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   Table of Contents - Current issue
July-December 2021
Volume 10 | Issue 2
Page Nos. 159-334

Online since Saturday, December 18, 2021

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A review on novel topical formulations of vitamins Highly accessed article p. 159
Juhi Desai, Rashmi Mallya
Cosmeceuticals are cosmetic products with biologically active ingredients purporting to have drug-like benefits. Cosmeceuticals are one of the fastest-growing segments of the personal care industry as their use has drastically increased over the years. Vitamins being one of the popular ingredients in cosmeceuticals have numerous skin benefits. Vitamins are organic micronutrients essential for the proper functioning of the body. The popular vitamins used in cosmetics are vitamin A, vitamin B3, vitamin C, vitamin E, and vitamin K. These vitamins play an important role in treating skin conditions like acne, hyperpigmentation, and photoaging, protecting from UV, deactivating free radicals, and improving skin moisture retention levels of the skin. This review article emphasizes on the novel formulation of the vitamins-based cosmeceuticals. The novel carriers system has gained importance in cosmetic delivery due to its advantages such as enhanced skin penetration, sustained and controlled drug release profile, maintenance of the concentration within the therapeutic range, with greater safety and targeted delivery of active to the desired tissues.
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Herbal nanoemulsion in topical drug delivery and skin disorders: Green approach p. 171
Chanchal Chaurasiya, Jitendra Gupta, Sachin Kumar
A topical drug delivery system can be a future trend for drug delivery because of the availability of the largest surface area of skin than any other organ. Although the skin has some advantages such as ease of application, patient compliance, and safety, it has many disadvantages such as permeability and bioavailability via first-pass metabolism and others. Nanoemulsion can be a future trend for topical delivery of drugs because of its very fine droplet size range, lipophilic and/or hydrophilic nature, and suitability for various administration routes such as parenteral, oral, topical, intranasal, ocular, and pulmonary. The contents of nanoemulsions make them suitable for human use because the oil/lipid, water, surfactants, and co-surfactants used in the formulation of nanoemulsion are relatively safe and nontoxic. Nowadays, people are more attracted to natural preparations as of their inherited qualities and fewer side effects. Due to herbal drugs’ compatibility in nanoemulsion, it is considered the best technology for the green approach of the medicine system. The article presented the foundation for the above statement by different literature surveys on the herbal nanoemulsion formulations.
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Clinical profile of patients with baclofen poisoning in an academic medical center p. 182
Mitra Rahimi, Peyman Erfan Talab Evini, Yavar Yousefi, Mahbobeh Oroei
Context: Baclofen overdose acutely affects the nervous system and induces a decrease in the consciousness level, coma, and death. The diagnosis of it is based on the patient’s history and clinical findings. Aims: The present study aims to investigate baclofen-induced poisoning based on medical reports in a 5-year period. Materials and Methods: This retrospective study was conducted in Loghman Hakim Hospital, Tehran, Iran. The medical profile of 135 patients with baclofen overdose was read out, collected, and analyzed using SPSS version 18. Results: The average age of 135 patients was 26.37±18.73 years. The majority of them were female (68.1%) and intentional attempts (66.7%). There were 117 patients (86.7%) with central nervous system symptoms. The most common nervous finding was drowsiness (n = 53, 45.3%). There was no patient with seizures. There was a significant statistical relationship between the dose of baclofen and consciousness level (GCS ≤12: 302.61 ± 236.40 mg, and GCS >12: 162.21 ± 121.02 mg, P < 0.001). Conclusion: Baclofen overdose should be considered in patients referred to the emergency department with drowsiness symptoms and decreased consciousness level. Because of this poisoning, it has no specific symptoms and is common in female and young people.
