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1.
Hum Immunol ; 83(11): 768-777, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36055899

RESUMO

Cancer is a disease having global consequences. Though several new strategies and treatments have been developed so far, they often come with malicious side effects and this paved ways for demand of naturally extracted/driven product as potent anti-cancer agent owing to their reduced toxicity and side effects. One such common Indian household plant Neem (Azadirachta Indica) and its extract have variegated immunomodulatory effects as anti-cancer agent. Neem Leaf Glycoprotein (NLGP) modifies immune cells present in the tumor surroundings as well as in the peripheral system, rather than directly attacking the cancer cells. NLGP acts as a natural immunomodulator showing several functions like sustained tumor growth regulation by stimulating central and effector memory cells as a vaccination adjuvant, normalization of angiogenic activities, controls hypoxia, improves immune evasion techniques as well as suppresses the activity of several immunological cells (Tregs, myeloid-derived suppressor cells, and tumor-associated macrophages) which promote tumor growth and metastasis in the tumor microenvironment (TME). NLGP prioritises type1 immune-microenvironment which consists of T-bet+IFN-γ-producing group 1 innate lymphoid cell (ILC) (ILC1 and natural killer cells), CD8+ cytotoxic T cells (TC1), and CD4+ T helper1 (Th1) cells. In this review we aim to summarize detailed activity of NLGP in cancer immunoregulation.


Assuntos
Azadirachta , Neoplasias , Glicoproteínas/uso terapêutico , Humanos , Imunidade Inata , Fatores Imunológicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Folhas de Planta , Proteínas de Plantas/uso terapêutico , Linfócitos T Citotóxicos , Microambiente Tumoral
2.
Anticancer Agents Med Chem ; 22(18): 3163-3171, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35692152

RESUMO

BACKGROUND: Calotropis procera is a laticiferous plant (Apocynaceae) found in tropical regions all over the world. The ultrastructural characteristics of laticifers, their restricted distribution among different taxonomic groups, and in some species in each clade, as peptidases from latex, make them very attractive for biological analysis. OBJECTIVE: The study aims to investigate the effects of LP-PII-IAA (laticifer protein (LP) sub-fraction II (PII) of C. procera presenting an iodoacetamide-inhibited cysteine proteinase activity) on irinotecan-induced intestinal mucositis, a serious adverse effect of this medicine for the treatment of cancer. METHODS: LP-PII-IAA is composed of closely related isoforms (90%) of peptidases derived from catalysis and an osmotin protein (5%). Animals receiving co-administration of LP-PII-IAA presented a significant decrease in mortality, absence of diarrhea, histological preservation, and normalization of intestinal functions. RESULTS: Clinical homeostasis was accompanied by a reduction in MPO activity and declined levels of IL-1ß, IL-6 and KC, while the IL-10 level increased in LP-PII-IAA-treated animals. COX-2 and NF-kB immunostaining was reduced and the levels of oxidative markers (GSH, MDA) were normalized in animals that received LP-PII-IAA. CONCLUSION: We suggest that peptidases from the latex of Calotropis procera were instrumental in the suppression of the adverse clinical and physiological effects of irinotecan.


Assuntos
Calotropis , Cisteína Proteases , Animais , Calotropis/química , Ciclo-Oxigenase 2 , Interleucina-10 , Interleucina-6 , Iodoacetamida , Irinotecano/farmacologia , Látex/química , Látex/farmacologia , NF-kappa B , Proteínas de Plantas/farmacologia , Proteínas de Plantas/uso terapêutico
3.
Crit Rev Food Sci Nutr ; 62(22): 6187-6203, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33703974

RESUMO

Isolation and utilization of proteins from seaweeds have been a novel trend in the world at present due to the increasing demand for healthy non-animal proteins. The attention of scientific community has been paid on the protein derived from seaweed Undaria pinnatifida due to their high nutritional quality and bioactivity. This article aims to provide an integrated overview on methods of extraction, isolation and purification of U. pinnatifida-derived proteins and composition, nutritional value and potential nutraceutical and food applications with an interest to stimulate further research to optimize the utilization. Potential food applications of U. pinnatifida derived proteins are nutritional components in human diet, food ingredients and additives, alternative meat and meat analogues and animal and fish feed. Excellent antioxidant, antihypertension, anticoagulant, anti-diabetes, antimicrobial and anti-cancer activities possessed by proteins of U. pinnatifida enable the use of these proteins in various nutraceutical applications. A number of studies have been carried out on antioxidant and antihypertensive activities of U. pinnatifida proteins, whereas other bioactivites are yet to be further studied. Hence, more research works are crucial to be done in order to facilitate and promote the emerging novel foods and nutraceuticals, using proteins from seaweed U. pinnatifida.


