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Annona muricata Extract Reduces Inflammation via Inactivation of NALP3 Inflammasome


Affiliations
1 Beirut Arab University, P.O. Box 115020 Riad El solh 11072809, Lebanon
 

Annona muricata (AM) is a herb traditionally used to treat various human ailments. The mechanistic effect of Annona muricata extract on NALP3 inflammasome activation is not well understood. Objective: The present study investigates the inhibitory effects of Annona muricata extract on NALP3 inflammasome activation and its role in sepsis prevention. Methods: Sepsis was induced in mice by intraperitoneal injection of Escherichia fergusonii. Mice were treated with Annona muricata extract. Its effect on liver was assessed both histologically and biochemically. Lipid peroxidation, level of IL-1β, TNF-α was measured colorimetrically and using Elisa kit in liver homogenates. The expression levels of IL-1β, TNF-α, caspase-1 and NALP3 genes were measured using RT-PCR. Results: AM extract significantly minimized the inflammation by decreasing the level and the expression levels of IL-1β and TNF-α in a time-dependent manner. Significant decrease in the gene expression level of caspase-1 and NALP3 was observed. Histopathologically, normal architecture of the liver of infected mice was regained after the herb treatment. Conclusion: Anonna Muricata can act as a potent therapeutic agent in treating various NALP3 associated inflammatory disorders.

