Effectiveness and Tolerability of a Standardized Extract from Ageratina pichinchensis in Patients with Diabetic Foot Ulcer: A Randomized, Controlled Pilot Study

Abstract

Previous works have shown that extracts obtained from Ageratina pichinchensis are capable of reducing the time needed for wounds to heal. By means of a randomized, double-blind pilot study, the objective of this work was to evaluate the effectiveness and tolerability of a phytopharmaceutical developed with a standardized extract (5 %, cream formulation) of A. pichinchensis, topically administered in patients with diabetic foot ulcer. Micronized silver sulfadiazine (1 %) was employed as a control treatment. Treatments were randomly assigned to each patient, and clinical evolution was evaluated weekly until complete healing of the wound. All patients who concluded the study achieved complete healing of their ulcers. After six weeks of treatment, patients in the experimental group exhibited a wound-healing process of 77.5 %, while that of patients in the control group was 69.8 %. A statistically significant difference was not found between groups. The average time needed for complete wound healing was 65.47 ± 47.08 days for patients treated with the A. pichinchensis extract and 77.46 ± 50.8 days for patients in the control group (p = 0.509). There was no case in either of the groups in which adverse side effects were identified. Thus, it was concluded that the A. pichinchensis extract showed the ability to improve the healing process in patients with diabetic foot ulcer; however, no statistically significant differences were observed when compared with results obtained in patients administered the control treatment (micronized silver sulfadiazine). Some limitations of this study must be addressed, such as small sample size. This work comprises a pilot study that could be useful in a future clinical trial with a greater number of patients.

Key words

Ageratina pichinchensis - Asteraceae - diabetic foot ulcer - wound healing - diabetes

• References

• 1 Olaiz FG, Rojas R, Aguilar SC, Rauda J, Villalpando S. Diabetes mellitus en adultos mexicanos. Resultados de la Encuesta Nacional de Salud 2000. Salud Publica Mex 2007; 49 (3) S331-S337
• 2 Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes; estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27: 1047-1053
• 3 Hernández RA, Elnecavé OA, Huerta UN, Reynoso NN. Análisis de una encuesta poblacional para determinar los factores asociados al control de la diabetes mellitus en México. Salud Publica Mex 2011; 53: 34-39
• 4 Bashmakov YK, Assaas-Khalil SH, Abou Seif M, Udumyan R, Megallaa M, Rohoma KH, Zeitoun M, Petyaev IM. Resveratrol promotes foot ulcer size reduction in type 2 diabetes patients. ISRN Endocrinol 2014; 2014: 816307
• 5 Arana CV, Méndez FJ. Fisiopatología de las complicaciones vasculares del pie diabético. Gac Med Mex 2003; 139: 255-264
• 6 Vilas MM, Pérez PL. La diabetes mellitus y sus complicaciones vasculares: un problema social de salud. Rev Cubana Angiol Cir Vasc 2000; 1: 68-73
• 7 Jirkovská A. The diabetic foot syndrome, one of the most serious complications in diabetics. Vnitr Lek 2001; 47: 311-314
• 8 Pinilla AE, Sánchez A, Mejía A, Barrera MP. Actividades de prevención del pie diabético en pacientes de consulta externa de primer nivel. Rev Salud Publica 2011; 13: 262-273
• 9 Monroy OC, Castillo P. Plantas medicinales utilizadas en el estado de Morelos. Cuernavaca: Universidad Autónoma del Estado de Morelos; 2000: 61-62
• 10 Rzedowski J, Rzedowski GC. Flora Fanerogámica del Valle de México. México D.F.: Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional, Instituto de Ecología; 1985: 454
• 11 Romero-Cerecero O, Zamilpa A, Ramos A, Alonso-Cortés D, Jiménez-Ferrer JE, Huerta-Reyes ME, Tortoriello J. Effect on the wound healing process and in vitro cell proliferation by the medicinal Mexican plant Ageratina pichinchensis . Planta Med 2011; 77: 979-983
• 12 Romero-Cerecero O, Zamilpa A, González-Cortázar M, Alonso-Cortés D, Jiménez-Ferrer JE, Nicasio-Torres MP, Aguilar-Santamaría L, Tortoriello J. Pharmacological and chemical study to identify wound-healing active compounds in Ageratina pichinchensis . Planta Med 2013; 79: 622-627
• 13 Romero-Cerecero O, Zamilpa A, Jiménez-Ferrer JE, Tortoriello J. Exploratory study on the effectiveness of standardized extract from Ageratina pichinchensis in patients with chronic venous leg ulcers. Planta Med 2012; 78: 304-310
• 14 Brownrigg JR, Griffin M, Hughes CO, Jones KG, Patel N, Thompson MM, Hinchliffe RJ. Influence of foot ulceration on cause-specific mortality in patients with diabetes mellitus. J Vasc Surg 2014; 60: 982-986
• 15 Francia P, Gulisani M, Anichini R, Seghieri G. Diabetic foot and exercise therapy: step by step the role of rigid posture and biomechanics treatment. Curr Diabetes Rev 2014; 10: 86-99
• 16 Özgür Keskek S, Kirim S, Karaca A, Saler T. Low serum magnesium levels and diabetic foot ulcers. Pak J Med Sci 2013; 29: 1329-1333
• 17 Shufa L, 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: 543-555
• 18 Brownrigg JRW, Apelqvist J, Bakker K, Schaper NC, Hinchliffe RJ. Evidence-based management of PAD & the diabetic foot. Eur J Vasc Endovasc Surg 2013; 45: 673-681
• 19 World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. Geneva: Council for International Organizations of Medical Sciences (CIOMS); 1993: 53-56