Mazandaran University of Medical Sciences Pharmaceutical and Biomedical Research 2423-4486 2423-4494 10 1 2024 12 1 Artificial Intelligence in Pharmaceuticals: Exploring Applications and Legal Challenges 1 10 EN Fatemeh Shaki Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. fshaki.tox@gmail.com N 0000-0001-5861-656X Mohamadsadegh Amirkhanloo Mehrandish Educational Law Institute, Gorgan, Iran. mohamadsadeghamirkhanloo@gmail.com N 0009-0000-6529-4845 Danial Jahani Unit of Medicinal Chemistry Associated With CSIC, Department of Toxicology and Therapeutical Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain. daniel.jahani.1987@gmail.com N 0000-0003-0885-031X Milad Chahardori Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. milad.chahardori@gmail.com Y 0000-0003-0466-8318 10.32598/PBR.10.1.1257.1 Background: The pharmaceutical sciences have the potential to benefit significantly from the advancements in artificial intelligence (AI). One of the primary areas where AI can prove invaluable is the discovery and development of new drugs. Compared to traditional methods, with the help of AI algorithms, vast amounts of data can be analyzed more efficiently, leading to the rapid identification of potential drug candidates. AI has the potential to expedite the drug discovery process, thereby leading to the development of new treatments for various diseases.  Objectives: This article delves into the manifold applications of AI in the pharmaceutical industry and the legal challenges that come with it. Methods: This study conducted a thorough search on the PubMed, Scopus, and Google Scholar databases using the following keywords: “Artificial intelligence”, “neural network”, “pharmacy”, “pharmaceutical”, “drug discovery”, “legal”, and “ethical”. In addition, we obtained further references by cross-referencing from essential articles. This article comprehensively overviews how AI is applied in the pharmaceutical industry and highlights the critical legal and ethical challenges. Results: AI can assist in personalized medicine by analyzing patient data and providing tailored treatment plans. By considering individual patient characteristics, such as genetics and medical history, AI algorithms can help healthcare professionals make more informed decisions about which treatments will most likely be effective for each patient. In addition to drug discovery and personalized medicine, AI can also enhance the efficiency of pharmaceutical manufacturing processes. AI-powered systems can monitor and optimize production lines, ensuring that quality standards are met while reducing the risks of errors or deviations. Additionally, AI can be an essential tool in pharmacovigilance through real-world data analysis, which can detect adverse drug reactions and other safety concerns. This approach can aid regulatory authorities and pharmaceutical companies identify and address potential medication risks more effectively. Conclusion: AI application in the pharmaceutical sciences has marked potential for improving drug discovery, clinical trials, personalized medicine, manufacturing processes, and pharmacovigilance. By using the power of AI, the industry can boost efficiency, cut costs, and ultimately deliver better healthcare outcomes for patients. Artificial intelligence, Drug design, Pharmacy, Legal, Ethics http://pbr.mazums.ac.ir/article-1-587-en.html http://pbr.mazums.ac.ir/article-1-587-en.pdf

Mazandaran University of Medical Sciences Pharmaceutical and Biomedical Research 2423-4486 2423-4494 10 1 2024 12 1 The Effects of Sodium Metabisulfite on the Hippocampus and Prefrontal Cortex in Wistar Rats: A Cognitive, Neurochemical, and Histological Study 11 22 EN Nathaniel Ohiemi Amedu Department of Anatomy, Faculty of Basic Medical Sciences, Adeleke University, Ede, Nigeria. amedunath11@gmail.com Y 0000-0002-8490-2292 Patrick Abolarin Department of Anatomy, Faculty of Basic Medical Sciences, Chrisland University, Abeokuta, Nigeria. natmedu01@gmail.com N Favour Wilcox Department of Anatomy, Faculty of Basic Medical Sciences, Adeleke University, Ede, Nigeria. favcox566@gmail.com N Habeeb Abdur-Rahman Department of Anatomy, Faculty of Basic Medical Sciences, Adeleke University, Ede, Nigeria. HAR@gmail.com N 10.32598/PBR.10.1.1065.2 Background: Studies have demonstrated that sub-chronic exposure to sodium metabisulfite (NaMBS) can have detrimental impacts on animal brain structure and function. However, there is scant research regarding its effect on certain brain regions and cognitive effects. Objectives: This study investigates the potential effect of sub-chronic exposure to NaMBS on the hippocampus and prefrontal cortex of female Wistar rats.  