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Context: Anti-inflammatory drugs and biologics can effectively treat inflammatory conditions and diseases but can also cause burdensome side effects. Many patients prefer to use time-tested, traditional medicinal products and dietary supplements, but such products seldom receive the rigorous testing required for regulatory approvals of drugs and biologics. Thus, it is advantageous to demonstrate by experimentation the pharmacological and toxicological properties of unapproved natural products and compared to benchmark approved drugs or biologics. Objective: The studies intended to evaluate Samento®, a commercial hydro-alcoholic extract of the pentacyclic chemotype of Uncaria Tomentosa (Willd.) DC, for the prophylactic and treatment effects of irritant-induced inflammation and antigen-induced arthritic inflammation in two rat models. The studies were also intended to create a clinical bridge rationale for the use of Samento® in the treatment of inflammation in humans, with a suggested allometrically scaled starting dose. Design: The research team performed two in vivo animal model studies of induced inflammation in rats. Setting: The studies took place at the Universidad Peruana Cayetano Heredia in Lima, Peru. Prophylaxis Model of Irritant-Induced Inflammation: Holtzman rats in five groups (five each per group) were administered 14 daily doses of Samento® at 250, 500, and 1000 mg/kg of wet weight, or 40 mg/kg of naproxen sodium as a positive control, or nothing as a negative control. At 14 days the right legs of the rats were challenged by injection into the connective tissue by the chemical irritant carrageenan. Two hours thereafter the weight of the irritant-injected right leg was compared to the non-injected left leg of each rat, to determine the level of irritant-induced inflammation. Treatment Model of Antigen-Induced Arthritic Inflammation: Arthritic inflammation was induced in five groups of Lewis rats (five each per group) by intradermal injection of the tail with non-allogeneic, bovine type II collagen in incomplete Freund's adjuvant. A sixth group was not injected with collagen antigen as a non-induced control. Ten days after the induction of arthritic inflammation in the five injected groups, individual groups were treated with Samento® at 250, 500, and 1000 mg/kg of wet weight daily for 21 days, or 0.2 mg/kg of methotrexate twice per week as a positive control, or nothing as a negative control. At 21 days the animals were assessed for antigen-induced arthritic inflammation and assigned an analog score ranging from 0 to 4. Results: The research team confirmed the presence of pentacyclic oxindoles and the absence of tetracyclic oxindoles within Samento®. In the prophylactic model, 14 days of pretreatment with oral Samento® produced dose-dependent, statistically significant reductions in inflammation in the rats' leg weights between the carrageenan induction and postintervention, for the 250, 500, and 1000 mg/kg Samento® groups (P < .05 for all groups). The 1000 mg/kg group had a 74% anti-inflammatory effect versus 97% with the 40 mg/kg of naproxen sodium in the positive control group. In the treatment model, 21 days of oral administration of Samento® produced dose-dependent, statistically significant reductions in arthritic inflammation postintervention, for the 250, 500, and 1000 mg/kg Samento® groups (P < .05 for all groups). Treatment with the highest tested dose of the extract (1000 mg/kg) yielded an 85% anti-inflammatory effect versus 90% with 0.2 mg/kg of methotrexate in the positive control group. Conclusions: The two rat models revealed that the Uncaria phytotherapy Samento® was an effective prophylactic as well as a treatment for induced inflammation in rats. The highest dose of the pentacyclic chemotype of Uncaria approached the anti-inflammatory activities of the established benchmark pharmaceutical positive controls. The results in the two rat models suggest an allometrically scaled starting dose of Samento® of 4 g daily in humans.

