The possible mechanisms of Picrasma quassiodes (D. Don) Benn. in the treatment of colitis induced by 2,4,6-trinitrobenzene sulfonic acid in mice

Ethnopharmacological relevance

Picrasma quassiodes (D. Don) Benn.(PQB) is used in folk medicines for the treatment of colds, upper respiratory infection, acute tonsillitis, acute gastroenteritis, bacillary dysentery and a variety of acute infectious diseases in Asia. Although recent reports indicate that PQB has antibacterial, and anti-inflammatory effects, its effects on colitis and its inhibitory mechanisms have not been previously reported.

Aim of the study

To assess the effects and the mode of action of the extract of Picrasma quassiodes (D. Don) Benn.(PQB) on a model of colitis in mice induced by trinitrobenzene sulfonic acid (TNBS).

Materials and methods

We induced mice colitis using TNBS/ethanol, then different doses of Picrasma quassiodes (D. Don) Benn.(PQB) extract (100, 200 and 400 mg/kg/day) and sulfasalazine (500 mg/kg/day) were administered by gavage for 7 days after the induction of colitis. The mice body weight, colonic wet weight, colonic lengths, myeloperoxidase (MPO) activity, macroscopic and histological colon injury were observed. Pro-inflammatory cytokines such as: tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) were assayed by enzyme-linked immunoassay. The protein expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the colons were determined by immunohistochemical analysis.

Results

PQB administration effectively prevented mice diarrhea, decreasing of the body weights, shortening of colon length and increasing of colon wet weight. Macroscopic and histological examinations also indicated that it was protected against colonic edema, ulceration and MPO activity elevation. Furthermore, PQB inhibited the abnormal secretions of pro-inflammatory cytokines, such as TNF-α and IL-8. Additionally, administration of PQB effectively inhibited COX-2 and iNOS protein expression.

Conclusions

These results suggest that PQB has an anti-inflammatory effect on TNBS-induced colitis due to the down-regulations of the productions and expressions of inflammatory mediators, and that it may be a potential inflammatory bowel disease (IBD) drug candidate.     

Relationships between pharmacokinetics and efficacy of Xie-xin decoction in rats with experimental ulcerative colitis

Ethnopharmacological relevance

Xie-xin decoction (XXD) has been used as a classic formula in China for the treatment of gastrointestinal dysfunction such as ulcerative colitis (UC). However, no potential action mechanisms and active compounds had been systematically investigated.

Aim of the study

To explore the effectiveness and the material basis of XXD in trinitrobenzene sulfonic acid (TNBS)-induced UC rats.

Materials and methods

XXD was administered orally for 8 days at a dosage of 2 or 4 g/kg/day. Plasma pharmacokinetic properties and colon tissue concentrations of multiple compounds from XXD were detected. Tissue damage scores, production of interleukin (IL)-10 and myeloperoxidase (MPO), expression of tumor necrosis factor-alpha (TNF-α) and nuclear factor-kappa Bp65 (NF-κBp65) in colon tissues were examined. Canonical correlation analysis was performed to evaluate the relationships between pharmacokinetics and efficacy to elucidate significantly active compounds of XXD.

Results

XXD promoted the recovery of colitis and inhibited the colonic inflammation damage in UC rats by reducing the level of MPO and the expression of TNF-α and NF-κBp65, and increasing the production of IL-10 in colon tissues. Efficacy of XXD was positively related with AUC of five plasma compounds (baicalin, berberine, wogonoside, wogonin, and rhein) and concentrations of six colon tissue compounds (coptisine, jatrorrhizine, palmatine, berberine, baicalein and emodin), respectively.

Conclusions

The multiple compounds in plasma and colon tissues from XXD might be the main material basis for therapeutic potentials in UC rats.     

