Background. Ixora coccinea L. (Rubiaceae) has been documented for traditional use in hypertension, menstrual irregularities, sprain, chronic ulcer, and skin diseases. In the present study, I. coccinea was subjected to in vitro and in vivo wound healing investigation. Methods. Petroleum ether, chloroform, methanol, and water sequential I. coccinea leaves extracts were evaluated for in vitro antioxidant, antimicrobial, and fibroblast proliferation activities. The promising I. coccinea methanol extract (IxME) was screened for in vivo wound healing activity in Wistar rat using circular excision model. Wound contraction measurement, hydroxyproline quantification, and western blot for collagen type III (COL3A1), basic fibroblast growth factor (bFGF), and Smad-2, -3, -4, and -7 was performed with 7-day postoperative wound granulation tissue. Gentamicin sulfate (0.01% w/w) hydrogel was used as reference standard. Results. IxME showed the potent antimicrobial, antioxidant activities, with significant fibroblast proliferation inducing activity, as compared to all other extracts. In vivo study confirmed the wound healing accelerating potential of IxME, as evidenced by faster wound contraction, higher hydroxyproline content, and improved histopathology of granulation tissue. Western blot analysis revealed that the topical application of I. coccinea methanol extract stimulates the fibroblast growth factor and Smad mediated collagen production in wound tissue. 1. Background The World Health Organization estimated that 80% of the world’s population still relies on plant-based medicines for their primary health care, and skin related disorders specially wounds, which is the most common reason for medical visits in the developing countries. Wounds and wound management therapy have a long history and in the different Ayurvedic classics of India like Charaka Samhita, Sushruta Samhita, and Ayurveda Siksha approximately 70% of the wound healing medicines are of plant origin. In the last few decades, traditional wound healing plants have received enough attention for scientific investigations [1–3], where pathophysiological process of wound healing and various related activities such as fibroblast growth stimulation and antioxidant and antimicrobial activities has been extensively studied and correlated to the rationale of the traditional plant medicines [1, 4, 5]. In thrust of finding for an effective wound healing herb,？ ？Ixora coccinea L. (Rubiaceae) was selected for the in vitro and in vivo wound healing investigations. I. coccinea is a small-medium evergreen shrub,
References
[1]
P. J. Houghton, P. J. Hylands, A. Y. Mensah, A. Hensel, and A. M. Deters, “In vitro tests and ethnopharmacological investigations: wound healing as an example,” Journal of Ethnopharmacology, vol. 100, no. 1-2, pp. 100–107, 2005.
[2]
B. Kumar, M. Vijayakumar, R. Govindarajan, and P. Pushpangadan, “Ethnopharmacological approaches to wound healing-exploring medicinal plants of India,” Journal of Ethnopharmacology, vol. 114, no. 2, pp. 103–113, 2007.
[3]
R. Thakur, N. Jain, R. Pathak, and S. S. Sandhu, “Practices in wound healing studies of plants,” Evidence-Based Complementary and Alternative Medicine, vol. 2011, Article ID 438056, 17 pages, 2011.
[4]
A. Adetutu, W. A. Morgan, and O. Corcoran, “Antibacterial, antioxidant and fibroblast growth stimulation activity of crude extracts of Bridelia ferruginea leaf, a wound-healing plant of Nigeria,” Journal of Ethnopharmacology, vol. 133, no. 1, pp. 116–119, 2011.
[5]
K. Annan and P. J. Houghton, “Antibacterial, antioxidant and fibroblast growth stimulation of aqueous extracts of Ficus asperifolia Miq. and Gossypium arboreum L., wound-healing plants of Ghana,” Journal of Ethnopharmacology, vol. 119, no. 1, pp. 141–144, 2008.
[6]
B. S. Nayak, A. L. Udupa, and S. L. Udupa, “Effect of Ixora coccinea flowers on dead space wound healing in rats,” Fitoterapia, vol. 70, no. 3, pp. 233–236, 1999.
[7]
W. D. Ratnasooriya, S. A. Deraniyagala, G. Galhena, S. S. P. Liyanage, S. D. N. K. Bathige, and J. R. A. C. Jayakody, “Anti-inflammatory activity of the aqueous leaf extract of Ixora coccinea,” Pharmaceutical Biology, vol. 43, no. 2, pp. 147–152, 2005.
[8]
N. Selvaraj, B. Lakshmanan, P. M. Mazumder, M. Karuppasamy, S. S. Jena, and A. K. Pattnaik, “Evaluation of wound healing and antimicrobial potentials of Ixora coccinea root extract,” Asian Pacific Journal of Tropical Medicine, vol. 4, no. 12, pp. 959–963, 2011.
[9]
P. G. Latha and K. R. Panikkar, “Cytotoxic and antitumour principles from Ixora caccinea flowers,” Cancer Letters, vol. 130, no. 1-2, pp. 197–202, 1998.
[10]
J. Annapurna, P. V. S. Amarnath, D. A. Kumar, S. V. Ramakrishna, and K. V. Raghavan, “Antimicrobial activity of Ixora caccinea leaves,” Fitoterapia, vol. 74, no. 3, pp. 291–293, 2003.
