DARU Journal of Pharmaceutical Sciences

Bladder cancer is the second common malignancy of genitourinary tract, and transitional cell carcinomas (TCCs) account for 90% of all bladder cancers. Due to acquired resistance of TCC cells to a wide range of chemotherapeutic agents, there is always a need for search on new compounds for treatment of these cancers. Coumarins represent a group of natural compounds, which some of them have exerted valuable anti-tumor activities. The current study was designed to evaluate anti-tumor properties and mechanism of action of 7-isopentenyloxycoumarin, a prenyloxycoumarin, on 5637 cells (a TCC cell line). MTT results revealed that the cytotoxic effects of 7-isopentenyloxycoumarin on 5637 cancerous cells were more prominent in comparison to HDF-1 normal cells. This coumarin increased the amount of chromatin condensation and DNA damage in 5637 cells by 58 and 33%, respectively. The results also indicated that it can induce apoptosis most probably via activation of caspase-3 in these cells. Moreover, propidium iodide staining revealed that 7-isopentenyloxycoumarin induced cell cycle arrest at G2/M stage, after 24 h of treatment. Our results indicated that 7-isopentenyloxycoumarin had selective toxic effects on this bladder cancer cell line and promoted its effects by apoptosis induction and cell cycle arrest. This coumarin can be considered for further studies to reveal its exact mechanism of action and also its anti-cancer effects in vivo.

Multiple organ dysfunction syndrome (MODS) and nosocomial infection following trauma-hemorrhage are among the most important causes of mortality in hemorrhagic shock patients. Dysregulation of the immune system plays a central role in MODS and a fluid having an immunomodulatory effect could be advantageous in hemorrhagic shock resuscitation. Hypertonic saline (HS) is widely used as a resuscitation fluid in trauma-hemorrhagic patients. Besides having beneficial effects on the hemodynamic parameters, HS has modulatory effects on various functions of immune cells such as degranulation, adhesion molecules and cytokines expression, as well as reactive oxygen species production. This article reviews clinical evidence for decreased organ failure and mortality in hemorrhagic shock patients resuscitated with HS. Despite promising results in animal models, results from pre-hospital and emergency department administration in human studies did not show improvement in survival, organ failure, or a reduction in nosocomial infection by HS resuscitation. Further post hoc analysis showed some benefit from HS resuscitation for severely-injured patients, those who received more than ten units of blood by transfusion, patients who underwent surgery, and victims of traumatic brain injury. Several reasons are suggested to explain the differences between clinical and animal models.

Previous studies suggest that chemical constituents present in Pinus eldarica Medw (P. eldarica) nut possess antioxidant properties that may positively influence lipid profile. The present study was conducted to evaluate the efficacy of P. eldarica nut on the experimental atherosclerosis development in hypercholesterolemic rabbits. Forty male 6 months old white New Zealand rabbits (1.8–2 kg) were randomly assigned into five equal groups. One group was kept as control (normal) group, fed on standard rabbit diet and other 4 groups were fed on high cholesterol diet (HCD). Out of four HCD groups one group was kept as control (HCD) and other three groups were treated with different doses (50, 100 and 200 mg/kg/day) of P. eldarica nut for 8 weeks. Percentage of aortic wall area changes as indication of atherosclerosis development and fasting blood cholesterol, LDL, HDL and triglyceride levels were determined in all groups. The results indicate that fasting blood cholesterol and aortic atherosclerotic involvements in 200 mg/kg/day and 100 mg/kg/day P. eldarica nut extract treated groups significantly decreased as compared to the high cholesterol-diet control group. P. eldarica nut lowers blood cholesterol level and aortic atherosclerotic involvement in hypercholesterolemic rabbits.

