RESUMEN
S-Limonene (s-Lim) is a monocyclic monoterpene found in a variety of plants and has been shown to present antioxidant and cardioprotective activity in experimental models of myocardial infarction. The aim of this study was to evaluate the potential mechanism by which s-Lim exerts its antiarrhythmic effect, focusing on the blockade of ß-adrenoceptor (ß-AR) and its effects on various in vivo and in vitro parameters, including electrocardiogram (ECG) measurements, left ventricular developed pressure (LVDP), the ß-adrenergic pathway, sarcomeric shortening and L-type calcium current (ICa,L). In isolated hearts, 10 µM of s-Lim did not alter the ECG profile or LVPD. s-Lim increased the heart rate corrected QT interval (QTc) (10.8%) at 50 µM and reduced heart rate at the concentrations of 30 (12.4%) and 50 µM (16.6%). s-Lim (10 µM) also inhibited the adrenergic response evoked by isoproterenol (ISO) (1 µM) reducing the increased of heart rate, LVDP and ECG changes. In ventricular cardiomyocyte, s-Lim antagonized the effect of dobutamine by preventing the increase of sarcomeric shortening, demonstrating a similar effect to atenolol (blocker ß1-AR). In vivo, s-Lim antagonized the effect of ISO (agonists ß1-AR), presenting a similar effect to propranolol (a non-selective blocker ß-AR). In ventricular cardiomyocyte, s-Lim did not alter the voltage dependence for ICa,L activation or the ICa,L density. In addition, s-Lim did not affect changes in the ECG effect mediated by 5 µM forskolin (an activator of adenylate cyclase). In an in vivo caffeine/ISO-induced arrhythmia model, s-Lim (1 mg/kg) presented antiarrhythmic action verified by a reduced arrhythmia score, heart rate, and occurrence of ventricular premature beats and inappropriate sinus tachycardia. These findings indicate that the antiarrhythmic activity of s-Lim is related to blockade of ß-AR in the heart.
Asunto(s)
Antiarrítmicos , Limoneno , Ratas Wistar , Receptores Adrenérgicos beta , Transducción de Señal , Animales , Ratas , Antiarrítmicos/farmacología , Masculino , Receptores Adrenérgicos beta/metabolismo , Limoneno/farmacología , Transducción de Señal/efectos de los fármacos , Terpenos/farmacología , Corazón/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Ciclohexenos/farmacología , Arritmias Cardíacas/tratamiento farmacológico , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/fisiopatología , Isoproterenol/farmacología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismoRESUMEN
Mosquito-borne diseases, such as malaria, dengue fever, and the Zika virus, pose significant global health challenges, affecting millions annually. Due to increasing insecticide resistance, there is a growing interest in natural alternatives for mosquito control. Lemongrass essential oil, derived from Cymbopogon citratus, has shown promising repellent and larvicidal properties against various mosquito species. In this study, we investigated the larvicidal effect of lemongrass oil and its major compounds on Anopheles sinensis, the primary malaria vector in China. GC-MS analysis identified the major compounds of lemongrass oil as ( +)-citronellal (35.60%), geraniol (21.84%), and citronellol (13.88%). Lemongrass oil showed larvicidal activity against An. sinensis larvae, with an LC50 value of 119.20 ± 3.81 mg/L. Among the major components, citronellol had the lowest LC50 value of 42.76 ± 3.18 mg/L. Moreover, citronellol demonstrated inhibitory effects on acetylcholinesterase (AChE) activity in An. sinensis larvae, assessed by homogenizing larvae at different time points following treatment. Molecular docking studies further elucidated the interaction between citronellol and AChE, revealing the formation of hydrogen bonds and Pi-Sigma bonds. Aromatic amino acid residues such as Tyr71, Trp83, Tyr370, and Tyr374 played a pivotal role in these interactions. These findings may contribute to understanding lemongrass oil's larvicidal activity against An. sinensis and the mechanisms underlying these effects.
