Research/Original Articles

In the present study, in-vivo and in-vitro approaches were utilised to investigate the antioxidant, anti-hyperglycemic and anti-hyperlipidemic activities of Ethanolic (EthEx) and Ethyl Acetate extracts (EthAcEx) of Dialium guineense (DG). In-vitro analysis of the plant extracts revealed the presence of Phenolics (43.89±0.65 and 12.16±0.27 µg/100 mg GAE for EthEx and EthAcEx respectively) and Flavonoids (3.59±0.09 and 2.56±0.39 µg/100 mg QE for EthEx and EthAcEx respectively). The in vitro antioxidant analysis revealed a DPPH IC50 of 43.45±1.14 and 108.45±0.89 µg/mL for EthEx and EthAcEx respectively. Similarly, FRAP values were EthEx 3.02±0.01 and EthAcEx 0.96±0.05 respectively. In-vitro hypoglycemic (IC50) activities were alpha-amylase: EthEx 17.15 ± 0.03 and EthAcEx 6.04±0.03 µg/mL; alpha-glucosidase EthEx 70.21±1.55 and EthAcEx 28.81±0.22 µg/mL. In-vivo analysis revealed that the plant extracts improved weight gain and alleviated glycemic impairment in Streptozotocin induced diabetic rats. In addition, the solvent extracts caused an improvement of dyslipidemia and increased the plasma activities of Superoxide Dismutase, Catalase and concentration of Glutathione. Malondialdehyde concentration was suppressed by administration of the plant extracts. Put together, the present study provides evidence for the antioxidant, anti-hyperglycemic, anti-hyperlipidemic and antidiabetic activities of DG. This suggests the potential of the plant as alternative therapy for the management of diabetes and its complications.

Effect of Olive Oil on Hesperidin Nanovesicles in Treatment of Induced Corneal Ulcers in Rabbits, Morphological and Histopathologic Study

Ahmed Ali, Iman S.A. Khallaf, Abeer S. Hassan, Marwa A. Sayed, Aya Hamdy, Magda Ali, Khaled M. A. Hassanein, Mahmoud El- Badry, Mohammed A. H. Abdelhakiem

Iranian Journal of Pharmaceutical Sciences, Vol. 20 No. 2 (2024), 23 June 2024, Page 96-114

Hesperidin (HSP) and Olive oil possess many biological activities that are required for the safe and effective treatment of corneal ulcers. However, the poor aqueous solubility of HSP hinders its topical utilization. This work aims at enhancing the dissolution of HSP and combining the powerful effectiveness of Olive oil in treating corneal ulcers.  HSP was isolated from orange peel and described by spectroscopic methods (1H NMR and 13C NMR), then HSP nanovesicles were prepared with and without Olive oil using the ethanol injection method. Nanovesicles were applied topically to rabbits’ eyes in which alkali burn corneal ulcers were induced. After five weeks, histopathological studies were performed. No ulcers were determined after topical application of HSP, and the inclusion of Olive oil returned the eye to its normal conditions. Thus, this study clarified the potential role of the HSP - Olive oil combination in managing corneal ulcers.

Phytochemical, Antioxidant, Cytotoxic, Antibacterial Activity, and Enzymatic Inhibition Study of Piper Betle Leaves

Ahmed Saad Al-Gburi, Kareem Khalid Mustafa, Saeed Ullah, Ajmal Khan, Usama Qayum, Salem Said Al Touby, Balamurugan Manickam, Najeeb Ur Rehman, Ahmed Al-Harrasi, Afaf Mohammed Weli

Iranian Journal of Pharmaceutical Sciences, Vol. 20 No. 2 (2024), 23 June 2024, Page 115-129

