Evaluation of cytotoxicity, acute toxicity, genotoxicity and antioxidant and antigenotoxicity activities of the sarcotesta fraction of punica granatum L. rich in lectin (PgTel).

Punica granatum, popularly known as pomegranate, is a fruit tree with wide worldwide distribution, containing numerous phytochemicals of great medicinal value. The aim of the present study was to determine the phytochemical profile and antioxidant potential of a protein fraction (PF) derived from P. granatum sarcotesta which is rich in lectin. In addition, the acute oral toxicity, genotoxicity and antigenotoxicity of this protein fraction (PF) from P. granatum sarcotesta was measured. The phytochemical profile of PF was determined using HPLC. The in vitro antioxidant effect was assessed using the methods of total antioxidant capacity (TAC) and DPPH and ABTS+ radical scavenging. Acute oral toxicity was determined in female Swiss mice administered a single dose of 2000 mg/kg. This PF was examined for genotoxicity and antigenotoxicity at doses of 500, 1000 and 2000 mg/kg, utilizing mouse peripheral blood cells. Phytochemical characterization detected a high content of ellagic acid and antioxidant capacity similar to that of ascorbic acid (positive control). PF was not toxic (LD50 >2000 mg/kg) and did not exert a genotoxic effect in mice. PF protected the DNA of peripheral blood cells against damage induced by cyclophosphamide. In conclusion, this PF fraction exhibited significant antioxidant activity without initiating toxic or genotoxic responses in mice.

Development of gel containing Psidium glaziovianum essential oil has in vitro antimicrobial activity and improves healing of excisional wounds in mice.

Wounds encompass physical, chemical, biological, induced damages to the skin or mucous membranes. In wound treatment, combating infections is a critical challenge due to their potential to impede recovery and inflict systemic harm on patients. Previously, the essential oil extracted from Psidium glaziovianum (PgEO) demonstrated antinociceptive and anti-inflammatory attributes, along with negligible oral toxicity. Hence, our study aimed to assess the effects of topically applying a gel formulation containing PgEO to excisional wounds in mice. Additionally, an in vitro antimicrobial assessment was conducted. The formulated gel underwent characterization and toxicological evaluation on erythrocytes, as well as a dermal irritation test. Its antimicrobial activity was tested against both gram-positive and gram-negative bacteria, as well as fungi. Subsequently, an assessment of its efficacy in excisional wound healing was conducted in mice. The findings of this investigation highlight the gel's efficacy against both gram-positive and gram-negative bacteria, as well as fungi. Moreover, this study underscores that the PgEO-gel treatment enhances skin wound healing, potentially due to its capacity to trigger antioxidant enzymes and suppress pro-inflammatory cytokines. Furthermore, the gel exhibited minimal toxicity to erythrocytes and skin irritation. These findings hold promise for prospective preclinical and clinical trials across diverse wound types. In conclusion, this study sheds light on the potential therapeutic applications of the gel formulation containing essential oil from P. glaziovianum in the context of wound healing.

Insecticidal activity of essential oil from leaves of Eugenia stipitata McVaugh against Aedes aegypti.

Aedes aegypti, a mosquito, is responsible for the spread of many diseases, including dengue, zika, and chikungunya. However, due to this mosquito's developed resistance to conventional pesticides, effectively controlling it has proven to be challenging. This study aimed to evaluate the insecticidal potential of the essential oil from the leaves of Eugenia stipitata against Ae. aegypti, offering a natural and sustainable alternative for mosquito control. Tests were conducted using third-stage larvae to evaluate larvicidal activity and pupae collected up to 14 h after transformation to investigate pupicidal activity. Throughout the bioassays, the organisms were exposed to various essential oil concentrations. The findings demonstrated that the essential oil of E. stipitata exhibited larvicidal action, resulting in 100% larval mortality after 24 h and an LC50 value of 0.34 mg/mL. The effectiveness of essential oil as a pupicidal agent was also demonstrated by its LC50 value of 2.33 mg/mL and 100% larval mortality in 24 h. It can be concluded that the essential oil of E. stipitata holds promise as a natural pest control agent. Its use may reduce the reliance on conventional chemical pesticides, providing a more sustainable and effective strategy to combat diseases spread by mosquitoes.