Inhibitory effects of Geijigajakyak-Tang on trinitrobenzene sulfonic acid-induced colitis

Aim of the study

Water extract of Geijigajakyak-Tang (GJT) consisting of five crude drugs [dried root of P. lactiflora Peony (Paeoniaceae), dried trunk bark of C. cassia Blume (Lauraceae), seed of Z. jujube var. inermis Mill (Rhamnaceae), fresh root of Z. officinale Rocoe (Zingiberaceae) and dried trunk bark of G. uralensis Fish (Leguminosae)] is a folk medicine used for the treatment of chronic colitis. This study was designed to further elucidate the effect of GJT on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.

Materials and methods

GJT orally given to mice before and after TNBS intoxication, and their clinical and morphological changes, myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels in colon tissues, were evaluated on Day 8 post-TNBS. Furthermore, the effect of six major constituents of individual herbs on ileum smooth muscle contraction and neutrophil chemotaxis was studied.

Results

GJT had a significant anti-inflammatory effect based on clinical and morphologic changes, MPO activity and MDA levels in colon tissues as compared with sham control. GJT and 5 major active constituents of individual herbs, paeoniflorin, cinnamaldehyde, jujuboside A, jujubogenin, and diammonium glycyrhhizinate significantly inhibited neutrophil chemotaxis. GJT significantly inhibited muscle contraction (IC₅₀; 2.10 ± 0.11 mg/ml), and 1,8-cineol has the most spasmolytic activity (IC₅₀; 0.10 ± 0.03 mg/ml).

Conclusion

GJT has significant anti-inflammatory effects on TNBS-induced colitis via inhibitions of smooth muscle contraction and neutrophil chemotaxis.     

Anti-inflammatory effects of iridoid glycosides fraction of Folium syringae leaves on TNBS-induced colitis in rats

Aim of the study

To investigate the effects and the protective mechanism of iridoid glycosides (IG) enriched from Folium syringae leaves on ulcerative colitis (UC) model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats.

Materials and methods

UC in rats was induced by colonic administration with TNBS. IG (80, 160 and 240 mg/kg) was administered for 2 week to experimental colitis rats. The inflammatory degree was assessed by macroscopic score, histology and myeloperoxidase (MPO) activity. Nitric oxide (NO) and malondialdehyde (MDA) levels were measured with biochemical methods. The protein expressions of nuclear factor-kappaBp65 (NF-κBp65) and mRNA expressions of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and NF-κBp65, were determined by immunohistochemistry and real-time quantitative PCR, respectively.

Results

IG significantly ameliorated macroscopic damage and histological changes, reduced the activity of MPO, depressed MDA and NO levels and effectively inhibited the protein and mRNA expressions of NF-κBp65, TNF-α and IL-6 in the colon tissues of experimental colitis in a dose-dependent manner. Moreover, the effects of IG (160 mg/kg and 240 mg/kg) were superior to salicylazosulfapyridine (150 mg/kg).

Conclusion

We demonstrated for the first time that IG possessed marked protective effects on experimental colitis through its antioxidation and inhibiting inflammatory mediators by down-regulation of the expressions of NF-κBp65.     

The possible mechanisms of Fructus Mume pill in the treatment of colitis induced by 2,4,6-trinitrobenzene sulfonic acid in rats

Ethnopharmacological relevance

Fructus Mume pill (FMP) has been used as a folk remedy for gastrointestinal diseases in China over thousands of years. FMP was approved for the treatment of gastrointestinal diseases in 2001 by the State Food and Drug Administration (SFDA) of China. Although FMP had significant efficacy for treatment of the patients with inflammatory bowel disease (IBD) in the clinic, the mechanism of action is still unclear.

Aim of the study

In the present study, the effects and possible mechanism of FMP on colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) were investigated.

Materials and methods

Fifty-four SD rats were divided into six groups. Nine rats for each group from three independent experiments were investigated for the effects of FMP.

Results

FMP protected against diarrhea, colon weight increase, colonic accretion, ulceration and myeloperoxidase (MPO) activity elevation. The effects of FMP on recovery of colonic damage and restoration of the normal structures of colorectums were superior to dexamethasone (DEX). FMP promoted the restoration of abnormal cytokine secretion after TNBS treatment. FMP was effective in restoring the balance of intestinal bacteria population from the imbalance of G⁺/G⁻ in rats with colitis.

