Article

Lemon Verbena Infusion Consumption Attenuates Oxidative Stress in Dextran Sulfate Sodium-Induced Colitis in the Rat

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Abstract

Inflammatory bowel diseases (IBD) consist of an uncontrolled intestinal inflammation leading to mucosal disruption. This inflammation is accompanied by an excessive production of reactive oxygen species (ROS). Polyphenols are micronutrients with antioxidative and anti-inflammatory properties, and may play an interesting role in the prevention of intestinal inflammation. Lemon verbena (Aloysia triphylla) infusion is a popular herbal infusion rich in polyphenols (flavones and verbascoside). This study evaluated the preventive effects of lemon verbena infusion consumption against mild-to-moderate dextran sulfate sodium (DSS)-induced colitis in rats. Wistar rats drank water or lemon verbena infusion for 14 days. On day 15, half of the rats received DSS (4%) in their drink for 7 days. At the end of the experimental period, the colon was taken for histopathological examination and determination of myeloperoxidase (MPO) activity, antioxidant enzyme activities (superoxide dismutase [SOD], glutathione peroxidase [GPx], glutathione reductase [GR], catalase [CAT]), glutathione and lipid peroxidation. Lymphocyte populations were determined in blood, mesenteric nodes and Peyer's patches. Rats ingested daily 5.6 μmol of polyphenols. DSS reduced food intake and induced colitis, as reflected by histological lesions and increased MPO activity. Although these alterations were not significantly counteracted by lemon verbena consumption, the herbal infusion increased colonic SOD activity and decreased lipid peroxidation (malondialdehyde). Other oxidative stress markers (GPx, GR, CAT, glutathione) were not significantly modified. Our study shows that the preventive consumption of lemon verbena infusion offered some antioxidative protection during experimental colitis by stimulating SOD activity and decreasing lipid peroxidation.

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... Several authors have reported that DSS-induced colitis depends on various factors, such as molecular weight and concentration of DSS and duration of administration, but also on genetic, microbiological and nutritional factors [4,6]. Previous studies in our laboratory using DSS administration (4 % for 7 days) to rats fed a non-purified commercial rodent diet showed that such conditions induced only a mild-to-moderate colitis and a somewhat high variability in its intensity [9]. On the other hand, we observed that identical administration of DSS (4 % for 7 days) to rats fed a purified diet made of refined ingredients, and widely used for nutritional studies, induced more exacerbated symptoms of colitis [10]. ...
... The section for histological examination was treated as previously described [9]. Rats were scored individually. ...
... For each rat, the score was the mean of three colonic sections analysed blindly by two operators. Nine parameters were considered and scored as described [9]: epithelium and crypt destruction, cryptic dilation, PMN infiltration, mononuclear infiltration, oedema, dystrophic epithelium detachment, erosion, vascular congestion, and depth of inflammation. ...
Thesis
Les polyphénols, micronutriments abondants dans notre alimentation, sont bien connus pour leurs propriétés antioxydantes et anti-inflammatoires et leur consommation a été associée à un moindre risque de maladies chroniques (maladies cardiovasculaires, cancers…). Ces composés suscitent un intérêt croissant dans le domaine de la santé digestive. En effet, les polyphénols sont faiblement absorbés au niveau de l’intestin grêle et sont présents en quantité relativement importante dans le côlon. Les polyphénols et leurs métabolites pourraient donc exercer des effets bénéfiques à ce niveau. Des études expérimentales récentes suggèrent que les polyphénols pourraient aider à prévenir ou retarder la progression de l’inflammation colique. Le raisin est l’un des fruits les plus riches en polyphénols. Divers co-produits du raisin ont montré des effets bénéfiques vis-à-vis de différentes situations d'inflammation, effets souvent attribués à leur richesse en composés polyphénoliques. Les objectifs de cette thèse étaient tout d’abord d’évaluer l’impact du régime de base sur le développement de l’inflammation colique induite par le sulfate de dextran sodique (DSS) chez le rat (1) puis d’évaluer les effets d’une supplémentation nutritionnelle en extraits de marc de raisin (EMR) riches en polyphénols dans la prévention de l’inflammation colique induite par le DSS (2). Pour cela, des rats Wistar ont été nourris ad libitum durant 21 jours avec un régime standard ou un régime semi-synthétique (1) ou les animaux ont été nourris avec un régime semi-synthétique supplémenté ou non avec un EMR (2). Dans tous les cas, l’inflammation colique a été induite par administration de DSS à 4% dans l’eau de boisson pendant les 7 derniers jours de l’expérimentation. Les effets ont été évalués au niveau colique par analyse histologique, détermination de différents marqueurs de l'inflammation et de la défense antioxydante et évaluation de l'expression de différents gènes impliqués dans l’inflammation et le stress oxydant.La consommation préventive de trois EMRs, issus de deux cépages différents (Alicante et Pinot) exerce des effets bénéfiques sur le développement de l’inflammation colique induite par le DSS. Globalement, la consommation à titre préventif d’EMRs prévient la perte de poids, retarde l’apparition des symptômes de la maladie et limite le développement des atteintes tissulaires induites par le DSS. Les EMRs atténuent l’inflammation comme en témoigne la diminution de l’activité de la MPO et le maintien des taux coliques en cytokines pro-inflammatoires au niveau des animaux témoins. De plus, ces EMRs modulent les activités des enzymes antioxydantes. Les EMRs limitent également la surexpression de plusieurs gènes impliqués dans la réponse inflammatoires et le stress oxydant (COX-2, iNOS, ICAM-1, MMP-9…). De plus, nous avons montré que les EMRs provenant du cépage Alicante exercent des effets protecteurs plus marqués que l’EMR Pinot.Ainsi, ces résultats soulignent d’une part l’influence du régime alimentaire de base dans l’induction de l’inflammation colique. D’autre part, la consommation à titre préventif d’EMRs exerce des effets protecteurs sur le développement de l'inflammation colique induite par le DSS via la modulation de marqueurs de l’inflammation et de la défense antioxydante. Ces résultats pourraient permettre d’envisager de nouvelles stratégies nutritionnelles dans la prévention des maladies inflammatoires de l’intestin.
... and treated as described previously. 20 Rats were scored individually. Each rat's score represented the mean of three colonic sections analyzed in a blind fashion by two operators. ...
... MPO activity in colon samples was determined by evaluating guaiacol oxidation by MPO-produced hydroxyl radicals in the presence of hydrogen peroxide (H 2 O 2 ) as described previously. 20 Protein concentration was determined using a Pierce BCA protein assay kit (Perbio, Brebières, France). MPO activity was defined as the quantity of enzyme degrading 1 μmol H 2 O 2 min −1 and expressed in units (U) mg −1 protein. ...
... A stimulatory effect of polyphenols on SOD or GPx activity has been reported in various colitis models. 20,25 Such effects could result in attenuation of oxidative stress occurring during colitis. ...
Article
Several studies have reported that polyphenols may exert beneficial effects on inflammatory bowel disease. This study aimed to evaluate the effects of a preventive consumption of polyphenol-rich red grape pomace extracts (GPEs) on dextran sodium sulfate (DSS)-induced colitis in rats. Rats were fed for 21 days with a semi-synthetic diet enriched with a GPE (Alicante-S, Alicante-P and Pinot-S) and colitis was induced by DSS administration in drinking water (40 g L(-1) ) during the last 7 days of experimentation. GPEs attenuated clinical signs and colon shortening and Alicante GPEs limited histological lesions induced by DSS. GPEs curbed the increase in myeloperoxidase activity and modulated antioxidant enzyme activities. Moreover, GPEs prevented the DSS-induced increase of pro-inflammatory cytokine levels and the upregulation of various genes implicated in colitis such as intercellular adhesion molecule-1 (ICAM-1) and matrix metalloproteinase 9 (MMP-9). These results suggest that polyphenol-rich red GPEs could provide prevention against colon inflammation. This article is protected by copyright. All rights reserved.
... Several authors have reported that DSS-induced colitis depends on various factors, such as molecular weight and concentration of DSS and duration of administration, but also on genetic, microbiological and nutritional factors [4,6]. Previous studies in our laboratory using DSS administration (4 % for 7 days) to rats fed a non-purified commercial rodent diet showed that such conditions induced only a mild-to-moderate colitis and a somewhat high variability in its intensity [9]. On the other hand, we observed that identical administration of DSS (4 % for 7 days) to rats fed a purified diet made of refined ingredients, and widely used for nutritional studies, induced more exacerbated symptoms of colitis [10]. ...
... The section for histological examination was treated as previously described [9]. Rats were scored individually. ...
... For each rat, the score was the mean of three colonic sections analysed blindly by two operators. Nine parameters were considered and scored as described [9]: epithelium and crypt destruction, cryptic dilation, PMN infiltration, mononuclear infiltration, oedema, dystrophic epithelium detachment, erosion, vascular congestion, and depth of inflammation. ...
Article
Dextran sodium sulphate (DSS)-induced colitis is a widely used model for inflammatory bowel disease. However, various factors including nutrition may affect the development of this colitis. This study aimed to compare and characterize the impact of purified and non-purified basal diets on the development of DSS-induced colitis in the rat. Wistar rats were fed a non-purified or a semi-synthetic purified diet for 21 days. Colitis was then induced in half of the rats by administration of DSS in drinking water (4 % w/v) during the last 7 days of experimentation. At the end of the experimental period, colon sections were taken for histopathological examination, determination of various markers of inflammation (myeloperoxidase: MPO, cytokines) and oxidative stress (superoxide dismutase: SOD, catalase: CAT, glutathione peroxidase: GPx and glutathione reductase: GRed activities), and evaluation of the expression of various genes implicated in this disorder. DSS ingestion induced a more marked colitis in animals receiving the purified diet, as reflected by higher histological score and increased MPO activity. A significant decrease in SOD and CAT activities was also observed in rats fed the purified diet. Also, in these animals, administration of DSS induced a significant increase in interleukin (IL)-1α, IL-1β and IL-6. In addition, various genes implicated in inflammation were over-expressed after ingestion of DSS by rats fed the purified diet. These results show that a purified diet promotes the onset of a more severe induced colitis than a non-purified one, highlighting the influence of basal diet in colitis development.
... Nrf2 has been shown to be an important transcription factor induced by the antioxidant response [10]. Nrf2 could activate a battery of antioxidant genes, HO-1, NQO1 and other genes, which regulated oxidative stress, inflammatory reactions and apoptosis in various disorders [12,38,39]. Furthermore, NF-κB is also an important transcription factor that plays an important role in redox changes [14]. ...