Essential oil from leaves of Myrciaria floribunda (H. West ex Willd.) O. Berg has antinociceptive and anti-inflammatory potential.

Myrciaria floribunda is a plant that is distributed across different Brazilian biomes such as the Amazon, Caatinga, Cerrado, and Atlantic Forest, and it possesses antioxidant, antimicrobial, and anticancer properties. The antinociceptive and anti-inflammatory properties of the essential oil from M. floribunda leaves (MfEO) were examined in this study using mouse models. Gas chromatography-mass spectrometry was employed to describe the oil, and the results revealed that δ-cadinene, bicyclogermacrene, α-cadinol, and epi-α-muurolol predominated in the chemical profile. The oil stimulated a decrease in nociception in the chemical and thermal models used to evaluate acute antinociceptive activity. Findings from the use of pain pathway blockers to study the presumed underlying mechanism indicated opioid pathway activity. The anti-edematogenic effect, decreased cell migration, and generation of pro-inflammatory cytokines provided evidence of the anti-inflammatory potential of the essential oil from M. floribunda. According to this research, the essential oil from M. floribunda can effectively alleviate acute pain and inflammation.

Toxicological safety, antioxidant activity and phytochemical characterization of leaf and bark aqueous extracts of Commiphora leptophloeos (Mart.) J.B. Gillett.

This study aimed to characterize the phytochemical profile of bark and leaves aqueous extract Commiphora leptophloeos, and conduct in vivo and in vitro assays to determine the presence of any toxicological consequences due to exposure. The phytochemical analysis was carried out using high-performance liquid chromatography (HPLC). The antioxidant activity was estimated utilizing DPPH free radical scavenging and phosphomolybdenum assays. Cell viability was measured by the MTT method on J774 and human adenocarcinoma cells, which were treated with concentrations of 12,5, 25, 50, 100 or 200 µg/ml of both extracts. Acute oral toxicity, genotoxicity, and mutagenicity assays were determined using a single oral dose of 2000 g/kg in male Swiss albino mice (Mus musculus). Biochemical analysis of the blood and histological analyses of the kidneys, liver, spleen, pylorus, duodenum and jejunum were undertaken. Genotoxicity and mutagenicity were determined utilizing blood samples. Gallic acid, catechin, and epicatechin were identified in the bark and chlorogenic acid in leaves. Data demonstrated a high content of phenolic compounds and flavonoids associated with significant antioxidant potential. No significant signs in damage or symptoms of toxicity were detected. No marked reduction in cell viability was found at lower concentrations tested. On histomorphometry, only the gastrointestinal organs exhibited significant difference. Renal hepatic and blood parameters were within the normal range. No apparent signs of toxicity, genotoxicity, mutagenicity or cytotoxicity were found in vivo and in vitro experiments.

Saline extract of Portulaca elatior leaves with photoprotective and antioxidant activities does not show acute oral and dermal toxicity in mice.

