Acute Oral Toxicity and Vasorelaxant Effects of Hydroethanolic Extract from Lannea microcarpa Engl. & K. Krause (Anacardiaceae) Trunk Barks in Mice Aortas: Possible Involvement of Intracellular Ca 2+ Mobilization
Lannea microcrapa Engl. & K. Krause(Anacardiaceae)is a fruit and medicinal plant widely used
in Burkina Faso. This plant is traditionally used in the treatment of
hypertension. The aim of the present study was to evaluate the vasorelaxant
effects of the hydroethanolic extract from Lannea microcarpa trunk barks
(HE_ELM) on the aorta isolated from NMRI mice. Phytochemical screening by
HPTLC, assay of phenolic and flavonoid compounds, assessment of antioxidant activity
(DPPH, ABTS, FRAP, and LPO), and myography of HE_ELM (1 - 2000 μg/mL) on mice
thoracic aortas in the presence and absence of endothelium were carried out.
Endothelium-dependent and endothelium-independant vasodilation were assessed by cumulative addition of Ach (1 nM - 10
μM) on aortic rings precontracted with the thromboxane analogue A2 agonist,
9,11-dideoxy9α,11α-methanoepoxy PGF2α (U46619). L-NAME was used to verify the involvement of NO production in the
relaxation mechanism of the extract. Acute oral toxicity of HE_ELM was also
evaluated. A phytochemical study revealed the presence of tannins, flavonoids,
sterols and triterpenes, saponosides, and high levels of total phenolics and
flavonoids. These compounds are thought to be responsible for the extract’s
antioxidant and vasorelaxant properties. HE_ELM demonstrated significant
antioxidant potential and induced aortic relaxation. Indeed, pharmacological
parameters gave EC50 values ranging from 596.45 ± 95.82 μg/mL to
749.48 ± 133.40 μg/mL and Emax values from 85.51% ± 9.59% to 96.81% ± 8.60% for the three
conditions of vasodilation of the extract (p > 0.05). A complete antagonism
of the contractile effect of U46619 was noted with 1 mg/mL HE_ELM. These
results suggest that HE_ELM induces aortic relaxation through a
concentration-dependent, endothelium-independent mechanism, possibly involving
intracellular calcium mobilization of vascular cells. Acute oral toxicity tests
of HE_ELM (2000 mg/kg) showed no mortality or adverse effects, suggesting the
extract’s safety and potential as a therapeutic agent for hypertension. This
discovery scientifically validates the use of the plant in alternative medicine
to treat hypertension.
References
[1]
Getiye, Y., Tolessa, T. and Engidawork, E. (2016) Antihypertensive Activity of 80% Methanol Seed Extract of Calpurnia aurea (Ait.) Benth. subsp. aurea (Fabaceae) Is Mediated through Calcium Antagonism Induced Vasodilation. Journal of Ethnopharmacology, 189, 99-106. https://doi.org/10.1016/j.jep.2016.04.056
[2]
World Heart Federation (2023) World Heart Report 2023: Confronting the World’s Number One Killer. World Heart Federation, Geneva, 49 p.
https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwimkJjv1qCDAxWgVUEAHSEPB_EQFnoECBQQAQ&url= https%3A%2F%2Fworld-heart-federation.org%2Fwp-content%2Fuploads%2FWorld-Heart-Report-2023.pdf&usg=AOvVaw19nQe6vg9WW08C19d7Id0J&opi=89978449
[3]
Kearney, P.M., Whelton, M., Reynolds, K., Muntner, P., Whelton, P.K. and He, J. (2005) Global Burden of Hypertension: Analysis of Worldwide Data. The Lancet, 365, 217-223. https://doi.org/10.1016/S0140-6736(05)17741-1
[4]
Getahun, G.K., Goshu, B.Y., Goshu, D.Y. and Mekuria, Z.N. (2023) Cardiovascular Disease Risk among Hypertensive Patients and Associated Determinants in Addis Ababa, Ethiopia: An Institutional-Based Cross-Sectional Study. BMJ Open, 13, e068948. https://doi.org/10.1136/bmjopen-2022-068948
[5]
Mota, A.H. (2016) A Review of Medicinal Plants Used in Therapy of Cardiovascular Diseases. International Journal of Pharmacognosy and Phytochemical Research, 8, 572-591.
