Journal of Pharmacopuncture (대한약침학회지)

KOREAN PHARMACOPUNCTURE INSTITUTE (대한약침학회)
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Phytochemical, Antidiabetic, Antioxidant, Antibacterial, Acute and Sub-Chronic Toxicity of Moroccan Arbutus unedo Leaves

  • Latifa, Doudach (Biomedical Engineering Department, National School of Arts and Crafts Rabat (ENSAM), Mohammed V University) ;
  • Hanae Naceiri, Mrabti (Laboratory of Pharmacology and Toxicology, Bio Pharmaceutical and Toxicological Analysis Research Team, Faculty of Medicine and Pharmacy, Mohammed V University) ;
  • Samiah Hamad, Al-Mijalli (Department of Biology, College of Sciences, Princess Nourah bint Abdulrahman University) ;
  • Mohamed Reda, Kachmar (Faculty of Sciences, Health and Environment Laboratory, Plant Protection Team, Moulay Ismail University) ;
  • Kaoutar, Benrahou (Laboratory of Pharmacology and Toxicology, Bio Pharmaceutical and Toxicological Analysis Research Team, Faculty of Medicine and Pharmacy, Mohammed V University) ;
  • Hamza, Assaggaf (Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University) ;
  • Ahmed, Qasem (Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University) ;
  • Emad Mohamed, Abdallah (Department of Science Laboratories, College of Science and Arts, Qassim University) ;
  • Bodour Saeed, Rajab (Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University) ;
  • Khouloud, Harraqui (Biology and Health Laboratory, Faculty of Sciences, Ibn Tofail University) ;
  • Mouna, Mekkaoui (Pharmacodynamics Research Team ERP, Laboratory of Pharmacology and Toxicology, Faculty of Medicine and Pharmacy, University Mohammed V) ;
  • Abdelhakim, Bouyahya (Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, and Genomic Center of Human Pathologies, Mohammed V University) ;
  • Moulay El Abbes, Faouzi (Laboratory of Pharmacology and Toxicology, Bio Pharmaceutical and Toxicological Analysis Research Team, Faculty of Medicine and Pharmacy, Mohammed V University)
  • Received : 2022.06.05
  • Accepted : 2022.12.12
  • Published : 2023.03.31
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Abstract

Objectives: Moroccan Arbutus unedo is an essential medicinal plant; however, little is known about the biological properties of its leaves mentioned in Moroccan traditional medicine. Methods: Various standard experiments were performed to evaluate the phytochemical, antidiabetic, antioxidant, antibacterial, and acute and sub-chronic toxicity characteristics of A. unedo leaves. Results: Phytochemical screening led to the identification of several phytochemical classes, including tannins, flavonoids, terpenoids, and anthraquinones, with high concentrations of polyphenols (31.83 ± 0.29 mg GAEs/g extract) and flavonoids (16.66 ± 1.47 mg REs/g extract). Further, the mineral analysis revealed high levels of calcium and potassium. A. unedo extract demonstrated significant antioxidant and anti-diabetic activities by inhibiting α-amylase (1.350 ± 0.32 g/mL) and α-glucosidase (0.099 ± 1.21 g/mL) compared to the reference drug Acarbose. Also, the methanolic extract of the plant exhibited significantly higher antibacterial activity than the aqueous extract. Precisely, three of the four examined bacterial strains exhibited substantial susceptibility to the methanolic extract . Minimum bactericidal concentration (MBC)/minimum inhibitory concentration (MIC) values indicated that A. unedo harbor abundant bactericidal compounds. For toxicological studies, mice were administered with A. unedo aqueous extract at single doses of 2,000 and 5,000 mg/kg. They did not exhibit significant abnormal behavior, toxic symptoms, or death during the 14-day acute toxicity test and the 90-day sub-chronic toxicity test periods. The general behavior, body weight, and hematological and biochemical status of the rats were assessed, revealing no toxicological symptoms or clinically significant changes in biological markers observed in the mice models, except hypoglycemia, after 90 days of daily dose administration. Conclusion: The study highlighted several biological advantages of A. unedo leaves without toxic effects in short-term application. Our findings suggest that conducting more comprehensive and extensive in vivo investigations is of utmost importance to identify molecules that can be formulated into pharmaceuticals in the future.