Asunto(s)
Monoterpenos Acíclicos , Anopheles , Inhibidores de la Colinesterasa , Insecticidas , Larva , Aceites Volátiles , Aceites de Plantas , Animales , Anopheles/efectos de los fármacos , Anopheles/enzimología , Larva/efectos de los fármacos , Insecticidas/farmacología , Insecticidas/química , Monoterpenos Acíclicos/farmacología , Aceites de Plantas/farmacología , Aceites de Plantas/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Cymbopogon/química , Simulación del Acoplamiento Molecular , Terpenos/farmacología , Terpenos/química , Cromatografía de Gases y Espectrometría de Masas , China , Acetilcolinesterasa/metabolismo , Mosquitos Vectores/efectos de los fármacos , Monoterpenos/farmacología , Monoterpenos/química , Aldehídos/farmacología , Aldehídos/químicaRESUMEN
BACKGROUND: In recent decades, natural compounds have been considered a significant source of new antitumor medicines due to their unique advantages. Several in vitro and in vivo studies have focused on the effect of terpenoids on apoptosis mediated by mitochondria in malignant cells. RECENT FINDINGS: In this review article, we focused on six extensively studied terpenoids, including sesquiterpenes (dihydroartemisinin and parthenolide), diterpenes (oridonin and triptolide), and triterpenes (betulinic acid and oleanolic acid), and their efficacy in targeting mitochondria to induce cell death. Terpenoid-induced mitochondria-related cell death includes apoptosis, pyroptosis, necroptosis, ferroptosis, autophagy, and necrosis caused by mitochondrial permeability transition. Apoptosis and autophagy interact in meaningful ways. In addition, in view of several disadvantages of terpenoids, such as low stability and bioavailability, advances in research on combination chemotherapy and chemical modification were surveyed. CONCLUSION: This article deepens our understanding of the association between terpenoids and mitochondrial cell death, presenting a hypothetical basis for the use of terpenoids in anticancer management.
Asunto(s)
Mitocondrias , Neoplasias , Terpenos , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Terpenos/farmacología , Terpenos/uso terapéutico , Apoptosis/efectos de los fármacos , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Transducción de Señal/efectos de los fármacos , Diterpenos/farmacología , Diterpenos/uso terapéuticoRESUMEN
Plant essential oils (EOs)-based acaricides have been recognized as environmentally-friendly alternatives to synthetic acaricides because of their low toxicity against non-target species. Despite this, there are knowledge gaps regarding the toxicity mechanisms of plant EOs against non-target species. Here, the toxicology and enzymatic mechanism of Citrus reticulata and Citrus lemon EOs were evaluated against the vector pest, Haemaphysalis longicornis, and non-target ladybird beetle, Harmonia axyridis. Both EOs were mainly composed of d-Limonene, followed by ß-Myrcene and γ-Terpinene in C. reticulata, and (-)-ß-Pinene and γ-Terpinene in C. lemon. Citrus reticulata and C. lemon EOs were toxic to Hae. longicornis, with 50 % lethal concentration (LC50) values estimated at 0.43 and 0.98 µL/mL via nymphal immersion test, and 42.52 and 46.38 µL/mL via spray application, respectively. Among the constituents tested, ß-Myrcene was the most effective, with LC50 values of 0.17 and 47.87 µL/mL via immersion and spray treatment, respectively. A significant mortality of non-target Har. axyridis was found when treated by the EOs at concentrations two times greater than LC50 estimated against H. longicornis. The biochemical assay revealed that the EOs induced changes in the antioxidant enzyme activity of superoxide dismutases, catalase, and glutathione peroxidase in Hae. longicornis and Har. axyridis. The results demonstrated the acaricidal potential of citrus EOs and their major constituents for tick control, revealed the risk of the EOs to non-target species, and provided relevant insights into the mechanisms underlying their toxicity.