The present study aimed to evaluate saline extracts from the leaves (LE) and stem (SE) of Portulaca elatior in relation to their phytochemical composition and photoprotective and antioxidant effects, as well as to evaluate the toxicity of the leaf extract. The extracts were characterized for protein concentration and phenol and flavonoid contents, as well as for thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) profiles. Total antioxidant capacity and DPPH and ABTS+ scavenging activities were determined. In the photoprotective activity assay, the sun protection factor (SPF) was calculated. The toxicity evaluation of LE included in vitro hemolytic assay and in vivo oral and dermal acute toxicity assays in Swiss mice. LE showed the highest protein, phenol, and flavonoid (8.79 mg/mL, 323.46 mg GAE/g, and 101.96 QE/g, respectively). TLC revealed the presence of flavonoids, reducing sugars, terpenes, and steroids in both extracts. In HPLC profiles, LE contained flavonoids, while SE contained flavonoids and ellagic tannins. The antioxidant activity assays showed the lowest IC50 values ​(34.15-413.3 µg/mL) for LE, which presented relevant SPF (> 6) at 50 and 100 µg/mL. LE demonstrated low hemolytic capacity, and no signs of intoxication were observed in mice treated orally or topically at 1000 mg/kg. However, at 2000 mg/kg, an increase in the mean corpuscular volume of erythrocytes and a reduction in lymphocytes were observed; animals treated topically with 2000 mg/kg displayed scratching behavior during the first hour of observation and showed edema and erythema that regressed after six days. In conclusion, LE did not present acute oral or dermal toxicity in Swiss mice at a dose of 1000 mg/kg and showed slight toxicity in animals treated with 2000 mg/kg. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-022-00160-2.

α-Pinene: Docking Study, Cytotoxicity, Mechanism of Action, and Anti-Biofilm Effect against Candida albicans.

Candida albicans is associated with serious infections in immunocompromised patients. Terpenes are natural-product derivatives, widely studied as antifungal alternatives. In a previous study reported by our group, the antifungal activity of α-pinene against C. albicans was verified; α-pinene presented an MIC between 128-512 µg/mL. In this study, we evaluate time-kill, a mechanism of action using in silico and in vitro tests, anti-biofilm activity against the Candida albicans, and toxicity against human cells (HaCaT). Results from the molecular-docking simulation demonstrated that thymidylate synthase (-52 kcal mol-1), and δ-14-sterol reductase (-44 kcal mol-1) presented the best interactions. Our in vitro results suggest that α-pinene's antifungal activity involves binding to ergosterol in the cellular membrane. In the time-kill assay, the antifungal activity was not time-dependent, and also inhibited biofilm formation, while rupturing up to 88% of existing biofilm. It was non-cytotoxic to human keratinocytes. Our study supports α-pinene as a candidate to treat fungal infections caused by C. albicans.

Eugenia gracillima essential oil has pharmaceutical applications in pain and inflammation without toxic effects in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Eugenia gracillima is widely used by the population in the manufacture of pulps and jellies, with popular reports of its use in the treatment of infections in the urinary system, respiratory and dermatological problems. A previous study reports that EO from E. gracillima leaves proved to be a promising antioxidant agent in combating the promastigote forms of protozoa. Despite this, this species has been little studied due to its pharmacological properties. STUDY OBJECTIVE: In this study, an essential oil extracted (EO) from Eugenia gracillima leaves was evaluated for its acute toxicity and anti-inflammatory, antinociceptive and behavioral effects in mice. METHODS: The EO was obtained by hydrodistillation, and the composition analysis was performed by gas chromatography coupled to mass spectrometry. Acute toxicity assessment was performed with observation of hematological parameters and histopathological evaluation, as well as tests to investigate antinociceptive, anti-inflammatory activities and behavioral effects. RESULTS: Chromatographic analysis showed D-germacrene (16.10%), γ-muurolene-g (15.60%) and bicyclogermacrene (8.53%) as the majority of compounds. In the toxicity evaluation, no death or physiological changes were observed in mice treated with a single oral dose of up to 5000 mg/kg, and it did not lyse erythrocytes in vitro. The hematological parameters evaluated were not changed after treatment; however, 5,000 mg/kg promoted an increase in transaminase levels. In the histopathological evaluation, only the animals that received the dose of 5000 mg/kg showed discrete leukocyte infiltration around the centrilobular vein in the liver. Antinociceptive activity was detected through tests of acetic acid-induced writhing, formalin, and tail flick, promoted in part by the opioid receptor pathway. In the evaluation of anti-inflammatory activity, a reduction in inflammation was observed in the paw edema test and a decrease in the migration of leukocytes and neutrophils in the peritonitis test. The open field and elevated plus maze tests showed that EO did not affect the animals' motor functions or exploratory activity. CONCLUSION: It was concluded that the essential oil of E. gracillima has potential for the development of pharmaceutical formulations with analgesic and anti-inflammatory actions in non-toxic concentrations.

