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1.
Turk Kardiyol Dern Ars ; 48(4): 410-424, 2020 06.
Artigo em Inglês | MEDLINE | ID: covidwho-595169

RESUMO

OBJECTIVE: The aim of this study was to evaluate the effectiveness of plants used in the formulations of traditional Chinese medicine (TCM), which were also used in clinical trials to treat patients with the novel coronavirus COVID-19, and to assess their effects on the cardiovascular system. METHODS: A literature review of PubMed, ResearchGate, ScienceDirect, the Cochrane Library, and TCM monographs was conducted and the effects of the plants on the cardiovascular system and the mechanisms of action in COVID-19 treatment were evaluated. RESULTS: The mechanism of action, cardiovascular effects, and possible toxicity of 10 plants frequently found in TCM formulations that were used in the clinical treatment of COVID-19 were examined. CONCLUSION: TCM formulations that had been originally developed for earlier viral diseases have been used in COVID-19 treatment. Despite the effectiveness seen in laboratory and animal studies with the most commonly used plants in these formulations, the clinical studies are currently insufficient according to standard operating procedures. More clinical studies are needed to understand the safe clinical use of traditional plants.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Infecções por Coronavirus/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Pneumonia Viral/terapia , Animais , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Antiarrítmicos/toxicidade , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Anticolesterolemiantes/farmacologia , Anticolesterolemiantes/uso terapêutico , Anticolesterolemiantes/toxicidade , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/toxicidade , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/toxicidade , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Bloqueadores dos Canais de Cálcio/toxicidade , Interações Medicamentosas , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/toxicidade , Humanos , Pandemias , Inibidores da Agregação de Plaquetas/farmacologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Inibidores da Agregação de Plaquetas/toxicidade , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico , Vasodilatadores/toxicidade
2.
PLoS One ; 15(6): e0234157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32516332

RESUMO

Brazilian native fruits are a rich source of polyphenolic compounds that can act as anti-inflammatory and antioxidant agents. Here, we determined the polyphenolic composition, anti-inflammatory mechanism of action, antioxidant activity and systemic toxicity in Galleria mellonella larvae of Eugenia selloi B.D.Jacks. (synonym Eugenia neonitida Sobral) extract (Ese) and its polyphenol-rich fraction (F3) obtained through bioassay-guided fractionation. Phenolic compounds present in Ese and F3 were identified by LC-ESI-QTOF-MS. The anti-inflammatory activity of Ese and F3 was tested in vitro and in vivo through NF-κB activation, cytokine release and neutrophil migration assays. The samples were tested for their effects against reactive species (ROO•, O2•-, HOCl and NO•) and for their toxicity in Galleria mellonella larvae model. The presence of hydroxybenzoic acid, ellagitannins and flavonoids was identified. Ese and F3 reduced NF-κB activation, cytokine release and neutrophil migration, with F3 being three-fold more potent. Overall, F3 exhibited strong antioxidant effects against biologically relevant radicals, and neither Ese nor F3 were toxic to G. mellonella larvae. In conclusion, Ese and F3 revealed the presence of phenolic compounds that decreased the inflammatory parameters evaluated and inhibited reactive oxygen/nitrogen species. E. selloi is a novel source of bioactive compounds that may provide benefits for human health.


Assuntos
Eugenia/química , Frutas/química , Polifenóis/química , Polifenóis/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CXCL2/metabolismo , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Depuradores de Radicais Livres/toxicidade , Lepidópteros/efeitos dos fármacos , Masculino , Camundongos , NF-kappa B/metabolismo , Polifenóis/toxicidade , Células RAW 264.7 , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
3.
Turk Kardiyol Dern Ars ; 48(4): 410-424, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32519978

RESUMO

OBJECTIVE: The aim of this study was to evaluate the effectiveness of plants used in the formulations of traditional Chinese medicine (TCM), which were also used in clinical trials to treat patients with the novel coronavirus COVID-19, and to assess their effects on the cardiovascular system. METHODS: A literature review of PubMed, ResearchGate, ScienceDirect, the Cochrane Library, and TCM monographs was conducted and the effects of the plants on the cardiovascular system and the mechanisms of action in COVID-19 treatment were evaluated. RESULTS: The mechanism of action, cardiovascular effects, and possible toxicity of 10 plants frequently found in TCM formulations that were used in the clinical treatment of COVID-19 were examined. CONCLUSION: TCM formulations that had been originally developed for earlier viral diseases have been used in COVID-19 treatment. Despite the effectiveness seen in laboratory and animal studies with the most commonly used plants in these formulations, the clinical studies are currently insufficient according to standard operating procedures. More clinical studies are needed to understand the safe clinical use of traditional plants.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Infecções por Coronavirus/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Pneumonia Viral/terapia , Animais , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Antiarrítmicos/toxicidade , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Anticolesterolemiantes/farmacologia , Anticolesterolemiantes/uso terapêutico , Anticolesterolemiantes/toxicidade , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/toxicidade , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/toxicidade , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Bloqueadores dos Canais de Cálcio/toxicidade , Interações Medicamentosas , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/toxicidade , Humanos , Pandemias , Inibidores da Agregação de Plaquetas/farmacologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Inibidores da Agregação de Plaquetas/toxicidade , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico , Vasodilatadores/toxicidade
4.
Chem Biol Interact ; 324: 109089, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32272095

