Amazonian fruits with potential effects on COVID-19 by inflammaging modulation: A narrative review.

The COVID-19 pandemic had a great impact on the mortality of older adults and, chronic non- transmissible diseases (CNTDs) patients, likely previous inflammaging condition that is common in these subjects. It is possible that functional foods could attenuate viral infection conditions such as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the causal agent of COVID-19 pandemic. Previous evidence suggested that some fruits consumed by Amazonian Diet from Pre-Colombian times could present relevant proprieties to decrease of COVID-19 complications such as oxidative-cytokine storm. In this narrative review we identified five potential Amazonian fruits: açai berry (Euterpe oleracea), camu-camu (Myrciaria dubia), cocoa (Theobroma cacao), Brazil nuts (Bertholletia excelsa), and guaraná (Paullinia cupana). Data showed that these Amazonian fruits present antioxidant, anti-inflammatory and other immunomodulatory activities that could attenuate the impact of inflammaging states that potentially decrease the evolution of COVID-19 complications. The evidence compiled here supports the complementary experimental and clinical studies exploring these fruits as nutritional supplement during COVID-19 infection. PRACTICAL APPLICATIONS: These fruits, in their natural form, are often limited to their region, or exported to other places in the form of frozen pulp or powder. But there are already some companies producing food supplements in the form of capsules, in the form of oils and even functional foods enriched with these fruits. This practice is common in Brazil and tends to expand to the international market.

Safety indicators of a novel multi supplement based on guarana, selenium, and L-carnitine: Evidence from human and red earthworm immune cells.

Neurodegenerative diseases are associated with chronic inflammatory states. There is evidence to support the design of novel supplements based on guarana (G) (Paullinia cupana), selenium (S), and L-carnitine (C), the use of which, potentially attenuates neuro oxi-inflammatory conditions. Therefore, this study analyzed the cytotoxic and redox effects of GSC on human leucocytes, the inflammatory activation of microglia BV-2 cells, and effect on mortality, oxidative metabolism, and the immune modulation of red earthworms (Eisenia fetida). The GSC concentrations tested in cell culture were in the range of 0.04-2.1 mg/mL. All the GSC-supplemented samples tested, reverted H2O2 oxidation in DNA molecules, suggesting its genoprotective potential. GSC did not induce mortality in leucocyte cultures. On the contrary, a reduction in the levels of oxidation of lipids, proteins, and cell apoptosis was observed, via downregulation of caspase 3 and 8 genes. GSC showed a dual effect on microglia, decreasing the cellular proliferation at lower concentrations (<0.24 mg/mL) and increasing the cellular proliferation mainly at concentrations > 1.0 mg/mL. GSC did not have a toxic effect on red earthworms, but induced an increase in amoebocyte cells and in brown body formation, indicating immune response activation. The results suggest that GSC could be safe for human consumption.

Astrocaryum aculeatum fruit improves inflammation and redox balance in phytohemagglutinin-stimulated macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Astrocaryum aculeatum G.Mey. (tucumã) is highly consumed by riverside communities in the Amazonian region. These communities have recently been shown to have increased longevity and reduced prevalence of age-related morbidity. Tucumã, which is locally used in their diet and traditional medicine may contribute to these features. AIM OF THE STUDY: To investigate the anti-inflammatory and antioxidant properties of A. aculeatum extract against phytohemagglutinin-induced inflammation in cell cultures. MATERIALS AND METHODS: Cell viability and cytotoxicity assays, gene expression of interleukins IL-1ß, IL-6, IL-10, levels of reactive oxygen species (ROS), nitric oxide (NO) and thiols were employed, as well as the activities of antioxidant enzymes in RAW 264.7 cells stimulated with phytohemagglutinin to mimic inflammation. RESULTS: The extract of A. aculeatum fruit inhibited macrophage proliferation (P < 0.05), arrested the cell cycle in G0/G1 phase (P < 0.001), increased antioxidant defenses (P < 0.01), reduced oxidative stress (P < 0.01), and modulated genes related to the inflammatory response (P < 0.001). CONCLUSION: Our results demonstrate that A. aculeatum fruit has anti-inflammatory and antioxidant capacities. These beneficial effects of tucumã on cells are also likely to be seen in vivo, thereby suggesting that its extract is a suitable therapeutic adjuvant in the prevention or treatment of inflammatory diseases.

Protective effect of guarana-loaded liposomes on hemolytic activity.

Paullinia cupana var. sorbilis (Mart.) Ducke, popularly known as guarana, is one of the most promising plants in Brazilian flora and has attracted considerable interest from the scientific community owing to its numerous therapeutic activities and less side effects. Hence, using nanotechnology is a viable alternative to primarily improve the physicochemical characteristics and bioavailability of guarana. The objective of the present study was to develop, characterize, and evaluate the stability of liposomes containing guarana powder and to evaluate their antioxidant and hemolytic activity in vitro. Three different concentrations of guarana powder and two methods of liposome preparation were tested. Liposomes were developed and characterized, and their stability was analyzed by evaluating physicochemical parameters. Hemolytic activity of guarana liposomal formulation (G-Lip) was compared with that of guarana in its free form (FG) and of liposome without guarana (W-Lip). Red blood cells from rats were exposed to these different formulations dissolved in phosphate buffer solution (PBS; pH 7.4). The best stability was achieved for the formulation containing 1 mg mL-1 guarana powder produced by the reverse phase evaporation method. FG showed dose-dependent antioxidant activity, which was maintained in G-Lip. W-Lip showed high hemolytic activity in PBS at pH 7.4 possibly because of the presence of polysorbate 80, and on addition of guarana to these structures, the hemolytic process was reversed. The same protective effect was observed for FG. It is believed that the complex structure of guarana, primarily the presence of polyphenols, exerts a powerful antioxidant action, helping to protect erythrocytes.

