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Quercetin can inhibit the growth of cancer cells with the ability to act as chemopreventers. Its cancer-preventive effect has been attributed to various mechanisms, including the induction of cell-cycle arrest and/or apoptosis as well as the antioxidant functions. Nuclear factor kappa-B (NF-κB) is a signaling pathway that controls transcriptional activation of genes important for tight regulation of many cellular processes and is aberrantly expressed in many types of cancer. Inhibitors of NF-κB pathway have shown potential anti-tumor activities. However, it is not fully elucidated in colon cancer. In this study, we demonstrate that quercetin induces apoptosis in human colon cancer CACO-2 and SW-620 cells through inhibiting NF-κB pathway, as well as down-regulation of B-cell lymphoma 2 and up-regulation of Bax, thus providing basis for clinical application of quercetin in colon cancer cases.

Background: Ficus deltoidea Jack or locally known as Mas Cotek belongs to the family Moraceae is a conventionally used Malaysian native medicinal plant. Objectives: The aim is to determine the anti-inflammatory mechanism of various solvent fractions of F. deltoidea methanol extract against Lipopolysaccharide (LPS)-induced nuclear factor-kappa B (NF-κB) inflammatory pathway in murine macrophage 264.7 cells and to identify the chemical constituents present in the active fraction. Materials and Methods: The effect of crude methanolic extract and its fractions (hexane, chloroform, ethyl acetate, and butanol) on murine macrophages against LPS-induced pro-inflammatory cytokines (interleukin [IL]-Iβ, tumor necrosis factor alpha [TNF-α], and IL-6) and biomarkers were tested using enzyme-linked immunosorbent assay and immunoblot analysis. The chemical constituents present in the active fraction were identified using liquid chromatography mass spectrometry and liquid chromatography tandem mass spectrometry analysis. Results: The findings indicated that among all the fractions, the ethyl acetate fraction of F. deltoidea substantially inhibits the LPS-induced inflammatory mediators such as nitric oxide (NO) and pro-inflammatory cytokine production including TNF-α, IL-6, and IL-1 β in a dose-dependent manner. The expression of inducible NO synthase, NO synthase, and cyclooxygenase-2 were also effectively downregulated by the treatment of ethyl acetate fraction. Moreover, it also suppressed the expression of LPS-induced NF-κB translocation correlated with the inhibition of NF-κB (inhibitor of kappa B alpha) degradation. The presence of bioactive phenolics, especially flavonoids such as catechin, vitexin, dodecadienyl coumaric acid, (epi)-afzelechin-(epi)-catechin, genistein, and apigenin derivatives were identified in the ethyl acetate fraction of F. deltoidea. Conclusion: Overall, it has been recommended that the ethyl acetate fraction of F. deltoidea could be utilized as a potential natural anti-inflammatory agent. [ABSTRACT FROM AUTHOR]

Background: Sepsis, one of the major life-threatening conditions and responsible for approximately 40% of clinical Acute Lung Injury (ALI) patients. Nevertheless, there are no specific medications available to reduce mortality. Bilobalide, a natural bioactive component present in Ginkgo biloba, has several medicinal properties. However, the effect of Bilobalide against ALI residues unknown. And so, the therapeutic property and underlying molecular mechanism of Bilobalide was investigated against sepsis-prompted ALI in the murine model. Materials and Methods: In C57BL/6J mice model, sepsis introduced by cecal ligation and puncture (CLP) to induce lung injury. Results: Our results showed that Bilobalide treatment increased the survival rate of CLP-induced sepsis mice. Pretreatment with Bilobalide substantially inhibits the sepsis-induced lung exudation, which is exposed by measuring the wet/dry weight of lung and lung permeability of the mice. Also, Bilobalide attenuated the histopathological alterations alike alveolar hemorrhage and infiltration of inflammatory cells are assessed by hematoxylin and eosin staining, tumor necrosis factor-α, interleukin (IL)-1 β, IL-6 and macrophage inflammatory protein-2 pro-inflammatory mediators and myeloperoxidase are measured by enzyme-linked immunosorbent assay. Molecular mechanism of Bilobalide in lung inflammation whereby cyclooxygenase-2 (COX-2), induced nitric oxide synthase (iNOS), heme oxygenase-1 (HO-1), and the activation of the nuclear factor-kappa B (kB) (p65)/IkB are determined by immunoblotting technique. Moreover, pretreatment of Bilobalide significantly downregulated the expression of COX-2, iNOS, and phosphorylation of p65 and induced the IkB activation in the lung. Further, Bilobalide prevented the oxidative stress by upregulating the expression of HO-1 in lung tissues, and gene expression of sepsis-induced anti-oxidative enzymes (catalase, MnSOD, CuZnSOD, and GPx-1) in the Bilobalide-treated mice were induced dose-dependently and it determined by a quantitative-real time-polymerase chain reaction. Conclusion: Hence, we suggested Bilobalide has the ability to act as a possible therapeutic candidate against sepsis caused ALI. [ABSTRACT FROM AUTHOR]

