Molecular Concept of Diabetic Wound Healing: Effective Role of Herbal Remedies

Author(s): Amro Mohamed Soliman, Seong Lin Teoh, Norzana Abd Ghafar, Srijit Das*.

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 19 , Issue 5 , 2019

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Graphical Abstract:


The incidence of diabetes mellitus (DM) is on the rise, worldwide. One of the main complications in DM is delayed wound healing and it often requires amputation. Various drugs were used to treat DM but they presented with adverse effects. Often, patients failed to comply with such treatment. This opened the door for complementary and alternative medicine. In the present review, we explored the molecular concept of wound healing occurring in different stages with special emphasis to DM. We also highlighted the potential herbal products such as NF3 (Chinese 2-Herb Formula), Zicao, Jing Wan Hong ointment, Aleo vera, mixture of Adiantum capillus-veneris, Commiphora molmol, Aloe vera, and henna, Phenol-rich compound sweet gel, Jinchuang ointment, San-huang-sheng-fu (S) oil, Yi Bu A Jie extract, Astragali Radix (AR) and Rehmanniae Radix (RR), Yiqi Huayu, Tangzu yuyang ointment, Shengji Huayu recipe, Angelica sinensis, Lithospermun erythrorhison, Hippophae rhamnoides L., Curcuma longa and Momordica charantia that could be used effectively to treat DM wounds. Future clinical trials are needed for designing potential drugs which may be effective in treating DM wounds.

Keywords: DM, treatment, wound, molecular biology, natural products, healing.

SMC. Standards of Medical Care in Diabetes-2016: Summary of Revisions. Diabetes Care, 2016, 39(Suppl. 1), S4-S5.
Chawla, A.; Chawla, R.; Jaggi, S. Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum? Indian J. Endocrinol. Metab., 2016, 20(4), 546-551.
ADM, American Diabetes Association. Standards of medical care in diabetes-2014. Diabetes Care, 2014, 37(Suppl. 1), S14-S80.
Han, Y.F.; Sun, T.J.; Han, Y.Q.; Xu, G.; Liu, J.; Tao, R. Clinical perspectives on mesenchymal stem cells promoting wound healing in diabetes mellitus patients by inducing autophagy. Eur. Rev. Med. Pharmacol. Sci., 2015, 19(14), 2666-2670.
CDA Types of diabetes. Toronto (ON): Canadian Diabetes Association. [31 MARCH 2017]
BrittleDiabetis, Brittle diabetes (labile diabetes). United Kingdom:[31 MARCH 2017]. 2015..
Khodaeian, M.; Enayati, S.; Tabatabaei-Malazy, O.; Amoli, M.M. Association between genetic variants and diabetes mellitus in iranian populations: A Systematic review of observational studies. J. Diabetes Res., 2015, 2015, 585917.
Wicker, L.S.; Clark, J.; Fraser, H.I.; Garner, V.E.; Gonzalez-Munoz, A.; Healy, B.; Howlett, S.; Hunter, K.; Rainbow, D.; Rosa, R.L.; Smink, L.J.; Todd, J.A.; Peterson, L.B. Type 1 diabetes genes and pathways shared by humans and NOD mice. J. Autoimmun., 2005, 25, 29-33.
Banatvala, J.E.; Bryant, J.; Schernthaner, G.; Borkenstein, M.; Schober, E.; Brown, D.; De Silva, L.M.; Menser, M.A.; Silink, M. Coxsackie B, mumps, rubella, and cytomegalovirus specific IgM responses in patients with juvenile-onset insulin-dependent diabetes mellitus in Britain, Austria, and Australia. Lancet, 1985, 1(8443), 1409-1412.
Honeyman, M.C.; Coulson, B.S.; Stone, N.L.; Gellert, S.A.; Goldwater, P.N.; Steele, C.E.; Couper, J.J.; Tait, B.D.; Colman, P.G.; Harrison, L.C. Association between rotavirus infection and pancreatic islet autoimmunity in children at risk of developing type 1 diabetes. Diabetes, 2000, 49(8), 1319-1324.
Honeyman, M.C.; Stone, N.L.; Harrison, L.C. T-cell epitopes in type 1 diabetes autoantigen tyrosine phosphatase IA-2: Potential for mimicry with rotavirus and other environmental agents. Mol. Med., 1998, 4(4), 231-239.
Lempainen, J.; Vaarala, O.; Makela, M.; Veijola, R.; Simell, O.; Knip, M.; Hermann, R.; Ilonen, J. Interplay between PTPN22 C1858T polymorphism and cow’s milk formula exposure in type 1 diabetes. J. Autoimmun., 2009, 33(2), 155-164.
Group, T.S. Study design of the trial to reduce IDDM in the genetically at risk (TRIGR). Pediat. Diabetes, 2007, 8(3), 117-137.