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BACKGROUND: The objective of this in vivo study is to evaluate in five rat models the pharmacologic effects and toxicity of a commercial hydro-alcoholic extract, GlucoMedix®, derived from Stevia rebaudiana and the pentacyclic chemotype of Uncaria Tomentosa (Willd.) DC, for use as a treatment for metabolic syndrome. The extract contains phytochemicals of Stevia (e.g., steviol glycosides) and Uncaria (e.g., pentacyclic oxindole alkaloids, but lacks tetracyclic oxindole alkaloids). METHODS: The pharmacologic assessments in three rat models include reductions in chemically induced hyperglycemia, hyperlipidemia (cholesterol and triglycerides), and hypertension, all of which are comorbidities of metabolic syndrome. Acute toxicity and 28-day subacute toxicity were assessed in rat models at doses higher than those used in the efficacy models. RESULTS: The acute oral toxicity was evaluated in Holtzman rats and the extract did not produce acute toxic effects or lethality, with the LD50 > 5000 mg/kg (extract wet weight). Furthermore, subacute oral toxicity was evaluated in rats for 28 days at daily doses as high as 2000 mg/kg without toxicity or abnormal clinical chemistry or hematological effects. Daily oral doses of 250 - 1000 mg/kg were used to evaluate the treatment effects in hyperglycemic (alloxan-induced and glibenclamide-controlled), hyperlipidemic (cholesterol-induced and atorvastatin-controlled), and hypertensive (L-NAME-induced and enalapril-controlled) rat models. Alloxan-induced hyperglycemia was reduced in a dose-dependent manner within 28 days or less. Cholesterol-induced hyperlipidemic rats exhibited dose-dependent reductions in cholesterol and triglycerides at 21 days. Furthermore, GlucoMedix® produced a dose-dependent decrease in systolic and diastolic arterial blood pressure in L-NAME-induced hypertensive rats at 28 days. CONCLUSIONS: The five in vivo rat models revealed that the all-natural phytotherapy GlucoMedix® is a safe and effective treatment for hyperglycemia, hyperlipidemia, and hypertension. This extract is expected to affect multiple comorbidities of metabolic syndrome, without any acute or subacute oral toxicity in humans. Although multiple prescription drugs are well known for the treatment of individual comorbidities of metabolic syndrome, no drug monotherapy concurrently treats all three comorbidities.

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Determinar la actividad antibacteriana in vitro del extracto etanólico de Origanum vulgare (orégano), Tagetes elliptica (chincho) y del Tagetes minuta (huacatay) comparado con Clorhexidina al 0.12% y Colgate Plax frente a cepas de Lactobacillus acidophilus ATCC 43121 y Porphyromonas gingivalis ATCC 33277. Material y métodos: Se evaluó la actividad antimicrobiana mediante el método de Difusión en Agar, Mínima Concentración Inhibitoria y Técnica Pour Plate (Técnica de Vertido en Placa). El diseño del estudio fue de tipo experimental in vitro de corte transversal. El análisis estadístico univariado y bivariado se hizo en el programa SPSS 17.0. Resultados: Se determinó que la actividad antibacteriana de las sustancias experimentales para la cepa Lactobacillus acidophilus ATCC 43121 fue el extracto etanólico del orégano al 100% tuvo un promedio en los halos de inhibición de 18,43 ± 3,96 mm, el extracto etanólico del chincho al 100% de 20,5 ± 2,99 mm, clorhexidina al 0,12% de 21,3 ± 0,38 m y Colgate Plax 14,93 ± 0,84 mm. Frente a la cepa Porphyromonas gingivalis ATCC 33277:el extracto etanólico de chincho 100% tuvo un promedio en los halos de inhibición de 16.27 ± 2,67, el extracto etanólico de orégano 100% tuvo un promedio en los halos de inhibición de 25,86 ± 1,18 mm, el extracto etanólico del huacatay 100% de 24,49 ± 3,21 mm, con clorhexidina al 0,12% de 19,59 ± 0,48 mm y con Colgate Plax 14,29 ± 0,3 mm. La MIC del extracto etanólico del chincho frente a la cepa Lactobacillus acidophilus ATCC 43121 fue de 125 mg/mL, encontrando la medida de los halos de inhibición de 10,33 mm. Conclusiones: Existe actividad antibacteriana in vitro del extracto etanólico de Origanum vulgare (orégano), Tagetes elliptica (chincho) comparado con Clorhexidina al 0,12% y Colgate Plax frente a cepas de Lactobacillus acidophilus ATCC 43121 y Porphyromonas gingivalis ATCC 33277; asimismo el Tagetes minuta (huacatay) tiene efectividad con esta última cepa bacteriana...

