Top

Hormones

Published in:

01-06-2022 | Original Article

Syzygium aromaticum bud (clove) essential oil is a novel and safe aldose reductase inhibitor: in silico, in vitro, and in vivo evidence

Authors: Imane Nait Irahal, Ismail Guenaou, Fatima Azzahra Lahlou, Fouzia Hmimid, Noureddine Bourhim

Published in: Hormones | Issue 2/2022

Abstract

Purpose

This study aimed to evaluate the antioxidant and antidiabetic properties of clove essential oil (CEO) and to elucidate its mode of action, using selected biochemical targets, relevant to diabetes, and, specifically, its inhibitory effect on the polyol pathway.

Methods

In the current study, CEO was examined for its inhibitory effects on aldose reductase in silico, in vitro, and in vivo, as well as its antioxidative activity.

Results

In silico docking studies showed that all the selected major compounds of CEO have an energy change ranging between − 5.5 and − 8.8 kcal/mol and an inhibition constant ranging between 357.08 nM and 93.12 µM. CEO significantly inhibits aldose reductase with an IC₅₀ value of 58.55 ± 5.84 µg/mL in a noncompetitive manner. The supplementation of CEO at 20 mg/kg BW decreases retinal sorbitol dehydrogenase activity via decreased aldose reductase activity in streptozotocin (STZ)-induced diabetic Sprague Dawley rats. Moreover, diabetic rats injected with CEO have exhibited improved levels of glycemia. The IC₅₀ values for ABTS, hydroxyl, and hydrogen peroxide scavenging activities of CEO were found to be 34.42, 277.4, and 39.99 µg/mL, respectively. Reducing power assay and phosphomolybdate assay exhibited a reduction force with the A_0.5 values of 50.25 and 140.16 µg/mL, respectively.

Conclusion

CEO potentially exerts a beneficial effect on diabetes-related complications due to its antioxidant and inhibitory effect on aldose reductase activity.

Giri B, Dey S, Das T, Sarkar M, Banerjee J, Dash SK (2018) Chronic hyperglycemia mediated physiological alteration and metabolic distortion leads to organ dysfunction, infection, cancer progression and other pathophysiological consequences: an update on glucose toxicity. Biomed Pharmacother 107:306–328. https://doi.org/10.1016/j.biopha.2018.07.157CrossRefPubMed

He J, Gao HX, Yang N, Zhu XD, Sun RB, Xie Y, Zeng CH, Zhang JW, Wang JK, Ding F, Aa JY, Wang GJ (2019) The aldose reductase inhibitor epalrestat exerts nephritic protection on diabetic nephropathy in db/db mice through metabolic modulation. Acta Pharmacol Sin 40:86–97. https://doi.org/10.1038/s41401-018-0043-5CrossRefPubMed

Mukherjee PK, Harwansh RK, Bahadur S, Chanda J, Biswas S, Banerjee S (2020) Chapter 31 - Enzyme inhibition assay for metabolic disorders—exploring leads from medicinal plants. In: Verma AS, Singh A (eds) Animal Biotechnology, 2nd edn. Academic Press, Boston, pp 631–653CrossRef

Wettschureck N, Strilic B, Offermanns S (2019) Passing the vascular barrier: endothelial signaling processes controlling extravasation. Physiol Rev 99:1467–1525. https://doi.org/10.1152/physrev.00037.2018CrossRefPubMed

Jannapureddy S, Sharma M, Yepuri G, Schmidt AM and Ramasamy R (2021) Aldose reductase: an emerging target for development of interventions for diabetic cardiovascular complications. Front Endocrinol 12.https://doi.org/10.3389/fendo.2021.636267

Yagihashi S (2016) Chapter eight - Glucotoxic mechanisms and related therapeutic approaches. In: Calcutt NA, Fernyhough P (eds) International Review of Neurobiology. Academic Press, Boston, pp 121–149

