RESUMO
Excess acetaminophen (APAP) commonly causes severe acute liver injury (ALI), characterized by oxidative stress, pro-inflammatory responses, and hepatocyte damage. Veronica persica (VP) is a traditional medicine with antioxidant and anti-inflammatory properties. There is a paucity of information on its medicinal value, especially its potential mechanisms for alleviating ALI. This study aimed to clarify the ameliorative effects and intracellular mechanisms of VP on APAP-induced ALI via attenuating oxidative stress and inflammation. Mice were given VP for 7 days before exposure to APAP (300 mg/kg). The HPLC and radical scavenging assay found that VP contains 12 phenolic acids and 6 flavonoids, as well as show robust antioxidant capacity. In the APAP-induced ALI model, pre-treatment with VP significantly reduces APAP-induced hepatotoxicity by observing improved hepatocyte pathological injury and further confirmed by serum biochemical indicator. Also, the reduction of TUNEL-positive regions and the regulation of Bcl-2-associated X protein indicated that VP attenuates hepatocytotoxicity. Moreover, VP pre-intervention inhibits the formation of liver pro-inflammatory cytokines, the expression of inflammatory response genes, and increases in myeloperoxidase (MPO) in APAP-exposed mice. The elevated reduced glutathione (GSH) levels and decreased oxidative stress markers indicate that VP reduces APAP-promoted oxidative stress. Further study revealed that VP inhibited the phosphorylation of NF-κB/STAT3 cascade, blocked ERK and JNK phosphorylation, and activated AMP-activated protein kinase (AMPK). To sum up, this study demonstrated that VP exists hepatoprotective abilities on APAP-induced ALI, primarily by suppressing the phosphorylation of NF-κB/STAT3 cascade and ERK-JNK and inducing AMPK activation to alleviate oxidative stress and inflammation.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Veronica , Camundongos , Animais , Acetaminofen/farmacologia , Antioxidantes/farmacologia , Antioxidantes/metabolismo , NF-kappa B/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Estresse Oxidativo , Fígado , Inflamação/metabolismo , Camundongos Endogâmicos C57BLRESUMO
The aim of this study is to investigate the efficacy and the underlying mechanism of Veronica incana in osteoarthritis (OA) induced by intraarticular injection of monosodium iodoacetate (MIA). The selected major four compounds (A-D) of V. incana were found from fractions 3 and 4. Its structure elucidation was determined by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) data analysis and nuclear magnetic resonance (NMR) data comparison with literature. MIA (50 µL with 80 mg/mL) for the animal experiment was injected into the right knee joint. The V. incana was administered orally every day to rats for 14 days from 7 days after MIA treatment. Finally, we confirmed the four compounds: (A) verproside; (B) catalposide; (C) 6-vanilloylcatapol; and (D) 6-isovanilloylcatapol. When we evaluated the effect of V. incana on the MIA injection-induced knee OA model, there were a noticeable initial decreased in hind paw weight-bearing distribution compared to the Normal group (P < .001), but V. incana supplementation resulted in a significant increase in the weight-bearing distribution to the treated knee (P < .001). Moreover, the V. incana treatment led to a decrease in the levels of liver function enzymes and tissue malondialdehyde (P < .05 and .01). The V. incana significantly suppressed the inflammatory factors through the nuclear factor-kappa B signaling pathway and downregulated the expression of matrix metalloproteinases, which are involved in the degradation of the extracellular matrix (P < .01 and .001). In addition, we confirmed the alleviation of cartilage degeneration through tissue stains. In conclusion, this study confirmed the major four compounds of V. incana and suggested that V. incana could serve as an anti-inflammatory candidate agent for patients with OA.
Assuntos
Osteoartrite do Joelho , Veronica , Ratos , Animais , Ácido Iodoacético , Modelos Animais de Doenças , Anti-Inflamatórios/farmacologia , Osteoartrite do Joelho/induzido quimicamente , Osteoartrite do Joelho/tratamento farmacológicoRESUMO
Bacterial Leaf Blight (BLB) disease is an extremely ruinous disease in rice, caused by Xanthomonas oryzae pv. oryzae (Xoo). Although various chemicals are available to manage BLB, they are toxic to the environment as well as humans. Hence there is a need to develop new pesticides as alternatives to hazardous chemicals. Therefore, a study was carried out to discover new potent natural pesticides against Xoo from different solvent extracts of Vernonia cinerea. Among all the fractions, the methanolic extract showed the highest inhibition zone. Further, to gain mechanistic insight of inhibitory action, 40 molecules of methanolic extracts were subjected for in silico study against two enzymes D-alanine-D-alanine ligase (Ddl) and Peptide deformylase (PDF). In silico study showed Rutin and Methanone, [1,4-dimethyl-7-(1- methylethyl)-2- azulenyl]phenyl have a good binding affinity with Ddl while Phenol, 2,4-bis(1-phenylethyl)- and 1,2-Benzenedicarboxylic acid, diisooctyl ester showed an excellent binding affinity to PDF. Finally, the system biology approach was applied to understand the agrochemical's effect in the cell system of bacteria against both the enzymes. Conclusively, these four-hit compounds may have strong potential against Xoo and can be used as biopesticides in the future.
