Abstract Because it promotes the lightening of pigment spots, tyrosinase inhibition is one of the mechanisms of depigmenting cosmetic products. Considering the adverse effects produced by synthetic depigmenting actives, the search for new therapeutic options is desirable, and plant extracts are possible candidates for hyperpigmentation treatment. Glycolic extracts of Cecropia pachystachya Trécul are, therefore, the focus of this study. Its chemical characterization, antioxidant activity, tyrosinase inhibition, and cell viability were evaluated. Glycolic extracts were obtained by macerating the leaves of C. pachystachya in grain alcohol and glycerin or propylene glycol. Both had a similar chemical constitution, the glycerin being more efficient in concentrating phenolic compounds and flavonoids. Analyses by UHPLC-MS detected quinic acid, chlorogenic acid isomers, proanthocyanidin dimers type B and C, catechin/epicatechin, orientin/isoorientin, isoorientin 2”-O-xyloside, vitexin/isovitexin, and rutin. 5-O-caffeoylquinic acid was then quantified was then quantified, with predominance in the extract produced with propylene glycol. These extracts showed a high antioxidant capacity by the method of DPPH, β-carotene, and nitric oxide. As for depigmenting activity, both extracts were able to inhibit tyrosinase. Cell viability assay also revealed that the extracts could safely be used in concentrations of ≤ 125 µg/mL. Thus, this study demonstrated for the first time that the glycolic extracts of C. pachystachya have promising chemical and biological characteristics for the development of a multifunctional cosmetic with antioxidant and tyrosinase-inhibition activities. spots products actives desirable treatment therefore characterization activity evaluated C glycol constitution flavonoids UHPLCMS UHPLC MS isomers catechinepicatechin catechin epicatechin catechin/epicatechin orientinisoorientin orientin orientin/isoorientin 2Oxyloside, 2Oxyloside Oxyloside 2 O xyloside, xyloside 2”-O-xyloside vitexinisovitexin vitexin isovitexin vitexin/isovitexin rutin 5Ocaffeoylquinic Ocaffeoylquinic 5 caffeoylquinic DPPH βcarotene, βcarotene β carotene, carotene β-carotene oxide 12 µgmL µg mL µg/mL Thus tyrosinaseinhibition activities 1

Abstract Syzygium malaccense is popularly used to treat inflammation and pain-related ailments. The species was assessed regarding its antioxidant, antiglycant, anti-inflammatory, including anti-neuroinflammatory, and antinociceptive activities. Different models were employed to measure S. malaccense extract (ESM) antioxidant activity. The antiglycant activity was determined using the glucose-induced protein glycation model. LPS-induced neuroinflammation on murine BV-2 microglial cell line was used for anti-neuroinflammatory activity evaluation. The croton oil-induced ear edema test was accomplished to evaluate the in vivo anti-inflammatory activity. Acetic acid-induced writhing together with formalin-induced paw licking assays were performed to evaluate the antinociceptive potential. Finally, the chemical characterization was accomplished by a UHPLC-MS analysis. ESM presented relevant antioxidant and antiglycant activity. NO production by BV-2 cells was reduced, indicating the relevant neuroprotective activity. ESM significantly decreased the mice ear edema induced by croton oil and the nociceptive stimulus induced by acetic acid and formalin by central and peripheral mechanisms. The flavonoids myricitrin, myricetin and quercetin were identified and, as far as we know, the alkaloid reserpine was reported in the species for the first time. The antioxidant and antiglycant potential of ESM, may be related to the in vivo anti-inflammatory and antinociceptive effects, and to the in vitro neuroinflammation inhibition.

