Antimicrobial and Wound Healing Potential of Dietary Flavonoid Naringenin

Author(s): Ankita Tripathi, Himani Awasthi*, Dan Bahadur Rokaya, Dipti Srivastava, Vivek Srivastava.

Journal Name: The Natural Products Journal

Volume 9 , Issue 1 , 2019

Submit Manuscript
Submit Proposal

Graphical Abstract:


Background: Naringenin belongs to the class flavanones, and chemically it is known as 5,7-dihydroxy-2-(4-hydroxyphenyl) chroman-4-one. It is one of the dietary poly-phenolic constituents of the citrus fruits and vegetables. Naringenin possesses excellent antioxidant, antiinflammatory, and antimicrobial activities. These activities promote wound healing activity. Naringenin has been incorporated in the gel base to be applied on the wounded skin. The wound healing property of naringenin gel has not been studied extensively in the literature to date.

Objective: The present study aims to unveil the wound healing property of naringenin gel formulation on excision and incision model.

Materials and Methods: 0.5% and 1% naringenin was incorporated in a carbopol gel base formulation and evaluated for physicochemical parameters. Incision and excision wound models were used to study wound contraction, tensile strength, healing index, the period of epithelization and histopathological parameters. Antimicrobial activity was performed using agar plate method.

Results: Naringenin (0.5% and 1%) treatment shows a significant increase in the percentage of wound contraction, good healing index and shorter epithelization period. Histopathology of naringenin gel treated wound tissue showed more fibroblasts, less macrophage infiltration, and wellformed collagen fibers as compared to control. In incision wound model, the animals were treated with 0.5% and 1% naringenin gel for nine days and showed a significant increase in the tensile strength. Naringenin exerts antimicrobial activity against fungus and E. coli.

Conclusion: The present study explored potent wound healing activity of naringenin gels.

Keywords: Excision wound, incision wound, healing index, tensile strength, naringenin, collagen fibers.

