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1.
World J Diabetes ; 14(2): 62-75, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36926656

RESUMO

Diabetes mellitus (DM) is one of the most common metabolic disorders characterized by elevated blood glucose levels. Prolonged uncontrolled hyperglycemia often leads to multi-organ damage including diabetic neuropathy, nephropathy, retinopathy, cardiovascular disorders, and diabetic foot ulcers. Excess production of free radicals causing oxidative stress in tissues is often considered to be the primary cause of onset and progression of DM and associated complications. Natural polyphenols can be used to induce or inhibit the expression of antioxidant enzymes such as glutathione peroxidase, heme oxygenase-1, superoxide dismutase, and catalase that are essential in maintaining redox balance, and ameliorate oxidative stress. Caffeic acid (CA) is a polyphenolderived from hydroxycinnamic acid and possesses numerous physiological properties includ-ing antioxidant, anti-inflammatory, anti-atherosclerotic, immune-stimulatory, cardioprotective, antiproliferative, and hepatoprotective activities. CA acts as a regulatory compound affecting numerous biochemical pathways and multiple targets. These include various transcription factors such as nuclear factor-B, tumor necrosis factor-α, interleukin-6, cyclooxygenase-2, and nuclear factor erythroid 2-related factor 2. Therefore, this review summarizes the pharmacological properties, molecular mechanisms, and pharmacokinetic profile of CA in mitigating the adverse effects of DM and associated complications. The bioavailability, drug delivery, and clinical trials of CA have also been discussed.

2.
World J Hepatol ; 15(1): 1-18, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36744169

RESUMO

Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year, with an estimated 5-year survival rate of 30%-35% after diagnosis. Hepatocellular carcinoma (HCC) constitutes a significant subtype of liver cancer (approximate75%) and is considered primary liver cancer. Treatment for liver cancer mainly depends on the stage of its progression, where surgery including, hepatectomy and liver transplantation, and ablation and radiotherapy are the prime choice. For advanced liver cancer, various drugs and immunotherapy are used as first-line treatment, whereas second-line treatment includes chemotherapeutic drugs from natural and synthetic origins. Sorafenib and lenvatinib are first-line therapies, while regorafenib and ramucirumab are second-line therapy. Various metabolic and signaling pathways such as Notch, JAK/ STAT, Hippo, TGF-ß, and Wnt have played a critical role during HCC progression. Dysbiosis has also been implicated in liver cancer. Drug-induced toxicity is a key obstacle in the treatment of liver cancer, necessitating the development of effective and safe medications, with natural compounds such as resveratrol, curcumin, diallyl sulfide, and others emerging as promising anticancer agents. This review highlights the current status of liver cancer research, signaling pathways, therapeutic targets, current treatment strategies and the chemopreventive role of various natural products in managing liver cancer.

3.
Pestic Biochem Physiol ; 188: 105279, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36464383

RESUMO

Gray blight caused by Pestalotiopsis-like species is a major disease of tea crop worldwide including India, causes significant losses in tea production. Management of disease using fungal biocontrol agents is considered an alternative eco-friendly approach to synthetic fungicides. The present study explores the efficacy of Trichoderma reesei in the gray blight management in tea crop and activation of defense related enzymes against gray blight pathogen by developing a tri-trophic interaction system. Out of 16 isolates of Trichoderma species screened in laboratory against Pseudopestalotiopsis theae, a gray blight pathogen, isolate TRPATH01 had highest antagonistic activity (81.2%) against Ps. theae and was found to produce inhibitory volatile and non-volatile metabolites. Based on ITS and TEF-1 alpha sequencing, the isolate TRPATH01 was recognised as T. reesei. The methanolic extract of T. reesei was also found effective against Ps. theae at 200 µg/mL also confirmed presence of highest volatile compounds. The isolate also produced hydrolytic enzymes such as chitinase, cellulase, protease, and lipase. Under nursery conditions, 2% and 5% concentrations with 2 × 106 conidia/ml of T. reesei were able to reduce 67.5% to 75.0% of disease severity over pathogen inoculated controls. Moreover, compared with positive and negative controls, T. reesei -treated tea plants showed increased shoot height, stem diameter, shoot and root fresh weight at 45 days after inoculation. Principal component analysis capturing 97.1% phenotypic variations, which revealed that the tea plants co-inoculated with Ps. theae and T. reesei exhibited significantly upregulated accumulation of defensive enzymes viz., polyphenol oxidase, peroxidase, phenylalanine ammonia lyase, phenolics, ß-1, 3-glucanase, and chitinase when compared to both controls. Hence, T. reesei could provide an eco-friendly and viable mitigation option for gray blight in tea gardens by inducing defense-related enzymes.