Assuntos
Proteínas de Plantas , Alga Marinha , Undaria , Animais , Suplementos Nutricionais , Humanos , Proteínas de Plantas/uso terapêutico , Proteínas de Vegetais Comestíveis , Alga Marinha/química , Undaria/química
4.
Nutrients ; 13(12)2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34959865

RESUMO

Bromelain is a major sulfhydryl proteolytic enzyme found in pineapple plants, having multiple activities in many areas of medicine. Due to its low toxicity, high efficiency, high availability, and relative simplicity of acquisition, it is the object of inexhaustible interest of scientists. This review summarizes scientific reports concerning the possible application of bromelain in treating cardiovascular diseases, blood coagulation and fibrinolysis disorders, infectious diseases, inflammation-associated diseases, and many types of cancer. However, for the proper application of such multi-action activities of bromelain, further exploration of the mechanism of its action is needed. It is supposed that the anti-viral, anti-inflammatory, cardioprotective and anti-coagulatory activity of bromelain may become a complementary therapy for COVID-19 and post-COVID-19 patients. During the irrepressible spread of novel variants of the SARS-CoV-2 virus, such beneficial properties of this biomolecule might help prevent escalation and the progression of the COVID-19 disease.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Bromelaínas/uso terapêutico , Tratamento Farmacológico da COVID-19 , Cardiotônicos/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Neoplasias/tratamento farmacológico , Proteínas de Plantas/uso terapêutico , SARS-CoV-2 , Ananas/enzimologia , Anti-Inflamatórios/química , Anticoagulantes/química , Bromelaínas/química , Cardiotônicos/química , Fibrinólise/efeitos dos fármacos , Humanos , Proteínas de Plantas/química
5.
J Cancer Res Ther ; 17(6): 1445-1453, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34916376

RESUMO

BACKGROUND: Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats and mice, with the cytotoxicity of AOM mediated by oxidative stress. AIM OF STUDY: This study investigated the protective effect of a natural antioxidant (GliSODin) against AOM-induced oxidative stress and carcinogenesis in rat colon. METHODS: Twenty male Wistar rats were randomly divided into four groups (five rats/group). The control group was fed a basal diet. AOM-treated group (AOM) was fed a basal diet and received intraperitoneal injections of AOM for 2 weeks at a dose of 15 mg/kg. The GliSODin treatment group (superoxide dismutase [SOD]) received oral supplementation of GliSODin (300 mg/kg) for 3 months, and the fourth combined group received AOM and GliSODin (AOM + SOD). All animals were continuously fed ad libitum until the age of 16 weeks when all rats were sacrificed. The colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, oxidant status (lipid peroxidation-LPO), and enzyme antioxidant system (glutathione [GSH], GSH-S-transferase, catalase, and SOD). RESULTS: Our results showed that AOM induced ACF development and oxidative stress (GSH depletion and lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with GliSODin significantly ameliorated the cytotoxic effects of AOM. CONCLUSION: The results of this study provide in vivo evidence that GliSODin reduced the AOM-induced colon cancer in rats, through their potent antioxidant activities.


Assuntos
Antioxidantes/farmacologia , Neoplasias do Colo/tratamento farmacológico , Gliadina/farmacologia , Proteínas de Plantas/farmacologia , Superóxido Dismutase/farmacologia , Animais , Antioxidantes/uso terapêutico , Azoximetano/toxicidade , Carcinogênese/induzido quimicamente , Carcinogênese/efeitos dos fármacos , Carcinogênese/patologia , Colo/efeitos dos fármacos , Colo/patologia , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/patologia , Cucurbitaceae/enzimologia , Ensaios de Seleção de Medicamentos Antitumorais , Gliadina/uso terapêutico , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Plantas/uso terapêutico , Ratos , Superóxido Dismutase/uso terapêutico , Triticum/química
6.
Food Funct ; 12(19): 8994-9006, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34382048

