RESUMO
Leishmaniasis is a neglected tropical disease that affects millions of people around the world. Available therapy causes severe side effects, has unacceptable prices for some specific formulations, and the existence of drug-resistant parasites limits the use of the currently available arsenal of antiparasitic drugs. Therefore, natural products serve as one of the main sources to develop new and effective alternative drugs against leishmaniasis. In this sense, the present study evaluated the potential of the triterpene Lupeol (Lu) entrapped in nanostructured lipid carriers (NLCs) for the treatment of experimental visceral leishmaniasis. The therapeutic efficacy of Lu or Lu entrapped in NLC (Lu-NLC) was investigated in golden hamsters infected with Leishmania (Leishmania) infantum. Lu-NLC presented a mean particle size of 265.3 ± 4.6 nm, a polydispersity index of <0.25 and a zeta potential of -37.2 ± 0.84 mV; the efficacy of encapsulation was 84.04 ± 0.57%. Studies on hamsters showed that Lu-NLC (5 mg/kg) administered intraperitoneally for 10 consecutive days caused a reduction of 99.9% in the number of parasites in the spleen and liver compared to the untreated infected control. On the contrary, Lu-treated animals (5 mg/kg) had 94.4 and 90.2% less parasites in the spleen and liver, respectively, than the infected group. Additionally, a significant preservation of splenic and hepatic tissues was observed in animals treated with Lu-NLC or Lu. Furthermore, Lu-NLC-treated animals produced high levels of anti-Leishmania IgG2 isotype. These data indicate that NLC potentialized Lu efficacy in experimental visceral leishmaniasis. This work suggests that Lu and nanoformulations carrying this compound may be considered as an important tool to be included in the alternative therapy of leishmaniasis.
RESUMO
Propolis is used by corbiculated bees to protect the bee hive; it is mostly used to seal cracks, to reduce or prevent microbial growth and to embalm invaders. Different factors have been reported to influence the chemical composition of propolis, including bee species and the flora surrounding the hive. Nevertheless, the majority of the studies are focused on propolis produced by Apis mellifera, while studies on the chemical composition of propolis produced by stingless bees are still limited. In this investigation, the chemical composition of 27 propolis samples collected in the Yucatan Peninsula from A. mellifera beehives, together with 18 propolis samples from six different species of stingless bees, were analyzed by GC-MS. Results showed that lupeol acetate and ß-amyrin were the characteristic triterpenes in propolis samples from A. mellifera, while grandiflorenic acid and its methyl ester were the main metabolites present in samples from stingless bees. Multivariate analyses were used to explore the relationship between bee species and botanical sources on the chemical composition of the propolis samples. Differences in body size and, therefore, foraging abilities, as well as preferences for specific botanical sources among bee species, could explain the observed variation in propolis chemical composition. This is the first report on the composition of propolis samples from the stingless bees Trigona nigra, Scaptotrigona pectoralis, Nannotrigona perilampoides, Plebeia frontalis and Partamona bilineata.
Assuntos
Ascomicetos , Própole , Animais , Própole/química , México , Cromatografia Gasosa-Espectrometria de Massas , Análise MultivariadaRESUMO
Pentacyclic triterpenes, including lupeol, α- amyrin, and ß-amyrin, present a large range of biological activities including anti-inflammatory, anti-cancer, and gastroprotective properties. The phytochemistry of dandelion (Taraxacum officinale) tissues has been widely described. Plant biotechnology offers an alternative for secondary metabolite production and several active plant ingredients are already synthesized through in vitro cultures. This study aimed to establish a suitable protocol for cell growth and to determine the accumulation of α-amyrin and lupeol in cell suspension cultures of T. officinale under different culture conditions. To this end, inoculum density (0.2% to 8% (w/v)), inoculum age (2- to 10-week-old), and carbon source concentration (1%, 2.3%, 3.2%, and 5.5% (w/v)) were investigated. Hypocotyl explants of T. officinale were used for callus induction. Age, size, and sucrose concentrations were statistically significant in cell growth (fresh and dry weight), cell quality (aggregation, differentiation, viability), and triterpenes yield. The best conditions for establishing a suspension culture were achieved by using a 6-week-old callus at 4% (w/v) and 1% (w/v) of sucrose concentration. Results indicate that 0.04 (±0.02) α-amyrin and 0.03 (±0.01) mg/g lupeol can be obtained in suspension culture under these starting conditions at the 8th week of culture. The results of the present study provide a backdrop for future studies in which an elicitor could be incorporated to increase the large-scale production of α-amyrin and lupeol from T. officinale.