Assuntos
Camellia sinensis , Quitinases , Hypocreales , Chá
4.
World J Gastroenterol ; 28(26): 3047-3062, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-36051349

RESUMO

Baicalin is a natural bioactive compound derived from Scutellaria baicalensis, which is extensively used in traditional Chinese medicine. A literature survey demonstrated the broad spectrum of health benefits of baicalin such as antioxidant, anticancer, anti-inflammatory, antimicrobial, cardio-protective, hepatoprotective, renal protective, and neuroprotective properties. Baicalin is hydrolyzed to its metabolite baicalein by the action of gut microbiota, which is further reconverted to baicalin via phase 2 metabolism in the liver. Many studies have suggested that baicalin exhibits therapeutic potential against several types of hepatic disorders including hepatic fibrosis, xenobiotic-induced liver injury, fatty liver disease, viral hepatitis, cholestasis, ulcerative colitis, hepatocellular and colorectal cancer. During in vitro and in vivo examinations, it has been observed that baicalin showed a protective role against liver and gut-associated abnormalities by modifying several signaling pathways such as nuclear factor-kappa B, transforming growth factor beta 1/SMAD3, sirtuin 1, p38/mitogen-activated protein kinase/Janus kinase, and calcium/calmodulin-dependent protein kinase kinaseß/adenosine monophosphate-activated protein kinase/acetyl-coenzyme A carboxylase pathways. Furthermore, baicalin also regulates the expression of fibrotic genes such as smooth muscle actin, connective tissue growth factor, ß-catenin, and inflammatory cytokines such as interferon gamma, interleukin-6 (IL-6), tumor necrosis factor-alpha, and IL-1ß, and attenuates the production of apoptotic proteins such as caspase-3, caspase-9 and B-cell lymphoma 2. However, due to its low solubility and poor bioavailability, widespread therapeutic applications of baicalin still remain a challenge. This review summarized the hepatic and gastrointestinal protective attributes of baicalin with an emphasis on the molecular mechanisms that regulate the interaction of baicalin with the gut microbiota.


Assuntos
Flavonoides , Gastroenteropatias , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Gastroenteropatias/patologia , Humanos , Fígado/patologia , Scutellaria baicalensis
5.
World J Hepatol ; 14(4): 729-743, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35646277

RESUMO

BACKGROUND: Fluoxetine is one of the most widely prescribed anti-depressant drugs belonging to the category of selective serotonin reuptake inhibitors. Long-term fluoxetine treatment results in hepatotoxicity. Baicalin, a natural compound obtained from the Chinese herb Scutellaria baicalensis is known to have antioxidant, hepatoprotective and anti-inflammatory effects. However, the beneficial effects of baicalin against fluoxetine-induced hepatic damage have not previously been reported. AIM: To evaluate the protective action of baicalin in fluoxetine-induced liver toxicity and inflammation. METHODS: Male albino Wistar rats were divided into seven groups. Group 1 was the normal control. Oral fluoxetine was administered at 10 mg/kg body weight to groups 2, 3, 4 and 5. In addition, groups 3 and 4 were also co-administered oral baicalin (50 mg/kg and 100 mg/kg, respectively) while group 5 received silymarin (100 mg/kg), a standard hepatoprotective compound for comparison. Groups 6 and 7 were used as a positive control for baicalin (100 mg/kg) and silymarin (100 mg/kg), respectively. All treatments were carried out for 28 d. After sacrifice of the rats, biomarkers of oxidative stress [superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione-S-transferase (GST), advanced oxidation protein products (AOPP), malondialdehyde (MDA)], and liver injury [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total protein, albumin, bilirubin] were studied in serum and tissue using standard protocols and diagnostic kits. Inflammatory markers [tumor necrosis factor (TNF-α), interleukin (IL)-6, IL-10 and interferon (IFN)-γ] in serum were evaluated using ELISA-based kits. The effect of baicalin on liver was also analyzed by histopathological examination of tissue sections. RESULTS: Fluoxetine-treated rats showed elevated levels of the serum liver function markers (total bilirubin, ALT, AST, and ALP) and inflammatory markers (TNF-α, IL-6, IL-10 and IFN-γ), with a decline in total protein and albumin levels. Biochemical markers of oxidative stress such as SOD, CAT, GST, GSH, MDA and AOPP in the liver tissue homogenate were also altered indicating a surge in reactive oxygen species leading to oxidative damage. Histological examination of liver tissue also showed degeneration of hepatocytes. Concurrent administration of baicalin (50 and 100 mg/kg) restored the biomarkers of oxidative stress, inflammation and hepatic damage in serum as well as in liver tissues to near normal levels. CONCLUSION: These findings suggested that long-term treatment with fluoxetine leads to oxidative stress via the formation of free radicals that consequently cause inflammation and liver damage. Concurrent treatment with baicalin alleviated fluoxetine-induced hepatotoxicity and liver injury by regulating oxidative stress and inflammation.