Keywords

Annona muricata, Cytokines, Escherichia fergusonii, NALP3 Inflammasome.
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  • Moghadamtousi SZ, Fadaeinasab M, Nikzad S, Mohan G, Ali HM, Kadir HA. Annona muricata (Annonaceae): a review of its traditional uses, isolated acetogenins and biological activities. Int J Mol Sci. 2015; 16(7):15625–58. https://doi.org/10.3390/ijms160715625
  • Adewole SO, Caxton-Martins EA. Morphological changes and hypoglycemic effects of Annona muricata Linn. (Annonaceae) leaf aqueous extract on pancreatic B-cells of streptozotocin-treated diabetic rats. Afr J Biomed Res. 2006; 9:173–87. https://doi.org/10.4314/ajbr.v9i3.48903
  • De Souza R, Benassi E, da Silva RR, Afonso S, Scarminio IS. Enhanced extraction yields and mobile phase separations by solvent mixtures for the analysis of metabolites in Annona muricata L. Leaves. J Sep Sci. 2009; 32:4176–85. https://doi.org/10.1002/jssc.200900375
  • Jimenez VM, Gruschwitz M, Schweiggert RM, Carle R, Esquivel P. Identification of phenolic compounds in soursop (Annona muricata) pulp by high-performance liquid chromatography with diode array and electrospray ionization mass spectrometric detection. Food Res Int. 2014; 65:42–6. https://doi.org/10.1016/j.foodres.2014.05.051
  • Mishra S, Ahmad S, Kumar N, Sharma BK. Annona muricata (the cancer killer): A review. Glob J Pharm Res. 2013; 2:1613–8.
  • Ong H, Norzalina J. Malay herbal medicine in Gemencheh, Negri Sembilan, Malaysia. Fitoterapia. 1999; 70:10–4. https://doi.org/10.1016/S0367-326X(98)00023-9
  • Wu FE, Gu ZM, Zeng L, Zhao GX, Zhang Y, McLaughlin JL, et al. Two new cytotoxic mono-tetrahydrofuran annonaceous acetogenins, annomuricins a and b from the leaves of Annona muricata. J Nat Prod. 1995; 58:830–6. https://doi.org/10.1021/np50120a002
  • Matsushige A, Matsunami K, Kotake Y, Otsuka H, Ohta S. Three new megastigmanes from the leaves of Annona muricata. J Nat Med. 2012; 66:284–91. https://doi.org/10.1007/s11418-011-0583-1
  • Pelissier Y, Marion C, Kone D, Lamaty G, Menut C, Bessiere J.-M. Volatile components of Annona muricata L. J. Essent. Oil Res. 1994; 6:411–4. https://doi.org/10.1080/10412905.1994.9698410
  • Yang C, Gundala SR, Mukkavilli R, Vangala S, Reid MD, Aneja R. Synergistic interactions among flavonoids and acetogenins in graviola (Annona muricata) leaves confer protection against prostate cancer. Carcinogenesis. 2015; 36(6):656–65. doi:10.1093/carcin/bgv1046
  • Morton JF. Caribbean and Latin american folk medicine and its influence in the United States. Q J Crude Drug Res. 1980; 18(2):57–75. https://doi.org/10.3109/13880208009065179
  • Gajalakshmi S, Vijayalakshmi S, Rajeshwari Devi V. Phytochemical and pharmacological properties of Annona muricata: A review. Int J Pharm Sci. 2012; 4(2):3–6.
  • Leboeuf M, Cave A, Bhaumik P, Mukherjee B, Mukherjee R. The phytochemistry of the Annonaceae. Phytochemistry. 1980; 21:2783–813. https://doi.org/10.1016/0031-9422(80)85046-1
  • De Souza EB, Benassi E, da Silva RR, Afonso S, Scarminio IS. Enhanced extraction yields and mobile phase separations by solvent mixtures for the analysis of metabolites in Annona muricata L. Leaves. J Sep Sci. 2009; 32:4176–85. https://doi.org/10.1002/jssc.200900375
  • Taylor L. Technical data report for graviola, Annona muricata, Vol. 10 Austin: Sage Press; 2002. p. 1–6.
  • Moghadamtousi SZ, Kadir HA, Paydar M, Rouhollahi E, Karimian H. Annona muricata leaves induced apoptosis in A549 cells through mitochondrial-mediated pathway and involvement of NF-κB. BMC Complement Altern Med. 2014; 14:29. https://doi.org/10.1186/1472-6882-14-299
  • Arroyo J, Prashad M, Vasquez Y, Li E, Tomas G. Actividadcitotoxica in vitro de la mezcla de Annona muricata y krameria lappacea sobre celulas cancerosas de glandula mamaria, pulmony Sistema nervioso central (in Spanish). Rev Peru Med Exp. 2005; 22:247–53.
  • George VC, Kumar DN, Suresh P, Kumar RA. Antioxidant, DNA protective efficacy and HPLC analysis of Annona muricata (soursop) extracts. J Food Sci Technol. 2015; 52(4):2328–35. https://doi.org/10.1007/s13197-014-1289-7
  • Nwokocha CR, Owu DU, Gordon A, Thaxter K, McCalla G, Ozolua RI. Possible mechanisms of action of the hypotensive effect of Annona muricata (soursop) in normotensive sprague-dawley rats. Pharm Biol. 2012; 50:1436–41. https://doi.org/10.3109/13880209.2012.684690
  • Hamid RA, Foong CP, Ahmad Z, Hussain MK. Antinociceptive and anti-ulcerogenic activities of the ethanolic extract of Annona muricata leaf. Rev Bras Farmacogn. 2012; 22:630– 41. https://doi.org/10.1590/S0102-695X2012005000001
  • Viera GHF, Mourao JA, Angelo AM, Costa RA, Vieira RHSDF. Antibacterial effect (in vitro) of Moringa oleifera and Annona Nuricata against gram positive and gram negative bacteria. Rev Inst Med Trop Sao Paulo. 2010; 52(3):129–32. PMid: 20602021. https://doi.org/10.1590/S0036-46652010000300003
  • Roslida A, Tay C, Zuraini A, Chan P. Anti-inflammatory and anti-nociceptive activities of the ethanolic extract of Annona muricata leaf. J Nat Rem. 2010; 10:97–104.
  • Martinon F, Mayor A, Tschopp J. The inflammasomes: Guardians of the body. Annu Rev Immunol. 2009; 27:229–65. https://doi.org/10.1146/annurev.immunol.021908.132715
  • Muruve DA, Petrilli V, Zaiss AK, White LR, Clark SA, Ross PJ, et al. The inflammasome recognizes cytosolic microbial and host DNA and trigger innate immune response. Nature. 2008; 452:103–7. https://doi.org/10.1038/nature06664
  • Schroder K, Tschopp J. The inflammasomes. Cell. 2010; 140:821–32. https://doi.org/10.1016/j.cell.2010.01.040
  • Martinon F, Burns K, Tschopp J. The inflammasome: A molecular platform triggering activation of inflammatory caspases and processing of pro IL-beta. Mol Cell. 2002; 10:417–26. https://doi.org/10.1016/S1097-2765(02)00599-3
  • Mandrekar P, Ambade A, Lim A, Szabo G, Catalano D. An essential role for monocyte chemoattractant protein 1 in alcoholic liver injury: Regulation of proinflammatory cytokines and hepatic steatosis in mice. Hepatology. 2011; 54:2185–97. https://doi.org/10.1002/hep.24599
  • Aksentijevich I, Putnam CD, Remmers EF, Mueller JL, Le J, Kolodner RD, et al. The clinical continuum of cryopyrinopathies. Arthritis Rheum. 2007; 56:1273–85. https://doi.org/10.1002/art.22491
  • Shinkai K, McCalmont TH, Leslie KS. Cryopyrin-associated periodic syndromes and auto-inflammation. Clin Exp. Dermatol. 2008; 33(1):1–9. https://doi.org/10.1111/j.1365-2230.2007.02540.x
  • Guo H, Callaway JB, Ting JB. Inflammasomes: Mechanism of action, role in disease and therapeutics. Nat Med. 2015; 21(7):677–87. https://doi.org/10.1038/nm.3893
  • Liston A, Masters SL. Homeostasis-altering molecular processes as mechanisms of inflammasome activation. Nat Rev Immunol. 2017; 17(3):208–14. https://doi.org/10.1038/nri.2016.151
  • Alvarez S, Munoz-Fernandez MA. TNF-α may mediate inflammasome activation in the absence of bacterial infection in more than one way. PLoS ONE 2013; 8(8):e71477. https://doi.org/10.1371/journal.pone.0071477
  • Yen H, Karino M, Tobe T. Modulation of the inflammasome signaling pathway by enteropathogenic and enterohemorrhagic Escherichia coli. Front Cell Infect Microbiol. 2016; 26(6):89. https://doi.org/10.3389/fcimb.2016.00089
  • Forgetta V, Rempel H, Malouin F, Vallencourt R Jr, Topp E, Dewar K. Pathogenic and multidrug-resistant Escherichia fergusonii from broiler chicken. Poultry Science. 2012; 91:512–25. https://doi.org/10.3382/ps.2011-01738
  • Janero DR. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med. 1990; 9:515–40. https://doi.org/10.1016/0891-5849(90)90131-2
  • Schroder K, Zhou R, Tschopp J. The NLRP3 inflammasome: A sensor for metabolic danger? Science. 2010; 327:296–300. https://doi.org/10.1126/science.1184003
  • Swystun LL, Liaw PC. The role of leukocytes in thrombosis. Blood. 2016; 128:753–62. https://doi.org/10.1182/blood-2016-05-718114
  • Massberg S, Grahl L, von Bruehl ML, Manukyan D, Pfeiler S, Goosman C, et al. Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med. 2010; 16(8):887–96. https://doi.org/10.1038/nm.2184
  • Kwiecien S, Pawlik MW, Brzozowski T, Pawlik WW, Konturek SJ. Reactive oxygen metabolite action in experimental, stress model of gastric mucosa damage. Gastroenterol Pol. 2010; 17:234–43.
  • Moldovan L, Moldovan NI. Oxygen free radicals and redox biology of organelles. Histochemistry and Cell Biology. 2004; 122(4):395–412. https://doi.org/10.1007/s00418-004-0676-y
  • George VC, Kumar DN, Suresh P, Kumar RA. Antioxidant, DNA protective efficacy and hplc analysis of Annona muricata (soursop) extracts. J Food Sci Technol. 2015; 52:2328–35. https://doi.org/10.1007/s13197-014-1289-7
  • Vijayameena C, Subhashini G, Loganayagi M, Ramesh B. Phytochemical screening and assessment of antibacterial activity for the bioactive compounds in Annona muricata. Int. J Curr Microbiol Appl Sci. 2013; 2:1–8.
  • Mohamed ET, El-Sayed Mahdy ME, Singer GM, ElKiki1 S, Elias MS. Role of Annona muricata (L.) in oxidative stress and metabolic variations in diabetic and gammairradiated rats. Egypt. J Rad Sci Applic. 2017; 30:1–11. https://doi.org/10.21608/ejrsa.2017.1183.1012
  • Bauernfeind F, Bartok E, Rieger A, Franchi l,Nú-ez G, HornungV. Cutting edge: Reactive oxygen species inhibitors block priming, but not activation, of the NLRP3 inflammasome. J Immunol. 2011; 187:613–7. https://doi.org/10.4049/jimmunol.1100613
  • Munoz-Planillo R, Kuffa P, Martinez-Colon G, Smith BL, Núñez G. K+ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity. 2013; 38:1142–53. https://doi.org/10.1016/j.immuni.2013.05.016