To determine the in vitro antibacterial activity of the ethanolic extract from Origanum vulgare (oregano), Tagetes elliptica (chincho) and Tagetes minuta (huacatay) compared with clorhexidine 0.12% and Colgate Plax against Lactobacillus acidophilus ATCC 43121 and Porphyromonas gingivalis ATCC 33277. Materials and Methods: Antimicrobial activity was evaluated by agar diffusion method, minimum inhibitory concentration (MIC) and pour plate technique. The study design was experimental in vitro cross sectional. The univariate and bivariate statistical analysis were done in SPSS 17.0. Results: it was found that the antibacterial activity of experimental substances against Lactobacillus acidophilus ATCC 43121 was: the 100% oregano ethanolic extract had an inhibition zone average of 18.43 ±3.96mm, the 100% chincho ethanolic extract of 20.5 +- 2.99mm, clorhexidine 0.12% 21.3 +- 0.38mm and Colgate Plax 14.93 +- 0.84mm. For Porphyromonas gingivalis ATCC 33277: the 100% chincho ethanolic extract had an inhibition zone average of 16.27 ±2.67mm, the 100% oregano ethanolic extract had an inhibition zone average of 25.86 +-1.18mm, the 100% huacatay ethanolic extract of 24.49 +- 3.21mm, clorhexidine 0.12% of 19.59 +- 0.48mm and Colgate Plax 14.29 +- 0.3mm. The MIC of the chincho ethanolic extract against Lactobacillus acidophilus ATCC 43121 was 125 mg/mL, finding inhibition zones of 10.33mm. Conclusions: there is an effective in vitro antibacterial activity of the Origanum vulgare (oregano) and Tagetes elliptica (chincho) ethanolic extracts compared to clorhexidine 0.12% and Colgate Plax against Lactobacillus acidophilus ATCC 43121 and Porphyromonas gingivalis ATCC 33277, however, the Tagetes minuta (huacatay) is effective only against Porphyromonas gingivalis ATCC 33277...

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Objetivo: Evaluar el efecto del extracto etanólico de Melissa officinalis (toronjil), a dosis de 3 y 6 mg/kg, contra placebo en el comportamiento de niños ansiosos de 6 y 7 años de edad, durante el examen clínico dental. Materiales y Métodos: Ensayo clínico randomizado a doble ciego en el cual participaron 90 niños (51 niñas y 39 niños) provenientes del Centro MaternoInfantil de Zapallal (Lima, Perú). Los participantes no tenían experiencia odontológica previa y presentaban ansiedad dental, que fue diagnosticada con la Escala de Imagen Facial. Se conformaron 3 grupos, de los cuales los 2 primeros recibieron una dosis única por vía oral del extracto etanólico (3 y 6 mg/kg respectivamente) mientras que el grupo restante recibió placebo. El examen clínico dental fue realizado 30 minutos después de la administración del jarabe o placebo. Durante el examen clínico fue evaluada la conducta de cada niño mediante la Escala Conductual de Frankl. Resultados: Al evaluar la conducta sobre el examen clínico dental se encontró diferencia estadísticamente significativa entre los grupos estudiados (Prueba de Kruskal- Wallis, P=0,016), encontrándose esta diferencia entre niños que recibieron placebo y extractoetanólico de 6mg/kg (P=0,008) así como entre niños que recibieron extracto etanólico de 3 y 6 mg/kg (P=0,017). Sin embargo, no se encontró diferencia entre aquellos que recibieron placebo y extracto etanólico de 3 mg/kg (P=0,759). Conclusión: Al evaluar el comportamiento del niño ansioso, durante el examen clínico dental, por medio de la Escala Conductual de Frankl se observó que el extracto etanólico de M. officinalis mostró tener un mayor efecto comparado con un placebo, siendo más efectiva la dosis de 6 mg/kg.

Objective: To assess the effect of the ethanol extract of the Melissa officinalis (lemon balm) in doses of 3 and 6 mg/kg against placebo on the behaviour of 6-7 year-old anxious children, during the dental examination. Materials and methods: Double-blind, randomized, controlled trial of 90 children (51 girls and 39 boys) from the Child Maternal Center of Zapallal (Lima, Peru). Theparticipants did not have any previous dental experience and presented dental anxiety, which was diagnosed with the Facial Image Scale. Three groups were conformed: the first two groups received an oral unique dose of the ethanol extract (3 and 6 mg/kg respectively) while the remaining group received a placebo. Each clinical dental examination was evaluated 30 minutes after of the administration of the ethanol extract or placebo. During examination, child behaviour was assessed using the Frankl Behaviour Rating Scale. Results: There was a statistically significant difference among groups for the behaviour during the dental examination (Test of Kruskal- Wallis, P=0.0016). Differences were located between children who received placebo and thosewho received ethanol extract of 6mg/kg (P=0.008), and between children who received ethanol extract of 3 and 6 mg/kg (P=0.017). However, there were no significant difference between those who received placebo and ethanol extract of 3 mg/kg (P=0.759). Conclusion: When the behaviour of anxious children was assessed during the dental examination, through the Frankl Behaviour Rating Scale, the ethanol extract of M. officinalis had a greater effect compared with a placebo, being more effective the dose of 6 mg/kg.

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Contiene: 1. Estudio farmacológico del veneno de Lachesis muta muta "SHUSHUPE"; 2. Antivenenos

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