The Piper betle plant, known for its pharmacological properties, has been traditionally used in Asian cultures. The objective of the current study is to assess the antioxidant, cytotoxic, antibacterial, and enzymatic inhibitions of leaf extracts of the P. betle. DPPH radicals were used to assess the antioxidant potential. The Lethality Assay for Brine Shrimp was used to assess the cytotoxic potential of plant extracts. The disc diffusion method was used to measure the leaves' antibacterial activity against various Gram stains. The inhibitory potential of four enzymes linked to different diseases was screened spectrophotometrically. Chromatographic procedures were used to isolate active substances, and their structures were determined using spectroscopic approaches. The results indicated that the P. betle leaves extracts to possess potent antioxidant activity, highest with the EAPB (ethylacetate, P. betle) followed by DCPB (dichloromethane, P. betle), HPB (n-hexane, P. betle), BPB (n-butanol, P. betle) and AQPB (aqueous P. betle). For cytotoxic activity, the EAPB has the most potent cytotoxic activity among the tested extracts. AQBP and HPB showed activity against all bacteria used, while (EAPB and DCPB displayed good activities against all organisms except Streptococcus aglaciate. For anti-diabetic activity, DCPB, and EAPB both showed high percent inhibition and low IC50. The identified compound, allylpyrocatechol, isolated from the EAPB fraction of betel leaf attributed higher inhibitory activity than the standard against α-glucosidase with an IC50 of 42.61 ± 1.27. For anti-ulcer activity, the DCPB had the highest urease % inhibition and the lowest IC50 value, while (BPB) and AQBP fractions had lower levels of inhibition and higher IC50 values. DCPB and EAPB exhibited neurodegenerative therapeutic potential by targeting prolyl endopeptidase with good activity having IC50 values of 26.82 ± 0.36 and 52.92 ± 21.30 µg/mL). Furthermore, these extracts were tested for their therapeutic potential for skin diseases by targeting the tyrosinase enzyme. Interestingly, HPB and DCPB displayed good inhibitory capability with IC50 values of 36.14 ± 0.72, and 44.72 ± 1.28 µg/mL, respectively, compared to the standard kojic acid (IC50 = 7.49 ± 0.21 µg/mL). In conclusion, crude extracts of Piper betle leaves exhibit potent antioxidant, antibacterial, and moderately cytotoxic effects. It also has strong anti-ulcer and anti-diabetic properties. Additionally, it exhibits strong anti-pigentation properties and good neurodegenerative potential.

Nanoparticles of Magnesium Oxide Improve Autistic-Like Behaviors Induced by the Maternal Separation Model Without Affecting Gonads Structure

Zeynab Dastyar, Mahnaz Kesmati, Mehran Dorostghoal, Mozhgan Torabi

Iranian Journal of Pharmaceutical Sciences, Vol. 20 No. 2 (2024), 23 June 2024, Page 130-142

Maternal separation in the early days after birth can induce autistic-like behaviors in animals. Nanoparticles of Magnesium oxide (nano-MgO) can decrease anxiety, pain perception and improve animal memory. Also, sex hormones are involved in the formation of many behaviors. In this study, the effects of nano-MgO on behavioral responses in immature rats and gonadal histological structures of adult rats in the autistic-like model of maternal separation were investigated. Juvenile male and female offspring (60±5g) were divided into control and maternal-separated groups. The maternal separation was done by separation of the pup from the mother for 1 hour/daily/1-10 postnatal days. Nano-MgO 2.5 and 5 mg/kg were injected intraperitoneally during the 31±2-35±2 postnatal days.  Pain perception and memory were evaluated after the first, third, and last injections and on 45±2 postnatal days. Social interaction, anxiety level, and motor activity were evaluated on 36±2 postnatal days. Tissue samples were removed from the testis and ovary for histological studies on 73±2 postnatal days. Maternal separation increased pain perception, anxiety, and motor activity, and also decreased social interaction index, and impaired memory in animals. Nano-MgO improved anxiety, and social interaction, induced analgesia, and modulated hyperactivity. Also, memory impairment was reversed by the nano-MgO2.5 mg/kg while it was not significant. There were no alterations in the histological and histometrical structure of the testis and ovary of adult rats between the studied groups. The behavioral complications caused by the autistic-like model can be corrected by nano-MgO; however, the gonads were not affected by the autism condition and nano-MgO application.

Scientific Authority in Iranian Pharmaceutical Sciences Research Centers: The Results of a Decade Research Evaluation

Monir Baradaran Eftekhari, Katayoun Falahat, Sahar Ashouri

Iranian Journal of Pharmaceutical Sciences, Vol. 20 No. 2 (2024), 23 June 2024, Page 143-152

The scientific authority refers to social power of scientific knowledge, in different sciences.  The aim of this study is to present the role of Iranian pharmaceutical research centers in scientific authority based on research evaluation for a decade. Iranian pharmaceutical research centers with more than one year of activity from 2013 to 2022 were assessed based on the intervention model of evaluation system. Three domains including stewardship, knowledge production and research impact with 20 indicators have been used in this process. 36 pharmaceutical sciences research centers (PhRCs) related to 23 universities of Medical Sciences (UMSs) were evaluated for a decade. The mean and standard deviation (SD) of age of the research activities in PhRCs was 12.2 ± 8.60. The ratio of faculty member to research center was 10.5. The total number of published articles was 20166 and 70% of which were indexed in ISI –WOS.34.2% and 21.7% of them were published in the first quantile journals and with international collaboration respectively. Based on research ranking, the first three centers were Tabriz Applied Pharmaceutical Science Research Center, Mashhad Pharmaceutical Sciences Research Center and Tabriz Pharmaceutical Nanotechnology research center. Mission oriented research activities in Iranian pharmaceutical research centers may lead them in achieving scientific authority.