RESUMO

Ulcerative colitis (UC) is a chronic, idiopathic and inflammatory disease of the rectal and colonic mucosa. Studies have shown that Toll-like receptors (TLR) 4 and Signal Transducer and Activator of Transcription 3 (STAT3)-mediated the decline in immune function and inflammatory infiltration are potential pathomechanism of UC occurrence and development. In this study, the anti-inflammation of Erianin, a natural bibenzyl compound with the antioxidant, antitumor, and anti-inflammatory activities, was investigated in a dextran sodium sulphate-induced UC mouse model. Three-week Erianin administration resulted in the increment on the body weight and colon length, and the reduction on the activity index score of UC mice. Liver, spleen, and renal organ indexes and pathological observations confirmed that Erianin was not cytotoxic and had an effect of improving immune organ function. The haematoxylin and eosin staining sections of colon tissue show Erianin's effect of reversing inflammation in the mucosal laye. Proteomic analysis and enzyme-linked immunosorbent assay indicated that Erianin regulated the levels of inflammatory and oxidative stress-related factors and immunochemokines in serum and colon tissues thereby reducing cell peroxidative damage and reducing immune inflammatory responses. Further data obtained by Western Blotting confirmed that Erianin's anti-UC activity was mediated by inhibiting the TLR4 and STAT3 signaling.


Assuntos
Anti-Inflamatórios/uso terapêutico , Bibenzilas/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Fator de Transcrição STAT3/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Anti-Inflamatórios/toxicidade , Antioxidantes/uso terapêutico , Bibenzilas/toxicidade , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colo/patologia , Sulfato de Dextrana , Rim/patologia , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Baço/patologia
5.
BMC Complement Med Ther ; 20(1): 64, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111207

RESUMO

BACKGROUND: The pressed juice of Barley Grass (BG) has become very popular among people for various assumed benefits along with many testimonies of people who have been healed from various ailments such as anemia, cancer, GI problems by consuming BG. The aim of our research was to validate the claims of its medicinal values such as chemo-protective action, high anti-oxidants, RBC membrane stabilization activity, and toxicity level. METHODS: Extracts of hexane, ethyl acetate and methanol were quantitatively estimated for total phenolic contents (TPC) and total flavonoid contents (TFC). The same extracts were assessed for their antioxidative potentials with the use of DPPH free radical scavenging assay followed by determination of HRBC membrane stabilization method, Brine Shrimp Lethality Assay (BSLA) and GC-MS analysis. RESULTS: All the extracts showed high TPC and TFC along with the stronger correlation with the antioxidant activity of the extracts suggesting phenolics and flavonoids contents of the extract might be attributed to showing antioxidant activity. The methanolic and ethyl acetate extracts of the plant also showed remarkable anti-inflammatory activity where methanolic extracts had the lowest EC50. During Brine Shrimp Lethality Assay, all extracts of BG were found to be bioactive and the degree of lethality was found to be concentration dependent. The GC-MS analysis of the methanolic extract of BG revealed 23 compounds which are reported to possess different biological activities. CONCLUSION: The study reveals the strong antioxidant and RBC membrane stabilization activity of BG. The Brine Shrimp Lethality Assay found extracts to be bioactive suggesting extracts as a promising candidate for plant-derived anti-tumor compounds. Further, studies are needed to validate the data on cancer cell lines.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Flavonoides/farmacologia , Hordeum/química , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/toxicidade , Antioxidantes/toxicidade , Artemia , Cromatografia Gasosa , Flavonoides/toxicidade , Hordeum/toxicidade , Espectrometria de Massas , Fenóis/toxicidade , Extratos Vegetais/toxicidade , Folhas de Planta/química
6.
Biochem Pharmacol ; 175: 113918, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32194056

RESUMO

BACKGROUND: Dexamethasone is widely used in the treatment of joint diseases due to its anti-inflammatory properties. However, it can cause serious adverse effects. The anterior cruciate ligament (ACL) is an important stabilizer of the knee joint. However, the effect of dexamethasone treatment on the ACL is unclear. OBJECTIVE: This study aims to explore the effects of dexamethasone on ACL tissues and cells through in vitro and in vivo experiments. RESULTS: In vitro, we found that after treatment with dexamethasone, human ACL cell apoptosis was increased, type I collagen (COL1A1) content was decreased, mineralization related genes (ENPP1 and ANKH) and calcified nodules were increased, and endoplasmic reticulum stress (ERS) was enhanced. However, ERS inhibitors could significantly inhibit the increase in calcification and the decrease in COL1A1 induced by dexamethasone. In vivo, Wistar rats received the infra-articular injection with dexamethasone (0.5 mg/kg) for 8 weeks. We found that dexamethasone treatment decreased the COL1A1 content and increased the COL2A1 content in the ACL tissues of rats and that chondroid differentiation and mineralization occurred. Meanwhile, the expression of ERS-related proteins was increased. CONCLUSION: Dexamethasone increased the calcification of ACL cells and caused ACL degeneration through ERS, suggesting that long-term treatment with dexamethasone may cause adverse effects on ACL tissue and increase the risk of long-term rupture.