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Study of monoamine oxidase inhibitory effects of seven Iranian medicinal plant extracts p. 187
Mohsen Shamsi, Maliheh Soodi, Homa Hajimehdipoor, Alireza Ghazanfari
Background: Monoamine oxidase (MAO) enzymes abundantly found in the central nervous system (CNS) play an essential role in CNS disorders, so monoamine oxidase inhibitors (MAOIs) have been used for the treatment of neurological ailments such as depression, Parkinson’s, and Alzheimer’s disease. Therefore, finding the new selective MAOIs is still on the focus of researchers’ attention. This study aimed to evaluate MAO-A and MAO-B inhibitory effects of seven methanolic extracts of Iranian medicinal plants including Sanguisorba minor, Cerasus microcarpa, Ferulago angulata, Stachys pilifera, Amygdalus scoparia, Rosa canina, and Alhagi pseudalhagi.Materials and Methods: The dried aerial parts of the plants were extracted with methanol by the maceration method. The inhibitory effects of extracts on MAO-A and MAO-B enzymes of rat brain mitochondria were measured by the fluorimetric method by using kynuramine as a substrate. Results: Among the extracts, S. minor (IC50 = 7.133 μg/mL) and C. microcarpa (IC50 = 49.53 μg/mL) were the most potent MAO-A and MAO-B inhibitors, respectively. A comparison of the IC50 value indicated that A. scoparia and S. pilifera had a higher affinity for MAO-A inhibition, whereas C. microcarpa and R. canina selectively inhibited the MAO-B enzyme. Moreover, F. angulata was recognized as a non-specific MAO inhibitor. The A. pseudalhagi and S. minor extracts did not show any MAO-B inhibitory effect. Conclusion: Our study showed that studied extracts have different MAO-A and MAO-B inhibitory effects. Therefore, they can be used for the treatment of various CNS disorders; also, these extracts are an excellent source for finding new compounds with MAO-A or MAO-B inhibitory effects.
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Investigation of the effects of Satureja edmondi on memory impairment caused by chemical kindling in adult male rats p. 194
Gelavij Mahmoodi, Somayeh Bohlouli
Introduction: Epilepsy causes neuronal damage that disturbs normal brain functioning, especially in the hippocampal formation. In addition, it has been shown that cognitive inconsistencies, changes in emotional behavior, and neuronal loss in the hippocampus occur during pentylenetetrazole (PTZ)-induced kindling. So, the purpose of the present research was to investigate whether administration of Satureja edmoni is able to prevent memory impairment, caused by PTZ-induced kindling in adult male rats. Materials and Methods: In this study, male rats were kindled by repeated (two or three) injection of PTZ intraperitoneally (i.p.) (25 mg/kg); then all animals in the extract groups were treated with 100, 200, or 400 mg/kg of S. edmondi. For behavior assessment, an inhibitory passive avoidance task was used. Results: Our results showed that animals in the kindled group took less time to enter dim hutch than control rats. There was a significant difference in step-through latency (STL) recorded from group of rats with PTZ-induced kindling treated with S. edmondi at concentrations 100 and 200 mg/kg and control rats, but differences between STL of PTZ-induced kindling animals treated with S. edmondi 400 mg/kg vs. control rats were not significant. Conclusion: In this study, we observed that PTZ induced impairing effects on passive avoidance memory; in contrast, administration of S. edmondi could abolish the impairment effect of epilepsy on memory.
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Solid SMEDDS: An approach for dissolution rate enhancement using telmisartan as model drug p. 198
Ashish Y Pawar, Yogesh S Harak, Santosh R Tambe, Swati G Talele, Deepak D Sonawane, Deelip V Derle
Bioavailability improvement of poorly water-soluble drugs is a challenging task for many of the drug candidates. In recent years, an area that is ahead in popularity for different formulation expertise is the use of lipid-based careers to formulate self-emulsifying drug delivery systems (SEDDS) for enhancing the oral bioavailability of lipophilic drugs. The self-microemulsifying drug delivery systems (SMEDDS) are thermodynamically stable and isotropic solutions containing an oil, surfactant, co-surfactant (CoS; or solubilizer), and mixtures of drug which forms oil-in-water microemulsions when incorporated in water and stirred. Different techniques are available to convert liquid–self-microemulsifying drug delivery systems (L-SMEDDS) to solid among which an adsorption technique is economical and very simple. The solid–self-microemulsifying drug delivery systems (S-SMEDDS) of telmisartan (TEL) was developed in the present study which is a poorly water-soluble drug. Different formulations of L-SMEDDS were developed using Capmul PG 8 as oil, Cremophor RH 40 as a surfactant, and Transcutol P as a CoS and were later transformed to S-SMEDDS. The formulations were assessed for dilution study by visual observation, differential scanning calorimetry, analysis of solid S-SMEDDS morphologically, in vitro dissolution test, zeta potential measurement, etc. Significantly higher drug release was observed from S-SMEDDS as compared to plain TEL. Hence, it can be concluded that the adsorption technique is a promising approach for the formulation of S-SMEDDS with improved dissolution rate and concomitantly bioavailability.
