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Mandalari G, Pennisi R, Gervasi T, Sciortino MT. Pistacia vera L. as natural source against antimicrobial and antiviral resistance. Front Microbiol 2024; 15:1396514. [PMID: 39011148 PMCID: PMC11246903 DOI: 10.3389/fmicb.2024.1396514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 06/10/2024] [Indexed: 07/17/2024] Open
Abstract
Increased global research is focused on the development of novel therapeutics to combat antimicrobial and antiviral resistance. Pistachio nuts represent a good source of protein, fiber, monounsaturated fatty acids, minerals, vitamins, and phytochemicals (carotenoids, phenolic acids, flavonoids and anthocyanins). The phytochemicals found in pistachios are structurally diverse compounds with antimicrobial and antiviral potential, demonstrated as individual compounds, extracts and complexed into nanoparticles. Synergistic effects have also been reported in combination with existing drugs. Here we report an overview of the antimicrobial and antiviral potential of pistachio nuts: studies show that Gram-positive bacterial strains, such as Staphylococcus aureus, are the most susceptible amongst bacteria, whereas antiviral effect has been reported against herpes simplex virus 1 (HSV-1). Amongst the known pistachio compounds, zeaxanthin has been shown to affect both HSV-1 attachment penetration of human cells and viral DNA synthesis. These data suggest that pistachio extracts and derivatives could be used for the topical treatment of S. aureus skin infections and ocular herpes infections.
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Affiliation(s)
- Giuseppina Mandalari
- Department of Chemical, Biological, Pharmaceutical, and Environmental Science, University of Messina, Messina, Italy
| | - Rosamaria Pennisi
- Department of Chemical, Biological, Pharmaceutical, and Environmental Science, University of Messina, Messina, Italy
| | - Teresa Gervasi
- Department of Biomedical and Dental Science and Morphofunctional Imaging, University of Messina, Messina, Italy
| | - Maria Teresa Sciortino
- Department of Chemical, Biological, Pharmaceutical, and Environmental Science, University of Messina, Messina, Italy
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Vieira RV, Peiter GC, de Melo FF, Zarpelon-Schutz AC, Teixeira KN. In silico prospective analysis of the medicinal plants activity on the CagA oncoprotein from Helicobacter pylori. World J Clin Oncol 2024; 15:653-663. [PMID: 38835850 PMCID: PMC11145963 DOI: 10.5306/wjco.v15.i5.653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 04/01/2024] [Accepted: 04/18/2024] [Indexed: 05/21/2024] Open
Abstract
BACKGROUND Colonization with Helicobacter pylori (H. pylori) has a strong correlation with gastric cancer, and the virulence factor CagA is implicated in carcinogenesis. Studies have been conducted using medicinal plants with the aim of eliminating the pathogen; however, the possibility of blocking H. pylori-induced cell differentiation to prevent the onset and/or progression of tumors has not been addressed. This type of study is expensive and time-consuming, requiring in vitro and/or in vivo tests, which can be solved using bioinformatics. Therefore, prospective computational analyses were conducted to assess the feasibility of interaction between phenolic compounds from medicinal plants and the CagA oncoprotein. AIM To perform a computational prospecting of the interactions between phenolic compounds from medicinal plants and the CagA oncoprotein of H. pylori. METHODS In this in silico study, the structures of the phenolic compounds (ligands) kaempferol, myricetin, quercetin, ponciretin (flavonoids), and chlorogenic acid (phenolic acid) were selected from the PubChem database. These phenolic compounds were chosen based on previous studies that suggested medicinal plants as non-drug treatments to eliminate H. pylori infection. The three-dimensional structure model of the CagA oncoprotein of H. pylori (receptor) was obtained through molecular modeling using computational tools from the I-Tasser platform, employing the threading methodology. The primary sequence of CagA was sourced from GenBank (BAK52797.1). A screening was conducted to identify binding sites in the structure of the CagA oncoprotein that could potentially interact with the