Calabek B, Callaghan B, Feldman EL (2014) Chapter 22 - Therapy for diabetic neuropathy: an overview. In: Zochodne DW, Malik RA (eds) Handbook of Clinical Neurology. Elsevier, pp 317–333

Hotta N, Akanuma Y, Kawamori R, Matsuoka K, Oka Y, Shichiri M, Toyota T, Nakashima M, Yoshimura I, Sakamoto N, Shigeta Y (2006) Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy. Diabetes Care 29:1538. https://doi.org/10.2337/dc05-2370CrossRefPubMed

Rios JL, Francini F, Schinella GR (2015) Natural products for the treatment of type 2 diabetes mellitus. Planta Med 81:975–994. https://doi.org/10.1055/s-0035-1546131CrossRefPubMed

10.

Xu L, Li Y, Dai Y, Peng J (2018) Natural products for the treatment of type 2 diabetes mellitus: pharmacology and mechanisms. Pharmacol Res 130:451–465. https://doi.org/10.1016/j.phrs.2018.01.015CrossRefPubMed

11.

Li W, Yuan G, Pan Y, Wang C, Chen H (2017) Network pharmacology studies on the bioactive compounds and action mechanisms of natural products for the treatment of diabetes mellitus: a review. Front Pharmacol 8:74. https://doi.org/10.3389/fphar.2017.00074CrossRefPubMedPubMedCentral

12.

Sekhon-Loodu S and Rupasinghe HPV (2019) Evaluation of antioxidant, antidiabetic and antiobesity potential of selected traditional medicinal plants. Front Nutr 6.https://doi.org/10.3389/fnut.2019.00053

13.

Guenaou I, Hmimid F, Lahlou FA, Errami A, Irahal IN, Fahde S, Ouafik Lh, Bourhim N (2021) Cytoprotective effect of ethyl acetate fraction from Ephedra fragilis on H2O2-induced oxidative damage in Tetrahymena pyriformis. Comp Biochem Physiol C Toxicol Pharmacol 239:108899. https://doi.org/10.1016/j.cbpc.2020.108899CrossRefPubMed

14.

Bi X, Lim J, Henry CJ (2017) Spices in the management of diabetes mellitus. Food Chem 217:281–293. https://doi.org/10.1016/j.foodchem.2016.08.111CrossRefPubMed

15.

Sanlier N, Gencer F (2020) Role of spices in the treatment of diabetes mellitus: a minireview. Trends Food Sci Technol 99:441–449. https://doi.org/10.1016/j.tifs.2020.03.018CrossRef

16.

Devkota HP, Adhikari-Devkota A (2020) Chapter 23 - Cold pressed clove (Syzygium aromaticum) oil. In: Ramadan MF (ed) Cold Pressed Oils. Academic Press, Boston, pp 273–276CrossRef

17.

Batiha GE, Alkazmi LM, Wasef LG, Beshbishy AM, Nadwa EH and Rashwan EK (2020) Syzygium aromaticum L. (Myrtaceae): traditional uses, bioactive chemical constituents, pharmacological and toxicological activities. Biomolecules 10. https://doi.org/10.3390/biom10020202

18.

Chaieb K, Hajlaoui H, Zmantar T, Kahla-Nakbi AB, Rouabhia M, Mahdouani K, Bakhrouf A (2007) The chemical composition and biological activity of clove essential oil, Eugenia caryophyllata (Syzigium aromaticum L. Myrtaceae): a short review. Phytother Res 21:501–506. https://doi.org/10.1002/ptr.2124CrossRefPubMed

19.

Imane NI, Fouzia H, Azzahra LF, Ahmed E, Ismail G, Idrissa D, Mohamed K-H, Sirine F, L’Houcine O, Noureddine B (2020) Chemical composition, antibacterial and antioxidant activities of some essential oils against multidrug resistant bacteria. Eur J Integr Med 35:101074. https://doi.org/10.1016/j.eujim.2020.101074CrossRef

20.

