Natural Autophagy Activators to Fight Age-Related Diseases.

The constant increase in the elderly population presents significant challenges in addressing new social, economic, and health problems concerning this population. With respect to health, aging is a primary risk factor for age-related diseases, which are driven by interconnected molecular hallmarks that influence the development of these diseases. One of the main mechanisms that has attracted more attention to aging is autophagy, a catabolic process that removes and recycles damaged or dysfunctional cell components to preserve cell viability. The autophagy process can be induced or deregulated in response to a wide range of internal or external stimuli, such as starvation, oxidative stress, hypoxia, damaged organelles, infectious pathogens, and aging. Natural compounds that promote the stimulation of autophagy regulatory pathways, such as mTOR, FoxO1/3, AMPK, and Sirt1, lead to increased levels of essential proteins such as Beclin-1 and LC3, as well as a decrease in p62. These changes indicate the activation of autophagic flux, which is known to be decreased in cardiovascular diseases, neurodegeneration, and cataracts. The regulated administration of natural compounds offers an adjuvant therapeutic alternative in age-related diseases; however, more experimental evidence is needed to support and confirm these health benefits. Hence, this review aims to highlight the potential benefits of natural compounds in regulating autophagy pathways as an alternative approach to combating age-related diseases.

Improving the medium composition for the production of the natural blue-violet pigment violacein by a new Janthinobacterium sp. isolate.

The interest in natural compounds has increased primarily due to their beneficial health and environmental aspects. However, natural sources of some compounds, such as bluish pigments, are limited, requiring the development of efficient processes to meet commercial demands. This study isolated a blue-violet bacterium from spoiled cooked rice and identified it as a potential new species of Janthinobacterium through 16S rDNA analysis. Ultra-high performance liquid chromatography-tandem mass spectrometry analyses confirmed that the blue-violet pigment violacein was responsible for the bluish color. In laboratory conditions, different carbon and nitrogen sources were evaluated in submerged culture media to enhance pigment production. Glycerol did not result in significant pigment production by this strain, as expected from previous reports. Instead, a culture medium composed of yeast extract and fructose yielded higher pigment production, reaching about 113.68 ± 16.68 mg l-1 after 120 h. This result provides crucial insights for future studies aiming for sustainable and commercially viable violacein production. Based on a bioeconomy concept, this approach has the potential to supply natural and economic bluish pigments for various industrial sectors, including pharmaceutical, cosmetic, and food.

Natural and Synthetic Capsaicin Analogues: A Comprehensive Review of Biological Effects and Synthetic Pathways.

Capsaicin analogs, whether sourced from natural origins or synthesized de novo, have garnered significant attention across diverse scientific disciplines. This comprehensive investigation explores the expansive domain of medicinal chemistry and pharmacology, focusing on capsaicin and its analogs. Notably, these analogs exhibit a wideranging pharmacological spectrum, with a particular emphasis on their potent antitumor properties. Researchers frequently explore structural modifications, particularly in region C, consistently enhancing their pharmacological activities. A highlighted finding is that analogs with alterations in both regions A and C manifest a diverse array of effects, spanning from anti-obesity to protection against ischemia. They also demonstrate anti- Alzheimer's, anti-fibrotic, anti-inflammatory, anti-diabetic, antimalarial, and anti-epileptic properties. This underscores the potential of structural adaptations in these regions, expanding the therapeutic applications of capsaicin-like compounds. Additionally, manipulations in regions B and C result in compounds that possess antioxidant and anti-obesity properties, providing valuable insights for the development of novel compounds. The therapeutic potential of capsaicin analogs opens innovative avenues for drug design and development, promising to address a broad spectrum of diseases and enhance global quality of life. Moreover, this article meticulously examines various synthetic methodologies for synthesizing capsaicin analogs, complementing the main review. These methodologies distinguish themselves through their simplicity, mild reaction conditions, and reliance on readily available commercial reagents. The accessible synthesis pathways enable researchers from diverse backgrounds to explore these compounds, fostering investigations and potential therapeutic applications.

Bioactive Insecticides from Chemometric Diverse Ant-Associated Symbionts Streptomyces novaecaesareae and Streptomyces nojiriensis against the Fall Armyworm Larvae.

