Phytosomes of Naphthoquinone Enriched Extract of Root bark of Onosma echioides Exhibit Wound Healing Activity in Rats
Abstract
The present study is aimed at evaluation of phytosomal gel of the petroleum ether extract of root bark of Onosma echiodes for wound healing activity in rats. Extract of root bark of O. echioides was standardized by isolated naphthoquinone dimer using HPTLC. Phytosomes (equivalent to 2% w/w of naphthoquinones) of the standardized extract were prepared by thin film hydration technique. The wound healing efficacy of the formulation was evaluated in rats by inflicting excision and incision wounds followed by treatment of the wounds topically. The parameters evaluated for healing included determination of breaking strength and tensile strength of healed skin for incision model and percentage wound contraction, hydroxyproline content, granulation tissue free radicals and catalase in excision wound model. The formulation treated group showed a significant healing (p<0.005) of both the excision and incision wounds with respect to wound contraction and tensile strength respectively, as compared to vehicle treated group. The oxidative stress of the granulation tissue was also found to be reduced as indicated by reduced lipid peroxidation and increase in catalase activity. The phytosomal gel of O. echioides effectively exhibited wound healing effect.
References
Ali-Seyed, M. & Siddiqua, A. 2020. Calotropis-A multi-potential plant to humankind: Special focus on its wound healing efficacy. Biocatalysis and Agricultural Biotechnology, 101725.
Awasthi, R., Kulkarni, G. & Pawar, V. K. 2011. Phytosomes: an approach to increase the bioavailability of plant extracts. International journal of pharmacy and pharmaceutical sciences, 3, 1-3.
Barreto, G., Ashraf, G. M. & Siddiqui, H. H. Beneficial effects of n‐hexane bark extract of O echioides L. on diabetic peripheral neuropathy.
Bennett, N. T. & Schultz, G. S. 1993a. Growth factors and wound healing: biochemical properties of growth factors and their receptors. The American Journal of Surgery, 165, 728-737.
Bennett, N. T. & Schultz, G. S. 1993b. Growth factors and wound healing: Part II. Role in normal and chronic wound healing. The American journal of surgery, 166, 74-81.
Brand-Williams, W., Cuvelier, M.-E. & Berset, C. 1995. Use of a free radical method to evaluate antioxidant activity. LWT-Food science and Technology, 28, 25-30.
Buchbauer, G., Jirovetz, L. & Kaul, V. K. 1995. Volatiles of the Absolute of Cestrum nocturnum L. Journal of Essential Oil Research, 7, 5-9.
Cai, L., Xiong, X., Kong, X. & Xie, J. 2017. The role of the lysyl oxidases in tissue repair and remodeling: a concise review. Tissue engineering and regenerative medicine, 14, 15-30.
Dev, S. K., Choudhury, P., Srivastava, R. & Sharma, M. 2019. Antimicrobial, anti-inflammatory and wound healing activity of polyherbal formulation. Biomedicine & Pharmacotherapy, 111, 555-567.
Direito, R., Reis, C., Roque, L., Gonçalves, M., Sanches-Silva, A., Gaspar, M. M., Pinto, R., Rocha, J., Sepodes, B. & Rosário Bronze, M. 2019. Phytosomes with persimmon (Diospyros kaki l.) extract: Preparation and preliminary demonstration of in vivo tolerability. Pharmaceutics, 11, 296.
Dorsett-Martin, W. A. & Wysocki, A. B. 2008. Rat models of skin wound healing. Sourcebook of models for biomedical research. Springer.
Dorsett‐Martin, W. A. 2004. Rat models of skin wound healing: a review. Wound Repair and Regeneration, 12, 591-599.
Dwivedi, D., Dwivedi, M., Malviya, S. & Singh, V. 2017. Evaluation of wound healing, anti-microbial and antioxidant potential of Pongamia pinnata in wistar rats. Journal of traditional and complementary medicine, 7, 79-85.
Ghosh, S., Samanta, A., Mandal, N. B., Bannerjee, S. & Chattopadhyay, D. 2012. Evaluation of the wound healing activity of methanol extract of Pedilanthus tithymaloides (L.) Poit leaf and its isolated active constituents in topical formulation. Journal of Ethnopharmacology, 142, 714-722.
Grada, A., Mervis, J. & Falanga, V. 2018. Research techniques made simple: animal models of wound healing. Journal of Investigative Dermatology, 138, 2095-2105. e1.
Guo, M., An, F., Yu, H., Wei, X., Hong, M. & Lu, Y. 2017. Comparative effects of schisandrin A, B, and C on Propionibacterium acnes-induced, NLRP3 inflammasome activation-mediated IL-1β secretion and pyroptosis. Biomedicine & Pharmacotherapy, 96, 129-136.
Gupta, A., Singh, R. L. & Raghubir, R. 2002. Antioxidant status during cutaneous wound healing in immunocompromised rats. Molecular and Cellular Biochemistry, 241, 1-7.
Harding, K. G., Moore, K. & Phillips, T. J. 2005. Wound chronicity and fibroblast senescence–implications for treatment. International wound journal, 2, 364-368.
Jain, P. G., Mahajan, U. B., Shinde, S. D. & Surana, S. J. 2018. Cardioprotective role of FA against isoproterenol induced cardiac toxicity. Molecular biology reports, 45, 1357-1365.
