Complementary and Alternative Therapies for Onychomycosis: A Systematic Review of the Clinical Evidence.

Introduction: Onychomycosis is notoriously difficult to treat. While oral antifungals are the most efficacious treatment for onychomycosis, they are contraindicated in certain patient populations, and patients may desire lower risk and accessible alternatives to systemic agents. In this study, we examine the clinical evidence supporting the use of complementary and alternative therapies in the treatment of onychomycosis. Methods: PubMed, Embase, and Cochrane Library were searched for clinical trials, observational studies, and case reports/case series, examining the efficacy of a complementary or alternative therapy for the treatment of onychomycosis. Results: We identified 17 articles studying a complementary and alternative therapy for onychomycosis, including tea tree oil (n = 5), Ageratina pichinchensis (n = 3), Arthrospira maxima (n = 2), natural coniferous resin lacquer (n = 2), Vicks VapoRub® (n = 2), propolis extract (n = 2), and ozonized sunflower oil (n = 1). Conclusion: Given the rise of antifungal resistance, complementary and alternative therapies should continue to be studied as adjunctive or alternative therapy for onychomycosis. While preliminary evidence exists for several complementary and alternative therapies in the treatment of onychomycosis, large-scale, randomized, placebo-controlled trials are needed prior to endorsing their use to patients.

Effectiveness of an encecalin standardized extract of Ageratina pichinchensis on the treatment of onychomycosis in patients with diabetes mellitus.

Ageratina pichinchensis is utilized in traditional medicine for the treatment of dermatomycosis and inflammation. The aim of this study was to evaluate the clinical and mycological effectiveness of the topical administration of an enecalin standardized extract of A. pichinchensis for treating onychomycosis in patients with type 2 diabetes mellitus (DM2). A double blind, randomized, and controlled clinical trial was carried out that included patients with DM2 and who had mild or moderate onychomycosis. Participants were administered topically, for 6 months, a lacquer containing the encecalin standardized extract of A. pichinchensis (experimental group) or 8% ciclopirox (control group). In a large percentage of both, the control group (77.2%) and the experimental group (78.5%), clinical efficacy was detected as a decrease in the number of affected nails and a reduction in the severity of nail involvement. Without exhibiting statistically significant differences between groups, the encecalin standardized extract of A. pichinchensis was clinically and mycologically effective in the treatment of mild and moderate onychomycosis in patients with DM2. The treatment of onychomycosis in patients with DM2 implies a greater challenge, while control of blood glucose levels in these patients, played a very important role in the response of patients to treatment.

Use of Some Asteraceae Plants for the Treatment of Wounds: From Ethnopharmacological Studies to Scientific Evidences.

Severe wounds result in large lesions and/or loss of function of the affected areas. The treatment of wounds has challenged health professionals due to its complexity, especially in patients with chronic diseases (such as diabetes), and the presence of pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. Taking this into consideration, the development of new therapies for wound healing requires immediate attention. Ethnopharmacological studies performed in different countries have shown the use of several plants from the Asteraceae family as wound-healing agents. Evidences gained from the traditional medicine have opened new ways for the development of novel and more efficient therapies based on the pharmacological properties of these plants. In this article, we discuss the literature data on the use of Asteraceae plants for the treatment of wounds, based on the ethnopharmacological relevance of each plant. Special attention was given to studies showing the mechanisms of action of Asteraceae-derived compounds and clinical trials. Ageratina pichinchensis (Kunth) R.M. King and H. Rob. and Calendula officinalis L. preparations/compounds were found to show good efficacy when assessed in clinical trials of complicated wounds, including venous leg ulcers and foot ulcers of diabetic patients. The compounds silibinin [from Silybum marianum (L.) Gaertn.] and jaceosidin (from Artemisia princeps Pamp.) were identified as promising compounds for the treatment of wounds. Overall, we suggest that Asteraceae plants represent important sources of compounds that may act as new and efficient healing products.

Establishment and Phytochemical Analysis of a Callus Culture from Ageratina pichinchensis (Asteraceae) and Its Anti-Inflammatory Activity.