Wherrett, D.K.; Daneman, D. Prevention of type 1 diabetes. Endocrinol. Metab. Clin. North Am., 2009, 38(4), 777-790.
Tabish, S.A. Is diabetes becoming the biggest epidemic of the twenty-first century? Intl. J. Health Sci. (Qassim), 2007, 1(2), V-VIII.
Jenkins, A.B.; Campbell, L.V. The genetics and pathophysiology of diabetes mellitus type II. J. Inherit. Metab. Dis., 2004, 27(3), 331-347.
Porte, D., Jr Banting lecture 1990. Beta-cells in type II diabetes mellitus. Diabetes, 1991, 40(2), 166-180.
Mitrakou, A.; Kelley, D.; Mokan, M.; Veneman, T.; Pangburn, T.; Reilly, J.; Gerich, J. Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance. New . Engl. J. Med., 1992, 326(1), 22-29.
Kahn, S.E. Clinical review 135: The importance of beta-cell failure in the development and progression of type 2 diabetes. J. Clin. Endocrinol. Metab., 2001, 86(9), 4047-4058.
DeFronzo, R.A.; Ferrannini, E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes care, 1991, 14(3), 173-194.
Kruszynska, Y.T.; Olefsky, J.M. Cellular and molecular mechanisms of non-insulin dependent diabetes mellitus. J. Investig. Med., 1996, 44(8), 413-428.
Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults--The Evidence Report. National Institutes of Health. Obes. Res., 1998, 6(Suppl. 2), 51S-209S.
Beard, J.C.; Ward, W.K.; Halter, J.B.; Wallum, B.J.; Porte, D., Jr Relationship of islet function to insulin action in human obesity. J. Clin. Endocrinol. Metab., 1987, 65(1), 59-64.
Olefsky, J.; Farquhar, J.W.; Reaven, G. Relationship between fasting plasma insulin level and resistance to insulin-mediated glucose uptake in normal and diabetic subjects. Diabetes, 1973, 22(7), 507-513.
Rosenbloom, A.L.; Joe, J.R.; Young, R.S.; Winter, W.E. Emerging epidemic of type 2 diabetes in youth. Diabetes Care, 1999, 22(2), 345-354.
Dabelea, D.; Pettitt, D.J.; Jones, K.L.; Arslanian, S.A. Type 2 diabetes mellitus in minority children and adolescents. An emerging problem. Endocrinol. Metab. Clin. North Am., 1999, 28(4), 709-729. viii.
Sinha, R.; Fisch, G.; Teague, B.; Tamborlane, W.V.; Banyas, B.; Allen, K.; Savoye, M.; Rieger, V.; Taksali, S.; Barbetta, G.; Sherwin, R.S.; Caprio, S. Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. New . Engl. J. Med., 2002, 346(11), 802-810.
Reinke, J.M.; Sorg, H. Wound repair and regeneration. Eur. Surg. Res., 2012, 49(1), 35-43.
Landen, N.X.; Li, D.; Stahle, M. Transition from inflammation to proliferation: A critical step during wound healing. Cell. Mol. Life Sci., 2016, 73(20), 3861-3885.
Mustoe, T.A.; O’Shaughnessy, K.; Kloeters, O. Chronic wound pathogenesis and current treatment strategies: A unifying hypothesis. Plast. Reconstr. Surg., 2006, 117(7)(Suppl.), 35S-41S.
Sen, C.K.; Gordillo, G.M.; Roy, S.; Kirsner, R.; Lambert, L.; Hunt, T.K.; Gottrup, F.; Gurtner, G.C.; Longaker, M.T. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen., 2009, 17(6), 763-771.
Sun, B.K.; Siprashvili, Z.; Khavari, P.A. Advances in skin grafting and treatment of cutaneous wounds. Science, 2014, 346(6212), 941-945.
Robson, M.C.; Steed, D.L.; Franz, M.G. Wound healing: Biologic features and approaches to maximize healing trajectories. Curr. Prob. Surg., 2001, 38(2), 72-140.
Strodtbeck, F. Physiology of wound healing. Newborn Infant Nurs. Rev., 2001, 1(1), 43-52.
Martin, P. Wound healing--aiming for perfect skin regeneration. Science, 1997, 276(5309), 75-81.
Woo, Y.C.; Park, S.S.; Subieta, A.R.; Brennan, T.J. Changes in tissue pH and temperature after incision indicate acidosis may contribute to postoperative pain. Anesthesiology, 2004, 101(2), 468-475.
Werner, S.; Grose, R. Regulation of wound healing by growth factors and cytokines. Physiol. Rev., 2003, 83(3), 835-870.
Eming, S.A.; Martin, P.; Tomic-Canic, M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci. Transl. Med., 2014, 6(265), 265-266.
Strbo, N.; Yin, N.; Stojadinovic, O. Innate and Adaptive Immune Responses in Wound Epithelialization. Adv. Wound Care (New Rochelle), 2014, 3(7), 492-501.