Assuntos
Ligamento Cruzado Anterior/efeitos dos fármacos , Ligamento Cruzado Anterior/metabolismo , Anti-Inflamatórios/toxicidade , Cálcio/metabolismo , Dexametasona/toxicidade , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Adulto , Animais , Ligamento Cruzado Anterior/patologia , Células Cultivadas , Relação Dose-Resposta a Droga , Estresse do Retículo Endoplasmático/fisiologia , Feminino , Humanos , Masculino , Ratos , Ratos Wistar , Adulto Jovem
7.
Environ Toxicol ; 35(6): 652-664, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31925992

RESUMO

1,2-Dimethylhydrazine (DMH), an environmental toxicant specifically targets the colon. The present study was aimed to evaluate the efficacy of gallic acid (GA) against colon toxicity induced by DMH in Wistar rats. GA, a phenolic acid has numerous beneficial properties, which include antiviral, antifungal and antioxidant properties which help cells to overcome oxidative stress and balance the redox homeostasis. GA was administered orally at two doses (25 and 50 mg/kg body weight) once daily for 14 days and a single dose (40 mg/kg body weight) of DMH was administered subcutaneously on 14th day. Animals were sacrificed on the 15th day and we could find that GA at both the doses significantly ameliorates DMH-induced increased toxicity markers and also substantially increases the glutathione content level and activities of detoxifying enzymes. It also ameliorates the expression of proliferation, inflammation, apoptosis, goblet cell disintegration, and mucin depletion in the colon that was elevated upon administration of DMH. Histological alterations provide further confirmation of the protective role of GA against DMH-induced colon toxicity. The results of this study clearly indicate supplementation of GA is beneficial in ameliorating DMH-induced oxidative stress, inflammation, proliferation, apoptosis, mucin depletion, and goblet cell disintegration in colon of Wistar rats.


Assuntos
1,2-Dimetilidrazina/toxicidade , Anti-Inflamatórios/toxicidade , Proliferação de Células/efeitos dos fármacos , Ácido Gálico/farmacologia , Células Caliciformes/efeitos dos fármacos , Mucinas/metabolismo , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Glutationa/metabolismo , Células Caliciformes/metabolismo , Células Caliciformes/patologia , Inflamação , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
8.
Food Chem Toxicol ; 135: 110929, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31678262

RESUMO

One of the most spread group of phenolics are flavonoids. Many studies focusing on the digestion and bioavailability of flavonoids have been carried out. Several possible directions of flavonoid metabolism are suspected and described in the literature. The aim of the present study was to evaluate the bioactivity of 8 flavonoid 3-O- and 7-O- glucuronides and 7 free aglycones on inflammatory response of PMNs and HUVECs in the context of their fate in humans after oral intake. The present study for the first time compared the activity of several most popular in plant flavonol and flavone aglycones and their beta-glucuronides. The results showed that in all in vitro experiments only aglycones have anti-inflammatory activity in PMNs and HUVECs models in the concentration range 1-50 µM. The most significant influence on the inflammatory response was observed in the case of HUVECs. Compounds were able to down-regulate levels of adhesion molecules (ICAM, VCAM and E-selectin). The possible deconjugation phenomenon at the inflammation site was evaluated using enzymes produces by stimulated PMNs. This is the first report suggesting the role of ß-glucuronidase in the inflammatory process taking place on the inflammation site. Additionally, the anti-inflammatory effect was significantly better for flavones.


Assuntos
Anti-Inflamatórios/farmacologia , Flavonoides/farmacologia , Glucuronídeos/farmacologia , Neutrófilos/efeitos dos fármacos , Anti-Inflamatórios/toxicidade , Moléculas de Adesão Celular/metabolismo , Endotélio/metabolismo , Flavonoides/toxicidade , Glucuronídeos/toxicidade , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Neutrófilos/metabolismo
9.
J Ethnopharmacol ; 248: 112360, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31676403

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In folkloric medicine the dried rhizome of the Jamaican sarsaparilla (Smilax ornate Lem.), is given as a decoction to treat chronic rheumatism and rheumatoid arthritis. This particular claim has been scientifically validated; however, the mechanism for its anti-inflammatory activity is still unknown and hence, it forms the reason for this investigation. OBJECTIVE: The objective of this study is to investigate the mechanism of the anti-inflammatory activity of the methanol extract of Smilax ornate Lem. METHOD: The methanol extract was prepared using the soxhlet apparatus. The preliminary mechanism of action was investigated using models of oedema induced by histamine, bradykinin and prostaglandin E2. RESULTS: For the histamine-induced oedema model, the methanol extract (400 mg/kg) reduced the oedema formation, however, it was not significant (P > 0.05). For the bradykinin-induced oedema model, the methanol extract (400 mg/kg) exhibited significant (P < 0.05) anti-inflammatory activity when compared with that of the control (saline) group, with an onset on 60 min and a duration of 2 h. For the prostaglandin-induced oedema model, the methanol extract (400 mg/kg) exhibited significant (P < 0.05) anti-inflammatory activity when compared with that of its control group, with an onset on 120 min and a duration of 1.5 h. CONCLUSION: The methanol extract of Smilax ornata Lem. produced significant anti-inflammatory activity in the bradykinin-induced and prostaglandin-induced oedema models. It is possible that the mechanism by which it acts is by reducing the concentration or blocking the action of these mediators.