Nguyen, D.T.; Orgill, D.P.; Murphy, G.F. The pathophysiologic basis for wound healing and cutaneous regeneration, biomaterials for treating skin loss; Biomater. Treating Skin Loss, 2009, pp. 25-57.
Omale, J.; Isaac, A.V. Excision and incision wound healing potential of Saba florida (Benth) leaf extract in Rattus novergicus. Int. J. Pharm. Biomed. Res, 2010, 1(4), 101-107.
Al-Henhena, N.; Mahmood, A.A.; Al-magrami, A.; Nor Syuhada, A.R.; Zahra, A.A.; Summaya, M.D. Histological study of wound healing potential by ethanol leaf extract of Strobilanthes crispus in rats. J. Med. Plants Res., 2011, 5(16), 3660-3666.
Pandith, H.; Zhang, X.; Liggett, J.; Min, K.W.; Gritsanapan, W.; Baek, S.J. Hemostatic and wound healing properties of Chromolaena odorata leaf extract. Int. J. Res. Dermatol, 2013, 45, 168-269.
Tsala, D.E.; Nga, N.; Thiery, B.N.; Bienvenue, T.; Theophile, D. Evaluation of the antioxidant activity and the healing action of the ethanol extract of Calotropis procera bark against surgical wounds. J. Intercult. Ethnopharmacol., 2014, 4(1), 64-69.
Vezza, R.; Mezzasoma, A.M.; Venditti, G.; Gresele, P. Prostaglandin endoperoxides and thromboxane A2 activate the same receptor isoforms in human platelets. Thromb. Haemost., 2002, 87(1), 114-121.
Aso, Y. Plasminogen activator inhibitor (PAI)-1 in vascular inflammation and thrombosis. Front. Biosci., 2007, 12(8), 2957-2966.
Martin, P.; Leibovich, S.J. Inflammatory cells during wound repair: The good, the bad and the ugly. Trends Cell Biol., 2005, 15(11), 599-607.
Fialkow, L.; Wang, Y.; Downey, G.P. Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function. Free Radic. Biol. Med., 2007, 42(2), 153-164.
Wagener, F.A.; van Beurden, H.E.; von den Hoff, J.W.; Adema, G.J.; Figdor, C.G. The heme-heme oxygenase system: A molecular switch in wound healing. Blood, 2003, 102(2), 521-528.
Stamenkovic, I. Extracellular matrix remodelling: The role of matrix metalloproteinases. J. Pathol., 2003, 200(4), 448-464.
Udegbunam, S.O.; Kene, R.O.C.; Anika, S.M.; Udegbunam, R.I.; Nnaji, T.O.; Anyanwu, M.U. Evaluation of wound healing potential of methanolic Crinum jagus bulb extract. J. Intercult. Ethnopharmacol., 2015, 4(3), 194-201.
Udegbunam, S.O.; Udegbunam, R.I.; Muogbo, C.C.; Anyanwu, M.U.; Nwaehujor, C.O. Wound healing and antibacterial properties of methanolic extract of Pupalia lappacea Juss in rats. BMC Complement. Altern. Med., 2014, 14(1), 157.
Udegbunam, S.O.; Nnaji, T.O.; Udegbunam, R.I.; Okafor, J.C.; Agbo, I. Evaluation of herbal ointment formulation of Milicia excelsa (Welw) C.C berg for wound healing. Afr. J. Biotechnol., 2013, 12(21), 3351-2359.
Patel, K.; Singh, G.K.; Patel, D.K. A review on pharmacological and analytical aspects of naringenin. Chin. J. Integr. Med., 2014, 14, 1-13.
Samanta, R.; Pattnaik, A.K.; Pradhan, K.K.; Mehta, B.K.; Pattanayak, S.P.; Banerjee, S. Wound healing activity of silibinin in mice. Pharmacogn. Rev., 2016, 8(4), 298.
Garg, A.; Aggarwal, D.; Garg, S.; Singla, A.K. Spreading of semisolid formulations: An update. Pharm. Technol., 2002, 26(9), 84-105.
Mandalari, G.l.; Bennett, R.N.; Bisignano, G.; Trombetta, D. Saija; A. Faulds, C.B.; Gasson, M.J.; Narbad, A. Antimicrobial activity of flavonoids extracted from bergamot (Citrus bergamia Risso) peel, a byproduct of the essential oil industry. J. Appl. Microbiol., 2007, 103(6), 2056-2064.
Capasso, R.; Fiorino, F.; Ascione, V.; Frecentese, F.; Borrelli, F. Inhibition of rat vas deferens contractions by flavonoids in-vitro. J. Pharm. Pharmacol., 2006, 58(3), 381-384.
Testai, L.; Calderone, V. Nutraceutical value of citrus flavanones and their implications in cardiovascular disease. Nutrients, 2017, 9(5), 16.
Barreca, D.; Gattuso, G.; Bellocco, E.; Calderaro, A.; Trombetta, D.; Smeriglio, A.; Laganà, G.; Daglia, M.; Meneghini, S.; Nabavi, S.M. Flavanones: Citrus phytochemical with health-promoting properties. Biofactors, 2017, 43(4), 495-506.
Nyane, N.A.; Tlaila, T.B.; Malefane, T.G.; Ndwandwe, D.E.; Owira, P.M.O. Metformin-like antidiabetic, cardio-protective and non-glycemic effects of naringenin: Molecular and pharmacological insights. Eur. J. Pharmacol., 2017, 15(803), 103-111.
Shimizu, N.; Watanabe, T.; Arakawa, T.; Fujiwara, Y.; Higuchi, K.; Kuroki, T. Pentoxifylline accelerates gastric ulcer healing in rats: Roles of tumor necrosis factor alpha and neutrophils during the early phase of ulcer healing. Digestion, 2000, 61, 157-164.
Cavia-Saiz, M.; Busto, M.D.; Pilar-Izquierdo, M.C.; Ortega, N.; Perez-Mateos, M. Antioxidant properties, radical scavenging activity and biomolecule protection capacity of flavonoid naringenin and its glycoside naringin: A comparative study. J. Sci. Food Agric., 2010, 90(7), 1238-1244.
Pinho-Ribeiro, F.A.; Zarpelon, A.C.; Fattori, V.; Manchope, M.F.; Mizokami, S.S.; Casagrande, R.; Verri, W.A., Jr Naringenin reduces inflammatory pain in mice. Neuropharmacology, 2016, 105, 508-519.
Ubaid, M.; Ilyas, S.; Mir, S.; Khan, A.K.; Rashid, R.; Khan, M.Z. Formulation and in vitro evaluation of carbopol 934-based modified clotrimazole gel for topical application. An. Acad. Bras. Cienc., 2016, 88(4), 2303-2317.
Mandalari, G.; Bennett, R.N.; Bisignano, G.; Trombetta, D.; Saija, A.; Faulds, C.B.; Gasson, M.J.; Narbad, A. Antimicrobial activity of flavonoids extracted from bergamot (Citrus bergamia Risso) peel, a byproduct of the essential oil industry. J. Appl. Microbiol., 2007, 103(6), 2056-2064.
Tan, N.S.; Wahli, W. Studying wound repair in the mouse. Curr. Protoc. Mouse Biol., 2013, 3, 171-185.
Rajesh, S.; Pawar, P.K.; Chaurasiya, H.R.; Pradeep, K.S.; Fedelic, A.T.; Ankit, J. Wound healing activity of Sida cordifolia Linn. in rats. Indian J. Pharmacol., 2013, 45(5), 474-478.
El-Ferjani, R.M.; Ahmad, M.; Dhiyaaldeen, S.M.; Harun, F.W.; Ibrahim, M.Y.; Adam, H. In vivo assessment of antioxidant and wound healing improvement of a new schiff base derived Co (II) complex in rats. Sci. Rep., 2016, 6(1), 2045-2322.
de Albuquerque, R.D.D.G.; Perini, J.A.; Machado, D.E.; Angeli-Gamba, T.; dos Santos Esteves, R.; Santos, M.G. Wound healing activity and chemical standardization of Eugenia Pruniformis. Cambess, 2016, 12(48), 288.
Mandalari, G.; Bennett, R.N.; Bisignano, G.; Trombetta, D.; Saija, A.; Faulds, C.B.; Gasson, M.J.; Narbad, A. Antimicrobial activity of flavonoids extracted from bergamot (Citrus bergamia Risso) peel, a byproduct of the essential oil industry. J. Appl. Microbiol., 2007, 103(6), 2056-2064.
Kaya, D.; Aldirmaz, A.C.; Yucel, M. Fungal agents as a cause of surgical wound infections: An overview of host factors. Wounds, 2007, 19(8), 218-222.
Živa, P.; Kristina, E.; Marija, G.; Darja, Ž-B.; Marjanca, S.E. Virulence potential of Escherichia coli isolates from skin and soft tissue infections. J. Clin. Microbiol., 2009, 47(6), 1811-1817.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [61 - 68]
Pages: 8
DOI: 10.2174/2210315508666180802104630
Price: $58

Article Metrics

PDF: 13