Kaisho, T.; Akira, S. Toll-like receptor function and signaling. J. Allergy Clin. Immunol., 2006, 117(5), 979-987.
Takeuchi, O.; Akira, S. Pattern recognition receptors and inflammation. Cell, 2010, 140(6), 805-820.
Sinno, H.; Prakash, S. Complements and the wound healing cascade: An updated review. Plast. Surg. Intl., 2013, 2013, 146764.
Vestweber, D. How leukocytes cross the vascular endothelium. Nat. Rev. Immunol., 2015, 15(11), 692-704.
Wilgus, T.A.; Roy, S.; McDaniel, J.C. Neutrophils and wound repair: Positive actions and negative reactions. Adv. Wound Care (New Rochelle), 2013, 2(7), 379-388.
Lipsky, P.E. Systemic lupus erythematosus: An autoimmune disease of B cell hyperactivity. Nat. Immunol., 2001, 2(9), 764-766.
Cowin, A.J.; Brosnan, M.P.; Holmes, T.M.; Ferguson, M.W. Endogenous inflammatory response to dermal wound healing in the fetal and adult mouse. Dev. Dyn., 1998, 212(3), 385-393.
Iwata, Y.; Yoshizaki, A.; Komura, K.; Shimizu, K.; Ogawa, F.; Hara, T.; Muroi, E.; Bae, S.; Takenaka, M.; Yukami, T.; Hasegawa, M.; Fujimoto, M.; Tomita, Y.; Tedder, T.F.; Sato, S. CD19, a response regulator of B lymphocytes, regulates wound healing through hyaluronan-induced TLR4 signaling. Am. J. Pathol., 2009, 175(2), 649-660.
Gillitzer, R.; Goebeler, M. Chemokines in cutaneous wound healing. J. Leukoc. Biol., 2001, 69(4), 513-521.
Loots, M.A.; Lamme, E.N.; Zeegelaar, J.; Mekkes, J.R.; Bos, J.D.; Middelkoop, E. Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds. J. Invest. Dermatol., 1998, 111(5), 850-857.
Nosbaum, A.; Prevel, N.; Truong, H.A.; Mehta, P.; Ettinger, M.; Scharschmidt, T.C.; Ali, N.H.; Pauli, M.L.; Abbas, A.K.; Rosenblum, M.D. Cutting edge: Regulatory T cells facilitate cutaneous wound healing. J. Immunol., 2016, 196(5), 2010-2014.
Merad, M.; Ginhoux, F.; Collin, M. Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat. Rev. Immunol., 2008, 8(12), 935-947.
Stojadinovic, O.; Yin, N.; Lehmann, J.; Pastar, I.; Kirsner, R.S.; Tomic-Canic, M. Increased number of Langerhans cells in the epidermis of diabetic foot ulcers correlates with healing outcome. Immunol. Res., 2013, 57(1-3), 222-228.
Gregorio, J.; Meller, S.; Conrad, C.; Di Nardo, A.; Homey, B.; Lauerma, A.; Arai, N.; Gallo, R.L.; Digiovanni, J.; Gilliet, M. Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons. J. Experiment. Med., 2010, 207(13), 2921-2930.
Bauer, S.M.; Bauer, R.J.; Velazquez, O.C. Angiogenesis, vasculogenesis, and induction of healing in chronic wounds. Vasc. Endovascul Surg., 2005, 39(4), 293-306.
Arnold, F.; West, D.C. Angiogenesis in wound healing. Pharmacol. Ther., 1991, 52(3), 407-422.
Endrich, B.; Menger, M.D. Regeneration of the microcirculation during wound healing? Unfallchirurg, 2000, 103(11), 1006-1008.
Madden, J.W.; Peacock, E.E., Jr Studies on the biology of collagen during wound healing. 3. Dynamic metabolism of scar collagen and remodeling of dermal wounds. Ann. Surg., 1971, 174(3), 511-520.
Lau, K.; Paus, R.; Tiede, S.; Day, P.; Bayat, A. Exploring the role of stem cells in cutaneous wound healing. Exp. Dermatol., 2009, 18(11), 921-933.
Miller, S.J.; Burke, E.M.; Rader, M.D.; Coulombe, P.A.; Lavker, R.M. Re-epithelialization of porcine skin by the sweat apparatus. J. Invest. Dermatol., 1998, 110(1), 13-19.
Roh, C.; Lyle, S. Cutaneous stem cells and wound healing. Pediatr. Res., 2006, 59(4 Pt 2), 100R-103R.
Jacinto, A.; Martinez-Arias, A.; Martin, P. Mechanisms of epithelial fusion and repair. Nat. Cell Biol., 2001, 3(5), E117-E123.