The Streptomyces genus has long been recognized as a prolific and valuable source of diverse secondary metabolites. These metabolites contribute significantly to the intricate chemical diversity exhibited by Streptomyces, making them an indispensable reservoir for drug discovery, agricultural applications, and industrial processes. Exploiting the potential of these natural compounds holds the promise of ushering in a new era in insect pest management, reducing reliance on synthetic chemicals and fostering ecologically sustainable solutions. This study dives into the realm of chemo diversity within isolates of Streptomyces nojiriensis and Streptomyces novaecaesareae, with a specific focus on the production of insecticidal compounds. We explored chromatographic techniques for the identification and isolation of insecticidal compounds, and two bioactive compounds were identified in extracts of S. novaecaesareae. Valinomycin was identified from hexanic extracts of strain Asp59, while naphthomycin from ethyl acetate extracts of strain Asp58. These compounds showed insecticidal activity against first instars of Spodoptera frugiperda (Asp59: LC50 = 10.82 µg/µL, LC90 = 26.25 µg/µL; Asp58: LC50 = 15.05 µg/µL, LC90 = 38.84 µg/µL). Notably, this is the first report of naphthomycin as an insecticidal compound. The present study suggests that valinomycin and naphthomycin may be a novel biological source for the control of Spodoptera frugiperda in early stages.

Coconut oil affects aging-related changes in Mongolian gerbil liver morphophysiology.

Aging causes changes in liver morphophysiology, altering hepatocyte morphology and organ function. Due to its antioxidant and anti-inflammatory properties, coconut oil has been used as a therapeutic agent in diets, in an attempt to attenuate alterations in the liver naturally caused by aging. Herein, we evaluated the effects of coconut oil consumption during aging on Mongolian gerbil liver morphophysiology. The animals were divided into three experimental groups: the gerbils in the Adult Control Group (AC) were euthanized at 3 months of age, the gerbils in the Old Control Group (OC) at 15 months of age, and the gerbils in the Coconut Oil Group (CO) received 0.1 ml/day of coconut oil for 12 months and were euthanized at 15 months of age. Prolonged consumption of coconut oil during aging prevented the animals and the liver from gaining mass. However, the other results showed that coconut oil intensified the morphophysiological alterations of aging, promoting an increase in the hepatocyte cytoplasm and nuclei. In addition, an increase in blood vessels, reticular fibers, lipid droplets, and lipofuscin granules were observed in the CO group. Finally, the results also demonstrated that coconut oil promotes an increase in lipid peroxidation, indicated by an increase in MDA levels. We therefore conclude that coconut oil has the potential to intensify the morphophysiological alterations that occur in the liver during aging.

Correlation between Molecular Docking and the Stabilizing Interaction of HOMO-LUMO: Spirostans in CHK1 and CHK2, an In Silico Cancer Approach.

Checkpoint kinases 1 and 2 (CHK1 and CHK2) are enzymes that are involved in the control of DNA damage. At the present time, these enzymes are some of the most important targets in the fight against cancer since their inhibition produces cytotoxic effects in carcinogenic cells. This paper proposes the use of spirostans (Sp), natural compounds, as possible inhibitors of the enzymes CHK1 and CHK2 from an in silico analysis of a database of 155 molecules (S5). Bioinformatics studies of molecular docking were able to discriminate between 13 possible CHK1 inhibitors, 13 CHK2 inhibitors and 1 dual inhibitor for both enzymes. The administration, distribution, metabolism, excretion and toxicity (ADMETx) studies allowed a prediction of the distribution and metabolism of the potential inhibitors in the body, as well as determining the excretion routes and the appropriate administration route. The best inhibition candidates were discriminated by comparing the enzyme-substrate interactions from 2D diagrams and molecular docking. Specific inhibition candidates were obtained, in addition to studying the dual inhibitor candidate and observing their stability in dynamic molecular studies. In addition, Highest Occupied Molecular Orbital-Lowest Unoccupied Molecular Orbital (HOMO-LUMO) interactions were analyzed to study the stability of interactions between the selected enzymes and spirostans resulting in the predominant gaps from HOMOCHKs to LUMOSp (Highest Occupied Molecular Orbital of CHKs-Lowest Unoccupied Molecular Orbital of spirostan). In brief, this study presents the selection inhibitors of CHK1 and CHK2 as a potential treatment for cancer using a combination of molecular docking and dynamics, ADMETx predictons, and HOMO-LUMO calculation for selection.

