to Vi-One Ginger mouthwash was evaluated in comparison with nystatin using disk diffusion method. One way analysis of variance (ANOVA) test was employed to evaluate the findings and P-values less than 0.05 were considered as significant. The data of the present study showed that the diameter of the inhibition zone in the nystatin group was 8.04 mm while, in the vi-one mouthwash group it was 1.16 mm. The difference between examined groups was significantly different (ANOVA, P-value=0.0001).  According to the findings, vi-one ginger mouthwash exhibited a very weak antifungal effect in comparison with nystatin in the laboratory environment.

Spironolactone has produced beneficial effects in animal models of neurodegenerative disorders. However, the underlying mechanisms of this agent on neurons and glia are mostly unknown. Therefore, we aimed to show the effects of spironolactone and fludrocortisone, a mineralocorticosteroid receptor agonist, on neuronal and glial toxicity induced by N-methyl-D-aspartate (NMDA) activation and chloroquine, an autophagy inhibitor, in the cell culture. We exposed the SHSY5Y neuroblastoma and 1321N1 astrocytoma exposed to NMDA (25µM), or chloroquine (40µM) for 24 and 48h to induce neuronal and glial toxicity. Spironolactone (1, 10, and 20µM) or fludrocortisone (300nM) were also added to the cells for 24 and 48h. Cell survival was measured using the MTT assay. Neurons and astrocytes treated with NMDA and spironolactone (1, 10, and 20µM) for 24 and 48h had lower cell death compared with the NMDA-treated group. Moreover, cells treated with NMDA and fludrocortisone for 24 and 48h had higher viability in comparison to the NMDA-treated group. The neuronal cells treated with chloroquine and spironolactone (10 and 20µM) for 24h had higher cell viability compared with the chloroquine group. Chloroquine plus spironolactone (20µM) treatment for 24 and 48h increased cell viability of astrocytes compared with the chloroquine-treated group. Moreover, the treatment of neurons and astrocytes with chloroquine plus fludrocortisone for 24h decreased cell death. Spironolactone and fludrocortisone protected neurons and astrocytes against NMDA- and chloroquine-induced toxicity. The mechanism of neuronal and glial protective effects of spironolactone possibly related to the inhibition of the mineralocorticosteroids. However, spironolactone might affect other non-mineralocorticoid systems.