Clark, R.A.; Lanigan, J.M.; DellaPelle, P.; Manseau, E.; Dvorak, H.F.; Colvin, R.B. Fibronectin and fibrin provide a provisional matrix for epidermal cell migration during wound reepithelialization. J. Invest. Dermatol., 1982, 79(5), 264-269.
Clark, R.A. Fibronectin matrix deposition and fibronectin receptor expression in healing and normal skin. J. Invest. Dermatol., 1990, 94(6)(Suppl.), 128S-134S.
Li, J.; Zhang, Y.P.; Kirsner, R.S. Angiogenesis in wound repair: angiogenic growth factors and the extracellular matrix. Microsc. Res. Tech., 2003, 60(1), 107-114.
Asahara, T.; Masuda, H.; Takahashi, T.; Kalka, C.; Pastore, C.; Silver, M.; Kearne, M.; Magner, M.; Isner, J.M. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ. Res., 1999, 85(3), 221-228.
Schultz, G.S.; Wysocki, A. Interactions between extracellular matrix and growth factors in wound healing. Wound Repair Regen., 2009, 17(2), 153-162.
Hinz, B.; Phan, S.H.; Thannickal, V.J.; Galli, A.; Bochaton-Piallat, M.L.; Gabbiani, G. The myofibroblast: One function, multiple origins. Am. J. Pathol., 2007, 170(6), 1807-1816.
Gurtner, G.C.; Evans, G.R. Advances in head and neck reconstruction. Plast. Reconstr. Surg., 2000, 106(3), 672-682.
Tziotzios, C.; Profyris, C.; Sterling, J. Cutaneous scarring: Pathophysiology, molecular mechanisms, and scar reduction therapeutics Part II. Strategies to reduce scar formation after dermatologic procedures. J. Am. Acad. Dermatol., 2012, 66(1), 13-24.
Profyris, C.; Tziotzios, C.; Do Vale, I. Cutaneous scarring: Pathophysiology, molecular mechanisms, and scar reduction therapeutics Part I. The molecular basis of scar formation. J. Am. Acad. Dermatol., 2012, 66(1), 1-10.
Tandara, A.A.; Mustoe, T.A. Oxygen in wound healing--more than a nutrient. World J. Surg., 2004, 28(3), 294-300.
Mathieu, D.; Linke, J-C.; Wattel, F. Non-Healing Wounds; Handbook on Hyperbaric Med, 2006, pp. 401-427.
Woo, K.; Ayello, E.A.; Sibbald, R.G. The edge effect: current therapeutic options to advance the wound edge. Adv. Skin Wound Care, 2007, 20(2), 99-117.
Brem, H.; Tomic-Canic, M. Cellular and molecular basis of wound healing in diabetes. J. Clin. Invest., 2007, 117(5), 1219-1222.
Gallagher, K.A.; Liu, Z.J.; Xiao, M.; Chen, H.; Goldstein, L.J.; Buerk, D.G.; Nedeau, A.; Thom, S.R.; Velazquez, O.C. Diabetic impairments in NO-mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF-1 alpha. J. Clin. Invest., 2007, 117(5), 1249-1259.
Quattrini, C.; Jeziorska, M.; Boulton, A.J.; Malik, R.A. Reduced vascular endothelial growth factor expression and intra-epidermal nerve fiber loss in human diabetic neuropathy. Diabetes care, 2008, 31(1), 140-145.
Kirchner, L.M.; Meerbaum, S.O.; Gruber, B.S.; Knoll, A.K.; Bulgrin, J.; Taylor, R.A.; Schmidt, S.P. Effects of vascular endothelial growth factor on wound closure rates in the genetically diabetic mouse model. Wound Repair Regen., 2003, 11(2), 127-131.
Galiano, R.D.; Tepper, O.M.; Pelo, C.R.; Bhatt, K.A.; Callaghan, M.; Bastidas, N.; Bunting, S.; Steinmetz, H.G.; Gurtner, G.C. Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. Am. J. Pathol., 2004, 164(6), 1935-1947.
Edwards, R.; Harding, K.G. Bacteria and wound healing. Curr. Opin. Infect. Dis., 2004, 17(2), 91-96.
Bjarnsholt, T.; Kirketerp-Moller, K.; Jensen, P.O.; Madsen, K.G.; Phipps, R.; Krogfelt, K.; Hoiby, N.; Givskov, M. Why chronic wounds will not heal: A novel hypothesis. Wound Repair Regen., 2008, 16(1), 2-10.
Menke, N.B.; Ward, K.R.; Witten, T.M.; Bonchev, D.G.; Diegelmann, R.F. Impaired wound healing. Clin. Dermatol., 2007, 25(1), 19-25.
Godbout, J.P.; Glaser, R. Stress-induced immune dysregulation: Implications for wound healing, infectious disease and cancer. J. Neuroimmune Pharmacol., 2006, 1(4), 421-427.