A protocol was established to produce bioactive compounds in a callus culture of Ageratina pichinchensis by using 1 mg L-1 NAA with 0.1 mg L-1 KIN. The phytochemical study of the EtOAc extract obtained from the callus biomass, allowed the isolation and characterization of eleven secondary metabolites, of which dihydrobenzofuran (5) and 3-epilupeol (7), showed important anti-inflammatory activity. Compound 5 inhibits in vitro the secretion of NO (IC50 = 36.96 ± 1.06 µM), IL-6 (IC50 = 73.71 ± 3.21 µM), and TNF-α (IC50 = 73.20 ± 5.99 µM) in RAW (Murine macrophage cells) 264.7 macrophages, as well as the activation of NF-κB (40% at 150 µM) in RAW-blue macrophages, while compound 7 has been described that inhibit the in vivo TPA-induced ear edema, and the in vitro production of NO, and the PLA2 enzyme activity. In addition, quantitative GC-MS analysis showed that the anti-inflammatory metabolites 5 and 7 were not detected in the wild plant. Overall, our results indicated that A. pichinchensis can be used as an alternative biotechnological resource for obtaining anti-inflammatory compounds. This is the first report of the anti-inflammatory activity of compound 5 and its production in a callus culture of A. pichinchensis.

Effectiveness of Ageratina pichinchensis Extract in Patients with Vulvovaginal Candidiasis. A Randomized, Double-Blind, and Controlled Pilot Study.

Previous clinical studies have demonstrated the antifungal effectiveness of Ageratina pichinchensis extracts when topically administered to patients with dermatomycosis. The objective of this study was to evaluate the effectiveness and tolerability of a 7% standardized extract of A. pichinchensis (intravaginal) in patients with vulvovaginal candidiasis. The extract was standardized in terms of its encecalin content and administered during 6 days to patients with Candida albicans-associated vulvovaginitis. The positive control group was treated with Clotrimazole (100 mg). On day 7 of the study, a partial evaluation was carried out; it demonstrated that 94.1% of patients treated with Clotrimazole and 100% of those treated with the A. pichinchensis extract referred a decrease or absence of signs and symptoms consistent with vulvovaginal candidiasis. In the final evaluation, 2 weeks after concluding administration, 86.6% of patients in the control group and 81.2% (p = 0.65) of those treated with the A. pichinchensis extract demonstrated therapeutic success. Statistical analysis evidenced no significant differences between the two treatment groups. With the results obtained, it is possible to conclude that the standardized extract from A. pichinchensis, intravaginally administered, showed therapeutic and mycological effectiveness, as well as tolerability, in patients with vulvovaginal candidiasis, without noting statistical differences in patients treated with Clotrimazole. Copyright © 2017 John Wiley & Sons, Ltd.

Pilot study that evaluated the clinical effectiveness and safety of a phytopharmaceutical elaborated with an extract of Ageratina pichinchensis in patients with minor recurrent aphthous stomatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: The plant species Ageratina pichinchensis (Schauer) R.M.King & H.Rob. (Asteraceae) in a wild plant native to Mexico that is utilized in traditional medicine for the treatment of skin problems and for mouth ulcers. AIM OF THE STUDY: The objective of the present study was to evaluate the clinical effectiveness and therapeutic safety of a phytopharmaceutical elaborated with a unpigmented hexane-ethyl acetate extract of A. pichinchensis at a concentration of 5% in patients with a clinical condition of Minor Recurrent aphthous stomatitis (MiRAS). MATERIALS AND METHODS: We conducted a double-blind, randomized, and controlled pilot study in which the experimental treatment was a phytopharmaceutical elaborated with a unpigmented hexane-ethyl acetate extract of A. pichinchensis at a 5% concentration and, as control treatment, we utilized Triamcinolone at 0.1%. Study participants were patients with a diagnosis of MiRAS, elderly males and females, with a disease evolution of no. >3 days. Lesion size was measured by means of a tracing sheet and pain, by the Visual analog scale (VAS). Output variables comprised clinical effectiveness, treatment adherence, therapeutic failure, and therapeutic success. RESULTS AND DISCUSSION: Fifty six patients participated in the study and we distributed these into two study groups (28 in each group). The results obtained did not show statistically significant differences between the experimental and the control treatments. Among patients treated with the A. pichinchensis extract, the time required for achieving the absence of pain was 4.0 days, while that of the control treatment was 4.1 days. In patients treated with A. pichinchensis, the time necessary for healing was 4.5 days and for the Triamcinolone 0.1%-treated group, this was 4.7 days. Greater clinical effectiveness was evidenced on days 2, 3, and 4 of treatment. During the first 7 follow-up days, there was clinical effectiveness in 92.8% of experimental-group and in 89.2% of control-group patients. At the end of the study, 100% therapeutic effectiveness was able to be scored.

Pharmacological effect of Ageratina pichinchensis on wound healing in diabetic rats and genotoxicity evaluation.