RESUMO

Moringa oleifera (MO) leaf is a potential plant protein resource with high nutritional and medicinal value. The study aims to investigate the hypotensive activity and stability of MO leaf peptides. MO leaf protein was extracted and then hydrolyzed with Alcalase to produce the MO leaf protein hydrolysate (MOPH). The MOPH was separated into peptide fractions with different molecular weights by membrane ultrafiltration. The MOPH and ultrafiltration fractions were evaluated for antihypertensive activity. Inhibition of the angiotensin-converting enzyme (84.71 ± 0.07%) and renin (43.72 ± 0.02%) was significantly higher for <1 kDa peptides when compared to other fractions. Oral administration of the <1 kDa component in spontaneously hypertensive rats positively lowers the blood pressure (∼17 mmHg). The <1 kDa component was isolated and purified subsequently; the final active component was identified by mass spectrometry and amino acid sequence analysis. Two highly active ACE (angiotensin-converting enzyme) and renin dual inhibitory peptides Leu-Gly-Phe-Phe (LGF) and Gly-Leu-Phe-Phe (GLFF) were obtained. The two peptides exhibited a good dual inhibitory activity of ACE and renin with IC50 values of LGF (0.29 ± 0.13 mM, 1.88 ± 0.08 mM) and GLFF (0.31 ± 0.04 mM, 2.80 ± 0.08 mM). Furthermore, in vivo models, LGF and GLFF significantly reduced the systolic blood pressure (19.4 mmHg; 18.2 mmHg) and diastolic blood pressure (12 mmHg; 13.8 mmHg) of SHRs (spontaneously hypertensive rats). The peptide transmembrane transport experiments and simulated gastrointestinal digestion experiments with LGF and GLFF showed that they can resist gastrointestinal digestion in a complete form. Thus, bioactive peptides from MO leaf may possess the potential to be used for treating hypertension in humans.


Assuntos
Anti-Hipertensivos/uso terapêutico , Moringa oleifera , Proteínas de Plantas/uso terapêutico , Administração Oral , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/farmacologia , Pressão Sanguínea , Alimento Funcional , Humanos , Concentração Inibidora 50 , Peptidil Dipeptidase A/química , Fitoterapia , Folhas de Planta , Proteínas de Plantas/administração & dosagem , Proteínas de Plantas/farmacologia , Ratos , Ratos Endogâmicos SHR , Renina/antagonistas & inibidores
7.
Mem Inst Oswaldo Cruz ; 115: e200458, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33237133

RESUMO

BACKGROUND: Calotropis procera latex protein fraction (LP) was previously shown to protect animals from septic shock. Further investigations showed that LP modulate nitric oxide and cytokines levels. OBJECTIVES: To evaluate whether the protective effects of LP, against lethal bacterial infection, is observed in its subfractions (LPPII and LPPIII). METHODS: Subfractions (5 and 10 mg/kg) were tested by i.p. administration, 24 h before challenging with lethal injection (i.p.) of Salmonella Typhimurium. LPPIII (5 mg/kg) which showed higher survival rate was assayed to evaluate bacterial clearance, histopathology, leukocyte recruitment, plasma coagulation time, cytokines and NO levels. FINDINGS: LPPIII protected 70% of animals of death. The animals given LPPIII exhibited reduced bacterial load in blood and peritoneal fluid after 24 h compared to the control. LPPIII promoted macrophage infiltration in spleen and liver. LPPIII restored the coagulation time of infected animals, increased IL-10 and reduced NO in blood. MAIN CONCLUSIONS: LPPIII recruited macrophages to the target organs of bacterial infection. This addressed inflammatory stimulus seems to reduce bacterial colonisation in spleen and liver, down regulate bacterial spread and contribute to avoid septic shock.


Assuntos
Antibacterianos/uso terapêutico , Calotropis/química , Homeostase/efeitos dos fármacos , Inflamação/tratamento farmacológico , Látex/química , Extratos Vegetais/farmacologia , Proteínas de Plantas/uso terapêutico , Infecções por Salmonella/tratamento farmacológico , Animais , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Regulação para Baixo , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/farmacologia , Infecções por Salmonella/imunologia , Infecções por Salmonella/microbiologia
8.
Mini Rev Med Chem ; 20(19): 2011-2018, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32955001

RESUMO

Liver disease is global health problem. Paracetamol (APAP) is used as an analgesic drug and is considered safe at therapeutic doses, but at higher doses, it causes acute liver injury. N-acetyl-p- Benzoquinone Imine (NAPQI) is a reactive toxic metabolite produced by biotransformation of APAP. NAPQI damages the liver by oxidative stress and the formation of protein adducts. The glutathione precursor N-acetylcysteine (NAC) is the only approved antidote against APAP hepatotoxicity, but it has limited hepatoprotective effects. The search for new drugs and novel therapeutic intervention strategies increasingly includes testing plant extracts and other natural products. Plumeria pudica (Jacq., 1760) is a plant that produces latex containing molecules with therapeutic potential. Proteins obtained from this latex (LPPp), a well-defined mixture of chitinases, proteinases proteinase inhibitors have shown anti-inflammatory, antinociceptive, antidiarrheal effects as well as a protective effect against ulcerative colitis. These studies have demonstrated that LPPp acts on parameters such as Glutathione (GSH) and Malondialdehyde (MDA) concentration, Superoxide Dismutase (SOD) activity, Myeloperoxidase (MPO) activity, and TNF- α IL1-ß levels. Since oxidative stress and inflammation have been reported to affect the initiation and progression of liver injury caused by APAP, it is suggested that LPPp can act on aspects related to paracetamol hepatoxicity. This article brings new insights into the potential of the laticifer proteins extracted from the latex of P. pudica and opens new perspectives for the treatment of this type of liver disease with LPPp.