Antimicrobial and anti-inflammatory effects of Eugenia brejoensis essential oil in mice wounds infected by Staphylococcus aureus.

Eugenia brejoensis Mazine (Myrtaceae) is source of an essential oil (EbEO) with anti-infective activities against Staphylococcus aureus. This study evaluated the antimicrobial and anti-inflammatory potentials of EbEO in S. aureus-infected skin wounds. The excisional lesions (64 mm2) were induced on Swiss mice back (6 to 8-week-old) that were allocated into 3 groups (n = 12): 1) non-infected wounds (CON); 2) wounds infected with S. aureus ATCC 6538 (Sa); 3) S. aureus-infected wounds and treated with EbEO (Sa + EbEO). The infected groups received approximately 104 CFU/wound. The animals were treated with EbEO (10 µg/wound/day) or vehicle from the 1-day post-infection (dpi) until the 10th dpi. The clinical parameters (wound area, presence of exudate, edema intensity, etc.) were daily analyzed. The levels of inflammatory mediators (cytokines, nitric oxide, VEGF) and bacterial load were measured at the cutaneous tissue at 4th dpi and 10th dpi. Topical application of EbEO accelerated wound contraction with an average contraction of 83.48 ± 11.27 % of the lesion area until 6th dpi. In this period, the rates of lesion contraction were 54.28 ± 5.57% and 34.5 ± 2.67% for CON and Sa groups, respectively. The positive effects of EbEO on wound contraction were associated with significantly (p < 0.05) reduction on bacterial load and the release of inflammatory mediators (IL-6, IL-17A, TNF-α, NO and VEGF). Taken together, these data confirm the antimicrobial potential of EbEO and provide insights into its anti-inflammatory effects, making this essential oil an interesting candidate for the development of new therapeutic alternatives for infected cutaneous wounds.

Evaluation of ellagic acid and gallic acid as efflux pump inhibitors in strains of Staphylococcus aureus.

The Gram-positive bacterium Staphylococcus aureus is responsible for a number of infections and has been described to exhibit resistance to antibacterial drugs through different resistance mechanisms. Among these, active efflux has been shown to be one of the main mechanisms of bacterial resistance associated with S. aureus. In this sense, the aim of the present study was to evaluate the ability of ellagic acid and gallic acid to reverse resistance by inhibiting the efflux pumps present in S. aureus strains IS-58 and K2068, which express the TetK and MepA flux pumps, respectively. In addition, the toxicity of both compounds was verified in Drosophila melanogaster. Broth microdilution assays were performed to obtain the minimum inhibitory concentration (MIC) values of ellagic acid and gallic acid, whereas efflux pump inhibition was tested using a subinhibitory concentration of standard efflux pump inhibitors, gallic acid and ellagic acid (MIC/8), where the ability of these compounds to decrease the MIC of ethidium bromide (EtBr) and antibiotics was verified. Toxicity was evaluated by mortality and negative geotaxis assays in D. melanogaster. Ellagic acid and gallic acid showed no direct antibacterial activity on S. aureus strains carrying the efflux pumps TetK and MepA. However, when we looked at the results for the TetK pump, we saw that when the two acids were associated with the antibiotic tetracycline, a potentiation of the antibacterial effect occurred; this behavior was also observed for the antibiotic ciprofloxacin in the MepA strain. For the efflux pump inhibition results, only the compound gallic acid showed potentiating effect on antibacterial activity when associated with the substrate EtBr for the IS-58 strain carrying the TetK efflux pump. Ellagic acid and gallic acid showed no toxicity on the model arthropod D. melanogaster. These results indicate the possible use of gallic acid as an adjuvant in antibiotic therapy against multidrug-resistant bacteria.