ETHNOPHARMACOLOGICAL RELEVANCE: Among the main causes affecting the wound healing process, we find diabetes mellitus, which is due to the occurrence of a prolonged inflammation phase, defects in angiogenesis, and a diminution in fibroblast proliferation. The species Ageratina pichinchensis has been utilized in Mexican traditional medicine for the treatment of skin wounds. Pharmacological models have demonstrated that an extract obtained from this species improves wound healing and, through a clinical study, it was evidenced that the extract (in a pharmaceutical form) is effective in the treatment of patients with chronic venous ulcers. The 7-O-(ß-D-glucopyranosyl)-galactin compound was recently identified as responsible for the pharmacological activity. The objective of the present study was to evaluate the wound healing activity of an aqueous extract and another hexane-ethyl acetate extract from Ageratina pichinchensis (both standardized in the active compound) in a diabetic foot ulcer rat model, as well as evaluating the possible genotoxic effects produced by the same species. MATERIALS AND METHODS: Rats with streptozotocin-induced diabetes were submitted (under anesthesia with pentobarbital) to a circular lesion on the skin (excisional) on the rear of the paw. All animals were topically treated daily until healing. 5-methyl-1 phenyl-2-(1H) Pyridone was used as a positive control treatment. Once the wound was healed, a skin sample was obtained and utilized for histopathological analysis. The possible genotoxic effects produced by the extract, in a model of spermatozoid viability and morphology, were evaluated. RESULTS: The results showed that 100% of animals treated with Ageratina pichinchensis extracts presented wound healing between days 4 and 11 of treatment, while in the positive control group (treated with 5-methyl-1 phenyl-2-(1H) pyridone) and in the negative control group (vehicle), only 70% and 40%, respectively, exhibited wound healing at day 11. Histological analysis demonstrated evidences of an active regenerative process in animals that received the extracts, in addition to that in the study, the effects of the plant extracts that could be compatible with genotoxicity were not observed. CONCLUSIONS: Aqueous and hexane-ethyl acetate extracts of the aerial parts of Ageratina pichinchensis (standardized in its content of 7-O-(ß-D-glucopyranosyl)-galactin), consistently improve wound healing induced on the skin of rats with streptozotocin-induced diabetes. The capacity was evidenced of the extracts to promote histological tissue regeneration, without exhibiting genotoxicity.

Chemical composition and evaluation of antibacterial activity of essential oils of Ageratina jahnii and Ageratina pichinchensis collected in Mérida, Venezuela / Composición química y evaluación de la actividad antibacteriana de los aceites esenciales de Ageratina jahnii y Ageratina pichinchensis recolectadas en Mérida,Venezuela

Essential oil from leaves of Ageratina jahnii (B.L.Rob.) R. M. King & H. Rob. and Ageratina pichinchensis (Kunth) R. M. King & H. Rob (Asteraceae) collected in January 2010 were analyzed by GC/MS. Oils extracted by hydrodistillation yielded 0.50 percent and 0.43 percent w/v, respectively. Fifteen and twenty five components were identified by comparison of their mass spectra with the Wiley GC-MS Library data and by their retention indices (RI). The major components identified in A. jahnii were beta-myrcene (37.6 percent, alpha-pinene (17.1 percent), limonene (8.8 percent and pentacosane (9.2 percent while for A. pichinchensis 8,9-epoxythymyl isobutyrate (20.2 percent, germacrene-D (19.8 percent, thymyl isobutyrate (10.8 percent, eupatoriochromene (6.5 percent) and encecalol (5.9 percent) were observed as main compounds. This is the first report regarding the essential oil composition and antibacterial activity of the essential oil of A. jahnii.

Aceites esenciales de las hojas de Ageratina jahnii (B.L.Rob.) R. M. King & H. Rob. y Ageratina pichinchensis (Kunth) R. M. King & H. Rob (Asteraceae) colectadas en enero 2010 fueron analizados por CG/EM. Los aceites extraídos por hidrodestilación produjeron 0,50 por ciento y 0,43 por ciento p/v de rendimiento, respectivamente. Quince y veinticinco compuestos fueron identificados por comparación de sus espectros de masas con la base de datos de la librería Wiley CG/EM y por sus índices de retención (IR). Los compuestos identificados como majoritarios en A. jahnii fueron beta-mirceno (37,6 por ciento), alfa-pineno (17,1 por ciento, limoneno (8.8 por ciento y pentacosano (9,2 por ciento mientras para A. pichinchensis isobutirato de 8,9-epoxitimilo (20,2 por ciento, germacreno-D (19,8 por ciento, isobutirato de timilo (10,8 por ciento), eupatoriocromeno (6,5 por ciento y encecalol (5,9 por ciento) fueron observados como compuestos mayoritarios. Este es el primer reporte sobre la composición química y actividad antibacteriana del aceite esencial de A. jahnii.