Assuntos
Anti-Inflamatórios/farmacologia , Edema/prevenção & controle , Inflamação/prevenção & controle , Metanol/química , Extratos Vegetais/farmacologia , Smilax , Solventes/química , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/toxicidade , Bradicinina , Dinoprostona , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/patologia , Histamina , Inflamação/induzido quimicamente , Inflamação/patologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Ratos Sprague-Dawley , Rizoma , Smilax/química , Smilax/toxicidade
10.
J Ethnopharmacol ; 248: 112349, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31756450

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Arenga pinnata (Wurmb) Merr. is a medicinal and edible plant belonging to family Palmae. The fruits of this plant were used in traditional folk medicine due to its analgesia and anti-inflammatory activities. This study aimed to investigate the analgesic and anti-inflammatory properties and the mechanism of the ethanol extract of A. pinnata (Wurmb) Merr. fruit (EAF) on different experimental models. MATERIALS AND METHODS: High-performance liquid chromatography (HPLC) was used to determine the chromatographic profile and to analyze the composition of EAF. In the acute toxicity test, all mice were orally administered EAF at a maximum dosage of 26 g/kg and were then monitored for 14 days. The potential analgesic activity of EAF was evaluated by using animal pain models, namely the acetic acid-induced writhing test and the hot plate test in mice. The underlying mechanisms of analgesia were determined by pretreating with naloxone, capsaicin and cinnamaldehyde to evaluate the involvement of the opioid system and transient receptor potential channels (TRP channels). The anti-inflammatory activity of EAF was evaluated by using the following inflammatory animal models: xylene-induced ear edema in mice and Complete Freund's adjuvant (CFA)-induced paw swelling in rats. EAF was orally administered at the doses of 1.625, 3.25 and 6.5 g/kg in mice and 1.125, 2.25 and 4.5 g/kg in rats. The underlying mechanism of the anti-inflammatory activity was determined by enzyme-linked immunosorbent assay (ELISA) kits and real time-PCR used to measure the expression levels of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2). Western blot analysis was used to determine the expression levels of proteins related to the nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPK) signaling pathways in paw tissues. RESULTS: Five compounds, namely (5-(hydroxymethyl) furan-2-yl) methanediol,4'-hydroxy-N-(4-hydroxy-3-methoxybenzoyl)-3',5'-dimethoxybenzamide, (+)-lyonirenisol-3a-O-ß-D-glucopyranoside, (-)-lyonirenisol-3a-O-ß-glucopyranoside and liquiritin, were firstly identified from A. pinnata (Wurmb) Merr. fruit by HPLC-UV analysis. In the acute toxicity test, no treatment-related toxicological signs or mortality was observed in mice administered doses up to 26 g/kg. Bodyweight was not obviously different among the treatment groups and the vehicle group. EAF significantly inhibited the pain response induced by acetic acid and increased the latency time in the hot plate test in mice. The anti-nociception effect of EAF in the formalin test was not alleviated by pretreatment with naloxone. However, the nociception induced by injection with capsaicin and cinnamaldehyde was significantly reduced by EAF. Compared with vehicle treatment, EAF significantly inhibited the formation of xylene-induced ear edema and CFA adjuvant-induced paw swelling. EAF markedly inhibited the production of IL-1ß, TNF-α, PGE2 and IL-6 induced by CFA in paw tissues. Furthermore, the phosphorylation of IKKα, IKKß, IκBα, p38, ERK1/2, and JNK and the nuclear translation of NF-κB p65 induced by CFA in paw tissues were significantly inhibited by EAF treatment compared with vehicle treatment. CONCLUSION: For the first time, this study provides pharmacological evidence for the analgesic and anti-inflammatory activities of EAF and the underlying mechanism, suggesting that EAF might be a potential candidate for reducing pain and inflammatory disorders.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Arecaceae , Edema/prevenção & controle , Etanol/química , Frutas , Inflamação/prevenção & controle , Dor/prevenção & controle , Extratos Vegetais/farmacologia , Solventes/química , Analgésicos/isolamento & purificação , Analgésicos/toxicidade , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/toxicidade , Arecaceae/química , Arecaceae/toxicidade , Citocinas/metabolismo , Modelos Animais de Doenças , Edema/metabolismo , Feminino , Frutas/química , Frutas/toxicidade , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Dor/fisiopatologia , Limiar da Dor/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Ratos Sprague-Dawley
11.
BMC Complement Altern Med ; 19(1): 373, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31856816