Keywords

Acknowledgement

Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2023R158) Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

References

  1. Zhang A, Sun H, Wang X. Recent advances in natural products from plants for treatment of liver diseases. Eur J Med Chem. 2013;63:570-7. https://doi.org/10.1016/j.ejmech.2012.12.062
  2. Attanayake AP, Jayatilaka KAPW, Pathirana C, Mudduwa LKB. Efficacy and toxicological evaluation of Coccinia grandis (Cucurbitaceae) extract in male Wistar rats. Asian Pac J Trop Dis. 2013;3(6):460-6. https://doi.org/10.1016/S2222-1808(13)60101-2
  3. Guaouguaou FE, Taghzouti K, Oukabli M, Masrar A, Chabraoui L, Bouabdellah M, et al. Acute and subchronic oral and dermal toxicological studies of Salvia verbenaca extracts in mice and rats. J Herbs Spices Med Plants. 2019;25(1):33-42. https://doi.org/10.1080/10496475.2018.1556372
  4. Mukinda JT, Syce JA. Acute and chronic toxicity of the aqueous extract of Artemisia afra in rodents. J Ethnopharmacol. 2007;112(1):138-44. https://doi.org/10.1016/j.jep.2007.02.011
  5. El Kabbaoui M, Chda A, El-Akhal J, Azdad O, Mejrhit N, Aarab L, et al. Acute and sub-chronic toxicity studies of the aqueous extract from leaves of Cistus ladaniferus L. in mice and rats. J Ethnopharmacol. 2017;209:147-56. https://doi.org/10.1016/j.jep.2017.07.029
  6. Neergheen-Bhujun VS. Underestimating the toxicological challenges associated with the use of herbal medicinal products in developing countries. Biomed Res Int. 2013;2013:804086.
  7. Abdallah EM. Plants: an alternative source for antimicrobials. J Appl Pharm Sci 2011;1(6):16-20.
  8. Jimenez S, Jimenez-Moreno N, Luquin A, Laguna M, Rodriguez-Yoldi MJ, Ancin-Azpilicueta C. Chemical composition of rosehips from different Rosa species: an alternative source of antioxidants for the food industry. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2017;34(7):1121-30. https://doi.org/10.1080/19440049.2017.1319071
  9. Naceiri Mrabti H, Marmouzi I, Sayah K, Chemlal L, El Ouadi Y, Elmsellem H, et al. Arbutus unedo L aqueous extract is associated with in vitro and in vivo antioxidant activity. J Mater Environ Sci. 2017;8(1):217-24.
  10. Miguel MG, Faleiro ML, Guerreiro AC, Antunes MD. Arbutus unedo L.: chemical and biological properties. Molecules. 2014;19(10):15799-823. https://doi.org/10.3390/molecules191015799
  11. Pabuccuoglu A, Kivcak B, Bas M, Mert T. Antioxidant activity of Arbutus unedo leaves. Fitoterapia. 2003;74(6):597-9. https://doi.org/10.1016/S0367-326X(03)00110-2
  12. Morgado S, Morgado M, Placido AI, Roque F, Duarte AP. Arbutus unedo L.: from traditional medicine to potential uses in modern pharmacotherapy. J Ethnopharmacol. 2018;225:90-102. https://doi.org/10.1016/j.jep.2018.07.004
  13. Naceiri Mrabti H, Bouyahya A, Ed-Dra A, Kachmar MR, Naceiri Mrabti N, Benali T, et al. Polyphenolic profile and biological properties of Arbutus unedo root extracts. Eur J Integr Med. 2021;42:101266.
  14. El Amine Dib M, Allali H, Bendiabdellah A, Meliani N, Tabti B. Antimicrobial activity and phytochemical screening of Arbutus unedo L. J Saudi Chem Soc. 2013;17(4):381-5. https://doi.org/10.1016/j.jscs.2011.05.001
  15. Fettach S, Mrabti HN, Sayah K, Bouyahya A, Salhi N, Cherrah Y, et al. Phenolic content, acute toxicity of Ajuga iva extracts and assessment of their antioxidant and carbohydrate digestive enzyme inhibitory effects. S Afr J Bot. 2019;125:381-5. https://doi.org/10.1016/j.sajb.2019.08.010
  16. Tuberoso CI, Boban M, Bifulco E, Budimir D, Pirisi FM. Antioxidant capacity and vasodilatory properties of Mediterranean food: the case of Cannonau wine, myrtle berries liqueur and strawberry-tree honey. Food Chem. 2013;140(4):686-91. https://doi.org/10.1016/j.foodchem.2012.09.071
  17. Mekkaoui M, Assaggaf H, Qasem A, El-Shemi A, Abdallah EM, Bouidida EH, et al. Ethnopharmacological survey and comparative study of the healing activity of Moroccan thyme honey and its mixture with selected essential oils on two types of wounds on albino rabbits. Foods. 2021;11(1):28.
  18. Mrabti HN, Sayah K, Jaradat N, Kichou F, Ed-Dra A, Belarj B, et al. Antidiabetic and protective effects of the aqueous extract of Arbutus unedo L. in streptozotocin-nicotinamide-induced diabetic mice. J Complement Integr Med. 2018;15(3):/j/jcim.2018.15.issue-3/jcim-2017-0165/jcim-2017-0165.xml.