Assuntos
Antibacterianos/farmacologia , Extratos Vegetais/farmacologia , Veronica/química , Xanthomonas/efeitos dos fármacos , Amidoidrolases/química , Amidoidrolases/metabolismo , Antibacterianos/química , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Ligantes , Metanol/química , Simulação de Acoplamento Molecular , Peptídeo Sintases/química , Peptídeo Sintases/metabolismo , Ácidos Ftálicos/análise , Ácidos Ftálicos/química , Ácidos Ftálicos/farmacologia , Extratos Vegetais/química , Ligação Proteica , Rutina/análise , Rutina/química , Rutina/farmacologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Veronica ciliata Fisch. existed in various Tibetan medicine prescriptions, which was recorded to treat liver diseases in the Tibetan medicine roll of Chinese materia medica. HYPOTHESIS/PURPOSE: The current study aimed to examine the effect of active constituents from V.ciliata relieving oxidative stress-mediated liver injury and clarify the underlying mechanism. MATERIALS AND METHODS: tert-Butyl hydroperoxide (BHP) induced liver injury in mice model was established to evaluate the hepatoprotective effect of ethyl acetate extract of V. ciliata (EAFVC). Serum and liver indicators, as well as the histopathological change of liver were examined. Next, the constituents of EAFVC were separated and characterized by high-speed countercurrent chromatography (HSCCC) and Ultra performance liquid chromatography-mass spectrometer (UPLC-MS), respectively. Based on the above, the antioxidant activity of EAFVC and two fractions was evaluated using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2, 2'-azino-bis (3-ethylbenzothiazoli- ne-6-sulfonic acid) (ABTS) free radical scavenging assays. The hepatoprotective activity of EAFVC and its fractions/compounds attenuating ethanol-induced hepatocyte damage in BRL-3A cells was evaluated using the MTT method. The effect of the fraction and compounds with the strongest protective activity on ethanol-induced cytotoxicity, reactive oxygen species (ROS) accumulation, and glutathione (GSH) depletion was investigated. mRNA expression of nuclear factor-E2-related factor 2 (Nrf2) and nuclear factor of κB (NF-κB), as well as their downstream target genes, was determined by RT-qPCR. Finally, the potential mechanism of fraction 1 and luteolin on the AMPK/p62/Nrf2 signal pathway was studied using western blotting. RESULTS: Firstly, EAFVC could relieve liver impairment induced by t-BHP in mice. Next, fraction 1 enriched with polyphenolic compounds and luteolin derived from EAFVC were screened to yield the highest hepatoprotective activity against ethanol-induced hepatocyte damage. Further study demonstrated that fraction 1 and luteolin relieved BRL-3A cells damage by decreasing the aspartate aminotransferase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) activities, ROS accumulation, as well as the depletion of GSH. Also, we determined that fraction 1 and luteolin suppressed inflammation and apoptosis of BRL-3A cells. The mechanistic studies indicated that fraction 1 could attenuate oxidative stress, inflammation, and apoptosis by activating AMPK phosphorylation, which promotes autophagy associated protein expression (LC3-B, Beclin1 and p62) as well as promote phosphorylation of p62 -dependent autophagic degradation of Keap1, to induce Nrf2 dissociation from Keap1 and translocate to nuclear. Nrf2 in the nuclear activate cytoprotective related genes to exert hepatoprotective function. Finally, we found that luteolin activated the protein expression of p-AMPK, p-p62, p62, Nrf2, and its downstream target genes. CONCLUSIONS: This study clarified that fraction 1 enriched phenolic compounds could attenuate ethanol-induced liver injury in BRL-3A cells via activating AMPK/p62/Nrf2 pathway. Luteolin could serve as the major bioactive component in the therapeutic effect of fraction 1. These active constituents in V. ciliata could be used as the potential drugs targeted activation of AMPK or p62 for relieving oxidative stress-mediated liver disorders.