Resumo Um iogurte probiótico feito com a polpa do fruto tumbo (Passiflora tripartita Kunth) apresentou capacidade antioxidante, qualidade físico-química e microbiológica, e estabilidade; entretanto, é necessário ser seguro para estudos posteriores de funcionalidade clínica. O presente estudo é considerado um precursor para a avaliação de segurança pré-clínica de um alimento funcional por meio de testes toxicológicos in vivo. O objetivo do estudo foi avaliar a segurança pré-clínica do iogurte feito com a polpa do fruto tumbo (Passiflora tripartita Kunth). Os estudos toxicológicos propostos foram baseados no padrão OECD 423:2001 sobre Toxicidade Oral Aguda, realizando uma única administração via oral do iogurte probiótico em uma dose de 2.000 mg/kg, em um grupo de ratos machos randomizados, para avaliação durante 14 dias, comparado a um grupo controle; e, no padrão OECD 407:2008 sobre Toxicidade Oral de Dose Repetida, administrando uma dose diária de 2.000 mg/kg do iogurte por 28 dias em ratos machos, considerando a avaliação de seus parâmetros clínicos, hematológicos e bioquímicos, para determinar qualquer possível efeito tóxico produzido pela formulação probiótica. Os resultados mostraram que, em ambos os estudos toxicológicos, não foram detectadas alterações adversas nos sinais clínicos, no peso relativo dos órgãos e nos perfis hematológicos e bioquímicos. Além disso, foi possível evidenciar uma possível melhora no status imunológico, na função hepática e no perfil hematológico. Em conclusão, foi possível estabelecer conhecimento sobre a segurança pré-clínica da formulação de um iogurte probiótico feito com a polpa do fruto tumbo, obtendo um valor de NOAEL (Nível Sem Efeito Adverso Observado) superior a 2.000 mg/kg de peso corporal em ratos machos. Passiflora Kunth antioxidante físicoquímica físico química microbiológica estabilidade entretanto clínica préclínica pré vivo Kunth. . 4232001 423 2001 423:200 Aguda 2000 2 000 2.00 mgkg mg kg randomizados 1 controle 4072008 407 2008 407:200 Repetida clínicos bioquímicos probiótica que disso imunológico hematológico conclusão Nível Observado 423200 42 200 423:20 00 2.0 407200 40 407:20 42320 4 20 423:2 0 2. 40720 407:2 4232 423: 4072 407:

Abstract A probiotic yogurt made from the pulp of the tumbo fruit (Passiflora tripartita Kunth) possesses antioxidant capacity, physicochemical and microbiological quality and stability; however, it needs to be safe for later studies of clinical functionality. The present study would be considered as a precursor to the preclinical safety evaluation of a functional food by in vivo toxicological testing. The study aimed to evaluate the preclinical safety of yogurt made from the pulp of the tumbo fruit (P. tripartita). The toxicological studies proposed were based on the OECD 423:2001 standard on Acute Oral Toxicity, performing the peroral administration of the probiotic yogurt at a dose of 2000 mg/kg one-time in a group of randomized male rats, for its evaluation during 14 days compared to a control group; and on the OECD 407: 2008 on Repeated Dose Oral Toxicity, a daily dose of 2000 mg/kg of the yogurt was administered for 28 days in male rats, considering the evaluation of their clinical, hematological and biochemical parameters, to determine any possible toxic effect produced by the probiotic formulation. The results showed that in both toxicological studies, no adverse alterations were detected in their clinical signs, relative organ weights and hematological and biochemical profiles. In addition, a possible improvement in the immunological status, liver function and hematological profile was evidenced as a finding. In conclusion, it was possible to establish knowledge on the preclinical safety of the formulation of a probiotic yogurt made with tumbo fruit pulp, obtaining a NOAEL (No Observed Adverse Effect Level) value higher than 2000 mg/kg body weight in male rats. Passiflora Kunth capacity stability however functionality testing P. P (P tripartita. . tripartita) 4232001 423 2001 423:200 Toxicity 200 mgkg mg kg onetime one time rats 1 407 2 parameters signs profiles addition status finding conclusion No Level 423200 42 423:20 20 40 42320 4 423:2 4232 423:

ABSTRACT Introduction: In military medicine, natural healing agents against incision wounds are relevant in the treatment of the military. Objective: To evaluate the healing activity of the hydroalcoholic extracts of Peperomia congona Sodiro (congona), Annona muricata L. (guanabana), Urtica urens L. (ortiga), Ormosia coccinea (Aubl) Jacks (huairuro), Opuntia ficus-indica L. Mill. (tuna) and Musa acuminata Colla (platano bellaco) in incised wounds of Rattus norvegicus albinus (albino rat). Methods: Experimental analytical study of prospective and longitudinal type. The preliminary phytochemical analysis of the 6 extracts was carried out. We used 80 male albino rats, randomized and distributed in 8 groups (n = 10). A dermal application was made during 10 consecutive days after the generation of incised wounds that were made on the back. Group I (0.9% sodium chloride). Group II (commercial healing gel). From Group III to VIII they were treated with hydroalcoholic extract of congona, guanábana, ortiga, huairuro, tuna and platano bellaco respectively. The evolution of healing was followed on days 1, 5 and 11 and measured in millimeters. Results: The presence of alkaloids, phenolic compounds and flavonoids was detected in the 6 extracts; in addition to coumarins in congona, tannins in guanábana, nettle, tuna and huayruro, quinonas in guanábana and plantain bellaco. The healing activity was verified in the extracts of guanabana (69.77 %), tuna (66.27 %), platano bellaco (64.38 %), ortiga (56.73 %), congona (55.74 %) and huayruro (54.50 %), compared with a commercial gel (72.21 %). Conclusions: The hydroalcoholic extract of the leaves of Annona muricata L. (guanábana) showed the highest healing activity in incised wounds of male albino rats.