ligands, utilizing the GRaSP online platform. Both the ligands and receptor were prepared for molecular docking using AutoDock Tools 4 (ADT) software, and the simulations were carried out using a combination of ADT and AutoDock Vina v.1.2.0 software. Two sets of simulations were performed: One involving the central region of CagA with phenolic compounds, and another involving the carboxy-terminus region of CagA with phenolic compounds. The receptor-ligand complexes were then analyzed using PyMol and BIOVIA Discovery Studio software. RESULTS The structure model obtained for the CagA oncoprotein exhibited high quality (C-score = 0.09) and was validated using parameters from the MolProbity platform. The GRaSP online platform identified 24 residues (phenylalanine and leucine) as potential binding sites on the CagA oncoprotein. Molecular docking simulations were conducted with the three-dimensional model of the CagA oncoprotein. No complexes were observed in the simulations between the carboxy-terminus region of CagA and the phenolic compounds; however, all phenolic compounds interacted with the central region of the oncoprotein. Phenolic compounds and CagA exhibited significant affinity energy (-7.9 to -9.1 kcal/mol): CagA/kaempferol formed 28 chemical bonds, CagA/myricetin formed 18 chemical bonds, CagA/quercetin formed 16 chemical bonds, CagA/ponciretin formed 13 chemical bonds, and CagA/chlorogenic acid formed 17 chemical bonds. Although none of the phenolic compounds directly bound to the amino acid residues of the K-Xn-R-X-R membrane binding motif, all of them bound to residues, mostly positively or negatively charged, located near this region. CONCLUSION In silico, the tested phenolic compounds formed stable complexes with CagA. Therefore, they could be tested in vitro and/or in vivo to validate the findings, and to assess interference in CagA/cellular target interactions and in the oncogenic differentiation of gastric cells.
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Affiliation(s)
| | | | - Fabrício Freire de Melo
- Universidade Federal da Bahia, Instituto Multidisciplinar em Saúde-Campus Anísio Teixeira, Vitória da Conquista 45029-094, Brazil
| | - Ana Carla Zarpelon-Schutz
- Universidade Federal do Paraná, Campus Toledo, Toledo 85919-899, Brazil
- Universidade Federal do Paraná-Setor Palotina, Programa de Pós-graduação em Biotecnologia, Palotina 85950-000, Brazil
| | - Kádima Nayara Teixeira
- Universidade Federal do Paraná, Campus Toledo, Toledo 85919-899, Brazil
- Universidade Federal do Paraná-Setor Palotina, Programa de Pós-graduação em Biotecnologia, Palotina 85950-000, Brazil
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Tewari D, Bawari S, Mishra ST, Gupta P, M A, Cziáky Z, Jeko J, Lazarova I, Zengin G. Metabolomics-based pharmaceutical evaluation of different parts of Swertia chirayita (Roxb.) Buch.-Ham. ex C.B. Clarke from the western Himalayas. J Sep Sci 2024; 47:e2300795. [PMID: 38234031 DOI: 10.1002/jssc.202300795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 12/11/2023] [Accepted: 12/22/2023] [Indexed: 01/19/2024]
Abstract
Swertia species are common ingredients in numerous herbal remedies. It is also used to treat a wide range of illnesses and possess diverse therapeutic activities. The aim of the study is to elucidate the comprehensive metabolomics profile of Swertia chirayita and the role of various extraction methods in the phytochemical compositions of the extracts of S. chirayita, and their antioxidant and enzyme inhibitory activities. Extraction of the stems, leaves, and flowering tops of S. chirayita was performed by maceration, infusion, and soxhlation using methanol and water as solvent. Extracts were subjected to phytochemical profiling by a liquid-chromatographic system. Antioxidant and enzyme inhibitory activity was carried out. The metabolomics profiling showed that a diverse range of specialized metabolites were present in the stems and leaves & flowering tops of the plant. All the extracts showed substantial antioxidant and enzyme inhibitory activities further confirmed by molecular docking studies. This study appraised the use of S. chirayita aerial parts as a potential antioxidant and its therapeutic application in various chronic illnesses including Alzheimer's disease, diabetes, and other skin-related disorders.