Conclusions

The results indicated that FMP is effective in treatment of colitis in an experimental rat model. The possible mechanisms may be through down-regulation of Th1-polarized immune response and opsonic effect of intestinal commensal bacteria in this model system.     

Anti-inflammatory intestinal activity of Abarema cochliacarpos (Gomes) Barneby & Grimes in TNBS colitis model

Aim of the study

To assess the anti-inflammatory effect of butanolic fraction of methanolic extract from bark of Abarema cochliacarpos in acute ulcerative colitis model induced by intracolonic administration of trinitrobenzene sulfonic acid (TNBS) in Wistar rats.

Materials and methods

Abarema cochliacarpos (100 and 150 mg/kg/day) was administered by gavage 48, 24 and 1 h prior to the induction of colitis with 10 mg/kg of TNBS and, 24 h later.

Results

Phytochemical studies by mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR) revealed that catechins were a major component into condensate class of tannins. Treatment with Abarema cochliacarpos decreased significantly macroscopic damage as compared with TNBS (p < 0.05). Histological analysis showed that both doses of the extract improved the microscopic structure and preserved some areas of the colonic mucosa structure. In addition, myeloperoxidase activity (MPO), as a marker of neutrophil infiltration, was decreased in a dose-dependent way (p < 0.01 and p < 0.001 respectively), TNF-α level was also diminished with the highest dose of the extract (p < 0.001) and, IL-10 level obtained no significant results. In order to elucidate some of the mechanisms, expression of inducible inflammatory enzymes, such as cyclooxygenase (COX)-2 and nitric oxide synthase (iNOS), were studied showing a significant reduction. Finally, the involvement of c-Jun N-terminal kinase (JNK) signalling demonstrated a reduction in the JNK activation with the highest dose (p < 0.05 vs TNBS).

Conclusions

We have shown for the first time that the extracts obtained from Abarema cochliacarpos bark possess active substances, which exert marked protective effects in acute experimental colitis, confirming and justifying, at least in part, the popular use of this plant to treat gastrointestinal diseases.     

Preventive and therapeutic effects of Danhong injection on lipopolysaccharide induced acute lung injury in mice

Ethnopharmacological relevance

Danhong injection (DHI), a Chinese Materia Medica standardized product extracted from Radix et Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Labiatae, Danshen in Chinese) and Flos Carthami (Carthamus tinctorius L., Compositae, Honghua in Chinese), has been reported to have anti-inflammatory, anti-oxidative and anti-fibrinolytic properties, which is used extensively for the treatment of cardiovascular diseases in clinic.

Aim of this study

The present study aimed to investigate the preventive and therapeutic effects of DHI on lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice.

Materials and methods

Lung injury was induced by intranasal instillation with 10 μg LPS. Mice were randomly divided into four groups:Control group; LPS group; LPS+5 ml/kg DHI group and LPS+10 ml/kg DHI group. The effects of DHI on LPS-induced neutrophils influx, inflammatory cytokines release, protein leakage, myeloperoxidase (MPO) and superoxide dismutase (SOD) activities, malondialdehyde (MDA) level were examined. In addition, the NF-κB activation in lung tissues was detected by Western blot.

Results

In LPS challenged mice, DHI significantly reduced the infiltration of activated neutrophils and decreased the levels of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF). DHI also inhibited protein extravasation in BALF, attenuated edema and the pathological changes in the lung. In addition, DHI markedly prevented LPS-induced elevation of MDA and MPO levels, as well as reduction of SOD activity. Further study demonstrated that DHI effectively inhibited the NF-κB activation in lung tissues.

Conclusion

DHI has been demonstrated to protect mice from LPS induced acute lung injury by its anti-inflammatory and anti-oxidant activities.     

Anti-inflammatory effects of Pulvis Fellis Suis extract in mice with ulcerative colitis

Ethnopharmacological relevance

Pulvis Fellis Suis is used in folk medicines to treat intestinal diseases, acute pharyngitis, whooping cough and asthma in China. Although several reports indicate that Pulvis Fellis Suis display diverse biological activities, such as antibacterial, anti-inflammatory and anti-infusorian effects, its effects on ulcerative colitis have not been previously explored.

