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   Table of Contents - Current issue
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January-June 2021
Volume 10 | Issue 1
Page Nos. 1-158

Online since Monday, May 31, 2021

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ORIGINAL ARTICLES  

Phytochemical and biological studies on Muscari inconstrictum seeds distributed in Iran Highly accessed article p. 1
Mahsa Kazemnezhad, Mohammadali Torbati, Solmaz Asnaashari, Fariba Heshmati Afshar
DOI:10.4103/jrptps.JRPTPS_49_19  
Background and Purpose: Muscari Miller. (Asparagaceae family) contains about 50 species worldwide, which are distributed in the Central and Southeastern Europe, Southern Russia, Africa, and some area of Asia such as Iran, Iraq, Afghanistan, Anatolia, and Syria. This study was designed to assess the antioxidant and antimalarial activities of Muscari inconstrictum Rech. f. seeds as one of the Iranian species of Muscari genus. In addition, preliminary phytochemical analysis of the extracts with different polarities was performed. Materials and Methods: The essential oil of M. inconstrictum seeds was prepared using Clevenger and extracted with n-hexane, chloroform, and methanol (MeOH) by Soxhlet apparatus. Gas chromatography-mass spectrometry (GC-MS) was used for the characterization of essential oil. Total phenol and flavonoid contents were measured using Folin–Ciocalteu and aluminum chloride reagents. Free radical scavenging and antimalarial activities were investigated via 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and cell-free ß-hematin formation methods. Results: GC-MS analysis of the volatile oil of seeds demonstrated the presence of sesquiterpenoid, alkanes, fatty acid, and linear alcohol structures as the main constituents. Among different extracts of M. inconstrictum seeds, the methanolic extract showed significant antioxidant activity, which can be related to the presence of flavonoid and other phenolic structures. Furthermore, chloroform extract is introduced as the most potent antimalarial part. Conclusion: It seems that further studies on the M. inconstrictum seeds are necessary to focus on pure compounds and their biological activities.
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Evaluation of the matrix-forming ability of Chrysophyllum albidum Linn fruit gum in sustained-release tablet formulations Highly accessed article p. 5
Ephraim Esla, Olubunmi J Olayemi, Babah A Isah, Susan T Allagh
DOI:10.4103/jrptps.JRPTPS_13_20  
Background: Plant gums are extensively being exploited as pharmaceutical excipients due to the ease of availability, biodegradability, and reduced costs. Aim: This study investigated the application of the fruit gum of Crysophyllum albidum (CFG) as a matrix former in the formulation of chlorpheniramine maleate and theophylline hydrochloride tablets. Materials and Methods: The gum was extracted using acetone and evaluated for flow, swelling, and hydration capacity. Effects of temperature on CFG and drug compatibility were evaluated using differential scanning calorimetry (DSC). Granules containing CFG at 10, 20, and 30% w/w were prepared using the wet granulation method and evaluated for flow properties. Compressed tablets were evaluated for uniformity of weight, hardness, friability, and drug content. In vitro drug release studies were carried out in simulated gastric (pH 1.2) and simulated intestinal (pH 6.8) fluids. Pearson’s similarity correlations were used to analyze results. Results: CFG had a swelling capacity of 22% and hydration capacity of 1.44 with an angle of repose of 30o and Carr’s index of 7.6 signifying good flow. DSC thermogram returned an endothermic glass transition peak at 72.1oC with no appreciable shifts in the peak when CFG was incorporated into the drug. Tablet hardness and friability were concentration dependent with values of 6.5–8.5kg F and 0.04–0.4%, respectively; drug content was within official specifications. Formulations containing 30%w/w CFG sustained drug release for over 12 h and showed better ability to control drug release than HPMC at same concentration. Conclusion: This study shows the propensity of CFG to be used in the formulation of sustained-release tablet formulations.
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Simultaneous RP-HPLC estimation and validation of metronidazole, furazolidone, and dicyclomine in capsule Highly accessed article p. 15
Amuthalakshmi Sivaperuman, Nalini Calambur Nagarajan, Uma Jayapaul
DOI:10.4103/jrptps.JRPTPS_104_19  
For the first time, a new, simple, precise reversed-phase high-performance liquid chromatography method was developed for the simultaneous estimation of metronidazole, furazolidone, and dicyclomine hydrochloride in capsule dosage form. The method was performed with Thermo, C8 (150 mm×4.6) column. The best separation was achieved by gradient elution with mobile phase of acetonitrile, water (40:60), and 20 mm phosphate buffer with 10% w/v sodium hydroxide (pH 7.5) with a detection wavelength of 215 nm. The separation was completed within 15 min of runtime. The retention time of metronidazole, furazolidone, and dicyclomine hydrochloride was found to be 1.79, 2.45, and 11.50 min, respectively. The proposed method was found to be linear. The method was statistically validated as per the ICH guidelines and shown to be simple, accurate, precise, linear, and reproducible in the range of 40.2–60, 40.2–60.4, and 3–5 µg/mL for metronidazole, furazolidone, and dicyclomine, respectively. For the first time, the developed method foretells the suitability of the method for the simultaneous estimation of three drugs in the commercially available dosage forms.