[11]
T. O. Idowu, A. O. Ogundaini, A. O. Salau, E. M. Obuotor, M. Bezabih, and B. M. Abegaz, “Doubly linked, A-type proanthocyanidin trimer and other constituents of Ixora caccinea leaves and their antioxidant and antibacterial properties,” Phytochemistry, vol. 71, no. 17-18, pp. 2092–2098, 2010.
[12]
A. Torey, S. Sasidharan, L. Y. Latha, S. Sudhakaran, and S. Ramanathan, “Antioxidant activity and total phenolic content of methanol extracts of Ixora caccinea,” Pharmaceutical Biology, vol. 48, no. 10, pp. 1119–1123, 2010.
[13]
L. Y. Latha, I. Darah, K. Jain, and S. Sasidharan, “Pharmacological screening of methanolic extract of Ixora species,” Asian Pacific Journal of Tropical Biomedicine, vol. 2, no. 2, pp. 149–151, 2012.
[14]
K. R. Khandelwal, Practical Pharmacognosy, Techniques & Experiments, Nirali Prakashan, 11th edition, 2004.
[15]
E. A. Hayouni, K. Miled, S. Boubaker et al., “Hydroalcoholic extract based-ointment from Punica granatum L. peels with enhanced in vivo healing potential on dermal wounds,” Phytomedicine, vol. 18, no. 11, pp. 976–984, 2011.
[16]
I. M. C. Brighente, M. Dias, L. G. Verdi, and M. G. Pizzolatti, “Antioxidant activity and total phenolic content of some Brazilian species,” Pharmaceutical Biology, vol. 45, no. 2, pp. 156–161, 2007.
[17]
I. Süntar, E. K. Akkol, F. S. Enol, H. Keles, and I. E. Orhan, “Investigating wound healing, tyrosinase inhibitory and antioxidant activities of the ethanol extracts of Salvia cryptantha and Salvia cyanescens using in vivo and in vitro experimental models,” Journal of Ethnopharmacology, vol. 135, no. 1, pp. 71–77, 2011.
[18]
X. H. Wang and J. T. Dai, “A comparative study on antioxidant activity of water and ethanol extracts of ten Chinese herbs,” Journal of Medicinal Plants Research, vol. 6, no. 11, pp. 2210–2215, 2012.
[19]
S. Maurya and D. Singh, “Quantitative analysis of total phenolic content in Adhatoda vasica nees extracts,” International Journal of PharmTech Research, vol. 2, no. 4, pp. 2403–2406, 2010.
[20]
OECD guideline for testing of chemicals-402, Acute Dermal Toxicity, 1987.
[21]
A. Upadhyay, P. Chattopadhyay, D. Goyary, P. M. Mazumder, and V. Veer, “Eleutherine indica L. accelerates in vivo cutaneous wound healing by stimulating Smad-mediated collagen production,” Journal of Ethnopharmacology, vol. 146, no. 2, pp. 490–494, 2013.
[22]
P. G. Bowler, B. I. Duerden, and D. G. Armstrong, “Wound microbiology and associated approaches to wound management,” Clinical Microbiology Reviews, vol. 14, no. 2, pp. 244–269, 2001.
[23]
M. Sch？fer and S. Werner, “Oxidative stress in normal and impaired wound repair,” Pharmacological Research, vol. 58, no. 2, pp. 165–171, 2008.
[24]
A. Shukla, A. M. Rasik, and G. K. Patnaik, “Depletion of reduced glutathione, ascorbic acid, vitamin E and antioxidant defence enzymes in a healing cutaneous wound,” Free Radical Research, vol. 26, no. 2, pp. 93–101, 1997.
[25]
B. P. Mudge, C. Harris, R. R. Gilmont, B. S. Adamson, and R. S. Rees, “Role of glutathione redox dysfunction in diabetic wounds,” Wound Repair and Regeneration, vol. 10, no. 1, pp. 52–58, 2002.
[26]
Y. Mimura, H. Ihn, M. Jinnin, Y. Asano, K. Yamane, and K. Tamaki, “Epidermal growth factor induces fibronectin expression in human dermal fibroblasts via protein kinase C δ signaling pathway,” The Journal of Investigative Dermatology, vol. 122, no. 6, pp. 1390–1398, 2004.
[27]
T. Kondo and Y. Ishida, “Molecular pathology of wound healing,” Forensic Science International, vol. 203, no. 1–3, pp. 93–98, 2010.
[28]
M. Schiller, D. Javelaud, and A. Mauviel, “TGF-β-induced SMAD signaling and gene regulation: consequences for extracellular matrix remodeling and wound healing,” Journal of Dermatological Science, vol. 35, no. 2, pp. 83–92, 2004.
[29]
J. Massagué and R. R. Gomis, “The logic of TGF-β signaling,” FEBS Letters, vol. 580, no. 12, pp. 2811–2820, 2006.