Aim of the study

The purpose of the present study is to assess the anti-inflammatory effect of Pulvis Fellis Suis (PFS) extract in acute ulcerative colitis model induced by trinitrobenzene sulfonic acid (TNBS) in mice.

Materials and methods

Different doses of Pulvis Fellis Suis extract (100, 200 and 400 mg/kg/day) and sulfasalazine (500 mg/kg/day) were administered by gavage for 7 days after the induction of colitis with TNBS. The efficacy of PFS was studied by macroscopical and histological scoring systems as well as myeloperoxidase (MPO) activity. Serum levels, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were assayed by enzyme-linked immunoassay. The expression of cyclooxygenase (COX)-2 in the colons was assessed by immunohistochemical analysis.

Results

Treatment with PFS significantly attenuated macroscopic damage as compared with TNBS (P < 0.01). Histological analysis showed that PFS improved the microscopic structure and preserved some areas of the colonic mucosa structure. In addition, administration of PFS effectively inhibited COX-2 protein expression and MPO activity accumulation. TNF-α and IL-6 levels were also diminished dose-dependently (P < 0.05, P < 0.01), and IL-6 level obtained had no significant results by small dose of PFS. All the effects of these parameters were comparable to that of the standard sulfasalazine, especially at the highest dose level.

Conclusions

We have shown for the first time that PFS has an anti-inflammatory effect in TNBS-induced ulcerative colitis which might be related to the reduction of up-regulated TNF-α and IL-6 production, and that it may have therapeutic value in the setting of inflammatory bowel disease (IBD).     

Effect of Rhizoma Polygonati on 12-O-tetradecanoylphorbol-acetate-induced ear edema in mice

Ethnopharmacological relevance

Rhizoma Polygonati is originated from the dried rhizomes of Polygonatum sibircum Red. It has long been used in traditional Chinese medicine for the treatment of inflammatory disorders.

Aim of the study

The present study aims to investigate the anti-inflammatory effect of aqueous extract of Rhizoma Polygonati (ERP) in a mouse model of inflammation induced by 12-O-tetradecanoylphorbol-acetate (TPA).

Materials and methods

The anti-inflammatory effect was evaluated by measuring the ear thickness and activity of myeloperoxidase (MPO). The anti-inflammatory mechanism was explored by determining the protein and mRNA levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6.

Results

The results showed that ERP significantly decreased the ear thickness and MPO activity in mouse model of inflammation induced by TPA. In addition, ERP also remarkably inhibited the protein and mRNA levels of iNOS, COX-2, TNF-α, IL-1β, and IL-6.

Conclusions

These results indicate that ERP has potential anti-inflammatory effect on TPA-induced inflammatory in mice, and the anti-inflammatory effect may be mediated, at least in part, by inhibiting the mRNA expression of a panel of inflammatory mediators including iNOS, COX-2, TNF-α, IL-1β, and IL-6.     

The in vivo and in vitro study of polysaccharides from a two-herb formula on ulcerative colitis and potential mechanism of action

Ethnopharmacological relevance

Lycium barbarum and Astragalus membranaceus are two traditional medicinal herbs widely used in China for nourishing Yin and reinforcing Qi. The purpose of the study was to investigate the prophylactic and curative effects of crude polysaccharides (QHPS) extracted from a two-herb formula composed of Lycium barbarum and Astragalus membranaceus at a ratio of 2:3 in colitis rats, and to further elucidate the potential mechanism of action in epithelial cell proliferation in vitro.

