Guttiferones: An insight into occurrence, biosynthesis, and their broad spectrum of pharmacological activities.

Guttiferones belong to the polyisoprenylated benzophenone, a class of compounds, a very restricted group of natural plant products, especially in the Clusiaceae family. They are commonly found in bark, stem, leaves, and fruits of plants of the genus Garcinia and Symphonia. Guttiferones have the following classifications according to their chemical structure: A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, Q, R, S, and T. All of them have received growing attention due to its multiple biological activities. This review provides a first comprehensive approach to plant sources, phytochemical profile, specific pharmacological effects, and mechanisms of guttiferones already described. Studies indicate a broad spectrum of pharmacological activities, such as: anti-inflammatory, immunomodulatory, antioxidant, antitumor, antiparasitic, antiviral, and antimicrobial. Despite the low toxicity of these compounds in healthy cells, there is a lack of studies in the literature related to toxicity in general. Given their beneficial effects, guttiferones are expected to be great potential drug candidates for treating cancer and infectious and transmissible diseases. However, further studies are needed to elucidate their toxicity, specific molecular mechanisms and targets, and to perform more in-depth pharmacokinetic studies. This review highlights chemical properties, biological characteristics, and mechanisms of action so far, offering a broad view of the subject and perspectives for the future of guttiferones in therapeutics.

Mapa de evidências sobre a efetividade clínica das plantas medicinais brasileiras: informe executivo / Evidence Map on the clinical effectiveness of Brazilian medicinal plants: executive report

O mapa apresenta uma visão geral das evidências sobre os efeitos das Plantas Medicinais Brasileiras para desfechos em saúde. A partir de uma ampla busca bibliográfica foram incluídos no mapa 214 estudos de revisão sistemática. Todos os estudos foram avaliados, caracterizados e categorizados por um grupo de pesquisadores de Laboratório de Tecnologia de Produtos Naturais (LTPN) da Faculdade de Farmácia da Universidade Federal Fluminense. Principais Achados: ● As revisões avaliaram o efeito de intervenções com 69 tipos de plantas organizadas em 4 categorias: cultivadas, nativas, exóticas e introduzidas no Brasil. ● As intervenções foram associadas a 130 desfechos de saúde organizados em 17 grupos: Bem-Estar, Vitalidade e Qualidade de Vida, Câncer, Condições Patológicas, Dermatopatias, Doenças Cardiovasculares, Doenças Nutricionais e Metabólicas, Doenças Respiratórias, Doenças Reumáticas, Doenças Urogenitais, Dor, Fatores Biológicos, Gastroenteropatias e Hepatopatias, Indicadores Psicológicos e Comportamentais, Indicadores Metabólicos e Fisiológicos, Saúde Mental, Saúde Bucal e Saúde Reprodutiva. ● No total foram 465 associações entre intervenções (as plantas) e desfechos de saúde, com destaque para as plantas cultivadas (251 associações, 54%). ● O grupo dos desfechos "Saúde Mental" foi o que recebeu mais associações (66 associações, 14%), seguido do grupo "Saúde Bucal" (42 associações, 9%). ● Quanto aos desfechos, destaque para: Transtornos de Ansiedade (20 associações), Demência (16 associações), Diabetes Mellitus (17 associações) e Distúrbios Menstruais (15 associações). ● Dentre as plantas, destaque para: Ginkgo biloba (76 associações), Aloe Vera (50), Zingiber officinale (39), Panax ginseng (28) e Curcuma longa (23). Implicações para a prática e pesquisa: ● Considerando o efeito das intervenções para os desfechos, os estudos reportaram efeito positivo ou potencialmente positivo para a maioria (68%) das associações (181 associações com efeito positivo e 137 com efeito potencialmente positivo). ● Destaque para os efeitos positivos ou potencialmente positivos reportados nas intervenções com Ginkgo biloba para os desfechos: Demência, Doença de Alzheimer e Desempenho Cognitivo (8, 7 e 7 associações respectivamente). ● Em 87 associações foi reportado "sem efeito" da intervenção para o desfecho (19,7%). ● Foi reportado efeito inconclusivo para uma pequena parte das associações (9%), que merece mais pesquisas. Nenhum efeito negativo ou potencialmente negativo foi reportado. O efeito não foi informado para 19 associações. ● Note-se que essa lista é dinâmica, podendo mudar com a publicações de novos estudos.