Background: Nowadays, the use of plant extracts is increasing in the world for the prevention and treatment of ulcer. Objective: The objective of this study was to explore the underlying mechanism of action of fisetin on ethanol-induced gastric ulcer model. Materials and Methods: In this study, gastric mucosal lesions were induced by ethanol in rats. Five groups of rats were formed based on the treatment administered: model group (model), omeprazole (40 mg/kg) group (omeprazole), high-dose fisetin group (100 mg/kg, H-fisetin), medium-dose fisetin group (50 mg/kg, M-fisetin), and low-dose fisetin group (25 mg/kg, L-fisetin). Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α levels were assessed in serum. The expression of peroxisome proliferator-activated receptor (PPAR)-γ, nuclear factor-kappa B (NF-κB), and p38-mitogen-activated protein kinase (p38-MAPK) in the gastric mucosa was also measured. Results: In the case of the high-dose fisetin group, the level of TNF-α, IL-1β, and IL-6 decreased from 9.57 pg/mL to 5.19 pg/mL, from 0.59 pg/mL to 0.27 pg/mL, and from 37.96 pg/mL to 21.09 pg/mL, respectively. In the case of the omeprazole group, the level of TNF-α, IL-1β, and IL-6 decreased to 4.38 pg/mL, 0.27 pg/mL, and 18.58 pg/mL, respectively. The expression of PPAR-γ protein in the high-dose fisetin and omeprazole groups was about 1.5 times higher than that in the model group. Compared with the model group, the expression of NF-κB protein reduced to 0.34 level and 0.47 level in the omeprazole and high-dose fisetin groups, respectively. Compared with the model group, the expression of p38-MAPK protein reduced to 0.55 level and 0.68 level in the omeprazole and high-dose fisetin groups, respectively. Conclusion: Fisetin might relieve the symptoms of ethanol-induced gastric ulcer in rats through the regulation of NF-κB pathway. [ABSTRACT FROM AUTHOR]

Background: Rhinitis is an allergen-induced, immunoglobulin E (IgE)-mediated, chronic immune-inflammatory disease affecting individuals worldwide. Chrysin has been well documented for its anti-allergic potential. Aim: This study aimed to determine the efficacy and mechanism of action of chrysin against allergic rhinitis (AR) induced by ovalbumin (OVA) in experimental mice. Materials and Methods: Induction of AR was performed in BALB/c mice via intraperitoneal administration sensitization and intranasal challenge with of OVA. Chrysin was concomitantly administered in mice at doses of 10, 20, and 40 mg/kg, p.o. Results: OVA challenge caused statistically significant (P < 0.05) increase in nasal rubbing, sneezing, and discharge as well as elevated serum histamine, β-hexosaminidase, IgE (OVA-specific and total) levels, whereas chrysin treatment at a dose of 20 and 40 mg/kg significantly (P < 0.05) inhibited these biomarkers and thus reduced nasal symptoms. The elevated total and differential cell count, splenic oxido-nitrosative stress, and myeloperoxidase levels after OVA administration decreased statistically significantly (P < 0.05) by chrysin. There was a significant increase in the levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-4, IL-1β, IL-4/interferon-gamma, IL-6, and IL-13 in nasal lavage fluid after OVA challenge, which was inhibited statistically significantly (P < 0.05) by chrysin. It also statistically significantly (P < 0.05) downregulated spleen GATA-3 and nuclear factor-kappa B (NF-κB), whereas upregulated T-box protein expressed in T cells (T-bet) and nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression in spleen. Histological alteration induced in nasal and spleen tissue after OVA challenge was statistically significantly (P < 0.05) ameliorated by chrysin treatment. Conclusion: Chrysin modulated GATA-3/T-bet pathways and inhibited NF-κB activation, thus attenuating the release of various inflammatory mediators (TNF-α, IL-1β, histamine, IgE, and β-hexosaminidase), Th2 cytokines (ILs), and oxido-nitrosative stress (Nrf2) to exert its anti-allergic potential in experimental AR. [ABSTRACT FROM AUTHOR]