Asunto(s)
Acaricidas , Citrus , Escarabajos , Ixodidae , Aceites Volátiles , Animales , Aceites Volátiles/farmacología , Aceites Volátiles/toxicidad , Escarabajos/efectos de los fármacos , Ixodidae/efectos de los fármacos , Ixodidae/enzimología , Acaricidas/farmacología , Acaricidas/toxicidad , Monoterpenos Ciclohexánicos , Monoterpenos Bicíclicos/farmacología , Monoterpenos Acíclicos/toxicidad , Monoterpenos Acíclicos/farmacología , Limoneno/farmacología , Monoterpenos/farmacología , Monoterpenos/toxicidad , Ciclohexenos/toxicidad , Ciclohexenos/farmacología , Terpenos/farmacología , Catalasa/metabolismo , Superóxido Dismutasa/metabolismo , Glutatión Peroxidasa/metabolismo , Antioxidantes/farmacología , Haemaphysalis longicornisRESUMEN
Systemic lupus erythematosus is an autoimmune disease characterized by excessive inflammation and production of pathogenic Abs. Histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase. It has been reported that selective HDAC6 inhibition decreases inflammation in lupus mouse models. In this study, sex- and age-matched wild-type (WT) and HDAC6-/- mice on the C57BL/6 background were administered 0.5 ml of pristane or PBS i.p. at 8-12 wk of age and were euthanized 10 d later. At sacrifice, body weight and spleen weight were measured, sera were collected, and splenocytes and peritoneal cells were harvested for flow cytometry. We found pristane administration increased the spleen weight with no difference between WT and HDAC6-/- mice. Pristane administration promoted the population of CD11b+Ly6C++ inflammatory monocytes and CD11b+Ly6G+ neutrophils. Peritoneal recruitment of these inflammatory monocytes and neutrophils was significantly decreased in HDAC6-/- mice compared with the WT mice. Flow cytometry results showed that the number of CD69+ T and B cells was increased in HDAC6-/- mice. Pristane administration also induced the IFN signature genes as determined by RT-qPCR. Furthermore, IFN signature genes were not affected in HDAC6-/- mice compared with the WT mice. In vitro studies in J774A.1 cells revealed that the selective HDAC6 inhibitor (ACY-738) increased acetylation of NF-κB while increasing Stat1 phosphorylation, which resulted in inducible NO synthase production in LPS/IFN-γ-stimulated cells. Taken together, these results demonstrate that although HDAC6 inhibition may inhibit some inflammatory pathways, others remain unaffected.
Asunto(s)
Histona Desacetilasa 6 , Inflamación , Ratones Endogámicos C57BL , Ratones Noqueados , Terpenos , Animales , Histona Desacetilasa 6/antagonistas & inhibidores , Histona Desacetilasa 6/genética , Histona Desacetilasa 6/metabolismo , Terpenos/farmacología , Ratones , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/inmunología , Bazo/inmunología , Bazo/metabolismo , Bazo/citología , Monocitos/metabolismo , Monocitos/inmunología , Monocitos/efectos de los fármacos , Femenino , Modelos Animales de Enfermedad , Neutrófilos/inmunología , Neutrófilos/metabolismo , Factor de Transcripción STAT1/metabolismo , Masculino , Linfocitos B/inmunología , Linfocitos B/metabolismoRESUMEN
Shigella flexneri is a gram-negative bacterium responsible for shigellosis and bacterial dysentery. Despite using various synthetic antimicrobial agents and antibiotics, their efficacy is limited, prompting concerns over antibiotic resistance and associated health risks. This study investigated eugenol, a polyphenol with inherent antioxidant and antibacterial properties, as a potential alternative treatment. We aimed to evaluate eugenol's antibacterial effects and mechanisms of action against S. flexneri and its impact on biofilm formation. We observed significant growth suppression of S. flexneri with eugenol concentrations of 8-10 mM (98.29%). Quantitative analysis using the Crystal Violet assay demonstrated a marked reduction in biofilm formation at 10 mM (97.01 %). Assessment of Cell Viability and morphology via Fluorescence-Activated Cell Sorting and Scanning Electron Microscopy confirmed these findings. Additionally, qPCR analysis revealed the downregulation of key genes responsible for adhesion (yebL), quorum sensing (rcsC, sdiA), and EPS production (s0482) associated with bacterial growth and biofilm formation. The present study suggests eugenol could offer a promising alternative to conventional antibiotics for treating shigellosis caused by S. flexneri.