The map provides an overview of the evidence on the effects of Brazilian Medicinal Plants on health outcomes. Based on an extensive literature search, the map includes 214 systematic review studies. All studies were assessed, characterized, and categorized by a group of researchers from the Laboratory of Natural Product Technology (LTPN) at the Faculty of Pharmacy of the Federal Fluminense University. Key Findings: - The reviews evaluated the effects of interventions using 69 types of plants organized into 4 categories: cultivated, native, exotic, and introduced to Brazil. - The interventions were associated with 130 health outcomes organized into 17 groups: Well-being, Vitality and Quality of Life, Cancer, Pathological Conditions, Dermatopathies, Cardiovascular Diseases, Nutritional and Metabolic Diseases, Respiratory Diseases, Rheumatic Diseases, Urogenital Diseases, Pain, Biological Factors, Gastroenteropathies and Hepatopathies, Psychological and Behavioral Indicators, Metabolic and Physiological Indicators, Mental Health, Oral Health, and Reproductive Health. - In total, there were 465 associations between interventions (plants) and health outcomes, with a significant emphasis on cultivated plants (251 associations, 54%). - The "Mental Health" group received the most associations (66 associations, 14%), followed by the "Oral Health" group (42 associations, 9%). - Notable health outcomes included Anxiety Disorders (20 associations), Dementia (16 associations), Diabetes Mellitus (17 associations), and Menstrual Disorders (15 associations). - Among the plants, notable ones included Ginkgo biloba (76 associations), Aloe Vera (50), Zingiber officinale (39), Panax ginseng (28), and Curcuma longa (23). Implications for Practice and Research: - Considering the effects of interventions on health outcomes, the studies reported a positive or potentially positive effect for the majority (68%) of the associations (181 associations with a positive effect and 137 with a potentially positive effect); - Noteworthy are the positive or potentially positive effects reported for interventions with Ginkgo biloba on the outcomes of Dementia, Alzheimer's Disease, and Cognitive Performance (8, 7, and 7 associations, respectively); - In 87 associations, the intervention was reported to have "no effect" on the outcome (19.7%); - An inconclusive effect was reported for a small portion of the associations (9%), indicating a need for further research. No negative or potentially negative effects were reported. The effect was not reported for 19 associations; - It should be noted that this list is dynamic and may change with the publication of new studies.

Baccharin from Brazilian green propolis induces neurotrophic signaling pathways in PC12 cells: potential for axonal and synaptic regeneration.

Neurodegenerative diseases are characterized by progressive loss of the structure and function of specific neuronal populations, and have been associated with reduced neurotrophic support. Neurotrophins, like NGF (nerve growth factor), are endogenous proteins that induce neuritogenesis and modulate axonal growth, branching, and synapsis; however, their therapeutic application is limited mainly by low stability, short half-life, and inability to cross the blood-brain barrier (BBB). Small neurotrophic molecules that have suitable pharmacokinetics and are able to cross the BBB are potential candidates for neuroprotection. Baccharin is a bioactive small molecule isolated from Brazilian green propolis. In the present study, we investigated the neurotrophic and neuroprotective potential of baccharin in the PC12 cell neuronal model. We used pharmacological inhibitors (K252a, LY294002, and U0126), and ELISA (phospho-trkA, phospho-Akt, and phospho-MEK) to investigate the involvement of trkA receptor, PI3k/Akt pathway, and MAPK/Erk pathway, respectively. Additionally, we evaluated the expression of axonal (GAP-43) and synaptic (synapsin I) proteins by western blot. The results showed that baccharin induces neuritogenesis in NGF-deprived PC12 cells, through activation of trkA receptor and the downstream signaling cascades (PI3K/Akt and MAPK/ERK), which is the same neurotrophic pathway activated by NGF in PC12 cells and neurons. Baccharin also induced the expression of GAP-43 and synapsin I, which mediate axonal and synaptic plasticity, respectively. Additionally, in silico predictions of baccharin showed favorable physicochemical properties, pharmacokinetics, drug-likeness, and medicinal chemistry friendliness. Altogether, these findings suggest that baccharin is a promising neurotrophic agent whose therapeutic application in neurodegeneration should be further investigated.