Assuntos
Apocynaceae/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Látex/metabolismo , Proteínas de Plantas/uso terapêutico , Acetaminofen/administração & dosagem , Acetaminofen/efeitos adversos , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Citocinas/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Extratos Vegetais/metabolismo , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/farmacologia , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico
9.
Food Funct ; 11(7): 5853-5865, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32589172

RESUMO

Colorectal cancer (CRC) is one of the most common types of cancer, especially in Western countries, and its incidence rate is increasing every year. In this study, for the first time Vigna unguiculata L. Walp. (cowpea) water boiled seed extracts were found to reduce the viability of different colorectal cancer (CRC) cell lines, such as E705, DiFi and SW480 and the proliferation of Caco-2 line too, without affecting CCD841 healthy cell line. Furthermore, the extracts showed the ability to reduce the level of Epidermal Growth Factor Receptor (EGFR) phosphorylation in E705, DiFi and SW480 cell lines and to lower the EC50 of a CRC common drug, cetuximab, on E705 and DiFi lines from 161.7 ng mL-1 to 0.06 ng mL-1 and from 49.5 ng mL-1 to 0.2 ng mL-1 respectively. The extract was characterized in its protein and metabolite profiles by tandem mass spectrometry and 1H-NMR analyses. A Bowman-Birk protease inhibitor was identified within the protein fraction and was supposed to be the main active component. These findings confirm the importance of a legume-based diet to prevent the outbreak of many CRC and to reduce the amount of drug administered during a therapeutic cycle.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Inibidores de Proteases/uso terapêutico , Sementes/química , Vigna/química , Antineoplásicos Fitogênicos/farmacologia , Células CACO-2 , Linhagem Celular Tumoral , Sobrevivência Celular , Cetuximab , Neoplasias Colorretais/prevenção & controle , Receptores ErbB/metabolismo , Humanos , Fosforilação , Extratos Vegetais/farmacologia , Proteínas de Plantas/farmacologia , Proteínas de Plantas/uso terapêutico , Inibidores de Proteases/farmacologia
10.
Inflamm Res ; 69(9): 951-966, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32488316

RESUMO

OBJECTIVE AND DESIGN: Oral mucositis (OM) is an intense inflammatory reaction progressing to tissue damage and ulceration. The medicinal uses of Calotropis procera are supported by anti-inflammatory capacity. PII-IAA, a highly homogenous cocktail of laticifer proteins (LP) prepared from the latex of C. procera, with recognized pharmacological properties was tested to treat OM. MATERIALS AND SUBJECTS: Male Golden Sirius hamsters were used in all treatments. TREATMENT: The latex protein samples were injected i.p. (5 mg/Kg) 24 h before mucositis induction (mechanical trauma) and 24 h later. METHODS: Histology, cytokine measurements [ELISA], and macroscopic evaluation [scores] were performed. RESULTS: PII-IAA eliminated OM, accompanied by total disappearance of myeloperoxidase activity and release of IL-1b, as well as reduced TNF-a. Oxidative stress was relieved by PII-IAA treatment, as revealed by MDA and GSH measurements. PII-IAA also reduced the expression of adhesion molecules (ICAM-1) and Iba-1, two important markers of inflammation, indicating modulatory effects. Histological analyses of the cheek epithelium revealed greater deposition of type I collagen fibers in animals given PII-IAA compared with the control group. This performance was only reached when LPPII was treated with iodoacetamide (IAA), an irreversible inhibitor of proteolytic activity of cysteine proteases. The endogenous proteolytic activity of LPPII induced adverse effects in animals. Candidate proteins involved in the phytomodulatory activity are proposed. CONCLUSIONS: Therapy was successful in treating OM with the laticifer protein fraction, containing peptidases and osmotin, from Calotropis procera. The effective candidate from the latex proteins for therapeutic use is PII-IAA.