RESUMO

BACKGROUND: Tempeh is a widely known fermented soybean that contains elevated level of bioactive contents. Our previous study has shown that anaerobic fermented Nutrient Enriched Soybean Tempeh (NESTE) with increase amino acid and antioxidant levels possessed better hepatoprotective effect than raw soybean. METHODS: In this study, the anti-inflammatory effect of the NESTE aqueous extract and raw soybean aqueous extract (SBE) were evaluated by quantifying the inhibition of IL-1ß, TNF-α and nitric oxide (NO) secretion in LPS treated RAW 264.7 cell in vitro. On the other hand, in vivo oral acute toxicity effect of the extract was tested on mice at the dose of 5000 mg/kg body weight. In vivo oral analgesic effect of both aqueous extracts at 200 and 1000 mg/kg body weight was evaluated by the hot plate test. RESULTS: In the in vitro anti-inflammatory study, 5 mg/mL NESTE was able to inhibit 25.50 ± 2.20%, 35.88 ± 3.20% and 28.50 ± 3.50% of NO, IL-1ß and TNF-α production in LPS treated RAW 264.7 cells without inducing cytotoxic effect on the cells. However, this effect was lower than 4 µg/mL of curcumin, which inhibited NO, IL-1ß and TNF-α production by 89.50 ± 5.00%, 78.80 ± 6.20% and 87.30 ± 4.00%, respectively. In addition, 1.5 to 2.5-fold increase of latency period up to 120 min for mice in the hot plate test was achieved by 1000 mg/kg NESTE. The analgesic effect of NESTE was better than 400 mg/kg of acetyl salicylic acid, which only increased ~ 1.7-fold of latency period up to 90 min. Moreover, NESTE did not show acute toxicity (no LD50) up to 5000 mg/kg body weight. CONCLUSION: NESTE is a nutritious food ingredient with potential anti-inflammatory and analgesic effects.


Assuntos
Analgésicos , Anti-Inflamatórios , Alimentos de Soja , Analgésicos/farmacologia , Analgésicos/toxicidade , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/toxicidade , Comportamento Animal/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico , Células RAW 264.7 , Testes de Toxicidade Aguda
12.
Int Immunopharmacol ; 76: 105856, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31480005

RESUMO

The search for new drugs with anti-inflammatory properties remains a challenge for modern medicine. Among the various strategies for drug discovery, deriving new chemical entities from known bioactive natural and/or synthetic compounds remains a promising approach. Here, we designed and synthesized CVIB, a codrug developed by association of carvacrol (a phenolic monoterpene) with ibuprofen (a non-steroidal anti-inflammatory drug). In silico pharmacokinetic and physicochemical properties evaluation indicated low aqueous solubility (LogP ≥5.0). Nevertheless, the hybrid presented excellent oral bioavailability, gastrointestinal tract absorption, and low toxicity. CVIB did not present cytotoxicity in peripheral blood mononuclear cells (PBMCs), and promoted a significant reduction in IL-2, IL-10, IL-17, and IFN-γ cytokine levels in vitro. The LD50 was estimated to be approximately 5000 mg/kg. CVIB was stable and detectable in human plasma after 24 h. In vivo anti-inflammatory evaluations revealed that CVIB at 10 and 50 mg/kg i.p. caused a significant decrease in total leukocyte count (p < 0.01) and provoked a significant reduction in IL-1ß (p < 0.01). CVIB at 10 mg/kg i.p. efficiently decreased inflammatory parameters better than the physical mixture (carvacrol + ibuprofen 10 mg/kg i.p.). The results suggest that the codrug approach is a good option for drug design and development, creating the possibility of combining NSAIDs with natural products in order to obtain new hybrid drugs may be useful for treatment of inflammatory diseases.


Assuntos
Anti-Inflamatórios , Cimenos , Ibuprofeno , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Carragenina , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cimenos/química , Cimenos/farmacocinética , Cimenos/uso terapêutico , Cimenos/toxicidade , Citocinas/imunologia , Combinação de Medicamentos , Humanos , Ibuprofeno/química , Ibuprofeno/farmacocinética , Ibuprofeno/uso terapêutico , Ibuprofeno/toxicidade , Dose Letal Mediana , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Camundongos , Pleurisia/induzido quimicamente , Pleurisia/tratamento farmacológico , Pleurisia/imunologia , Solubilidade
13.
J Steroid Biochem Mol Biol ; 194: 105457, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31454535

RESUMO

Breast cancer is the most prevalent cancer in women affecting about 12% of world's female population. It is a multifactorial disease, mostly invasive in nature. Diosgenin and related compounds are potent antiproliferative agents. Carbamate derivatives have been synthesized at C26 of furostene ring after opening spiroketal bond (F-ring) of diosgenin. Compound 10 possessed significant antiproliferative activity against human breast cancer cells by arresting the population at G1 phase of cell division cycle and induced apoptosis. Induction of apoptosis was observed through the caspase signalling cascade by activating caspase-3. Moreover, carbamate 10 exhibited moderate antiinflammatory activity by decreasing the expression of cytokines, TNF-α and IL-6 in LPS-induced inflammation in primary macrophage cells. Furthermore, compound 10 significantly reduced Ehrlich ascites carcinoma significantly in mice. It was well tolerated and safe in acute oral toxicity in Swiss albino mice. The concomitant anticancer and antiinflammatory properties of carbamate 10 are important and thus, can further be optimized for a better anti-breast cancer candidate.