Methods: A total of 24 adolescent female Wistar rats were randomly divided into four groups (6 rats each) as follows: Group 1 (control) received 0.5 mL of normal saline; group 2 was administered by 100 mg/kg of NaMBS; group 3 was issued by 300 mg/kg of NaMBS; group 4 received 500 mg/kg of NaMBS. The route of administration was oral for 28 days. After completing the administration phase, the Y-maze test was conducted. Subsequently, the rats were euthanized, and tissue samples from the prefrontal cortex and hippocampus were collected for biochemical assays, precisely measuring malondialdehyde (MDA) and acetylcholinesterase (AChE) levels, as well as histological studies, such as hematoxylin and eosin, and glial fibrillary acidic protein (GFAP). Meanwhile, the neuronal count was done.  Results: The learning and memory functions of rats in the treated and control groups were similar (number of alternations: P>0.05). The group treated with 500 mg/kg NaMBS presented indications of neurodegeneration in CA1 of the hippocampus and high glial fibrillary acidic protein-immunoreactivity but had no noticeable effects on layer II/III of the prefrontal cortex. Regardless of the dosage of NaMBS, malondialdehyde level was the same (P>0.05) for all groups; however, in the group that received 500 mg/kg NaMBS, the acetylcholinesterase level was significantly reduced (P˂0.05).  Conclusion: This study revealed that while NaMBS can lead to neurodegeneration in the hippocampus of Wistar rats at 500 mg/kg, the prefrontal cortex remains resilient and spatial memory is unaffected, but a decrease in acetylcholinesterase activity raises cognitive concerns, emphasizing the need for cautious consideration of its use. Sodium metabisulfite, Hippocampus, Prefrontal cortex, Neurodegeneration, Acetylcholinesterase, Cognition http://pbr.mazums.ac.ir/article-1-589-en.html http://pbr.mazums.ac.ir/article-1-589-en.pdf

Mazandaran University of Medical Sciences Pharmaceutical and Biomedical Research 2423-4486 2423-4494 10 1 2024 12 1 Examining the Isolation of Bioactive Compounds, Antinociceptive, and Anti-inflammatory Activities of Strychnos Spinosa Lam. (Loganiaceae) Stembark Extract 23 32 EN Cletus Anes Ukwubile Department of Pharmacognosy, Faculty of Pharmacy, University of Maiduguri, Maiduguri, Nigeria. doccletus@yahoo.com Y 0000-0001-7183-4510 Troy Salvia Malgwi Department of Pharmacognosy, Faculty of Pharmacy, University of Maiduguri, Maiduguri, Nigeria. troysm2013@gmail.com N 0000-0001-5051-8754 Nnamdi David Menkiti Department of Chemistry, Faculty of Science, Ahmadu Bello University, Zaria, Nigeria. menkitind54@yahoo.com N 0000-0003-3746-6325 10.32598/PBR.10.1.1162.1 Background: Strychnos spinosa is a tree whose parts are popularly used in Southeast Nigeria to treat pains, infections, inflammations, hypertension, malaria fever, and ulcers.  Objectives: This study isolates the bioactive compounds in methanol stembark extract and evaluates the antinociceptive and anti-inflammatory potentials of S. spinosa.  Methods: Bioactive compounds were isolated using silica gel column chromatography, and their structures were elucidated using Fourier-transform infrared spectroscopy, gas chromatography/mass spectrometry, liquid chromatography/mass spectrometry, and nuclear magnetic resonance spectroscopy apparatus. The antinociceptive activity was determined using the acetic acid-induced writhing mice model, hot plate method, and tail immersion. In contrast, the anti-inflammatory activity was assessed using carrageenan-induced paw-edema in mice.  