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Apoptotic, MDA, and FGF2 level of quercitrin treatment on hypoxic-induced EA.hy926 Cell Line p. 22
Chrismis Novalinda Ginting, I Nyoman E Lister, Ermi Girsang, Dwi Surya Artie, Jenifer Kiem Aviani, Wahyu Widowati
DOI:10.4103/jrptps.JRPTPS_70_20  
Background: Preeclampsia (PE) is pregnancy disorder that is characterized by hypertension, proteinuria, and an enhanced maternal systemic inflammatory response. PE affects 5% to 10% of all pregnancies and remains a leading factor of fetal and maternal morbidity and mortality. The existence of oxygen deprivation is involved in PE. Inflammation is a requisite to the pathogenesis of PE. Quercitrin belongs to the flavonoid group that is known to have antioxidant and anti-inflammatory activity. Aims: This study aims at determining the potential of quercitrin to reduce the percentage of apoptosis, levels of lipid peroxidase (MDA), and FGF2 in the human endothelial cell (EA.hy926) line that is induced by hypoxia (2% O2) as a PE model. Materials and Methods: Five treatments were used in this study (negative control, vehicle control, hypoxia control, quercitrin 25 µg/mL, and quercitrin 6.25 µg/mL) to determine the live, necrotic, and apoptotic cells percentage; MDA and FGF2 levels toward hypoxia-induced endothelial cells as a PE model. ELISA method was used to measure the MDA and FGF2 levels. Live, necrotic, and apoptotic cells were measured by using the flow cytometry method. Result: Quercitrin was capable of decreasing the MDA and FGF2 levels compared with hypoxia control; of increasing live cells percentage; and of decreasing apoptotic and necrotic cells percentage compared with hypoxia control cells. Conclusion: This study showed that quercitrin possesses antioxidant and anti-inflammatory properties that can decrease the percentage of the apoptotic cells, suppress MDA levels and FGF2 levels, and increase live cells percentage in hypoxia-induced endothelial cells as a PE model.
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Evaluation of the therapeutic effect of Achillea wilhelmsii C. Koch aqueous extract in acetic-acid-induced ulcerative colitis in rat p. 29
Ali Ghobadi, Mohammad Heydarian, Gholamreza Bahrami, Leila Hosseinzadeh, Yalda Shokoohinia, Mohammad Hosein Farzaei, Hosna Khazaei, Kimia Aghaei
DOI:10.4103/jrptps.JRPTPS_4_20  
Context: Ulcerative colitis (UC) is a chronic, idiopathic, and recurrent disease with unknown etiology. Achillea wilhelmsii has been introduced as a herbal remedy for gastrointestinal ulcers and UC in traditional Persian medicine. Aims: We examined the effectiveness of A. wilhelmsii aqueous extract against acetic-acid-induced UC in rats. Settings and Design: Fifty-six male Wister albino rats weighing 180–200g were randomly divided into eight groups and after induction of UC were treated with five doses of aqueous extract of A. wilhelmsii.Materials and Methods: After induction of UC by acetic acid, the aerial parts of A. wilhelmsii (6.25, 12.5, 25, 50, and 100 mg/kg) were administered orally. On 11th day, the animals were euthanized by overdose of ether inhalation and the intestinal tissue was rapidly dissected for macroscopic, histological, and microscopic scores. Statistical Analysis Used: Data were analyzed by stats Directver.2.7.9 (SAS, Cary, North Carolina). One-way analysis of variance (ANOVA) followed by Newman–Keul’s post hoc test for multiple comparisons. A value of P < 0.05 was considered as significant level. Results were expressed as mean ± standard error of the mean (SEM). Results: All doses of A. wilhelmsii extract significantly reduced macroscopic and microscopic scores of colitis without significant changes in bodyweight of animals. Conclusions: Treatment of the rats with A. wilhelmsii extract improved UC via its anti-inflammatory, antioxidant, and antimicrobial activities. According to the results of this study, A. wilhelmsii has a therapeutic effect against acetic-acid-induced UC in the animal model.