RESUMO
Visceral leishmaniasis (VL) is a severe and potentially fatal neglected tropical disease, being considered a public health concern in many countries worldwide. There are still no vaccines against human VL, and the existing chemotherapy is often toxic. Thereby, alternative treatments have been investigated, and byproducts from plant metabolism have been a source of promising pharmacological compounds. Terpenes are secondary metabolites that exhibit a large spectrum of therapeutic activities. Herein, we conducted a systematic review to evaluate the effects of terpenes in the treatment of VL in rodents. After an extensive search using the PubMed/MEDLINE, Scopus, and Web of Science databases, we included 34 articles in this review. Our results revealed that triterpenes were the most used terpenes by the eligible studies. Overall, terpene treatment showed no or negligible toxicity, causing an increase in the Th1-type immune response profile and nitric oxide production. It also reduced the Th2 cytokines levels and parasite load (> 90% to > 99%). Moreover, terpenes induced apoptosis by damaging the plasma membrane and inhibiting DNA topoisomerases in the parasite. The use of terpene carriers increased the terpene bioavailability in the body, preventing their rapid excretion and promoting the drug delivery at the site of Leishmania infection. Terpene derivatives showed better pharmacokinetics than the original terpenes. Altogether, the benefits of VL treatment with terpenes in preclinical studies may open new directions for other preclinical and human trials.
Assuntos
Leishmaniose Visceral , Triterpenos , Sistemas de Liberação de Medicamentos , Humanos , Leishmaniose Visceral/tratamento farmacológico , Fitoterapia , Terpenos/farmacologia , Terpenos/uso terapêuticoRESUMO
In our previous work, lupeol was isolated from aerial parts of V. scorpioides and modified by semisynthetic approach. The purpose of this study was to investigate the cytotoxicity of lupeol and its derivatives previously prepared on the human K562 acute myeloid leukemia cell and human Jurkat acute lymphoid leukemia cell in vitro. Compounds 3ß-hydroxylup-20(29)-en-30-al (2), lup-20(30)-en-3ß,29-diol (3), 3ß-acetoxylup-20(29)-en-30-al (5) and 3ß-acetoxy-30-hydroxylup-20(29)-ene (6) presented cytotoxicity with IC50 ranging from 11.72 to 56.15 µM at 24 h of incubation for both cell lines. Most of the active compounds (3, 5 and 6) were selective to leukemia cells, in compare with healthy cells. The hemolysis assay showed high blood compatibility of the cytotoxic lupeol derivatives which makes possible an intravenous administration of these compounds aiming to the potential to development of anti-leukemic drugs.
Assuntos
Extratos Vegetais , Humanos , Células Jurkat , Triterpenos Pentacíclicos/farmacologiaRESUMO
Triplaris gardneriana is used by traditional medicine. The objective of this work was the leaves chemical study with isolate, identify and quantify the chemical constituent, validate the analytical method and evaluate the antibacterial activity. The ethyl acetate and chloroform fractions were subjected to column chromatography for isolation of the compounds quercetin and lupeol, respectively. For the identification, quantification of quercetin in the samples and validation of method were performed using HPLC-DAD. The antibacterial activity was evaluated by the microdilution method. The isolated phytochemicals are being reported for the first time in the species. The ethyl acetate fraction showed a higher content of quercetin with 9.967 ± 1.01 mg.g-1. The method was validated. The samples showed good antibacterial activity. In this study, quercetin was isolated and quantified in the species being a great alternative as a producer of this secondary metabolite, which can be safely applied in the quality control analysis.
Assuntos
Antibacterianos/farmacologia , Polygonaceae/química , Quercetina , Antibacterianos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais , Folhas de Planta/química , Quercetina/isolamento & purificação , Quercetina/farmacologiaRESUMO
Skin wound healing is a highly complex event that involves different mediators at the cellular and molecular level. Lupeol has been reported to possess different biological activities, such as anti-inflammatory, antioxidant, antidiabetic, and in vitro wound healing properties, which motivated us to proceed with in vivo studies. We aimed to investigate the wound healing effect of lupeol-based cream for 3, 7, and 14 days. Wound excisions were induced on the thoraco-lumbar region of rats and topically treated immediately after injury induction. Macroscopic, histopathological, and immunohistochemical analyses were performed. Cytokine levels were measured by ELISA and gene expression was evaluated by real-time RT-qPCR. Our results showed a strong wound-healing effect of lupeol-based cream after 7 and 14 days. Lupeol treatment caused a reduction in proinflammatory cytokines (TNF-a, IL-1ß, and IL-6) and gene and protein NF-κB expression, and positively altered IL-10 levels, showing anti-inflammatory effects in the three treatment periods. Lupeol treatment showed involvement in the proliferative phase by stimulating the formation of new blood vessels, increasing the immunostaining of Ki-67 and gene expression, and immunolabeling of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), and increasing gene expression of transforming growth factor beta-1 (TGF-ß1) after seven days of treatment. Lupeol was also involved in the tissue regeneration phase by increasing the synthesis of collagen fibers noted in the three treatment periods analyzed. Our findings suggest that lupeol may serve as a novel therapeutic option to treat cutaneous wounds by regulating mechanisms involved in the inflammatory, proliferative, and tissue-remodeling phases.