Sankeshi V, Kumar PA, Naik RR, Sridhar G, Kumar MP, Gopal VV, Raju TN (2013) Inhibition of aldose reductase by Aegle marmelos and its protective role in diabetic cataract. J Ethnopharmacol 149:215–221. https://doi.org/10.1016/j.jep.2013.06.025CrossRefPubMed

21.

Hmimid F, Lahlou FA, Guenaou I, NaitIrahal I, Errami A, Fahde S, Bourhim N (2021) Purification and characterization of aldose reductase from jerboa (Jaculus orientalis) and evaluation of its inhibitory activity by Euphorbia regis-jubae (Webb & Berth) extracts. Comp Biochem Physiol C: Toxicol Pharmacol 244:109001. https://doi.org/10.1016/j.cbpc.2021.109001CrossRef

22.

de la Garza-Rodea AS, Knaan-Shanzer S, den Hartigh JD, Verhaegen AP, van Bekkum DW (2010) Anomer-equilibrated streptozotocin solution for the induction of experimental diabetes in mice (Mus musculus). J Am Assoc Lab Anim Sci 49:40–44PubMedPubMedCentral

23.

Berrada W, Naya A, Ouafik Lh, Bourhim N (2000) Effect of hibernation, thyroid hormones and dexamethasone on cytosolic and mitochondrial glycerol-3-phosphate dehydrogenase from jerboa (Jaculus orientalis). Comp Biochem Physiol B Biochem Mol Biol 125:439–449. https://doi.org/10.1016/S0305-0491(00)00161-9CrossRefPubMed

24.

Kanda H, Toyama T, Shinohara-Kanda A, Iwamatsu A, Shinkai Y, Kaji T, Kikushima M, Kumagai Y (2012) S-Mercuration of rat sorbitol dehydrogenase by methylmercury causes its aggregation and the release of the zinc ion from the active site. Arch Toxicol 86:1693–1702. https://doi.org/10.1007/s00204-012-0893-4CrossRefPubMed

25.

Oyeyinka BO, Afolayan AJ (2020) Comparative and correlational evaluation of the phytochemical constituents and antioxidant activity of Musa sinensis L. and Musa paradisiaca L. Fruit Compartments (Musaceae). ScientificWorldJournal 2020:4503824. https://doi.org/10.1155/2020/4503824CrossRefPubMedPubMedCentral

26.

Haida Z, Hakiman M (2019) A comprehensive review on the determination of enzymatic assay and nonenzymatic antioxidant activities. Food Sci Nutr 7:1555–1563. https://doi.org/10.1002/fsn3.1012CrossRefPubMedPubMedCentral

27.

Ghosal M, Chhetri PK, Ghosh MK, Mandal P (2013) Changes in antioxidant activity of Cyphomandra betacea (Cav.) Sendtn. Fruits During Maturation and Senescence. Int J Food Prop 16:1552–1564. https://doi.org/10.1080/10942912.2011.600493CrossRef

28.

Khaled-Khodja N, Boulekbache-Makhlouf L, Madani K (2014) Phytochemical screening of antioxidant and antibacterial activities of methanolic extracts of some Lamiaceae. Ind Crops Prod 61:41–48. https://doi.org/10.1016/j.indcrop.2014.06.037CrossRef

29.

Atere TG, Akinloye OA, Ugbaja RN, Ojo DA, Dealtry G (2018) In vitro antioxidant capacity and free radical scavenging evaluation of standardized extract of Costus afer leaf. Food Sci Hum Wellness 7:266–272. https://doi.org/10.1016/j.fshw.2018.09.004CrossRef

30.

Lorenzi M, Oates P (2008) The polyol pathway and diabetic retinopathy. Contemp Diabetes. https://doi.org/10.1007/978-1-59745-563-3_6CrossRef

31.

Yilmaz-Oral D, Onder A, Gur S, Carbonell-Barrachina ÁA, Kaya-Sezginer E, Oztekin CV, Zor M (2020) The beneficial effect of clove essential oil and its major component, eugenol, on erectile function in diabetic rats. Andrologia 52:e13606. https://doi.org/10.1111/and.13606CrossRefPubMed

32.