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  • Annona muricata Extract Reduces Inflammation via Inactivation of NALP3 Inflammasome

Abstract Views: 173  |  PDF Views: 61

Authors

Rana Mohamad Bitar
Beirut Arab University, P.O. Box 115020 Riad El solh 11072809, Lebanon
Ragaee Ramzi Fahmi
Beirut Arab University, P.O. Box 115020 Riad El solh 11072809, Lebanon
Jamilah Mohamad Borjac
Beirut Arab University, P.O. Box 115020 Riad El solh 11072809, Lebanon

Abstract


Annona muricata (AM) is a herb traditionally used to treat various human ailments. The mechanistic effect of Annona muricata extract on NALP3 inflammasome activation is not well understood. Objective: The present study investigates the inhibitory effects of Annona muricata extract on NALP3 inflammasome activation and its role in sepsis prevention. Methods: Sepsis was induced in mice by intraperitoneal injection of Escherichia fergusonii. Mice were treated with Annona muricata extract. Its effect on liver was assessed both histologically and biochemically. Lipid peroxidation, level of IL-1β, TNF-α was measured colorimetrically and using Elisa kit in liver homogenates. The expression levels of IL-1β, TNF-α, caspase-1 and NALP3 genes were measured using RT-PCR. Results: AM extract significantly minimized the inflammation by decreasing the level and the expression levels of IL-1β and TNF-α in a time-dependent manner. Significant decrease in the gene expression level of caspase-1 and NALP3 was observed. Histopathologically, normal architecture of the liver of infected mice was regained after the herb treatment. Conclusion: Anonna Muricata can act as a potent therapeutic agent in treating various NALP3 associated inflammatory disorders.

Keywords


Annona muricata, Cytokines, Escherichia fergusonii, NALP3 Inflammasome.

References





DOI: https://doi.org/10.18311/jnr%2F2018%2F22709