Assuntos
Anti-Inflamatórios/uso terapêutico , Calotropis/química , Látex/química , Proteínas de Plantas/uso terapêutico , Estomatite/tratamento farmacológico , Animais , Fluoruracila/toxicidade , Masculino , Mesocricetus , Estomatite/patologia
11.
Trials ; 21(1): 354, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32326966

RESUMO

BACKGROUND: Primary hypertension accounts for almost 95% of all cases of high blood pressure and is a major modifiable risk factor for cardiovascular diseases. Lifestyle interventions have been shown to prevent hypertension. One of the prominent potential therapeutic lifestyle strategies to prevent or manage hypertension is increasing dietary protein as a macronutrient or as bioactive peptides. An emerging plant-based protein source that may have anti-hypertensive properties is hemp seed. METHODS/DESIGN: A randomized, double-blind, crossover clinical trial will be conducted on 35 hypertensive participants aged 18-75 years, with a BMI between 18.5 and 40 kg/m2, systolic blood pressure (SBP) between 130 and 160 mmHg and diastolic blood pressure (DBP) ≤ 110 mmHg. The trial will be conducted for a period of 22 weeks and will consist of three treatment periods of 6 weeks, separated by 2-week washout periods. The treatments will be consumed twice a day and consist of 25 g casein, hemp seed protein (HSP), or HSP plus HSP hydrolysate (HSP+). The primary outcome of this trial is 24-h SBP, measured on the first day of first phase and the last day of each phase. Office-measured blood pressure, pulse-wave velocity and augmentation index and anthropometrics will be determined at the first and last days of each period. Also, body composition will be assessed by dual x-ray absorptiometry (DXA) scan on the first day of the first phase and within the last 2 days of each treatment period. Blood samples will be collected on the first and last 2 days of each treatment phase whereas urine samples will be collected on the first day of the first phase plus the last day of each phase to be analyzed for specific biomarkers. DISCUSSION: This trial protocol is designed to evaluate the hypotensive potential of consuming whole HSP, and HSP+, in comparison to casein protein. This study will be the first trial investigating the potential anti-hypertensive benefit of dietary hemp protein plus bioactive peptide consumption in humans. TRIAL REGISTRATION: National Clinical Trial (NCT), ID: NCT03508895. Registered on 28 June 2018. Retrospectively registered on the publicly accessible Registry Databank at ClinicalTrials.gov (http://ClinicalTrials.gov).


Assuntos
Anti-Hipertensivos/uso terapêutico , Cannabis/química , Suplementos Nutricionais , Hipertensão/dietoterapia , Hipertensão/prevenção & controle , Proteínas de Plantas/uso terapêutico , Hidrolisados de Proteína/uso terapêutico , Sementes/química , Adolescente , Adulto , Idoso , Pressão Sanguínea , Ensaios Clínicos Fase II como Assunto , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
12.
Complement Med Res ; 27(4): 260-271, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31927541

RESUMO

PURPOSE: We aimed at updating the evidence found in controlled studies addressing general and event-free survival of cancer patients treated with the fermented mistletoe extract Iscador. METHODS: The databases Embase, PubMed, CAMbase, Scopus, AMED and Cochrane were searched for clinical studies on cancer patients treated with Iscador. Quality of studies and risk of bias were evaluated according to the Cochrane guidelines and the Newcastle Ottawa Scale. Outcome data were expressed as hazard ratios (HR) and the respective 95% confidence intervals (CI). Meta-analysis was carried out using a random-effects model. RESULTS: Eighty-two controlled studies met the inclusion criteria, of which 32 with 55 strata provided data for extracting HR and CI. The overall HR was 0.59 (95% CI: [0.53; 0.65], p < 0.0001) in favour of Iscador treatment. Heterogeneity of study results was moderate (I2 = 50.9%; p < 0.0001, τ2 = 0.053). Meta-regression did not reveal significant effects of sample size or study design. However, significant differences were found between cancer entities (p < 0.01), with most pronounced effects in cervical (HR = 0.43) and less pronounced effects in lung cancer (HR = 0.84). CONCLUSIONS: We found almost identical effects on cancer survival based on a broader database of higher quality. However, none of the studies was blinded and, therefore, there might be risk of performance bias. Implications for cancer survivors are as follows: findings indicate that adjuvant treatment of cancer patients with Iscador can be associated with a better survival.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Extratos Vegetais/uso terapêutico , Proteínas de Plantas/uso terapêutico , Humanos , Taxa de Sobrevida
13.
J Ethnopharmacol ; 247: 112213, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31562951