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Proteína Sequestossoma-1/metabolismo , Veronica/química , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular , Doença Hepática Induzida por Substâncias e Drogas/patologia , Etanol/toxicidade , Inflamação/tratamento farmacológico , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Luteolina/farmacologia , Masculino , Camundongos Endogâmicos ICR , Simulação de Acoplamento Molecular , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , terc-Butil Hidroperóxido/toxicidadeRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Veronica ciliata Fisch. is a traditional medical herb that present in more than 100 types of Tibetan medicine prescriptions, most of which are used for liver disease therapy. Iridoid glycosides have been identified as the major active components of V.ciliata with a variety of biological activities. AIMS OF THE STUDY: The aim of this study is to explore the protective effect and potential mechanism of n-Butanol extract (BE) and iridoid glycosides (IG) from V.ciliata against É-naphthyl isothiocyanate (ANIT)-induced hepatotoxicity and cholestasis in mice. MATERIALS AND METHODS: Mice were intragastrically (i.g.) given BE and IG at different dose or positive control ursodeoxycholic acid (UCDA) once a day for 14 consecutive days, and were treated with ANIT to cause liver injury on day 12th. Serum levels of hepatic injury markers and cholestasis indicators, liver index and liver histopathology were measured to evaluate the effect of BE and IG on liver injury caused by ANIT. The protein levels of tumor necrosis factor-α (TNF-α), nuclear factor kappa B(NF-κB), interleukin-6 (IL-6), Na+/taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2), and the levels of oxidative stress indicators in liver tissue were investigated to reveal the underlying protective mechanisms of BE and IG against ANIT-induced hepatotoxicity and cholestasis. RESULTS: The n-Butanol extract (BE) and iridoid glycosides (IG) isolated from V.ciliata significantly decreased serum level of cholestatic liver injury markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total bile acid (TBA), total bilirubin (TBIL), and direct bilirubin (DBIL) in ANIT-treated mice. Histopathology of the liver tissue showed that pathological damages were relieved upon BE and IG treatment. Meanwhile, the results indicated BE and IG notably restored relative liver weights, inhibited oxidative stress induced by ANIT through increasing hepatic level of superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) and decreasing hepatic content of malondialdehyde (MDA). Western blot revealed that BE and IG inhibited the expression of pro-inflammatory factors TGF-α, IL-6 and NF-κB. Furthermore, the decreased protein expression of bile acid transporters NTCP, BSEP, MRP2 were upregulated by BE and IG in a dose-dependent manner. CONCLUSION: The results have demonstrated that BE and IG exhibited a dose-dependently protective effect against ANIT-induced liver injury with acute intrahepatic cholestasis in mice, which might be related to the regulation of oxidative stress, inflammatory response and bile acid transport. In addition, these findings pointed out that iridoid glycosides as main active components of V.ciliata play a critical role in hepatoprotective effect of V.ciliata.
Assuntos
Colestase/tratamento farmacológico , Glicosídeos Iridoides/farmacologia , Extratos Vegetais/farmacologia , Veronica/química , 1-Butanol/química , 1-Naftilisotiocianato , Animais , Ácidos e Sais Biliares/metabolismo , Transporte Biológico/efeitos dos fármacos , Colestase/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Glicosídeos Iridoides/administração & dosagem , Glicosídeos Iridoides/isolamento & purificação , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Medicina Tradicional Tibetana , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagemRESUMO
Breast cancer is one of the most common cancers in women and is associated with a high mortality rate. The majority of deaths resulting from breast cancer are attributable to metastatic growth; in addition, chemoresistance is a major concern in the treatment of patients with breast cancer. However, limited drugs are available for the treatment of metastatic breast cancer. In this study, the chemoadjuvant effects of a methanolic extract from the leaves of Pseudolysimachion rotundum var. subintegrum (NC13) and an active component isolated from the plant, verminoside (Vms), were evaluated. Furthermore, their potent anti-metastatic activities were validated in vitro and in vivo in animal models. The anti-metastatic and chemosensitizing activities of NC13 and Vms on cisplatin treatment were found to be partly mediated by suppression of the epithelial-mesenchymal transition of cancer cells. Collectively, our results implied that NC13 and its bioactive component Vms could be developed as effective chemoadjuvants in combination with conventional therapeutics.