Assuntos
Anti-Inflamatórios , Antineoplásicos , Carbamatos , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Carbamatos/farmacologia , Carbamatos/uso terapêutico , Carbamatos/toxicidade , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Simulação de Acoplamento Molecular , Carga Tumoral/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
15.
J Ethnopharmacol ; 242: 112052, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31265886

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Combretum aculeatum Vent was traditionally used in Sudan, Eretria and Ethiopia as anti-inflammatory in case of skin inflammation, catarrh, wounds, scorpion stings and snake bites. Nevertheless, there is no scientific information regarding this activity. AIM OF STUDY: The present study aimed to evaluate the phytochemical constituents and the scientific basis for the traditional use of Combretum aculeatum Vent through studying its anti-inflammatory properties for the first time to illustrate the putative mechanisms behind this bioactivity. MATERIALS AND METHODS: the ethanolic extract was partitioned by petroleum ether, methylene chloride, ethyl acetate, and n-butanol saturated with water. The petroleum ether fraction was saponified and the saponifiable and unsaponifiable fractions were analyzed on GC/MS. The different fractions were subjected to phytochemical investigation to isolate pure compounds. In-vivo anti-inflammatory activity of the ethanolic extract was evaluated using carrageenan induced rat paws edema method at doses of 200, 400 and 600 mg/kg and proved based on histopathological and biochemical parameters. RESULTS: Five known compounds were isolated for the first time from the aerial parts of Combretum aculeatum Vent: quercetin, vitexin, isorhamnetin 3-O-ß-glucoside, isovitexin and rutin, in addition to two previously isolated ones: ß-sitosterol and its glucoside. The ethanolic extract evidenced in-vivo anti-inflammatory activity by oral intake of 400 mg/kg of the ethanolic extract significantly (P ≥ 0.05) decreased the paw edema (only 32±1.9% increase in paw weight after 4 h) compared to indomethacin (28.6±2.5%). Moreover, it significantly suppressed the serum malondialdehyde (MDA) and nitric oxide (NO) and increased the GSH to be 11.76±0.85, 5.13±0.62 µmol/mL and 5.66±0.28 µM/mL, respectively. It diminished the serum cytokines TNF-α, IL-6 and IL-1ß levels to be 39.1±1.2, 32.6±1.1 and 37.5±1.2 pg/mL, respectively. Results are accompanied by histopathological examination. CONCLUSION: Overall, the results herein presented significant anti-inflammatory properties traditionally ascribed to Combretum aculeatum Vent. Moreover, the biochemical mechanisms associated to this action were highlighted, introducing new prospects for the development of effective anti-inflammatory herbal medicinal products.


Assuntos
Anti-Inflamatórios , Combretum , Edema/tratamento farmacológico , Compostos Fitoquímicos , Extratos Vegetais , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Carragenina , Citocinas/imunologia , Edema/induzido quimicamente , Edema/imunologia , Edema/patologia , Dose Letal Mediana , Masculino , Camundongos , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/toxicidade , Componentes Aéreos da Planta , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Ratos , Sudão
16.
Drug Dev Res ; 80(6): 800-806, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31243798

RESUMO

Gymnosperma glutinosum (Spreng) Less (Asteraceae) is a shrub used in traditional medicine for the treatment of inflammatory and renal diseases. The ent-dihydrotucumanoic acid (DTA) is a diterpene obtained from G. glutinosum. This study evaluated the antioxidant, genotoxic, and diuretic properties of DTA, as well as its in vitro and in vivo anti-inflammatory actions. The antioxidant actions of DTA were assessed with the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) assays, the genotoxic action was assessed with the comet assay, and the diuretic effects of DTA were assessed using metabolic cages. The anti-inflammatory actions were evaluated using primary murine peritoneal macrophages stimulated with LPS and the λ-carrageenan-induced hind paw edema test. DTA lacked antioxidant (IC50 > 25,000 µg/mL) activity in the ABTS, FRAP, and DPPH assays. DTA at 500-1,000 µg/mL showed moderate genotoxicity. In LPS-stimulated macrophages, DTA showed IC50 values of 74.85 µg/mL (TNF-α) and 58.12 µg/mL (NO), whereas the maximum inhibition of IL-6 (24%) and IL-1ß (36%) was recorded at 200 µg/mL. DTA induced in vivo anti-inflammatory effects with ED50 = 124.3 mg/kg. The in vitro anti-inflammatory activity of DTA seems to be associated with the decrease in the release of TNF-α and NO. DTA promoted the excretion of urine (ED50 = 86.9 mg/kg), Na+ (ED50 = 66.7 mg/kg), and K+ (ED50 = 8.6 mg/kg). The coadministration of DTA with L-NAME decreased the urinary excretion shown by DTA alone. Therefore, the diuretic activity is probably associated with the participation of nitric oxide synthase. In conclusion, DTA exerted anti-inflammatory and diuretic effects, but lacked antioxidant effects.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Diuréticos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Antioxidantes/química , Antioxidantes/uso terapêutico , Antioxidantes/toxicidade , Asteraceae , Benzotiazóis/química , Compostos de Bifenilo/química , Carragenina , Ensaio Cometa , Citocinas/metabolismo , Diuréticos/química , Diuréticos/uso terapêutico , Diuréticos/toxicidade , Edema/induzido quimicamente , Edema/tratamento farmacológico , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Picratos/química , Ácidos Sulfônicos/química
17.
Food Chem Toxicol ; 131: 110583, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31220533