Results: The structural elucidation of the major bioactive compounds showed that the compounds are 18-methylnonadecanoate ester, 2-pyridin-3yl-ethanimidamide, 2-ethylformanilide, and acetamide. The extract at the doses of 200, 400, and 800 mg/kg, intraperitoneal significantly decreased (P<0.05) pains in acetic acid-induced writhing in mice, hot plate, and tail immersion assays in a dose-dependent fashion. In the hot plate and tail immersion assays, the extract produced significant pain inhibition of >50% after 120 min at a 400 mg/kg dose. In contrast, the stembark extract of S. spinosa produced the highest inhibition of paw edema formation at a dose of 400 mg/kg in 6 h in the carrageenan-induced paw edema model.  Conclusion: The results affirmed using S. spinosa stembark extract in traditional medicine to treat pain and inflammation. This was possible due to the presence of the isolated compounds. Bioactive compounds, Column chromatography, Strychnos spinosa, Antinociceptive, Anti-inflammatory http://pbr.mazums.ac.ir/article-1-530-en.html http://pbr.mazums.ac.ir/article-1-530-en.pdf

Mazandaran University of Medical Sciences Pharmaceutical and Biomedical Research 2423-4486 2423-4494 10 1 2024 12 1 Effects of Melissa officinalis Alcoholic Extract on Kidney Tissue and Apoptosis Gene Expression in a Wistar Rat Model With Spinal Cord Injury 33 46 EN Ali salehi Department of Cellular and Molecular Biology, Faculty of New Science and Technology, Tehran Medical Branch, Islamic Azad University, Tehran, Iran. salehiali618@gmail.com Y 0009-0007-3637-8987 10.32598/PBR.10.1.1223.1 Background: Spinal cord injury (SCI) is a severe neurological condition that can cause widespread inflammation, affecting vital organs, such as the kidneys. The kidneys are essential for filtering waste and maintaining blood components. This condition poses a serious threat to the person’s life. Additionally, studies have demonstrated that the alcoholic extract of Melissa officinalis, known for its ability to protect the nervous system, may be utilized in treating neurological disorders and secondary injuries associated with these conditions. Objectives: This study investigates the effects of the alcoholic extract of M. officinalis on histological changes in kidney tissue and the expression of apoptosis-related genes (Bax, Bcl-2, and CASP3) in rats with SCI. Methods: A total of 36 male Wistar rats, weighing between 225 and 250 g, were separated into four different groups for the experiment as follows: A control group (undergoing laminectomy), an SCI group, and two groups that received treatment with an alcoholic extract of the M. officinalis plant at doses of 100 and 150 mg/kg. The rats underwent SCI using the contusion method. Subsequently, 24 h after the injury, the plant extract was given once daily for 4 weeks. Kidney tissue samples were stained with hematoxylin-eosin for histomorphometric evaluation, and changes in gene expression were assessed using quantitative real-time ​polymerase chain reaction. Results: The concentrated form of the M. officinalis plant boosted the production of CASP3, Bax, and the inflammatory factor TNF-α and decreased the expression of the Bcl-2 gene. It also enhanced the structural and tissue alterations caused by SCI in the kidney tissue, improving kidney function for individuals with spinal cord injuries. Conclusion: The concentrated liquid from the M. officinalis plant can serve as a medicinal remedy for people with spinal cord injuries, and it may also enhance kidney function in those with similar injuries. Spinal cord injuries, Melissa, Apoptosis, Inflammation, Kidney http://pbr.mazums.ac.ir/article-1-578-en.html http://pbr.mazums.ac.ir/article-1-578-en.pdf

Mazandaran University of Medical Sciences Pharmaceutical and Biomedical Research 2423-4486 2423-4494 10 1 2024 12 1 Investigating the Quality Control, Antimicrobial, and Antioxidant Evaluation of the Ointment “Marham-i-Raal” Used in the Unani System of Medicine 47 56 EN Athar Parvez Ansari Regional Research Institute of Unani Medicine, Chennai (NABH Accredited), New Delhi, India. aatharparvez@gmail.com Y 0000-0002-5755-3525 Mary Shamya Arokiarajan Regional Research Institute of Unani Medicine, Chennai (NABH Accredited), New Delhi, India. sowmi.ms.92@gmail.com N 0000-0002-2900-1475 Wasim Akram Syed Akbar Regional Research Institute of Unani Medicine, Chennai (NABH Accredited), New Delhi, India. N 0000-0002-3234-1075 N Zaheer Ahmed Central Council for Research in Unani Medicine, Ministry of Ayush, Government of India, New Delhi, India. N 0000-0002-6906-2301 Noman Anwar Regional Research Institute of Unani Medicine, Chennai (NABH Accredited), New Delhi, India. N 0000-0003-0327-0033 10.32598/PBR.10.1.1228.1 Background: The global promotion of herbal products is not at par due to a lack of quality control studies. Marham-i-Raal, a pharmacopoeial ointment, treats various types of ulcers and wounds.  