Exploring the potential of tocopherols: mechanisms of action and perspectives in the prevention and treatment of breast cancer.

Currently, breast cancer is the most common cause of mortality caused by neoplasia in women worldwide. The unmet challenges of conventional cancer therapy are chemoresistance and lack of selectivity, which can lead to serious side effects in patients; therefore, new treatments based on natural compounds that serve as adjuvants in breast cancer therapy are urgently needed. Tocopherols are naturally occurring antioxidant compounds that have shown antitumor activity against several types of cancer, including breast cancer. This review summarizes the antitumoral activity of tocopherols, such as the antiproliferative, apoptotic, anti-invasive, and antioxidant effects of tocopherols, through different molecular mechanisms. According to the studies described, α-T, δ-T and γ-T are the most studied in breast tumor cells; however, α-T and γ-T show a more critical antitumor activity and significant potential as a complements to chemotherapeutic drugs against breast cancer, enhancing toxicity against tumor cells and preventing cytotoxicity in nontumor cells. However, the possible relationship between tocopherol intake, related to concentration, and the promotion of cancer in particular cases should not be ruled out, so additional studies are required to determine the correct dose to obtain the desired antitumor effect. Moreover, nanomicelles of D-α-tocopherol have promising potential as pharmaceutical excipients for drug delivery to improve the cytotoxicity and selectivity of first-line chemotherapeutics against breast cancer.

ß-Carboline derivatives are potent against Acute Myeloid Leukemia in vitro and in vivo.

BACKGROUND: ß-carboline alkaloids exert a distinguished ability to impair cell growth and induce cell death in a variety of cancers and the evaluation of such new therapeutic candidates may denote new possibilities for leukemia treatment. In this present study, we screened 12 ß-carboline derivatives containing different substituents at 1- and 3-positions of ß-carboline nucleus for their antineoplastic activities in a panel of leukemia cell lines. METHODS: The cytotoxic effects of the ß-carboline derivatives were evaluated in different leukemia cell lines as well as reactive oxygen species (ROS) generation, autophagy, and important signaling pathways. RESULTS: Treatment with the ß-carboline derivatives resulted in a potent antineoplastic activity leading to a reduced cell viability that was associated with increased cell death in a concentration-dependent manner. Interestingly, the treatment of primary mononuclear cells isolated from the peripheral blood of healthy donors with the ß-carboline derivatives showed a minor change in cell survival. The antineoplastic activity occurs by blocking ROS production causing consequent interruption of the PI3K/AKT and MAPK/ERK signaling and modulating autophagy processes. Notably, in vivo, AML burden was diminished in peripheral blood and bone marrow of a xenograft mouse model. CONCLUSIONS: Our results indicated that ß-carboline derivatives have an on-target malignant cell-killing activity and may be promising candidates for treating leukemia cells by disrupting crucial events that promote leukemia expansion and chemotherapy resistance.

Thymol as adjuvant in oncology: molecular mechanisms, therapeutic potentials, and prospects for integration in cancer management.

Cancer remains a global health challenge, prompting a search for effective treatments with fewer side effects. Thymol, a natural monoterpenoid phenol derived primarily from thyme (Thymus vulgaris) and other plants in the Lamiaceae family, is known for its diverse biological activities. It emerges as a promising candidate in cancer prevention and therapy. This study aims to consolidate current research on thymol's anticancer effects, elucidating its mechanisms and potential to enhance standard chemotherapy, and to identify gaps for future research. A comprehensive review was conducted using databases like PubMed/MedLine, Google Scholar, and ScienceDirect, focusing on studies from the last 6 years. All cancer types were included, assessing thymol's impact in both cell-based (in vitro) and animal (in vivo) studies. Thymol has been shown to induce programmed cell death (apoptosis), halt the cell division cycle (cell cycle arrest), and inhibit cancer spread (metastasis) through modulation of critical signaling pathways, including phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), extracellular signal-regulated kinase (ERK), mechanistic target of rapamycin (mTOR), and Wnt/ß-catenin. It also enhances the efficacy of 5-fluorouracil (5-FU) in colorectal cancer treatments. Thymol's broad-spectrum anticancer activities and non-toxic profile to normal cells underscore its potential as an adjunct in cancer therapy. Further clinical trials are essential to fully understand its therapeutic benefits and integration into existing treatment protocols.