Asunto(s)
Antibacterianos , Biopelículas , Eugenol , Shigella flexneri , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Shigella flexneri/efectos de los fármacos , Shigella flexneri/genética , Shigella flexneri/crecimiento & desarrollo , Shigella flexneri/fisiología , Eugenol/farmacología , Antibacterianos/farmacología , Percepción de Quorum/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Disentería Bacilar/tratamiento farmacológico , Disentería Bacilar/microbiología , Terpenos/farmacologíaRESUMEN
Ten new drimane meroterpenoids talarines A-J (1-10), along with six known analogues (11-16), were isolated from desert soil-derived fungus Talaromyces pinophilus LD-7. Their 2D structures were elucidated by comprehensive interpretation of NMR and HRESIMS data. Electronic circular dichroism calculation was used to establish their absolute configurations. Compounds 2, 10, and 11 showed antiviral activities toward vesicular stomatitis virus with IC50 values of 18, 15, and 23 nM, respectively. The structure-bioactivity relationship indicated that chlorine substitution at C-5 contributed greatly to their antiviral activities. Finally, we identified a new halogenase outside the biosynthetic gene cluster, which was responsible for C-5 halogenation of the precursor isocoumarin 17 as a tailoring step in chlorinated meroterpenoids assembly.
Asunto(s)
Antivirales , Talaromyces , Antivirales/farmacología , Antivirales/química , Antivirales/aislamiento & purificación , Vías Biosintéticas , Halogenación , Estructura Molecular , Sesquiterpenos Policíclicos/farmacología , Relación Estructura-Actividad , Talaromyces/química , Terpenos/farmacología , Terpenos/química , Terpenos/aislamiento & purificaciónRESUMEN
Halophila stipulacea (Forsskål and Niebuhr) Ascherson is a small marine seagrass that belongs to the Hydrocharitaceae family. It is native to the Red Sea, Persian Gulf, and Indian Ocean and has successfully invaded the Mediterranean and Caribbean Seas. This article summarizes the pharmacological activities and phytochemical content of H. stipulacea, along with its botanical and ecological characteristics. Studies have shown that H. stipulacea is rich in polyphenols and terpenoids. Additionally, it is rich in proteins, lipids, and carbohydrates, contributing to its nutritional value. Several biological activities are reported by this plant, including antimicrobial, antioxidant, anticancer, anti-inflammatory, anti-metabolic disorders, and anti-osteoclastogenic activities. Further research is needed to validate the efficacy and safety of this plant and to investigate the mechanisms of action underlying the observed effects.
Asunto(s)
Fitoquímicos , Fitoquímicos/química , Fitoquímicos/farmacología , Humanos , Hydrocharitaceae/química , Animales , Antioxidantes/farmacología , Antioxidantes/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Polifenoles/química , Polifenoles/farmacología , Antiinfecciosos/farmacología , Antiinfecciosos/química , Terpenos/química , Terpenos/farmacologíaRESUMEN
Currently, there is an urgent need for new antibacterial and antifungal agents to combat the growing challenge of antibiotic resistance. As the largest ecosystem on Earth, the marine ecosystem includes a vast array of microorganisms (primarily bacteria and fungi), plants, invertebrates, and vertebrates, making it a rich source of various antimicrobial compounds. Notably, terpenoids, known for their complex structures and diverse bioactivities, are a significant and promising group of compounds in the battle against bacterial and fungal infections. In the past five years, numerous antimicrobial terpenoids have been identified from marine organisms such as bacteria, fungi, algae, corals, sea cucumbers, and sponges. This review article provides a detailed overview of 141 terpenoids with antibacterial and/or antifungal properties derived from marine organisms between 2019 and 2024. Terpenoids, a diverse group of natural organic compounds derived from isoprene units, are systematically categorized based on their carbon skeleton structures. Comprehensive information is provided about their names, structures, biological sources, and the extent of their antibacterial and/or antifungal effectiveness. This review aims to facilitate the rapid identification and development of prospective antimicrobials in the pharmaceutical sector.
Asunto(s)
Organismos Acuáticos , Terpenos , Terpenos/farmacología , Terpenos/química , Animales , Antiinfecciosos/farmacología , Antiinfecciosos/química , Bacterias/efectos de los fármacos , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Hongos/efectos de los fármacos , Antifúngicos/farmacología , Antifúngicos/químicaRESUMEN
Ten new B-ring aromatized 6/6/6-tricyclic dearomatized benzocogeijerene-based meroterpenoids with unusual methyl 1,2-shift or demethylation (2-9b), and two new geranylquinol derivatives (1 and 10), together with two known compounds (11 and 12), were isolated from the roots of Arnebia euchroma. Their structures were elucidated by extensive spectroscopic methods, X-ray diffraction crystallography, and ECD calculations. The plausible biosynthetic pathways including the unusual methyl 1,2-shfit and demethylation for B-ring aromatized 6/6/6-tricyclic meroterpenoids were discussed. Compounds 1, 2, 5, 6, 11, and 12 showed significant cardioprotective activities comparable to diltiazem against isoprenaline (ISO)-induced H9C2 cell damage in vitro. Compound 11 probably exerted heart-protective effect on ISO-induced H9C2 cells by modulating the PI3K-AKT-mTOR pathway, reducing excessive autophagy, and decreasing myocardial apoptosis.
