Acetogenins-Rich Fractions of Annona coriacea Suppress Human Glioblastoma Viability and Migration by Regulating Necroptosis and MMP-2 Activity In Vitro.

Glioblastoma (GBM) is an incurable primary brain tumor with a poor prognosis. Resection, radiation therapy, and temozolomide (TMZ) are insufficient to increase survival, making the treatment limited. Thus, the search for more effective and specific treatments is essential, making plants a promising source for elucidating new anti-glioblastoma compounds. Accordingly, this study investigated the effects of four fractions of hexane and ethyl acetate extract of Annona coriacea Mart., enriched with acetogenins, against GBM cell lines. All four fractions were selectively cytotoxic to GBM cells when compared to TMZ. Moreover, A. coriacea fractions delayed cell migration; reduced cytoplasmic projections, the metalloproteinase 2 (MMP-2) activity; and induced morphological changes characteristic of necroptosis, possibly correlated with the increase in receptor-interacting protein kinase 1 and 3 (RIP-1 and RIP-3), apoptosis-inducing factor (AIF), and the non-activation of cleaved caspase 8. The present findings reinforce that fractions of A. coriacea Mart. should be considered for more studies focusing treatment of GBM.

An Integrative Approach to the Flavonoid Profile in Some Plants' Parts of the Annona Genus.

The Annonaceae family is widely distributed in subtropical and tropical regions. Several species of this family are known for their pharmacological and beneficial properties to human health, mainly attributed to flavonoids. The objective of this work was to carry out an integrative review in order to identify the main flavonoids found in some plant parts belonging to the Annona genus: araticum tree (Annona crassiflora Mart.), graviola tree (Annona muricata), atemoya tree (Annona cherimolia Mill × Annona squamosa L.), pinha tree (Annona squamosa), bananinha tree (Annona leptopetala), and marolinho tree (Annona coriacea). Only articles published between the years 2016 to 2021 that answered the guiding question were considered, in order to obtain recent data. Then, search strategies were designated for each database used: Science Direct, CAPES Periodicals, and Scielo. Most of the studies retrieved from the databases are related to fruits. The results showed that the number of flavonoids identified varies according to the analytical methodology used to identify and quantify the compounds. Quercetin was the most commonly found compound in all fruits of the Annona genus studied, and epicatechin, rutin, and kaempferol were also found to a lesser extent. The presence of these compounds in Annona makes the fruit promising, with potential applicability in the pharmaceutical and food industry.

Qualitative analysis of the acetogenins from Annona coriacea (Annonaceae) leaves by HPLC-Q-Orbitrap and their antibacterial potential against oral pathogens.

Araticum is an edible and appreciable fruit of Annona coriacea, which is popularly known as a traditional herb in the Brazilian cerrado. A phytochemical study from the leaves of A. coriacea showed that HPLC-ESI-Q-Orbitrap® provided through PRM experiments (MS2) is an efficient method for the fast and accurate analysis of a complex mixture of annonaceous acetogenins, with the identification of sylvaticin and gigantetrocin-A type acetogenins for the first time. In addition, the crude leaf extract and acetogenin-rich fractions were assayed against Streptococcus mutans, S. mitis, S. sanguinis and S. salivarius strains, which are usually related to oral infections.

Phytochemicals and biological properties of Annona coriacea Mart. (Annonaceae): A systematic review from 1971 to 2020.

Annona coriacea Mart., popularly known as "marolo", "araticum" and "araticum-liso" is a species distributed in Paraguay and Brazil, and easily found in Caatinga, Cerrado, and Pantanal biomes. The araticum has been used in folk medicine to treat stomatitis, neuralgia, rheumatism, headaches, furuncle, ulcers, and dermatitis. This systematic review aimed to provide a comprehensive overview of the ethnomedicinal use, phytochemistry, and pharmacological activity of A. coriacea. A search for scientific articles of electronic databases (Science Direct, PubMed, Lilacs, Scopus, Google Scholar, Scielo, and Web of Science) was performed identifying studies published until November 2020. All papers considering traditional medicinal uses, phytochemistry, and pharmacological properties were included. Forty-six articles (n = 212 subjects) met the inclusion criteria set for this review. Of the 46 articles reviewed, 34 were focused on biological activity investigations, while 12 were limited to phytochemical studies. These studies showed the presence of a diversity of secondary metabolites such as acetogenins, sesquiterpenes, alkaloids, flavonoids, and diterpenes. To date, pharmacological tests have demonstrated significant biological activities of this plant, being the most promising anticancer, anti-inflammatory, antiulcer, and insecticide activities. Additionally, the medicinal utilization of A. coriacea appears to be promising, supporting its possible uses for human health with antioxidant, anxiolytic, antiulcer, insecticide, and antiparasitic activities. Ultimately, comprehensive studies involving clinical trials are required to validate the existing traditional practices and their related health benefits scientifically.