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Affiliation(s)
- Devesh Tewari
- Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi, India
| | - Sweta Bawari
- Department of Pharmacology, Amity Institute of Pharmacy, Amity University, Noida, India
| | - Saurabh T Mishra
- Department of Career Services, Edvancer - a part of Global University System, India, Mumbai, India
| | - Pawan Gupta
- Department of Pharmaceutical Chemistry, Shri Vile Parle Kelavani Mandal's Institute of Pharmacy, Dhule, India
| | - Aryalaxmi M
- Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi, India
| | - Zoltán Cziáky
- Agricultural and Molecular Research and Service Institute, University of Nyíregyháza, Nyiregyhaza, Hungary
| | - József Jeko
- Agricultural and Molecular Research and Service Institute, University of Nyíregyháza, Nyiregyhaza, Hungary
| | - Irina Lazarova
- Department of Chemistry, Faculty of Pharmacy, Medical University-Sofia, Sofia, Bulgaria
| | - Gökhan Zengin
- Department of Biology, Faculty of Science, Selçuk University, Konya, Turkey
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Wang Z, Yang L. The Therapeutic Potential of Natural Dietary Flavonoids against SARS-CoV-2 Infection. Nutrients 2023; 15:3443. [PMID: 37571380 PMCID: PMC10421531 DOI: 10.3390/nu15153443] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 07/28/2023] [Accepted: 08/02/2023] [Indexed: 08/13/2023] Open
Abstract
The exploration of non-toxic and cost-effective dietary components, such as epigallocatechin 3-gallate and myricetin, for health improvement and disease treatment has recently attracted substantial research attention. The recent COVID-19 pandemic has provided a unique opportunity for the investigation and identification of dietary components capable of treating viral infections, as well as gathering the evidence needed to address the major challenges presented by public health emergencies. Dietary components hold great potential as a starting point for further drug development for the treatment and prevention of SARS-CoV-2 infection owing to their good safety, broad-spectrum antiviral activities, and multi-organ protective capacity. Here, we review current knowledge of the characteristics-chemical composition, bioactive properties, and putative mechanisms of action-of natural bioactive dietary flavonoids with the potential for targeting SARS-CoV-2 and its variants. Notably, we present promising strategies (combination therapy, lead optimization, and drug delivery) to overcome the inherent deficiencies of natural dietary flavonoids, such as limited bioavailability and poor stability.
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Affiliation(s)
- Zhonglei Wang
- Key Laboratory of Green Natural Products and Pharmaceutical Intermediates in Colleges and Universities of Shandong Province, School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, China
- School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorus, Chemistry & Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, China
| | - Liyan Yang
- School of Physics and Physical Engineering, Qufu Normal University, Qufu 273165, China
- Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
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Lei S, Chen X, Wu J, Duan X, Men K. Small molecules in the treatment of COVID-19. Signal Transduct Target Ther 2022; 7:387. [PMID: 36464706 PMCID: PMC9719906 DOI: 10.1038/s41392-022-01249-8] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 11/02/2022] [Accepted: 11/08/2022] [Indexed: 12/11/2022] Open
Abstract
The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies and economies. Until now, effective therapeutics against COVID-19 are in high demand. Along with our improved understanding of the structure, function, and pathogenic process of SARS-CoV-2, many small molecules with potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition of viral proteins such as RdRp and Mpro, interference of host enzymes including ACE2 and proteases, and blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, and NLRP3 pathways, are regarded feasible in drug development. The development of small molecules to treat COVID-19 has been achieved by several strategies, including computer-aided lead compound design and screening, natural product discovery, drug repurposing, and combination therapy. Several small molecules representative by remdesivir and paxlovid have been proved or authorized emergency use in many countries. And many candidates have entered clinical-trial stage. Nevertheless, due to the epidemiological features and variability issues of SARS-CoV-2, it is necessary to continue exploring novel strategies against COVID-19. This review discusses the current findings in the development of small molecules for COVID-19 treatment. Moreover, their detailed mechanism of action, chemical structures, and preclinical and clinical efficacies are discussed.