Materials and methods

An acetic acid (AA)-induced ulcerative colitis rat model was applied in the study. Two independent protocols were used to assess the prophylactic and curative effects of QHPS, respectively, in which rats were either pre-treated with QHPS (0.18 g/kg) for 14 days prior to AA induction, or post-treated with QHPS for 7 days after AA induction. The stool consistency and weight loss were used to evaluate disease activity. The morphological changes in intestinal mucosa at the end of the experiments were observed. The serum levels of endotoxin (EDT), diamine oxidase (DAO) and d-lactate (DLA), important biochemical markers for evaluating intestinal mucosal structure and function, were measured. In the in vitro mechanistic studies, rat intestinal epithelial cells (IEC-6) were used to access for epithelium regeneration.

Results

The intra-colonic instillation of AA induced ulcerative colitis in rat, as indicated by diarrhea, weight loss, and colonic mucosal damage. Both prophylactic and curative treatments effectively reduced the weight loss and diarrhea and attenuated the colonic mucosal damage associated with inducible colitis. The significant increase in serum levels of DAO, DLA and EDT was induced by AA and inhibited by QHPS treatment. Moreover, QHPS could significantly stimulate IEC-6 proliferation in a dose-dependent manner (p<0.05).

Conclusion

The present study indicated for the first time that polysaccharides extracted from this two-herb formula can protect against experimental ulcerative colitis, presumably by promoting the recovery of the intestinal barrier.     

Production of Th1- and Th2-dependent cytokines induced by the Chinese medicine herb, Rhodiola algida, on human peripheral blood monocytes

Ethnopharmacological relevance

Rhodiola algida, an herb ingredient used in Chinese medicine, has been clinically proven to be effective in enhancing human immune responses.

Aim of study

This study attempted to identify the potential immunomodulatory effect of Rhodiola algida extract in human immune system in vitro, and to examine its underlying molecular effects.

Materials and methods

Firstly, the bioactive marker compound salidroside was used for standardization of Rhodiola algida extract by reversed-phase HPLC. Secondly, the regulation of human immune responses was investigated in human peripheral blood monocytes. A series of cytokines known to play important roles in the human immune responses were examined.

Results

The current study provided quantitative assay for the marker compound, salidroside, in the Rhodiola algida extract for ensuring the quality consistency of Rhodiola algida used in the following experiments. Biological assay indicated that Rhodiola algida stimulates human peripheral blood lymphocytes and its underlying immunomodulatory effects probably through its regulation of IL-2 in Th1 cells and IL-4, IL-6, IL-10 in Th2 cells.

Conclusion

The findings may enable us to further explain the pharmacological properties in Chinese medicine and make Rhodiola algida a very promising immunomodulating agent.     

Orally administered aqueous extract of Inonotus obliquus ameliorates acute inflammation in dextran sulfate sodium (DSS)-induced colitis in mice

Ethnopharmacological relevance

Chaga mushroom (Inonotus obliquus) has been used in folk medicine to treat several disorders through its various biological functions. I. obliquus is claimed to produce general immune-potentiating and strengthening, antiinflammatory, and antitumor properties, but its effects on intestinal inflammation (ulcerative colitis) are clearly not understood.

Aim of the study

To determine the effects and mode of action of an aqueous extract of I. obliquus (IOAE) on experimental colitis in mice induced by dextran sulfate sodium (DSS).

Materials and methods

Female 5-week-C57BL/6 mice were randomized into groups differing in treatment conditions (prevention and treatment) and doses of IOAE (50 and 100 mg/kg body weight). Mice were exposed to DSS (2%) in their drinking water over 7 day to induce acute intestinal inflammation. In colon tissues, we evaluated histological changes by hematoxylin and eosin staining, levels of iNOS by immuno-histochemical staining, and neutrophil influx by myeloperoxidase assay. mRNA expression of pro-inflammatory mediators TNF-α, IL-1β, IL-6, and IFN-γ was determined by RT-PCR.

Results

Histological examinations indicated that IOAE suppressed edema, mucosal damage, and the loss of crypts induced by DSS. IOAE markedly attenuated DSS-induced iNOS levels and myeloperoxidase accumulation in colon tissues, demonstrating its suppressive effect on infiltration of immune cells. In addition, IOAE significantly inhibited mRNA expression of pro-inflammatory cytokines induced by DSS in colon tissues.