Jain, P. G., Nayse, P. G., Patil, D. J., Shinde, S. D. & Surana, S. J. 2020. The possible antioxidant capabilities of formononetin in guarding against streptozotocin-induced diabetic nephropathy in rats. Future Journal of Pharmaceutical Sciences, 6, 1-9.
Jiang, W. G., Sanders, A. J., Ruge, F. & Harding, K. G. 2012. Influence of interleukin-8 (IL-8) and IL-8 receptors on the migration of human keratinocytes, the role of PLC-γ and potential clinical implications. Experimental and therapeutic medicine, 3, 231-236.
Kumar, B., Vijayakumar, M., Govindarajan, R. & Pushpangadan, P. 2007. Ethnopharmacological approaches to wound healing—exploring medicinal plants of India. Journal of ethnopharmacology, 114, 103-113.
Kumar, N., Kumar, R. & Kishore, K. 2013. O L.: A review of phytochemistry and ethnopharmacology. Pharmacognosy reviews, 7, 140.
Mackay, D. J. & Miller, A. L. 2003. Nutritional Support For Wound Healing. Alternative Medicine Review, 8.
Moyer, K., Saggers, G., Allison, G., Mackay, D. & Ehrlich, H. 2002. Effects of interleukin‐8 on granulation tissue maturation. Journal of cellular physiology, 193, 173-179.
Nikita, G., Vivek, P. & Chhaya, G. 2015. Wound-healing activity of an oligomer of alkannin/shikonin, isolated from root bark of O echioides. Natural product research, 29, 1584-1588.
Ozaki, Y., Ohno, A., Saito, Y. & Satake, M. 1994. Accelerative effect of shikonin, alkannin and acetylshikonin on the proliferation of granulation tissue in rats. Biological and Pharmaceutical Bulletin, 17, 1075-1077.
Parente, L. M. L., Lino Júnior, R. D. S., Tresvenzol, L. M. F., Vinaud, M. C., De Paula, J. R. & Paulo, N. M. 2012. Wound healing and anti-inflammatory effect in animal models of Calendula officinalis L. growing in Brazil. Evidence-based complementary and alternative medicine, 2012.
Pastar, I., Stojadinovic, O., Yin, N. C., Ramirez, H., Nusbaum, A. G., Sawaya, A., Patel, S. B., Khalid, L., Isseroff, R. R. & Tomic-Canic, M. 2014. Epithelialization in wound healing: a comprehensive review. Advances in wound care, 3, 445-464.
Paul, T. S., Das, B. B., Talekar, Y. P. & Banerjee, S. 2020. Exploration of the role of a lithophytic fern, Pteris vittata L. in wound tissue regeneration and remodelling of genes in hyperglycaemic rat model. Clinical Phytoscience, 6, 1-12.
Rumalla, V. K. & Borah, G. L. 2001. Cytokines, growth factors, and plastic surgery. Plastic and reconstructive surgery, 108, 719-733.
Schultz, G., Chin, G., Moldawer, L. & Diegelmann, R. 2011. Ch23 Mechanisms of Vascular Disease, University of Adelaide Press.
Sharma, S. & Sahu, A. N. 2016. Development, characterization, and evaluation of hepatoprotective effect of Abutilon indicum and Piper longum phytosomes. Pharmacognosy research, 8, 29.
Shinde, S. D., Cheke, R. S., Tathe, P. R., Jain, P. G. & NARKHEDE, R. R. 2020. The Berberis aristata Ameliorates oxazolone induced contact dermatitis: in-vivo and in silico evidences. Advances in Traditional Medicine, 1-8.
Shinde, S. D., Jain, P. G., Cheke, R. S., Surana, S. J. & Gunjegaonkar, S. M. 2021. Abrogation of cisplatin-induced nephrotoxicity in rats and HEK-293 cell lines by formononetin: in vivo and in vitro study. Comparative Clinical Pathology, 1-9.
Shoaib, A., Dixit, R. K., Badruddeen, Rahman, M. A., Bagga, P., Kaleem, S., Siddiqui, S., Arshad, M. & Siddiqui, H. H. 2019. Cure of human diabetic neuropathy by HPLC validated bark extract of O echioides L. root. Natural product research, 33, 2699-2703.
Shoaib, A., Siddiqui, H. H., Badruddeen, A. R. & Dixit, R. K. 2017. Physicochemical, phytochemical and high-performance thin layer chromatography analysis of the root barks of O echioides. Asian J Pharm Clin Res, 10, 196-199.
Shrivastav, A., Mishra, A. K., Ali, S. S., Ahmad, A., Abuzinadah, M. F. & Khan, N. A. 2018. In vivo models for assesment of wound healing potential: A systematic review. Wound medicine, 20, 43-53.
Singh, I. P., Ahmad, F., Chatterjee, D., Bajpai, R. & Sengar, N. 2021. Natural products: drug discovery and development. Drug Discovery and Development: From Targets and Molecules to Medicines, 11-65.
Swamy, H. K., Krishna, V., Shankarmurthy, K., Rahiman, B. A., Mankani, K., Mahadevan, K., Harish, B. & Naika, H. R. 2007. Wound healing activity of embelin isolated from the ethanol extract of leaves of Embelia ribes Burm. Journal of ethnopharmacology, 109, 529-534.
Wu, Y., Wang, J., Scott, P. G. & Tredget, E. E. 2007. Bone marrow‐derived stem cells in wound healing: a review. Wound Repair and Regeneration, 15, S18-S26.