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Formulation and evaluation of a tablet containing pioglitazone HCl microspheres p. 35
Ganesh Bharat Vambhurkar, Asha Mohan Jagtap, Akshata Suhas Gavade, Dheeraj Suhas Randive, Mangesh Anil Bhutkar, Somnath Devidas Bhinge
DOI:10.4103/jrptps.JRPTPS_29_19  
Solubility is an important physicochemical factor for any drug molecule that affects its absorption along with its therapeutic effectiveness. Drug absorption is predominantly dependent upon its prompt dissolution. In the case of poorly water-soluble drugs, dissolution is the rate-limiting step in the process of drug absorption. Microspheres were prepared by solvent evaporation method using polymers namely Eudragit L100 and Eudragit RL100. Direct compression technique was used for the preparation of tablets. Tablets were prepared with MCC and PVP K-30 as polymers using an 8mm punch on a rotary press machine with a constant force. Microspheres and the prepared tablets were evaluated using various evaluation tests. The prepared microspheres showed >80% entrapment efficiency and percent yield. Batch F3 exhibited the highest drug release up to 98.30%. Fourier transform infrared (FT-IR) studies revealed no drug–polymer interaction. The results of SEM exhibited that the microspheres are spherical in shape with an average size 5µm. The result of all batches was within an acceptable limit. F2 batch tablet showed a higher drug release of 98.30% as compared with other batches. It was concluded that microcrystalline cellulose or PVP K-30, when used separately, caused retardation in drug release, whereas when used in combination (1:1) it achieved drug release in a controlled manner.
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Development and evaluation of injectable hydrogel as a controlled drug delivery system for metformin p. 42
Santosh S Bhujbal, Ravi V Badhe, Shradha B Darade, Siddharth S Dharmadhikari, Suresh K Choudhary
DOI:10.4103/jrptps.JRPTPS_140_19  
Aim: Chitosan-dialdehyde cellulose/DAC-based injectable hydrogel for controlled release of Metformin. Materials and Methods: Biomaterial-based injectable hydrogel was prepared by incorporating chitosan and dialdehyde cellulose. Dialdehyde cellulose (A cross-linker) was prepared by periodate oxidation method. The antidiabetic agent metformin was easily mixed with the chitosan and dialdehyde cellulose cross-linked solution, for the controlled drug delivery applications. The prepared injectable hydrogel showed the shear thinning property. Results: IR spectra confirmed the presence of cross-linked network between chitosan and dialdehyde cellulose. The physical appearance, injectability, pH, sol–gel phase transition, drug content, DSC, FTIR, and SEM studies were investigated. DSC and SEM studies revealed the degradation pattern and the topographical nature of prepared injectable hydrogel, respectively. The %drug release of metformin was found to be 87.25% prolonged for 84 h. The drug release pattern revealed the effective controlled drug delivery of metformin as compared to marketed tablet formulation. Conclusion: The study suggested that the controlled drug delivery system can be incorporated into the injectable hydrogel system; it would be more potential as compared to conventional controlled drug delivery system and preformed hydrogel system.
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Immunosensor design based on Chitosan-QDs, a nanocomposite-modified electrode for selective procalcitonin sensing in clinic analyses p. 53
Sajad Naghizadeh, Babak Paknejad, Seyed Reza Abtahi, Ebrahim Hazrati, Mohsen Chamanara
DOI:10.4103/jrptps.JRPTPS_83_20  
A simple free labeled electrochemical immunosensor based on chitosan (CHI) and quantum dots (QDs) was developed for the determination of procalcitonin (ProCT) antigen (Ag) which can act as a target biomarker of infectious diseases. The antibodies of the ProCT biomarker were successfully incubated on the CHI-QDs platform. Electrochemical impedance spectroscopy and cyclic voltammetry were used for the evaluation and characterization of various layers coated onto the electrode. Under the optimum conditions, the electron transfer resistance (Rct) of the immunosensor was altered linearly by the ProCT concentration. The proposed immunosensor was proportional to the ProCT biomarker concentration from 0.005 to 0.35ng/mL with a calculated detection limit of 0.015 pg/mL. The proposed biosensing device also exhibited high stability and reproducibility, which can be used for the quantitative assay of the ProCT biomarker in clinic analyses.