Boyapati, L.; Wang, H.L. The role of stress in periodontal disease and wound healing. Periodontol. 2000, 2007, 44, 195-210.
Kiecolt-Glaser, J.K.; Marucha, P.T.; Malarkey, W.B.; Mercado, A.M.; Glaser, R. Slowing of wound healing by psychological stress. Lancet, 1995, 346(8984), 1194-1196.
Marucha, P.T.; Kiecolt-Glaser, J.K.; Favagehi, M. Mucosal wound healing is impaired by examination stress. Psychosomat. Med., 1998, 60(3), 362-365.
Galkowska, H.; Olszewski, W.L.; Wojewodzka, U.; Rosinski, G.; Karnafel, W. Neurogenic factors in the impaired healing of diabetic foot ulcers. J. Surg. Res., 2006, 134(2), 252-258.
Gary Sibbald, R.; Woo, K.Y. The biology of chronic foot ulcers in persons with diabetes. Diabetes Metabol. Res. Rev., 2008, 24(Suppl. 1), S25-S30.
Maritim, A.C.; Sanders, R.A.; Watkins, J.B., 3rd Diabetes, oxidative stress, and antioxidants: A review. J. Biochem. Mol. Toxicol., 2003, 17(1), 24-38.
Jankovic, A.; Ferreri, C.; Filipovic, M.; Ivanovic-Burmazovic, I.; Stancic, A.; Otasevic, V.; Korac, A.; Buzadzic, B.; Korac, B. Targeting the superoxide/nitric oxide ratio by L-arginine and SOD mimic in diabetic rat skin. Free Radic. Res., 2016, 50(Suppl. 1), S51-S63.
Kowluru, R.A.; Atasi, L.; Ho, Y.S. Role of mitochondrial superoxide dismutase in the development of diabetic retinopathy. Invest. Ophthalmol. Vis. Sci., 2006, 47(4), 1594-1599.
Pessoa, A.F.; Florim, J.C.; Rodrigues, H.G.; Andrade-Oliveira, V.; Teixeira, S.A.; Vitzel, K.F.; Curi, R.; Saraiva Camara, N.O.; Muscara, M.N.; Lamers, M.L.; Santos, M.F. Oral administration of antioxidants improves skin wound healing in diabetic mice. Wound Repair Regen., 2016, 24(6), 981-993.
Game, F.; Apelqvist, J.; Attinger, C.; Hartemann, A.; Hinchliffe, R.; Löndahl, M.; Price, P.E.; Jeffcoate, W. IWGDF guidance on use of interventions to enhance the healing of chronic ulcers of the foot in diabetes. Diabetes Metabol. Res. Rev., 2016, 32(S1), 75-83.
Wong, M.W.; Leung, P.C.; Wong, W.C. Limb salvage in extensive diabetic foot ulceration-a preliminary clinical study using simple debridement and herbal drinks. Hong Kong Med. J., 2001, 7(4), 403-407.
Tam, J.C.; Ko, C.H.; Lau, K.M.; To, M.H.; Kwok, H.F.; Siu, W.S.; Lau, C.P.; Chan, W.Y.; Leung, P.C.; Fung, K.P.; Lau, C.B. Enumeration and functional investigation of endothelial progenitor cells in neovascularization of diabetic foot ulcer rats with a Chinese 2-herb formula. J. Diabetes, 2015, 7(5), 718-728.
Tam, J.C.; Ko, C.H.; Koon, C.M.; Cheng, Z.; Lok, W.H.; Lau, C.P.; Leung, P.C.; Fung, K.P.; Chan, W.Y.; Lau, C.B. Identification of target genes involved in wound healing angiogenesis of endothelial cells with the treatment of a chinese 2-herb formula. PLoS One, 2015, 10(10), e0139342.
Akkol, E.K.; Koca, U.; Peşin, I.; Yılmazer, D.; Toker, G.; Yeşilada, E. Exploring the wound healing activity of Arnebia densiflora (Nordm.) Ledeb. by in vivo models. J. Ethnopharmacol., 2009, 124(1), 137-141.
Sidhu, G.S.; Singh, A.K.; Banaudha, K.K.; Gaddipati, J.P.; Patnaik, G.K.; Maheshwari, R.K. Arnebin-1 Accelerates Normal and Hydrocortisone- Induced Impaired Wound Healing. J. Investigat. Dermatol., 113(5), 773-781.
Zeng, Z.; Zhu, B.H. Arnebin-1 promotes the angiogenesis of human umbilical vein endothelial cells and accelerates the wound healing process in diabetic rats. J. Ethnopharmacol., 2014, 154(3), 653-662.
Zeng, Z.; Huang, W.D.; Gao, Q.; Su, M.L.; Yang, Y.F.; Liu, Z.C.; Zhu, B.H. Arnebin-1 promotes angiogenesis by inducing eNOS, VEGF and HIF-1alpha expression through the PI3K-dependent pathway. Intl. J. Mol. Med., 2015, 36(3), 685-697.