Asunto(s)
Apoptosis , Autofagia , Boraginaceae , Miocitos Cardíacos , Terpenos , Apoptosis/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Autofagia/efectos de los fármacos , Boraginaceae/química , Ratas , Terpenos/farmacología , Terpenos/química , Terpenos/aislamiento & purificación , Animales , Estructura Molecular , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Insuficiencia Cardíaca/tratamiento farmacológico , Cardiotónicos/farmacología , Cardiotónicos/química , Cardiotónicos/aislamiento & purificación , Línea CelularRESUMEN
Cisplatin is a widely used drug for the clinical treatment of tumors. However, nephrotoxicity limits its widespread use. A series of compounds including eight analogs (G3-G10) and 40 simplifiers (G11-G50) were synthesized based on the total synthesis of Psiguamer A and B, which were novel meroterpenoids with unusual skeletons from the leaves of Psidium guajava. Among these compounds, (d)-G8 showed the strongest protective effect on cisplatin-induced acute kidney injury (AKI) in vitro and vivo, and slightly enhanced the antitumor efficacy of cisplatin. A mechanistic study showed that (d)-G8 promoted the efflux of cisplatin via upregulating the copper transporting efflux proteins ATP7A and ATP7B. It enhanced autophagy through the activation of the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. (d)-G8 showed no acute toxicity or apparent pathological damage in the healthy mice at a single dose of 1 g/kg. This study provides a promising lead against cisplatin-induced AKI.
Asunto(s)
Lesión Renal Aguda , Antineoplásicos , Cisplatino , Psidium , Cisplatino/farmacología , Animales , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/patología , Ratones , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Psidium/química , Terpenos/farmacología , Terpenos/síntesis química , Terpenos/química , Masculino , Relación Estructura-ActividadRESUMEN
Despite ongoing research on antimicrobial peptides (AMPs) and cell-penetrating peptides (CPPs), their precise translocation mechanism remains elusive. This includes Buforin 2 (BF2), a well-known AMP, for which spontaneous translocation across the membrane has been proposed but a high barrier has been calculated. Here, we used computer simulations to investigate the effect of a nonequilibrium situation where the peptides are adsorbed on one side of the lipid bilayer, mimicking experimental conditions. We demonstrated that the asymmetric membrane adsorption of BF2 enhances its translocation across the lipid bilayer by lowering the energy barrier by tens of kJ mol-1. We showed that asymmetric membrane adsorption also reduced the free energy barrier of lipid flip-flop but remained unlikely even at BF2 surface saturation. These results provide insight into the driving forces behind membrane translocation of cell-penetrating peptides in nonequilibrium conditions, mimicking experiments.
Asunto(s)
Membrana Dobles de Lípidos , Membrana Dobles de Lípidos/química , Membrana Dobles de Lípidos/metabolismo , Adsorción , Terpenos/química , Terpenos/farmacología , Simulación de Dinámica Molecular , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/química , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/metabolismo , Péptidos de Penetración Celular/química , Péptidos de Penetración Celular/metabolismo , Termodinámica , Membrana Celular/metabolismo , Membrana Celular/química , ProteínasRESUMEN
Garcinia indica, known as kokum, has been extensively researched for its therapeutic potential. Among the wide variety of phytoconstituents, garcinol is the most efficacious, holding anti-inflammatory, anti-cancer, and anti-diabetic properties. Hydrophobicity and a certain level of toxicity have constrained the drug's application and necessitated a modified dosage form design. The drug has been well explored in the form of extracts but bears very limited application in dosage forms. These prompted in implementation of protein polymers, due to non-toxicity, biocompatibility, and biodegradability. BSA encapsulates the drug, by the desolvation method. The unavailability of past exploration of garcinol with protein polymer accelerated the novelty of this study, to improve the solubility and bioavailability of the drug, modify the drug release kinetics, and ascertain the effectiveness of the NPs to combat inflammation in-vitro. NPs were characterized and satisfactory outcomes were retrieved in terms of all characterizations. The drug release studies depicted a sustained release of up to 85 % over 16 h, ensuring that garcinol can be modulated to give a desired scale of modified release. In vitro cellular uptake studies suggested a substantial uptake of NPs in cell lines and its effectiveness to mitigate inflammation was affirmed by in-vitro anti-inflammatory studies, using ELISA.