6.
Plant Dis ; 106(11): 2911-2919, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35259308

RESUMO

Macrophomina phaseolina, a fungus that causes dry root rot, is a relatively new threat to blackgram in South Asia. Because this pathogen is a polyphagic necrotroph, it remains viable in the soil for several years, making disease management challenging. One of the most economical methods for managing dry root rot in blackgram is through an integrated approach that uses resistant varieties. This study examined M. phaseolina associated with dry root rot in blackgram and screened 41 blackgram genotypes for dry root rot resistance. The present work also characterized morphological features and internal transcribed sequence regions of the nuclear rDNA operon to identify M. phaseolina from blackgram. Evaluation of the 41 blackgram genotypes against M. phaseolina by the paper towel technique identified two genotypes, CO-5 and IPU 07-3, with dry root rot resistance (disease scores: ≤3) and 18 genotypes with moderate resistance (disease scores: >3 to ≤5). Five genotypes with disease scores <4.0 and two susceptible genotypes were reevaluated using the paper towel method, which revealed moderate resistance reactions of CO-5, IPU 07-3, and MASH 1-1. To confirm dry root rot resistance of these seven genotypes, further screening was done in a greenhouse using the sick pot assay. Results revealed moderate resistance of CO-5, IPU 07-3, and MASH 1-1 genotypes. As compared with susceptible check (VO 2135-B-BL), CO-5 consistently excelled in plant survival with 13.4% disease incidence, followed by IPU 07-3 (16.7%) and MASH 1-1 (19.9%). Therefore, these three genotypes can be used as parents in blackgram breeding programs for developing blackgram cultivars with improved dry root rot resistance.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Assuntos
Ascomicetos , Vigna , Doenças das Plantas/microbiologia , Melhoramento Vegetal , Ascomicetos/genética
7.
Phytomedicine ; 77: 153278, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32781393

RESUMO

BACKGROUND: Terminalia bellirica (Gaertn.) Roxb. is one of the oldest medicinal herbs of India, Pakistan, Nepal, Bangladesh and Sri Lanka as well as South-East Asia. Its medicinal utility has been described in the different traditional medicinal systems, such as Ayurveda, Unani, Siddha, and traditional Chinese medicine. PURPOSE: The present study is aimed at providing a comprehensive overview on the traditional medicinal use, major phytoconstituents, biological and pharmacological activities and related mechanisms of actions and clinical studies of T. bellirica. Another objective is to describe current limitations and future direction of T. bellirica-related research. METHODS: PubMed, ScienceDirect, Scopus, Cochrane Library, and EBOSCO host databases were selected to explore literature published between 1980 and 2020 (till March). Keywords used in various combinations comprised of Terminalia bellirica, phytoconstituents, health effects, pharmacological activities, molecular targets, in vitro, in vivo, clinical studies, and disease prevention. RESULTS: A broad spectrum in vitro and in vivo studies suggested various biological and pharmacological effects, including antioxidant, anti-inflammatory, immunomodulatory, antimicrobial, hepatoprotective, renoprotective, antidiabetic, anti-hyperlipidemic, and anticancer activities. Diverse bioactivities of T. bellirica have been ascribed to the presence of many bioactive phytochemicals, such as glucoside, tannins, gallic acid, corilagin, ellagic acid, ethyl gallate, galloyl glucose, chebulagic acid, and arjunolic acid. CONCLUSION: Preclinical and clinical studies have suggested that T. bellirica plant and its phytoconstituents have immense potential for prevention and treatment of various diseases. Additional in vivo studies and clinical trials are warranted to realize the complete medicinal attributes of this plant.


Assuntos
Compostos Fitoquímicos/análise , Extratos Vegetais/farmacologia , Terminalia/química , Animais , Antioxidantes/farmacologia , Ácido Gálico/análogos & derivados , Ácido Gálico/análise , Glucosídeos/análise , Humanos , Taninos Hidrolisáveis/análise , Ayurveda , Extratos Vegetais/química , Plantas Medicinais/química , Taninos/análise , Triterpenos/análise
8.
Int J Mol Sci ; 20(19)2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31597283

RESUMO

A balanced metabolic profile is essential for normal human physiological activities. Disproportions in nutrition give rise to imbalances in metabolism that are associated with aberrant immune function and an elevated risk for inflammatory-associated disorders. Inflammation is a complex process, and numerous mediators affect inflammation-mediated disorders. The available clinical modalities do not effectively address the underlying diseases but rather relieve the symptoms. Therefore, novel targeted agents have the potential to normalize the metabolic system and, thus, provide meaningful therapy to the underlying disorder. In this connection, polyphenols, the well-known and extensively studied phytochemical moieties, were evaluated for their effective role in the restoration of metabolism via various mechanistic signaling pathways. The various flavonoids that we observed in this comprehensive review interfere with the metabolic events that induce inflammation. The mechanisms via which the polyphenols, in particular flavonoids, act provide a promising treatment option for inflammatory disorders. However, detailed clinical studies of such molecules are required to decide their clinical fate.