Ocotea pulchellaas an alternative against schistosomiasis: chemical analysis, development of nanoemulsion and biological control activity / Ocotea pulchellacomo una alternativa ante esquistosomiasis: análisis químico, desarrollo de una nanoemulsión y actividad en control biológico

The aim of this work was to evaluate the potential of the essential oil (EO) from Ocotea pulchella leaves as an alternative in the control of schistosomiasis. It was tested O. pulchella EO nanoformulation to assess its activity against adult Biomphalaria glabrata, their spawning and Schistossoma mansoni cercariae. Additionally, the EO chemical composition was investigated by gas-chromatography. Nanoemulsion were elaborated by the low energy method. The adult mollusks, their spawning and cercariae were placed in contact with nanoemulsion to calculate lethal concentrations. Myristicin, bicyclogermacrene and α-Pinene were the main substances in the EO. Nanoemulsion caused mortality of adult B. glabrata, its egg embryos and S. mansoni. These results suggest the use of this nanoemulsion as an alternative in the control of the schistosomiasis cycle.

El objetivo de este trabajo fue evaluar el potencial de los aceites esenciales (AE) de las hojas de Ocotea pulchellacomo una alternativa en el control de esquistosomiasis. Se probó una nanoformulación de AE de O. pulchellapara evaluar su actividad ante adultos de Biomphalaria glabrata, sus huevos y cercarías de Schistossoma mansoni. La nanoemulsión fue elaborada por el método de baja energía. Los moluscos adultos, sus huevos y cercarías se colocaron en contacto con la nanoemulsión para calcular concentraciones letales. Los compuestos mayoritarios en el AE fueron miristicina, biciclogermacreno y α-pineno. La nanoemulsión causó mortalidad en adultos de B. glabrata, sus huevos y a S. mansoni. Los resultados sugieren el uso de esta nanoemulsión como una alternativa en el control del ciclo de esquistosomiasis.

Nanoemulsion containing essential oil from Xylopia ochrantha Mart. produces molluscicidal effects against different species of Biomphalaria (Schistosoma hosts).

BACKGROUND: This work describes a chemical study of the essential oil from leaves of Xylopia ochrantha, an endemic Annonaceae species from Brazil, and its activity against Biomphalaria species. Considering its poor solubility in aqueous medium, the essential oil was nanoemulsified to evaluate its action on controlling some mollusc species of genus Biomphalaria, snail hosts of Schistosoma mansoni that causes schistosomiasis, which mainly affects tropical and subtropical countries. OBJECTIVES: The main aims of this work were to analyse the chemical composition of essential oil from X. ochrantha, and to evaluate the effect of its nanoemulsion on molluscs of genus Biomphalaria and their oviposition. METHODS: Chemical analysis was performed by gas chromatography coupled to mass spectrometry. Nanoemulsions were prepared by a low energy method and characterised by particle size and polydispersity index. Biological assays evaluating the mortality of adult species of B. glabrata, B. straminea and B. tenagophila and their ovipositions upon contact with the most stable nanoemulsion during 24 and 48 h were performed. FINDINGS: Chemical analysis by mass spectrometry revealed the majority presence of bicyclogermacrene and germacrene D in the essential oil. The formulation with a hydrophilic-lipophilic balance (HLB) of 9.26 was the most suitable for the oil delivery system. This nanoemulsion caused the mortality in B. tenagophila, B. straminea and B. glabarata of different sizes at levels ranging from 50 to 100% in 48 h. Additionally, the formulation could inhibit the development of deposited eggs. CONCLUSION: Thus, these results suggest the use of nanoemulsified essential oil from X. ochrantha as a possible alternative in controlling some Biomphalaria species involved in the schistosomiasis cycle.