Objectives: The acute lung injury was a very severe health consequence and it was allied with the highest morbidity as well as mortality rate among the peoples. The acute lung injury can be induced through the various direct or indirect causative factors such as serious septic conditions, inflammation of the lung tissues, swelling of the lungs, injury of inhalation, pulmonary vasculitis, pancreatitis, and severe burnings which can lead to the unrestrained inflammation. Materials and Methods: The sepsis was a major clinical syndrome that can cause by severe infection or injury and it was distinguished by the response to the entire body inflammation. The current research work aimed to assess the curative properties of fucoxanthin against the lipopolysaccharides (LPS)-induced acute lung injury in the experimental animal model. Results: The fucoxanthin treatment followed by the LPS administration was exhibited the marked reduction in the wet-to-dry ratio of the lungs, reduced level of infiltration of inflammatory cells in BALF, reduced the enzymatic action of myeloperoxidase in the lungs, reduced the interleukin-6 (IL-6), IL-1 β, and tumor necrosis factor-alpha levels, possessed the notable suppression and downregulation in the expression of immunoreactivity of inflammatory markers like NF-κB p65 and decreased the oozing of mucus and the inflammatory cellular infiltration in lung histopathology which is stimulated by the LPS administration. Conclusion: The fucoxanthin was effectively attenuated the LPS-stimulated acute lung injury in an animal model. Hence, it can be concluded that the fucoxanthin had potent therapeutic properties against the LPS-stimulated acute lung injury. [ABSTRACT FROM AUTHOR]

Background: Gastric ulcer is also known as stomach ulcer which is complex with multifactor-associated disease and shows high prevalent worldwide. It affects most of the people around the world, and the initiation and progression of the disease are due to the imbalance in the destructive and defensive mechanism and associated factors present in the mucosa of gastric. The current study is interested to evaluate the ethanolic extract of Sargassum fusiforme polysaccharides (SFPee) toward gastric ulcer induced by ethanol in rat model. Materials and Methods: S. fusiforme is a Chinese pharmacopeia and used as a medicinal ingredient. It contains polysaccharides, phlorotannins, and meroterpenoids which are the major contributors for its pharmacological properties. While the polysaccharides are the predominant ingredients, which account for 40%-60% of the algae dry weight. S. fusiforme polysaccharides show a potent antioxidation, anticancer, antiaging, and anticlotting function and thus promote health benefits. However, the mechanisms behind its pharmacological properties remain largely unknown. Here, we assessed the SFPee ameliorative effects on gastric ulcer induced by ethanol in male Wistar rats. We are also interested to identify the molecular machinery involvement of antigastric ulcer property of SFPee in gastric ulcer-induced rats. Results: Based on the investigation, the role of SFPee on gastric ulcer on various molecules, oxidative stress markers, antioxidant enzymes, the expression of nuclear factor-kappa B, I-B, nitrotyrosine, cyclooxygenase-2, and the assessment of the inflammatory response. Conclusion: Our results show that SFPee exhibited significant anti-inflammatory and antioxidant properties against ethanol-induced gastric ulcer by altering various molecules involved in the gastric ulcer initiation. [ABSTRACT FROM AUTHOR]

Objective: Argyreia speciosa is a popular Indian medicinal plant. It has long been used in the traditional Ayurvedic Indian medicine for various diseases. The present work was designed to evaluate anti-inflammatory potential of hydroalcoholic extract of A. speciosa roots using mouse model of HCl-induced acute lung injury (ALI) by conducting a dose-response studies. Materials and Methods: The extract was given once orally at a dose of 50, 100, or 200 mg/kg b.wt. 90 min before HCl administration. Lung tissue of different group of mice was analyzed for the recruitment of inflammatory cells, redox status, and mRNA expression of pro-inflammatory genes to evaluate the anti-inflammatory effects of the extract. Results: Our results showed that the extract reduced HCl-induced lung inflammation in a dose-dependent manner. The neutrophil numbers in bronchoalveolar lavage fluid (BALF) were almost completely abrogated at a dose of 100 mg/kg b. wt. The severe reduction in neutrophils was accompanied with reduced pulmonary edema as the total protein content in BALF was found to be decreased substantially. In addition, the extract prevented the HCl-mediated oxidative stress in lungs as reflected by the normalization of levels of reactive oxygen species, malondialdehyde, redox status, and catalase activity. Extract seems to blunt the activity of redox-sensitive transcription factor nuclear factor-kappa B (NF-κB) as it suppressed the gene expression of ALI-linked pro-inflammatory cytokines, namely, interleukin-1 β and tumor necrosis factor-alpha. Conclusion: Overall, our data provide evidence that cocktail of natural phytochemicals present in hydroalcoholic extract of A. speciosa protects against HCl-induced ALI in mice potentially by curbing oxidative stress and consequent activation of NF-κB in the tissue. [ABSTRACT FROM AUTHOR]