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Anti-inflammatory effects of memantine in carrageenan-induced paw edema model in rats p. 60
Mahtab Azarbaijani, Mehdi Kian, Hamid Soraya
DOI:10.4103/jrptps.JRPTPS_37_20  
Background: The anti-inflammatory effect of memantine (MEM) was investigated using carrageenan-induced hind paw edema model in rats. Materials and Methods: Thirty male Wistar rats were randomly assigned to five groups (n = 6). Group 1 received 0.1 mL of 1% carrageenan at the right hind paw. Group 2 received dexamethasone (10 mg/kg) and Groups 3, 4, and 5 received 5, 10, and 20 mg/kg MEM intraperitoneally (ip), 20 min after injection of carrageenan into the right hind paw, respectively. Animals’ paw thickness was measured at 0, 1, 2, 3, 4, and 5 h after carrageenan injection. Then, animals were euthanized and myeloperoxidase (MPO) and malondialdehyde (MDA) levels were measured in the paw tissues. The tissue samples were further examined histopathologically using light microscopy. One-way ANOVA and Tukey post hoc test was used to compare the mean values between the groups. Results: Treating with MEM at all doses significantly decreased hind paw thickness at 2 (P < 0.05 and P < 0.01 at MEM 10 mg/kg and MEM 5 and 20 mg/kg, respectively), 3 (P < 0.001), and 4 (P < 0.001 at 5 mg/kg and P < 0.01 at MEM 10 and 20 mg/kg) hours after carrageenan injection in comparison to the carrageenan group. There was a significant (P < 0.05 and P < 0.001, respectively) reduction in MPO activity and MDA levels in MEM-treated groups when compared with the carrageenan group. Conclusion: This study showed that MEM decreased paw edema, leukocyte infiltration, MPO activity, and MDA levels, and MEM can be considered as an effective anti-inflammatory agent.
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Synergistic effect of cumin (Cuminum cyminum L.) decoction alongside with three-drug and four-drug treatment protocols on Helicobacter pylori eradication p. 66
Touraj Ahmadi-Jouybari, Abbas Aghaei, Mary Ataee, Jafar Navabi, Bita Anvari, Hadi Ahmadi Jouybari, Mohammad Bagher Majnooni
DOI:10.4103/jrptps.JRPTPS_30_20  
Background: Helicobacter pylori is a major cause of peptic ulcer. On the other hand, cumin (Cuminum cyminum L.) is an effective medicinal plant for the treatment of gastrointestinal disease in traditional Persian medicine. This study aimed at investigating the synergistic effect of the decoction of cumin with the three- and four-drug protocols against H. pylori in patients with peptic ulcer. Patients with peptic ulcer infected with H. pylori were treated with cumin decoction, three- and four-drug protocols, and their co-administration to eradicate H. pylori. Materials and Methods: Patients were randomly divided into five groups, including group (1) omeprazole with cumin decoction, (2) cumin decoction with the three-protocol treatment, (3) cumin decoction with the four-drug protocol treatment, and (4 and 5) three- and four-drug protocols alone. The cumin fruit powder was given to patients in 3-g packages and decoction was prepared according to the traditional Iranian medicine guidelines. H. pylori eradication was measured by the 14C–urea breath test (14C-UBT) after 4 weeks of intervention. The Kolmogorov–Smirnov test, χ2 test, logistic regression, and ANOVA (SPSS, 11.5) were used for data analyses. Results: In total, 75 patients (48 male and 27 female patients) participated in this study. The results showed that eradication of H. pylori was observed in all five study groups. Eradication of H. pylori in cumin decoction with the three-drug protocol group was more than the other groups (85.72%), although this difference was not statistically significant. In addition, this eradication was 61.5% in the cumin + omeprazole group, while the H. pylori eradication rates for the three-drug and four-drug protocols were 77.8% and 58.33%, respectively. Conclusions: The results showed that decoction of cumin could be used as a complementary treatment alongside conventional medicine therapy to increase the H. pylori eradication.
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The wound healing effect of allogeneic freeze-dried platelet-rich plasma in a full-thickness wound animal model p. 71
Iswinarno D Saputro, Andi Muhammad Ardan, Wiwik M Yuniarti, Oki N Putra
DOI:10.4103/jrptps.JRPTPS_77_19  
Background: Epithelialization is an indicator of wound healing. Platelet-rich plasma (PRP) may accelerate the epithelialization of the wound due to high amount of growth factors. Generally, allogeneic PRP provides a smaller immunological effect than autologous PRP. By a freeze-drying method, it is assumed that allogeneic PRP has lower allergenic activity. Aims and Objectives: The aim of this study was to investigate the effect of allogeneic freeze-dried PRP on wound healing of a full-thickness wound in New Zealand rabbits. About 2 × 2 cm2 full-thickness wounds were created on rabbits using a template on both sides of the dorsum and divided into treatment group and control group. The treatment group was treated with allogeneic freeze-dried PRP and the control group was treated with moist dressing. Acceleration of wound healing was shown by the epithelialization and measured on day 7 using digital Visitrak. Nine New Zealand rabbits were used in this study. Results: In the treatment group, the epithelialization was significantly higher 3.00 ± 0.96 cm2 than the control group 1.35 ± 0.85 cm2 (P < 0.000) by independent t test. Another finding of our study was the allergic reaction was not observed after the administration of allogeneic freeze-dried PRP in rabbits. Conclusion: Our results indicate that allogeneic freeze-dried PRP accelerates epithelialization compared to the control group and does not cause an allergic reaction in full-thickness wounds in rabbits. The effect of allogeneic PRP, prepared with a freeze-drying method, on the process of wound healing is reported for the first time in this article.