Assuntos
Anti-Inflamatórios/farmacologia , Flavonoides/farmacologia , Inflamação/metabolismo , Doenças Metabólicas/metabolismo , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Biomarcadores , Ensaios Clínicos como Assunto , Suscetibilidade a Doenças , Avaliação Pré-Clínica de Medicamentos , Flavonoides/química , Flavonoides/uso terapêutico , Humanos , Inflamação/complicações , Inflamação/diagnóstico , Mediadores da Inflamação/metabolismo , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/etiologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
9.
Molecules ; 24(18)2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31546767

RESUMO

Corilagin (ß-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose), an ellagitannin, is one of the major bioactive compounds present in various plants. Ellagitannins belong to the hydrolyzable tannins, a group of polyphenols. Corilagin shows broad-spectrum biological, and therapeutic activities, such as antioxidant, anti-inflammatory, hepatoprotective, and antitumor actions. Natural compounds possessing antitumor activities have attracted significant attention for treatment of cancer. Corilagin has shown inhibitory activity against the growth of numerous cancer cells by prompting cell cycle arrest at the G2/M phase and augmented apoptosis. Corilagin-induced apoptosis and autophagic cell death depends on production of intracellular reactive oxygen species in breast cancer cell line. It blocks the activation of both the canonical Smad and non-canonical extracellular-signal-regulated kinase/Akt (protein kinase B) pathways. The potential apoptotic action of corilagin is mediated by altered expression of procaspase-3, procaspase-8, procaspase-9, poly (ADP ribose) polymerase, and Bcl-2 Bax. In nude mice, corilagin suppressed cholangiocarcinoma growth and downregulated the expression of Notch1 and mammalian target of rapamycin. The aim of this review is to summarize the anticancer efficacy of corilagin with an emphasis on the molecular mechanisms involving various signaling pathways in tumor cells.


Assuntos
Antineoplásicos/uso terapêutico , Glucosídeos/uso terapêutico , Taninos Hidrolisáveis/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Disponibilidade Biológica , Glucosídeos/efeitos adversos , Glucosídeos/química , Humanos , Taninos Hidrolisáveis/efeitos adversos , Taninos Hidrolisáveis/química , Modelos Biológicos , Neoplasias/metabolismo , Transdução de Sinais/efeitos dos fármacos
10.
Nutrients ; 11(9)2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31540270

RESUMO

The human intestine contains an intricate ecological community of dwelling bacteria, referred as gut microbiota (GM), which plays a pivotal role in host homeostasis. Multiple factors could interfere with this delicate balance, including genetics, age, antibiotics, as well as environmental factors, particularly diet, thus causing a disruption of microbiota equilibrium (dysbiosis). Growing evidences support the involvement of GM dysbiosis in gastrointestinal (GI) and extra-intestinal cardiometabolic diseases, namely obesity and diabetes. This review firstly overviews the role of GM in health and disease, then critically reviews the evidences regarding the influence of dietary polyphenols in GM based on preclinical and clinical data, ending with strategies under development to improve efficiency of delivery. Although the precise mechanisms deserve further clarification, preclinical and clinical data suggest that dietary polyphenols present prebiotic properties and exert antimicrobial activities against pathogenic GM, having benefits in distinct disorders. Specifically, dietary polyphenols have been shown ability to modulate GM composition and function, interfering with bacterial quorum sensing, membrane permeability, as well as sensitizing bacteria to xenobiotics. In addition, can impact on gut metabolism and immunity and exert anti-inflammatory properties. In order to overcome the low bioavailability, several different approaches have been developed, aiming to improve solubility and transport of dietary polyphenols throughout the GI tract and deliver in the targeted intestinal regions. Although more research is still needed, particularly translational and clinical studies, the biotechnological progresses achieved during the last years open up good perspectives to, in a near future, be able to improve the use of dietary polyphenols modulating GM in a broad range of disorders characterized by a dysbiotic phenotype.