Copaifera spp. oleoresins and two isolated compounds (ent-kaurenoic and ent-polyalthic acid) inhibit Toxoplasma gondii growth in vitro.

Toxoplasmosis affects about one-third of the world's population. The disease treatment methods pose several side effects and do not efficiently eliminate the parasite, making the search for new therapeutic approaches necessary. We aimed to assess the anti-Toxoplasma gondii activity of four Copaifera oleoresins (ORs) and two isolated diterpene acids, named ent-kaurenoic and ent-polyalthic acid. We used HeLa cells as an experimental model of toxoplasmosis. Uninfected and infected HeLa cells were submitted to the treatments, and the parasite intracellular proliferation, cytokine levels and ROS production were measured. Also, tachyzoites were pre-treated and the parasite invasion was determined. Finally, an in silico analysis was performed to identify potential parasite targets. Our data show that the non-cytotoxic concentrations of ORs and diterpene acids controlled the invasion and proliferation of T. gondii in HeLa cells, thus highlighting the possible direct action on parasites. In addition, some compounds tested controlled parasite proliferation in an irreversible manner. An additional and non-exclusive mechanism of action involves the modulation of host cell components, by affecting the upregulation of the IL-6. Additionally, molecular docking suggested that ent-polyalthic acid has a high affinity for the active site of the TgCDPK1 protein. Copaifera ORs have great antiparasitic activity against T. gondii, and this effect can be partially explained by the presence of the isolated compounds ent-kaurenoic and ent-polyalthic acid.

Ultrasound-Assisted Nanoemulsion Loaded with Optimized Antibacterial Essential Oil Blend: A New Approach against Escherichia coli, Staphylococcus aureus, and Salmonella Enteritidis in Trout (Oncorhynchus mykiss) Fillets.

This study aimed to obtain and characterize an oil-in-water nanoemulsion (NE) loaded with an in vitro optimized bactericidal essential oil blend of 50% oregano, 40% thyme, and 10% lemongrass and to evaluate its potential at three different concentrations (0.5%, 1%, and 2%) in the inactivation of Escherichia coli, Staphylococcus aureus, and Salmonella enterica serotype Enteritidis inoculated in rainbow trout fillets stored at 4 °C for 9 days. Regarding the NE, the nanometric size (<100 nm) with low polydispersion (0.17 ± 0.02) was successfully obtained through ultrasound at 2.09 W/cm2. Considering the three concentrations used, S. Enteritidis was the most susceptible. On the other hand, comparing the concentrations used, the NE at 2% showed better activity, reducing S. Enteritidis, E. coli, and S. aureus by 0.33, 0.20, and 0.73 log CFU/g, respectively, in the trout fillets. Thus, this data indicates that this is a promising eco-friendly alternative to produce safe fish for consumption and reduce public health risks.

Humic Acid Derived from Agricultural Biomass Mitigates Alveolar Bone Loss and Modulates Systemic Inflammatory Cytokines in Rats with Periodontitis.

BACKGROUND: Humic acid (HA) is a bioproduct that can be extracted from different sources and has anti-inflammatory properties that have been little explored in the treatment and prevention of Periodontal Disease (PD). Thus, we aimed to investigate the effects of oral administration of HA on the progression of PD in rats. METHODS: Twenty-four male Wistar rats were distributed into three experimental groups (Control/ Sham, PD, and PD + HA). HA was administered by gavage (80 mg/kg/day) for 28 days, and PD was induced 14 days after the beginning of treatment. Bone loss, bone topography, and surface elemental composition were analyzed. Circulating IL1-beta, TNF-alpha, and IL-10 levels were evaluated through Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: The animals treated with HA showed lower bone loss (p < 0.05). Calcium and phosphorus levels on the alveolar bone surface were lower in the PD group (p < 0.05) compared to the control group, whereas the animals treated with HA exhibited attenuation in this loss (p < 0.05). The animals treated with HA showed reduced TNF-alpha, IL1-beta, IL-10, and the TNF-alpha/IL-10 ratio compared to those with PD (p < 0.05). CONCLUSION: Treatment with HA attenuated the parameters of alveolar bone loss and modulated systemic inflammatory parameters in rats with ligature-induced PD.