Background: Thymoquinone (TQ), the basic bioactive phytochemical constituent of seed oil of Nigella sativa, is one of these herbal drugs known for antidiabetic effects. This study was carried out to assess the effects of the possible role of TQ on nuclear factor kappa B (NF-κB) and oxidative DNA damage levels in experimental diabetic rats. Materials and Methods: Twenty-eight male Wistar Albino rats (200-250 g) were used as experimental subjects. The rats were divided into four groups, including the control, control supplemented with TQ (CT), diabetic (D), and diabetic supplemented with TQ (DT), each containing seven rats. The D and the DT groups were treated with 45 mg/kg streptozotocin (STZ) (intraperitoneal). TQ was administered 30 mg/kg/day for 21 days by oral gavage in the DT and the T groups. Results: It was determined that glucose, glycosylated hemoglobin (HbA1c) levels and alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase activities were decreased significantly and approached the control group in the DT group after TQ supplement (P < 0.05). Urea levels were the lowest in CT (P < 0.05). Oxidative DNA damage (8 hydroxy-2-deoxyguanosine) was increased in both of the diabetic groups (D and DT). The NF-κB levels were the highest in Group D (P < 0.05). Conclusion: It was observed that increased glucose and HbA1c levels and the indicators of liver and kidney damages were decreased significantly after TQ supplementation. Oxidative DNA damage and NF-κB levels were increased in the diabetic group, and TQ administration caused a statistically insignificant reduction. [ABSTRACT FROM AUTHOR]

Quercetin can inhibit the growth of cancer cells with the ability to act as chemopreventers. Its cancer-preventive effect has been attributed to various mechanisms, including the induction of cell-cycle arrest and/or apoptosis as well as the antioxidant functions. Nuclear factor kappa-B (NF-κB) is a signaling pathway that controls transcriptional activation of genes important for tight regulation of many cellular processes and is aberrantly expressed in many types of cancer. Inhibitors of NF-κB pathway have shown potential anti-tumor activities. However, it is not fully elucidated in colon cancer. In this study, we demonstrate that quercetin induces apoptosis in human colon cancer CACO-2 and SW-620 cells through inhibiting NF-κB pathway, as well as down-regulation of B-cell lymphoma 2 and up-regulation of Bax, thus providing basis for clinical application of quercetin in colon cancer cases. [ABSTRACT FROM AUTHOR]

Background: Artemisiae annuae herba (AAH) has been traditionally used as a drug for the treatment of malaria, heat stroke, bacterial infection, and fever in East-Asia. Although AAH has been used for the treatment of inflammation-related symptoms, the underlying mechanism of antiinflammatory activity of AAH is still unknown. Objective: We investigated whether AAH have an inhibitory effect on the production of pro-inflammatory mediators in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Materials and Methods: The investigation was forced on the inhibitory effect of AAH on the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, nitric oxide (NO), and inducible NO synthase (iNOS) in macrophages. Furthermore, we examined the effect of AAH on the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) pathways. Results: We found that AAH suppresses NO production and TNF-α, IL-6, and iNOS gene expression. Moreover, AAH inhibited the nuclear translocation of p65 and IκBα degradation in NF-κB pathway and decreased the extracellular signal-regulated kinase, p38, c-Jun NH2-terminal kinase phosphorylation in MAPK signaling pathway. Conclusions: Consequently, these results indicate that AAH contains antiinflammatory activity and this effect is derived from the repression on the activation of NF-κB and MAPKs pathways. We first demonstrated that antiinflammatory effect of AAH and its underlying mechanism in macrophage cells. [ABSTRACT FROM AUTHOR]

Background: Artemisiae annuae herba (AAH) has been traditionally used as a drug for the treatment of malaria, heat stroke, bacterial infection, and fever in East-Asia. Although AAH has been used for the treatment of inflammation-related symptoms, the underlying mechanism of antiinflammatory activity of AAH is still unknown., Objective: We investigated whether AAH have an inhibitory effect on the production of pro-inflammatory mediators in lipopolysaccharide-stimulated RAW 264.7 macrophage cells., Materials and Methods: The investigation was forced on the inhibitory effect of AAH on the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, nitric oxide (NO), and inducible NO synthase (iNOS) in macrophages. Furthermore, we examined the effect of AAH on the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) pathways., Results: We found that AAH suppresses NO production and TNF-α, IL-6, and iNOS gene expression. Moreover, AAH inhibited the nuclear translocation of p65 and IκBα degradation in NF-κB pathway and decreased the extracellular signal-regulated kinase, p38, c-Jun NH2-terminal kinase phosphorylation in MAPK signaling pathway., Conclusions: Consequently, these results indicate that AAH contains antiinflammatory activity and this effect is derived from the repression on the activation of NF-κB and MAPKs pathways. We first demonstrated that antiinflammatory effect of AAH and its underlying mechanism in macrophage cells.