Assuntos
Dieta , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Polifenóis/administração & dosagem , Polifenóis/farmacocinética , Animais , Disponibilidade Biológica , Diabetes Mellitus/microbiologia , Disbiose/complicações , Disbiose/imunologia , Disbiose/microbiologia , Gastroenteropatias/etiologia , Gastroenteropatias/microbiologia , Humanos , Imunidade , Inflamação , Obesidade/complicações , Obesidade/microbiologia , Prebióticos/administração & dosagem , Probióticos/administração & dosagem
11.
Phytomedicine ; 60: 152996, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31272819

RESUMO

BACKGROUND: Aloe vera is commonly used in the primary health care of human beings since time immemorial. It is an herb widely used in various traditional systems of medicine worldwide. Systematic and scientific investigation on A. vera as a medicinal plant has drawn considerable attention, and many laboratories are involved in isolation, characterization and evaluation of phytoconstituents for their nutraceutical and pharmaceutical applications. PURPOSE: The aim of this study was to provide an overview of the phytochemical, biological and medicinal attributes of A. vera against various diseases with special emphasis on underlying mechanisms of action. METHODS: PubMed, EBOSCO host, Science Direct, Scopus, and Cochrane library databases were utilized to search literature published between1977 and 2019 (till March). Major keywords used in various combinations included: Aloe vera, phytochemistry, metabolism, pharmacological activity, prevention, treatment, health, disease, in vivo, in vitro, and clinical studies. RESULTS: Various biological and pharmacological activities of A. vera, such as antioxidant, anti-inflammatory, immuno-modulatory, antimicrobial, antiviral, antidiabetic, hepatoprotective, anticancer, and skin-protective and wound-healing responses, have been attributed to the presence of many active compounds, including anthraquinones, anthrones, chromones, flavonoids, amino acids, lipids, carbohydrates, vitamins and minerals. CONCLUSION: Based on various preclinical studies, A. vera constituents have enormous potential to prevent and treat various diseases. Randomized clinical trials are needed to understand the full therapeutic potential of this unique medicinal plant.


Assuntos
Aloe/química , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Animais , Anti-Infecciosos/química , Anti-Inflamatórios/química , Antineoplásicos/química , Antioxidantes/química , Humanos , Masculino , Compostos Fitoquímicos/química , Extratos Vegetais/química , Plantas Medicinais , Ratos Wistar , Cicatrização/efeitos dos fármacos
12.
J Cell Physiol ; 234(10): 17212-17231, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30916407

RESUMO

Diabetes affects a large population of the world. Lifestyle, obesity, dietary habits, and genetic factors contribute to this metabolic disease. A target pathway to control diabetes is the 5'-adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. AMPK is a heterotrimeric protein with α, ß, and γ subunits. In several studies, AMPK activation enhanced glucose uptake into cells and inhibited intracellular glucose production. Impairment of AMPK activity is present in diabetes, according to some studies. Drugs used in the treatment of diabetes, such as metformin, are also known to act through regulation of AMPK. Thus, drugs that activate and regulate AMPK are potential candidates for the treatment of diabetes. In addition, many patients encounter important adverse effects, like hypoglycemia, while using allopathic drugs. As a result, the investigation of plant-derived natural drugs that lack adverse side effects and treat diabetes is necessary. Natural products like berberine, quercetin, resveratrol, and so forth have shown significant potential in regulating and activating the AMPK pathway which can lead to manage diabetes mellitus and its complications.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Complicações do Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Produtos Biológicos/farmacologia , Humanos
13.
Artigo em Inglês | MEDLINE | ID: mdl-30069430

RESUMO

Hepatocellular Carcinoma (HCC) is one of the most common malignant tumours in the world. It is a heterogeneous group of a tumour that vary in risk factor and genetic and epigenetic alteration event. Mortality due to HCC in last fifteen years has increased. Multiple factors including viruses, chemicals, and inborn and acquired metabolic diseases are responsible for its development. HCC is closely associated with hepatitis B virus, and at least in some regions of the world with hepatitis C virus. Liver injury caused by viral factor affects many cellular processes such as cell signalling, apoptosis, transcription, DNA repair which in turn induce important effects on cell survival, growth, transformation and maintenance. Molecular mechanisms of hepatocellular carcinogenesis may vary depending on different factors and this is probably why a large set of mechanisms have been associated with these tumours. Various biomarkers including α-fetoprotein, des-γ-carboxyprothrombin, glypican-3, golgi protein-73, squamous cell carcinoma antigen, circulating miRNAs and altered DNA methylation pattern have shown diagnostic significance. This review article covers up key molecular pathway alterations, biomarkers for diagnosis of HCC, anti-HCC drugs and relevance of key molecule/pathway/receptor as a drug target.