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Affiliation(s)
- Sibei Lei
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Xiaohua Chen
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Jieping Wu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Xingmei Duan
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China.
| | - Ke Men
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
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Periferakis A, Periferakis K, Badarau IA, Petran EM, Popa DC, Caruntu A, Costache RS, Scheau C, Caruntu C, Costache DO. Kaempferol: Antimicrobial Properties, Sources, Clinical, and Traditional Applications. Int J Mol Sci 2022; 23:ijms232315054. [PMID: 36499380 PMCID: PMC9740324 DOI: 10.3390/ijms232315054] [Citation(s) in RCA: 108] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 11/23/2022] [Accepted: 11/26/2022] [Indexed: 12/03/2022] Open
Abstract
Flavonoids are a category of plant-derived compounds which exhibit a large number of health-related effects. One of the most well-known and studied flavonoids is kaempferol, which can be found in a wide variety of herbs and plant families. Apart from their anticarcinogenic and anti-inflammatory effects, kaempferol and its associated compounds also exhibit antibacterial, antifungal, and antiprotozoal activities. The development of drugs and treatment schemes based on these compounds is becoming increasingly important in the face of emerging resistance of numerous pathogens as well as complex molecular interactions between various drug therapies. In addition, many of the kaempferol-containing plants are used in traditional systems all over the world for centuries to treat numerous conditions. Due to its variety of sources and associated compounds, some molecular mechanisms of kaempferol antimicrobial activity are well known while others are still under analysis. This paper thoroughly documents the vegetal and food sources of kaempferol as well as the most recent and significant studies regarding its antimicrobial applications.
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Affiliation(s)
- Argyrios Periferakis
- Department of Physiology, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Akadimia of Ancient Greek and Traditional Chinese Medicine, 16675 Athens, Greece
| | - Konstantinos Periferakis
- Akadimia of Ancient Greek and Traditional Chinese Medicine, 16675 Athens, Greece
- Pan-Hellenic Organization of Educational Programs (P.O.E.P), 17236 Athens, Greece
- Orasis Acupuncture Institute, 11526 Athens, Greece
| | - Ioana Anca Badarau
- Department of Physiology, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Elena Madalina Petran
- Department of Biochemistry, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Toxicology, Grigore Alexandrescu Emergency Children’s Hospital, 011743 Bucharest, Romania
| | - Delia Codruta Popa
- Department of Biochemistry, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Correspondence: (D.C.P.); (C.S.)
| | - Ana Caruntu
- Department of Oral and Maxillofacial Surgery, ‘Dr. Carol Davila’ Central Military Emergency Hospital, 010825 Bucharest, Romania
- Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine, ‘Titu Maiorescu’ University, 031593 Bucharest, Romania
| | - Raluca Simona Costache
- Department of Gastroenterology, Gastroenterology and Internal Medicine Clinic, ‘Dr. Carol Davila’ Central Military Emergency Hospital, 010825 Bucharest, Romania
- Department of Internal Medicine and Gastroenterology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Cristian Scheau
- Department of Physiology, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Correspondence: (D.C.P.); (C.S.)