Protective effect of Myrsine parvifolia plant extract against the inflammatory process induced by Bothrops jararaca snake venom.

Accidents involving snakes from the genus Bothrops sp. constitute the most important cause of snake envenomation in Brazil. The Myrsine genus has been reported to be used in folk medicine against snakebites. In this work, the phytochemical profiles and ability of extracts from Myrsine parvifolia leaves to reduce the inflammatory process (edema, vascular permeability increase and leukocyte migration) induced by Bothrops jararaca venom were investigated in vivo. Chemical compounds were identified by chromatographic and spectroscopy techniques. Total polyphenol, tannin, and flavonoid contents were determined by spectrophotometric methods. Swiss male mice received an oral administration of extracts (100 mg/kg) in different protocols. Paw edema, intraperitoneal vascular permeability and pleurisy models in mice were used to evaluate the antiophidic potential of the extracts. Paw edema was induced by subplantar injection of B. jararaca venom and quantified as the increase in paw volume. Changes in vascular permeability were assessed by measuring the amount of Evans blue dye extravasation. Leukocyte migration was assessed by total and differential counts in the pleural cavity washes. Myricetin, myricetin-3-O-ß-arabinopyranoside, quercetin and kaempferol were isolated from the ethyl acetate extract and identified as the primary compounds of the dichloromethane extract. Terpenes and fatty acids were identified in the hexane and dichloromethane extracts. The pretreated group with hydroethanolic and dichloromethane extract reduced total edema (40 and 52%, respectively), vascular permeability increase (32.4 and 32.2%, respectively) and leukocyte influx into the pleural cavity (42 and 39%, respectively), while the group treated with hexane extract showed only reduced edema (37%) induced by B. jararaca venom. The hydroethanolic extract showed better results in all of the tests performed and was also administered by the protocol of post-poisoning, showing maintenance of paw edema reduction and cell migration. These data indicate a potential anti-inflammatory activity of M. parvifolia in poisoning by B. jararaca, especially to reduce local poison effects.

Nanoemulsion containing essential oil from Xylopia ochrantha Mart. produces molluscicidal effects against different species of Biomphalaria (Schistosoma hosts)

BACKGROUND This work describes a chemical study of the essential oil from leaves of Xylopia ochrantha, an endemic Annonaceae species from Brazil, and its activity against Biomphalaria species. Considering its poor solubility in aqueous medium, the essential oil was nanoemulsified to evaluate its action on controlling some mollusc species of genus Biomphalaria, snail hosts of Schistosoma mansoni that causes schistosomiasis, which mainly affects tropical and subtropical countries. OBJECTIVES The main aims of this work were to analyse the chemical composition of essential oil from X. ochrantha, and to evaluate the effect of its nanoemulsion on molluscs of genus Biomphalaria and their oviposition. METHODS Chemical analysis was performed by gas chromatography coupled to mass spectrometry. Nanoemulsions were prepared by a low energy method and characterised by particle size and polydispersity index. Biological assays evaluating the mortality of adult species of B. glabrata, B. straminea and B. tenagophila and their ovipositions upon contact with the most stable nanoemulsion during 24 and 48 h were performed. FINDINGS Chemical analysis by mass spectrometry revealed the majority presence of bicyclogermacrene and germacrene D in the essential oil. The formulation with a hydrophilic-lipophilic balance (HLB) of 9.26 was the most suitable for the oil delivery system. This nanoemulsion caused the mortality in B. tenagophila, B. straminea and B. glabarata of different sizes at levels ranging from 50 to 100% in 48 h. Additionally, the formulation could inhibit the development of deposited eggs. CONCLUSION Thus, these results suggest the use of nanoemulsified essential oil from X. ochrantha as a possible alternative in controlling some Biomphalaria species involved in the schistosomiasis cycle.