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Effects of Aegle marmelos (L.) methanolic leaf extracts on biochemical parameters in diabetic rats p. 209
Ravi Babu Birudu, Padmavathi Pamulapati, Sathish Kumar Manoharan
Background: Aegle marmelos (L.) Correa is a widely found plant in India as well as in South Asia. For more than several centuries, it is being widely used for its medicinal properties. Objective: The objective of this study was to evaluate the biochemical changes in alloxan-induced diabetic rats treated with methanolic leaf extracts of A. marmelos. Materials and Methods: Six treatment groups (namely control, diseased, standard (glimepiride), low dose (100 mg/kg), medium dose (250 mg/kg), and high dose (500 mg/kg) of methanolic leaf extracts were used in the study. The biochemical effects were evaluated by the determination of albumin-to-globulin ratio (A/G ratio), albumin, amylase, bilirubin, blood urea, blood urea nitrogen, calcium, direct bilirubin, globulin, glucose-6-phosphate, glycated hemoglobin (HbA1c), homocysteine, indirect bilirubin, inorganic phosphate, lipase, mean blood glucose, serum uric acid, and vitamin D3. Results: No significant changes were observed in A/G ratio among the treatment groups when compared with the diseased and control treatment groups. Low- and medium-dose-treated animals showed a significant change in albumin, bilirubin, calcium, direct bilirubin, indirect bilirubin, globulin, glucose-6-phosphate, homocysteine, inorganic phosphate, lipase, and vitamin D3 levels when compared with standard treatment group as well as diseased group. Low-dose treatment group animals showed a significant increase in amylase and mean blood glucose levels than the diseased treatment groups, whereas low-dose treatment group animals showed a significant decrease in HbA1c levels than the diseased treatment groups. Conclusion: Through the biochemical changes, it is evident that the low and medium dose of methanolic leaf extract of A. marmelos can be used in the treatment of diabetes and its complications.
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Hepatoprotective effects of Hertia cheirifolia butanolic extract and selenium against CCl4-induced toxicity in rats p. 216
Mouna Menakh, Saber Boutellaa, Djahida Mahdi, Amar Zellagui, Mesbah Lahouel, Mehmet Ozturk
Background: Hertia cheirifolia, a traditional plant endemic to both Tunisia and Algeria, is used for the treatment of various disorders. This study investigates the antioxidant and protective effects of H. cheirifolia butanolic extract (BEHC) alone and combined with selenium (Se) against carbon tetrachloride (CCl4)-induced liver damage in rats. Experimental Procedure: Thirty male Wistar rats were randomly divided into six groups: (1) normal control, (2) hepatotoxic control, (3) positive control received silymarin 100 mg/kg body weight (bw), (4) BEHC (100 mg/kg bw), (5) BEHC (400 mg/kg bw), and (6) BEHC (400 mg/kg bw) + Se (0,3 mg/kg bw) once daily for 14 consecutive days, followed by hepatotoxicity induction with CCl4 in olive oil 0.6 mL/kg bw intraperitoneally. Some biochemical and oxidative stress parameters were investigated. Quantity and quality of phenolics in BEHC were determined by spectrophotometer and high-performance liquid chromatography with diode-array detection (HPLC-DAD) analysis, respectively. Results and Conclusion: BEHC contained high amounts of total phenolics and flavonoids where seven compounds were identified. The pretreatment with BEHC or with BEHC and Se significantly reduced the levels of plasma aminotransferases (alanine aminotransferase [AST] and aspartate aminotransferase [ALT]), alkaline phosphatase, malondialdehyde (MDA), and increasing glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) levels in hepatic tissues. In conclusion, BEHC has a potent natural antioxidant activity that can be used with Se to reduce hepatotoxicity.
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Tin (IV) oxide (SnO2) nanoparticles inhibit the viability of cervical cancer HeLa cells through induction of apoptosis p. 225
Parisa Bazsefidpar, Shabnaz Koochakkhani, Behnaz Rahnama Inchehsablagh, Ebrahim Eftekhar, Elahe Aliasgari
Introduction: Resistance to chemotherapy and severe side effects have been reported as the main reasons for treatment failure in patients with cervical cancer. Therefore, it is necessary to find new treatment strategies with fewer side effects and more efficacy. This study aimed to investigate the cytotoxic property of tin (IV) oxide (SnO2) nanoparticles (NPs) against human cervical cancer cells (HeLa cells). In addition, the molecular mechanism of anticancer activity of SnO2 NPs was evaluated. Materials and Methods: The cytotoxicity of SnO2 NPs against HeLa cells and normal mouse fibroblast cells (L929) was studied using an MTT assay. To determine the mechanism of action of SnO2 NPs, the cells were treated with the half maximal inhibitory concentration values of SnO2 NPs for 24 h and apoptotic cell percentage was assessed by Annexin-PI and flow cytometry. In addition, real-time quantitative polymerase chain reaction (PCR) was used to evaluate the mRNA expression levels of apoptotic genes (Bax and Bcl-2). Results: SnO2 NPs suppress the viability of HeLa cells in a dose-dependent manner. This compound was more cytotoxic against HeLa cells than L929 cells. Flow-cytometry analysis revealed that SnO2 NPs significantly caused cell growth arrest. Moreover, real-time PCR results showed that SnO2 NPs treatment decreased Bcl-2 and increased Bax expression level. Conclusion: SnO2 NPs treatment significantly inhibit HeLa cells viability through the induction of apoptosis. Interestingly SnO2 NPs were more cytotoxic against HeLa cells than normal fibroblast cells, which may provide promising evidence for their applications as an anticancer drug.