RESUMO

We investigated the anti-inflammatory activity of protopine (PTP) and sought to determine its mechanism of action in LPS-stimulated BV2 cells and a carrageenan (CA)-induced mouse model. Treatment with PTP (5, 10, and 20 µM) significantly suppresses the secretion of NO and PGE2 in a concentration-dependent manner without affecting cell viability by downregulating iNOS and COX-2 expression in LPS-induced BV2 cells. PTP also attenuates the production of pro-inflammatory chemokines, such as MCP-1, and cytokines, including TNF-α, IL-1ß and IL-6, and augments the expression of the anti-inflammatory cytokine IL-10. In addition, PTP suppresses the nuclear translocation of NF-κB by hindering the degradation of IκB and downregulating the expression of mitogen-activated protein kinases (MAPKs), including p38, ERK1/2 and JNK protein. Furthermore, PTP treatment significantly suppresses CA-induced paw oedema in mice compared to that seen in untreated mice. Expression of iNOS and COX-2 proteins is also abrogated by PTP (50 mg/kg) treatment in CA-induced mice. PTP treatment also abolishes IκB phosphorylation, which hinders the activation of NF-κB. Collectively, these results suggest PTP has potential for attenuating CA- and LPS-induced inflammatory symptoms through modulation of MAPKs/NF-κB signaling cascades.


Assuntos
Anti-Inflamatórios/uso terapêutico , Benzofenantridinas/uso terapêutico , Alcaloides de Berberina/uso terapêutico , Inflamação/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Animais , Anti-Inflamatórios/toxicidade , Benzofenantridinas/toxicidade , Alcaloides de Berberina/toxicidade , Carragenina , Linhagem Celular Transformada , Quimiocinas/metabolismo , Inflamação/induzido quimicamente , Lipopolissacarídeos , Camundongos Endogâmicos ICR , Proteínas Quinases Ativadas por Mitógeno/química , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Subunidade p50 de NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos
18.
Pharmacol Rep ; 71(4): 603-613, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31176102

RESUMO

BACKGROUND: Polydatin (PD) is a compound, originally isolated from the root and rhizome of the Chinese herb Polygonum cuspidatum. To date, various biological properties of this compound, such as analgesic, anti-pyretic or diuretic effects, have been shown. Recently, anti-oxidant and anti-inflammatory properties have been widely postulated, yet PD instability and low bioavailability limit its beneficial actions. Therefore, it has been suggested that an encapsulation process may be a promising strategy for overcoming these limitations and increasing the therapeutic efficacy of PD. METHODS: We examined the effects of PD in two forms, including free and in PD-loaded polymeric nanocapsules, on lipopolysaccharide (LPS)-induced changes in hippocampal organotypic cultures. RESULTS: Our results indicated that free and encapsulated PD diminished cell death processes and attenuated the secretion of pro-inflammatory cytokines induced by LPS administration. Additionally, PD in both forms strongly inhibited the production of nitric oxide and down-regulated the level of iNOS enzyme in LPS-stimulated hippocampal cultures. CONCLUSION: Taken together, our study showed that PD exerts anti-inflammatory and anti-oxidant properties in LPS-treated hippocampal organotypic cultures. Furthermore, we show that the encapsulation procedure preserved the features of the free form of this compound, and therefore, the polymeric nanocapsules containing PD may be used as a novel and promising delivery system in therapeutic strategies.


Assuntos
Anti-Inflamatórios/farmacologia , Glucosídeos/farmacologia , Hipocampo/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Nanocápsulas/química , Fármacos Neuroprotetores/farmacologia , Estilbenos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/toxicidade , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Composição de Medicamentos , Glucosídeos/química , Glucosídeos/toxicidade , Hipocampo/imunologia , Hipocampo/patologia , Nanocápsulas/toxicidade , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/toxicidade , Ratos Sprague-Dawley , Estilbenos/química , Estilbenos/toxicidade , Propriedades de Superfície , Técnicas de Cultura de Tecidos , Testes de Toxicidade
19.
Food Chem Toxicol ; 131: 110539, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31158404