Jin, S.; Zhang, M.; Gao, Y.; Zhang, X.; Cui, G.; Zhang, Y. The efficacy of Jing Wan Hong ointment for nerve injury diabetic foot ulcer and its mechanisms. J. Diabetes Res., 2014, 2014, 259412.
Sun, Y.H.; Yu, D.N.; Chen, X.; Hu, X.H.; Zhang, G.A.; Yan, R.Y.; Tan, F.J. Preliminary study on the improvement of wound microcirculation and retrospection on several methods of the management of deep partial thickness burn wound. Zhonghua Shao Shang Za Zhi, 2005, 21(1), 17-20.
Nilforoushzadeh, M.A.; Javanmard, S.H.; Ghanadian, M.; Asghari, G.; Jaffary, F.; Yakhdani, A.F.; Dana, N.; Fatemi, S.A. The Effects of adiantum capillus-veneris on wound healing: An experimental in vitro evaluation. Intl. J. Prev. Med., 2014, 5(10), 1261-1268.
Fraternale, D.; Sosa, S.; Ricci, D.; Genovese, S.; Messina, F.; Tomasini, S.; Montanari, F.; Marcotullio, M.C. Anti-inflammatory, antioxidant and antifungal furanosesquiterpenoids isolated from Commiphora erythraea (Ehrenb.) Engl. resin. Fitoterapia, 2011, 82(4), 654-661.
Atiba, A.; Ueno, H.; Uzuka, Y. The effect of aloe vera oral administration on cutaneous wound healing in type 2 diabetic rats. J. Vet. Med. Sci., 2011, 73(5), 583-589.
Nayak, B.S.; Isitor, G.; Davis, E.M.; Pillai, G.K. The evidence based wound healing activity of Lawsonia inermis Linn. Phytother. Res., 2007, 21(9), 827-831.
Mikhaeil, B.R.; Badria, F.A.; Maatooq, G.T.; Amer, M.M. Antioxidant and immunomodulatory constituents of henna leaves. Z. Naturforsch. C, 2004, 59(7-8), 468-476.
Galehdari, H.; Negahdari, S.; Kesmati, M.; Rezaie, A.; Shariati, G. Effect of the herbal mixture composed of Aloe Vera, Henna, Adiantum capillus-veneris, and Myrrha on wound healing in streptozotocin-induced diabetic rats. BMC Complement. Altern. Med., 2016, 16(1), 386.
Haffor, A.S. Effect of Commiphora molmol on leukocytes proliferation in relation to histological alterations before and during healing from injury. Saudi J. Biol. Sci., 2010, 17(2), 139-146.
Haffor, A.S. Effect of myrrh (Commiphora molmol) on leukocyte levels before and during healing from gastric ulcer or skin injury. J. Immunotoxicol., 2010, 7(1), 68-75.
Gebrehiwot, M.; Asres, K.; Bisrat, D.; Mazumder, A.; Lindemann, P.; Bucar, F. Evaluation of the wound healing property of Commiphora guidottii Chiov. ex. Guid. BMC Complement. Altern. Med., 2015, 15, 282.
Wang, X.W.; Yu, Y.; Gu, L. Dehydroabietic acid reverses TNF-alpha-induced the activation of FOXO1 and suppression of TGF-beta1/Smad signaling in human adult dermal fibroblasts. Int. J. Clin. Exp. Pathol., 2014, 7(12), 8616-8626.
Daburkar, M.; Lohar, V.; Rathore, A.S.; Bhutada, P.; Tangadpaliwar, S. An in vivo and in vitro investigation of the effect of Aloe vera gel ethanolic extract using animal model with diabetic foot ulcer. J. Pharm. Bioallied Sci., 2014, 6(3), 205-212.
Inpanya, P.; Faikrua, A.; Ounaroon, A.; Sittichokechaiwut, A.; Viyoch, J. Effects of the blended fibroin/aloe gel film on wound healing in streptozotocin-induced diabetic rats. Biomed. Mater., 2012, 7(3), 035008.
Abdullah, K.M.; Abdullah, A.; Johnson, M.L.; Bilski, J.J.; Petry, K.; Redmer, D.A.; Reynolds, L.P.; Grazul-Bilska, A.T. Effects of Aloe vera on gap junctional intercellular communication and proliferation of human diabetic and nondiabetic skin fibroblasts. J. Altern. Complement. Med., 2003, 9(5), 711-718.
Chithra, P.; Sajithlal, G.B.; Chandrakasan, G. Influence of aloe vera on the healing of dermal wounds in diabetic rats. J. Ethnopharmacol., 1998, 59(3), 195-201.
Tsao, R. Chemistry and biochemistry of dietary polyphenols. Nutrients, 2010, 2(12), 1231-1246.