Gülçin İ, Elmastaş M, Aboul-Enein HY (2012) Antioxidant activity of clove oil – a powerful antioxidant source. Arab J Chem 5:489–499. https://doi.org/10.1016/j.arabjc.2010.09.016CrossRef

33.

Yan L-j (2018) Redox imbalance stress in diabetes mellitus: role of the polyol pathway. Anim Model Exp Med 1:7–13. https://doi.org/10.1002/ame2.12001CrossRef

34.

Solomon SD, Chew E, Duh EJ, Sobrin L, Sun JK, VanderBeek BL, Wykoff CC, Gardner TW (2017) Diabetic retinopathy: a position statement by the American Diabetes Association. Diabetes Care 40:412–418. https://doi.org/10.2337/dc16-2641CrossRefPubMedPubMedCentral

35.

Kalita D, Holm DG, LaBarbera DV, Petrash JM, Jayanty SS (2018) Inhibition of alpha-glucosidase, alpha-amylase, and aldose reductase by potato polyphenolic compounds. PLoS One 13:e0191025. https://doi.org/10.1371/journal.pone.0191025CrossRefPubMedPubMedCentral

36.

Yawadio R, Tanimori S, Morita N (2007) Identification of phenolic compounds isolated from pigmented rices and their aldose reductase inhibitory activities. Food Chem 101:1616–1625. https://doi.org/10.1016/j.foodchem.2006.04.016CrossRef

37.

Ezzat SM, Abdel Motaal A, El Awdan SAW (2017) In vitro and in vivo antidiabetic potential of extracts and a furostanol saponin from Balanites aegyptiaca. Pharm Biol 55:1931–1936. https://doi.org/10.1080/13880209.2017.1343358CrossRefPubMedPubMedCentral

38.

Benlarbi-Ben Khedher M, Hajri K, Dellaa A, Baccouche B, Hammoum I, Boudhrioua-Mihoubi N, Dhifi W, Ben Chaouacha-Chekir R (2019) Astaxanthin inhibits aldose reductase activity in Psammomys obesus, a model of type 2 diabetes and diabetic retinopathy. Food Sci Nutr 7:3979–3985. https://doi.org/10.1002/fsn3.1259CrossRefPubMedPubMedCentral

39.

Marrelli M, Statti G and Conforti F (2020) A review of biologically active natural products from Mediterranean wild edible plants: benefits in the treatment of obesity and its related disorders. Molecules 25.https://doi.org/10.3390/molecules25030649

40.

Prasad S, Sajja RK, Naik P, Cucullo L (2014) Diabetes mellitus and blood-brain barrier dysfunction: an overview. J Pharmacovigil 2:125. https://doi.org/10.4172/2329-6887.1000125CrossRefPubMedPubMedCentral

41.

Obrosova IG (2009) Diabetes and the peripheral nerve. Biochim Biophysica Acta Mol Basis Dis 1792:931–940. https://doi.org/10.1016/j.bbadis.2008.11.005CrossRef

42.

Li R, Reddy VA, Jin J, Rajan C, Wang Q, Yue G, Lim CH, Chua N-H, Ye J, Sarojam R (2017) Comparative transcriptome analysis of oil palm flowers reveals an EAR-motif-containing R2R3-MYB that modulates phenylpropene biosynthesis. BMC Plant Biol 17:219. https://doi.org/10.1186/s12870-017-1174-4CrossRefPubMedPubMedCentral

43.

Habtemariam S (2019) Chapter 16 - The chemical and pharmacological basis of cloves (Syzygium aromaticum (L.) Merr & L.M.Perry) as potential therapy for type 2 diabetes and associated diseases. In: Habtemariam S (ed) Medicinal Foods as Potential Therapies for Type-2 Diabetes and Associated Diseases. Academic Press, Boston, pp 551–578CrossRef

44.