... More and more studies have proved that oxidative stress could be regulated by multiple molecular mechanisms [38][39][40]. As research progresses, microRNAs has been shown to be one of the potential targets for the treatment of human diseases [41][42][43]. ...
Article
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The present study was performed to determine the protective effect of Zinc on the rat testicular ischemia-reperfusion (I/R) injury and its mechanism. In vivo, the pathological changes and the apoptosis index were significantly relieved in the rats with Low-dose Zinc pretreatment, compared to the I/R group. After Low-dose Zinc treatment, the levels of tissue Malondialdehyde (MDA) were significantly decreased, while tissue antioxidant indices were significantly increased. Meanwhile, the level of NF-κB was significantly lower compared to I/R group, while the levels of Nrf2-dependent antioxidant enzymes were significantly higher in Low-dose Zinc+I/R group. In vitro, Low-dose Zinc markedly increased Leydig cell (TM3) cell viability, and relieved testicular oxidative damage via down-regulating ROS. A total of 22 differently expressed microRNAs were screened out using microRNA microarray in rat testicular tissue caused by I/R injury, especially showing that miR-101-3p was selected as the target miRNA. Furthermore, the levels of Nrf2 and NF-κB were apparently increased/decreased in TM3 cells treated with Hypoxic/Reoxygenation (H/R) after miR-101-3p mimics/inhibitor. In addition, H/R-induced testicular oxidative damage was recovered in TM3 administrated with miR-101-3p inhibitor and si-Nrf2. Therefore, this study provided a novel insight for investigating protective effect of Zinc on testicular I/R injury by promoting antioxidation via miR-101-3p/Nrf2.
... Verbascoside has been isolated from some medicinal plants (Verbascum, Buddleja, Striga genus, and from species of the Gesneriaceae family) (Filho et al., 2012;Huang et al., 2013;Alipieva et al., 2014). The metabolite has anti-inflammatory properties: inhibition of paw edema formation in rat (Akdemir et al., 2011), inhibition of the induced nitric oxide synthase (NOS) enzyme (Marzocco et al., 2007), decreased ear edema formation in mice (Sánchez et al., 2013), inhibition of myeloperoxidase and nuclear factor kappa B (NF-B) (Paola et al., 2011), decreased levels of interferon gamma (IFN-␥), interleukin 1␤, TNF-␣, and an increase in superoxide dismutase (SOD) activity (Hausmann et al., 2007;Mazzon et al., 2009;Esposito et al. 2010;Lenoir et al., 2011). ...
... Other minor secondary metabolites in the M. deppeana EtOH extract, such as ursolic and oleanolic acids (triterpenes), and polyphenols such as apigenin and hesperetin have been identified in this medicinal plant, and it is well-known that these are potent inhibitors of the oxidative pathway of acute and chronic inflammation, decreasing free radical concentration and aiding in the regulation of the immune response through their indirect antioxidant effect in vivo (Recio et al., 2000;García-Rodríguez et al., 2012;Gutiérrez-Rebolledo et al., 2015;Kumar et al., 2016). In addition, verbascoside has been described as a compound that decreases LPO values and that also increases SOD activity during dextran sulfate sodium-induced colitis in rats (Lenoir et al., 2011). Other main metabolites identified in the EtOH extract included ursolic and oleanolic acids possess important anti-inflammatory and immune-modulatory activities (López-García et al., 2015;Tsao and Yin, 2015). ...
Article
Moussonia deppeana (Schltdl. & Cham.) Klotzsch ex Hanst., Gesneriaceae, known as tlachichinole, is a Mexican medicinal plant used for treatment of chronic inflammation-related diseases such as arthritis. In this paper, the main metabolite verbascoside was quantified in ethanolic extract; anti-arthritic and antioxidant activities were also evaluated in Complete Freund’s Adjuvant induced arthritis in mice, with complete hematological evaluation, and oxidative stress measure in edema and ganglionic tissues on day 28. In popliteal ganglion, CD4+ lymphocytes and tumor necrosis factor alpha concentration were measured in addition to histological analysis. Ethanolic extract contained 79.2 mg of verbascoside/g extract, and this extract at 450 mg/kg generated an inhibition of 24% over paw edema development and increased body weight gain on final day. For hematological parameters, same dose decreased total leukocytes and lymphocytes, as well as decreased oxidation rate over biomolecules in edema and ganglionic tissues, and increased antioxidant enzyme activity. In ganglionic tissue, CD4+ lymphocytes and tumor necrosis factor alpha level showed no differences at any tested dose compared to complete Freund’s adjuvant untreated group. Histological analysis of popliteal ganglion revealed moderate reduction of follicular hyperplasia, leukocyte infiltration and lipid inclusions at 450 mg/kg dose. Ethanolic extract of M. deppeana possesses anti-edematous activity associated to a moderate reduction in follicular hyperplasia, with immune-modulatory and antioxidant effects during experimental arthritis in mice.
... Lemon verbena (Aloysia citriodora (L.)) is an annual eatable herbaceous plant native to South America commonly used as tea, refreshing beverage, food, or spice. Traditional medicinal applications are related to digestion and nervous discomfort [11]. A literature search focusing on peer-reviewed publications showed that only limited data are available for lemon verbena in connection with muscular recovery after exercise. ...
... Analytical references demonstrate that water-based extracts out of lemon verbena leaves are high in polyphenols [12,13]. Several in vitro and in vivo studies have shown antioxidative and anti-inflammatory effects [11,[14][15][16][17][18]. Out of six human studies [19][20][21][22][23][24], only one human pilot study was published investigating lemon verbena extract on the muscular damage biomarker, creatine kinase and liver biomarker related to oxidative stress [19]. ...
Article
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Background Exhaustive exercise causes muscle damage accompanied by oxidative stress and inflammation leading to muscle fatigue and muscle soreness. Lemon verbena leaves, commonly used as tea and refreshing beverage, demonstrated antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effects of a proprietary lemon verbena extract (Recoverben®) on muscle strength and recovery after exhaustive exercise in comparison to a placebo product. Methods The study was performed as a randomized, placebo-controlled, double-blind study with parallel design. Forty-four healthy males and females, which were 22–50 years old and active in sports, were randomized to 400 mg lemon verbena extract once daily or placebo. The 15 days intervention was divided into 10 days supplementation prior to the exhaustive exercise day (intensive jump-protocol), one day during the test and four days after. Muscle strength (MVC), muscle damage (CK), oxidative stress (GPx), inflammation (IL6) and volunteer-reported muscle soreness intensity were assessed pre and post exercise. ResultsParticipants in the lemon verbena group benefited from less muscle damage as well as faster and full recovery. Compared to placebo, lemon verbena extract receiving participants had significantly less exercise-related loss of muscle strength (p = 0.0311) over all timepoints, improved glutathione peroxidase activity by trend (p = 0.0681) and less movement induced pain (p = 0.0788) by trend. Creatine kinase and IL-6 didn’t show significant discrimmination between groups. Conclusion Lemon verbena extract (Recoverben®) has been shown to be a safe and well-tolerated natural sports ingredient, by reducing muscle damage after exhaustive exercise. Trial registrationThe trial was registered in the clinical trials registry (clinical trial.gov NCT02923102). Registered 28 September 2016
... Indeed, most studies have focused on the effects of dietary supplementation before and/or during the induction of colitis. 39,[49][50][51][52] This is related to the fact that only recently has emerged MH as a therapeutic goal that would allow diminishing the risk of relapse in patients in remission for IBD. 8 , colitis was induced in rats by adding DSS in the drinking water for 6 days. Then, the animals received drinking water without DSS but with either a mixture of threonine, methionine, and monosodium glutamate (DSS-AA mixture) or a control isonitrogenous amount of alanine (DSS-Ala) for 3, 7, and 10 days. ...
... 56,57 Surprisingly, the amount of glutathione in its reduced (GSH) and oxidized (GSSG) forms in inflamed colon was not affected by colitis, despite presumed intense production of reactive oxygen and nitrogen oxidative species. 58 These results that were already observed in previous studies using the model of DSS-induced colitis, 49,50,59 suggest that the colonic content in glutathione can be dissociated from regulating major inflammation, at least in this experimental model. ...
Article
Mucosal healing (MH) decreases the relapse risk in patients with inflammatory bowel disease, but the role of dietary supplementation in this process has been poorly investigated. Here, we investigated the effect of an amino acid mixture supplement on rat MH. Colitis was induced using 5% of dextran sodium sulfate for 6 days. Then, rats received a mixture of threonine (0.50 g/d), methionine (0.31 g/d), and monosodium glutamate (0.57 g/d) or an isonitrogenous amount of alanine (control group). Colons were recovered after colitis induction and after dietary supplementation for measuring colon characteristics, myeloperoxidase, cytokine gene expression, glutathione content, protein synthesis rate, and for histological analysis. Short-chain fatty acids were measured in the colonic content. Colitis induction resulted in anorexia, thickening and shortening of the colon, and ulceration. Colonic cytokine expression and neutrophil infiltration were increased. An increased amount of water and a decreased amount of butyrate, propionate, and acetate were measured in the colonic content. Supplementation with the amino acid mixture coincided with a reduced protein synthesis rate in the colon compatible with the observed increased colonic MH. Mucosal regeneration/re-epithelialization was visible within 3 days after colitis induction at a time when mucosal inflammation was severe. Histological analysis revealed an increased regeneration/re-epithelialization after 10-day supplementation. In contrast, the spontaneous resolution of inflammation was not affected by the supplementation. Amino acid supplementation ameliorates colonic MH but not mucosal inflammatory status. Our data sustain the use of adjuvant dietary intervention on initiated intestinal MH.
... Data were presented as mean ± standard error of mean (SEM). Results were examined by one-way ANOVA followed by Fisher's least significant difference (LSD) test tissue according to Lenoir et al. (2011). In a 50-mM phosphate buffer with hexadecyl trimethyl ammonium bromide (0.5%), a section of colon was homogenized in ice with a T25 Ultra-Turrax system (HTAB; IKA, Staufen, Germany). ...
Article
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In this study, we explored the effects of marjoram oil (MO) on dextran sulfate sodium (DSS)-induced colitis in Balb/c mice. Marjoram oil was found to significantly reduce the severity of DSS-induced colonic inflammation, as reflected by improved disease activity index, prevented colon length shortening, lower histopathological score, decreased myeloperoxidase activity, and reduced interlukin 6 (IL-6) levels. Moreover, marjoram oil pretreatment enhanced the colonic epithelial integrity by decreasing paracellular permeability. Marjoram oil was found to clearly reduce the colonic levels of thiobarbituric acid reactive substances assay and enhance the activity of superoxide dismutase, catalase, and glutathione sulfhydryl content. Marjoram oil could exert a protective effect on ulcerative colitis through its anti-inflammatory and antioxidant properties.