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Phytochemical screening, antioxidant, antibacterial, and antidandruff activities of leaf extract of Artemisia indica p. 231
Pragyan Dahal, Govinda Bista, Prasanna Dahal
Background: Artemisia indica is a traditionally used medicinal plant in the treatment of various conditions such as loss of appetite, abdominal discomfort, antimalarial infection, dermal wound infection, etc. Objectives: This study aims to determine the presence of phytochemical content, antioxidant, antibacterial, and antidandruff activity of leaf extract of A. indica. Materials and Methods: Dried ground leaves were subjected to a cold extraction method using an absolute concentration of methanol, ethanol, and water. Total phenolic, flavonoid, and proanthocyanidin content was estimated by using a linear regression equation from the calibration curve and expressed in terms of gallic acid equivalent (GAE) and rutin equivalent (RE). Antioxidant properties were determined using DPPH (1,1-diphenyl-2-picryl-hydrazyl), nitric oxide, and hydrogen peroxide assay, and their IC50 values were calculated. The antibacterial activity was tested using the agar well diffusion method against the common five pathogenic strains, and the zone of inhibition is compared with gentamicin (1 mg/mL) as a positive control. The minimum inhibitory concentration (MIC) value was obtained by the microbroth dilution method. The antidandruff assay was performed on Malassezia furfur by the disk diffusion method into Sabouraud dextrose agar overlaid with 1 mL of olive oil, and the MIC value was determined by the microtiter plate method. Results: The result showed that the Artemisia methanolic extract represents ample content of phenolics (248±3.29 mg/g of GAE), flavonoids (222.33±4.41 mg/g of RE), and proanthocyanidin (222.83±1.62 mg/g of RE equivalent). The antioxidant assay revealed that methanolic extract has the highest radical scavenging activity followed by aqueous extract and then ethanolic extract. The antibacterial activity of leaf extract shows MIC value ranging from 6 to 25 μg/mL against various human pathogenic bacteria. The antidandruff assay showed that MIC value of methanolic extract is lesser than that of ethanolic extract (350<400) mg/mL. Conclusion: The results concluded that leaf extract of A. indica contains phenolics, flavonoids, and proanthocyanidin and exhibits adequate antibacterial, antidandruff, and antioxidant activity.
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Formulation and evaluation of transdermal patch of rabeprazole sodium p. 240
Manisha Soral, Shivakumar H Nanjappa, Prajila Alayadan
Aim: The goal of the current study is to design and evaluate transdermal patches of rabeprazole sodium (RPS). Materials and Methods: Transdermal patches of RPS were prepared using polymers such as hydroxyl propyl cellulose (HPC-EF), polyvinyl pyrrolidone K-30 (PVP K-30), and polyvinyl pyrrolidone K-90 (PVP K-90) as film formers, polyethylene glycol (PEG-400) as a plasticizer, and Tween-80 and azone as permeation enhancers. The solvent casting technique was employed to develop the patches using aluminum foil as the backing membrane. These patches were evaluated for compatibility using Fourier transform infrared (FTIR) spectrophotometry and for content by ultraviolet (UV) spectrophotometry besides physicochemical properties such as thickness, adhesion, moisture content, moisture loss, and folding endurance. The patches were tested for in vitro release in United States Pharmacopoeia (USP) dissolution apparatus V and ex vivo permeation across shed snake skin in vertical Franz diffusion cell (FDC). Results: The characteristic FTIR spectra of RPS were also evident in the spectra of the patches, indicating drug-excipient compatibility. In vitro drug release indicated that the release of the drug was maximum from patches composed of HPC-EF (60.08±1.04%), which was much higher when compared with patches made of PVP K-30 (47.53±0.40%) and PVP K-90 (42.84±0.74%). The ex vivo permeation studies suggested that about 116.79±1.99 µg/cm2 of the drug was permeated in 24 h from formulation patches composed of HPC-EF that resulted in flux of nearly 7.06 µg/cm2/h. Conclusion: The studies indicated that feasibility of transdermal delivery of rabeprazole as a patch of 16 cm2 is likely to suffice the therapeutic requirement.