Assuntos
Adjuvantes Farmacêuticos/farmacologia , Antineoplásicos/administração & dosagem , Neoplasias da Mama/metabolismo , Cisplatino/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Iridoides/farmacologia , Fitoterapia/métodos , Extratos Vegetais/farmacologia , Veronica/química , Aloenxertos , Animais , Neoplasias da Mama/dietoterapia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos dos fármacos , Dieta , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica/tratamento farmacológico , Folhas de Planta/químicaRESUMO
Plants from the Veronica genus are used across the world as traditional remedies. In the present study, extracts from the aerial part of the scarcely investigated Veronica austriaca L., collected from two habitats in Bulgaria-the Balkan Mountains (Vau-1) and the Rhodopi Mountains (Vau-2), were analyzed by nuclear magnetic resonance (NMR) spectroscopy. The secondary metabolite, arbutin, was identified as a major constituent in both extracts, and further quantified by high-performance liquid chromatography (HPLC), while catalpol, aucubin and verbascoside were detected at lower amounts. The effect of the extracts and of pure arbutin on the survival of neutrophils isolated from murine bone marrow (BM) were determined by colorimetric assay. The production of cytokines-tumor necrosis factor (TNF)-α and interferon (IFN)-γ was evaluated by flowcytometry. While Vau-1 inhibited neutrophil vitality in a dose-dependent manner, arbutin stimulated the survival of neutrophils at lower concentrations, and inhibited cell density at higher concentrations. The Vau-1 increased the level of intracellular TNF-α, while Vau-2 and arbutin failed to do so, and expanded the frequency of mature double TNF-α+/IFN-γhi neutrophils within the BM pool.
Assuntos
Medula Óssea/metabolismo , Interferon gama/biossíntese , Neutrófilos/metabolismo , Extratos Vegetais/farmacologia , Fator de Necrose Tumoral alfa/biossíntese , Veronica/química , Animais , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/citologia , Extratos Vegetais/químicaRESUMO
Linariifolioside II (1) and (2S)-2-hydroxy-5-oxoproline methyl ester (2), two new compounds along with 13 known compounds were obtained from the aerial part of Pseudolysimachion linariifolium Holub subsp. dilatatum (Nakai & Kitag.) D.Y. Hong. Their chemical structures were revealed mainly through NMR and MS data. The absolute configuration of 2 was deduced by comparing its experimental CD with the calculated ECD spectra. At a concentration of 1â mm, total antioxidant capacities of compounds 1-15 were measured using a rapid ABTS method inâ vitro. Compounds 1, 3-5, and 11-14 exhibited approximately equal antioxidant capacity to that of vitamin C (Vc).
Assuntos
Antioxidantes/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Lactamas/farmacologia , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Veronica/química , Antioxidantes/química , Antioxidantes/isolamento & purificação , Benzotiazóis/antagonistas & inibidores , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Lactamas/química , Lactamas/isolamento & purificação , Medicina Tradicional Chinesa , Estrutura Molecular , Fenóis/química , Fenóis/isolamento & purificação , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Ácidos Sulfônicos/antagonistas & inibidoresRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Veronica ciliata Fisch. is used in numerous of Tibetan medicine prescriptions because of its hepatoprotective effect. AIMS OF THIS STUDY: Here, we aimed to investigate the hepatoprotective effect and mechanism of phenolic fraction (PF) of V. ciliata Fisch. on liver injury induced by free radical. MATERIALS AND METHODS: BRL 3A cells were pre-treated with PF and luteolin (Lut) following tert-butyl hydroperoxide (t-BHP) treatment. The cell viability, lactate dehydrogenase (LDH) levels, reactive oxygen species (ROS) generation, apoptosis, cell cycle and autophagy were analyzed. Apoptotic, inflammatory, and autophagy,- related proteins were analyzed using Western blotting. The combination of molecular docking and drug affinity targeting experiments (DARTS) were first utilized to analysis the target protein of Lut. RESULTS: PF effectively suppressed t-BHP-induced apoptosis caused by mitochondrial dysfunction, which were associated with inhibiting ROS generation. Further investigation indicated that PF significantly suppressed apoptosis, inflammation, and autophagy by regulating the expression of related proteins. The results of molecular docking and drug affinity targeting experiments (DARTS) revealed that PI3K was the target protein of PF and Lut. Further studies have shown that PF relieved liver injury induced by t-BHP via suppressing phosphorylated expression of PI3K. CONCLUSION: Our results indicate that PF effectively protect against hepatotoxicity induced by t-BHP through inhibiting the abnormal activation of PI3K-Akt signaling pathway and highlight the health benefits of PF regarding oxidative stress, proving it to be an important source of bioactive compounds associated with Nonalcoholic fatty liver disease (NAFLD).