... Lippia extracts and verbascoside, the most common ingredient, have been shown to have analgesic (Amin et al., 2018), neuroprotective (Razavi et al., 2017), antiulcerogenic (Lenoir et al., 2012), antibacterial (Ghaemi et al., 2007), antifungal, anti-tumor (Cushnie and Lamb, 2005), anti-proliferative (Lee et al., 2007), and learning and memory-improving properties (Lee et al., 2006). Pharmacological studies revealed the antioxidant (Bahramsoltani et al., 2018;Lenoir et al., 2011), anti-inflammatory (Sanchez et al., 2013), and anti-apoptotic (Amin et al., 2018) properties of this plant. ...
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Objective: Acrylamide (ACR) neurotoxicity is induced by different mechanisms such as oxidative stress and apoptosis. Scientific researchs have indicated the antioxidative properties of Lippia citriodora. The protective effect of L. citriodora aqueous and ethanolic extracts on ACR-induced neurotoxicity was investigated. Materials and methods: Male Wistar rats were randomly divided into 13 groups: (1) control, (2) ACR (50 mg/kg, i.p.), (3-6) ACR+aqueous extract (12.5, 25, 50, and 100 mg/kg, i.p.), (7-10) ACR+ethanolic extract (12.5, 25, 50, and 100 mg/kg, i.p.), (11) aqueous extract (100 mg/kg), (12) ethanolic extract (100 mg/kg), and (13) ACR+Vitamin E (200 mg/kg, every other day, i.p.). After 11 days, gait score, MDA, and GSH levels in brain cortical tissue were measured. In the in vitro test, the viability of PC12 cells (using MTT test), the amount of reactive oxygen species (ROS; using DCFH-DA method), and the protein levels of Bax, Bcl2 and caspase 3 (by western blotting) were measured. Results: In the in vitro study, the IC50 for the treatment of PC 12 cells with ACR after 24 hr was 6 mM. ACR decreased cell viability, but increased ROS level, Bax/Bcl-2 ratio, and caspase-3 protein level. Pre-treatment by L. citriodora extracts (15-120 µg/ml) ameliorated the toxic effects of ACR on PC12 cells. In the in vivo experiment, ACR-induced movement disorders increased MDA but decreased GSH content. The extracts of L. citriodora improved ACR toxic effects. Conclusion: Aqueous and ethanolic extracts of L. citriodora were found to reduce ACR-induced neurotoxicity via inhibiting oxidative stress and apoptosis.
... In this study, apigenin was the major flavonoid found in ethanol:water extract (1:10) of V. macrurum, in agreement with Karalija et al. (2020) who reported apigenin as the major flavonoid in water extracts of Verbascum sp. Apigenin was reported to be one of the most potent anti-inflammatory flavonoids and may explain the use of Verbascum sp. as herbal drug against inflammation (Tatli and Akdemir, 2006;Tatli et al., 2008) and to ameliorate the clinical symptoms of colitis (Hausmann et al., 2007;Lenoir et al., 2011). ...
Article
A short-term study was performed to assess the effects of diets supplemented with polyphenols (CSVP), extracted from the chestnut (Castanea sativa) shell, agri-food waste rich in tannins, and mullein (Verbascum macrurum), a perennial spontaneous plant rich in flavonoids, on a zebrafish (Danio rerio) model of k-carrageenan-induced intestinal inflammation. Morphological asset of intestine, immunodensity of the pro-inflammatory mediator Tumor necrosis factor α (TNFα) and Cyclooxygenase-2 (COX-2), immunoexpression of the two antioxidant enzymes Catalase (Cat) and Superoxide dismutase 2 (Sod2), quantitative gene expression of pro- and anti-inflammatory cytokines including TNFα, COX2A, Interleukin-1β (IL-1β) and IL-10, and the activated cell pathways were analyzed. Seven experimental diets were formulated including: peeled A. salina (Control group), peeled A. salina + 0.1% of k-carrageenan (Inflamed group), peeled A. salina + CSVP followed by k-carrageenan inflammatory diet (CSVP pre-treated group), peeled A. salina + 0.1% of k-carrageenan + CSVP (CSVP co-treated group), peeled A. salina + 0.1% of k-carrageenan followed by CSVP (CSVP post-treated group), peeled A. salina + CSVP (CSVP group) and peeled A. salina + 0.1% of k-carrageenan followed by 10 days of control diet (polyphenols control group or CP) to determine the efficacy of schedule administering polyphenols in preventing or ameliorating the intestinal inflammation induced in adult zebrafish by k-carrageenan with mean weight of 400 ± 100 mg (mean ± SD; total n = 250). The obtained results indicated that k-carrageenan caused morphological alterations such as the decrease of intestinal folds with consequent expansion of gut lumen, and increased number of goblet cells. Moreover, an over-regulation of pro-inflammatory markers and reduction of the antioxidant enzymes immunoexpression was found. Polyphenols supplementation improved the inflammatory status, downregulated the pro-inflammatory markers, and upregulated IL-10, the main anti-inflammatory cytokine, and antioxidant activity when administered before the inflammation caused by k-carrageenan. The post- and co-treatment reverted only in part the morphological and physiological alterations. Moreover, the results showed that polyphenols modulated the anti-inflammatory effects acting on the Mitogen-activated protein kinase (MAPK) pathway, by inhibiting p38 phosphorylation and increasing extracellular-signal-regulated kinase (ERK) activation, which subsequently led to suppression of nuclear factor kappa B cells (NF-kB) pathway. Based on the findings achieved, the scheduled administration of bioactive phytochemicals like polyphenols could represent a suitable strategy for ameliorating intestinal inflammation in zebrafish and could be considered as a beneficial and sustainable feed additive in the aquaculture sector.
... Previous studies have demonstrated that the dietary ingredient Metabolaid can contribute to reducing blood pressure in pre-hypertensive individuals and body weight [15,16,27,28]. This is at least due in part to the antioxidant and anti-inflammatory properties of the lemon verbena [29], which has been shown to reduce lipid accumulation both in the fat tissue as well as in the liver [30]. Furthermore, the hibiscus extract has been shown to contribute to lowering cholesterol and triglycerides, fat accumulation, as well as lower blood pressure [16,31,32]. ...
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Consumer digital technology is rapidly evolving, allowing users to manage their health in a simple, non-invasive manner. However, there are few studies revealing if using digital technology as part of an intervention really has an impact in consumer health compared with traditional strategies. The objective of the current study is to compare two groups (MTB; n = 18, 46.1 ± 10.4 years and MTBAPP; n = 19, 45.3 ± 6.40 years) of overweight, prehypertensive individuals in losing weight and lowering their blood pressure. Both were provided with nutritionist-guided recommendations, a wearable tracking device and a dietary supplement that has previously been proven to help lose body weight and lower blood pressure. In addition, one of the groups (MTBAPP) used a mobile app specifically designed for the intervention. Blood pressure, body composition, triglyceride level, peak expiratory flow, forced expiratory volume in the first second and maximum oxygen volume were measured at different time points. In addition, participants were monitored with an activity bracelet throughout the intervention. As a result, both groups significantly lost body weight, while the group using the app additionally improved blood pressure levels and lowered fat mass. Furthermore, the app users significantly increased the number of daily steps and decreased sedentary time. In conclusion, the addition of a mobile app with daily reminders to follow healthy lifestyle recommendations increased physical activity and overall improved blood pressure and fat mass levels when compared with a group performing the same intervention but in absence of the mobile application.
... The extracts from the Boussalem region showed the best activity inhibiting the production of NO • at an IC 50 = 2.74 µg/mL, the lemon verbena collected in Kairouan gave an activity of an IC 50 = 3.39 µg/mL. In line with our results, Lenoir et al. [54] showed that the preventative consumption of lemon verbena infusion could help manage oxidative stress by stimulating antioxidant enzymes, such as SOD, and reducing lipid peroxidation in a colonic inflammation model in rats. ...
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Citation: Tammar, S.; Salem, N.; Aidi Wannes, W.; Limam, H.; Bourgou, S.; Fares, N.; Dakhlaoui, S.; Hammami, M.; Khammassi, S.; Re, G.D.; et al. Chemometric Profiling and Bioactivity of Verbena (Aloysia citrodora) Abstract: This research aimed to study the chemical composition of Aloysia citrodora methanolic extract and its biological activities as an antioxidant, and its antibacterial, antifungal and anti-inflammatory activities based on four bioclimatic collection stages. The contents of total phenols, total flavonoids and total tannins were determined. Nine phenolic compounds were identified by LC-DAD-ESI-MS/MS. The major compound was acteoside, a phenylpropanoid which represented about 80% of the methanolic fraction in the various regions. The antioxidant activities of different locations were measured by different analytical assays, such as DPPH, ABTS and iron reducing power. The results showed that phenolic compounds and antioxidant activities varied with climatic and environmental factors. Moreover, there was a significant dependency between regions and biological activities. The use of a principal component analysis showed that there was a close relationship among phenylpropanoids, phenolic compounds and the studied biological activities.
... It has medicinal use in lowering the risk of cardiovascular disease and stroke (Paterson et al. 2006), cancer (Kim et al. 2012), blood pressure (Sari et al. 2012). Lemon helps in maintaining a healthy complexion, preventing asthma (Gründemann et al. 2011), respiratory disorders (Nagalingam et al. 2013), throat infections, constipation (Kim et al. 2005), rheumatism, dental problems (Hurst et al. 1977), fever, internal bleeding, diarrhea (Lenoir et al. 2011), indigestion (Ledesma-Escobar et al. 2016, antifungal (Viuda-Martos et al. 2008), antibacterial, and anti-oxidant (Baratta et al. 1998). The fruit juice boosts the immune system and aids in weight loss. ...
Article
Natural products, especially plants and herbs, have always been a common medicament source, either as pure active principles or traditional preparations. Traditional medicine has been used in developing and developed countries for centuries, and still, 80% of the population uses plant-based medicines for their health care needs. The present review discusses all the possible pharmacological activity reported in various literature and active chemical constituents of herbs. A list of various herbs/plants used by Ayurvedacharya Ratiram Sharma (93-year-old and practicing since 1952) and mentioned in Ayurvedic texts. The curated list was prepared by their general availability in the household and local market. This study comprehensively documented the medicinal value of sixty-six dominant plant species used in Ayurveda and local people. In the present review, each herb is discussed with its scientific and common names, geographical distribution, traditional medicinal uses, beneficial plant parts, and active chemical constituents. For each plant, pharmacological activities of different parts of plants are displayed with their chemical constituents and structure. Toxicologists, phytologists, medicinal chemists, and other researchers who are interested in the various therapeutic and related applications of plant materials will be benefited from present review. This information will open new horizons of application for the many novel drugs and drug candidates.