Dexamethasone-induced neurotoxicity has been previously reported. However, the molecular mechanisms are still not completely understood. The current work aimed to investigate the modulatory effects of α- and β-adrenergic receptors on dexamethasone-induced neurotoxicity in rats focused on changes in β-arrestin2 and molecular markers of neural injury in cerebral cortex. Male Wistar rats were subcutaneously injected with dexamethasone (10 mg/kg/day) for 7 days to induce neural injury in the cerebral cortex. The experiment involved 5 groups: control, dexamethasone, carvedilol, propranolol, and doxazosin. In the last 3 groups, drugs were given 2 hours before dexamethasone injection. At the end of experiment, brain samples were collected for measurement of brain derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), kinase activity of protein kinase B (Akt), diacylglycerol (DAG), α-smooth muscle actin (α-SMA), Smad3, β-amyloid and phospho-tau protein levels in addition to histopathological examination of brain tissue using hematoxylin-eosin, Nissl, and Sirius red stains. Moreover, β-arrestin2 levels in the cerebral cortex were measured using immunohistochemical examination. Dexamethasone slightly reduced brain weight and significantly decreased BDNF, Akt kinase activity and β-arrestin2 but markedly induced degeneration of cortical neurons and significantly increased GFAP, DAG, α-SMA, Smad3, β-amyloid and phospho-tau protein levels compared to controls. Carvedilol, propranolol, and doxazosin reversed all dexamethasone-induced molecular changes and slightly ameliorated the histopathological changes. Carvedilol significantly increased brain weight and β-arrestin2 levels compared to dexamethasone, propranolol, and doxazosin groups. blocking α- and/or β-adrenergic receptors alleviate dexamethasone-induced neurotoxicity despite their distinct effects on β-arrestin2 levels in the cerebral cortex.

Medicinal and aromatic plants are natural raw materials. Since ancient times these herbal materials are being commonly used as herbal drugs, food products, and cosmetics. The phytomolecules isolated from the medicinal and aromatic plants (MAPs) are in high demand specifically in drug industries. However, these phytomolecules have certain limitations of low absorption, high toxicity, and other side effects, bioavailability and efficacy. These limitations may be overcome by using nanotechnological tools. The plant extract or essential oil of MAPs are also useful in the synthesis of nanoparticles. In future this combinatorial application of MAPs and nanotechnology would be advantageous in the healthcare area. Literature search was performed using databases like Pubmed, Scopus and Google Scholar with the keywords “nanoparticles,” “phytomolecules,” “medicinal and aromatic plants” and “green synthesis of nanoparticles” in the text. Phytomolecules of medicinal and aromatic plants like curcumin, camptothecin, thymol, and eugenol have certain limitations of bioavailability, efficacy, and solubility. It limits its biological activity and therefore application in the biomedical area. The increment in the biological activity and sustained delivery was observed after the encapsulation of these potent phytomolecules encapsulated in the nanocarriers. Besides, MAPs and/or their molecules/oils mediate the synthesis of metal nanocarriers with less toxicity. This review highlights the impact of the combination of the MAPs with the nanotechnology along with the challenges. It would be an effective technique for the efficient delivery of different phytomolecules and also in the synthesis of novel nano-materials, which escalates the opportunity of exploration of potential molecules of MAPs.

Tribulus terrestris as a herbal remedy has shown beneficial aphrodisiac effects in a number of animal and human experiments. This study was designed as a randomized double-blind placebo-controlled trial to assess the safety and efficacy of Tribulus terrestris in women with hypoactive sexual desire disorder during their fertile years. Sixty seven women with hypoactive sexual desire disorder were randomly assigned to Tribulus terrestris extract (7.5 mg/day) or placebo for 4 weeks. Desire, arousal, lubrication, orgasm, satisfaction, and pain were measured at baseline and after 4 weeks after the end of the treatment by using the Female Sexual Function Index (FSFI). Two groups were compared by repeated measurement ANOVA test. Thirty women in placebo group and thirty women in drug group completed the study. At the end of the fourth week, patients in the Tribulus terrestris group had experienced significant improvement in their total FSFI (p < 0.001), desire (p < 0.001), arousal (p = 0.037), lubrication (p < 0.001), satisfaction (p < 0.001) and pain (p = 0.041) domains of FSFI. Frequency of side effects was similar between the two groups. Tribulus terrestris may safely and effectively improve desire in women with hypoactive sexual desire disorder. Further investigation of Tribulus terrestris in women is warranted.