Dashtdar, M.; Dashtdar, M.R.; Dashtdar, B.; Khan, G.A.; Kardi, K. Phenol-Rich compounds sweet gel: A statistically more effective antibiotic than cloxacillin against pseudomonas aeruginosa. J. Pharmacopuncture, 2016, 19(3), 246-252.
Dashtdar, M.; Dashtdar, M.R.; Dashtdar, B.; Shirazi, M.K.; Khan, S.A. In-Vitro, Anti-Bacterial Activities of Aqueous Extracts of Acacia catechu (L.F.)Willd, Castanea sativa, Ephedra sinica stapf and shilajita mumiyo Against Gram Positive and Gram Negative Bacteria. J. Pharmacopuncture, 2013, 16(2), 15-22.
Arias, M.E.; Gomez, J.D.; Cudmani, N.M.; Vattuone, M.A.; Isla, M.I. Antibacterial activity of ethanolic and aqueous extracts of Acacia aroma Gill. ex Hook et Arn. Life Sci., 2004, 75(2), 191-202.
Ho, T.J.; Jiang, S.J.; Lin, G.H.; Li, T.S.; Yiin, L.M.; Yang, J.S.; Hsieh, M.C.; Wu, C.C.; Lin, J.G.; Chen, H.P. The In Vitro and In Vivo wound healing properties of the chinese herbal medicine “Jinchuang Ointment”. Evid. Based Complement. Alternat. Med., 2016, 2016, 1654056.
Namjoyan, F.; Kiashi, F.; Moosavi, Z.B.; Saffari, F.; Makhmalzadeh, B.S. Efficacy of Dragon’s blood cream on wound healing: A randomized, double-blind, placebo-controlled clinical trial. J. Tradit. Complement. Med., 2016, 6(1), 37-40.
Wan, Y.; Yang, Y.J.; Li, Y.S.; Li, X.J.; Zhang, W.; Liu, M.; Tang, H.B. Effects of San-huang-sheng-fu oil on peripheral circulatory disorders and foot ulcers in diabetic rats and the mechanisms. Zhonghua Shao Shang Za Zhi, 2016, 32(3), 168-175.
Jia, M.M.; Li, Y.S.; Pei, L.J.; Liu, M.; Li, X.J.; Tang, H.B. Effect of San-huang-sheng-fu oil on wounds of full-thickness scald in rabbits. Zhonghua Shao Shang Za Zhi, 2013, 29(1), 50-54.
Lu, L.L.; Wan, P.; Li, L.Z.; Zhao, M.J.; Hu, J.Y.; Zhao, Y.F. Experimental study on topical treatment of diabetic skin ulcers with yi medicine “yi bu a jie” extract. Chin. J. Integr. Med., 2013, 19(6), 464-467.
Lau, K.M.; Lai, K.K.; Liu, C.L.; Tam, J.C.; To, M.H.; Kwok, H.F.; Lau, C.P.; Ko, C.H.; Leung, P.C.; Fung, K.P.; Poon, S.K.; Lau, C.B. Synergistic interaction between Astragali Radix and Rehmanniae Radix in a Chinese herbal formula to promote diabetic wound healing. J. Ethnopharmacol., 2012, 141(1), 250-256.
Zhang, R.X.; Li, M.X.; Jia, Z.P. Rehmannia glutinosa: review of botany, chemistry and pharmacology. J. Ethnopharmacol., 2008, 117(2), 199-214.
Zhang, Q.; Fong, C.C.; Yu, W.K.; Chen, Y.; Wei, F.; Koon, C.M.; Lau, K.M.; Leung, P.C.; Lau, C.B.; Fung, K.P.; Yang, M. Herbal formula Astragali Radix and Rehmanniae Radix exerted wound healing effect on human skin fibroblast cell line Hs27 via the activation of transformation growth factor (TGF-beta) pathway and promoting extracellular matrix (ECM) deposition. Phytomedicine, 2012, 20(1), 9-16.
Lau, T.W.; Lam, F.F.; Lau, K.M.; Chan, Y.W.; Lee, K.M.; Sahota, D.S.; Ho, Y.Y.; Fung, K.P.; Leung, P.C.; Lau, C.B. Pharmacological investigation on the wound healing effects of Radix Rehmanniae in an animal model of diabetic foot ulcer. J. Ethnopharmacol., 2009, 123(1), 155-162.
Li, F.L.; Li, B.; Wang, Z.Y.; Fan, B.; Xu, W.B.; Xu, R. Effects of resolving stagnation and promoting granulation therapy on expressions of Bax and Bcl-2 in granulation tissue of diabetic rats during wound healing. Zhong Xi Yi Jie He Xue Bao., 2007, 5(6), 661-664.