... Although VB has been shown to have direct antioxidant and free radical scavenging activities compared with other polyphenolic compounds (Pastore et al. 2012, Alipieva et al. 2014), its metabolites were also able to improve the function of the major antioxidant enzymes. In the experimental model of mild-to-moderate colitis, consumption of lemon verbena infusion induced an increase of the SOD activity (Lenoir et al. 2011). Similarly, it has been shown in heroin-dependent mice that treatment with VB significantly increased activities of SOD, CAT and GPx in the brain (Qiusheng et al. 2005). ...
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Paraquat (PQ), one of the most frequently used herbicides, can cause serious health problems in an exposed individual. In the present study, we investigated the protective effect of verbascoside (VB), a phenylpropanoid glycoside from lemon verbena, against PQ-induced A549 cell injury with a particular focus on the possible molecular pathways involved. A549 cells were exposed to PQ (300 µM) and different concentrations of VB (12.5, 25, and 50 µM). Cell viability, ROS content, the level of antioxidant enzymes (SOD, CAT and GPx) and inflammatory markers (IL-6 and TNF-α), as well as 8-OHdG, were detected using MTT assay and an ELISA kit. Western blotting and qRT-PCR were performed to measure the levels of caspase3 and NF-κB mRNA and protein expression. Exposure of cells to PQ caused viability loss and ROS increase. PQ also increased the levels of IL-6, TNF-α and 8-OHdG and decreased the antioxidant enzymes content. PQ treatment resulted in cell death by increasing the gene and protein expression level of caspase 3 and NF-κB. Treatment with VB notably increased cell survival, antioxidant enzymes activity, which concomitantly attenuated ROS, NF-κB and inflammatory mediator production. VB also inhibited apoptosis expression markers. These results indicated that VB could protect A549 cells against PQ induced cell injury by attenuation of ROS and inflammatory marker production and modulation of antioxidant enzymes. VB efficiently suppressed increased NF-κB and caspase-3 activity and formation of 8-OHdG and ultimately improved cell viability. Therefore, VB may be useful in the development of a new therapy for PQ-induced pulmonary toxicity.
... A growing body of research shows that lutein has antioxidant, anti-cancer, anti-inflammatory and neuroprotective properties (Lin et al., 2008;Qiao et al., 2012;Theoharides et al., 2015). Finally, verbascoside has demonstrated antiinflammatory properties and it has been suggested that it could has anti-cancer properties (Lee et al., 2006;Korkina, 2007;Lenoir et al., 2011;Akdemir et al., 2011). ...
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Mediterranean diet is almost synonymous to the healthy lifestyle and diet nowadays. Some of the major components of the diet are the products of the olive tree, fruits and olive oil, which are classified as medical foods, due to their nutraceutical benefits and their protective properties against cancer, cardiovascular diseases, age-related diseases, neurodegenerative disorders and other diseases. The key contributors to these properties are the phenolic compounds such as hydroxytyrosol, tyrosol and oleuropein. Table olives are being processed with several methods in order to reduce the bitterness of the olive fruit and the impact of the processing on phenolic compounds has not been studied extensively. In the present study, changes in the concentration of the most important phenolic compounds were quantified in fresh, Greek-style and Spanish-style processed olive fruits of cv. ‘Kalamata’, using two different analytical methods for identification and quantification: high-performance liquid chromatography diode array detector (HPLC-DAD) and ultrahigh-performance liquid chromatography tandem mass spectrometry (LC-(ESI)-MS/MS). The phenolic compounds that were identified and quantified were hydroxytyrosol, tyrosol, verbascocide, rutin, oleuropein and luteolin. Both processing methods used altered the phenolic compounds concentration in ‘Kalamata’ olive fruits compared to untreated fruits. In both analytical methods, a statistically significant increase in verbascoside and hydroxytyrosol concentration and a statistically significant decrease in rutin concentration was observed in both, Greek-style and Spanish-style, processed olive fruits.
... 15 Recently, two compounds were isolated from the two endemic Phlomis species, P. brevibracteata, and P. cypria growing in Cyprus. 16 Verbascoside attracted great attention due to its pharmacological features, 17 such as anti-inflammatory effect, [18][19][20][21][22][23][24] antioxidative effect, 25-32 neuroprotective effect, [33][34][35][36][37][38][39][40][41][42][43] antimicrobial effect [44][45][46] ultraviolet radiation protective effect [47][48][49][50][51] antimetastatic effect, 52 and cytotoxic effects on many types of cancer such as myeloma and leukemia [53][54][55][56] human gastric carcinoma, 57 colorectal cancer, 58 human oral squamous cell carcinoma, 59 glioblastoma, 60 and inhibitory effect on tumor cell proliferation. 61 In this study, we aimed to determine the cytotoxic effects of pure verbascoside isolated from the Phlomis nissolii L. plant in both MCF-7 and MDA-MB-231 cell lines in vitro. ...
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Objectives: Verbascoside, also known as acteoside/kusaginin, has attracted a great attention due to its pharmacological features. In this study, we aimed to determine the cytotoxic effects of pure verbascoside isolated from Phlomis nissolii L. plant in both MCF-7 and MDA-MB-231 cell lines in vitro. Materials and methods: MCF-7 and MDA-MB 231 cells were treated with verbascoside (100, 48, 25, 10, 1, 0.5, and 0.1 μM) for 24, 48, and 72 hours. Cytotoxic effect of verbascoside in MCF-7 and MDA-MB-231 cells was assessed using TEBU-BIO cell counting kit 8. Results and conclusion: IC50 values for 24, 48, and 72 h verbascoside exposure of MCF-7 cells were determined as 0.127, 0.2174, and 0.2828 μM, respectively. R2 values were calculated as 0.9630, 0.8789 and 0.8752, respectively. Two-Way ANOVA multiple comparison test results showed that 100 μM verbascoside has the highest cytotoxic effect on MCF-7 breast cancer (BC) cells after 72 h of exposure. IC50 values for 24, 48 and 72 h verbascoside exposure of MDA-MB 231 cells were determined as 0.1597, 0.2584 and 0.2563 μM, respectively and R2 values were calculated as 0.8438, 0.5107 and 0.9203, respectively. Two-Way ANOVA multiple comparisons test results showed that 100 μM verbascoside has the highest cytotoxic effect on MDA-MB 231 BC cells after 24, 48 and 72 h of exposure.
... In previous works, extracts with high amount of Vb generated a protective effect against lipid peroxidation during chronic inflammation in rodents evaluated in different pre-clinical experiments such as CFA-induced arthritis (Lenoir et al., 2011;Gutiérrez-Rebolledo et al., 2018b). The possible mechanism through which this metabolite exerted this protection against oxidation is that it has proven to be a great radical scavenger of reactive oxigen species like anion superoxide in HT-29 human colon carcinoma cells (Cardinali et al., 2012). ...
Article
Ethnopharmacological relevance: Buddleja cordata Humb. Bonpl. & Kunth, known by the population as Tepozán blanco, is a shrub plant used in traditional herbal medicine in Mexico for the treatment of tumors, cancer, sores, skin burns, rheumatic pains and diseases related to inflammatory processes such as arthritis; authors adjudicate this etno-medicinal effect to the presence of secondary metabolites in the plant such as verbascoside, however due to its low concentration in recent years biotechnological tools are applied as cell culture to biosynthesize these pharmacological active metabolites in greater quantities. Aim of the study: Evaluate the possible toxic effect after a daily administration of MeOH extracts from wild plant leaves (Bc-Wp), and cell culture (Bc-Cc) of B. cordata for 28 days, and after their anti-edematous and antioxidant activities in vivo, as well their effect on the cytokines profile during experimental arthritis induced by complete Freund’s adjuvant. Materials and methods: Both extracts were evaluated in CD1 male mice first in a toxicity test of repeated dose administrations (1 g/kg) for 28 days, after which pharmacological activity of both extracts was measure during experimental induced arthritis where three doses were tested, at the end of the study edema formation, body weight gain and antioxidant activity were measure in edema and ganglionic tissues. Finally, dose that exerted. the best protective effect (250 mg/kg) was evaluated to quantify its effect over ganglionic tissue concentration of lymphocytes T CD4+, and cytokines (IL-1β, TNF-α and IL-10), as well histological analysis in arthritic mice. Results: Both extracts (Bc-Wp and Bc-Cc) did not exert lethality, however body weight gain and food in-take were lower than in healthy mice administered with vehicles, also extract-treated animals showed a decrease in serum lipid concentration and only Bc-Wp extract treated animals decrease serum alkaline phosphatase after 28 daily administration compared to healthy un-treated mice. During experimental arthritis best inhibition effect over edema development was observed in those animals administered with both extracts at dose of 250 mg/kg (Bc-Wp and Bc-Cc) on day 28, compared to CFA un-treated mice. Also both extracts reduce oxidative damage over lipids and proteins at the same dose, in both ganglionic and edema tissue, as well antioxidant enzymatic response was reduced in both tissues compared to arthritic un-treated group. In ganglionic tissue of arthritic mice, CD4+ lymphocytes concentration was reduced by Bc-Wp and Bc-Cc treatment (250 mg/kg) respectively, as well IL-1β, and TNF-α levels. Only arthritic animals treated with Bc-Cc extract at 250 mg/kg generated a significant increase of IL-10 doubling the levels compared to CFA un-treated group. Histological analysis of popliteal ganglion showed that both extracts decrease the incidence of lytic lesions, lipid inclusions and leukocyte infiltration. Conclusion: Methanolic extracts of Buddleja cordata wild and their cell cultures did not generated lethality after a daily administration for 28 days at 1 g/kg, but it was observed that both showed a lipid-lowering effect. Also at dose of 250 mg/kg both extracts exerted anti-edematous, protection against the oxidation of lipid and proteins, regulation on antioxidant enzymatic response, down-regulation on lymphocytes CD4+ producers of IL1β and TNF-α, an increase in IL-10 levels, which caused a decrease in leukocyte infiltration in ganglionic tissue during experimental arthritis.
... Beneficial effect generated by both MeOH extracts prepared from Wp (Bc-Wp) and cell suspension cultures (Bc-Cc) of B. cordata may be due to their content of their main phenylpropanoid Vb. In an early work, Lenoir et al. (2011), found that aqueous extract of leaves from Aloysia triphylla (Lemon verbena) with a high content of Vb generated a decrease of chronic inflammation damage in a model of dextran sulfate sodium-induced colitis in Wistar rats at a dose of 5% of extract in their drinking water. It also reduced oxidative damage and favored regulation of antioxidant enzymes activity in intestinal tissue. ...