14.
Nutrients ; 10(6)2018 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-29882797

RESUMO

Cancer initiation and progression are the result of genetic and/or epigenetic alterations. Acetylation-mediated histone/non-histone protein modification plays an important role in the epigenetic regulation of gene expression. Histone modification is controlled by the balance between histone acetyltransferase and (HAT) and histone deacetylase (HDAC) enzymes. Imbalance between the activities of these two enzymes is associated with various forms of cancer. Histone deacetylase inhibitors (HDACi) regulate the activity of HDACs and are being used in cancer treatment either alone or in combination with other chemotherapeutic drugs/radiotherapy. The Food and Drug Administration (FDA) has already approved four compounds, namely vorinostat, romidepsin, belinostat, and panobinostat, as HDACi for the treatment of cancer. Several other HDACi of natural and synthetic origin are under clinical trial for the evaluation of efficiency and side-effects. Natural compounds of plant, fungus, and actinomycetes origin, such as phenolics, polyketides, tetrapeptide, terpenoids, alkaloids, and hydoxamic acid, have been reported to show potential HDAC-inhibitory activity. Several HDACi of natural and dietary origin are butein, protocatechuic aldehyde, kaempferol (grapes, green tea, tomatoes, potatoes, and onions), resveratrol (grapes, red wine, blueberries and peanuts), sinapinic acid (wine and vinegar), diallyl disulfide (garlic), and zerumbone (ginger). HDACi exhibit their antitumor effect by the activation of cell cycle arrest, induction of apoptosis and autophagy, angiogenesis inhibition, increased reactive oxygen species generation causing oxidative stress, and mitotic cell death in cancer cells. This review summarizes the HDACs classification, their aberrant expression in cancerous tissue, structures, sources, and the anticancer mechanisms of HDACi, as well as HDACi that are either FDA-approved or under clinical trials.


Assuntos
Antineoplásicos/uso terapêutico , Descoberta de Drogas/métodos , Inibidores de Histona Desacetilases/uso terapêutico , Histona Desacetilases/metabolismo , Histonas/metabolismo , Neoplasias/tratamento farmacológico , Acetilação , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/síntese química , Inibidores de Histona Desacetilases/efeitos adversos , Inibidores de Histona Desacetilases/síntese química , Histona Desacetilases/classificação , Histona Desacetilases/genética , Humanos , Terapia de Alvo Molecular , Mutação , Neoplasias/enzimologia , Neoplasias/genética , Neoplasias/patologia , Especificidade por Substrato
15.
BMC Complement Altern Med ; 16: 156, 2016 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-27245453

RESUMO

BACKGROUND: Excessive production of free radicals has been implicated in many diseases including cancer. They are highly reactive and bring about oxidation of biomolecules i.e., proteins, lipids and nucleic acids which are associated with many degenerative diseases. Natural products acting as antioxidants have ability to neutralize free radicals and their actions and hence they mitigate their harmful effects. The present study was designed to investigate pharmacological properties viz., antioxidant, antibacterial and antiproliferative activities of cinnamaldehyde and eugenol, the two naturally occurring phenylpropanoids present in Cinnamomum spp. and other plants. METHODS: The antioxidant potential of test compounds was evaluated by measuring DPPH free radical scavenging, reducing power and metal ion chelating activities. Protection against membrane damage was assayed by inhibition of lipid peroxidation in rat liver homogenate. Antibacterial activity was measured by Kirby-Bauer disc diffusion method while antiproliferative activity of test compounds was measured by sulforhodamine-B (SRB) assay. RESULTS: Eugenol exhibited noticeable antioxidant potential in DPPH radical scavenging (81 %) and reducing power (1.12) assays at 1.0 µM/ml and 0.1 µM/ml concentrations, respectively. IC50 value of eugenol for radical scavenging activity was found to be 0.495 µM/ml. Cinnamaldehyde demonstrated considerable metal ion chelating ability (75 %) at 50 µM/ml and moderate lipo-protective activity in lipid peroxidation assay at 3 µM/ml. In addition cinnamaldehyde also showed appreciable antibacterial activity (zone of inhibition 32-42 mm) against Bacillus cereus (MTCC 6840), Streptococcus mutans (MTCC 497), Proteus vulgaris (MTCC 7299), Salmonella typhi (MTCC 3917) and Bordetella bronchiseptica (MTCC 6838) while eugenol produced moderate activity at 80 µM/disc. Cinnamaldehyde exhibited comparatively better antiproliferative potential against breast (T47D) and lung (NCI-H322) cancer cell lines than eugenol in SRB assay at 50 µM concentration. CONCLUSION: Cinnamaldehyde possessed metal ion chelating, lipo-protective, antibacterial and antiproliferative activities while eugenol showed potent H-atom donating potential indicating radical quenching and reducing power abilities. Medicinal attributes shown by both the compounds indicated their usefulness in food and pharmaceutical sector.