Analysis of In Vitro Cyto- and Genotoxicity of Barbatimão Extract on Human Keratinocytes and Fibroblasts.

Barbatimão (Stryphnodendron adstringens, Mart.) is a native Brazilian species used in traditional medicine and some commercial preparations owing to its strong wound-healing activity. However, controversy regarding its use due to safety concerns over the potential genotoxic effect of this plant remains. In order to clarify this issue, the effect of hydroalcoholic extract of barbatimão in vitro on cell viability, DNA damage, and induction of apoptosis in two commercial cell lines of keratinocytes (HaCaT) and fibroblasts (HFF-1) was evaluated. Barbatimão stem bark hydroalcoholic extract (70% ethanol) was obtained and lyophilized for subsequent use in all experiments. The main bioactive molecules quantified by HPLC were gallic acid, caffeic acid, quercetin, catechin, and epigallocatechin gallate (EGCG). Barbatimão (0.024 to 1.99 mg/mL) was found to decrease cellular mortality as compared to the control group. GEMO assay, a noncellular DNA protocol that uses H2O2-exposed calf thymus DNA, revealed not only a genotoxic effect of barbatimão, but also a potential genoprotective action against H2O2-triggered DNA fragmentation. These results indicated that barbatimão at concentrations of 0.49 and 0.99 mg/mL, which are near to the levels found in commercial preparations, exerted an in vitro genoprotective effect on cells by decreasing the levels of DNA oxidation quantified by 8-hydroxy-2'-deoxyguanosine (8-OHdG) and reactive oxygen species (ROS) levels. Gene and protein apoptotic markers, quantified by qRT-PCR (BAX/Bcl-2 genes) and immunoassays (Caspases 3 and 8), respectively, also indicated a decrease in apoptotic events in comparison with control cells. Collectively, the results suggest that barbatimão could exert genoprotective and antiapoptotic effects on human keratinocytes and fibroblasts.

Guaraná, a Highly Caffeinated Food, Presents in vitro Antitumor Activity in Colorectal and Breast Cancer Cell Lines by Inhibiting AKT/mTOR/S6K and MAPKs Pathways.

The mammalian target of rapamycin (mTOR) and mitogen-activated protein kinases (MAPKs) pathways are frequently upregulated in cancer. Some authors have reported that some antioxidant molecules could be potential inhibitors of these pathways. Therefore, we investigated the in vitro antitumor effect of guaraná by inhibiting the AKT/mTOR/S6K and MAPKs pathways. Colorectal and breast cancer cell lineages, HT-29 and MCF-7 cells, respectively, were exposed to different guaraná concentrations (0.1, 1, 10, and 100 µg/mL) as well as its main bioactive molecule, caffeine, in proportional concentrations to those found in the extract. Western blot, clonogenic assay, and growth curve were performed. Moreover, we investigated the potential cytotoxic effect of guaraná in normal cells. The results revealed that guaraná and caffeine inhibited some MAPKs proteins (p-p38 and p-HSP27) in MCF-7 cells. However, they did not affect this pathway in HT-29 cells. Furthermore, guaraná inhibited mTORC1 (p-S6K) and mTORC2 (p-AKT) in MCF-7 cells, but only mTORC1 in HT-29 cells. Caffeine only inhibited the mTOR pathway in MCF-7 cells. Guaraná decreased the colony formation and cell growth in MCF-7 and HT-29 cells. Guaraná did not affect normal cells. In conclusion, guaraná could be an important agent in antitumor pharmacologic therapies by inhibiting the mTOR and MAPKs pathways.

Association between T102C 5-HT2A receptor gene polymorphism and 5-year mortality risk among Brazilian Amazon riparian elderly population.

OBJECTIVE: Serotonin (5-HT) is a pleiotropic molecule that exerts several functions on brain and peripheral tissues via different receptors. The gene for the 5-HT2A receptor shows some variations, including a T102C polymorphism, that have been associated with increased risk of neuropsychiatric and vascular disorders. However, the potential impact of 5-HT2A imbalance caused by genetic variations on the human lifespan has not yet been established. METHODS: We performed a prospective study involving an Amazon riparian elderly free-living population in Maués City, Brazil, with a 5-year follow-up. Out of a cohort of 637 subjects selected in July, 2009, we genotyped 471 individuals, including 209 males (44.4%) and 262 females (55.6%), all averaging 72.3 ± 7.8 years of age (ranging from 60 to 100 years). RESULTS: The T102C-SNP genotypic frequencies were 14.0% TT, 28.0% CC, and 58.0% CT. From 80 elderly individuals who died during the period investigated, we observed significantly (P = .005) higher numbers of TT carriers (27.3%) and CC carriers (21.2%), compared to heterozygous CT carriers (12.5%). Cox-regression analysis showed that association between the T102C-SNP and elderly survival was independent of age, sex, and other health variables. CONCLUSIONS: Our findings strongly suggest that imbalance in 5-HT2A may cause significant disturbances that lead to an increased susceptibility to death for individuals who are over 60 years of age.