Article
Buddleja cordata is a species used by Mexican folk medicine for treating illnesses related to inflammation such as skin wounds and arthritis. It bio-synthesizes metabolites such as verbascoside that contributes to its ethno-therapeutic properties as anti-inflammatory remedy. HPLC analysis showed that the methanolic extract from cell suspension cultures (Bc-Cc) and wild plant leaves (Bc-Wp) contained verbascoside, but concentration was higher in Bc-Cc (87.48 mg/g) than in wild plant (47.34 mg/g). In the acute toxicity model, none of the extracts generated any lethality or adverse effects. In acute inflammation model induced with TPA, Bc-Cc extract showed a greater edema inhibition at 2 mg/ear (61.72%), as well for carrageenan model at 200 mg/kg (48.87%). Bc-Wp showed lesser anti-inflammatory effect in both acute inflammation models than Bc-Cc. For Adjuvant-induced arthritis both extracts at 250 mg/kg generated a moderate inhibition over edema (≈ 33%) at day 28, and they were statistically no different to phenilbutazone. The culture in suspension of B. cordata obtained by biotechnological process contains greater amount of verbascoside and showed better anti-inflammatory activity; thus, representing a source for obtaining this type of secondary metabolite of pharmacological interest.
... Interestingly, infusion of carob leaves and infusion of OFI-cladodes were effective in modulating inflammation severity probably through inhibition of NF-κβ pathway, as carob leaf and OFI-cladode extracts inhibited NF-κβ translocation into nucleus in RAW 264.7 macrophages cells. Consistent with our findings, polyphenol of Lemon Verbena Infusion exhibited protective effects against DSS-induced colitis [93]. Similarly, green tea polyphenols have been reported to decrease serum levels of pro-inflammatory cytokines among which TNF-α and IL-6 [45]. ...
Article
In the present study, we have investigated the effects of polyphenol-rich infusions from carob leaves and OFI-cladodes on inflammation associated with obesity and dextran sulfate sodium (DSS)-induced ulcerative colitis in Swiss mice. In vitro studies revealed that aqueous extracts of carob leaves and OFI-cladodes exhibited anti-inflammatory properties marked by the inhibition of IL-6, TNF-α and nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells concomitant with NF-κβ nucleus translocation inhibition. For in vivo investigations, Swiss male mice were subjected to control or high fat diet (HFD). At the 8th week after the start of study, animals received or not 1% infusion of either carob leaves or OFI-cladode for 4 weeks and were subjected to 2% DSS administration in drinking water over last 7 days. After sacrifice, pro-inflammatory cytokines levels in plasma and their mRNA expression in different organs were determined. Results showed that carob leaf and OFI-cladode infusions reduced inflammation severity associated with HFD-induced obesity and DSS-induced acute colitis indicated by decrease in pro-inflammatory cytokines expression (as such TNF-α, IL1b and IL-6) in colon, adipose tissue and spleen. In addition, plasma levels of IL-6 and TNF-α were also curtailed in response to infusions treatment. Thus, carob leaf and OFI-cladode infusions prevented intestinal permeability through the restoration of tight junction proteins (Zo1, occludins) and immune homeostasis. Hence, the anti-inflammatory effect of carob leaves and OFI-cladodes could be attributed to their polyphenols which might alleviate inflammation severity associated with obesity and colitis.
... The leaves of this plant are utilized for the treatment of fever, neuropathic and stomach pains, dizziness, headaches, hypnotic, anemia, migraine, and cold symptoms (Pascaul et al., 2001). Furthermore, pharmacological studies indicated that L. citriodora leaves exhibit different properties including antioxidant (Lenoir et al., 2011), antinociceptive and anti-inflammatory (Mehrabizadeh Honarmand et al., 2011) and anti-bacterial (Koohsari et al., 2013) effects. ...
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Objectives: The extract of Lippia citriodora and its main component, verbascoside, are known for their hypnotic effects in traditional medicine. In this study, the anxiolytic and hypnotic effects of L. citriodora leave extracts and verbascoside were evaluated in mice. Materials and methods: Animals were divided into 11 groups of six mice each. Group I received normal saline, Group II received Diazepam (2 mg/kg) as positive control, Groups III, IV and V received L. citriodora ethanolic extracts (50, 100 and 200 mg/kg, respectively), Groups VI, VII and VIII received L. citriodora aqueous extracts (50, 100 and 200 mg/kg, respectively) and Groups IX, X and XI received Verbascoside (25, 50 and 100 mg/kg, respectively). All agents were administrated intraperitoneally. To evaluate hypnotic activity, pentobarbital sleeping test, and for anxiolytic activity, elevated plus-maze (EPM), locomotor activity, open field and motor coordination (rotarod test) tests were used. To understand the role of GABAA receptor, flumazenil was also administered. Results: The extracts and verbascoside increased the time spent and number of entries in the open arms of EPM. Moreover, these agents significantly increased the sleeping time induced by pentobarbital. In addition, the highest dose of extracts and verbascoside reduced time spent on the rod and total locomotion in the open field tests, respectively. Flumazenil inhibited the effects of extracts and verbascoside in EPM and hypnotic tests. Conclusion: These results suggested that ethanolic and aqueous extracts of L. citriodora and verbascoside exhibit anxiolytic, hypnotic and muscle relaxant effects especially at the highest doses and these effects are partially due to the interaction with GABAA receptor.
... Protein concentrations were measured by a BCA assay kit (Pierce, Jiancheng Bioengineering Institute, Nanjing, China). Guaiacol oxidation by MPOproduced hydroxyl radicals in the presence of hydrogen peroxide was evaluated as previously described [33]. This activity, expressed in units per mg of protein, was defined as the quantity of enzyme degrading 1 µmol of hydrogen peroxide per minute. ...
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A strong correlation exists between inflammatory bowel disease (IBD) and oxidative stress involving alterations of several key signaling pathways. It is known that methionine promotes reactive oxygen species (ROS) production; we therefore hypothesize that a methionine restriction diet would reduce ROS production, inflammatory responses, and the course of IBD. We generated a murine colitis model by dextran sodium sulfate (DSS) treatment and tested the effects of the methionine restriction diet. Forty-eight mice were randomly divided into four groups of equal size, which included a control (CON) group, an MR (methionine restriction diet) group, a DSS treated group and an MR-DSS treated group. Mice in the first two groups had unrestricted access to water for one week. Mice in the two DSS-treated groups had unrestricted access to 5% DSS solution supplied in the drinking water for the same period. Mice in the CON and DSS groups were given a basal diet, whereas mice in the MR-DSS and MR groups were fed a 0.14% MR diet. We found that DSS reduced daily weight gain, suppressed antioxidant enzyme expression, increased histopathology scores and activated NF-κB and nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling. We also showed that the MR diet upregulated catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities, decreased myeloperoxidase (MPO), TNF-α and IL-1β, and reversed activation of the NF-κB signaling pathway in MR-DSS mice. Taken together, our results imply that the MR diet may be considered as an adjuvant in IBD therapeutics.
... Besides, a stimulating effect of polyphenols on antioxidant enzymes activity has previously been reported in various models. 31 In addition, we have shown that CPAE might have depleted ROS level, what relieved the alteration of the antioxidant enzymes and/or may have triggered their synthesis, which in turn attenuated the oxidative damage in DSS-treated rats. However, CPAE did not significantly change other antioxidative enzymes, such as GPx activity in DSS-treated rats. ...
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The aim of the present study is to investigate the potential protective role of Ceratonia siliqua L. against dextran sodium sulfate (DSS)-induced oxidative damage and inflammation in liver and kidney of rats. The hepatotoxicity and nephrotoxicity were induced in rats by oral administration of synthetic DSS (5%) in the drinking water for over 7 days. However, carob pods aqueous extract (CPAE; 50 and 100 mg/kg body weight) was given by oral administration for 21 days. Myeloperoxidase (MPO) activity, malondialdehyde, H2O2 content, as well as the levels of antioxidant enzymes in organs were measured to observe the possible mechanisms. As a result, the CPAE counteracted DSS-induced increase of MPO activity, lipoperoxidation, and the activity of antioxidant enzymes, such as superoxide dismutase and catalase (CAT). DSS administration increased also in the organs hydrogen peroxide (H2O2) and free iron levels, whereas the CPAE pretreatment reversed all intracellular mediator perturbations. It was concluded that the CPAE exerted a potential protective effect against DSS-induced inflammation and oxidative stress in the rat organs. Consequently, it is essential that adequate care is taken when we use carob pods for patients with hepatotoxicity and nephrotoxicity.
... As mentioned above, reactive oxygen induces inflammatory diseases including IBD [34][35][36]. Therefore, foods having antioxidant capacity and compounds such as polyphenols were surveyed for their ameliorative effects in bowel diseases [37,38]. Furthermore, there are several reports on the inhibitory effects of LAB [6,39] and water-soluble saccharides including oligosaccharides and polysaccharides [40,41]. ...
Article
Most wakame Undaria pinnatifida, a brown algae, products are made from the frond portion. In this study, the polysaccharide content and antioxidant property of aqueous extract solutions (AESs) of the four parts (frond: wakame, stem of the frond: kuki-wakame, sporophyll: mekabu, and kuki-mekabu) of wakame were investigated. Polysaccharide content was high in both the wakame and mekabu. Superoxide anion (O2⁻) radical-scavenging capacities were high in the mekabu. These AESs could be fermented by Lactobacillus plantarum Sanriku-SU7. The O2⁻ radical-scavenging activity of the kuki-wakame, mekabu, and kuki-mekabu were increased by the fermentation. Fermented mekabu clearly showed a protective effect on human enterocyte-like HT-29-luc cells and in a mouse model of dextran sodium sulphate-induced inflammatory bowel disease (IBD). These results suggest that the mekabu fermented by L. plantarum Sanriku-SU7 has anti-IBD effect related to O2⁻ radical-scavenging.
... Additionally, the infiltration of leukocytes, monocytes, and neutrophils during inflammation can further enhance intestinal ROS production through both respiratory burst enzymes and prostaglandin and leukotriene metabolism (Babbs, 1992). Several studies have demonstrated increased ROS/RNS levels within the intestinal epithelium of patients with IBD (Kruidenier and Verspaget, 2002;Pravda, 2005;Rezaie et al., 2007) and in murine models of experimental colitis (Girgin et al., 1999;Tham et al., 2002;Narushima et al., 2003;Sundaram et al., 2003;Oz et al., 2005;Siddiqui et al., 2006;dos Reis et al., 2009;Kajiya et al., 2009;Abdolghaffari et al., 2010;Yao et al., 2010;Lenoir et al., 2011;Ock et al., 2011;Sengül et al., 2011;Borrelli et al., 2013;Arab et al., 2014). High concentrations of oxidized molecules have also been measured in the plasma, serum, exhaled air, and saliva of patients with IBD (Tüzün et al., 2002;Rezaie et al., 2006). ...