Asunto(s)
Portadores de Fármacos , Liberación de Fármacos , Interacciones Hidrofóbicas e Hidrofílicas , Nanopartículas , Albúmina Sérica Bovina , Terpenos , Albúmina Sérica Bovina/química , Terpenos/química , Terpenos/farmacología , Animales , Portadores de Fármacos/química , Cinética , Nanopartículas/química , Humanos , Bovinos , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/farmacocinética , Ratones , SolubilidadRESUMEN
Staphylococcus aureus, particularly multi-drug resistant strains, presents significant challenges in dairy farming due to its role in causing bovine mastitis, which leads to substantial economic losses and limited treatment options. Seeking alternative therapies, we investigated the potential of a topical formulation derived from the medicinal herb Salvia officinalis to combat S. aureus growth and biofilms associated with bovine mastitis. Through systematic extraction in different solvents and fractionation by column chromatography, we isolated and identified three key multicyclic terpenoids-ferruginol, sugiol, and sclareol-exhibiting significant antimicrobial activity. The formulation effectively inhibited biofilm formation, with minimum inhibitory concentration (MIC) values ranging from 0.09 to 0.74 mg ml-1 against clinical S. aureus strains, comparable to or lower than those of the pure compounds. Moreover, it displayed robust anti-adhesive properties, reducing biofilm formation by 20%-79% at subinhibitory concentrations. Furthermore, the formulation successfully disrupted pre-existing biofilms, achieving reductions ranging from 30% to 82%. Cytotoxicity assays confirmed the safety of the formulation on mammary epithelial cells, with cell viability maintained at 100% at MIC. Our findings underscore the therapeutic potential of Sa. officinalis-derived compounds in managing bovine mastitis caused by S. aureus, emphasizing their antimicrobial efficacy and safety profile.
Asunto(s)
Antibacterianos , Biopelículas , Mastitis Bovina , Pruebas de Sensibilidad Microbiana , Extractos Vegetales , Plantas Medicinales , Salvia officinalis , Staphylococcus aureus , Terpenos , Staphylococcus aureus/efectos de los fármacos , Biopelículas/efectos de los fármacos , Animales , Bovinos , Salvia officinalis/química , Terpenos/farmacología , Terpenos/química , Terpenos/aislamiento & purificación , Mastitis Bovina/microbiología , Mastitis Bovina/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antibacterianos/farmacología , Antibacterianos/aislamiento & purificación , Antibacterianos/química , Plantas Medicinales/química , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , FemeninoRESUMEN
Terpenoids are a large class of natural secondary plant metabolites which are highly diverse in structure, formed from isoprene units (C-5), associated with a wide range of biological properties, including antioxidant, antimicrobial, anti-inflammatory, antiallergic, anticancer, antimetastatic, antiangiogenesis, and apoptosis induction, and are considered for potential application in the food, cosmetics, pharmaceutical, and medical industries. In plants, terpenoids exert a variety of basic functions in growth and development. This review gives an overview, highlighting the current knowledge of terpenoids and recent advances in our understanding of the organization, regulation, and diversification of core and specialized terpenoid metabolic pathways and addressing the most important functions of volatile and non-volatile specialized terpenoid metabolites in plants. A comprehensive description of different aspects of plant-derived terpenoids as a sustainable source of bioactive compounds, their biosynthetic pathway, the several biological properties attributed to these secondary metabolites associated with health-promoting effects, and their potential industrial applications in several fields will be provided, and emerging and green extraction methods will also be discussed. In addition, future research perspectives within this framework will be highlighted. Literature selection was carried out using the National Library of Medicine, PubMed, and international reference data for the period from 2010 to 2024 using the keyword "terpenoids". A total of 177,633 published papers were found, of which 196 original and review papers were included in this review according to the criteria of their scientific reliability, their completeness, and their relevance to the theme considered.