Assuntos
Hepatócitos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Fenóis/farmacologia , Veronica/química , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Radicais Livres/toxicidade , Hepatócitos/patologia , Simulação de Acoplamento Molecular , Estresse Oxidativo/efeitos dos fármacos , Fenóis/isolamento & purificação , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Endogâmicos BUF , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , terc-Butil Hidroperóxido/toxicidadeRESUMO
Veronica is the largest genus in the flowering plant family Plantaginaceae and comprises approximately 500 species. The genus was formerly placed in the Scrophulariaceae family, some species of which have been used in traditional medicine for the treatment of influenza, respiratory diseases, hemoptysis, laryngopharyngitis, cough, hernia, cancer, edema, and wounds. This review comprehensively summarizes the current information on the traditional uses, phytochemistry, and pharmacology of the genus Veronica on the basis of articles published from 1970 to 2018. More than 260 compounds have been isolated, and chemotaxonomic investigations of Veronica have revealed that iridoid glucosides - including aucubin, catalpol, and 6-O-catalpol derivatives - are characteristic of this genus. Modern pharmacological studies and clinical practice have demonstrated that extracts or monomeric compounds from Veronica have several pharmacological actions, such as anti-inflammatory, anti-oxidative, anticancer, antibacterial, anti-angiogenic, antineurodegenerative, neuroprotective, and hepatoprotective effects both in vivo and in vitro.
Assuntos
Glucosídeos Iridoides/isolamento & purificação , Glucosídeos Iridoides/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Veronica/química , Inibidores da Angiogênese , Animais , Antibacterianos , Anti-Inflamatórios , Antineoplásicos Fitogênicos , Antioxidantes , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Humanos , Glucosídeos Iridoides/química , Medicina Tradicional , Conformação Molecular , Fármacos Neuroprotetores , Fitoterapia , Terpenos/síntese química , Terpenos/isolamento & purificação , Terpenos/farmacologiaRESUMO
The Veronica genus, with more than 200 species, belongs to the Plantaginaceae family and is distributed over most of the Northern Hemisphere and in many parts of Southern Hemisphere. These plants are traditionally used in medicine for wound healing, in the treatment of rheumatism, and in different human diseases. This paper reviews the chemical composition of some valuable Veronica species, the possibilities Veronica extracts have in food preservation and as food ingredients, and their functional properties. Veronica species represent a valuable source of biological active secondary metabolites, including iridoid glycosides and phenolic compounds. In particular, due to presence of these phytochemicals, Veronica species exhibit a wide spectrum of biological activities, including antimicrobial and antioxidant. In fact, some studies suggest that some Veronica extracts can inhibit foodborne pathogens, such as Listeria monocytogenes, but only a few of them were performed in food systems. Moreover, anticancer, anti-inflammatory, and other bioactivities were reported in vitro and in vivo. The bioactivity of Veronica plants was demonstrated, but further studies in food systems and in humans are required.
Assuntos
Alimentos , Medicina Tradicional , Compostos Fitoquímicos/uso terapêutico , Fitoterapia , Veronica/química , Antioxidantes/farmacologia , Compostos Fitoquímicos/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Veronica ciliata Fisch, a traditional Tibetan medicine, used to cure hepatitis and existed in lots of Tibetan medicine prescriptions owing to its hepatoprotective activity. AIMS OF THIS STUDY: In this study, we are aimed to systematically analysis and isolate the chemical constituents of the ethyl acetate fraction from V. ciliata (EAFVC), and test the hepatoprotective effect and mechanism of EAFVC and its compounds on attenuating the liver injury induced by acetaminophen (APAP) in vivo and vitro. MATERIALS AND METHODS: UPLC-PDA-ESI-MS method was established for the analysis of the components in EAFVC, which was further separated using multiple chromatographic techniques. The MS, 1H and 13C NMR were applied to elucidate their structures. UPLC-PDA method was applied for the simultaneous quantification of major compounds of EAFVC. Furthermore, the protective effect of the EAFVC was determined using APAP-induced acute hepatotoxicity in mice and BRL-3A cells model, respectively. In addition, the hepatoprotective activity of two main compounds in EAFVC on relieving APAP-induced liver injury was further evaluated. Finally, we have some concerns about the protective mechanism of EAFVC via enzyme-linked immunosorbent assay (ELISA), reactive oxygen species (ROS) detection, quantitative