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Inflammatory Bowel Disease (IBD) represents a group of idiopathic disorders characterized by chronic or recurring inflammation of the gastrointestinal tract. While the exact etiology of disease is unknown, IBD is recognized to be a complex, multifactorial disease that results from an intricate interplay of genetic predisposition, an altered immune response, changes in the intestinal microbiota, and environmental factors. Together, these contribute to a destruction of the intestinal epithelial barrier, increased gut permeability, and an influx of immune cells. Given that most cellular functions as well as maintenance of the epithelial barrier is energy-dependent, it is logical to assume that mitochondrial dysfunction may play a key role in both the onset and recurrence of disease. Indeed several studies have demonstrated evidence of mitochondrial stress and alterations in mitochondrial function within the intestinal epithelium of patients with IBD and mice undergoing experimental colitis. Although the hallmarks of mitochondrial dysfunction, including oxidative stress and impaired ATP production are known to be evident in the intestines of patients with IBD, it is as yet unclear whether these processes occur as a cause of consequence of disease. We provide a current review of mitochondrial function in the setting of intestinal inflammation during IBD.
... Several studies were consulted [68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84] and despite the model used, whenever oxidative stress is assessed, all studies reflect an increase in oxidative markers; some of them refer intervention studies with antioxidant molecules and reveal a potential for modulating oxidative stress through these compounds. The main findings and the hypothesis that these studies attempted to elucidate are given in Table 1. ...
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This review will focus on published human studies on oxidative stress and DNA damage in inflammatory bowel disease (IBD), both ulcerative colitis and Crohn's disease, assessing their role in the pathophysiology of these diseases. Search was performed over PubMed and ScienceDirect databases to identify relevant bibliography, using keywords including "oxidative stress," "DNA damage," "IBD," and "oxidative DNA damage." Whether as cause or effect, mechanisms underlying oxidative stress have the potential to condition the course of various pathologies, particularly those driven by inflammatory scenarios. IBDs are chronic inflammatory relapsing conditions. Oxidative stress has been associated with some of the characteristic clinical features exhibited in IBD, namely tissue injury and fibrosis, and also to the ulcerative colitis-associated colorectal cancer. The possible influence of oxidative stress over therapeutic behavior and response, as well as their contribution to the oxidative burden and consequences, is also addressed. Due to the high prevalence and incidence of IBD worldwide, and also to its associated morbidity, complications, and disease and treatment costs, it is of paramount importance to better understand the pathophysiology of these diseases.
... 18,19 Therefore, recently plant extracts or blend tea from plant leaves for IBD management have been growing interest by their therapeutic effects. [20][21][22] Natural herbal medicines have shown to be beneficial for the treatment of IBD and they also help to maintain healthy intestinal functions. 23 In particular, a bamboo grass that is widely grown in Korea, China, and Russia, named Sasa leaves, has exhibited antiinflammatory, antidiabetic, and antipyretic properties. ...
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Oxidative stress plays an important role in the pathogenesis of inflammatory bowel disease. The objective of this study is to investigate the protective effect of Sasa quelpaertensis leaf extract (SQE) against oxidative stress in mice with dextran sulfate sodium (DSS)-induced colitis. Mice were treated with SQE (100 mg/kg or 300 mg/kg body weight) by gavage in advance two weeks before inflammation was induced. Then, the mice were administered with 2.5% DSS in drinking water for 7 days and normal drinking water for 7 days between two DSS treatment. Disease activity index values, gut motility, and severity of the resulting oxidative DNA damage were analyzed. The antioxidant effect of SQE was evaluated by measuring malondialdehyde (MDA) and superoxide dismutase (SOD) activity in plasma samples. Catalase activity and expressions levels of glutathione peroxidase 1 (Gpx1), SOD1, and SOD2 were also detected in colon tissues. Administration of SQE significantly reduced the severity of DSS-induced colitis compared to the control (Ctrl) group. Levels of 8-oxo-dG, an oxidative DNA damage marker, were significantly lower in the SQE group compared to the untreated DSS Ctrl group. In the SQE (300 mg/kg) group, MDA levels were significantly lower, while SOD and catalase activity levels in the plasma samples were significantly higher compared with the DSS Ctrl group. The expression levels of the antioxidant enzymes, SOD2 and Gpx1, were significantly higher, while the levels of SOD 1 expression were lower, in the colon tissues of the DSS Ctrl group compared with those of the Ctrl group. In contrast, administration of SQE significantly down-regulated SOD2 and Gpx1 expressions and up-regulated SOD1 expression. These results indicate that SQE efficiently suppresses oxidative stress in DSS-induced colitis in mice, and its action is associated with the regulation of antioxidant enzymes.
... The botanical supplements HPL, HVO, and VO have been shown to demonstrate antioxidant and free radical scavenging abilities. 28 Previous research has only investigated the dynamic parameters of their free radical scavenging activities with respect to hydroxyl radical scavenging, so new data are needed for other radicals. VO is widely used for the treatment of anxiety and unrest. ...
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Objectives: The purpose of this research was to compare the dynamic antioxidant activities and the free radical scavenging abilities of three botanical supplements, Hypericum perforatum L. (HPL), Herba Verbena Officinalis (HVO), and Valeriana officinalis L. (VO), which have been reported to effectively treat menopause symptoms. Methods: The antioxidant activities of the three supplements were determined by the ferric reducing ability of plasma (FRAP) assay. In addition, their free radical scavenging abilities were studied by ftheir interactions with the stable radicals of 2, 2'- Azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH). Results: The results indicated that the HPL ethanolic extract exhibited greater antioxidant activity (1.2688 ± 0.01 mmol Trolox/g) than the HVO ethanolic extract (1.1686± 0.043 mmol Trolox/g) and the VO ethanolic extract (0.2579 ± 0.0031 mmol Trolox/g) as compared to Nilestriol (0.0026±0.0012), a positive control agent in the experiment. Moreover, the HPL extract showed remarkable free radical scavenging activity against ABTS•+, and the HVO extract was the most potent against DPPH•. Conclusion: These activities may be attributed to the total flavonoid or phenolic acid contents of among these extracts.
... Oxidative stress is known to damage cellular macromolecules such as DNA, lipids, and proteins. MDA is considered as a byproduct of lipid peroxidation known to be increased in UC [27,32]. We noted that the level of MDA ( Figure 5(a)) was increased in DSS-induced mice. ...
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The objective of this study is to evaluate the effect of allicin (10mg/kg body weight, orally) in an experimental murine model of UC by administering 2.5% dextran sodium sulfate (DSS) in drinking water to BALB/c mice. DSS-induced mice presented reduced body weight, which was improved by allicin administration. We noted increases in CD68 expression, myeloperoxidase (MPO) activities, and Malonaldehyde (MDA) and mRNA levels of proinflammatory cytokines, such as tumor necrosis factor- (TNF-) 𝛼, interleukin- (IL-) 1𝛽, IL-6, and IL-17, and decrease in the activities of enzymic antioxidants such as superoxide dismutase (SOD), Catalase (CAT), Glutathione reductase (GR), and Glutathione peroxidase (GPx) in DSS-induced mice. However, allicin treatment significantly decreased CD68, MPO, MDA, and proinflammatory cytokines and increased the enzymic antioxidants significantly (𝑃 < 0.05). In addition, allicin was capable of reducing the activation and nuclear accumulation of signal transducer and activator of transcription 3 (STAT3), thereby preventing degradation of the inhibitory protein I𝜅B and inducing inhibition of the nuclear translocation of nuclear factor (NF)-𝜅B-p65 in the colonic mucosa.These findings suggest that allicin exerts clinically useful antiinflammatory effects mediated through the suppression of the NF-𝜅B and IL-6/p-STAT3Y705 pathways.
... Moreover, it can be interpreted under the light of current literature. In fact, recent in vivo and in vitro studies report different effects of VB on the antioxidant enzyme network [6,[63][64][65]. Other studies show that VB increased the expression of the transcription factor peroxisome proliferator activated receptor (PPAR-) in nuclear extracts of colon cells [4]. ...
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Verbascoside (VB), a bioactive polyphenol from olive mill wastewater with known antioxidant activity, was shown to act as a pro-oxidant molecule, by impairing energy/redox status and embryo developmental competence of prepubertal ovine oocytes when added at micromolar concentrations in a continuative 24-h in vitro maturation (IVM) exposure protocol (1). The aim of the present study was to determine whether a lower (nanomolar) VB concentration and a shorter exposure time (2 v. 24h) during IVM may improve the maturation rates of prepubertal ovine oocytes and their subsequent embryonic development in vitro. Cumulus-oocyte complexes derived from the ovaries of slaughtered 1-mo-old prepubertal sheep oocytes underwent IVM in TCM 199 with 10% oestrus sheep serum, 0.1IUmL(-1) of FSH/LH, and 100µM cysteamine, in 5% CO2 in air at 38.5°C for 24h. Based on our previous results (Dell'Aquila et al. 2014 Biomed. Res. Int. 2014, 878062), VB was added in the IVM medium at 1.03nM, and 2 incubation times (24 and 2h) were tested. In the 2-h exposure group, after 2h of exposure to VB, oocytes were washed and cultured up to 24h without VB. A group of oocytes were cultured in absence of VB, as controls. Matured oocytes were fertilized with frozen-thawed ram semen in SOF medium for 22h and zygotes were cultured in vitro for 8 days. Metaphase II (MII) cleavage and blastocyst rates were analysed by Chi-squared test. Embryo quality was evaluated by staining and total cell count of the blastocyst and analysis of variance (ANOVA) was applied. Differences were considered to be significant when P<0.05. Compared to controls, VB treatment at the concentration of 1.03nM and 24h of exposure had no effect on MII rates (196/268, 73% v. 226/323, 70% MII/cultured oocytes; P>0.05). However, this treatment allowed to obtain significantly higher rates of cleaved embryos/MII oocytes (156/196, 80% v. 165/226, 73%; respectively; P<0.05), blastocyst yield/cleaved embryos (59/156, 38% v. 45/165, 27%, respectively; P<0.05), and total blastocyst cell numbers (108.62±19.87 v. 89.61±26.32, respectively; P<0.05) compared to control oocytes. The VB treatment at the same concentration but for 2h induced only significantly higher cleavage rate (196/210, 93% v. 165/226, 73%; P<0.05). In conclusion, our results showed that VB treatment at 1.03nM during 24h of IVM exerted a positive effect on in vitro embryo development of prepubertal ovine oocytes by increasing the blastocyst yield and their quality. The hypothesis that VB at nanomolar concentrations may improve cumulus-oocyte energy/redox status is under investigation.