Objectives: The present study evaluates the quality control, antimicrobial, and antioxidant properties of Marham-i-Raal. Methods: The quality control parameters, including loss of weight on drying, pH, total ash value, acid-insoluble ash value, heavy metal analysis, microbial load, and high-performance thin-layer chromatography of Marham-i-Raal, were carried out. Moreover, the antimicrobial and antioxidant activities of Marham-i-Raal were also investigated.  Results: The quality control findings of Marham-i-Raal, including weight loss on drying, pH, total ash value, acid-insoluble ash value, heavy metal analysis, and microbial load, were found within the normal limits. The antimicrobial study of Marham-i-Raal has shown promising effects against gram-positive bacteria and Candida albicans. The antioxidant effects of the test drug were also found to be significant at higher concentrations against 2,2-diphenyl-1-picrylhydrazyl and 2,2’-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid methods.  Conclusion: The standards developed for the quality control of Marham-i-Raal may be referred to in the future for further studies. This important Unani ointment may be clinically used to treat non-healing ulcers and wounds. Marham-i-Raal, Unani ointment, Quality control, HPTLC, Antimicrobial, Antioxidant http://pbr.mazums.ac.ir/article-1-572-en.html http://pbr.mazums.ac.ir/article-1-572-en.pdf

Mazandaran University of Medical Sciences Pharmaceutical and Biomedical Research 2423-4486 2423-4494 10 1 2024 12 1 Examining the Phytochemical Analysis, In Vitro Cytotoxicity, and Antimicrobial Effects of Rotundine Glycoside Isolated From Cyperus rotundus L. Rhizomes 57 72 EN Mohammed N Sabir Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, University of Sulaimani, Sulaymaniyah, Iraq. mohammed.sabir@univsul.edu.iq N 0000-0001-8826-880X Selar Izzat Department of Biology, College of Science, University of Sulaimani, Sulaymaniyah, Iraq. selar.izzat@univsul.edu.iq N Shahlaa M Abdullah Department of Medical Laboratory Science, College of Science, University of Raparin, Ranya, Iraq. shahla.mohammed@uor.edu.krd N 0000-0001-5296-8206 Bahez O Ismael Kurdistan Institution for Strategic Studies and Scientific Research, Sulaymaniyah, Iraq. bahez.osman@kissr.edu.krd N 0000-0001-9652-5853 Kawkab Y Saour Department of Pharmaceutical Chemistry, College of Pharmacy, University of Baghdad, Baghdad, Iraq. Dr.ksaour@yahoo.com N 0000-0002-8922-0696 Shwan Rachid Charmo Center for Research and Training, Charmo University, Chamchamal, Iraq. shwan.rachid@charmouniversity.org Y 0000-0003-0834-5153 10.32598/PBR.10.1.1234.1 Background: Plant metabolites, like antimicrobial and cytotoxic effects, exhibit therapeutic benefits. The crude extract of Cyperus rotundus (CR) rhizomes demonstrates such activities; however, the specific components responsible for these functions have not been determined. Objectives: This study identifies the bioactive alkaloids in CR rhizome extract.  Methods: The crude methanolic extract of CR rhizomes was acidified, followed by basification. The precipitate was then purified using sequential chromatographic and high-performance liquid chromatography techniques. Structural elucidation of the derived compound was performed using the Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance, and mass spectroscopy. Disc dilution and diffusion assays were used to evaluate the isolated compound’s minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) against selected microbial species. The cytotoxicity of the isolated compound was determined against HeLa cancer cells using MTT cell proliferation assays.  