ABSTRACT This study aimed to further investigate the cytotoxicity against tumor cell lines and several bacterial strains of Annona squamosa and its mode of action. Methanol extracts of A. squamosa leaves (ASL) and seeds (ASS) were used. ASL showed significant antibacterial activity against S. aureus, K. pneumoniae and E. faecalis with MIC values of 78, 78 and 39 µg/mL respectively. Moreover, ASL exhibited significant biofilm disruption, rapid time dependent kinetics of bacterial killing, increased membrane permeability and significantly reduced the cell numbers and viability. Regarding the cytotoxicity against tumor cell lines, ASS was more active against Jurkat and MCF-7 cells, with CI50 1.1 and 2.1 µg/mL, respectively. ASL showed promising activity against Jurkat and HL60, with CI50 4.2 and 6.4 µg/mL, respectively. Both extracts showed lower activity against VERO cells and reduced the clonogenic survival at higher concentrations (IC90) to MCF-7 and HCT-116 lineages. The alkaloids anonaine, asimilobine, corypalmine, liriodenine nornuciferine and reticuline were identified in extracts by UPLC-ESI-MS/MS analysis. This study reinforced that A. squamosa presents a remarkable phytomedicinal potential and revealed that its antimicrobial mechanism of action is related to bacterial membrane destabilization.

As leishmanioses são um complexo de doenças causadas por protozoários Leishmania, cujo tratamento é restrito a um número limitado de fármacos que apresentam toxicidade elevada, efeitos colaterais e geralmente custos elevados. Existe uma enorme variedade de plantas tropicais distribuídas no Brasil e para muitas pessoas pobres a terapia para várias doenças baseia-se principalmente no uso de remédios tradicionais obtidos de plantas. Neste trabalho, a atividade citotóxica de 17 extratos metanólicos de plantas foi avaliada em várias espécies de Leishmania e em macrófagos murinos. Dentre eles, os extratos de Casearia sylvestris, Piptocarpha macropoda, Trembleya parviflora, Samanea Tubulosa e Plectranthus neochilus mostraram atividade leishmanicida promissora, exibindo valores de CI50 abaixo de 20 µg/mL em pelo menos uma das espécies de Leishmania. Casearia sylvestris apresentou a atividade mais expressiva em todas as formas promastigotas de espécies de Leishmania (valores de CI50 de 5,4 µg/mL, 5,0 µg/mL, 8,5 µg/mL and 7,7 µg/mL em L. amazonensis, L. braziliensis, L. chagasi e L. major, respectivamente), sendo mais eficaz que o fármaco de referência miltefosina. Apesar do efeito citotóxico em macrófagos (valor de CC50 de 5,2 µg/mL), C. sylvestris exibiu uma forte inibição em formas amastigotas de L. braziliensis (valor de CI50 de 1,3 µg/mL). Mais estudos, incluindo fracionamento bio-guiado, serão realizados para identificar os compostos ativos.

Leishmaniasis is a complex of diseases caused by Leishmania protozoa which treatment is restricted to a limited number of drugs that exhibit high toxicity, collateral effects and are often costly. There are a variety of tropical plants distributed in Brazil, and for many poor people the therapy for several diseases is based mainly on the use of traditional herbal remedies. In this work, the cytotoxic activity of 17 plant methanol extracts was evaluated on several Leishmania species and murine macrophages. Among them, the extract of Casearia sylvestris, Piptocarpha macropoda, Trembleya parviflora, Samanea tubulosa and Plectranthus neochilus showed a promissing leishmanicidal activity, exhibiting IC50 values below of 20 µg/mL against at least one species of Leishmania. Casearia sylvestris showed the most expressive activity against all promastigote forms of Leishmania species (IC50 values of 5.4 µg/mL, 5.0 µg/mL, 8.5 µg/mL and 7.7 µg/mL for L. amazonensis, L. braziliensis, L. chagasi and L. major, respectively), being more effective than the reference drug miltefosine. In spite of the cytotoxic effect on macrophages (CC50 value of 5.2 µg/mL), C. sylvestris exhibited a strong inhibition against intracellular amastigotes of L. braziliensis (IC50 value of 1.3 µg/mL). Further studies, including bio-guided fractionation will be conducted to identify the active compounds.