Curcumin and quercetin co-encapsulated in nanoemulsions for nasal administration: A promising therapeutic and prophylactic treatment for viral respiratory infections.

One of the most frequent causes of respiratory infections are viruses. Viruses reaching the airways can be absorbed by the human body through the respiratory mucosa and mainly infect lung cells. Several viral infections are not yet curable, such as coronavirus-2 (SARS-CoV-2). Furthermore, the side effect of synthetic antiviral drugs and reduced efficacy against resistant variants have reinforced the search for alternative and effective treatment options, such as plant-derived antiviral molecules. Curcumin (CUR) and quercetin (QUE) are two natural compounds that have been widely studied for their health benefits, such as antiviral and anti-inflammatory activity. However, poor oral bioavailability limits the clinical applications of these natural compounds. In this work, nanoemulsions (NE) co-encapsulating CUR and QUE designed for nasal administration were developed as promising prophylactic and therapeutic treatments for viral respiratory infections. The NEs were prepared by high-pressure homogenization combined with the phase inversion temperature technique and evaluated for their physical and chemical characteristics. In vitro assays were performed to evaluate the nanoemulsion retention into the porcine nasal mucosa. In addition, the CUR and QUE-loaded NE antiviral activity was tested against a murine ß-COV, namely MHV-3. The results evidenced that CUR and QUE loaded NE had a particle size of 400 nm and retention in the porcine nasal mucosa. The antiviral activity of the NEs showed a percentage of inhibition of around 99 %, indicating that the developed NEs has interesting properties as a therapeutic and prophylactic treatment against viral respiratory infections.

Clinically Effective Molecules of Natural Origin for Obesity Prevention or Treatment.

The prevalence and incidence of obesity and the comorbidities linked to it are increasing worldwide. Current therapies for obesity and associated pathologies have proven to cause a broad number of adverse effects, and often, they are overpriced or not affordable for all patients. Among the alternatives currently available, natural bioactive compounds stand out. These are frequently contained in pharmaceutical presentations, nutraceutical products, supplements, or functional foods. The clinical evidence for these molecules is increasingly solid, among which epigallocatechin-3-gallate, ellagic acid, resveratrol, berberine, anthocyanins, probiotics, carotenoids, curcumin, silymarin, hydroxy citric acid, and α-lipoic acid stand out. The molecular mechanisms and signaling pathways of these molecules have been shown to interact with the endocrine, nervous, and gastroenteric systems. They can regulate the expression of multiple genes and proteins involved in starvation-satiety processes, activate the brown adipose tissue, decrease lipogenesis and inflammation, increase lipolysis, and improve insulin sensitivity. This review provides a comprehensive view of nature-based therapeutic options to address the increasing prevalence of obesity. It offers a valuable perspective for future research and subsequent clinical practice, addressing everything from the molecular, genetic, and physiological bases to the clinical study of bioactive compounds.

Trypanocidal and Anti-Inflammatory Effects of Three ent-Kaurane Diterpenoids from Gymnocoronis spilanthoides var. subcordata (Asteraceae).