Effects of Acetogenins from Annona coriacea on the in Vitro Reactions of Photosynthesis.

Our search for candidates for photosynthesis inhibitors is allowing us to report the effect of two acetogenins identified in Annona coriacea Mart. leaves, ACG-A and ACG-B, a non-adjacent bis-THF and a mono-THF types, respectively. This is an important class of natural products which presents biological properties such as anticancer, neurotoxic, larvicidal and insecticidal. However, this is only the second report associated to its herbicidal activity. Their mechanisms of action on the light reactions of the photosynthesis were elucidated by polarographic techniques. Compounds inhibited the noncyclic electron transport on basal, phosphorylating, and uncoupled conditions from H2 O to methyl viologen (MV); therefore, they act as Hill reaction inhibitors. Studies on fluorescence of chlorophyll a (ChL a) indicated that they inhibited the acceptor side of PSII between P680 and PQ-pool, exactly as the commercial herbicide DCMU does.

Anxiolytic and antidepressant-like effects of Annona coriacea (Mart.) and caffeic acid in mice.

This research evaluated the anxiolytic and antidepressant-like effects of a hydroethanolic extract from the leaves of Annona coriacea (EHFAC) and caffeic acid (CA). Mice were intraperitoneally treated with saline, EHFAC (1, 10, 20 mg/kg) or CA (0.15 mg/kg) and subject to the elevated plus-maze, open field, rota-rod, forced swimming and reserpine-induced akinesia tests. Pro-convulsant and anticholinergic effects were also evaluated. EHFAC presented anxiolytic-like effect on the elevated plus-maze, which was partially reversed by flumazenil. A similar effect was observed with CA. In the forced swimming test, EHFAC and CA reduced the immobility time of mice; such effect was potentiated when EHFAC or CA were associated with imipramine, bupropion and fluoxetine. The antidepressant-like effect was reinforced as EHFAC partially reversed the reserpine-induced akinesia. In addition, a pre-treatment with EHFAC and CA did not decrease the latency to 1st seizure of animals that received a sub-convulsive dose of PTZ, nor reduced the intensity of oxotremorine-induced tremors. Taken together, the results indicate that EHFAC and CA have anxiolytic and antidepressant-like effects, which involve important neurotransmitter systems, such as GABAergic and monoaminergic ones, being devoid of side effects, commonly associated with classical psychotropic drugs.

Chemical Characterization and Cytoprotective Effect of the Hydroethanol Extract from Annona coriacea Mart. (Araticum).

INTRODUCTION: Annona coriacea Mart. (araticum) is a widely distributed tree in the cerrado. Its value is attributed principally to the consumption of its fruit which possesses a large nutritive potential. The objective was to identify the chemical profile and evaluate the antimicrobial and cytoprotective activity of the hydroethanol extract of A. coriacea Mart. (HEAC) leaves against the toxicity of mercury chloride. MATERIALS AND METHODS: The characterization of components was carried out using high-performance liquid chromatography (HPLC). The minimum inhibitory concentration (MIC) was determined by microdilution method in broth with strains of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. For evaluation of the modulatory and cytoprotective activity of aminoglycoside antibiotics (gentamicin and amikacin) and mercury chloride (HgCl2), the substances were associated with the HEAC at subinhibitory concentrations (MIC/8). RESULTS AND DISCUSSION: The HPLC analysis revealed the presence of flavonoids such as Luteolin (1.84%) and Quercetin (1.19%) in elevated concentrations. The HEAC presented an MIC ≥512 µg/mL and significant antagonistic action in aminoglycosides modulation, and it also showed cytoprotective activity to S. aureus (significance P < 0.0001) and E. coli (significance P < 0.05) bacteria against the mercury chloride heavy metal with significance, this action being attributed to the chelating properties of the flavonoids found in the chemical identification. CONCLUSIONS: The results acquired in this study show that the HEAC presents cytoprotective activity over the tested strains in vitro and can also present antagonistic effect when associated with aminoglycosides, reinforcing the necessity of taking caution when combining natural and pharmaceutical products. SUMMARY: The hydroalcoholic extract of A. coriacea Mart. presents in vitro cytoprotective activity against the toxic effect of Hg. Abbreviations Used: HPLC-DAD: High-performance liquid chromatography with a diode array detector; MIC: Minimum inhibitory concentration; DMSO: Dimethyl sulfoxide.