Asunto(s)
Terpenos , Terpenos/química , Terpenos/metabolismo , Terpenos/farmacología , Humanos , Plantas/química , Plantas/metabolismo , Antioxidantes/farmacología , Antioxidantes/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antiinfecciosos/farmacología , Antiinfecciosos/químicaRESUMEN
This is a nonclinical, controlled, and triple-blind study to investigate the effects of codeine-associated geraniol on the modulation of orofacial nociception and its potential central nervous system depressing effect in an animal model. The orofacial antinociceptive activity of geraniol in combination with codeine was assessed through the following tests: (i) formalin-induced pain, (ii) glutamate-induced pain, and (iii) capsaicin-induced pain. Six animals were equally distributed into six groups and received the following treatments, given intraperitoneally (i.p.) 30 minutes before the experiments: a) geraniol/codeine 50/30 mg/kg; b) geraniol/codeine 50/15 mg/kg; c) geraniol/codeine 50/7.5 mg/kg; d) geraniol 50 mg/kg; e) codeine 30 mg/kg (positive control); or f) 0.9% sodium chloride (negative control). We performed pain behavior analysis after the injection of formalin (20 µL, 20%), glutamate (20 µL, 25 µM), and capsaicin (20 µL, 2.5 µg) into the paranasal region. Rubbing time of the paranasal region by the hind or front paw was used as a parameter. In the neurogenic phase of the formalin test, the geraniol/codeine at 50/7.5 mg/kg was able to promote the maximum antinociceptive effect, reducing nociception by 71.9% (p < 0.0001). In the inflammatory phase of the formalin test, geraniol/codeine at 50/30 mg/kg significantly reduced orofacial nociception (p < 0.005). In the glutamate test, geraniol/codeine at 50/30 mg/kg reduced the rubbing time by 54.2% and reduced nociception in the capsaicin test by 66.7% (p < 0.005). Geraniol alone or in combination does not promote nonspecific depressing effects on the central nervous system. Based on our findings, we suggest the possible synergy between geraniol and codeine in the modulation of orofacial pain.
Asunto(s)
Monoterpenos Acíclicos , Analgésicos , Capsaicina , Codeína , Dolor Facial , Dimensión del Dolor , Terpenos , Animales , Codeína/farmacología , Dolor Facial/inducido químicamente , Dolor Facial/tratamiento farmacológico , Monoterpenos Acíclicos/farmacología , Masculino , Dimensión del Dolor/efectos de los fármacos , Capsaicina/farmacología , Terpenos/farmacología , Analgésicos/farmacología , Ratones , Factores de Tiempo , Modelos Animales de Enfermedad , Reproducibilidad de los Resultados , Formaldehído , Ácido Glutámico , Resultado del Tratamiento , Nocicepción/efectos de los fármacos , Análisis de Varianza , Estadísticas no Paramétricas , Conducta Animal/efectos de los fármacosRESUMEN
Research studies on plant secondary metabolites have increased over the last decades as a consequence of the growing consumer demand for natural products in pharmaceutics and therapeutics, as well as in perfumery and cosmetics. In this perspective, many Mediterranean plant species could be an appreciated source of bioactive compounds with pharmacological and health-promoting properties, including antioxidant, antimicrobial, antiviral, anti-inflammatory, and antitumor ones. Calendula officinalis and Foeniculum vulgare are commercially important plants of the Mediterranean flora, with great therapeutic use in the treatment of many disorders since ancient times, and are now listed in several world pharmacopoeias and drug agencies. The present review offers an overview of the main phytochemicals, phenols, terpenes, and alkaloids, biosynthesized in C. officinalis and F. vulgare, both species endemic to the Mediterranean region. Further, all current knowledge and scientific data on taxonomic classification, botanical description, traditional uses, pharmacological studies, and potential toxicity of both species were reported. The principal aim of this review is to point out the prospective use of C. officinalis and F. vulgare as valuable reservoirs of beneficial plant-derived products with interesting biological properties, also providing suggestions and future challenges for the full exploitation of these two Mediterranean species for human life improvement.
