Antônio José Cantanhede Filho

1. The Humiriaceae family comprises eight genera: Duckesia, Endopleura, Humiria, Humiriastrum, Hylocara, Sacoglottis, Schistostemon, and Vantenea. Of these, 39 species are found in the genus Humiri...

Background/Objectives: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) necessitates innovative strategies to overcome conventional resistance mechanisms. This study investigated the potential of the natural flavonolignan silibinin (SIL) as an antivirulence agent against S. aureus, with a particular emphasis on its putative multi-target antibacterial activity and its capacity to potentiate the effects of ciprofloxacin (CIP). Methods: The antibacterial and antivirulence properties of SIL were assessed using both in vitro and in silico approaches. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined, and its synergistic interaction with CIP was evaluated using checkerboard assays. Inhibition of biofilm formation, as well as disruption of established biofilms, was assessed using an MTT-based viability assay. Staphyloxanthin (STX) inhibition was examined through pigment extraction and spectrophotometric quantification of pathway intermediates. Molecular docking studies were conducted to predict the binding affinities of the compounds to key bacterial targets, while safety was evaluated through haemolytic and cytotoxicity assays. Results: SIL exhibited weak to moderate direct antibacterial activity (MICs of 256–512 µg/mL), which is characteristic of many natural product scaffolds. Notably, SIL potentiated the activity of CIP, reducing its MIC by up to fourfold against selected resistant strains of S. aureus. SIL significantly inhibited biofilm formation and disrupted established mature biofilms in a strain-dependent manner. In vitro metabolic profiling and in silico analyses provided mechanistic insights into the effects of SIL on STX biosynthesis. Precursor accumulation data suggest inhibition at the diapophytoene desaturase (CrtN) catalytic step, representing a potential mechanism not previously reported for flavonolignans. Molecular docking studies further predicted favourable binding affinities for CrtM and other key targets. Importantly, SIL exhibited no haemolytic activity and low cytotoxicity in macrophages at synergistic concentrations. Conclusions: This study provides evidence that SIL functions as a dual-action agent, potentiating ciprofloxacin efficacy while reducing STX production and inhibiting biofilm formation, thereby impairing key virulence mechanisms of S. aureus. These findings, together with its favourable safety profile, provide a strong rationale for the development of silibinin-based topical adjuvants to combat drug-resistant Staphylococcus infections in humans.

The two-spotted spider mite, Tetranychus urticae, is a global pest with increasing resistance to conventional acaricides, prompting the search for sustainable alternatives. Essential oils (EOs) are promising botanical biocides due to ecological safety and multitarget action. We evaluated lethal and sublethal effects of EOs from Alpinia zerumbet and Mesosphaerum suaveolens against T. urticae. Oils were obtained by hydrodistillation and characterized by GC–MS (major constituents: A. zerumbet—1,8-cineole 14.05%, sabinene 12.6%; M. suaveolens—β-sabinene (predominant), spathulenol 12.28%, 1,8-cineole 11.01%). In adult bioassays, M. suaveolens was more toxic (LC₅₀ = 4.24 µL mL⁻¹), whereas A. zerumbet showed LC₅₀ = 8.74 and LC₉₀ = 46.24 µL mL⁻¹. In ovicidal assays at LC₉₀, egg viability declined to 2% with A. zerumbet versus 57% with M. suaveolens. Repellency at sublethal concentrations (LC₂₀–LC₃₀) was high for both oils (≥75%) and exceeded 90% for M. suaveolens. Both oils suppressed population growth (instantaneous rate r_i reduced from 0.5848 in the control to 0.4746–0.5155 under treatments). PCA confirmed lethal concentration and repellency as the main discriminators among treatments. These data demonstrate the multitarget potential of A. zerumbet and M. suaveolens EOs as botanical acaricides for sustainable management of T. urticae.

Background/Objectives: Endophytic fungi are valuable sources of bioactive compounds with potential therapeutic applications. This study aimed to evaluate the antifungal activity of secondary metabolites produced by Fusarium sp. isolated from Dizygostemon riparius, with particular focus on the impact of culture medium supplementation with halogenated and metallic additives on metabolite production. Methods: The fungus was cultivated in standard Czapek medium and media supplemented with NH₄Br or MnCl₂. Methanolic extracts were obtained, fractionated, and chemically characterised via LC-ESI-HRMS. In vitro antifungal assays, including MIC and MFC determinations and biofilm inhibition tests, were performed against Candida albicans strains. In vivo toxicity and efficacy were assessed using Tenebrio molitor larvae. Results: Fifteen metabolites were annotated, including known antifungals such as fusaric acid and cyclosporin A. Fractions EMBr4 and EMC5 demonstrated fungicidal activity with MIC values close to fluconazole and significantly inhibited biofilm formation and maturation. In vivo, these fractions displayed low acute toxicity and improved survival in infected larvae, comparable to fluconazole treatment. Conclusions: The results indicate that culture medium modulation enhances the production of bioactive metabolites by Fusarium sp., leading to extracts with notable antifungal efficacy and safety. EMBr4 and EMC5 are promising candidates for further development as antifungal agents, particularly for targeting biofilm-associated Candida infections. These findings support the potential of endophytic fungi as sources of novel therapeutics and warrant further mechanistic and pharmacological investigations.