Lau, T.W.; Sahota, D.S.; Lau, C.H.; Chan, C.M.; Lam, F.C.; Ho, Y.Y.; Fung, K.P.; Lau, C.B.; Leung, P.C. An in vivo investigation on the wound-healing effect of two medicinal herbs using an animal model with foot ulcer. Eur. Surg. Res., 2008, 41(1), 15-23.
Wang, Y.F.; Que, H.F. Effects of Chinese herbal medicine Yiqi Huayu formula on substance P expression in skin ulcers of rats with diabetes mellitus. Zhong Xi Yi Jie He Xue Bao., 2011, 9(12), 1367-1372.
Li, S.F.; Zhao, J.Y.; Liu, J.P. Effect of tangzu yuyang ointment on the outcome event of patients with chronic diabetic foot ulcers. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2011, 31(6), 775-779.
Li, S.; Zhao, J.; Liu, J.; Xiang, F.; Lu, D.; Liu, B.; Xu, J.; Zhang, H.; Zhang, Q.; Li, X.; Yu, R.; Chen, M.; Wang, X.; Wang, Y.; Chen, B. Prospective randomized controlled study of a Chinese herbal medicine compound Tangzu Yuyang Ointment for chronic diabetic foot ulcers: a preliminary report. J. Ethnopharmacol., 2011, 133(2), 543-550.
Gupta, A.; Upadhyay, N.K.; Sawhney, R.C.; Kumar, R. A poly-herbal formulation accelerates normal and impaired diabetic wound healing. Wound Repair Regen., 2008, 16(6), 784-790.
Wang, Y.F.; Li, X.; Xu, R.; Jiang, W.C.; Li, F.L.; Ze, K.; Li, B. Effect of Shengji Huayu Recipe on the expression of MMP-3 and TIMP-1 in skin ulcer tissue of diabetic rats. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2014, 34(2), 218-223.
Li, B.; Wang, Z.Y.; Xiao, X.L.; Li, F.L.; Fan, B. Effects of Shengji Huayu Recipe and its decomposed formulas on synthesis of collagen types I and III in granulation tissue of rats in early wound healing. Zhong Xi Yi Jie He Xue Bao., 2005, 3(3), 216-219.
Dong, L.; Li, B.; Zhang, Y. Effect of shengji huayu recipe and its disassembled formulae on type I and III collagen synthesis in wound healing fibroblasts. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2002, 22(3), 200-202.
Zhao, H.; Mortezaei, R.; Wang, Y.; Sheng, X.; Aria, F.; Bojanowski, K. SBD.4 stimulates regenerative processes in vitro, and wound healing in genetically diabetic mice and in human skin/severe-combined immunodeficiency mouse chimera. Wound Repair Regen., 2006, 14(5), 593-601.
Zhao, H.; Deneau, J.; Che, G.O.; Li, S.; Vagnini, F.; Azadi, P.; Sonon, R.; Ramjit, R.; Lee, S.M.; Bojanowski, K. Angelica sinensis isolate SBD.4: composition, gene expression profiling, mechanism of action and effect on wounds, in rats and humans. Eur. J. Dermatol., 2012, 22(1), 58-67.
Sakaguchi, I.; Tsujimura, M.; Ikeda, N.; Minamino, M.; Kato, Y.; Watabe, K.; Yano, I.; Kaneda, K. Granulomatous tissue formation of shikon and shikonin by air pouch method. Biol. Pharmaceut. Bull., 2001, 24(6), 650-655.
Fujita, N.; Sakaguchi, I.; Kobayashi, H.; Ikeda, N.; Kato, Y.; Minamino, M.; Ishii, M. An extract of the root of Lithospermun erythrorhison accelerates wound healing in diabetic mice. Biol. Pharm. Bull., 2003, 26(3), 329-335.
Leung, P.C.; Wong, M.W.; Wong, W.C. Limb salvage in extensive diabetic foot ulceration: an extended study using a herbal supplement. Hong Kong Med. J., 2008, 14(1), 29-33.
Piskin, A.; Altunkaynak, B.Z.; Tumentemur, G.; Kaplan, S.; Yazici, O.B.; Hokelek, M. The beneficial effects of Momordica charantia (bitter gourd) on wound healing of rabbit skin. J. Dermatol. Treat., 2014, 25(4), 350-357.
Teoh, S.L.; Latiff, A.A.; Das, S. The effect of topical extract of Momordica charantia (bitter gourd) on wound healing in nondiabetic rats and in rats with diabetes induced by streptozotocin. Clin. Exp. Dermatol., 2009, 34(7), 815-822.
Hussan, F.; Teoh, S.L.; Muhamad, N.; Mazlan, M.; Latiff, A.A. Momordica charantia ointment accelerates diabetic wound healing and enhances transforming growth factor-beta expression. J. Wound Care, 2014, 23(8), 400-402, 404-407.

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Year: 2019
Page: [381 - 394]
Pages: 14
DOI: 10.2174/1389557518666181025155204
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