Manihot multifida(L.) Crantz (Euphorbiaceae) é amplamente utilizada na medicina popular no tratamento de feridas infectadas. Esse estudo avaliou o potencial antioxidante e antimicrobiano in vitrode extratos dessa espécie frente às cepas bacterianas Gram-positiva e Gram-negativa e fungo que causam infecções em humanos. Os extratos mostraram concentração inibitória mínima (CIM) variando de 39 a 2500µg/mL para a atividade antimicrobiana. O extrato metanólico de frutos, hexânico e aquoso de folhas mostraram atividade muito forte para Candida albicans (ATCC 18804), com CIM de 39µg/mL. Além disso, o extrato metanólico de folhas deM. multifidamostrou potencial antioxidante contra o radical DPPH com valor de concentração inibitória (CI50) de 46,9μg/mL, seguido pelo extrato hexânico de folhas, com valor de CI50 de 59,2μg/mL. A atividade citotóxica foi maior no extrato hexânico de folhas com concentração letal (CL50) de 15,6μg/mL. Esses resultados sugerem que M. multifida possui atividades antimicrobiana e antioxidante interessantes. Sendo assim, corroboram o uso popular dessa espécie no tratamento de infecções fúngicas, uma vez que demonstrou uma atividade significativa frente à C. albicans.

Manihot multifida (L.) Crantz (Euphorbiaceae) is widely used in popular medicine for the treatment of infected wounds. This study evaluated thein vitro antioxidant and antimicrobial potential of this species against strains of Gram-positive and Gram-negative bacteria and fungi, known to cause infections in humans. The extracts showed minimal inhibitory concentration (MIC) varying from 39 to 2500 µg/mL for antimicrobial activity. The methanolic extract of fruits, aqueous and hexane extracts of leaves showed a very strong activity against Candida albicans(ATCC 18804) with MIC of 39 µg/mL. Furthermore, the methanolic extract of M. multifida leaves exhibited DPPH (1,1-diphenyl-2-picrylhydrazyl) scavenging potential with inhibitory concentration (IC50) values of 46.9 μg/mL, followed by hexane extract of leaves with IC50 values of 59.2 μg/mL. The cytotoxic activity against brine shrimp was stronger for the methanolic extract of leaves (lethal concentration - LC50 of 15.6 µg/mL). These results suggest that M. multifida has interesting antimicrobial and antioxidant activities. Moreover, these results corroborate the popular use of this specie in treating fungal infections since it demonstrates significant activity againstC. albicans.

The anti-inflammatory and apoptotic activity of the essential oil of Syzygium cumini (L.) Skeels, Myrtaceae, leaves was investigated in vivo. The anti-inflammatory action and chronic granulomatous inflammation in BALB/c mice, intravenously infected with Mycobacterium bovis, BCG, (Bacillo Calmet Guerim), was judged by measuring and classifying the granulomas formed in the hepatic parenchyma. The degree of apoptosis in the inflammatory cells was also measured. A reduction in the granulomatous area and a change in the pattern of the granulomas were found. Anti-mycobacterial activity of the essential oil against M. bovis was detected in vitro by an interferometric method in liquid culture medium. The chemical constituents of the essential oil were determined by GC/MS. Higher yields of the essential oil of S. cumini leaves were obtained by extraction in a Clevenger apparatus when the fresh leaves were previously frozen as a pre-processing step. The essential oil obtained from this plant demonstrated a statistically significant and dramatic effect in the chosen model system.

Em nosso trabalho anterior (Fabri et al. 2009), mostramos que diferentes extratos de Mitracarpus frigidus apresentaram atividades antibacteriana, antifúngica e leishmanicida significativas. Com o objetivo de aprofundar o conhecimento sobre essa espécie, esse trabalho objetiva identificar os constituintes químicos e avaliar as atividades biológicas in vitro de seu óleo essencial. Dessa forma, o óleo essencial das partes aéreas de M.frigidus foi obtido por hidrodestilação e analisado por CG/EM. Entre os compostos detectados, 11 foram identificados, sendo linalol e o acetato de eugenol os componentes majoritários. O óleo essencial de M. frigidus exibiu moderada atividade antibacteriana contra Staphyloccocus aureus, Bacillus cereus, Pseudomonas aeruginosa e Enterobacter cloacae (CIM 250 µg/mL). Por outro lado, apresentou forte efeito antifúngico contra Cryptoccocus neoformans (CIM 8 µg/mL) e Candida albicans (CIM 63 µg/mL). Expressiva atividade contra as formas promastigostas de Leishmania major e Leishmania amazonensis com valores CI50 de 47, 2 e 89, 7 µg/mL, respectivamente, também foi observada. Além disso, a atividade antioxidante foi investigada através do ensaio com o radical DPPH e este apresentou uma significativa atividade com CI50 de 38 µg/mL. A citotoxidade contra Artemia salina foi moderada com CL50 de 88 µg/mL. Os resultados aqui apresentados são o primeiro relato sobre a composição química e propriedades biológicas do óleo essencial M. frigidus.