Climacteric is a period in which several symptoms are triggered in women's health, bringing about profound changes of both positive and negative nature. Among these, the onset of menopause, characterized by the last menstruation, stands out, which results in the reduction of the woman's reproductive capacity. In this sense, intimate lubricating gels were manufactured to combat atrophic vaginitis in climacteric women. This research aimed to prepare and develop intimate lubricating gels based on water and hydroalcoholic extract of medicinal plants (phytoestrogens) aiming at revitalizing the vaginal mucosa and improving the quality of life of climacteric women. The preliminary stability assessment revealed that the gels produced presented organoleptic and physicochemical parameters by the ANVISA Cosmetic Product Stability Guide, given that they showed signs of constancy throughout the evaluation. Therefore, the gels produced are capable of mitigating vaginal dryness, genital burning (dyspareunia), irritation, lack of lubrication and discomfort during sexual intercourse and recurrent urinary infections.

DETERMINATION OF THE FLAVONOID QUERCETIN IN PLANT EXTRACTS BY INFRARED SPECTROSCOPY (ATR-FTIR) AND CHEMOMETRICS. This work evaluated mid-infrared spectroscopy combined with chemometrics for qualitative and quantitative analysis of flavonoids in plant extracts. The exploratory data analysis was conducted using principal component analysis (PCA) and hierarchical cluster analysis (HCA), while the calibration model was developed using the partial least squares (PLS) regression technique. Methanolic extracts were obtained from 15 plant species collected during rainy and dry seasons, totaling 26 samples. Ultraviolet-visible (UV-Vis) spectroscopy was used as a reference method for the determination of flavonoids. PCA and HCA grouped the samples according to their chemical composition, with no significant variations due to seasonality. The extract of “quebra-pedra” (Phyllanthus niruri) formed a distinct cluster related to the spectral bands at 1012 and 1047 cm–1, attributed to C–O stretching in carbohydrates and cellulose derivatives. The regression model presented a root mean square error of calibration (RMSEC) of 0.06, root mean square error of cross-validation (RMSECV) of 0.13, root means square error of prediction (RMSEP) of 0.20, and residual predictive deviation (RDP) of 1.62. These results demonstrate that the combination of Fourier transform infrared spectroscopy (FTIR) and PLS presents itself as an alternative to predicting the concentration of flavonoids in complex samples, such as plant extracts.

Background/Objectives: This study evaluates the effect of Mn(II) and Co(II) ions on the production of anti-Candida metabolites by the endophytic fungus Aspergillus sp., isolated from Dizygostemon riparius. The objective was to identify metal-induced secondary metabolites with antifungal potential against drug-resistant Candida species. Methods: Aspergillus sp. was cultivated in Czapek agar supplemented with MnCl₂ (400 µM) or CoCl₂ (200 µM). Metabolite profiles were analyzed using UHPLC-DAD and LC-ESI-HRMS, followed by structural elucidation via NMR. Antifungal and biofilm inhibition activities were tested against Candida albicans and Candida parapsilosis. Toxicity was assessed using Tenebrio molitor larvae. Results: Key metabolites, including pyrophen, penicillquei B, and fonsecinone B, demonstrated antifungal activity with MIC values of 4.37–280.61 µg/mL. Fonsecinone B exhibited superior biofilm inhibition, surpassing fluconazole in reducing biofilm biomass and viability. In vivo assays showed low toxicity, with survival rates above 80% at 2× MIC/kg. Conclusions: Mn(II) and Co(II) significantly modulated the production of antifungal metabolites in Aspergillus sp. Fonsecinone B emerged as a promising candidate for antifungal therapy due to its potent activity and low toxicity. These findings support further investigation into the therapeutic potential of metal-induced fungal metabolites for combating drug-resistant Candida infections.

Osteoarthritis (OA) remains a chronic incurable condition, presenting substantial challenges in treatment. This study explores a novel strategy by investigating the concurrent use of cuminaldehyde, a natural compound, with indomethacin in animal models of MIA-induced OA. Our results demonstrate that the co-administration of cuminaldehyde and indomethacin does indeed produce a superior effect when compared to these compounds individually, significantly enhancing therapeutic outcomes. This effect is evidenced by a marked reduction in pro-inflammatory cytokines IL-6 and IFN-γ, alongside a significant increase in the anti-inflammatory cytokine IL-10, compared to treatments with each compound alone. Radiographic analyses further confirm the preservation of joint integrity and a reduction in osteoarthritic damage, highlighting the association’s efficacy in cartilage-reducing damage. These findings suggests that the association of cuminaldehyde and indomethacin not only slows OA progression but also offers enhanced cartilage-reducing damage and fosters the production of protective cytokines. This study underscores the potential benefits of integrating natural products with pharmaceuticals in OA management and stresses the importance of further research to fully understand the mechanisms underlying the observed potentiated effects.