RESUMEN Introducción: En la medicina militar, los agentes cicatrizantes naturales frente a heridas por incisión son relevantes en el tratamiento de los militares. Objetivo: Evaluar la actividad cicatrizante de los extractos hidroalcohólicos de Peperomia congona Sodiro (congona), Annona muricata L. (guanábana), Urtica urens L. (ortiga),Ormosia coccinea (Aubl) Jacks (huayruro), Opuntia ficus-indica L. Mill. (tuna) y Musa acuminata Colla (plátano bellaco) en heridas incisas de Rattus norvegicus albinus (rata albina). Métodos: Estudio analítico experimental de tipo prospectivo y longitudinal. Se realizó el análisis fitoquímico preliminar de los 6 extractos. Se emplearon 80 ratas albinas machos, aleatorizadas y distribuidas en 8 grupos (n = 10). Se realizó una aplicación dermal durante 10 días consecutivos posteriores a la generación de heridas incisas que se realizaron en el dorso. Grupo I (cloruro de sodio al 0,9 %). Grupo II (gel cicatrizante comercial). Del Grupo III al VIII fueron tratados con extracto hidroalcohólico de congona, guanábana, ortiga, huairuro, tuna y plátano bellaco respectivamente. La evolución de la cicatrización fue seguida en los días 1, 5 y 11 y medida en milímetros. Resultados: Se detectó la presencia de alcaloides, compuestos fenólicos y flavonoides en los 6 extractos; además de cumarinas en congona, taninos en guanábana, ortiga, tuna y huayruro, y quinonas en guanábana y plátano bellaco. Se comprobó la actividad cicatrizante en los extractos de guanábana (69,77 %), tuna (66,27 %), plátano bellaco (64,38 %), ortiga (56,73 %), congona (55,74 %) y huayruro (54,50 %), comparados con un gel comercial (72,21 %). Conclusiones: El extracto hidroalcohólico de las hojas de Annona muricata L. (guanábana) presentó la mayor actividad cicatrizante en heridas incisas de ratas albinas machos.

Objective: To evaluate the inhibitory potential of the α-amylase and α-glucosidase enzymes, as well as the inhibition of glucose diffusion, using polysaccharides isolated from Nostoc sphaericum Vaucher ex Bornet & Flahault and treated by in vitro simulated gastrointestinal digestion. Materials and methods: The polysaccharides obtained from the microalga were purified and treated through in vitro gastrointestinal digestibility in order to simulate digestion. The hypoglycemic activity was evaluated by methods such as the inhibition of α-glucosidase and α-amylase, and glucose diffusion of the digested polysaccharides, and compared with the medication acarbose. Results: The results showed that the concentration of 50 mg/mL of digested polysaccharides decreases by 85.26 % the spread of in vitro glucose. The inhibitory concentration (IC50) of the α-glucosidase enzyme was 314.23 ± 4.87 mg/mL and that of the α-amylase enzyme was 113.59 ± 3.10 mg/mL. Conclusions: Nostoc sphaericum polysaccharides treated by in vitro gastrointestinal digestion showed the ability to inhibit the α-amylase and α-glucosidase enzymes, and glucose diffusion. Therefore, this species would be considered promising for a possible adjuvant treatment of type 2 diabetes

Objetivo: Evaluar el potencial inhibitorio de las enzimas α-amilasa y α-glucosidasa, así como la inhibición de la difusión de la glucosa, por los polisacáridos aislados de Nostoc Sphaericum Vaucher ex Bornet & Flahault tratados mediante digestión gastrointestinal simulada a nivel in vitro. Materiales y métodos: Los polisacáridos obtenidos de microalga fueron purificados y tratados mediante digestibilidad gastrointestinal in vitro, con la finalidad de simular su digestión. Se evaluó la actividad hipoglucemiante mediante los métodos de inhibición de la α-glucosidasa, α-amilasa y la difusión de la glucosa de los polisacáridos digeridos, comparados con el medicamento acarbosa. Resultados: Los resultados mostraron que la concentración de 50 mg/mL de polisacáridos digeridos disminuye en un 85,26 % la difusión de la glucosa a nivel in vitro. La concentración inhibitoria (CI50) de la enzima α-glucosidasa fue de 314,23 ± 4,87 mg/mL y la enzima α-amilasa 113,59 ± 3,10 mg/mL. Conclusiones: Los polisacáridos de Nostoc sphaericum tratados mediante digestión gastrointestinal in vitro, mostraron capacidad de inhibir las enzimas α-amilasa, α-glucosidasa y la difusión de glucosa; motivo por el cual la especie sería considerado promisoria para un posible tratamiento coadyuvante de la diabetes tipo 2