A Validated Stability-Indicating RP-HPLC Method for Quantification of Glycyrrhizic Acid and Piperine in Polyherbal Formulations

Rahul Koli, Vinodhkumar. S. Mannur, Shankar Gharge, Sachin Gudasi

Iranian Journal of Pharmaceutical Sciences, Vol. 20 No. 2 (2024), 23 June 2024, Page 153-168

Glycyrrhizic acid and piperine are frequently used in conjunction with other therapies to treat a variety of disorders, although both medications have low water solubility and photosensitivity issues. The objective of this study is to develop a Reverse-phase High-Performance Liquid Chromatography (RP-HPLC) method, known for its selectivity, precision, sensitivity, and accuracy. This method is intended for the quantification of phytoconstituents in formulating polyherbal tablets as well as in certain Ayurvedic formulations. Glycyrrhizic acid and piperine were successfully separated by liquid chromatography using the phenomenex Luna C-18 column and an isocratic elution mode with a mobile phase made up of a combination of methanol and HPLC grade water. A photodiode array (PDA) detector was used to determine the retention times for glycyrrhizic acid and piperine, which were determined to be 2.06 minutes and 9.0 minutes and the method was found to be accurate (>95%) and precise (%RSD < 25) respectively. The method was established to be specific for the quantification of glycyrrhizic acid and piperine in in-house polyherbal tablets and some Ayurvedic formulations. Additionally, both phytoconstituents stress degradation studies were examined, and in the presence of degradation products, good drug peak separation was observed. Thus, glycyrrhizic acid and piperine may be regularly estimated in vitro and in vivo using this method.

A Framework of National Pharmacovigilance System for Developing Countries

Maryam Nikookalam, Azamossadat Hosseini, Hamid Moghaddasi, Farkhondeh Asadi, Afshin Zarghi

Iranian Journal of Pharmaceutical Sciences, Vol. 20 No. 2 (2024), 23 June 2024, Page 169-181

Pharmacovigilance is defined as “the science and activities related to the detection, assessment, understanding, and prevention of adverse drug reactions or any other drug-related problems”. The framework of the national pharmacovigilance system illustrates the general pattern of how the health system approaches the care of health products, defines the philosophy of supervision and policy orientation, and outlines the structure and development priorities of pharmacovigilance. The present study was conducted with the aim of presenting a framework of the national pharmacovigilance system framework for developing countries. The present study is of an applied study that was conducted descriptively in 2023. To present a framework of the national pharmacovigilance system framework, the main components of the national pharmacovigilance system framework were first identified and determined through a review of valid scientific sources and texts and national pharmacovigilance systems of the countries under study, considering the conditions and requirements of these countries. Then, the proposed model was put to the opinion of 65 experts for validation, and the Delphi method was implemented with a three-point scale in two rounds. Based on the results of the present study, the main components of the national pharmacovigilance system framework include: functions, infrastructure, and network. Each component includes sub-components and related operations and was agreed upon by experts with an average agreement rate of 95%. The framework of the national pharmacovigilance system is essential as a guide for the implementation of the national pharmacovigilance system. This framework enables a comprehensive evaluation of the structures and national and regional institutions affecting pharmacovigilance and can lead to the optimal implementation of the national pharmacovigilance system in developing countries. The national pharmacovigilance system can reduce drug-related problems, and its ultimate result can be a reduction in mortality and morbidity rates.

Investigating intricate plant extracts poses a formidable task in unearthing new bioactive compounds with therapeutic potential. Thus, the need for a rapid and sensitive method is crucial to ensure the quality and efficacy of herbal products in the botanical industry. A robust RP-HPLC technique was created, validated, and employed to separate, detect, and measure phytoconstituents. This method was then utilized for the analysis of chloroform extracts from the leaves of Eclipta prostrata and hydroethanolic extracts from Ziziphus nummularia. The RP-HPLC method involved employing a mobile/solvent phase of acetonitrile: methanol (7:3 v/v) at a constant flow rate of 1 mL/min, and the analysis was conducted at a wavelength of 208 nm. Eluted peaks were detected at retention times of 2.11±0.023 min, 3.233±0.045 min, 3.437±0.126 min, and 4.120±0.137 min, corresponding to rutin, stigmasterol, β-sitosterol, and quercetin, respectively. The response exhibited linearity in the range of 0.2-0.8 μg/ml, with a regression coefficient exceeding 0.991. The limits of detection (LOD) and quantification (LOQ) for these components ranged from 0.692-1.92 ng/ml and 2.10-10.45 ng/ml, respectively. This developed method demonstrated precision, specificity, reproducibility, and accuracy. It was subsequently applied to assess the content of dried leaf powder from E. prostrata and Z. nummularia. The RP-HPLC method has the potential to be beneficial for assessing both the qualitative and quantitative aspects of the components found in plant extracts and herbal products.