RESUMO

The chemical characterization and protective role against ethanol-induced gastric ulcerated rats of a polysaccharide fraction from Bletilla striata (BSP) collected by ultrafiltration membrane approach were evaluated. This BSP faction was consisted of mannose and glucose at a molar ratio of 2.4:1 approximately, with a molecular weight of 146 KDa. FT-IR, NMR and XRD spectra indicated that BSP faction contained α-Man and ß-Glc residues with low overall crystallinity. The polysaccharide exhibited significant scavenging activities of ABTS and FRAP, as well as non-toxicity against human gastric epithelial GES-1 cells. Oral administration with 100 mg/kg of BSP for 3 days continuously could significantly prevent the formation of ethanol-induced gastric mucosal lesion. It could also reduce the levels of pro-inflammatory cytokines, including TNF-α, IL-1ß, IL-6, and IL-18, and MPO activity in gastric tissue. Additionally, the BSP faction exhibited antioxidant activity, increased the content of PEG2 as a defensive factor, and suppressed MAPK/NF-κB signaling pathway in gastric tissue. These results indicated that the gastroprotective activity of BSP faction could be attributed to the reduction of pro-inflammatory cytokines and oxidative stress and the inhibition of MAPK/NF-κB pathways. Our results provided substantial evidence that BSP could be a promising phytomedicine for gastric ulcer prevention.


Assuntos
Fármacos Gastrointestinais/farmacologia , Orchidaceae/química , Polissacarídeos/farmacologia , Úlcera Gástrica/tratamento farmacológico , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/toxicidade , Linhagem Celular , Citocinas/metabolismo , Dinoprostona/metabolismo , Etanol , Depuradores de Radicais Livres/isolamento & purificação , Depuradores de Radicais Livres/farmacologia , Depuradores de Radicais Livres/toxicidade , Mucosa Gástrica/patologia , Fármacos Gastrointestinais/isolamento & purificação , Fármacos Gastrointestinais/toxicidade , Humanos , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Polissacarídeos/isolamento & purificação , Polissacarídeos/toxicidade , Ratos , Transdução de Sinais/efeitos dos fármacos , Úlcera Gástrica/induzido quimicamente , Superóxido Dismutase/metabolismo
20.
Eur J Med Chem ; 176: 456-475, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31128448

RESUMO

H2S donors are substitutes of H2S with various biological activities like inhibiting the inflammatory response and protecting myocardial cells from injury. In order to confirm whether the H2S donors have drug-like properties, two series thiophosphamide H2S donors were evaluated including toxicity, bioactivity and pharmacokinetic properties in vivo and in vitro. The following results were obtained. Firstly, all the compounds released H2S under measuring condition; with the increase of pH value, the H2S release rate of all the compounds decreased and the amount reduced, but pH value had little effect on the maximum release of H2S. Secondly, in the organs and tissues of rats, the compounds released H2S in the same way as in PBS. In plasma, compound 1 reached the Cmax after administration 55 min, and no compound 1 was detected after 12 h; for compound 18, the Cmax reached only after administration 100 min, and after 6 h, compound 18 was not detected; in organs and tissues, the H2S-release rates were different from those in PBS, but the mechanism of H2S release was the same. Thirdly, in the test of toxicity, all the compounds displayed low toxicities to 5 cancer cells and W138 cell lines; compounds 1 and 18 had slight effect on the physiological tissue and function of rat liver at low concentration; the compounds had almost no effect on the hatching rate, survival rate of zebrafish embryos, and the spontaneous movement of zebrafish embryos at below 0.5 µM, but when they were over 1 µM, the compounds displayed inhibitory effect in the manner of concentration dependence. Fourthly, in the course of anti-inflammatory test, all the tested compounds significantly reduced the level of TNF-α and increased the level of IL-10; when they were 100 µM, the levels of IL-10 were three times as high as those in the control group. Among them, compounds 10 and 18 displayed stronger activities than the others. In addition, the compounds protected H9c2 cells from injure and improved myocardial injury through anti-oxidation pathway. In summary, the compounds have druglike properties due to low toxicity, better activity and good pharmacokinetic property. Therefore, they have potential to be as candidates to investigate further.


Assuntos
Anti-Inflamatórios/farmacocinética , Cardiotônicos/farmacocinética , Sulfeto de Hidrogênio/metabolismo , Compostos Organotiofosforados/farmacocinética , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/toxicidade , Cardiotônicos/síntese química , Cardiotônicos/química , Cardiotônicos/toxicidade , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Feminino , Humanos , Sulfeto de Hidrogênio/sangue , Sulfeto de Hidrogênio/química , Concentração de Íons de Hidrogênio , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Modelos Químicos , Miocárdio/metabolismo , Compostos Organotiofosforados/síntese química , Compostos Organotiofosforados/química , Compostos Organotiofosforados/toxicidade , Células RAW 264.7 , Ratos Wistar , Baço/efeitos dos fármacos , Baço/metabolismo , Baço/patologia , Temperatura , Teratogênios/síntese química , Teratogênios/química , Teratogênios/farmacocinética , Teratogênios/toxicidade , Peixe-Zebra
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