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Improvement of bioavailability of poorly soluble racecadotril by solid dispersion with surface adsorption method: A case study p. 77
Bhaskar Daravath, Girmannagari Prasanna Kumari
DOI:10.4103/jrptps.JRPTPS_129_19  
Introduction: Biopharmaceutics classification system class II drugs show unpredictable bioavailability based on their solubility. Unfortunately, very few products were manufactured by this technique owing to their poor flowability and stability. The objective of the current investigation was used to improve the flowability by surface solid dispersion (SSD; SD with surface adsorption technology) and improve the absorption of racecadotril (RT) under low pH conditions (i.e., in stomach) to show anti-diarrheal effect by reducing water and electrolyte secretion into the intestine. Materials and Methods: SSDs and physical mixtures (PMs) were prepared using various ratios of hydrophilic carriers (polyethylene glycol 4000, polyethylene glycol 6000, and Gelucire 50/13) and an adsorbent (lactose monohydrate). Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffractometry , and dissolution studies (in vitro) were conducted to characterize SSDs and PMs. Results: Phase solubility curves represent AL type, indicating that the solubility of drug linearly increased with an increase in the concentration of carrier. Characterization studies indicated that no interactions between carrier and drug. Solid-state characterization showed a reduction in crystallinity that further supports increment in solubility and dissolution. The optimized formulation (SDG4) showed 99.84 ± 1.5% drug release in 15 min compared to RT plain drug (11.95 ± 1.72%). In vivo bioavailability studies of SDG4 revealed a significant (P < 0.05) increase in Cmax 65.38 ± 1.34 µg/mL (1.75-fold) with increased relative bioavailability (180.22-fold) against the RT plain drug. Conclusion: Formulation of SD with surface adsorption method could enhance solubility, dissolution, and bioavailability of RT.
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Artocarpus altilis leaf extract protects pancreatic islets and improves glycemic control in alloxan-induced diabetic rats p. 87
Yulia Yusrini Djabir, Hardi Hardi, Hesty Setiawati, Subehan Lallo, Risfah Yulianty, M Husni Cangara, Veni Hadju
DOI:10.4103/jrptps.JRPTPS_57_20  
The antioxidant capacity of Artocarpus altilis leaf extract may offer protection against stress oxidative-induced damage to pancreatic cells. This study aimed to examine the effect of Artocarpus leaf extract on pancreatic islets structure, blood glucose (BG), and insulin serum levels in alloxan-induced diabetic rats. Diabetes mellitus was induced in rats with an intraperitoneal injection of alloxan (155 mg/kg). Rats’ BG levels were measured daily. Only rats with BG >250 mg/dL (n = 25) proceeded to receive different treatments: placebo, Artocarpus leaf extract at the dose of 100, 200, or 400 mg/kg, or insulin 6 IU/200g. All treatments were administered daily for 14 days before blood and pancreatic tissue samples were collected. Five healthy rats (n = 5) were included to serve as normal controls. The result shows that alloxan-induced atrophy of pancreatic islets and Artocarpus leaf extract administration at all given doses reduced the severity of pancreatic islet’s atrophy. However, only at 400 mg/kg dose, Artocarpus leaf extract significantly reduced rats’ BG level (P < 0.05), similar to that of insulin-treated rats. Artocarpus leaf extract, especially at 100 and 400 mg/kg doses, also improved insulin serum levels compared with placebo treatment (P < 0.05). In conclusion, Artocarpus leaf extract protected rats’ pancreatic islets against alloxan-induced damage. This protection could improve the BG and insulin serum levels in Artocarpus-treated rats.
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Formulation and evaluation of the novel herbal antibacterial gel to the treatment of cutaneous burn infections p. 93
Mahsa Bagheri, Yalda Shokoohinia, Zahra Pourmanouchehri, Fereshteh Jalilian, Salar Khaledian, Shahla Mirzaie, Leila Behbood
DOI:10.4103/jrptps.JRPTPS_100_20  
Due to the rapid development of antibiotic resistance, the strong need for alternative strategies to tackle this problem is inevitable. The objective of this study was to prepare and evaluate the antibacterial effects of a pharmaceutical gel containing herbal extracts including Lawsonia inermis (henna) and Matricaria chamomilla. Using hydroxypropyl methylcellulose (HPMC), carboxymethylcellulose (CMC), and propylene glycol (PEG), the pharmaceutical gel was formulated and the physical properties of the formulation were specified at 37 ± 2°C. The total phenolic content (TPC) of extracts was determined using the Folin–Ciocalteu method and expressed as mg gallaic acid (GA) per gram extract (Ex). The release of the polyphenol compounds from the optimum formulation was investigated using the Franz cell device. Eventually, the disc diffusion method was used to evaluate the antibacterial activity of optimum formulation against the two pathogenic bacteria strains Staphylococcus aureus and Pseudomonas aeruginosa. The results showed that the optimum formulation was stable at least for 3 months. The TPC of the aqueous extract of henna leaves, the hydroalcoholic extract of chamomile flowers, and the optimum formulation was 57.8, 181.08, and 202.75 mg GA/g Ex, respectively. Nearly 80% of the phenolic compounds in the optimum formulation were released over 4 h. The phenolic compounds have inhibitory effects on the growth of S. aureus and P. aeruginosa. On the basis of this finding, the formulation had excellent stability, viscosity, homogeneity, extrudability, and antibacterial activity which can be employed as a topical pharmaceutical gel in cutaneous burn infection treatment.