real-time PCR (qPCR), western blot analysis and molecular docking. RESULTS: Thirteen compounds were successfully identified using UPLC-PDA-ESI-MS for the first time. Meanwhile, other twelve compounds were separated from EAFVC. Eventually, twenty-five compounds were successfully identified from the EAFVC. Among these compounds, fourteen compounds (3, 8, 10, 14-17, 19-25) were separated from V.ciliata for the first time. In addition, UPLC-PDA analysis method was first to establish for simultaneous determination of the main compounds (1, 2, 4, 5, 7, 9, 12). Further assay indicated that the liver injury in mice induced by APAP showed a significant reversal by EAFVC, as evidenced by reducing the activities of liver function enzymes, suppressing the lipid peroxidation as well as increasing the serum total antioxidant capacity (T-AOC) and the activities of antioxidant enzymes. Pathological sections showed that the liver in the high dose has significant improvement in mice. In vitro experiment also showed that EAFVC elevate the viability, inhibiting the activities of liver function enzymes as well as the generation of ROS of BRL-3A cells. In addition, Catalposide and verproside could reverse the low cell viability of BRL-3A cells induced by APAP. The mechanism research in vitro demonstrated that EAFVC could promote the mRNA and protein expression of heme oxygenase-1 (HO-1), NAD(P) H dehydrogenase quinone 1 (NQO-1) and catalytic or modify subunit of glutamate-cysteine ligase (GCLC/GCLCM) via enhancing nuclear factor-E2-related factor 2 (Nrf2) and p62/SQSTM1 (p62) expression in protein level. Molecular docking results demonstrated that catalposide and verproside have strong affinity to the kelch-like ECH-associated protein-1(Keap1) Kelch domain. CONCLUSION: This research is the first to clarify the substance basis of the hepatoprotective activity of the EAFVC and provide the further scientific data for the traditional use of this Tibetan Medicine. EAFVC is valuable to be further investigated as active preparations for application in liver protection via activating p62- Keap1-Nrf2 pathway.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Extratos Vegetais , Substâncias Protetoras , Veronica , Acetaminofen , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Ratos , Espécies Reativas de Oxigênio/metabolismo , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
The aim of this work is the phytochemical study of the butanolic extract of the aerial parts of Veronica rosea. Four compounds 1-4 have been isolated using different chromatographic methods. The structures of these compounds were determined by NMR spectral analysis and mass spectroscopy. The adsorption and anticorrosion effects of this extract were investigated towards the corrosion of copper in 1 M HNO3 aqueous by the weight loss technique and potentiodynamic polarization. The results showed that the butanolic extract is a good inhibitor and the inhibition efficiency increases with increasing of concentration of the inhibitor. The adsorption of this extract on the copper specimen surface was spontaneous and obeyed the Langmuir's adsorption isotherm. Large value of adsorption equilibrium Constant (K ads = 35 L g-1) was obtained. The polarization experiments confirmed the data obtained by gravimetric weight-loss. Tafel plot of polarization curves indicates that the extract acts as a mixed type inhibitor.
Assuntos
Corrosão , Compostos Fitoquímicos/química , Veronica/química , Adsorção , Oxirredutases do Álcool/química , Cobre/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Componentes Aéreos da Planta/química , Extratos Vegetais/químicaRESUMO
The lack of an effective anti-viral agent and the emergence of drug-resistant strains dictate a real need for discovery of novel therapies able to ameliorate viral infections. In this regards, medicinal plants and natural products offer safe and inexpensive platforms for discovery of efficient and novel anti-viral agents. We have investigated the potential anti-viral activities of Veronica persica Poir. as a medicinal plant against herpes simplex viruses (HSVs). In vitro screening of the ethanol plant extract against HSV-1 and HSV-2 infected Vero cells revealed the extract to show a dose-dependent inhibitory activity against both virus strains. After fractionation of the extract by a stepwise methanol gradient and evaluation of each fraction, the 80% methanol fraction displayed a pronounced inhibitory activity against the herpes viruses. The highest antiviral activity was observed when the Vero cells were treated with the extract both during and after infection by viruses. Moreover, the extract showed a prominent synergistic activity in combination with acyclovir anti-HSV therapy. Our findings revealed the potential of V. persica extract, especially its 80% methanol fraction, in inhibition of herpes simplex viral infections.