Essential oil from the leaves of Eugenia pohliana DC. (Myrtaceae) alleviate nociception and acute inflammation in mice.

Eugenia pohliana DC.(Myrtaceae) is used in folk medicine by communities in Brazil. However, there are no reports on its biological activity. This is the first study to identify the components of E. pohliana essential oil (EpEO) and evaluate their antinociceptive and anti-inflammatory activities in an in vivo model at doses of 25, 50, and 100 mg/kg. The essential oil (EO) was obtained by hydrodistillation, and the analysis was performed by gas chromatography coupled with mass spectrometry. Antinociceptive activity was evaluated by writhing tests, tail movement, and formalin (neurogenic and inflammatory pain); naloxone was used to determine the nociception mechanism. Anti-inflammatory activity was assessed by oedema and peritonitis tests. We found that (E)-ß-caryophyllene (BCP) (15.56%), δ-cadinene (11.24%) and α-cadinol (10.89%) were the major components. In the writhing test, there was a decrease in writing by 42.95-70.70%, in the tail movement, an increase in latency time by 69.12-86.63%, and in the formalin test, there was a reduction in pain neurogenic by 29.54-61.74%, and inflammatory pain by 37.42-64.87%. The antinociceptive effect of EpEO occurs through the activation of opioid receptors. In addition, a reduction in inflammation by 74.93‒81.41% was observed in the paw edema test and inhibition of the influx of leukocytes by 51.86‒70.38% and neutrophils by 37.74‒54.72% in the peritonitis test. It was concluded that EpEO has antinociceptive effect by the opioid pathway, as shown by the inhibitory effect of naloxone, and anti-inflammatory actions, and that its use does not cause hemolytic damage or behavioral change.

Inhibition of Staphylococcus aureus Efflux Pump by O-Eugenol and Its Toxicity in Drosophila melanogaster Animal Model.

Background: Efflux pumps are transmembrane proteins that expel drugs out of a bacterial cell contributing to microorganism drug resistance. Several studies addressing the use of natural products with medicinal properties have intensified given the above. Thus, the aim of the present study was to investigate the antibacterial activity and the O-eugenol potential in Staphylococcus aureus resistance reversal by efflux pump inhibition, as well as to evaluate its toxicity in the Drosophila melanogaster arthropod model. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) and the O-eugenol efflux pump inhibition. For the D. melanogaster toxicity assays, mortality and locomotor system damage were performed using the fumigation method. Results: O-eugenol presented a MIC of 1024 µg/mL against S. aureus. The association of this compound with the antibiotic tetracycline demonstrated a synergistic effect (p < 0.0001), this also being observed when the antibiotic was associated with ethidium bromide (p < 0.0001); thus, these results may be attributable to an efflux pump inhibition. The D. melanogaster mortality and geotaxis assays revealed the compound is toxic, with an EC50 of 18 µg/mL within 48 hours of exposure. Conclusions: While we can conclude that the tested product has an efflux pump inhibitory effect, further studies are needed to elucidate its mechanisms of action, in addition to assays using other strains to verify whether the substance has the same inhibitory effect.

Influence of Seasonal Variation on the Chemical Composition and Biological Activities of Essential Oil from Eugenia pohliana DC Leaves.