... In fact Aldini et al. (2006) and Tatli, Takamatsu, Khan, and Akdemir (2007) found EC 50 values of 7.22 and 4 ppm on erythrocytes and a leukemia cell line, respectively. Antioxidant activity induced by VB has been confirmed by in vivo studies, as a reduction of lipid peroxidation after lemon verbena extract administration Lenoir et al., 2011;Liu, 2003). Table 2 shows that IsoVB has EC 50 values 3 and 6 times higher than those found for VB on the HT-29 and Caco2 cell lines, respectively. ...
... In the experimental model of intestinal inflammation that is induced by dextran sulphate, which resembles immune-mediated inflammatory bowel disease in humans, the systemic administration of verbascoside that was isolated from Plantago lanceolata L. substantially improved the histological patterns and clinical symptoms of colitis, downregulated pro-inflammatory IFN-γ secretion and inhibited the NADPH-oxidase-connected oxidative burst (indirect antioxidant effect) in the intestinal macrophages (Hausmann et al., 2007;Lenoir et al., 2011). Further studies with verbascoside from plant cell cultures of Syringa vulgaris L. have confirmed its protective and curative effects through reduced NFκB activation. ...
... Moreover, it can be interpreted under the light of current literature. In fact, recent in vivo and in vitro studies report different effects of VB on the antioxidant enzyme network [6,[63][64][65]. Other studies show that VB increased the expression of the transcription factor peroxisome proliferator activated receptor (PPAR-) in nuclear extracts of colon cells [4]. ...
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Verbascoside (VB) is a bioactive polyphenol from olive oil mill wastewater with known antioxidant activity. Oxidative stress is an emerging problem in assisted reproductive technology (ART). Juvenile ART is a promising topic because, in farm animals, it reduces the generation gap and, in human reproductive medicine, it helps to overcome premature ovarian failure. The aim of this study was to test the effects of VB on the developmental competence of ovine prepubertal oocytes and the bioenergetic/oxidative stress status of fresh and vitrified oocytes. In fresh oocytes, VB exerted prooxidant short-term effects, that is, catalase activity increase and uncoupled increases of mitochondria and reactive oxygen species (ROS) fluorescence signals, and long-term effects, that is, reduced blastocyst formation rate. In vitrified oocytes, VB increased ROS levels. Prooxidant VB effects in ovine prepubertal oocytes could be related to higher VB accumulation, which was found as almost one thousand times higher than that reported in other cell systems in previous studies. Also, long exposure times of oocytes to VB, throughout the duration of in vitro maturation culture, may have contributed to significant increase of oocyte oxidation. Further studies are needed to identify lower concentrations and/or shorter exposure times to figure out VB antioxidant effects in juvenile ARTs.
... The flavone luteolin attenuated dextran sodium sulphate (DSS)-induced colonic injury and inflammation in mice (12) . We have also recently shown that lemon verbena infusion offered beneficial effects against DSS-induced colonic inflammation in rats (13,14) . ...
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Lemon verbena (Aloysia triphylla) infusion, a widely consumed herbal tea, contains significant amounts of polyphenols such as flavone diglucuronides and phenylpropanoid glycosides (mainly verbascoside). We have recently shown that lemon verbena infusion offers beneficial effects against dextran sodium sulphate (DSS)-induced colonic inflammation in rats. The present study aimed to evaluate the bioavailability and intestinal absorption of polyphenols derived from lemon verbena infusion in both healthy and colitic rats. For this purpose, lemon verbena infusion was given to rats ad libitum for 14 d, and then 4 % DSS was added to the infusion for 7 d. Before and after DSS administration, 24 h urinary excretion of polyphenols was determined. Flavones were excreted in the urine as conjugated aglycones, and their excretion was not significantly altered by colonic inflammation. Only trace amounts of verbascoside were excreted in the urine, but various metabolites (hydroxycinnamic acids) were detected. The urinary excretion of hydroxycinnamic acids, particularly that of caffeic acid, increased after DSS administration (P< 0·05). Only flavone aglycones (luteolin and diosmetin) were excreted in the faeces in small proportions (3·2 % of ingested flavones). Intestinal absorption of lemon verbena polyphenols was examined using an in situ intestinal perfusion model. Intestinal absorption of verbascoside and flavone diglucuronides did not significantly differ between the healthy and colitic rats. Collectively, these results show that intestinal absorption and urinary excretion of lemon verbena flavone diglucuronides were not altered by colonic inflammation, but that urinary excretion of hydroxycinnamic acids derived from verbascoside was affected in a colitic situation.
... However, a study using a cocoa diet in a dextran sodium sulfate (DSS) model demonstrated that cocoa intake did not improve clinical colitis, although it certainly contributed to reducing colonic oxidative activity and serum inflammatory mediator concentrations . These results agree with those obtained with luteolin and with a lemon verbena infusion rich in polyphenolic compounds (Karrasch et al., 2007;Lenoir et al., 2011). More interestingly, it has recently been reported that a polyphenol-enriched cocoa extract was able to decrease acute DSS colitis in mice (Andújar et al., 2011), thus evidencing the need for a high polyphenol content in the cocoa to achieve anti-inflammatory activity in the IBD. ...
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Cocoa is a food relatively rich in polyphenols, which makes it a potent antioxidant. Due to its activity as an antioxidant, as well as through other mechanisms, cocoa consumption has been reported to be beneficial for cardiovascular health, brain functions, and cancer prevention. Furthermore, cocoa influences the immune system, in particular the inflammatory innate response and the systemic and intestinal adaptive immune response. Preclinical studies have demonstrated that a cocoa-enriched diet modifies T cell functions that conduce to a modulation of the synthesis of systemic and gut antibodies. In this regard, it seems that a cocoa diet in rats produces changes in the lymphocyte composition of secondary lymphoid tissues and the cytokines secreted by T cells. These results suggest that it is possible that cocoa could inhibit the function of T helper type 2 cells, and in line with this, the preventive effect of cocoa on IgE synthesis in a rat allergy model has been reported, which opens up new perspectives when considering the beneficial effects of cocoa compounds. On the other hand, cocoa intake modifies the functionality of gut-associated lymphoid tissue by means of modulating IgA secretion and intestinal microbiota. The mechanisms involved in these influences are discussed here. Further research may elucidate the cocoa compounds involved in such an effect and also the possible medical approaches to these repercussions.
... 20 Moreover, consumption of a lemon verbena infusion rich in polyphenolic compounds did not improve the histopathological changes induced by 4% DSS in rats, despite stimulating the activity of the antioxidant enzyme superoxide dismutase and reducing lipid peroxidation in the colon. 21 However, it has been recently reported that a polyphenol-enriched cocoa extract was able to decrease acute DSS colitis in mice, 22 thus evidencing the promising anti-inflammatory effects of cocoa flavonoids. These results may also suggest that we did not observe a clear colitis reduction because of the lower polyphenol content in the cocoa that we used. ...
Article
Cocoa is a rich source of fiber and flavonoids with recognized antioxidant and anti-inflammatory potential. The aim of this study was to evaluate the effects of a cocoa-enriched diet on rats with dextran sulfate sodium (DSS)-induced colitis. Wistar rats were fed with either a 5% cocoa diet or standard diet. Colon inflammation was induced by DSS in the drinking water: 5% for six days and 2% over the following nine days. Colitis was assessed by body weight loss, stool consistency and blood presence in stools. A group of animals fed standard diet was treated with quercitrin (1 mg/kg) after colitis establishment. After two weeks of DSS treatment, the colon oxidative and inflammatory status and lymphocyte composition from blood and mesenteric lymph nodes (MLNs) were assessed. The cocoa-fed group did not exhibit amelioration of clinical colitis but displayed higher antioxidant activity than the colitic reference group by the restoration of colon glutathione content and prevention of lipid peroxidation. The cocoa diet showed anti-inflammatory potential because it down-regulated serum tumor necrosis factor-α, colon inducible nitric oxide synthase activity and decreased colon cell infiltration. The lymphocyte composition in MLNs was not modified by drinking DSS, but there was an increase in the proportion of natural killer and regulatory T-cells in the blood. These changes were not modified by cocoa. In conclusion, cocoa intake may help to inhibit the negative oxidative effects consequent to colitis, although this action is not enough to abrogate the intestinal inflammation significantly.
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Ethnopharmacological relevance Duranta erecta Linn. belonging to the Verbenaceae family is widely used in the traditional systems of medicines practiced in Bangladesh, India, Nigeria, the Philippines, and Brazil. The ethnomedicinal application as vermifuge, febrifuge, diuretic, anti-parasitic, and anti-malarial are well documented. D. erecta is also a significant source of phenylethanoid glycoside known as acteoside-a drug in clinical trials for IgA nephropathy patients. Aim of this review This review aims to critically highlight the existing studies on D. erecta, including its botanical authentication, geographical distribution, ethnomedicinal uses, phytochemistry, and pharmacological properties. Critical discussion is focused on the overview and gap in knowledge for future research. Additionally, the clinical significance of its major secondary metabolite, i.e., acteoside, has also been discussed with emphasis on biosynthesis, distribution, pre-clinical, and clinical outcomes. Materials and methods Professional research data from 1963 to 2021 appeared in scholarly journals, and books were retrieved from scientific database platforms viz. Sci-Finder, PubMed, CNKI, Science Direct, Web of Science, Wiley, Google Scholar, Taylor and Francis, Springer, and Scopus. The chemical structures for all the phytomolecules were validated using Sci-finder and first-hand references. While plant name and synonyms were corroborated by “The Plant List” (www.theplantlist.org). Results D. erecta and its key metabolite acteoside display various biological actions like antimalarial, antimicrobial, antioxidant, anticancer, antinephritic, hepatoprotective, neuroprotective, and antiviral properties. Acteoside literature analysis shows its presence in different stages of clinical trials for anti-nephritic, hepatoprotective, and osteoarthritic activity. The phytochemical review of D. erecta exhibited 64 compounds that have been isolated and identified from D. erecta, such as iridoid glycosides, phenylethanoid glycosides, flavonoids, steroids, phenolics, terpenoids, and saponins. The other significant secondary metabolites responsible for its medicinal properties are acteoside, durantol, pectolinaringenin, repenins, scutellarein, and repennoside. Conclusion Duranta erecta is one of the Verbenaceae plants, widely used in ethnomedicines having various phytochemicals with understandable pharmacological actions mainly confined at the crude extract level. However, further bioactivity-guided or fingerprint-assisted studies are required to validate the ethnomedicinal uses, concerning cellular and molecular mechanisms, quality standardization, and safety with respect to its bioactive constituent(s). Therefore, the present review identified the gap in the research on scientific validation of Duranta based ethnomedicines and may provide critical information for the development of phytopharmaceuticals/Phyto-cosmeceuticals.