Conclusion

Our results suggest anti-inflammatory effect of IOAE at colorectal sites due to down-regulation of the expression of inflammatory mediators. Suppression of TNF-α and iNOS together with IL-1β by IOAE denotes that it might be a useful supplement in the setting of inflammatory bowel disease.     

Anti-inflammatory intestinal activity of Arctium lappa L. (Asteraceae) in TNBS colitis model

Ethnopharmacological relevance

In Brazilian traditional medicine, Arctium lappa (Asteraceae), has been reported to relieve gastrointestinal symptoms.

Aim of the study

In the present study, we investigated the effects of the lactone sesquiterpene onopordopicrin enriched fraction (ONP fraction) from Arctium lappa in an experimental colitis model induced by 2,4,6 trinitrobenzene sulfonic acid and performed experiments to elucidate the underlying action mechanisms involved in that effect.

Materials and methods

ONP fraction (25 and 50 mg/kg/day) was orally administered 48, 24 and 1 h prior to the induction of colitis and 24 h after. The inflammatory response was assessed by gross appearance, myeloperoxidase (MPO) activity, tumor necrosis factor alpha (TNF-α) levels and a histological study of the lesions. We determined cyclooxygenase (COX)-1 and -2 protein expressions by western blotting and immunohistochemistry assays.

Results

TNBS group was characterized by increased colonic wall thickness, edema, diffuse inflammatory cell infiltration, increased MPO activity and TNF-α levels. On the contrary, ONP fraction (25 and 50 mg/kg) treatment significantly reduced the macroscopic inflammation scores (p<0.05 and p<0.01, respectively) and morphological alterations associated with an increase in the mucus secretion. Similarly, the degree of neutrophil infiltration and the cytokine levels were significantly ameliorated. Moreover, COX-2 expression was up regulated in TNBS-treated rats. In contrast, ONP fraction (50 mg/kg) administration reduced COX-2 overexpression.

Conclusions

We have shown that the ONP fraction obtained from Arctium lappa exert marked protective effects in acute experimental colitis, confirming and justifying, at least in part, the popular use of this plant to treat gastrointestinal diseases.     

Intestinal anti-inflammatory activity of hydroalcoholic extracts of Phlomis purpurea L. and Phlomis lychnitis L. in the trinitrobenzenesulphonic acid model of rat colitis.

Ethnopharmacological relevance

Different species from genus Phlomis, frequently native from the the eastern Mediterranean zone, have been used in traditional medicine as an anti-inflammatory remedy. Among other constituents, they contain polyphenols that show antioxidant properties, which are interesting for the treatment of inflammatory pathologies associated with oxidative stress in humans, such as inflammatory bowel disease (IBD). The aim of this study was to evaluate the intestinal anti-inflammatoy effect of hydroalcoholic extracts of Phlomis lychnitis and P. purpurea in the trinitrobenzenesulphonic acid (TNBS) model of rat colitis, a well characterized experimental model with some resemblance to human IBD.

Materials and methods

Hydroalcoholic extracts of both plants were characterized by determining their polyphenolic content and then assayed in the TNBS model of rat colitis. For this purpose, female Wistar rats were assigned to seven groups (n=10): healthy control, untreated TNBS-colitis and five TNBS- colitis groups treated with Phlomis lychnitis (10 and 20 mg/kg), P. purpurea (10 and 25 mg/kg) and sulphasalazine (200 mg/kg), as a positive control. Treatments started the same day of TNBS colitis induction, and rats were sacrificed one week later. Colonic inflammation was evaluated both histologically and biochemically.

Results

The histological (macroscopic and microscopic) analysis of colonic samples revealed that both extracts showed an anti-inflammatory effect, which was confirmed biochemically by a decreased colonic MPO activity, a maker of neutrophil infiltration, an increased colonic glutathione content, which counteracts the oxidative status associated with the inflammatory process, and a down-regulated iNOS expression. However, only the extract of P. purpurea reduced the expression of the proinflammatory cytokines IL-1β and IL-17, the chemokines CINC-1 and MCP-1, as well as the adhesion molecule ICAM-1, ameliorating the altered immune response associated with the colonic inflammation. Furthermore, both P. lychnitis and P. purpurea extracts were able to significantly increase the expression of markers of epithelial integrity such as MUC-2, MUC-3 and villin, thus revealing an improvement in the altered colonic permeability that characterizes colonic inflammation.