Impact of functional determinants on 5.5-year mortality in Amazon riparian elderly.

Objective To ascertain whether modifiable physical performance-based measurements predicted 5.5-year mortality in a riparian elderly cohort in the Amazon rainforest region. Methods A longitudinal study evaluating the impact of functional determinants on 5.5-year mortality in a riparian elderly cohort from Maués City in the state of Amazonas, Brazil, was performed. The study was a follow-up of a previous observational investigation that evaluated various fitness tests in 630 Amazonian riparian elderly (291 males and 339 females) aged 72.3 ± 8.0 (60-99) years old. The cohort was selected for its adverse environmental conditions, which increased the risk of falls yet required maintenance of good physical condition for carrying out relatively rigorous daily activities, and restricted access to specialized health services. Official death records were obtained from the Maués Municipal Health Department. Results A total of 80 study participants (12.7%) died over the 5.5-year study period. Kaplan-Meier regression analysis showed significant association between Timed Up and Go (TUG) test scores ≥ 14 seconds and mortality risk, independent of sex, age, and other health variables. Conclusions The study results suggest that the TUG test can be used as an indicator for initiating therapeutic and preventive actions, including conducting exercises or physical activities adapted to the health and functional conditions of the elderly, by identifying elderly people with a higher relative risk of mortality.

Impact of functional determinants on 5/5-year mortality in Amazon riparian elderly / Influencia de los determinantes de la capacidad funcional sobre la mortalidad a 5/5 años de los ancianos de las zonas ribereñas del Amazonas

ABSTRACT Objective To ascertain whether modifiable physical performance–based measurements predicted 5.5-year mortality in a riparian elderly cohort in the Amazon rainforest region. Methods A longitudinal study evaluating the impact of functional determinants on 5.5-year mortality in a riparian elderly cohort from Maués City in the state of Amazonas, Brazil, was performed. The study was a follow-up of a previous observational investigation that evaluated various fitness tests in 630 Amazonian riparian elderly (291 males and 339 females) aged 72.3 ± 8.0 (60–99) years old. The cohort was selected for its adverse environmental conditions, which increased the risk of falls yet required maintenance of good physical condition for carrying out relatively rigorous daily activities, and restricted access to specialized health services. Official death records were obtained from the Maués Municipal Health Department. Results A total of 80 study participants (12.7%) died over the 5.5-year study period. Kaplan-Meier regression analysis showed significant association between Timed Up and Go (TUG) test scores ≥ 14 seconds and mortality risk, independent of sex, age, and other health variables. Conclusions The study results suggest that the TUG test can be used as an indicator for initiating therapeutic and preventive actions, including conducting exercises or physical activities adapted to the health and functional conditions of the elderly, by identifying elderly people with a higher relative risk of mortality.

RESUMEN Objetivo Evaluar si los parámetros modificables del rendimiento físico permiten predecir la mortalidad a 5,5 años en una cohorte de ancianos de las zonas ribereñas de la selva tropical del Amazonas. Métodos En este estudio longitudinal se evaluó la influencia de los determinantes de la capacidad funcional sobre la mortalidad a 5,5 años en una cohorte de ancianos de la ciudad ribereña de Maués del estado de Amazonas (Brasil). El estudio consistió en un seguimiento de una investigación observacional anterior en la que se efectuaron diversas pruebas para determinar el estado físico de 630 ancianos de las zonas ribereñas del Amazonas (291 hombres y 339 mujeres) de 72,3 años de edad ± 8,0 (60-99) años. La cohorte fue seleccionada en función de las condiciones ambientales adversas, que aumentan el riesgo de caídas pero exigen un buen estado físico para llevar adelante las actividades relativamente rigurosas de la vida cotidiana, así como del acceso limitado a servicios de salud especializados. Los certificados de defunción oficiales se obtuvieron del Ministerio de Salud del Municipio de Maués. Resultados En el transcurso del estudio, que tuvo una duración de 5,5 años, fallecieron 80 participantes (12,7 %). El análisis de regresión de Kaplan-Meier reveló una relación significativa entre los valores de la prueba cronometrada de levantarse y caminar (TUG) ≥ 14 segundos y el riesgo de mortalidad, que fue independiente del sexo, la edad y demás variables de salud. Conclusiones Los resultados de este estudio indican que la prueba TUG puede emplearse como indicador de la necesidad de instituir medidas terapéuticas y preventivas, como ejercicios o actividades físicas adaptadas a la salud y el estado funcional de los ancianos, dado que permite detectar a aquellos que están expuestos a un riesgo relativo de muerte más alto.