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Historical literature and pharmacological studies demonstrate that ginseng, one of the most popular herbal medicines in China, holds potential benefits for Parkinson's disease (PD). AIM OF THE STUDY: Studies in Drosophila melanogaster (Dm) have highlighted mitochondrial dysfunction upon loss of PTEN-induced putative kinase 1 (PINK1) as a central mechanism of PD pathogenesis. Using PINK1B9 mutant Dm, we aimed to explore the therapeutic action of ginseng total protein (GTP) on PD and provide in-depth scientific interpretation about the traditional efficacy of ginseng. MATERIALS AND METHODS: We first used gel chromatography to purify GTP and confirmed its molecular weight by SDS-PAGE. Effects of GTP on PINK1B9 mutants, which were supplied with standard diet from larvae to adult stages, were assayed in flies aged 3-6 (I), 10-15 (II), and 20-25 (III) days. Parkinson-like phenotypes were analyzed by evaluating lifespan, dopaminergic neurons, dopamine levels, and locomotor ability. Mitochondrial function was assessed by evaluating ATP production, respirometry, and mitochondrial DNA. In addition, reactive oxygen species were measured using dihydroethidium and 2',7'-dichlorodihydrofluorescein diacetate staining. PD-related oxidative stress was simulated by paraquat and rotenone, and mitochondrial membrane potential was measured using JC-10 reagent. Protein and mRNA expression was detected by Western blot and real-time quantitative reverse transcription polymerase chain reaction, respectively. RESULTS: This study demonstrates for the first time that GTP treatment delays the onset of a Parkinson-like phenotype in PINK1B9 Dm, including prolongation of lifespan and rescue of climbing ability, as well as rescue of the progressive loss of a cluster of dopaminergic neurons in the protocerebral posterior lateral 1 region, which was accompanied by a significant increase of dopamine content in the brain. In addition, GTP notably reduced the penetrance of abnormal wing position, indicating a strong inhibitory effect on indirect flight muscle degeneration. We further showed that GTP could promote maintenance of mitochondrial function and protect mitochondria from PD-associated oxidative stress by activating the mitochondrial unfolded protein response (UPRmt). CONCLUSIONS: GTP protected against mitochondrial dysfunction and neurodegeneration by inducing UPRmt in the Dm PINK1B9 model of PD. Our results suggest that GTP is a promising candidate for PD, and reveal a new mechanism by which ginseng is neuroprotective.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Fármacos Neuroprotetores/farmacologia , Panax/química , Doença de Parkinson/tratamento farmacológico , Proteínas de Plantas/farmacologia , Animais , Animais Geneticamente Modificados , Modelos Animais de Doenças , Proteínas de Drosophila/genética , Drosophila melanogaster , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/genética , Doença de Parkinson/patologia , Proteínas de Plantas/uso terapêutico , Proteínas Serina-Treonina Quinases/genética , Resposta a Proteínas não Dobradas/efeitos dos fármacos
14.
Curr Protein Pept Sci ; 21(5): 443-487, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31746291

RESUMO

Biologically active molecules obtained from plant sources, mostly including secondary metabolites, have been considered to be of immense value with respect to the treatment of various human diseases. However, some inevitable limitations associated with these secondary metabolites like high cytotoxicity, low bioavailability, poor absorption, low abundance, improper metabolism, etc., have forced the scientific community to explore medicinal plants for alternate biologically active molecules. In this context, therapeutically active proteins/peptides from medicinal plants have been promoted as a promising therapeutic intervention for various human diseases. A large number of proteins isolated from the medicinal plants have been shown to exhibit anti-microbial, anti-oxidant, anti-HIV, anticancerous, ribosome-inactivating and neuro-modulatory activities. Moreover, with advanced technological developments in the medicinal plant research, medicinal plant proteins such as Bowman-Birk protease inhibitor and Mistletoe Lectin-I are presently under clinical trials against prostate cancer, oral carcinomas and malignant melanoma. Despite these developments and proteins being potential drug candidates, to date, not a single systematic review article has documented the therapeutical potential of the available biologically active medicinal plant proteome. The present article was therefore designed to describe the current status of the therapeutically active medicinal plant proteins/peptides vis-à-vis their potential as future protein-based drugs for various human diseases. Future insights in this direction have also been highlighted.


Assuntos
Antibacterianos/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Antifúngicos/uso terapêutico , Antineoplásicos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Proteínas de Plantas/uso terapêutico , Plantas Medicinais/química , Antibacterianos/isolamento & purificação , Fármacos Anti-HIV/isolamento & purificação , Antifúngicos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Antioxidantes/isolamento & purificação , Antioxidantes/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Micoses/tratamento farmacológico , Micoses/microbiologia , Micoses/patologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/patologia , Fármacos Neuroprotetores/isolamento & purificação , Extratos Vegetais/química , Proteínas de Plantas/isolamento & purificação , Inibidores da Síntese de Proteínas/isolamento & purificação , Inibidores da Síntese de Proteínas/uso terapêutico
15.
Mem. Inst. Oswaldo Cruz ; 115: e200458, 2020. graf
Artigo em Inglês | LILACS, SES-SP | ID: biblio-1135229