Assuntos
Antivirais/farmacologia , Herpes Zoster/tratamento farmacológico , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Veronica/química , Aciclovir/farmacologia , Animais , Antivirais/química , Chlorocebus aethiops/virologia , Etanol/química , Herpes Zoster/virologia , Herpesvirus Humano 1/patogenicidade , Herpesvirus Humano 2/patogenicidade , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Células Vero/efeitos dos fármacosRESUMO
Leishmania major is an intracellular parasite generally responsible for cutaneous leishmaniasis (CL), one of the most encountered skin diseases especially in Pakistan, Iran, Iraq, and Saudi Arabia. Current treatment options are not ideal, due to unwanted side effects and increasing resistance and availability is often limited in developing countries. Medicinal plants continue to attract attention because of their beneficial effects in the prevention or/and accelerating the healing process of various diseases. In this study, in vitro and in vivo susceptibility of L. major to Veronica persica Poir. extract, a medicinal plant with many applications, has been evaluated. Antileishmanial activity of plant extract was investigated both on cultured L. major promastigotes and in mice challenged with L. major. Animals were divided into three groups including control (without any treatment), test (treated with plant extract) and glucantime (the reference drug) treated groups. After treatments, skin lesion sizes and body weights of animals were checked during 4 weeks. The potential of the plant extract in decreasing the number of parasites in spleen cells of animals as well as inducing the nitric oxide (NO) production by macrophage cells was also investigated. In vitro tests showed that the plant extract was able to reduce the survival time of promastigotes in a concentration-dependent manner. In vivo experiments also revealed a significant influence of V. persica extracts on accelerating the healing process as well as reducing the overall disease burden in animal model by inducing NO production in macrophage cells. Our findings indicated the promising potential of V. persica extract as an ideal candidate in the treatment of CL caused by L. major.
Assuntos
Leishmania major/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Extratos Vegetais/farmacologia , Veronica/química , Animais , Modelos Animais de Doenças , Humanos , Irã (Geográfico)/epidemiologia , Leishmania major/patogenicidade , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/parasitologia , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Camundongos , Paquistão , Extratos Vegetais/química , Plantas Medicinais/químicaRESUMO
Veronica persica (Persian speedwell) is a flowering plant local to Eurasia. In this study, several analyses were done to discover the antimicrobial and scolicidal activities and acetyl cholinesterase (AChE), tyrosinase (TYR), lipoxygenase (LOX), and xanthine oxidase (XO) inhibitory activities of V. persica extract. The results presented that B. subtilis was the most susceptible to the extract (MIC = 40.3 µg/mL), while P. aeruginosa was the most resistant strain (MIC = 250.9 µg/mL) among all bacteria evaluated. The extracts demonstrated significant activity versus E. granulosus (P < 0.5) with dose-dependent inhibitions of the protoscolices. The analyzed plant extract exhibited a high AChE and TYR inhibitory activity 55.3% and 52.7% (at the highest utilized dose - 3 mg/mL), respectively. The extract also showed high anti-inflammatory activities in analyses tested. Our research proposed that extract of this plant could be promising to the human health, markedly in the infectious, neurodegenerative and inflammatory disorders.
Assuntos
Antibacterianos/química , Antifúngicos/uso terapêutico , Extratos Vegetais/química , Veronica/química , Acetilcolinesterase/química , Antibacterianos/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antifúngicos/química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/uso terapêutico , Humanos , Lipoxigenase/efeitos dos fármacos , Monofenol Mono-Oxigenase/antagonistas & inibidores , Fenóis/química , Fenóis/uso terapêutico , Extratos Vegetais/farmacologia , Xantina Oxidase/antagonistas & inibidoresRESUMO
With the appearance of new disorders along with inability of some conventional therapies for the treatment of diseases without any side effects, the discovery of safe and efficient therapeutic agents is of utmost importance in the medical area. In this context, medicinal plants as promising therapeutic candidates can provide a reliable and efficient profile. Since free radicals are at the center of various disorder pathways, reducing their production or complete removal of these chemical species could be advantageous for prevention and treatment of many diseases. In this experiment, free radical scavenging and antioxidant activities of Veronica persica Poir., a known medicinal plant, were evaluated using in vitro and in vivo assays. Chemical characterization results showed a high phenolic content in the V. persica methanol extract. In addition, in vitro assays including DPPH radical-scavenging assay, nitric oxide-scavenging activity assay, hydrogen peroxide scavenging test and bleomycin-dependent DNA damage test revealed significant antioxidant power and radical scavenging capacity of this plant. In accordance, in vivo experiments showed inhibitory effects of the methanol extract on lipid peroxidation, a main cause of cell damage. Our findings revealed the promising potential of this plant in reducing free radicals through different pathways. Moreover, our data suggested a correlation between the high phenolic content of the V. persica extract and its free radical scavenging and antioxidant activities.