The purpose of this study was to analyses the influence of seasonal variation on the chemical composition and antimicrobial, antioxidant and cytotoxicity activities of the essential oil (EO) extracted from the leaves of Eugenia pohliana. Chemical characterization of the samples - by gas chromatography-mass spectrometry - found 35 and 38 components for summer and winter, respectively, of the EO from E. pohliana leaves, totaling 47 different compounds. Analysis of antioxidant capacity (DPPH, ABTS and TAC) revealed that the summer EO showed greater free radical scavenging capacity than the winter. Similarly, the summer EO exhibited superior antimicrobial potential (MIC=128-512 µg/mL and MMC=128-1024 µg/mL, compared to the winter EO (128-2048 µg/mL and 256-2048 µg/mL, respectively). Results showed that both oils had a low potential to cause hemolysis. This study provides new scientific evidence on the influence of seasonality on the pharmacological properties of E. pohliana leaves and its potential for the development of herbal medicines.

Oral administration of essential oil from Psidium glaziovianum Kiaersk leaves alleviates pain and inflammation in mice.

Plants of the genus Psidium have been employed in "in natura" consumption and agroindustry, and owing to the diversity of phytochemicals, the development of new pharmaceutical forms has received remarkable research interest. In this study, the essential oil obtained from Psidium glaziovianum (PgEO) leaves were evaluated antinociceptive and anti-inflammatory activities were evaluated in mouse models. Initially, PgEO was characterized by gas chromatography-mass spectrometry and gas chromatography with flame ionization detection, and the profile was dominated by sesquiterpene compounds. In the evaluation of acute antinociceptive activity (abdominal contortions induced by acetic acid, formalin, tail immersion, and hot plate tests), PgEO promoted a reduction in nociception in the chemical and thermal models. Additionally, the potential underlying mechanism was investigated using pain pathway blockers, and the results revealed a combined action of opioidergic and muscarinic pathways. The anti-inflammatory potential was confirmed by anti-edematogenic action, reduced cell migration, pro-inflammatory cytokine production, and granuloma formation in chronic processes. This study provides evidence that PgEO can be effective for the treatment of pain and acute and chronic inflammation.

Leishmanicidal and cytotoxic activity of essential oil from the fruit peel of Myrciaria floribunda (H. West ex Willd.) O. Berg: Molecular docking and molecular dynamics simulations of its major constituent onto Leishmania enzyme targets.

Cutaneous Leishmaniasis (CL) is a neglected disease characterized by highest morbidity rates worldwide. The available treatment for CL has several limitations including serious side effects and resistance to the treatment. Herein we aimed to evaluate the activity of essential oil from the peel of Myrciaria floribunda fruits (MfEO) on Leishmania amazonensis. The cytotoxic potential of MfEO on host mammalian cells was evaluated by MTT. The in vitro leishmanicidal effects of MfEO were investigated on the promastigote and intracellular amastigote forms. The ultrastructural changes induced by MfEO were evaluated by Scanning Electron Microscopy (SEM). The molecular docking of the major compounds δ-Cadinene, γ-Cadinene, γ-Muurolene, α-Selinene, α-Muurolene and (E)-Caryophyllene onto the enzymes trypanothione reductase (TreR) and sterol 14-alpha demethylase (C14DM) were performed. Our results showed that MfEO presented moderate cytotoxicity for Vero cells and macrophages. The MfEO inhibited the growth of promastigote and the survival of intracellular amastigotes, in a dose- and time- dependent way. The MfEO presented high selectivity towards amastigote forms, being 44.1 times more toxic for this form than to macrophages. Molecular docking analysis showed that the major compounds of MfEO interact with Leishmania enzymes and that δ-Cadinene (δ-CAD) presented favorable affinity energy values over TreR and C14DM enzymes, when compared with the other major constituents. Molecular dynamics (MD) simulation studies revealed a stable binding of δ-CAD with lowest binding free energy values in MMGBSA assay. Our results suggested that δ-CAD may be a potent inhibitor of TreR and C14DM enzymes. Communicated by Ramaswamy H. Sarma.

Tannic acid is a gastroprotective that regulates inflammation and oxidative stress.