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Antidiabetic potential yacon (Smallanthus sonchifolius (Poepp.) H. Rob.) leaf extract via antioxidant activities, inhibition of α-glucosidase, α-amylase, G-6-Pase by in vitro assay p. 247
Wahyu Widowati, Rita Tjokropranoto, Roro Wahyudianingsih, Fen Tih, Lisawati Sadeli, Hanna Sari Widya Kusuma, Nerissa Arviana Fuad, Ermi Girsang, Faustina Audrey Agatha
Background: Diabetes is a chronic disease characterized by glucose levels and results in impaired insulin secretion. This disorder has triggered oxidative stress and excess free radicals condition. Smallanthus sonchifolius is a traditional medicine that acts as a diabetic therapy. This research aims to bring out the antidiabetic and antioxidant potential of S. sonchifolius extract (SSE). Materials and Methods: This study was conducted to measure the qualitative phytochemical identification, antioxidant and anti-diabetic activity of SSE. The antioxidant assay was carried out using 2,2-diphenyl-1-picrylhydrazine (DPPH)-scavenging activity, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)-scavenging and hydrogen peroxide (H2O2)-reducing activity assays, ferric reducing antioxidant power (FRAP) potency, while anti-diabetic activity of SSE assay was carried out using inhibitory of α-amylase, α-glucosidase, and Glucose-6-Phosphatase (G-6-Pase). Results: SSE contained phenols, flavonoids, steroids/triterpenoids, saponins, tannins, and alkaloids. The antioxidant and antidiabetic activities of samples were calculated based on median inhibitory concentration (IC50). The IC50 values of SSE antioxidant, respectively, were DPPH (IC50 = 62.72 μg/mL), ABTS (IC50 = 61.03 μg/mL), H2O2 (IC50 = 438.36 μg/mL), the highest FRAP activity was 125.31 μM Fe(II)/μg extract at a concentration level of SSE 50 μg/mL. The IC50 values of SSE antidiabetic were α-amylase inhibition (IC50 = 37.86 μg/mL), α-glucosidase inhibition (IC50 = 90.41 μg/mL), and G-6-Pase inhibition (IC50 = 98.07 μg/mL), respectively. Conclusions: SSE has antidiabetic potential through antioxidant activities and α-glucosidase, α-amylase, and G-6-Pase inhibition activities.
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Anredera cordifolia (Ten.) Steenis and Sonchus arvensis L. inhibit gentamicin-induced nephrotoxicity: The role of urinary N-acetyl beta-D-glucosaminidase p. 256
Nova Suliska, Neng Fisheri Kurniati, Elin Yulinah Sukandar
Introduction: Anredera cordifolia (Ten.) v Steenis and Sonchus arvensis L. have been used traditionally to treat many diseases such as inflammation, hypercholesterolemia, and kidney stones. This study investigated the renoprotective effect of the best combination of A. cordifolia (Ten.) Steenis and S. arvensis L. against gentamicin-induced nephrotoxicity in rats reduced the urinary N-acetyl beta-D-glucosaminidase (NAGase) specific marker. Materials and Methods: This study used male Wistar rats, weighing 200–300 g. The experiment consisted of a negative control group, a positive control group, A. cordifolia 100 mg/kg (body weight) b.w. group (AE), S. arvensis 100 mg/kg b.w. group (SE), A. cordifolia 50 mg/kg b.w. + S. arvensis 50 mg/kg b.w. (AE50 + SE50), A. cordifolia 100 mg/kg b.w. + S. arvensis 100 mg/kg b.w. (AE100 + SE100), A. cordifolia 75 mg/kg b.w. + S. arvensis 25 mg/kg b.w. (AE75 + SE25), and A. cordifolia 25 mg/kg b.w. + S. arvensis 75 mg/kg b.w. (AE25 + SE75). All groups were given the extract according to the group for 14 days orally. On day 15, all groups except the negative control group induced renal failure by administering gentamicin 100 mg/kg b.w. for 8 days along with the extract. On day 22, the evaluation was carried out by measuring urea, creatinine, and NAGase. Results: All treatment groups showed significantly decreased levels of creatinine and urea in serum and urinary NAGase when compared with the positive control group (P < 0.05). The AE75 + SE25 group showed the smallest elevated levels of creatinine (14, 36%) and urea (17.4%) in serum and urinary NAGase (29.4%) when compared with the positive control group (P < 0.05). Conclusion: The combination of A. cordifolia 75 mg/kg b.w. and S. arvensis 25 mg/kg b.w. extract showed a better nephroprotective effect in decreasing the NAGase as the early biomarker in kidney failure.