[6]
Nitiéma, M., Soleti, R., Koffi, C., Belemnaba, L., Mallegol, P., Ouédraogo, N., Kini, F.B., Ouédraogo, S., Guissou, I.P. and Andriantsitohaina, R. (2019) Ethyl Acetate Fraction of Lannea microcarpa Engl. and K. Krause (Anacardiaceae) Trunk Barks Corrects Angiotensin II-Induced Hypertension and Endothelial Dysfunction in Mice. Oxidative Medicine and Cellular Longevity, 2019, Article ID: 9464608.
https://doi.org/10.1155/2019/9464608
[7]
Calhoun, D.A., Jones, D., Textor, S., Goff, D.C., Murphy, T.P., Toto, R.D., White, A., Cushman, W.C., White, W. and Sica, D. (2008) Resistant Hypertension: Diagnosis, Evaluation, and Treatment. Circulation, 117, e510-e526.
https://doi.org/10.1161/CIRCULATIONAHA.108.189141
[8]
Ouedraogo, W.R.C., Belemnaba, L., Nitiéma, M., Kaboré, B., Koala, M., Ouedraogo, S., Semde, R. and Ouedraogo, S. (2023) Phytochemical Study, Antioxidant and Vasodilatation Activities of Leafy Stem Extracts of Flemingia faginea Guill. & Perr. (Barker), A Medicinal Plant Used for the Traditional Treatment of Arterial Hypertension. Pharmacological Research-Modern Chinese Medicine, 7, Article ID: 100231. https://doi.org/10.1016/j.prmcm.2023.100231
[9]
Nitiéma, M., Koala, M., Belemnaba, L., Ouédraogo, J.C.W., Ouédraogo, S., Kini, F.B., Ouédraogo, S. and Guissou, I.P. (2019) Endothelium-Independent Vasorelaxant Effects of Anthocyanins-Enriched Extract from Odontonema strictum (Nees) Kuntze (Acanthaceae) Flowers: Ca2+ Channels Involvement. European Journal of Medicinal Plants, 29, 1-11. https://doi.org/10.9734/ejmp/2019/v29i330155
[10]
Ouedraogo, W.R.C., Belemnaba, L., Nitiema, M., Kabore, B., Ouedraogo, N. and Koala, M. (2023) Antioxidant and Vasorelaxant Properties of Phaseolus vulgaris Linn (Fabaceae) Immature Pods Extract on the Thoracic Aorta of NMRI Mice. Biomedical and Pharmacology Journal, 16, 533-548.
https://doi.org/10.13005/bpj/2635
[11]
Bazongo, P., Bassolé, I.H.N., Nielsen, S., Hilou, A., Dicko, M.H. and Shukla, V.K. (2014) Characteristics, Composition and Oxidative Stability of Lannea microcarpa Seed and Seed Oil. Molecules, 19, 2684-2693.
https://doi.org/10.3390/molecules19022684
[12]
Belemnaba, L., Nitiema, M., Traoré, S., Somé, N., Traoré, A., Ouédraogo, S. and Guissou, I.P. (2014) Recherche de plantes à potentialités antihypertensives dans la biodiversité du Burkina Faso. Pharmacopée et Médecine Traditionnelle Africaine, 17, 33-40.
[13]
Compaore, S., Belemnaba, L., Hounkpevi, A., Idohou, R., Zerbo, I., Ouedraogo, S. and Thiombiano, A. (2020) Diversity of Plants Used in the Management of Hypertension by Three Associations of Traditional Healers along a Climate Gradient in Burkina Faso. Advances in Traditional Medicine, 21, 151-162.
https://doi.org/10.1007/s13596-020-00495-x
[14]
Traore, N.S.G.Y.V., Belemnaba, L., Nitiema, M., Ouedraogo, C.W.R., Traore, T.K., Compaore, S., Ouedraogo, S., Ouedraogo, N. and Ouedraogo, S. (2022) Antihypertensive Effect of the Lyophilized Aqueous Extract of Lannea microcarpa in L-NAME-Induced Hypertensive Wistar Rats. International Journal of Pharmacology, 18, 1401-1411. https://doi.org/10.3923/ijp.2022.1401.1411
[15]
Belemnaba, L., Soubeiga, M., Ouédraogo, G.G., Traoré, T.K., Nitiéma, M., Ilboudo, S., Belemlilga, B.M., Compaoré, S., Sondé, R., Ouédraogo, J.C.R.P., et al. (2019) Antioxidant Properties and Subchronic Toxicity of the Standardized Extract of LAMIC, A Phytomedicine Prototype Based on Aqueous Extracts from Trunk Bark of Lannea microcarpa Engl and K. Krause. Journal of Drug Delivery and Therapeutics, 9, 1-8. https://doi.org/10.22270/jddt.v9i5.3285
[16]
Antwi-Adjei, M., Owusu, G. and Ameade, E.P. (2017) Aqueous Extract of Lannea microcarpa Attenuates Dextran Sulphate-Induced Paw Oedema and Xylene-Induced Ear Oedema in Rodents. International Journal of Basic & Clinical Pharmacology, 6, 1048-1053. https://doi.org/10.18203/2319-2003.ijbcp20171655
[17]
Ouédraogo, S., Belemnaba, L., Zague, H., Traore, A., Lompo, M., Guissou, I.P., Lugnier, C. and Bucher, B. (2010) Endothelium-Independent Vasorelaxation by Extract and Fractions from Lannea microcarpa Engl. and K. Krause (Anacardiaceae): Possible Involvement of Phosphodiesterase Inhibition. International Journal of Pharmacology and Biological Sciences, 4, 9-16.