This study investigated the gastroprotective effect of TA against gastric ulcer in mice, and its possible mechanisms of action. The effects were investigated in a model of ethanol and ethanol/HCl induced ulcers, and physical barrier test. Quantification of oxidative stress mediators and inflammatory cytokines in gastric tissue was performed. The involvement of sulfhydryl compounds (-SH), nitric oxide (NO), prostaglandin E2 (PGE2), potassium channels (K +ATP) and opioid receptors in gastroprotection were investigated. Oral treatment with TA at a dose of 50 mg/kg resulted in 97.96% and 94.20% (reduction in gastric injury) of gastroprotection, against injuries caused by ethanol and ethanol/HCL, respectively, in addition to having a systematic effect. TA promotes increased levels of superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH), as well as reduced levels of malondialdehyde (MDA) reaction to thiobarbituric acid and myeloperoxidase (MPO). In addition, there was reduction in levels of tumor necrosis factor alpha (TNF-α) and interleukins (IL) IL-1ß and IL-6 and increased IL-10. The gastroprotective activity of TA involved K +ATP channels and the production of -SH, NO and PGE2, demonstrating multiple mechanisms of action. The results of the present study suggest that TA may be a gastroprotective agent counteracting oxidative and inflammatory stress.

Novel Therapeutic Options for Chagas Disease Based on Bioactive Compounds from Algae, Bacteria and Fungi Species.

Chagas Disease, also known as American trypanosomiasis, is a Neglected Tropical Disease that affects around seven million people, especially in Latin America. Noteworthy, there has been an increase in the numbers of case reports in non-endemic areas, such as North America, Europe, Japan, and Australia. The disease is a vector-borne disease caused by the pathogen Trypanosoma cruzi being transmitted by infected bugs. It is known that about forty percent of infected patients develop cardiac, digestive, or neurological alterations. There are only two drugs currently used for treatment, benznidazole and nifurtimox. However, both therapeutic regimens present several limitations, such as toxicity, mutagenicity and low efficiency during the chronic phase. Some reports in the literature point to the occurrence of parasite resistance. To overcome these limitations, the bioprospection of novel molecules as alternatives is one of the major goals to improve therapeutic success in this chronic disease. Bioprospecting active metabolites from natural resources might bring new hopes for disease control and parasite elimination. Here we summarize the most recent advances to identify and test Algae, Bacteria and Fungi-derived bioactive compounds with trypanocidal activity using experimental models, in vitro testing and in silico approaches.

Toxic effect of Croton rudolphianus leaf essential oil against Biomphalaria glabrata, Schistosoma mansoni cercariae and Artemia salina.

This research investigated the effect of the Croton rudolphianus leaf essential oil (EO) on Biomphalaria glabrata embryos (at different development stages) and adults, Schistosoma mansoni cercariae, and Artemia salina (non-target organism). It was possible to identify 31 compounds in the C. rudolphianus EO through GC-MS analysis. The major compounds from this oil were (E)-caryophyllene (17.33%), an unknown compound (16.87%), bicyclogermacrene (7.1%), δ-cadinene (6.62%) and germacrene D (5.38%). After incubation for 24 h, the EO of C. rudolphianus induced the occurrence of non-viable embryos (dead and malformed), with an LC50 value of 126.54, 133.51, 143.53 and 161.95 µg/mL and an LC90 value of 202.61, 216.48, 232.98 and 271.16 µg/mL to blastula, gastrula, trochophore and veliger embryonic stages, respectively. The EO was more effective against B. glabrata adults (LC50 and LC90 = 47.89 and 78.86 µg/mL, respectively), and S. mansoni cercariae (LC50 and LC90 = 14.81 and 22.15 after 120 mins of exposure, respectively) than against B. glabrata embryos. Concerning the micronucleus assay, the mean frequency of apoptosis, binucleation and micronucleus were 45.33 ± 3.51, 19.33 ± 1.53 and 0.67 ± 0.58 per 1000 cells at 25 µg/mL, which is the highest concentration tested. The oil killed A. salina with LC50 and LC90 values (68.33 and 111.5 µg/mL, respectively) higher than those determined for adult snails and S. mansoni cercariae. In conclusion, C. rudolphianus EO had a toxic effect against B. glabrata adults and embryos, and S. mansoni cercariae. Furthermore, this oil showed to be cytotoxic to hemocytes of B. glabrata. Concerning the non-target organism assay, C. rudolphianus EO was less toxic to A. salina then to adult snails and S. mansoni cercariae. Due to this, the EO from C. rudolphianus leaves is a potential alternative for schistosomiasis control.