Chagas disease, caused by the protozoan Trypanosoma cruzi, affects 6-7 million people worldwide. The dichloromethane extract obtained from the aerial parts of Gymnocoronis spilanthoides var subcordata showed trypanocidal activity in vitro. The fractionation of the dewaxed organic extract via column chromatography led to the isolation of three diterpenoids: ent-9α,11α-dihydroxy-15-oxo-kaur-16-en-19-oic acid or adenostemmoic acid B, (16R)-ent-11α-hydroxy-15-oxokauran-19-oic acid and ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid. These compounds showed IC50 values of 10.6, 15.9 and 4.8 µM against T. cruzi epimastigotes, respectively. When tested against amastigotes, the diterpenoids afforded IC50 values of 6.1, 19.5 and 60.6 µM, respectively. The cytotoxicity of the compounds was tested on mammalian cells using an MTT assay, resulting in CC50s of 321.8, 23.3 and 14.8 µM, respectively. The effect of adenostemmoic acid B on T. cruzi was examined at the ultrastructural level using transmission microscopy. Treatment with 20 µM for 48 h stimulated the formation of abnormal cytosolic membranous structures in the parasite. This compound also showed an anti-inflammatory effect in murine macrophages stimulated with LPS and other TLR agonists. Treatment of macrophages with adenostemmoic acid B was able to reduce TNF secretion and nitric oxide production, while increasing IL-10 production. The combination of adenostemmoic acid B with benznidazole resulted in greater inhibition of NF-kB and a decrease in nitrite concentration. The administration of adenostemmoic acid B to mice infected with trypomastigotes of T. cruzi at the dose of 1 mg/kg/day for five days produced a significant decrease in parasitemia levels and weight loss. Treatment with the association with benznidazole increased the survival time of the animals. In view of these results, adenostemmoic acid B could be considered a promising candidate for further studies in the search for new treatments for Chagas disease.

Protective effect of Bougainvillea glabra Choisy bract in toxicity induced by Paraquat in Drosophila melanogaster.

Paraquat (PQ) is a herbicide widely used in agriculture to control weeds. The damage caused to health through intoxication requires studies to combating its damage to health. Bougainvillea glabra Choisy is a plant native to South America and its bracts contain a variety of compounds, including betalains and phenolic compounds, which have been underexplored about their potential applications and benefits for biological studies to neutralize toxicity. In this study, we evaluated the antioxidant and protective potential of the B. glabra bracts (BBGCE) hydroalcoholic extract against Paraquat-induced toxicity in Drosophila melanogaster. BBGCE demonstrated high antioxidant capacity in vitro through the assays of ferric-reducing antioxidant power (FRAP), radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), free radical ABTS and quantification of phenolic compounds, confirmed through identifying the main compounds. Wild males of D. melanogaster were exposed to Paraquat (1.75 mM) and B. glabra Choisy (1, 10, 50 and 100 µg/mL) in agar medium for 4 days. Flies exposed to Paraquat showed a reduction in survival rate and a significant decrease in climbing capacity and balance test when compared to the control group. Exposure of the flies to Paraquat caused a reduction in acetylcholinesterase activity, an increase in lipid peroxidation and production of reactive species, and a change in the activity of the antioxidant enzymes. Co-exposure with BBGCE was able to block toxicity induced by PQ exposure. Our results demonstrate that bract extract has a protective effect against PQ on the head and body of flies, attenuating behavioral deficit, exerting antioxidant effects and blocking oxidative damage in D. melanogaster.

Oil-in-water emulsion loaded with optimized antioxidant blend improved the shelf-life of trout (Oncorhynchus mykiss) fillets: a study with simplex-centroid design.

This study aimed to obtain optimized mixture with three essential oils (EOs) for maximum antioxidant activity through the augmented simplex-centroid mixture design and evaluate the effect of this optimized blend on total aerobic psychrotrophic count (TAPC), lipid and protein oxidation, instrumental color parameters and texture profile in rainbow trout fillets at refrigerated storage for nine days. Considering the DPPH and FRAP assays, the ideal EO blend was 66% lemongrass and 34% oregano. During refrigerated storage, this blend at 2000 ppm was equally effective as BHT (100 ppm) (p > 0.05), mitigating the discoloration (a* and b*), lipid, and protein oxidation in 38.83%, 12.95%, 76.13%, and 35.13%, respectively, besides shows greater effectiveness for preserving texture changes (p < 0.05) and extending the shelf life in 13 h. The lemongrass + oregano EO blend reveals a promising natural alternative to enhance the quality of rainbow trout fillets under refrigerated storage. Furthermore, the multiresponse optimization showed to be a strong ally in enabling the use of these EOs by food industries.

Design and elucidation of an insecticide from natural compounds targeting mitochondrial proteins of Aedes aegypti.