Assuntos
Acroleína/análogos & derivados , Eugenol/farmacologia , Extratos Vegetais/farmacologia , Acroleína/química , Acroleína/farmacologia , Animais , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Cinnamomum zeylanicum , Eugenol/química , Técnicas In Vitro , Extratos Vegetais/química , Ratos , Ratos Wistar
16.
J Food Sci ; 81(4): M928-34, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26928885

RESUMO

During mycofloral analysis of green gram (Vigna radiata (L.) R. Wilczek) seed samples taken from different grocery stores by agar and standard blotter paper methods, 5 fungal species were identified, of which Aspergillus flavus exhibited higher relative frequency (75.20% to 80.60%) and was found to produce aflatoxin B1 . On screening of 11 plant essential oils against this mycotoxigenic fungi, Lippia alba essential oil was found to be most effective and showed absolute inhibition of mycelia growth at 0.28 µL/mL. The oil of L. alba was fungistatic and fungicidal at 0.14 and 0.28 µL/mL, respectively. Oil had broad range of fungitoxicity at its MIC value and was absolutely inhibited the AFB1 production level at 2.0 µL/mL. Chemical analysis of this oil revealed geranial (36.9%) and neral (29.3%) as major components followed by myrcene (18.6%). Application of a dose of 80 µL/0.25 L air of Lippia oil in the storage system significantly inhibited the fungal proliferation and aflatoxin production without affecting the seed germination rate. By the virtue of fungicidal, antiaflatoxigenic nature and potent efficacy in storage food system, L. alba oil can be commercialized as botanical fungicide for the protection of green gram seeds during storage.


Assuntos
Aflatoxina B1/metabolismo , Aspergillus flavus/efeitos dos fármacos , Fabaceae/microbiologia , Armazenamento de Alimentos , Lippia/química , Óleos Voláteis/farmacologia , Sementes/microbiologia , Monoterpenos Acíclicos , Alcenos/análise , Alcenos/farmacologia , Antifúngicos/análise , Antifúngicos/farmacologia , Microbiologia de Alimentos , Fungicidas Industriais/análise , Fungicidas Industriais/farmacologia , Humanos , Monoterpenos/análise , Monoterpenos/farmacologia , Óleos Voláteis/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Óleos de Plantas/farmacologia
17.
Int J Med Mushrooms ; 17(1): 87-92, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25746409

RESUMO

Eleven essential oils isolated from higher plant species were assessed against the four isolates of Verticillium fungicola found on fruiting bodies of Agaricus bisporus. Eucalyptus citriodora and Lippia alba oils were more efficacious and completely inhibited the mycelial growth of fungal isolates. L. alba oil was fungistatic and fungicidal at 10- and 20-µL concentrations against all of the isolates, respectively, and was more potent than E. citriodora oil as well as some prevalent synthetic fungicides such as benomyl, ethylene dibromide, and phosphine. Eighty microliters of L. alba oil protected 500 g of fruiting bodies of A. bisporus for up to 7 d from infection of the fungus under in vivo conditions. The findings strengthen the possibility of L. alba oil as a plant-based protectant to enhance the shelf life of A. bisporus fruiting bodies.


Assuntos
Agaricus/química , Conservação de Alimentos/métodos , Conservantes de Alimentos/farmacologia , Lippia/química , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Verticillium/efeitos dos fármacos , Conservantes de Alimentos/química , Armazenamento de Alimentos , Fumigação , Óleos Voláteis/química , Óleos de Plantas/química , Verticillium/crescimento & desenvolvimento
18.
J Sci Food Agric ; 95(9): 1932-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25199920

RESUMO

BACKGROUND: In order to get a potent botanical fungicide for the management of fungal decay of table grapes, an experiment was conducted in which 20 essential oils of higher plants were screened at 0.33 µL mL(-1) against dominant fungi causing decay of table grapes, including Aspergillus flavus, A. niger and A. ochraceus. Furthermore, the minimum inhibitory/fungicidal concentration, fungitoxic spectrum and mycotoxin inhibition activity of the most potent oil were determined. The efficacy of the most potent oil in preservation of table grapes, along with organoleptic evaluation, was also carried out by storing 1 kg of grapes in the oil vapour. RESULTS: Artemisia nilagirica oil was found to be most toxic, exhibiting 100% mycelia inhibition of all test fungi. Moreover, 0.29 µL mL(-1) A. nilagirica oil was fungistatic and 0.58 µL mL(-1) was fungicidal for all tested species of Aspergillus. The oil exhibited a broad range of fungitoxicity against other grape berry-rotting fungi. Artemisia nilagirica oil completely suppressed the growth and mycotoxin (AFB1 and OTA) secretion of aflatoxigenic and ochratoxigenic strains of Aspergillus at 1.6 µL mL(-1) . During the in vivo experiment, fumigation of 1 kg of table grapes with 200 and 300 µL dosage of A. nilagirica oil enhanced the shelf life for up to 9 days. The oil did not show any phytotoxic effect. Besides, oil application did not substantively change the sensory properties of the fruits. CONCLUSION: Artemisia nilagirica oil can be used as an alternative botanical fungicide for the control of fruit-rotting fungi of stored grapes.