Assuntos
Anti-Inflamatórios/uso terapêutico , Colágeno/metabolismo , Citocinas/metabolismo , Fármacos Dermatológicos/uso terapêutico , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Antígeno Ki-67/metabolismo , NF-kappa B/metabolismo , Triterpenos Pentacíclicos/uso terapêutico , Fitoterapia , Cicatrização/efeitos dos fármacos , Administração Cutânea , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação , Peptídeos e Proteínas de Sinalização Intercelular/genética , Antígeno Ki-67/genética , Masculino , NF-kappa B/genética , Neovascularização Fisiológica/efeitos dos fármacos , Triterpenos Pentacíclicos/administração & dosagem , Triterpenos Pentacíclicos/farmacologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Wistar , Regeneração/efeitos dos fármacos , Fenômenos Fisiológicos da Pele/efeitos dos fármacosRESUMO
In this study, we investigated the protective effects of Hedera nepalensis crude extract, its fractions and lupeol in alloxan-induced diabetic rats. Lupeol and n-hexane (HNN) fraction significantly reduced the blood glucose level by increasing insulin level in time dependent manner, and also significantly increased amylase and lipase activity in diabetic rats. Elevated levels of alanine transaminases (ALT), aspartate transaminases (AST), thiobarbituric acid reactive substances (TBARS), nitrite, hydrogen peroxide (H2O2), total bilirubin and total protein in blood serum were efficiently restored to normal levels. Suppressed enzymatic activity of catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and peroxidase (POD) were also restored to their normal levels. Kidney functions were also restored to normal level after treatment with HNN and lupeol. HNN fraction and lupeol of H. nepalensis prevented oxidative stress in alloxan-induced diabetic rats. This study signifies the importance of H. nepalensis and lupeol in ameliorating diabetes by inducing insulin secretion in diabetic model rats.
Assuntos
Animais , Masculino , Ratos , Plantas Medicinais/metabolismo , Araliaceae/classificação , Hedera/efeitos adversos , Diabetes Mellitus Tipo 1/induzido quimicamente , Misturas Complexas/efeitos adversos , Aloxano/efeitos adversos , InsulinaRESUMO
In the central nervous system (CNS), neuroinflammation, especially that modulated by the cell response of astrocytes and microglia, is associated with damage to neurons in neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and, Multiple Sclerosis. Lupeol is a dietary triterpene that has demonstrated biological activities as antioxidant. This study investigated the anti-inflammatory and neuroprotective effects of lupeol in an in vitro model of neuroinflammation in primary cerebellar cultures. Cultures were obtained from 6-day-old Wistar rats, subjected to inflammatory damage with lipopolysaccharide (LPS, 1⯵g/mL) and treated with lupeol (0.1⯵M). We observed, after a 48-hour treatment, through Fluorjade-B staining and immunocytochemistry (ICQ) for ßIII-tubulin, that lupeol induced neuroprotection in cultures submitted to inflammatory damage. On the other hand, through ICQ for GFAP, it was possible to observe that lupeol modulated the astrocyte morphology for Bergmann glia-like phenotype and, especially for velate astrocyte-like phenotype, both phenotypes associated with the neuroprotective profile. Moreover, RT-qPCR analysis showed that lupeol induced the down-regulation of the mRNA expression for proinflammatory markers TNF, iNOS and NLRP3, as well as the production of nitric oxide (method of Greiss), which were up-regulated by LPS, and also induced up-regulation of the mRNA expression for arginase and IL-6 mRNA. In addition, lupeol induced up-regulation of mRNA expression for neurotrophins GDNF and NGF and also for the sonic hedgehog-Gli pathway. Together, these results lead to the conclusion that lupeol inhibits neuroinflammation in cerebellar cultures and induces neuroprotection associated with the modulation of astrocyte response and expression of neurotrophic and inflammatory factors.
Assuntos
Anti-Inflamatórios/farmacologia , Astrócitos/fisiologia , Cerebelo/patologia , Inflamação Neurogênica/tratamento farmacológico , Triterpenos Pentacíclicos/farmacologia , Animais , Astrócitos/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fatores de Crescimento Neural/metabolismo , Inflamação Neurogênica/imunologia , Neuroproteção , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Wistar , Tubulina (Proteína)/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Lupeol is a dietary triterpene that shows limited water solubility, which affects its bioavailability. It is well known that poor oral bioavailability is one of the major causes of therapeutic variability. Lupeol has been reported to have multiple biological activities; however, there are no reports about its bioavailability. Therefore, the objective of this research was to evaluate the systemic bioavailability of lupeol. An experimental strategy with three groups of female CD-1 strain mice was proposed (control, olive oil and lupeol in olive oil), at six experimental times (0.5, 2, 4, 8, 12 and 24 h) with four animals per experimental point. Mice were sacrificed for organs, urine, feces and blood collection. Lupeol was extracted from samples and analyzed by UPLC-APCI+ -MS/MS, obtaining the pharmacokinetics parameters time to peak concentration 6.444 ± 0.851 h and peak concentration 8.071 ± 2.930 µg/mL. Study of direct digestion and absorption in various organs showed important concentrations of lupeol at earlier post-administration times (stomach, 137.25 ± 19.94 ng/mg and small intestine, 99.00 ± 12.99 ng/mg). The main excretion route was fecal, with a peak at 12 h post-administration (163.28 ± 9.83 µg/mg). Absorption of lupeol by the animals was better than expected despite its nonpolar nature (extent of absorption F = 0.645 ± 0.0581).