Resumen Se evaluó el ácido úsnico (1), aislado del liquen Evernia prunastri (Cajamarca-Perú), producto natural conocido por sus actividades biológicas, y, del mismo modo, se evaluó la síntesis de su derivado acil-hidrazona (2), obtenido a partir de una reacción de condensación entre el ácido úsnico y la isoniazida en solución etanólica a reflujo, con un rendimiento global de 95%. Ambos compuestos fueron evaluados y comparados con la isoniazida según su actividad anti-Mycobacterium tuberculosis basada en el ensayo de susceptibilidad mediante el método TEMA. Los resultados mostraron que el compuesto 1 presenta valores de MIC de 16,0 μg/mL frente a las cepas H37Rv, TB DM 97 y MDR DM 1098, mientras que el compuesto 2 presenta valores de MIC de 2,0; 64,0 y 64,0 μg/mL respectivamente.

Abstract Compound usnic acid (1), isolated from lichen Evernia prunastri (Cajamarca-Peru) and the synthesis and characterization of its acyl-hydrazone (2), from the condensation reaction between usnic acid and isoniazid in an ethanol solution under reflux, giving an overall yield of 95%, were evaluated. Both compounds were evaluated and compared with isoniazid according to its anti-Mycobacterium tuberculosis activity based on the tetrazolium microplate assay (TEMA). Compound 1 had MIC (minimal inhibitory concentration) value of 16.0 μg/mL in each test of H37Rv (susceptible type), TB DM 97 (resistant wild type) and MDR DM 1098 (multi drug resistances type) strains. In similar tests, compound 2 MIC values were 2.0, 64.0 and 64.0 μg/mL respectively.

Resumo Foi avaliado o ácido úsnico (1), um produto natural conhecido pelas suas atividades biológicas, isolado a partir do líquen Evernia prunastri (Cajamarca-Peru), assim mesmo foi avaliada a síntese do seu derivado, a acil-hidrazona (2), obtido a partir de uma reação de condensação com refluxo entre o ácido úsnico e a isoniazida em solução etanólica, com um rendimento global de 95%. A atividade anti-Mycobacterium tuberculosis de ambos compostos foi avaliada e comparada com a isoniazida mediante testes de sensibilidade obtidos pelo método TEMA. Os resultados mostraram que o composto 1 apresenta o valor de MIC de 16,0 μg/mL contra variedades H37Rv, TB DM 97 e MDR DM 1098; enquanto que para o composto 2 os valores de MIC são de 2,0; 64,0 e 64,0 μg/mL, respectivamente.

It was developed and validated the quantification of tannins of the hydroalcoholic extract, by means of ultraviolet-visible spectrophotometry, where the method turned out to be selective, lineal, precise (repeat and reproduce) and exact; they were obtained as a result for compound total phenolic: 13,5158 0,1825 g of tannic acid/ 100 g of bark; for tannins: 11,8590 0,5453 g of tannic acid/ 100 g of bark, and for condensed tannins: 1,62368 0,0784 g of tannic acid/ 100 g of bark.

Se desarrollo y valido la cuantificacion de taninos del extracto hidroalcoholico, mediante espectrofotometria ultravioleta-visible, donde el metodo resulto ser selectivo, lineal, preciso (repetible y reproducible) y exacto; se obtuvo como resultado para compuestos fenolicos totales: 13,5158 0,1825 g de acido tanico/100 g de corteza; para taninos: 11,8590 0,5453 g de acido tanico/ 100 g de corteza; y para taninos condensados: 1,62368 0,0784 g de acido tanico/ 100 g de corteza.

In the pharmacognostic analysis of the hydroalcoholic extract of the bark of Triplaris americana L., has been evidenced phenolics compound: tannins and flavonoids. The antioxidant activity of the extract hydroalcoholic was evaluated, applying the method of the DPPH obtaining as inhibitory concentration IC50 9, 5498 ug/mL, with slightly superior result compared with the standard trolox. When evaluating the toxicity to unique dose of the hydroalcoholic extract (2000 mg/kg of corporal mass), mortality didn't take place neither they showed indicative symptoms of toxicity in the experimental animals.

En el análisis farmacognóstico del extracto hidroalcohólico de la corteza de Triplaris americana L., se han evidenciado compuestos fenólicos: taninos y flavonoides. Se evaluó la actividad antioxidante del extracto hidroalcohólico, aplicando el método del DPPH, obteniendo como concentración inhibitoria IC50 9,5498 ug/mL, con resultado levemente superior comparado con el estándar trolox. Al evaluar la toxicidad a dosis límite del extracto hidroalcohólico (2000 mg/kg de masa corporal), no se produjo mortalidad ni se manifestaron síntomas indicativos de toxicidad en los animales de experimentación.