RESUMO

BACKGROUND Calotropis procera latex protein fraction (LP) was previously shown to protect animals from septic shock. Further investigations showed that LP modulate nitric oxide and cytokines levels. OBJECTIVES To evaluate whether the protective effects of LP, against lethal bacterial infection, is observed in its subfractions (LPPII and LPPIII). METHODS Subfractions (5 and 10 mg/kg) were tested by i.p. administration, 24 h before challenging with lethal injection (i.p.) of Salmonella Typhimurium. LPPIII (5 mg/kg) which showed higher survival rate was assayed to evaluate bacterial clearance, histopathology, leukocyte recruitment, plasma coagulation time, cytokines and NO levels. FINDINGS LPPIII protected 70% of animals of death. The animals given LPPIII exhibited reduced bacterial load in blood and peritoneal fluid after 24 h compared to the control. LPPIII promoted macrophage infiltration in spleen and liver. LPPIII restored the coagulation time of infected animals, increased IL-10 and reduced NO in blood. MAIN CONCLUSIONS LPPIII recruited macrophages to the target organs of bacterial infection. This addressed inflammatory stimulus seems to reduce bacterial colonisation in spleen and liver, down regulate bacterial spread and contribute to avoid septic shock.


Assuntos
Animais , Proteínas de Plantas/uso terapêutico , Infecções por Salmonella/tratamento farmacológico , Extratos Vegetais/farmacologia , Calotropis/química , Homeostase/efeitos dos fármacos , Inflamação/tratamento farmacológico , Látex/química , Antibacterianos/uso terapêutico , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/farmacologia , Infecções por Salmonella/imunologia , Infecções por Salmonella/microbiologia , Regulação para Baixo , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia
16.
Eur J Pharmacol ; 863: 172669, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31542486

RESUMO

The antiresorptive agents still are the mainstay of osteoporosis treatment. This study aimed to investigate the efficacy of recombinant Lingzhi-8 (rLZ-8) on osteoclast in vitro and bone resorption in vivo. The rLZ-8 protein was derived from Ganoderma lucidum transformation and produced by a genetic system. Receptor activator of nuclear factor kappa-Β ligand induced RAW 264.7 cells to differentiate into osteoclastic cells in vitro. Cells were exposed to different doses of rLZ-8 for 7 days to measure differences of osteoclastic differentiation, apoptosis rate and gene expression. rLZ-8 was labeled with Alexa Fluor 568 to observe its intracellular distribution under super-resolution light microscopy. In addition, retinoic acid was administered to female rats for 14 days to develop osteopenia changes. Different doses of rLZ-8 were simultaneously administered to rats treated with retinoic acid to observe changes of bone mineral density, biochemical parameters and organ weight ratio. Results indicated that rLZ-8 regulated receptor activator of nuclear factor kappa-Β (RANK) - tumor necrosis factor receptor-associated factor 6 (TRAF6) - c-Jun N-terminal kinase (JNK) signaling pathway, by which rLZ-8 inhibited osteoclastic differentiation and promoted osteoclastic apoptosis. Through 3D-structured illumination microscopy, it was observed that rLZ-8 entered RAW264.7 cells and accumulated gradually into the cytoplasm but little into nucleus. Administration with rLZ-8 reversed loss of bone mass and improved ALP activity in osteoporotic rats. Low-to high-dose rLZ-8 treatments displayed little toxic effects on rat organs and did not seem to impact their overall health. All data suggested that rLZ-8 has possible action against osteoporosis.


Assuntos
Doenças Ósseas Metabólicas/induzido quimicamente , Doenças Ósseas Metabólicas/tratamento farmacológico , Proteínas de Plantas/farmacologia , Proteínas Recombinantes/farmacologia , Reishi/química , Tretinoína/efeitos adversos , Animais , Apoptose/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Proteínas de Plantas/uso terapêutico , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/uso terapêutico
18.
Food Res Int ; 116: 71-78, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30716999

RESUMO

Non-communicable diseases have become the medical challenge of the 21st century because of their high incidence and mortality rates. Accumulating evidence has suggested that the modulation of diet and other lifestyle habits is the best strategy for the prevention of these diseases. An increasing number of dietary compounds have been found to exert health promoting benefits beyond their nutritional effects. Among them, lunasin is considered one of the most studied bioactive peptides. Since its discovery in soybean twenty years ago, many researchers around the world have focused their studies on demonstrating the chemopreventive and chemotherapeutic activity of lunasin. Moreover, in the last years, promising protective effects of this peptide against hypercholesterolemia, obesity, metabolic syndrome and associated cardiovascular disorders, and inflammatory and immune-regulated diseases have been described. This review summarizes recent remarkable advances on the use of peptide lunasin as a potential functional ingredient to provide health benefits. Moreover, novel aspects related to the influence of lunasin's digestion and bioavailability, the mechanisms of action proposed to explain the underlying biological properties, and the incorporation of this peptide into nutritional supplements are critically discussed.