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The randomized clinical trial of safety and efficacy of oral tramadol in patients undergoing colonoscopy p. 261
Mehdi Zobeiri, Teimour Kamari, Mansour Rezaei, Mohammad Hosein Farzaei
Background and Study Aims: Colonoscopy is a wide-spreading procedure with pain as a habitual challenge for the therapeutic team. The aim of this study is to evaluate safety and efficacy of oral tramadol in patients undergoing colonoscopy. Patients and Methods: This randomized controlled trial was performed in 124 consecutive patients who completed total colonoscopy, which is randomly divided into two groups, receiving either 100 mg single dose oral tramadol or placebo. Pain intensity during colonoscopy is evaluated by numerical rating scale (NRS) criteria in four levels: no pain, mild, moderate, and severe pain. This study was registered in www.IRCT.ir, number: IRCT2015010820610N1. Results: Two groups were matched in age, sex, and colonoscopy indication. The pain intensity in patients receiving tramadol was significantly lower than that in patients receiving placebo (P <0.05). Nausea, sweating, moaning, and palpitation during colonoscopy were significantly lower, and desire to do a colonoscopy without sedation was significantly higher in the tramadol group. Conclusion: Oral tramadol in patients undergoing colonoscopy is effective in reducing pain and symptoms.
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Attenuation of hyperinsulinemia-induced DNA damage of peripheral lymphocytes by carvedilol p. 265
Farshad Naghsh-Nilchi, Mahmoud Etebari
Context: Most people with diabetes suffer from cardiovascular problems; however, increased oxidative stress caused by diabetes can increase the risk of DNA damage and cancer. Carvedilol is a third-generation beta-blocker that can both improve heart function and prevent oxidative stress. Aims: The present study aimed to assess carvedilol’s genoprotective effects against hyperinsulinemia-induced DNA strand break in rats. Materials and Methods: To evaluate the extent of DNA damage caused by high insulin concentrations and the effect of carvedilol on these lesions, isolated lymphocytes of high-fat type 2 diabetic rats were evaluated using the comet method. Results: Our results in this study using the comet method showed that hyperinsulinemia and hyperglycemia of high-fat diet have significant genotoxic parameters in rats (tail length 84.35 ± 0.23 vs. 0.90 ± 0.02, % DNA in tail 16.09 ± 0.09 vs. 7.63 ± 0.04, and tail moment 13.58 ± 0.09 vs. 0.07 ± 0.01) compared with the control group (P < 0.001). In rats receiving carvedilol, we observed the genoprotective effect in a dose-dependent manner, which is predicted due to the antioxidant activity of carvedilol and its metabolites. Conclusion: It does not have an adverse effect on the blood sugar profile of diabetics and reduction of cardiovascular complications of the disease; carvedilol can prevent genetic damage and cancer risk in hyperinsulinemia induced by the high-fat diet.
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Enhancing cognitive performance with rejuvenation of brain antioxidant markers and acetylcholinesterase activity by ethanolic extract of Cucurbita pepo L. seeds in scopolamine-induced model of dementia in rats p. 271
Parminder Nain, Sunil Kumar, Manisha Bhatia, Jaspreet Kaur
Background: Cucurbita pepo L. herb has been traditionally used for treating numerous disorders in Asian and African countries, including India. Objective: The aim of the present study was to evaluate the memory-enhancing activity of C. pepo L. seeds based on its antioxidant potential in cognitive impairment rat model induced by scopolamine. Materials and Methods: The experimental animals were treated with the ethanolic extract of C. pepo L. seeds (EECPS) (200, 400, and 800 mg/kg, p.o.). Piracetam (200 mg/kg, p.o.) was used as standard drug and given for 14 consecutive days. Cognitive impairment was evaluated by a passive avoidance apparatus and the Morris water maze test. The oxidative parameters in brain of rats were estimated to explore oxidative stress in experimental animals. Data were analyzed by using one-way analysis of variance followed by Student’s t-test. Results: The phytochemical analysis revealed the presence of active ingredients such as terpenoids, phenols, alkaloids, and flavonoids in the EECPS. The total phenol content was estimated quantitatively in EECPS and found to be 8.37±0.2 mg gallic acid equivalent/g. The EECPS at a dose of 400 mg/kg has depicted a maximum increase in step-down latency and reduction in escape latency on behavioral tests, with decrease in oxidative stress by showing an increase in levels of superoxide dismutase, catalase, and glutathione and subsequently a decrease in the malondialdehyde level. Cholinesterase activity was also found to decrease with 400 and 800 mg/kg EECPS when compared with the scopolamine group. Conclusion: The results of the study clearly suggest that EECPS ameliorated spatial memory impairment induced by scopolamine, which could further attribute to their antioxidant properties.