In our previous work (Fabri et al. 2009), we showed that different extracts of Mitracarpus frigidus had significant antibacterial, antifungal and leishmanicidal activities. In order to increase our knowledge about this species, this work assesses the chemical composition and the in vitro biological activity of its essential oil. Thus, the essential oil obtained by hydrodistillation of the aerial parts of M. frigidus was analyzed by GC/MS. Among several compounds detected, 11 were identified, being linalool and eugenol acetate the major components. The essential oil exhibited a moderate antibacterial effect against Staphyloccocus aureus, Bacillus cereus, Pseudomonas aeruginosa and Enterobacter cloacae (MIC 250 µg/mL). On the other hand, it showed a strong antifungal effect against Cryptoccocus neoformans (MIC 8 µg/mL) and Candida albicans (MIC 63 µg/mL). Expressive activity against L. major and L. amazonensis promastigote forms with IC50 values of 47.2 and 89.7 µg/mL, respectively, were also observed. In addition, the antioxidant activity was investigated through DPPH radical-scavenging and showed a significative activity with IC50 of 38 µg/mL. The cytotoxicity against Artemia salina was moderate with LC50 of 88 µg/mL. The results presented here are the first report on the chemical composition and biological properties of M. frigidus essential oil.

O fracionamento biomonitorado do extrato diclorometânico de Mitracarpus frigidus forneceu a piranonaftoquinona psicorubrina. Essa substância, até então desconhecida no gênero Mitracarpus, teve sua atividade biológica avaliada contra várias bactérias e dois fungos, três linhagens de células tumorais (HL60, Jurkat e MCF-7) e quatro espécies de Leishmania. Sua estrutura foi confirmada por meio de ¹H, 13C, ¹H-COSY, IR e UV-Vis e espectrometria de massas. Psicorubrina exibiu uma atividade antitumoral promissora com CI50 de 4,5, 5,6 e 1,1 µM para HL60, Jurkat e MCF-7, respectivamente. Atividade antimicrobiana, principalmente contra Cryptococcus neoformans (CIM de 87,3 µM), foi observada. Um pronunciado potencial leishmanicida também foi verificado com CI50 variando de 1,7 - 2,7 µM para as diferentes espécies de Leishmania testadas. Este é o primeiro relato da presença de piranonaftoquinonas no gênero Mitracarpus, que poderão ser úteis como marcadores quimiotaxonômicos.

The bioactivity guided fractionation of the dichloromethane extract of Mitracarpus frigidus afforded the pyranonaphthoquinone psychorubrin. This compound, hitherto unknown in the genus Mitracarpus, had its biological activity evaluated against one panel of bacteria and two fungi, three tumor cell lines (HL60, Jurkat and MCF-7) and four Leishmania species. Its identity was confirmed unambiguously by ¹H, 13C, ¹H-COSY, IR and UV-Vis spectroscopy and mass spectrometry. Psychorubrin displayed a very promising antitumor with IC50 of 4.5, 5.6 and 1.1 µM for HL60, Jurkat and MCF-7 cell lines, respectively. Antimicrobial activity, mainly against Cryptococcus neoformans (MIC of 87.3 µM) was observed. A pronounced antileishmanial potential was also verified with IC50 varying from 1.7 to 2.7 µM for the Leishmania species tested. This is the first report of the presence of pyranonapthoquinones in the Mitracarpus genus, which may serve as a chemotaxonomical marker.