Asunto(s)
Calendula , Foeniculum , Fitoquímicos , Fitoquímicos/química , Fitoquímicos/farmacología , Calendula/química , Región Mediterránea , Humanos , Foeniculum/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Fenoles/química , Fenoles/farmacología , Antioxidantes/farmacología , Antioxidantes/química , Terpenos/química , Terpenos/farmacología , Terpenos/aislamiento & purificación , Alcaloides/química , Alcaloides/farmacología , Alcaloides/aislamiento & purificaciónRESUMEN
Sleep insufficiency is a significant health problem worldwide, and adolescent sleep restriction (SR) could induce multiple neurodevelopmental disorders in the central nervous system (CNS). Microglial-mediated neuroinflammation plays a vital role in multiple neurological diseases, and recent research showed the regulation effect of immunoproteasome on microglia functions. Geraniol (GER), an important ingredient in many essential oils, possesses diverse pharmacological properties like anti-inflammatory and antioxidant. The present study was designed to evaluate the neuroprotective effect of GER on SR in adolescent mice and further investigate the underlying mechanisms. Our results displayed that 14 days of chronic sleep restriction (CSR) induced cognitive decline, and anxiety-like and attention-deficit behaviors, which were mitigated by GER pretreatment. GER administration also reversed microglial pro-inflammatory response under CSR stimulation in the anterior cingulate cortex (ACC) regions by reducing the expression and secretion of cytokines like IL-1ß and TNF-α. Mechanism research showed that LMP7 mRNA was selectively up-regulated under CSR treatment but down-regulated by GER administration. Proteasome activity and protein expression of LMP7 were consistent with mRNA data. ONX-0914 was applied to inhibit LMP7 selectively, and data validated that GER might alleviate CSR-induced neuroinflammation by regulating LMP7. Our study provides evidence that LMP7 is a critical regulator of CSR-induced proinflammation, and geraniol might be a promising therapy against CSR-induced neurodevelopmental disorders.
Asunto(s)
Monoterpenos Acíclicos , Enfermedades Neuroinflamatorias , Privación de Sueño , Animales , Monoterpenos Acíclicos/farmacología , Monoterpenos Acíclicos/uso terapéutico , Ratones , Privación de Sueño/complicaciones , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/etiología , Masculino , Fármacos Neuroprotectores/farmacología , Terpenos/farmacología , Microglía/efectos de los fármacos , Microglía/metabolismoRESUMEN
Ganoderma lucidum, a medicinal mushroom with a long history in traditional Chinese medicine, is widely used for chronic diseases. Ganospirones A-G (1-7), seven pairs of undescribed spiro-meroterpenoids, were isolated from the fruiting bodies of G. lucidum. Their structures including absolute configurations were characterized by using NMR spectroscopic data, ECD computational and X-ray diffraction methods. The anti-inflammatory and anti-renal fibrosis activities of the meroterpenoids 1-7 were tested, and the results revealed that (-)-2 and (+)-2 could inhibit iNOS expression in lipopolysaccharide-induced RAW264.7 cells at 20 µM.
Asunto(s)
Lipopolisacáridos , Reishi , Ratones , Animales , Células RAW 264.7 , Reishi/química , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Estructura Molecular , Compuestos de Espiro/química , Compuestos de Espiro/farmacología , Compuestos de Espiro/aislamiento & purificación , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/metabolismo , Terpenos/farmacología , Terpenos/química , Terpenos/aislamiento & purificación , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Relación Estructura-Actividad , Relación Dosis-Respuesta a DrogaRESUMEN
Gastrointestinal cancers continue to pose a significant global health challenge, with millions of new cases diagnosed each year. Despite advancements in treatment, the prognosis for many patients remains poor. This article explores the potential of garcinol, a polyisoprenylated benzophenone found in various Garcinia species, as a therapeutic agent against gastrointestinal malignancies. The objective is to review recent research on garcinol's anticancer properties, its mechanisms of action, and safety aspects. Garcinol exhibits anticancer effects in esophageal, gastric, colorectal, pancreatic, and liver cancers by inhibiting metastasis, inducing apoptosis, and targeting key molecular pathways in cancer progression. Nanotechnology is explored as a means to enhance garcinol delivery and efficacy. Safety assessments suggest a promising toxicity profile. Garcinol shows significant potential as a natural therapeutic agent for gastrointestinal cancers, and future research is needed on optimizing its delivery, exploring synergistic combinations, and conducting clinical trials to validate its efficacy and safety for clinical applications.