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A randomized, double-blind controlled clinical study to evaluate the efficacy and safety of minoxidil topical 2% nanosuspension with aqueous base in the treatment of androgenetic alopecia areata p. 279
Shahla Mirzaeei, Ashkan Barfar, Saba Mehrandish, Ali Ebrahimi
Background and Purpose: Using the commercially manufactured forms of minoxidil, the only approved topical drug preparation for hair regrowth in patients with androgenetic alopecia (AGA) comes across with challenges such as limited permeation through the superficial layers of the skin to reach the site of action and topical adverse reactions like itching and inflammation occur because of the ethanol in the formulations. In this study, a novel nanosuspension formulation with an aqueous base was prepared and evaluated to overcome the discussed challenges. Materials and Methods: The nanosuspension formulation was characterized by size, zeta potential, morphology, and in vitro release. Seventy patients were subjected to use either 1 mL of nanosuspension or the commercial product twice daily for six months and were then examined for changes in hair follicle diameter and hair density within a 1 × 1-cm2 area of the scalp as the primary endpoints besides any adverse reaction manifestation as the secondary endpoint. Results: The nanosuspension formulation showed uniform morphology, 200-nm particle size, and suitable zeta potential that ensures the stability. The in vitro release study exhibited almost 90% release in the first 6 h. It was observed that there were no significant differences between the efficacy of aqueous-based topical 2% nanosuspension of minoxidil and the commercial product in the treatment of AGA (P > 0.05). However, the aqueous-based topical 2% nanosuspension formulation showed better safety and tolerability compared to the marketed profile. Conclusions: It could be concluded that aqueous-based topical 2% nanosuspension is a suitable form with enhanced patient compliance compared to commercially manufactured products.{Figure 6}
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Quantitative and qualitative analyses of the constituents of the hydroalcoholic extract of Quercus infectoria gall from Kermanshah and evaluation of its antioxidant and antibacterial activities p. 287
Negar Mohammadzadeh, Masoud Ghiasian, Javad Faradmal, Dara Dastan
Background and Purpose: Quercus infectoria is a species of Quercus genus (Fagaceae) whose galls are known in traditional medicine for their antibacterial, analgesic, anti-inflammatory, and astringent effects. The present study aimed to carry out quantitative and qualitative analyses of the constituents of the hydroalcoholic extract of the Q. infectoria galls from Kermanshah and to evaluate its antioxidant and antibacterial activities. Materials and Methods: Following the extraction process using ethanol/water (70/30), phytochemical tests were done. Total phenol and flavonoid and antioxidant and antibacterial activities against specific strains of bacteria were evaluated. Some of the constituents of the extract were identified using high-performance liquid chromatography-photodiode array, and their amount was obtained. Results: The phytochemical tests proved that the extract contained alkaloid, flavonoid, tannin, saponin, and phenolic compounds. The amount of total phenolic and flavonoid compounds was 16.21 and 1.78 mg/g dried galls, respectively. The IC50 value of the antioxidant constituents of the extract was 47 μg/mL. The results of the antimicrobial assay showed the high activity of the extract against Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, and S. epidermidis. The quantitative analysis of the extract confirmed the presence of gallic acid, rutin, quercetin, benzoic acid, and caffeic acid (12.30, 10.72, 5.00, 9.25, and 3.94 mg/g dried galls, respectively). Conclusion: Considering the results of this study, the extract of Q. infectoria galls could be used as a primary substance in treating bacterial infections and oxidative stress-related diseases.