| | - Constantin Caruntu
- Department of Physiology, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Dermatology, ‘Prof. N.C. Paulescu’ National Institute of Diabetes, Nutrition and Metabolic Diseases, 011233 Bucharest, Romania
| | - Daniel Octavian Costache
- Department of Dermatology, ‘Dr. Carol Davila’ Central Military Emergency Hospital, 010825 Bucharest, Romania
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Antimicrobial Alkaloids from Marine-Derived Fungi as Drug Leads versus COVID-19 Infection: A Computational Approach to Explore their Anti-COVID-19 Activity and ADMET Properties. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:5403757. [PMID: 35911157 PMCID: PMC9325633 DOI: 10.1155/2022/5403757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 06/11/2022] [Indexed: 11/28/2022]
Abstract
Therapeutic strategies based upon enzyme inhibition have recently gained higher attention in treating hazardous ailments. Herein, the potential use of seventy-two antimicrobial alkaloids isolated from marine-derived fungi to fight COVID-19 infection via inhibition of SARS-CoV-2 lethal virus was performed using in silico analyses. Molecular modelling was performed to assess their enzyme inhibitory potential on the main protease SARS-CoV-2 MPro, 3-chymotrypsin-like protease SARS-CoV-2 3CLpro, and papain-like protease SARS-CoV-2 PLpro using Discovery Studio 4.5. Validation of the docking experiments was done by determination of RMSD (root mean square deviation) after redocking the superimposition of the cocrystalized ligands. Results showed that gymnastatin Z (72) showed the best fitting score in SARS-CoV-2 MPro and SARS-CoV-2 3CLpr active sites with ∆G equal −34.15 and −34.28 Kcal/mol, respectively. Meanwhile, scalusamide C (62) displayed the highest fitting within SARS-CoV-2 PLpro active sites (∆G = −26.91 Kcal/mol) followed by eutypellazine M (57). ADMET/TOPKAT prediction displayed that eutypellazine M and scalusamide C showed better pharmacokinetic and pharmacodynamic properties. Gymnastatin Z is safer showing better toxicity criteria and higher rat oral LD50 and rat chronic LOAEL (lowest observed adverse effect level). Chemometric analysis using principle component analysis (PCA) based on the binding energies observed for the compounds with respect to the three tested enzymes revealed the clustering of the compounds into different clusters. Eutypellazine M, scalusamide C, and gymnastatin Z appear in one cluster due to their closeness in activity. Thus, these compounds could serve as promising SARS-CoV-2 enzymes inhibitors that could help in alleviation of COVID-19 infection. Further investigations are recommended to confirm the results of molecular modelling.
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Elkolli M, Elkolli H. The management of COVID 19 by plant extracts, essential oils and phytoconstituents: A review. ACTA PERIODICA TECHNOLOGICA 2022:188-205. [DOI: 10.2298/apt2253188e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome
virus 2 (SARSCoV- 2), it is a virus belonging to the family Coronaviridae
which includes zoonotic viruses infecting mammals and birds. This disease
emerged in December 2019 in Wuhan, China, and quickly developed into a
global pandemic with high mortality rates. The magnitude of the pandemic has
involved a global collaborative scientific response to develop effective
preventive and therapeutic means using both traditional and advanced
techniques. However, to date specific therapies for COVID-19 are not well
established and only a few vaccines are approved for emergency use. Herbal
remedies, especially essential oils (EOs) can boost immunity which plays a
decisive role in the initiation and progression of the disease in the
preliminary stage of a COVID-19 infection. The low cost and availability of
medicinal plants as well as the almost non-existent side effects encourages
their widespread use during the pandemic, hence a great need to identify
plant extracts for anti-COVID 19 use. Although the majority of studies are
done in silico, with little in vivo or in vitro study, we can have an idea
for further later experiments.
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Affiliation(s)
- Meriem Elkolli
- Laboratory of applied microbiology. University of Sétif, Sétif, Algeria
| | - Hayet Elkolli
- Laboratory of multiphasic polymeric materials, University of Setif, Algeria
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Elhady SS, Youssef FS, Alahdal AM, Almasri DM, Ashour ML. Anti-Hyperglycaemic Evaluation of Buddleia indica Leaves Using In Vitro, In Vivo and In Silico Studies and Its Correlation with the Major Phytoconstituents. PLANTS (BASEL, SWITZERLAND) 2021; 10:plants10112351. [PMID: 34834714 PMCID: PMC8617869 DOI: 10.3390/plants10112351] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 10/22/2021] [Accepted: 10/26/2021] [Indexed: 06/13/2023]
Abstract
Buddleia indica Lam. is an ornamental evergreen shrub with few reports concerning its phytoconstituents and biological activities. Herein, the antihyperglycaemic activity of B. indica leaves methanol extract (BIT) was evaluated for the first time using in vitro and in vivo studies. Molecular modelling was performed for its major phytoconstituents that were further subjected to ADME/TOPAKT (absorption, distribution, metabolism, excretion and toxicity) prediction. BIT revealed considerable reduction in glucose concentration by 9.93% at 50 μg/mL using 3T3-L1 adipocyte culture. It displayed substantial inhibition versus α-glucosidase and α-amylase with IC50 205.2 and 385.06 μg/mL, respectively. In vivo antihyperglycaemic activity of BIT and the ethyl acetate fraction (BIE) was performed using streptozotocin-induced diabetes in rat model. BIT and BIE effectively ameliorate oxidative stress markers in addition to reducing serum blood glucose by 56.08 and 54.00%, respectively, and are associated with a substantial increase in serum insulin by 4.1 and 12.7%, respectively. This can be attributed to its richness with polyphenolic compounds comprising flavonoids, phenolic acids, phenyl propanoids and iridoids. Molecular docking showed that verbascoside and kaempferol displayed the highest fitting within human α-amylase (HA) and human α-glucosidase (HG) active sites, respectively. They showed reasonable pharmacokinetic, pharmacodynamic and toxicity properties, as revealed by ADME/TOPKAT study.