Assuntos
Artemisia/química , Aspergillus/metabolismo , Conservantes de Alimentos/metabolismo , Frutas/microbiologia , Fungicidas Industriais/metabolismo , Óleos Voláteis/metabolismo , Vitis/microbiologia , Aflatoxina B1/antagonistas & inibidores , Aflatoxina B1/metabolismo , Aspergillus/crescimento & desenvolvimento , Aspergillus/isolamento & purificação , Aspergillus flavus/crescimento & desenvolvimento , Aspergillus flavus/isolamento & purificação , Aspergillus flavus/metabolismo , Aspergillus niger/crescimento & desenvolvimento , Aspergillus niger/isolamento & purificação , Aspergillus niger/metabolismo , Aspergillus ochraceus/crescimento & desenvolvimento , Aspergillus ochraceus/isolamento & purificação , Aspergillus ochraceus/metabolismo , Fenômenos Químicos , Contaminação de Alimentos/prevenção & controle , Conservantes de Alimentos/efeitos adversos , Conservantes de Alimentos/química , Conservantes de Alimentos/isolamento & purificação , Qualidade dos Alimentos , Armazenamento de Alimentos , Frutas/química , Frutas/economia , Fumigação/efeitos adversos , Fungicidas Industriais/efeitos adversos , Fungicidas Industriais/química , Fungicidas Industriais/isolamento & purificação , Humanos , Índia , Viabilidade Microbiana , Micélio/crescimento & desenvolvimento , Micélio/isolamento & purificação , Micélio/metabolismo , Ocratoxinas/antagonistas & inibidores , Ocratoxinas/metabolismo , Óleos Voláteis/efeitos adversos , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Sensação , Vitis/química
19.
J Food Sci Technol ; 51(12): 4066-71, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25477682

RESUMO

Essential oils from 35 aromatic and medicinal plant species of Gorakhpur Division (U. P., India) were evaluated for their repellent activity against pulse bruchids Callosobruchus chinensis L. and C. maculatus F. of stored pigeon pea seeds. The oil concentration was at 0.36 µl/ml. Out of 35 essential oils, Adhatoda vasica Ness and Chenopodium ambrosioides L. oils showed absolute (100 %) insect repellency. Chenopodium oil exhibited 100 % mortality for both the test insects at 10 µl concentration (LD50 = 2.8 µl for C. chinensis & 2.5 µl for C. maculatus) and more toxic than Adhatoda oil (LD50 = 6.8 µl for C. chinensis & 8.4 µl for C. maculatus). During in vivo evaluation, 0.29 and 0.58 µl/ml of Chenopodium oil significantly enhanced feeding deterrence in insects and reduced the seed damage as well as weight loss of fumigated pigeon pea seeds up to 6 months of storage as compared to control set. Thus, Chenopodium oil can be used as an effective option of commercial fumigants for the storage of pigeon pea seeds against pulse bruchids.

20.
Biomed Res Int ; 2014: 459452, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25162013

RESUMO

The present study reports the in vitro antioxidant, antibacterial, and cytotoxic potential of Syngonium podophyllum (SP) and Eichhornia crassipes (EC) leaf aqueous extracts as well as their in vivo effect on oxidative stress and hepatic biomarkers in isoniazid induced rats. Phytochemical screening of extracts revealed the presence of flavonoids, terpenoids, reducing sugars, alkaloids, and saponins. Phenolic content in SP and EC extracts was 5.36 ± 0.32 and 10.63 ± 0.13 mg PGE/g, respectively, while flavonoid content was 1.26 ± 0.03 and 0.51 ± 0.03 µg QE/mg, respectively. EC extract exhibited comparatively better antioxidant activity as indicated by reducing power (0.197-0.775), DPPH radical scavenging potential (11%-96%), and metal ion chelating ability (42%-93%). Both the extracts provided 13%-65% protection against lipid peroxidation in rat tissue (liver, kidney, and brain) homogenate. SP and EC extracts exhibited 51% and 43% cytotoxicity against lung cancer (NCI-H322) cell line, respectively. Both extracts demonstrated considerable antibacterial activity against Proteus vulgaris, Salmonella typhi, and Bordetella bronchiseptica. Coadministration of E. crassipes extract with isoniazid in rats accounted for 46% decrease in malondialdehyde content and 21% increase in FRAP value of plasma. It also mitigated the isoniazid induced alterations in serum enzymes (SGOT, SGPT, and ALP), total bilirubin, creatinine, and hemoglobin contents. S. podophyllum extract was found to be hepatotoxic.


Assuntos
Antibacterianos/administração & dosagem , Antioxidantes/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Animais , Antibacterianos/química , Antioxidantes/química , Eichhornia/química , Sequestradores de Radicais Livres , Isoniazida/toxicidade , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Extratos Vegetais/química , Folhas de Planta/química , Ratos , Salmonella/efeitos dos fármacos
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