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Clinical effectiveness and safety of sofosbuvir–velpatasvir as add-on treatment for COVID-19 patients: Study protocol and preliminary data for the randomized controlled trial p. 294
Babak Sayad, Masomeh Mehrabi, Reza Khodarahmi, Farid Najafi, Ronak Miladi, Zeinab Mohseni Afshar, Feizollah Mansouri, Maria Shirvani, Mehdi Salimi, Fatemeh Khosravi Shadmani
Objectives: COVID-19 is a worldwide health problem. Although the most infected patients experience a mild-to-moderate disease, some patients (especially older people) develop pulmonary distress with fatal lung failure and multi-organ damage. There is currently no known effective treatment for this disease. Sofosbuvir, an FDA-approved drug for the treatment of hepatitis C virus, is also able to inhibit other members of positive strand RNA viruses with conserved polymerase and may be helpful for the treatment of SARS-CoV-2. The goal of the current trial is to determine the usefulness of “standard of care (SOC) plus hydroxychloroquine and lopinavir/ritonavir” vs. “SOC plus a combination of lopinavir/ritonavir hydroxychloroquine and sofosbuvir/velpatasvir” in patients hospitalized with COVID-19. The Design of Clinical Trial: In this randomized controlled trial, patients over 18 years who have been diagnosed with COVID-19 by the positive SARS-CoV-2 reverse transcriptase–polymerase chain reaction (RT–PCR) test or compatible chest computed tomography (CT) scan were candidates for the study. Eighty patients from Kermanshah province, West of Iran were allocated to treatment with SOC plus hydroxychloroquine and lopinavir/ritonavir (dual therapy) or SOC plus a combination of hydroxychloroquine and lopinavir/ritonavir and sofosbuvir/velpatasvir (triple therapy) for 10 days. Allocation was conducted using simple randomization. The primary outcomes were reducing mortality up to 28 days after hospitalization. Adverse events were handled and reported in accordance with the Good Clinical Practice guidelines. Participants: Patients who were hospitalized with COVID-19 (with positive SARS-CoV-2 RT–PCR test and/or compatible chest CT scan) were screened for eligibility at Farabi Hospital, Kermanshah University of Medical Sciences (KUMS), Kermanshah, Iran. Intervention and Comparator: Both arms received active treatment and none was given placebo. The intervention arm received hydroxychloroquine 400 mg single dose and lopinavir–ritonavir (400 and 100 mg) twice daily plus sofosbuvir–velpatasvir (400 and 100 mg) once daily orally, plus SOC for 10 days. The comparator arm received hydroxychloroquine 400 mg single dose and lopinavir–ritonavir (400 and 100 mg) twice daily orally, plus SOC for 10 days. SOC includes oxygen therapy, non-invasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, and corticosteroids. Primary Outcomes: The main outcomes are reducing mortality until 28 days after hospitalization. Other outcomes can be found in full protocol file. Randomization: For the purpose of allocation sequence generation, using an Excel file (random-numbers table) and simple random allocation, 80 included patients entered to the study, 40 patients in each group (1:1 ratio). In order to maintain the allocation sequence concealment, the details of treatment for each patient were contained in a sealed envelope, labeled by the numbers from 1 to 80. In fact, our study was a randomized open label clinical trial in which all the physicians and nurses plus all patients were aware of the type of treatment. Blinding: Our study was a randomized open label clinical trial in which all the physicians and nurses plus all patients were aware of the type of treatment. Numbers to be Randomized (Sample Size): Eighty included patients entered to the study, 40 patients in each group using simple random allocation. Trial Status: The finalized protocol version 1.5 was used in the trial study and the recruitment/intervention process started on April 11, 2020, finished on May 11, and the related follow-up finished on June 8, 2020. Registry of Clinical Trial: This clinical trial has been registered on March 30, 2020 under IRCT number 46790, in the Iranian Registry of Clinical Trials (https://www.irct.ir/trial/46790) and by KUMS under Grant No. 990097. Full Protocol: The full protocol and other details are attached as a Supplementary File (full protocol), accessible from the journal website. Preliminary Data: The sofosbuvir/velpatasvir regimen does not improve survival, clinical improvement, and duration of hospitalization in hospitalized COVID-19 patients.
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Quantitative structure–activity relationship modeling of some naphthoquinone derivatives as inhibitors of pathogenic agent IDO1 p. 317
Sajjad Jazayeri Farsani, Saeid Asadpour, Abolfazl Semnani, Shima Ghanavati Nasab
Quantitative structure–activity relationship (QSAR) was performed to analyze naphthoquinone derivatives as an inhibitor of indoleamine 2,3-dioxygenase pathogen via multivariate regression (MLR) and artificial neural network. The best descriptors were picked to construct the QSAR. Two sets of exercises and experiments were also performed using Principal Component Analysis for multiple linear regression (MLR). A quantitative model was then proposed based on these analyses and the activity of the compounds based on multivariate statistical analysis was interpreted. The study finally revealed that although the MLR model can predict the activity of the compounds to some extent, the artificial neural network (ANN) model results indicate that the predictions obtained by the neural network are much better and more efficient than other models. The neural network was also used where three coefficients of correlation were used. The results uncovered that the ANN model is statistically significant and has good stability for data validation for the validation method. Share Descriptive relationships of structure and activity were also examined.
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