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Thesis
Dans la présente étude, nous avons étudié les effets des infusions de feuilles de caroube et de cladodes OFI riches en polyphénols sur l'inflammation associée à l'obésité et la colite ulcéreuse induite par le dextran de sulfate de sodium (DSS) chez les souris suisse.Des études in vitro ont révélé que les extraits aqueux de feuilles de caroube et de cladodes OFI présentaient des propriétés anti-inflammatoires marquées par l'inhibition de la production d'IL-6, de TNF-α et d'oxyde nitrique (NO) dans les cellules RAW 264.7 stimulées par des lipopolysaccharides (LPS). Inhibition de la translocation du noyau NF-κβ.Pour des investigations in vivo, des souris mâles suisses ont été soumises à un régime contrôle (ND) ou à un régime riche en graisses (HFD). A la 4ème semaine après le début de l'étude, les animaux ont reçu ou non 1% d'infusion de feuilles de caroube ou d'OFI-cladode pendant 6 semaines et ont été soumis à une administration de DSS à 2% dans l'eau potable au cours des 7 derniers jours. Après sacrifice, les niveaux de cytokines pro-inflammatoires dans le plasma et l'expression de leur ARNm dans différents organes ont été déterminés. Les résultats ont montré que les infusions de feuille de caroube et de OFI-cladode réduisaient la sévérité de l'inflammation associée à l'obésité induite par HFD et la colite aiguë induite par le DSS indiquée par une diminution de l'expression des cytokines pro-inflammatoires (comme TNF-α, IL1b et IL-6) tissu adipeux et rate. En outre, les taux plasmatiques d'IL-6 et de TNF-α ont également été réduits en réponse au traitement par les infusions. Ainsi, les infusions de feuilles de caroube et d'OFI-cladode ont empêché la perméabilité intestinale grâce à la restauration des protéines de jonctions serrées (Zo1, occludines) et à l'homéostasie immunitaire. Ainsi, l'effet anti-inflammatoire des feuilles de caroube et des cladodes OFI pourrait être attribué à leurs polyphénols qui pourraient atténuer la gravité de l'inflammation associée à l'obésité et à la colite.
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Crohn's disease and ulcerative colitis, collectively known as the inflammatory bowel diseases (IBD), are largely diseases of the twentieth century, and are associated with the rise of modern, Westernized industrial society. Although the causes of these diseases remain incompletely understood, the prevailing model is that the intestinal flora drives an unmitigated intestinal immune response and inflammation in the genetically susceptible host. A review of the past and present of these diseases shows that detailed description preceded more fundamental elucidation of the disease processes. Working out the details of disease pathogenesis, in turn, has yielded dividends in more focused and effective therapy for IBD. This article highlights the key descriptions of the past, and the pivotal findings of current studies in disease pathogenesis and its connection to medical therapy. Future directions in the IBD will likely explicate the inhomogeneous causes of these diseases, with implications for individualized therapy.
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Inflammatory mediators play a critical role in ulcerative colitis immune and inflammatory processes. The aim of the study was to investigate the effects of Ginkgo biloba extract on inflammatory mediators (SOD, MDA, TNF-alpha, NF-kappaBp65, IL-6) in TNBS-induced colitis in rats. Colitis in rats was induced by colonic administration with 2,4,6-trinitrobenzene sulfonic acid (TNBS, 150 mg/kg). EGB in doses of (50, 100, 200 mg/kg) was administered for 4 weeks to protect colitis. The results showed that EGB could significantly ameliorate macroscopic and histological damage, evidently elevate the activities of SOD and reduce the contents of MDA, inhibit the protein and mRNA expressions of TNF-alpha, NF-kappaBp65, and IL-6 in the colon tissues of experimental colitis in a dose-dependent manner compared with the model group. We concluded that the probable mechanisms of EGB ameliorated inflammatory injury in TNBS-induced colitis in rats by its modulation of inflammatory mediators and antioxidation.
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The flavonoid luteolin has anti-inflammatory properties both in vivo and in vitro. However, the impact of luteolin on experimental models of colitis is unknown. To address the therapeutic impact of luteolin, NF-kappaB(EGFP) transgenic mice were fed a chow diet containing 2% luteolin- or isoflavone-free control chow (AIN-76), and acute colitis was induced using 3% dextran sodium sulfate (DSS). Additionally, development of spontaneous colitis was evaluated in IL-10(-/-);NF-kappaB(EGFP) transgenic mice fed 2% luteolin chow diet or control chow diet. Interestingly, NF-kappaB(EGFP) transgenic mice exposed to luteolin showed worse DSS-induced colitis (weight loss, histological scores) compared to control-fed mice, whereas spontaneous colitis in IL-10(-/-);NF-kappaB(EGFP) mice was significantly attenuated. Macroscopic imaging of live resected colon showed enhanced EGFP expression (NF-kappaB activity) in luteolin-fed mice as compared to control-fed animals after DSS exposure, while cecal EGFP expression was attenuated in luteolin-fed IL-10(-/-) mice. Interestingly, confocal microscopy showed that EGFP positive cells were mostly located in the lamina propria and not in the epithelium. Caspase 3 activation was significantly enhanced whereas COX-2 gene expression was reduced in luteolin-fed, DSS-exposed NF-kappaB(EGFP) transgenic mice as assessed by Western blot and immunohistochemical analysis. In vitro, luteolin sensitized colonic epithelial HT29 cells to TNFalpha-induced apoptosis, caspase 3 activation, DNA fragmentation and reduced TNFalpha-induced C-IAP1, C-IAP2 and COX-2 gene expression. We conclude that while luteolin shows beneficial effects on spontaneous colitis, it aggravates DSS-induced experimental colitis by blocking NF-kappaB-dependent protective molecules in enterocytes.
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The development of inflammatory bowel disease may involve immune dysfunction. Because enteral glutamine is the main source of amino acids for the intestinal mucosa and is metabolized at high rates by both enterocytes and immunocytes, the aim of this study was to ascertain the protective role of glutamine supplementation in a DSS-induced model of mild experimental colitis on metabolic, immune, and intestinal variables. Lewis rats were fed diets supplemented with glutamine (glutamine diet, G group) or an isoenergetic isonitrogenous control diet (C group) from postnatal d 21 (weaning) and continuing to d 35. On d 30, half of the rats from both groups were given 0.5% DSS in drinking water (G-DSS and C-DSS groups). Glutamine supplementation increased the plasma concentrations of Thr, Gln, Cit, His, and Arg and enhanced the ratio of essential to nonessential amino acids irrespective of DSS treatment. DSS administration increased the plasma Gln concentration, indicating a reduced utilization of this amino acid by the intestinal tissue. Regarding the gut-associated lymphoid tissue lymphocyte populations, DSS increased the percentages of CD3(+) T lymphocytes from Peyer's patches, NK and B lymphocytes from mesenteric lymph nodes, and NK CD8(-) cells from intraepithelial lymphocytes. The administration of glutamine did not affect the inductive populations nor did it modify T-cell subtypes or the percentage of intraepithelial lymphocytes of gut-associated lymphoid tissue. However, glutamine supplementation reduced the feces water contents in the DSS-treated but not in the untreated rats. These results indicate that glutamine supplementation can improve barrier function in rats with colitis.
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Cysteinyl leukotrienes play a part in inflammatory processes such as inflammatory bowel diseases. The present study aimed to evaluate the effects of the cys-LT-1 receptor antagonist montelukast on a mild colitis model in rats. Colitis was induced by administrating 4% dextran sulphate sodium (DSS, MW 45,000) in drinking water for 9 days. Montelukast (10 mg/kg/day) or vehicle was given by gastric gavage once daily simultaneously with DSS administration. A healthy control group receiving water as drinking fluid and vehicle by gastric gavage was included. Body weight loss, consistency of faeces (loose/diarrhoea) and occult blood in the faeces/ gross bleeding were assessed on days 6 - 9. After sacrifice, the following were assessed: colonic histology, the expression of inducible nitric oxide synthase, macrophage/monocyte marker ED1, cyclooxygenase-1 and cyclooxygenase-2, as well as the production of leukotriene B(4) and E(4), prostaglandin E(2), its metabolite bicyclic-prostaglandin E(2) and thromboxane B(2) in the colonic tissue incubation in vitro. Rats receiving DSS exhibited bloody diarrhoea from day 6 onwards. Montelukast significantly reduced the occult blood in the faeces/ gross bleeding, maintained normal body weight gain and tended to decrease the ratio of leukotriene B(4)/ prostaglandin E(2) production in the colon in vitro. The results indicate that montelukast has some potential to ameliorate mild experimental colitis induced by DSS.
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The chemical composition of the largely used tea from lemon verbena, Aloysia triphylla, was investigated. The qualitative and quantitative composition of the main aromatic and polyphenolic constituents of tea made by infusion from leaves were examined. The results showed that the relative proportions of the active constituents differ from those of the original leaves. The tea contained a large amount of polyphenolic compounds (mean value 675 mg/l; extraction yield 65%) including verbascoside (400 mg/l) and luteolin 7-diglucuronide (100 mg/l). It contained also 42 mg/l of essential oil (extraction yield 51%) with much more citral (77% of the essential oil) than the original leaves (41%).
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Virtually all inflammatory mediators investigated to date seem to be dysregulated in the inflamed intestinal mucosa of patients with inflammatory bowel disease. However, which of these are actually involved in the initiation and perpetuation of intestinal tissue damage is still not fully understood. Amongst these mediators are the reactive oxygen metabolites, produced in large amounts by the massively infiltrating leucocytes. These reactive oxygen metabolites are believed to constitute a major tissue-destructive force and may contribute significantly to the pathogenesis of inflammatory bowel disease. This paper provides a concise overview of reactive oxygen metabolite biochemistry, the types of cell and tissue damage potentially inflicted by them, and the endogenous antioxidants which should prevent these harmful effects. An up-to-date summary of the available human experimental data suggests that reactive oxygen metabolite-mediated injury is important in both the primary and downstream secondary pathophysiological mechanisms underlying intestinal inflammation. Nonetheless, how the individual components of the mucosal antioxidant enzymatic cascade respond to inflammatory conditions is a neglected area of research. This particular aspect of intestinal mucosal oxidative stress therefore merits further study, in order to provide a sound, scientific basis for the design of antioxidant-directed treatment strategies for inflammatory bowel disease patients.