Assuntos
Antioxidantes/química , Sequestradores de Radicais Livres/química , Extratos Vegetais/química , Veronica/química , Dano ao DNA/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Óxido Nítrico/biossíntese , Fenóis/química , Extratos Vegetais/uso terapêutico , Plantas Medicinais/químicaRESUMO
Ulcerative colitis (UC) is a major inflammatory bowel disease (IBD) has become a worldwide emergent disease. Veronica polita (VP) is a medicinal herb that has strong antioxidant and anti-inflammatory properties. In the present study, we studied the protective effect of VP on dextran sulfate sodium (DSS)-induced experimental colitis in mice. Phytochemical screening of VP extract demonstrated the presence of high total phenolic and flavonoid contents. Compared with the DSS group, VP significantly reduced clinical symptoms with less weight loss, bloody stool, shortening of the colon, and the severity of colitis was considerably inhibited as evidenced by the reduced disease activity index (DAI) and degree of histological damage in the colon and spleen. Also, treatment with VP considerably decreased the nitric oxide (NO) and malondialdehyde (MDA) level. VP remarkably downregulated the expression of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), inducible nitric oxide synthetase (iNOS) and cyclooxygenase-2 (COX-2) in the colon tissue. Likewise, activation of the signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappa B (NF-κB) was effectively blocked by VP. Taken together, these results demonstrate that VP has an ameliorative effect on colonic inflammation mediated by modulation of oxidative stress and inflammatory mediators by suppressing the JAK2/STAT3 and NF-κB signaling pathways.
Assuntos
Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Janus Quinase 2/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/uso terapêutico , Fator de Transcrição STAT3/metabolismo , Veronica/química , Animais , Anti-Inflamatórios/isolamento & purificação , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Transdução de SinaisRESUMO
The present study aims to evaluate the potential uses of hydroalcoholic extracts obtained from Romanian native wild-growing plants. The hydroalcoholic extracts were obtained from the burdock roots and respectively the aerial parts of birdeye speedwell. The extracts were characterised by HPLC (quantifying 13 compounds in the V. persica extract, 6 compounds in the A. lappa extract and confirming the presence of arctiin and arctigenin in the burdock extract). The antioxidant potential of the crude extracts was evaluated using two methods: the DPPH assay (79.91% for speedwell extract, 76.23% for burdock extract) and the phosphomolybdate method (296.5 mg/g ascorbic acid equivalents for burdock, 324.4 mg/g for speedwell). The crude extracts were found to be active against both fungal lines used (Aspergillus niger and Penicillium hirsutum), inhibition zones - 17.1 mm and 13.1 mm against P. hirsutum, respectively ca. 22 mm for both extracts against A. niger. The cytogenetic effects (assessed using the Allium cepa assay) revealed a series of chromosomal aberrations and nuclear aberrations induced in the meristematic root cells. The anti-inflammatory effect, estimated in two inflammation experimental models, showed a significant effect, especially for the speedwell extract. The results recommend the evaluated extracts as promising sources of biologically-active compounds.
Assuntos
Anti-Inflamatórios/farmacologia , Antifúngicos/farmacologia , Antioxidantes/farmacologia , Arctium/química , Extratos Vegetais/farmacologia , Veronica/química , Animais , Anti-Inflamatórios/química , Antifúngicos/química , Antioxidantes/química , Compostos de Bifenilo/química , Divisão Celular/efeitos dos fármacos , Masculino , Cebolas/citologia , Picratos/química , Extratos Vegetais/química , Raízes de Plantas/citologia , Ratos , Ratos Wistar , RomêniaRESUMO
Neuroprotective potential of V. teucrium and V. jacquinii methanol extracts was analyzed. Chemical analysis of investigated extracts showed the presence of phenolic acid derivatives, flavonoids and one secoiridoid. The detected flavonoids derived from flavones (luteolin and isoscutellarein in V. jacquinii; apigenin, isoscutellarein and luteolin in V. teucrium) and flavonol (quercetin in V. jacquinii). Acteoside was the dominant compound in V. jacquinii, while plantamajoside and isoscutellarein 7-O-(6â´-O-acetyl)-ß-allosyl (1â´â2â´)-ß-glucoside were the major phenolics in V. teucrium. Additionally, the antineurodegenerative activity was tested at concentrations of 25, 50, and 100 µg/ml using acetylcholinesterase (AChE) and tyrosinase (TYR) assays. The inhibition of both enzymes was achieved with the investigated extracts, ranging from 22.78 to 35.40% for AChE and from 9.57 to 16.38% for TYR. There was no statistical difference between the activities of the analyzed extracts. Our data indicate that V. teucrium and V. jacquinii may have beneficial effects against Alzheimer's and Parkinson's disease.