Insecticidal activity of a chemotype VI essential oil from Lippia alba leaves collected at Caatinga and the major compound (1,8-cineole) against Nasutitermes corniger and Sitophilus zeamais.

Lippia alba is an aromatic shrub known to produce a diversity of essential oils, which can be classified into chemotypes. This study reports on the insecticidal activity of essential oil from L. alba leaves collected at Caatinga and its major compound against termite Nasutitermes corniger and maize weevil Sitophilus zeamais. The chromatographic analysis revealed the presence of 19 compounds, with 1,8-cineole being the most common (70.01%). When ingested, the oil promoted the mortality of N. corniger (LC50: 18.25 and 8.4 nL/g for workers and soldiers, respectively). The compound 1,8-cineole was also termiticidal for workers (LC50: 13.7 nL/g). The oil inhibited the activity of N. corniger exoglucanase, xylanase, and proteases. Toxicity by ingestion to S. zeamais was detected for the oil (LC50: 0.297 µL/g) but not for 1,8-cineole; however, both the oil and 1,8-cineole showed anti-nutritional effects. Fumigant effects of the oil and 1,8-cineole against S. zeamais (LC50 of 78.0 and 13.64 µL/L in air, respectively) were detected. This is the first record of a chemotype VI oil from L. alba collected at Caatinga and the first report of the insecticidal activity of a chemotype VI oil. Our study demonstrates that essential oil from L. alba and 1,8 cineole have the potential for the development of natural insecticides.

Evaluation of the antioxidant, antibacterial, and antibiofilm activity of the sesquiterpene nerolidol.

The aim of this study was to evaluate the antioxidant, antibacterial, and antibiofilm activities of nerolidol. The antioxidant activity of nerolidol was determined using the total antioxidant activity method. Antibacterial activity was performed using the microdilution method to determine the minimum inhibitory concentration (MIC) against seven standard strains of the ATCC and four bacterial clinical isolates with a resistance profile, following the Clinical and Laboratory Standards Institute (CLSI). The antibiofilm activity of nerolidol was performed using the crystal violet method. The results of the antioxidant test revealed a total antioxidant activity of 93.94%. Nerolidol inhibited the growth of Staphylococcus aureus (MIC = 1 mg/mL), Streptococcus mutans (MIC = 4 mg/mL), Pseudomonas aeruginosa (MIC = 0.5 mg/mL), and Klebsiella pneumoniae (MIC = 0.5 mg/mL). For clinical isolates, nerolidol showed an inhibitory potential against multidrug-resistant P. aeruginosa, K. pneumoniae carbapenemase (MIC = 0.5 mg/mL), methicillin-susceptible S. aureus (MIC = 2 mg/mL), and methicillin-resistant S. aureus (MIC = 2 mg/mL). Nerolidol showed similar antibacterial activity against ATCC strains and hospital clinical isolates with resistance profile, suggesting that even though these strains are resistant to antibiotics, they are still sensitive to nerolidol. Nerolidol exerted a dose-dependent effect on the inhibition of biofilm formation, even at subinhibitory concentrations. Nerolidol inhibited bacterial biofilms of ATCC strains at a rate ranging from 51 to 98%, at concentrations ranging from 0.5 to 4 mg/mL. For clinical bacterial isolates, biofilm inhibition ranged from 6 to 60%. Therefore, the present study showed the antioxidant, antibacterial, and antibiofilm properties of nerolidol.