Conclusions

Both extracts showed intestinal anti-inflammatory activity in the TNBS model of rat colitis, thus confirming their traditional use in digestive inflammatory complaints. In addition to their antioxidant properties, other mechanisms can contribute to this beneficial effect, like an improvement in the intestine epithelial barrier and a downregulation of the immune response.     

Hymenaea stigonocarpa Mart. ex Hayne: A tropical medicinal plant with intestinal anti-inflammatory activity in TNBS model of intestinal inflammation in rats

Ethnopharmacological relevance

Stem bark and fruit pulp of Hymenaea stigonocarpa Mart ex. Hayne (Fabaceae) has been popularly used to treat inflammation and gastrointestinal diseases including ulcers, diarrhea and gastric pain. The aim of this study was to investigate the intestinal anti-inflammatory activity of a methanol extract derived from the stem bark and diet with fruit pulp of Hymenaea stigonocarpa in the TNBS model of intestinal inflammation in rats.

Material and methods

The intestinal anti-inflammatory activity of stem bark extract (100, 200 and 400 mg/kg) and fruit pulp (10% and 5% in diet) was measured against the intestinal inflammatory process induced by TNBS (trinitrobenzesulphonic acid) in rats. The protective effects were evaluated as follows: evaluation of intestinal damage (damage score, extension of lesion, colon weight/length ratio), incidence of diarrhea and adherence to adjacent organs, colon glutathione (GSH) and malondialdehyde (MDA) contents, myeloperoxidase (MPO) and alkaline phosphatase (AP) activities. In addition, in vitro studies on lipid peroxidation in rat brain membranes and phytochemical profile were performed with both stem bark and fruit pulp.

Results

Treatment with 100, 200 and 400 mg/kg of stem bark extract and 10% fruit pulp flour showed protective effects in the TNBS-induced colon damage, which was related to inhibition of MPO and AP activities, reduction in colon MDA content, and counteraction of GSH depletion induced by inflammatory process. A concentration-dependent inhibitory effect on the lipid peroxidation in rat brain membranes for stem bark and fruit pulp was determined, with an IC₅₀ value of 5.25±0.23 μg/mL and 27.33±0.09 μg/mL, respectively. Similar phytochemical composition was observed in fruit and stem bark, including mainly flavonoids, condensed tannins and terpenes.

Conclusions

Stem bark extract and fruit pulp flour of Hymenaea stigonocarpa prevented TNBS-induced colonic damage in rats and this protective effect were associated to an improvement of intestinal oxidative stress. The observed anti-inflammatory and antioxidant effects may be associated to the presence of flavonoids and tannins in the stem bark and fruit pulp of Hymenaea stigonocarpa.     

Effect of Zhuyeshigao granule on tumor necrosis factor-α and interleukins serum protein levels in rats with radiation esophagitis

Objective

To investigate the effects of Zhuyeshigao granule (ZSG) on tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-2, IL-6, and IL-8 in rats with radiation esophagitis.

Methods

Fifty Wistar rats were randomly divided into five groups (10 rats in each group): control (without radiation), saline-treated, and low, medium, and high-dose ISG-treated groups. Rats were given normal saline (10 mL/kg) or 1.15, 2.3, or 4.6 g/kg ZSG by intragastric administration once a day for 7 days. A rat model of radiation esophagitis was established by local irradiation of Co60 (490.25 cGy/min, totaling 30 Gy). The administration of ZSG was continued for another 7 days and on the 7th day post-irradiation, inferior vena cava blood was collected. The serum was separated, and TNF-α, IL-1, IL-2, IL-6, and IL-8 protein levels were determined.