Currently, people are more interested to traditional medicine. The traditional formulations should be converted to modern drug delivery systems to be more acceptable for the patients. In the present investigation, a poly herbal medicine “Ayarij-e-Faiqra” (AF) based on Iranian traditional medicine (ITM) has been formulated and its quality control parameters have been developed. The main ingredients of AF including barks of Cinnamomum zeylanicum Blume and Cinnamomum cassia J. Presl, the rhizomes of Nardostachys jatamansi DC., the fruits of Piper cubeba L.f., the flowers of Rosa damascena Herrm., the oleo gum resin of Pistacia terebinthus L. and Aloe spp. dried juice were powdered and used for preparing seven tablet formulations of the herbal mixture. Flowability of the different formulated powders was examined and the best formulations were selected (F6&F7). The tablets were prepared from the selected formulations compared according to the physical characteristics and finally, F7 was selected and coated. Physicochemical characters of core and coated AF tablets were determined and the HPLC method for quantitation of aloin as a marker of tablets was selected and verified according to selectivity, linearity, precision, recovery, LOD and LOQ. The results showed that core and coated AF tablets were in agreement with USP requirements for herbal drugs. They had acceptable appearance, disintegration time, friability, hardness, dissolution behavior, weight variation and content uniformity. The amount of aloin in tablets was found 123.1 mg/tab. The HPLC method for aloin determination in AF tablets was verified according to selectivity, linearity (5–500 μg/ml, r2:0.9999), precision (RSD: 1.62%), recovery (108.0%), LOD & LOQ (0.0053 & 0.0161 μg/ml). The formulated tablets could be a good substitute for powder and capsules of AF in ITM clinics with a feasible and precise method for its quality control. Ayarij-e-Faiqra formulation

Nhiều hợp chất 2,4-dinitrophenyl và 2,4-dinitrophenylamine gắn 5-FU (5-fluorouracil) so với các thành phần của chúng đã cho thấy độc tính tối thiểu hoặc không có độc tính với dòng tế bào HT-29 dưới điều kiện hiếu khí nhưng có độc tính cao và hiệu ứng cảm ứng bức xạ dưới điều kiện thiếu oxy. Trong nghiên cứu hiện tại, độc tính tế bào và sự tăng cường bức xạ của ba dẫn xuất mới của các hợp chất này bằng cách thay thế nhóm 2,4-dinitrophenyl bằng 2-methyl-5-nitroimidazole, một tác nhân cảm ứng bức xạ và độc tính đã được biết đến, đã được điều tra.

Các hợp chất gắn 7–9 được chuẩn bị bằng cách phản ứng 1-(t-butoxycarbonyl)-5-fluorouracil 6 với các este metronidazole 2–4 theo sau là việc loại bỏ nhóm bảo vệ t-butoxycarbonyl. Độc tính của các hợp chất trong tế bào HT-29 có hoặc không có bức xạ đã được xác định bằng phương pháp 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), iodua propidium (PI)-digitonin và các thử nghiệm clonogenic.

Các hợp chất gắn 7–9 đã gây ra độc tính phụ thuộc vào thời gian và nồng độ dưới điều kiện thiếu oxy nhưng không có ảnh hưởng đáng kể dưới điều kiện hiếu khí. Những hợp chất này cũng cho thấy hiệu ứng cảm ứng bức xạ phân chọn lọc và phụ thuộc nồng độ dưới điều kiện thiếu oxy.

Các hợp chất gắn 7–9 so với 5-FU 5 đã cho thấy độc tính tối thiểu dưới điều kiện hiếu khí và hoạt tính cảm ứng bức xạ chọn lọc dưới điều kiện thiếu oxy. Ngoài ra, hiệu ứng của các hợp chất này còn cao hơn so với metronidazole 1, vốn là một chất độc tế bào và tác nhân cảm ứng bức xạ đã được biết đến dưới các điều kiện thiếu oxy.