[18]
Belem-Kabré, W.L.M.E., Nitiéma, M., Odjo, S.B., Noura, M.O., Yaro, B., Kaboré, B., Somda, D.G., Traoré, T.K., Koala, M., Ilboudo, S., et al. (2023) Phytochemical Analysis and Contractile Effects of Aqueous and Hydroethanolic Extracts of Anastatica hierochuntica L.(Brassicaceae) on the Isolated Uterus of Mice. Pharmacology & Pharmacy, 14, 252-270.
[19]
OCDE (2001) OECD Guideline for Testing of Chemicals, Acute Oral Toxicity—Acute Toxic Class Method.
https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwimmYbC_p2DAxXAT0EAHVJfDYwQFnoECAwQAQ&url= https%3A%2F%2Fntp.niehs.nih.gov%2Fsites%2Fdefault%2Ffiles%2Ficcvam%2Fsuppdocs%2Ffeddocs%2Foecd%2Foecd_gl423.pdf&usg=AOvVaw2vMjpM5rJ1RzitVvtwOj-D&opi=89978449
[20]
Ouédraogo, W.R.C., Belemnaba, L., Nitiéma, M., Kaboré, B., Compaoré, S., Koala, M., Semdé, R. and Ouédraogo, S. (2023) Evaluation of Acute, Subacute Toxicity and in Vivo Impact of Aqueous Decoction of Flemingia faginea Guill. & Perr. (Barker) Leafy Stems on NMRI Mice and Normotensive Wistar Rats. Journal of Drug Delivery and Therapeutics, 13, 1-10. https://doi.org/10.22270/jddt.v13i1.5819
[21]
Bachheti, R.K., Worku, L.A., Gonfa, Y.H., Zebeaman, M., Pandey, D. and Bachheti, A. (2022) Prevention and Treatment of Cardiovascular Diseases with Plant Phytochemicals: A Review. Evidence-Based Complementary and Alternative Medicine, 2022, Article ID: 5741198. https://doi.org/10.1155/2022/5741198
[22]
Ouedraogo, S., Ouedraogo, B., Kabore, B., Traore, T., Yaro, A., Koala, M., Yoda, J., Ouedraogo, S. and Semde, R. (2021) Research of Phytochemical Marker in Trunk Bark Extracts of Lannea microcarpa, A Traditional Herbal Used to Treat High Blood Pressure. Medicinal and Analytical Chemistry International Journal, 5, Article ID: 000171. https://doi.org/10.23880/macij-16000171
[23]
Kaboré, B., Koala, M., Nitiema, M., Ouedraogo, W.R.C., Compaoré, S., Belemnaba, L., Ouedraogo, S., Ilboudo, S., Ouedraogo, N. and Dabiré, C.M. (2022) Phytochemical Screening by High-Performance Thin-Layer Chromatography, Antioxidant Activities and Acute Toxicity of Trunk Barks Extracts of Lannea velutina A. Rich. American Journal of Analytical Chemistry, 13, 365-381.
https://doi.org/10.4236/ajac.2022.1310025
[24]
Knox, M., Vinet, R., Fuentes, L., Morales, B. and Martínez, J.L. (2019) A Review of Endothelium-Dependent and -Independent Vasodilation Induced by Phytochemicals in Isolated Rat Aorta. Animals, 9, Article No. 623.
https://doi.org/10.3390/ani9090623
[25]
Castro-Ruiz, J.E., Rojas-Molina, A., Luna-Vázquez, F.J., Rivero-Cruz, F., García-Gasca, T. and Ibarra-Alvarado, A.C. (2017) (Spilanthol), Isolated from Heliopsis longipes, Induces Vasodilation via Activation of Gasotransmitters and Prostacyclin Signaling Pathways. International Journal of Molecular Sciences, 18, Article No. 218. https://doi.org/10.3390/ijms18010218
[26]
Luna-Vázquez, F., Ibarra-Alvarado, C., Camacho-Corona, M., Rojas-Molina, A., Rojas-Molina, J., García, A. and Bah, M. (2018) Vasodilator Activity of Compounds Isolated from Plants Used in Mexican Traditional Medicine. Molecules, 23, Article No. 1474. https://doi.org/10.3390/molecules23061474
[27]
Schini-Kerth, V.B., Auger, C., étienne-Selloum, N. and Chataigneau, T. (2010) Polyphenol-Induced Endothelium-Dependent Relaxations: Role of NO and EDHF. Advances in Pharmacology, 60, 133-175.
https://doi.org/10.1016/B978-0-12-385061-4.00006-4
[28]
Castro, C. (2022) Natural Plant Antioxidants and Cardiovascular Disease. Frontiers in Physiology, 13, Article ID: 848497. https://doi.org/10.3389/fphys.2022.848497
[29]
Shahidi, F. and Ambigaipalan, P. (2015) Phenolics and Polyphenolics in Foods, Beverages and Spices: Antioxidant Activity and Health Effects—A Review. Journal of Functional Foods, 18, 820-897. https://doi.org/10.1016/j.jff.2015.06.018
[30]
Singla, R.K., Dubey, A.K., Garg, A., Sharma, R.K., Fiorino, M., Ameen, S.M., Haddad, M.A. and Al-Hiary, M. (2019) Natural Polyphenols: Chemical Classification, Definition of Classes, Subcategories, and Structures. Journal of AOAC International, 102, 1397-1400. https://doi.org/10.1093/jaoac/102.5.1397
[31]
Hrelia, S. and Angeloni, C. (2021) New Mechanisms of Action of Natural Antioxidants in Health and Disease II. Antioxidants, 10, Article No. 1200.
https://doi.org/10.3390/antiox10081200
[32]
Ali, J., Aziz, M.A., Rashid, M.M.O., Basher, M.A. and Islam, M.S. (2022) Propagation of Age-Related Diseases Due to the Changes of Lipid Peroxide and Antioxidant Levels in Elderly People: A Narrative Review. Health Science Reports, 5, e650.
https://doi.org/10.1002/hsr2.650
[33]
Bationo, J., Hilou, A., Savadogo, P. and Nacoulma, O. (2012) Content of Polyphenolics Constituents and the Antioxidant and Antimicrobial Activities of Extracts from Leaves and Fruits of “Lannea microcarpa” Engl. & K. Kraus (Anacardiaceae). Current Research Journal of Biological Sciences, 4, 290-296.
[34]
Hilou, A., Bougma, A. and Dicko, M.H. (2017) Phytochemistry and Agro-Industrial Potential of Native Oil Seeds from West Africa: African Grape (Lannea microcarpa), Marula (Sclerocarya birrea), and Butter Tree (Pentadesma butyracea). Agriculture, 7, Article No. 24. https://doi.org/10.3390/agriculture7030024
[35]
Belemnaba, L., Ouédraogo, S., Nitiéma, M., Chataigneau, T., Guissou, I.P., Schini-Kerth, V.B., Bucher, B. and Auger, C. (2018) An Aqueous Extract of the Anogeissus leiocarpus Bark (AEAL) Induces the Endothelium-Dependent Relaxation of Porcine Coronary Artery Rings Involving Predominantly Nitric Oxide. Journal of Basic and Clinical Physiology and Pharmacology, 29, 599-608.
https://doi.org/10.1515/jbcpp-2017-0084
[36]
Heikkila, H., Maalouf, W. and Campello, G. (2021) The United Nations Office on Drugs and Crime’s Efforts to Strengthen a Culture of Prevention in Low- and Middle-Income Countries. Prevention Science, 22, 18-28.
https://doi.org/10.1007/s11121-020-01088-5
[37]
Owusu, G. and Antwi-Adjei, M. (2017) Acute and Sub-Acute Oral Toxicity Studies of the Aqueous Extract of Lannea microcarpa Stem Bark on Rats. International Journal of Pharmacy & Pharmaceutical Research, 9, 17-30.
[38]
Nitiéma, M., Ilboudo, S., Belemnaba, L., Ouédraogo, G.G., Ouédraogo, S., Ouédraogo, N., Sylvin, O. and Guissou, I.P. (2018) Acute and Sub-Acute Toxicity Studies of Aqueous Decoction of the Trunk Barks from Lannea microcarpa Engl. and K. Krause (Anacardiaceae) in Rodents. World Journal of Pharmacy and Pharmaceutical Sciences, 7, 30-42.