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A herbal syrup: Formulation and antidepressant effect in male rat p. 101
Sara Zakerin, Homa Hajimehdipoor, Seyed Alireza Mortazavi, Masoumeh Sabetkasaei, Rasool Choopani, Shirin Fahimi
DOI:10.4103/jrptps.JRPTPS_136_19  
Introduction: Herbal medicines play a significant role in global health-care systems. In this investigation, a polyherbal syrup has been reformulated pursuant to Iranian traditional medicine and its antidepressant effect has been evaluated. Materials and Methods: The syrup was prepared by decocting a mixture containing: Lavandula angustifolia, Melissa officinalis, Echium amoenum, Cordia myxa, Glycyrrhiza glabra, Ziziphus jujuba, Foeniculum vulgare, Fumaria parviflora, Adiantum capillus-veneris, and Alhagi spp. along with glycerin and potassium sorbate. Physicochemical characteristics of the syrup were examined. An accelerated stability test was carried out for syrup as well. Moreover, antidepressant evaluations were performed by the forced swimming test using the drug as gavage (3.3 mL/kg/day) for three consecutive weeks. The serum levels of serotonin (5-HT), noradrenaline (NA), and brain-derived neurotropic factor (BDNF) were determined in rats as well. Finally histopathological examinations were done on liver, kidney and spleen. Results: The herbal syrup was brown in color with a special taste and flavor. Density, pH, viscosity, dry residue, and total phenolics content were 1.085g/ml, 5.56, 5.35 cP, 15.22%, and 194 mg/100 mL, respectively. The syrup was stable during accelerated stability tests, and no significant changes were observed. The polyherbal syrup exhibited significant antidepressant effects by decreasing immobility time through increasing in NA and 5-HT levels without affecting BDNF levels. Formulated syrup also did not have any toxic effects on the liver, kidney, and spleen. Conclusion: The syrup could be an appropriate candidate for pharmaceutical companies after complementary tests such as toxicity and clinical trials.
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Incidence and cost of chemotherapy-induced adverse drug reactions among cancer patients in a charitable hospital p. 110
Jeeshma Varghese, Uday Venkat Mateti, Jayarama Shetty, Malona Lilly Philip, Barma Naga Raju
DOI:10.4103/jrptps.JRPTPS_68_20  
Introduction: Chemotherapy-induced adverse drug reactions (ADRs) are one of the major consequences of cancer therapy that affects patients’ quality of life, outcomes of the treatment, morbidity, and mortality and increases the economic burden. The study’s objective was to evaluate the incidence, causality, severity, and preventability and to calculate the direct medical cost of chemotherapy-induced ADRs among cancer patients. Materials and Methods: A prospective observational study was conducted for 8 months in patients above 18 years and receiving chemotherapy. ADRs were evaluated for their causality, severity, and preventability using different ADR assessment scales, and the economic burden for different ADRs was based on their direct medical costs. Results: A total number of 230 patients were enrolled in the study, out of which 84 patients developed 148 ADRs. Patients who received chemotherapy showed a higher incidence of ADRs in 45–55 years of age group (30.95%), females (69.04%), solid tumors (92.85%), stage III (55.95%), and double regimen (61.90%). Paclitaxel and carboplatin were reported to cause most ADRs, such as anemia (14.18%) and leucopenia (6.75%). ADRs were assessed using scales. As per the WHO-UMC scale, 59.4% ADRs were possible, followed by probable (39.2%). The majority of the ADRs were mild (52%) in severity. About 41.9% reactions were probably preventable, and 3.4% were definitely preventable. Conclusion: The overall incidence of ADRs was 36.52%. The direct medical cost incurred for the management of ADRs was 457.23 USD.