  19. National Research Council of the National Academies. Guide for the care and use of laboratory animals. 8th ed. Washington, D.C.: National Academies Press; 2011.
  20. Botham PA. Acute systemic toxicity--prospects for tiered testing strategies. Toxicol In Vitro. 2004;18(2):227-30. https://doi.org/10.1016/S0887-2333(03)00143-7
  21. OECD. Test No. 408: repeated dose 90-day oral toxicity study in rodents. In: OECD, editor. OECD guideline for the testing of chemicals. Paris: OECD; 2018.
  22. Dib MA, Djabou N, Allali H, Tabti B. Identification of phenolic compounds and antimicrobialactivity of roots of Arbutus unedo L. Asian J Chem. 2010;22(5):4045-53.
  23. Oliveira I, Baptista P, Bento A, Pereira JA. Arbutus unedo L. and its benefits on human health. J Food Nutr Res. 2012;50(2):73-8.
  24. Pavlovic DR, Brankovic S, Kovacevic N, Kitic D, Veljkovic S. Comparative study of spasmolytic properties, antioxidant activity and phenolic content of Arbutus unedo from Montenegro and Greece. Phytother Res. 2011;25(5):749-54. https://doi.org/10.1002/ptr.3460
  25. Bouyahya A, El Moussaoui N, Abrini J, Bakri Y, Dakka N. Determination of phenolic contents, antioxidant and antibacterial activities of strawberry tree (Arbutus unedo L.) leaf extracts. BJI. 2016;14(3):1-10. https://doi.org/10.9734/BBJ/2016/26488
  26. Orak HH, Yagar H, Isbilir SS, Demirci AS, Gumus T, Ekinci N. Evaluation of antioxidant and antimicrobial potential of strawberry tree (Arbutus Unedo L.) leaf. Food Sci Biotechnol. 2011;20(5):1249.
  27. Jurica K, Gobin I, Kremer D, Cepo DV, Grubesic RJ, Karaconji IB, et al. Arbutin and its metabolite hydroquinone as the main factors in the antimicrobial effect of strawberry tree (Arbutus unedo L.) leaves. J Herb Med. 2017;8:17-23. https://doi.org/10.1016/j.hermed.2017.03.006
  28. Malheiro R, Sa O, Pereira E, Aguiar C, Baptista P, Pereira JA. Arbutus unedo L. leaves as source of phytochemicals with bioactive properties. Ind Crops Prod. 2012;37(1):473-8. https://doi.org/10.1016/j.indcrop.2011.07.023
  29. Andrade D, Gil C, Breitenfeld L, Domingues F, Duarte AP. Bioactive extracts from Cistus ladanifer and Arbutus unedo L. Ind Crops Prod. 2009;30(1):165-7. https://doi.org/10.1016/j.indcrop.2009.01.009
  30. Fortalezas S, Tavares L, Pimpao R, Tyagi M, Pontes V, Alves PM, et al. Antioxidant properties and neuroprotective capacity of strawberry tree fruit (Arbutus unedo). Nutrients. 2010;2(2):214-29. https://doi.org/10.3390/nu2020214
  31. Hoffmann S, Kinsner-Ovaskainen A, Prieto P, Mangelsdorf I, Bieler C, Cole T. Acute oral toxicity: variability, reliability, relevance and interspecies comparison of rodent LD50 data from literature surveyed for the ACuteTox project. Regul Toxicol Pharmacol. 2010;58(3):395-407. https://doi.org/10.1016/j.yrtph.2010.08.004
  32. Clark M, Steger-Hartmann T. A big data approach to the concordance of the toxicity of pharmaceuticals in animals and humans. Regul Toxicol Pharmacol. 2018;96:94-105. https://doi.org/10.1016/j.yrtph.2018.04.018
  33. Rhiouani H, El-Hilaly J, Israili ZH, Lyoussi B. Acute and subchronic toxicity of an aqueous extract of the leaves of Herniaria glabra in rodents. J Ethnopharmacol. 2008;118(3):378-86. https://doi.org/10.1016/j.jep.2008.05.009
  34. Ziyyat A, Legssyer A, Mekhfi H, Dassouli A, Serhrouchni M, Benjelloun W. Phytotherapy of hypertension and diabetes in oriental Morocco. J Ethnopharmacol. 1997;58(1):45-54. https://doi.org/10.1016/S0378-8741(97)00077-9
  35. Jouad H, Haloui M, Rhiouani H, El Hilaly J, Eddouks M. Ethnobotanical survey of medicinal plants used for the treatment of diabetes, cardiac and renal diseases in the North centre region of Morocco (Fez-Boulemane). J Ethnopharmacol. 2001;77(2-3):175-82. https://doi.org/10.1016/S0378-8741(01)00289-6
  36. Ingawale DK, Mandlik SK, Naik SR. Models of hepatotoxicity and the underlying cellular, biochemical and immunological mechanism(s): a critical discussion. Environ Toxicol Pharmacol. 2014;37(1):118-33. https://doi.org/10.1016/j.etap.2013.08.015
  37. Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S. The current state of serum biomarkers of hepatotoxicity. Toxicology. 2008;245(3):194-205. https://doi.org/10.1016/j.tox.2007.11.021