Biocide activity of Annona coriacea seeds extract on Rhodnius neglectus (Hemiptera: Reduviidae)

The use of synthetic insecticides for insect control may lead to different kind of problems, such as vector resistance to insecticides. To avoid these problems, a new research area to study botanical products as possible disease vectors controls, has become a feasible alternative. The purpose of this research was to evaluate the biocide activity of the ethanol extract of seeds of Annona coriacea on Rhodnius neglectus (Chagas disease vector) nymphs and adults. For this, different concentrations extracts were evaluated: 25, 50, 100 and 200mg/ mL, and water in DMSO (20%) was used as control. The experimental design was completely randomized and we conducted the bioassay with nymphs and adults, with 10 nymphs and 10 adults (five males and five females) per treatment. Extract action was evaluated in both bioassays, in order to identify possible effects of mortality and life cycle interruption of nymphs and adults during a 28-day-period. The results obtained showed that the extract of A. coriacea was able to disrupt the development of nymphs and adults of R. neglectus, with a mortality rate of more than 90%, 36% and 100%, at the highest concentrations, respectively. There was also molting inhibition in nymphs, lower reproductive capacity in females, feeding deterrence and morphological changes in nymphs and adults. We concluded that the extract of A. coriacea has insecticide action on nymphs and adults of R. neglectus.

La enfermedad de Chagas se convirtió en un problema de salud debido a su importancia epidemiológica, es producida por el protista Trypanosoma cruzi, cuyos insectos vectores son del género Triatoma y Panstrongylus. El objetivo de este estudio fue evaluar la actividad biocida del extracto de Annona coriacea en las ninfas de Rhodnius neglectus y en sus adultos. Se evaluaron 14 concentraciones de 25, 50, 100 y 200mg/ml del extracto etanólico, así como el control, en este caso agua de DMSO (20%). Se utilizo un diseño completamente aleatorizado con tres repeticiones para el bioensayo con 10 ninfas y 10 adultos (cinco machos y cinco hembras) para cada tratamiento. La acción del extracto se observo durante 28 días en ambos bioensayos. Los resultados obtenidos mostraron que el extracto de A. coriacea fue capaz de interrumpir el desarrollo de las ninfas y adultos de R. neglectus, con una mortalidad de más del 90%, 36% y 100%, correspondiendo a las concentraciones más altas. También hubo inhibición de la muda de las ninfas, una menor capacidad reproductiva de las hembras, disuasión alimentaria y cambios morfológicos en las ninfas y adultos. Se concluye que el extracto de A. coriacea presentó acción insecticida en ninfas y adultos de R. neglectus.

Investigation of the toxic potential of crude ethanol extract of Annona coriacea (araticum) seeds in acute exposed mice

In this study, Annona coriacea Mart., Annonaceae, was examined for possible toxic effects on brain, liver and kidney of mice exposed to crude extract of the seeds (CESAN) of this plant. CESAN was administered by gavage for four days at doses of 12.5, 25, 50, and 100 mg/kg/day. Significant changes on liver were observed, which showed reduction in the number of hepatocytes per area and increase the apoptotic index in the exposed groups, and changes in the cytoplasm and nucleus of these cells and reduced consumption of water and feed in these animals. For the other studied areas, brain and kidneys showed no changes in the parameters used in this study. The results suggest hepatotoxic effects of CESAN, but without damage to brain and kidneys in this experiment, showing a toxic potential to this species, as to the Annonaceae family.

Chemical constituents of the volatile oil from leaves of Annona coriacea and in vitro antiprotozoal activity

The essential oil of the leaves from Annona coriacea Mart., Annonaceae, was extracted by hydrodistillation in a Clevenger apparatus and analyzed by GC/MS and GC/FID. The oil yield was 0.05 percent m/m. Sixty compounds were identified, in a complex mixture of sesquiterpenes (76.7 percent), monoterpenes (20.0 percent) and other constituents (3.3 percent). Bicyclogermacrene was its major compound (39.8 percent) followed by other sesquiterpenes. Most of the monoterpenes were in low concentration (<1 percent). Only β-pinene and pseudolimonene presented the highest level of 1.6 percent. The volatile oil presented anti-leishmanial and trypanocidal activity against promastigotes of four species of Leishmania and trypomastigotes of Trypanosoma cruzi, showing to be more active against Leishmania (L.) chagasi (IC50 39.93 µ g/mL) (95 percent CI 28.00-56.95 µ g/mL).