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Immunoregulatory effects of paroxetine in healthy volunteers: An in vitro investigation p. 118
Alireza Karimollah, Anahid Hemmatpur, Maryam Asadi, Mohammad Hossein Hadinedoushan
DOI:10.4103/jrptps.JRPTPS_66_20  
Background: Paroxetine has been a commonly prescribed antidepressant for treatment of major depression and various anxiety disorders for almost 30 years due to its fewer side effects and toxicity compared with its counterparts. Despite several investigations performed, the paroxetine immunoregulatory effect in healthy subjects is still controversial. In this study, the paroxetine effect on the cell proliferation along with IL-4 and interferon-gamma (IFN-γ) secretion in peripheral blood mononuclear cells (PBMCs) of physically and mentally healthy subjects is investigated. Materials and Methods: Blood was drawn from 20 healthy subjects and PBMCs were isolated. Cells were treated with paroxetine and/or phytohemagglutinin (PHA) for 72 h. IL-4 and IFN-γ concentrations were assessed in the supernatant using an enzyme-linked immunosorbent assay. The BrdU cell proliferation assay was also performed to evaluate the paroxetine effect on PBMCs in the absence or presence of PHA. Results: Paroxetine (25 μM) significantly inhibited the production of IL-4 and IFN-γ in PHA-stimulated human PBMC cultures. Surprisingly, paroxetine suppressed cell proliferation in the unstimulated culture in a dose-independent manner. Paroxetine also attenuated cell proliferation in the PHA-stimulated culture, especially at 25 μM concentration. Conclusion: The obtained results suggest that paroxetine can be a potent therapeutic option in inflammatory diseases by balancing immune responses.
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Creatine and α-lipoic acid improved depressive behavior induced by interferon-α in mice: Malondialdehyde level remained unchanged p. 124
Azadeh Mesripour, Zahra Karimi, Mohsen Minaiyan
DOI:10.4103/jrptps.JRPTPS_142_20  
Objective: Interferon-alpha (IFNa) is a cytokine with various biological roles but it may induce psychological adverse effects. Introducing alternative medicine is essential to prevent this side effect. This study was performed to determine the antidepressant effects of creatine (Crt) and α-lipoic acid (ALA). Materials and Methods: Female albino mice (6–8 weeks old) were used. IFNa (16×105 IU/kg/day, SC), Crt (5 and 10 mg/kg, gavage feeding tube), and ALA (20 and 40 mg/kg, IP) were administered for 6 days. After the locomotor test, behavioral parameters of depression, including immobility during the forced swimming test (FST), and finally serum malondialdehyde (MDA) were measured as factors for oxidative stress. Results: There was not important difference regarding the locomotor test. Crt 5 mg/kg and ALA 40 mg/kg when administered alone reduced the immobility time during FST when compared with the control groups (75±15 and 82±16 s, respectively, P < 0.05). Crt 5 mg/kg and IFN co-administration reduced the immobility time to 108±23 s, which was lower than that of the IFNa alone group (156±8 s, P < 0.05). Administrating ALA 40 mg/kg and IFNa together showed same results (95±11 s vs. IFNa alone group, P < 0.01). The results of measuring MDA did not show noticeable difference. Conclusion: In general, improvement of behavioral parameters in mice treated with Crt and ALA indicates a clear effect of these two compounds in modulating mood and depressive behaviors. Although MDA level differences were not observed, Crt and ALA modulation in the neurotransmitter system may be involved in their antidepressant effects.
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Evaluation of total phenolics, flavonoids, and antioxidant and cytotoxic potential of Ailanthus altissima (Mill.) swingle leaves p. 130
Heba Raafat Mohamed, Eman Ahmed El-Wakil, El-Sayed Saleh Abdel-Hameed, Maher Mahmoud El-Hashash, Mohamed Shemis
DOI:10.4103/jrptps.JRPTPS_7_21  
Context: People all over the world are suffering from cancer. Liver cancer is considered the second most common malignancy among Egyptian men and the sixth most common malignancy among Egyptian women. Plant-derived antioxidants are believed to prevent or delay the occurrence of many chronic diseases such as cancer. Ailanthus altissima has been used in many traditional prescriptions. Aims: The current study aimed at investigating the phytochemical profile of A. altissima leaves’ extract and its derived fractions, determining their content of phenolics and flavonoids as well as assessing their antioxidant and cytotoxic potential. Materials and Methods: The phytochemical screening was carried out using standard methods. The total phenolic, flavonoid, and flavonol contents were determined using Folin-Ciocalteu, aluminum chloride, and aluminum chloride/ sodium acetate assays, respectively. The antioxidant activity was evaluated using different in vitro methods: DPPH, total antioxidant capacity, hydroxyl (OH), nitric oxide (NO) radical scavenging activities, and permanganate-reducing antioxidant capacity (PRAC). The antiproliferative potential against HepG2 cells was evaluated using sulforhodamine-B assay (SRB). Results: The results showed that the ethyl acetate fraction had the highest content of phenolics, flavonoids, and flavonols (551.72 ± 1.81 mg GAE/g ext., 371.24 ± 4.36 mg RE/g ext., and 100.47 ± 1.30 mg QE/g ext., respectively). It also had the most potent reducing power (DPPH SC50 = 7.19 ± 0.05 µg/mL, TAC= 369.88 ± 1.51 mg AAE/g ext., OH SA = 95.46 ± 0.14%, NO SA = 40.65 ± 0.91%, and PRAC = 77.19 ± 0.27%). The n-butanol fraction exhibited the most potent cytotoxic potential against HepG2 cells (IC50 = 16.70 µg/mL). Conclusion: A. altissima leaves could be considered potent antioxidant and cytotoxic alternatives.