Koeduka T, Fridman E, Gang DR, Vassao DG, Jackson BL, Kish CM, Orlova I, Spassova SM, Lewis NG, Noel JP, Baiga TJ, Dudareva N, Pichersky E (2006) Eugenol and isoeugenol, characteristic aromatic constituents of spices, are biosynthesized via reduction of a coniferyl alcohol ester. Proc Natl Acad Sci U S A 103:10128–10133. https://doi.org/10.1073/pnas.0603732103CrossRefPubMedPubMedCentral

45.

Neelam KA, Sharma KK (2020) Phenylpropanoids and its derivatives: biological activities and its role in food, pharmaceutical and cosmetic industries. Crit Rev Food Sci Nutr 60:2655–2675. https://doi.org/10.1080/10408398.2019.1653822CrossRefPubMed

46.

Wang J, Hu S, Nie S, Yu Q, Xie M (2016) Reviews on mechanisms of in vitro antioxidant activity of polysaccharides. Oxid Med Cell Longev 2016:5692852. https://doi.org/10.1155/2016/5692852CrossRefPubMed

47.

Sroka Z, Cisowski W (2003) Hydrogen peroxide scavenging, antioxidant and anti-radical activity of some phenolic acids. Food Chem Toxicol 41:753–758. https://doi.org/10.1016/S0278-6915(02)00329-0CrossRefPubMed

48.

Adefegha SA, Oboh G, Adefegha OM, Boligon AA, Athayde ML (2014) Antihyperglycemic, hypolipidemic, hepatoprotective and antioxidative effects of dietary clove (Szyzgium aromaticum) bud powder in a high-fat diet/streptozotocin-induced diabetes rat model. J Sci Food Agric 94:2726–2737. https://doi.org/10.1002/jsfa.6617CrossRefPubMed

49.

Gooderham NJ, Cohen SM, Eisenbrand G, Fukushima S, Guengerich FP, Hecht SS, Rietjens IMCM, Rosol TJ, Davidsen JM, Harman CL, Murray IJ, Taylor SV (2020) FEMA GRAS assessment of natural flavor complexes: clove, cinnamon leaf and West Indian bay leaf-derived flavoring ingredients. Food Chem Toxicol 145:111585. https://doi.org/10.1016/j.fct.2020.111585CrossRefPubMed

50.

Vijayasteltar L, Nair GG, Maliakel B, Kuttan R, I.M K, (2016) Safety assessment of a standardized polyphenolic extract of clove buds: subchronic toxicity and mutagenicity studies. Toxicol Rep 3:439–449. https://doi.org/10.1016/j.toxrep.2016.04.001CrossRefPubMedPubMedCentral

Title: Syzygium aromaticum bud (clove) essential oil is a novel and safe aldose reductase inhibitor: in silico, in vitro, and in vivo evidence
Authors: Imane Nait Irahal
Ismail Guenaou
Fatima Azzahra Lahlou
Fouzia Hmimid
Noureddine Bourhim
Publication date: 01-06-2022
Publisher: Springer International Publishing
Published in: Hormones / Issue 2/2022
Print ISSN: 1109-3099
Electronic ISSN: 2520-8721
DOI: https://doi.org/10.1007/s42000-021-00347-6

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 2/2022

Painless thyroiditis following mRNA vaccination for COVID-19

Role of diabetes mellitus in the clinical course and outcome of SARS-CoV-2 infected patients

Correction: Postoperative complications after endoscope-assisted transsphenoidal surgery for pituitary adenomas: a case series, systematic review, and meta-analysis of the literature

Familial autoimmunity in pediatric patients with type 1 diabetes (T1D) and its associations with the severity of clinical presentation at diabetes diagnosis and with coexisting autoimmunity

Connective tissue disease as a cause of discrepant capillary and serum glucose levels — a case report

A rare case of a giant prolactinoma with atypical histological features: 5 years of follow-up

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials