Anti-inflammatory activity and mechanism of action of ethanolic leaf extract of Morinda lucida Benth

10.1016/j.jtcme.2020.07.001

Frederick Ayertey；Ebenezer Ofori-Attah；Stephen Antwi；Michael Amoa-Bosompem；Georgina Djameh；Nathaniel Lartey Lartey；Mistuko Ohashi；Kwadwo Asamoah Kusi；Alfred Ampomah Appiah；Regina Appiah-Opong；Laud Kenneth Okine

Cyclooxygenase-2 ； Cytokines ； Edema ； Inflammation ； Nitric oxide

Journal of Traditional and Complementary Medicine

11卷3期（2021 / 05 / 01）

249 - 258

英文

Background and aim: Most developing countries resort to medicinal plants for treating diseases, but few of these have scientific backing for their use. The aim of the study was to validate traditional use of Morinda lucida leaves in treating inflammation and determine the mechanism of action. Experimental procedure: Effect of hydroethanolic leaf extract of M. lucida (HEML) on localized inflammation was evaluated using rat paw edema presented by sub-planter injections of λ-carrageenan, histamine or serotonin in separate experiments. Systemic inflammation was evaluated by lipopolysaccharide (LPS)-induced hyperthermia. Antioxidant activity of HEML was also evaluated using the free-radical scavenging assay. Results and conclusion: No mortalities were recorded in acute toxicity assay after administering 5000 mg/ kg HEML to rats. It showed very good activity against localized and systemic inflammation in inverse dose-dependent manner and caused reduction in nitric oxide and prostaglandin E-2 levels by affecting expression of inducible nitric oxide synthase, but not cyclooxygenases-2 in LPS-activated RAW 264.7 murine macrophages. HEML reduced pro-inflammatory cytokines interleukin (IL)-1β and tumor necrotic factor, but elevated levels of anti-inflammatory cytokine IL-10 in vitro. HEML contains saponins, reducing sugars, polyphenols and flavonoids and showed antioxidant activity with EC_(50)=0.6415 ± 0.0027 mg/ml. In conclusion, this study provides evidence that HEML possesses anti-inflammatory activity, possibly through modulation of production of early/late phase inflammation mediators.

1. Acheampong, F,Larbie, C,Arthur, FNA,Appiah-Opong, R,Tuffour, I(2015).Antioxidants and anticancer study of Ageratum conyzoides aqueous extracts.J Global Biosci,4(1),1804-1815.
2. Appiah-Opong, R,Asante, IK,Osei-Safo, D(2016).Cytotoxic effects of Albizia zygia (DC) JF Macbr, a Ghanaian medicinal plant, against human T-lymphoblast-like leukemia, prostate and breast cancer cell lines.Int J Pharm Pharmaceut Sci.,8(5),392-396.
3. Aquila, S,Giner, RM,Recio, MC,Spegazzini, ED,Ríos, JL(2009).Anti-inflammatory activity of flavonoids from Cayaponia tayuya roots.J Ethnopharmacol,121(2),333-337.
4. Arslan, R,Bektas, N,Ozturk, Y(2010).Antinociceptive activity of methanol extract of fruits of Capparis ovata in mice.J Ethnopharmacol,131(1),28-32.
5. Ayertey, F.(2016).Legon, Accra, Ghana,Department of Biochemistry, Cell and Molecular Biology, University of Ghana.
6. Baker, PR,Schopfer, FJ,O’Donnell, VB,Freeman, BA(2008).Convergence of nitric oxide and lipid signaling: anti-inflammatory nitro-fatty acids.Free Radic Biol Med,46(8),989-1003.
7. Bradford, MM(1976).A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Anal Biochem,72(1-2),248-254.
8. Branco, ACCC,Yoshikawa, FSY,Pietrobon, AJ,Sato, MN(2018).Role of histamine in modulating the immune response and inflammation.Mediat Inflamm
9. Celotti, F,Laufer, S(2001).Anti-inflammatory drugs: new multitarget compounds to face an old problem. The dual inhibition concept.Pharmacol Res,43(5),429-436.
10. Cloëz-Tayarani, I,Petit-Bertron, A-F,Venters, HD,Cavaillon, J-M(2003).Differential effect of serotonin on cytokine production in lipopolysaccharide-stimulated human peripheral blood mononuclear cells: involvement of 5-hydroxytryptamine 2A receptors.Int Immunol,15(2),233-240.
11. Ferrero-Miliani, L,Nielsen, O,Andersen, P,Girardin, SE(2007).Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1b generation.Clin Exp Immunol,147(2),227-235.
12. Fleming, BD,Chandrasekaran, P,Dillon, LA(2015).The generation of macrophages with anti-inflammatory activity in the absence of STAT6 signaling.J Leukoc Biol,98(3),395-407.
13. Gabay, C,Kushner, I(1999).Acute-phase proteins and other systemic responses to inflammation.N Engl J Med,340(6),448-454.
14. Gilligan, JP,Lovato, SJ,Erion, MD,Jeng, AY(1994).Modulation of carrageenan-induced hind paw edema by substance P.Inflammation,18(3),285-292.
15. Halici, Z,Dengiz, GO,Odabasoglu, F,Suleyman, H,Cadirci, E,Halici, MJ(2007).Amiodarone has anti-inflammatory and anti-oxidative properties: an experimental study in rats with carrageenan-induced paw edema.Eur J Pharmacol,566(1-3),215-221.
16. Hou, Y-Z,Yang, J,Zhao, G-R,Yuan, Y-J(2004).Ferulic acid inhibits vascular smooth muscle cell proliferation induced by angiotensin II.Eur J Pharmacol,499(1-2),85-90.
17. Huang, G-J,Reddy, MVB,Kuo, P-C(2012).A concise synthesis of viscolin, and its anti-inflammatory effects through the suppression of iNOS, COX-2, ERK phosphorylation and proinflammatory cytokines expressions.Eur J Med Chem,48,371-378.
18. Joo, T,Sowndhararajan, K,Hong, S(2014).Inhibition of nitric oxide production in LPS-stimulated RAW 264.7 cells by stem bark of Ulmus pumila L.Saudi J Biol Sci,21(5),427-435.
19. Koffuor, GA,Kyei, S,Woode, E,Ekuadzi, E,Ben, IO(2012).Possible mechanism of anti-inflammatory activity and safety profile of aqueous and ethanolic leaf extracts of Pistia stratiotes Linn (Araceae).GJSA.,14(1)
20. Lamien, CE,Guissou, IP,Nacoulma, OG(2006).Anti-inflammatory, analgesie and anti-pyretic activities of Dicliptera verticillata.Int J Pharmacol,2,435-438.
21. Liu, T,Zhang, L,Joo, D,Sun, S-C(2017).NF-kB signaling in inflammation.Signal Transduct Target Ther
22. Maier, JA,Voulalas, P,Roeder, D,Maciag, T(1990).Extension of the life-span of human endothelial cells by an interleukin-1 alpha antisense oligomer.Science,249(4976),1570-1574.
23. Mantovani, A,Biswas, SK,Galdiero, MR,Sica, A,Locati, M(2013).Macrophage plasticity and polarization in tissue repair and remodelling.J Pathol,229,176-185.
24. Mantovani, A,Sica, A,Sozzani, S,Allavena, P,Vecchi, A,Locati, M(2004).The chemokine system in diverse forms of macrophage activation and polarization.Trends Immunol,25(12),677-686.
25. Mill, CD,Kincaid, K,Alt, JM,Heilman, MJ,Hill, AM(2000).M-1/M-2 macrophages and the Th1/Th2 paradigm.J Immunol,164(12),6166-6173.
26. Pan, M-H,Lai, Ching-Shu,Ho, C-T(2010).Anti-inflammatory activity of natural dietary flavonoids.Food Funct,1,15-31.
27. Pattanayak, SP,Mazumder, PM,Sunita, P(2012).Total phenolic content, flavonoid content and in vitro antioxidant activities of Dendrophthoe falcata (Lf) Ettingsh.Res J Med Plant,6,136-148.
28. Quero, L,Hanser, E,Manigold, T,Tiaden, AN,Kyburz, D(2017).TLR2 stimulation impairs anti-inflammatory activity of M2-like macrophages, generating a chimeric M1/M2 phenotype.Arthritis Res Ther
29. Rainsford, KD(1999).Profile and mechanisms of gastrointestinal and other side effects of nonsteroidal anti-inflammatory drugs (NSAIDs).Am J Med,107(6),27-35.
30. Rezania, S,Amirmozaffari, N,Tabarraei, B(2011).Extraction, purification and characterization of lipopolysaccharide from Escherichia coli and Salmonella typhi.Avicenna J Med Biotechnol,3(1),3-9.
31. Roth, S,Wyatt, J,Baudin, J(2001).Neurodevelopmental status at 1 year predicts neuropsychiatric outcome at 14e15 years of age in very preterm infants.Early Hum Dev.,65(2),81-89.
32. Salvemini, D,Kim, SF,Mollace, V(2013).Reciprocal regulation of the nitric oxide and cyclooxygenase pathway in pathophysiology: relevance and clinical implications.Am J Physiol Regul Integr Comp Physiol,304(7),R473-R487.
33. Schottenfeld, D,Beebe-Dimmer, J(2006).Chronic inflammation: a common and important factor in the pathogenesis of neoplasia.CA A Cancer J Clin,56(2),69-83.
34. Sowemimo, A,Onakoya, M,Fageyinbo, MS,Fadoju, T(2013).Studies on the anti-inflammatory and anti-nociceptive properties of Blepharis maderaspatensis leaves.Rev Bras Farmacogn,23(5),830-835.
35. Trease, GE,Evans, WC.(2002).Pharmacognosy.London:Saunders Publishers.
36. Yim, M-J,Lee, JM,Choi, G(2018).Anti-inflammatory potential of Carpomitra costata ethanolic extracts via inhibition of NF-kB and AP-1 activation in LPS-Stimulated RAW264.7 Macrophages.Evid base Compl Alternative Med
37. Zhang, J-M,An, J(2007).Cytokines, inflammation and pain.Int Anestheiol Clin,45(2),27-43.