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REVIEW ARTICLE Top

A review on solubility enhancement methods for poorly water-soluble drugs p. 137
Ahmad Ainurofiq, David Sarono Putro, Dhea Aqila Ramadhani, Gemala Mahendra Putra, Laura Da Costa Do Espirito Santo
DOI:10.4103/jrptps.JRPTPS_134_19  
One of the most important parameters in pharmacy is drug solubility. Solubility affects the efficacy of a drug. Drug solubility has an important role in determining the concentration of a drug to achieve the necessary pharmacological response, as all drugs absorbed by the body must be in the form of a solution. Drug solubility is quite a common issue and affects the bioavailability of a drug in the body. Drugs with low solubility are poorly absorbed, resulting in poor bioavailability. Many methods have been developed for increasing the solubility of a drug. In this review, we will describe possible efforts for improving the solubility of a drug, e.g., reducing particle size, surfactants, the use of nanosuspension technology, solid dispersion, salt formation, pH adjustment, hydrotropy, cocrystal, amorphous compound formation, and inclusion complexes. The main objective of this review was to focus on efforts that can increase the solubility of a drug to obtain good drug efficacy.
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SHORT COMMUNICATION Top

Comparative antibacterial study of black cumin oil of Saudi and Syrian origin seeds with the commercial product p. 148
Mohammad Rashid, Majid A Ganaie, Shamshir Khan, Naseem Akhtar, Makhmur Ahmad, Saiba Shams, Omer S Hamid Bilal, Dheeraj Bisht
DOI:10.4103/jrptps.JRPTPS_118_20  
Background: A literature survey showed that significant work has been done to evaluate antimicrobial activity of medicinal plants and their constituents. Thousands of phytoconstituents are tested against a wide range of microbial strains in vitro, in vivo, and clinically. Black cumin oil obtained from the seeds of Nigella sativa L. is used as carminative, stimulant, diuretic, emmenagogue, lactagogue, and anthelmintic. Seed oil is applied externally on skin as antiseptic, emollient, and to prevent cold symptoms. Many studies have displayed the antimicrobial activity of black seed oil against a variety of microorganisms including Gram-positive and Gram-negative bacteria. In the present study, a comparative antibacterial activity of black cumin oil of Saudi Arabian, Syrian seeds, and marketed/branded oil was undertaken. Materials and Methods: Black cumin oil (12%) is obtained from Saudi and Syrian originated seeds by the soxhlet extraction method. Agar disc diffusion method was applied for antibacterial activity of each oil and two marketed oils. Antibacterial activity of different black cumin oil samples has been evaluated against standard Escherichia coli, standard Klebsiella pneumonia, and standard Staphylococcus aureus. Phytochemical screening is also done to check the presence of phytoconstituents, which might be responsible for the activity. Results: All black cumin oil samples are found to be sensitive to S. aureus only. Black cumin of Saudi originated seeds showed higher activity than Syrian. Seeds oil of Syria had almost similar activity to one of the marketed oils (M1). Another marketed black cumin oil (M2) showed highest antibacterial activity among all types of oils. Phytochemical screening of these oils showed the presence of steroids and alkaloids, which might be responsible for the activity. Several factors that affect the phytochemical variations are environmental, geographical, agricultural, and extraction conditions, which result in differences in their antibacterial activity. Conclusion: The results of this study showed that all samples of black cumin oils have antibacterial activity against S. aureus (Gram-positive bacteria). Therefore, they might be considered as possible alternatives to antibiotics for the treatment of S. aureus infections.
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LETTER TO THE EDITOR Top

Management of COVID-19 by phytotherapy: A pharmacological viewpoint p. 153
Mahdieh Eftekhari, Aref Salehi, Ayesheh Enayati
DOI:10.4103/jrptps.JRPTPS_135_20  
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ERRATUM Top

Erratum: The Modulating Effect of Carumopticum on Human Peripheral Blood T-Cells Radiation Toxicity p. 158

DOI:10.4103/jrptps.JRPTPS_5_45_Erratum  
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