Results: Spectral analysis confirmed the presence of norrotundine-6-O-glucoside plus appreciable amounts of flavonoids nootkatone, quercetin, chlorogenic acid, catechin, and β-sitosterol. The isolated alkaloid inhibited the growth of Staphylococcus aureus (MIC=MBC=64 µg/mL), Escherichia coli (MIC=100 µg/mL), and Candida albicans (MIC=MBC=64 µg/mL). The alkaloid’s half-maximal inhibitory concentration (IC50) was 203.7 µg/mL. The obtained alkaloid from the CR rhizomes’ crude extract revealed bactericidal and fungicidal effects against S. aureus and C. albicans, respectively, at 64 µg/mL, bacteriostatic against E. coli at 100 µg/mL, and cytotoxic against HeLa cells at an IC50 equal to 203.7 µg/mL. Conclusion: The elucidated alkaloid from the CR rhizomes’ crude extract exhibited bactericidal and fungicidal effects against S. aureus and C. albicans, respectively, at 64 µg/mL, bacteriostatic activity against E. coli at 100 µg/mL and cytotoxicity against HeLa cells at IC50 of 203.7 µg/mL. Alkaloids, Antimicrobial, Chromatography, Cyperus rotundus, Anticancer, Natural products http://pbr.mazums.ac.ir/article-1-577-en.html http://pbr.mazums.ac.ir/article-1-577-en.pdf

Mazandaran University of Medical Sciences Pharmaceutical and Biomedical Research 2423-4486 2423-4494 10 1 2024 12 1 Acute Efavirenz Intoxication in a 16-year-old HIV Negative Girl: A Case Report and Literature Review 73 78 EN Minoo Moghimi Department of Clinical Pharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. minoomoghimii@gmail.com N 0000-0002-6521-3360 Zahra Nekoukar Department of Clinical Pharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. nazanin.nekoukar@gmail.com N 0000-0003-2663-9024 Navid Khosravi Department of Emergency Medicine, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. n.khosravi@mazums.ac.ir Y 0000-0003-4046-8313 10.32598/PBR.10.1.931.1 Background: There are only rare case reports that revealed the efavirenz (EFV) toxicity. Case Report: This study presents an acute intoxication with 12 g of efavirenz in a 16-year-old healthy girl whose main problem was dose-dependent neurotoxicity. No other serious EFV-related side effects were seen. Previous serious side effects of EFV were observed in HIV-infected patients who underwent long-term combination drug therapy.  Conclusion: Accordingly, in terms of the key clinical messages, serious adverse effects of efavirenz are expected to be observed in long-term use in combination with other antiretroviral drugs. Efavirenz, Intoxication, Neurotoxicity, Human immunodeficiency virus, Toxicology http://pbr.mazums.ac.ir/article-1-549-en.html http://pbr.mazums.ac.ir/article-1-549-en.pdf

Mazandaran University of Medical Sciences Pharmaceutical and Biomedical Research 2423-4486 2423-4494 10 1 2024 12 1 Investigating the Excessive Sweating Induced by Aripiprazole: Two Case Reports 79 82 EN Seyed Hamzeh Hosseini Psychosomatic Research Center, Mazandaran University of Medical Sciences, Sari, Iran. hosseinish20@gmail.com N 0000-0002-0987-4295 Hamed Ghazvini Department of Neuroscience, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran. hghazvini1@gmail.com N 0000-0002-7644-4834 Seyedeh Masoumeh Seyedhosseini Tamijani Psychiatry and Behavioral Sciences Research Center, Addiction Institute, Mazandaran University of Medical Sciences, Sari, Iran. seyedhoseini_sm@yahoo.com N 0000-0001-7228-4071 Raheleh Rafaiee Department of Neuroscience, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran. rahelerafaie@gmail.com Y 0000-0003-2796-5868 10.32598/PBR.10.1.1231.1 Background: Many drugs, including antipsychotics, cause an adverse effect, such as excessive sweating (hyperhidrosis). Hyperhidrosis occurs by drugs that act on the thermoregulatory centers in the hypothalamus, spinal, and sympathetic ganglia or on the endocrine system.  Case Report: This study reports two patients who developed hyperhidrosis while taking aripiprazole. A 38-year-old woman who had a diagnosis of obsessive-compulsive disorder and a 17-year-old boy who developed multiple motor tics continued to take aripiprazole even though they had hyperhidrosis. The dosage of aripiprazole was adjusted to reduce diaphoresis. Conclusion: Besides the potential risks of dehydration, electrolyte depletion, and hypothermia, hyperhidrosis may be a distressing and embarrassing symptom that, if not addressed properly, can promote noncompliance with the medication. Therefore, it is imperative to create awareness of this unusual potential adverse effect of aripiprazole. Aripiprazole, Hyperhidrosis, Sweating, Adverse drug event http://pbr.mazums.ac.ir/article-1-576-en.html http://pbr.mazums.ac.ir/article-1-576-en.pdf