Developing new pesticides poses a significant challenge in designing next-generation natural insecticides that selectively target specific pharmacological sites while ensuring environmental friendliness. In this study, we aimed to address this challenge by formulating novel natural pesticides derived from secondary plant metabolites, which exhibited potent insecticide activity. Additionally, we tested their effect on mitochondrial enzyme activity and the proteomic profile of Ae. aegypti, a mosquito species responsible for transmitting diseases. Initially, 110 key compounds from essential oils were selected that have been reported with insecticidal properties; then, to ensure safety for mammals were performed in silico analyses for toxicity properties, identifying non-toxic candidates for further investigation. Subsequently, in vivo tests were conducted using these non-toxic compounds, focusing on the mosquito's larval stage. Based on the lethal concentration (LC), the most promising compounds as insecticidal were identified as S-limonene (LC50 = 6.4 ppm, LC95 = 17.2 ppm), R-limonene (LC50 = 9.86 ppm, LC95 = 27.7 ppm), citronellal (LC50 = 40.5 ppm, LC95 = 68.6 ppm), R-carvone (LC50 = 61.4 ppm, LC95 = 121 ppm), and S-carvone (LC50 = 62.5 ppm, LC95 = 114 ppm). Furthermore, we formulated a mixture of R-limonene, S-carvone, and citronellal with equal proportions of each compound based on their LC50. This mixture specifically targeted mitochondrial proteins and demonstrated a higher effect that showed by each compound separately, enhancing the insecticidal activity of each compound. Besides, the proteomic profile revealed the alteration in proteins involved in proliferation processes and detoxification mechanisms in Ae. aegypti. In summary, our study presents a formulation strategy for developing next-generation natural insecticides using secondary plant metabolites with the potential for reducing the adverse effects on humans and the development of chemical resistance in insects. Our findings also highlight the proteomic alteration induced by the formulated insecticide, showing insight into the mechanisms of action and potential targets for further exploration in vector control strategies.

Exploring the Potential of Natural Products as Antiparasitic Agents for Neglected Tropical Diseases.

Recent developments in the use of natural product-based molecules as antiparasitic agents for Malaria, leishmaniasis (LE), Chagas disease (CD), and Human African trypanosomiasis (HAT) are reviewed. The role of diverse plants in developing bioactive species is discussed in addition to analyzing the structural diversity of natural products as active agents and the diverse biological applications in CD, HAT, LE, and Malaria. This review focuses on medicinal chemistry, emphasizing the structural characteristics of natural molecules as bioactive agents against parasitic infections caused by Leishmania, Trypanosoma, and Plasmodium parasites.

Mygalin, an Acanthoscurria gomesiana spider-derived synthetic, modulates haloperidol-induced cataleptic state in mice.

BACKGROUND: Haloperidol (HAL) is an antipsychotic used in the treatment of schizophrenia. However, adverse effects are observed in the extrapyramidal tracts due to its systemic action. Natural compounds are among the treatment alternatives widely available in Brazilian biodiversity. Mygalin (MY), a polyamine that was synthesized from a natural molecule present in the hemolymph of the Acanthoscurria gomesian spider, may present an interesting approach. AIMS: This study aimed to evaluate the effect of MY in mice subjected to HAL-induced catalepsy. METHODS: Male Swiss mice were used. Catalepsy was induced by intraperitoneal administration of HAL (0.5 mg/kg - 1 mL/Kg) diluted in physiological saline. To assess the MY effects on catalepsy, mice were assigned to 4 groups: (1) physiological saline (NaCl 0.9 %); (2) MY at 0.002 mg/Kg; (3) MY at 0.02 mg/Kg; (4) MY at 0.2 mg/Kg. MY or saline was administered intraperitoneally (IP) 10 min b HAL before saline. Catalepsy was evaluated using the bar test at 15, 30, 60, 90, and 120 min after the IP administration of HAL. RESULTS: The latency time in the bar test 15, 30, 60, and 90 min increased (p < 0.05) after IP administration of HAL compared to the control group. Catalepsy was attenuated 15, 30, 90, and 120 min (p < 0.05) after the IP-administration of MY at 0.2 mg/Kg; while MY at 0.02 mg/Kg attenuated catalepsy 15 min after the HAL treatment. Our findings showed that MY attenuates the HAL-induced cataleptic state in mice.