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Affiliation(s)
- Sameh S. Elhady
- Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
| | - Fadia S. Youssef
- Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Abbasia, Cairo 11566, Egypt
| | - Abdulrahman M. Alahdal
- Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (A.M.A.); (D.M.A.)
| | - Diena M. Almasri
- Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (A.M.A.); (D.M.A.)
| | - Mohamed L. Ashour
- Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Abbasia, Cairo 11566, Egypt
- Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia
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Youssef FS, Ovidi E, Musayeib NMA, Ashour ML. Morphology, Anatomy and Secondary Metabolites Investigations of Premna odorata Blanco and Evaluation of Its Anti-Tuberculosis Activity Using In Vitro and In Silico Studies. PLANTS (BASEL, SWITZERLAND) 2021; 10:1953. [PMID: 34579484 PMCID: PMC8467642 DOI: 10.3390/plants10091953] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 09/11/2021] [Accepted: 09/14/2021] [Indexed: 06/06/2023]
Abstract
In-depth botanical characterization was performed on Premna odorata Blanco (Lamiaceae) different organs for the first time. The leaves are opposite, hairy and green in color. Flowers possess fragrant aromatic odors and exist in inflorescences of 4-15 cm long corymbose cyme-type. In-depth morphological and anatomical characterization revealed the great resemblance to plants of the genus Premna and of the family Lamiaceae, such as the presence of glandular peltate trichomes and diacytic stomata. Additionally, most examined organs are characterized by non-glandular multicellular covering trichomes, acicular, and rhombic calcium oxalate crystals. P. odorata leaves n-hexane fraction revealed substantial anti-tuberculous potential versus Mycobacterium tuberculosis, showing a minimum inhibition concentration (MIC) of 100 μg/mL. Metabolic profiling of the n-hexane fraction using gas-chromatography coupled to mass spectrometry (GC/MS) analysis revealed 10 major compounds accounting for 93.01%, with trans-phytol constituting the major compound (24.06%). The virtual screening revealed that trans-phytol highly inhibited MTB C171Q receptor as M. tuberculosis KasA (β-ketoacyl synthases) with a high fitting score (∆G = -15.57 kcal/mol) approaching that of isoniazid and exceeding that of thiolactomycin, the co-crystallized ligand. Absorption, distribution, metabolism, excretion and toxicity predictions (ADME/TOPKAT) revealed that trans-phytol shows lower solubility and absorption levels when compared to thiolactomycin and isoniazid. Still, it is safer, causing no mutagenic or carcinogenic effects with higher lethal dose, which causes the death of 50% (LD50). Thus, it can be concluded that P. odorata can act as a source of lead entities to treat tuberculosis.
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Affiliation(s)
- Fadia S. Youssef
- Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Abbasia, Cairo 11566, Egypt
| | - Elisa Ovidi
- Department for the Innovation in Biological, Agrofood and Forestal Systems, Tuscia University, 01100 Viterbo, Italy;
| | - Nawal M. Al Musayeib
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia;
| | - Mohamed L. Ashour
- Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Abbasia, Cairo 11566, Egypt
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