Assuntos
Glycine max/química , Peptídeos/química , Proteínas de Plantas/química , Proteínas de Plantas/uso terapêutico , Proteínas de Soja/química , Proteínas de Soja/uso terapêutico , Disponibilidade Biológica , Doenças Cardiovasculares/prevenção & controle , Quimioprevenção , Doença Crônica , Suplementos Nutricionais , Hipercolesterolemia/prevenção & controle , Síndrome Metabólica/prevenção & controle , Obesidade/prevenção & controle
19.
Curr Mol Med ; 19(1): 12-19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30806316

RESUMO

Diabetes is a metabolic hyperglycemic condition that progressively develops, effect small and large sensory fibers in the affected population. It has various complications as hypertension, coronary artery disease, stroke, blindness, kidney disease as well as peripheral neuropathy. Sulfonylureas, thiazolidinediones, metformin, biguanidine, acarbose and insulin are commonly used drugs for diabetic patients, but these all have certain side effects. Even metformin, that is known as the miracle drug for diabetes has been found to be associated with side effects, as during treatment it involves complications with eyes, kidneys, peripheral nerves, heart and vasculature. In the present article, we hypothesize recent discoveries with respect to active ingredients from Indian medicinal plants i.e., polypeptide-p (protein analogue act as artificial insulin), charantin (a steroidal saponin), momordicin (an alkaloid) and osmotin (ubiquitous plant protein and animal analogue of human adeponectin) possessing anti-hyperglycemic potential for diabetes type II. Therefore, plants as herbal therapy have preventive care of hyperglycemia accompanied with healthy lifestyle which can provide significant decline in the incidences of diabetes in future.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fitoterapia , Animais , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Hiperglicemia/epidemiologia , Hipoglicemiantes/química , Metformina/efeitos adversos , Metformina/uso terapêutico , Peptídeos/uso terapêutico , Proteínas de Plantas/uso terapêutico , Saponinas/uso terapêutico , Esteróis/uso terapêutico , Tiazolidinedionas/uso terapêutico
20.
Nutrients ; 11(1)2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30669313

RESUMO

Quality protein maize (QPM) varieties are biofortified, or nutritionally improved, to have higher lysine and tryptophan levels to increase quality protein intakes particularly among young children. This study assesses adequacy of children's protein intakes in Ethiopia, where QPM is being promoted, accounting for protein quality and seasonal dietary changes, and estimates potential increases in intakes if QPM replaced conventional maize in diets. Diets of randomly sampled children aged 12⁻36 months in rural southern Ethiopia (n = 218) were assessed after harvest during relative food security and 3⁻4 months later during relative food insecurity using 24-h weighed food records. Diets were analyzed for protein adequacy, accounting for protein quality using the protein digestibility corrected amino acid score (PDCAAS) method, and potential improvements from QPM substitution were estimated. Stunting was prevalent (38%) at the first assessment. Across seasons, 95⁻96% of children consumed maize, which provided 59⁻61% of energy and 51⁻55% of total protein in 24 h. Dietary intakes decreased in the food insecure season, though children were older. Among children no longer breastfeeding, QPM was estimated to reduce inadequacy of utilizable protein intakes from 17% to 13% in the food secure season and from 34% to 19% in the food insecure season. However, breastfed children had only 4⁻6% inadequate intakes of utilizable protein, limiting QPM's potential impact. Due to small farm sizes, maize stores from home production lasted a median of three months. Young Ethiopian children are at risk of inadequate quality protein intakes, particularly after breastfeeding has ceased and during food insecurity. QPM could reduce this risk; however, reliance on access through home production may result in only short-term benefits given the limited quantities of maize produced and stored.


Assuntos
Deficiências Nutricionais/prevenção & controle , Dieta , Proteínas Alimentares/administração & dosagem , Grão Comestível , Melhoramento Vegetal , Proteínas de Plantas/administração & dosagem , Zea mays/química , Aminoácidos/análise , Pré-Escolar , Deficiências Nutricionais/complicações , Proteínas Alimentares/análise , Proteínas Alimentares/normas , Proteínas Alimentares/uso terapêutico , Ingestão de Energia , Etiópia , Comportamento Alimentar , Feminino , Abastecimento de Alimentos , Jardinagem , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/etiologia , Transtornos do Crescimento/prevenção & controle , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Masculino , Estado Nutricional , Proteínas de Plantas/análise , Proteínas de Plantas/uso terapêutico , Avaliação de Programas e Projetos de Saúde , População Rural , Estações do Ano , Zea mays/classificação
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