Results

Inflammatory response factors were found in the serum of each group. However, levels in ZSG-treated groups were significantly lower than in the saline-treated group (P<0.05).

Conclusion

ZSG may prevent the development of radiation esophagitis, perhaps by inhibiting the generation and release of the inflammatory response factors TNF-α, IL-1, IL-2, IL-6, and IL-8.     

Therapeutic effects of total alkaloids of Tripterygium wilfordii Hook f. on collagen-induced arthritis in rats

Ethnopharmacological relevance

Tripterygium wilfordii Hook f. is one of Traditional Chinese Medicines which is commonly used to treat rheumatoid arthritis (RA). The total alkaloids were the main constituent part of Tripterygium wilfordii Hook f. It has a great significance to study the effects of the total alkaloids of Tripterygium wilfordii Hook f. (ATW) on RA.

Aim of the study

This paper aims at investigating the therapeutic effect of ATW on RA and its possible mechanism, and providing a theoretical and experimental basis for the clinical use of ATW.

Materials and methods

The model of wistar rats of type II collagen-induced arthritis (CIA) was made, and the rats were perfused a stomach with ATW for 4 weeks continuously. Then the levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-<alpha>, in the serum of CIA rats were detected by enzyme linked immunosorbent assay (ELISA), and the joint pathological section of CIA rats was observed by hematoxylin and eosin (HE) staining method and the expression of IL-6, IL-8, nuclear factor kappa B (NF-κB), TNF-α were measure by immunohistochemistry staining method.

Results

Compared with model group, ATW could significantly reduce paw swelling and suppresse articular cartilage degenerated. The results also found that there was significant reduction levels of IL-6, IL-8 and TNF-α in serum of CIA rats treated with ATW and ATW inhibited the expression of IL-6, IL-8, NF-κB, TNF-α in synovial tissue.

Conclusion

ATW not only could inhibit the symptom of CIA rats significantly but also could inhibit the production of IL-6, IL-8, TNF-α in serum and the expression of IL-6, IL-8, NF-κB and TNF-α in synovial tissue targeting the inflammatory. ATW would be a drug as a novel botanical drug for the treatment of RA.     

Effects of magnolialide isolated from the leaves of Laurus nobilis L. (Lauraceae) on immunoglobulin E-mediated type I hypersensitivity in vitro

Ethnopharmacological relevance

Laurus nobilis L. (Lauraceae) has been used for folk medicines in the Mediterranean area and Europe to treat various disorders including skin inflammation (dermatitis) and asthma.

Aim of the study

Our aim was to investigate the scientific evaluation of the compounds from Laurus nobilis L. on immuniglobulin E (IgE)-mediated type I hypersensitivity responses in vitro such as atopic dermatitis and asthma.

Methods and materials

Seven compounds were isolated and examined for the mast cell stabilizing effect on IgE-sensitized RBL-2H3 mast cells by measuring the β-hexosaminidase activity. In addition, the effects on interleukin (IL)-4 production and IL-5-dependent Y16 early B cell proliferation were investigated as well as their cytotoxic effects on RBL-2H3 cells.

Results

Among the seven isolated compounds, magnolialide attenuated the release of β-hexosaminidase from RBL-2H3 cells with an IC₅₀ value of 20.2 μM, while the other compounds revealed no significant effects at concentrations tested. Furthermore, magnolialide significantly inhibited the IL-4 release with an IC₅₀ value of 18.1 μM and IL-4 mRNA expression with an IC₅₀ value of 15.7 μM in IgE-sensitized RBL-2H3 cells. In addition, the inhibition of IL-5-dependent proliferation of early B cells (Y16 cells) by magnolialide was demonstrated with an IC₅₀ value of 18.4 μM.

Conclusion

These results suggest that the magnolialide might be a candidate for the treatment of IgE-mediated hypersensitivity responses such as atopic dermatitis and asthma by inhibiting mast cell degranulation, the IL-4 production, and IL-5-dependent early B cell proliferation, key factors in the development and amplification of type I hypersensitivity reactions.     

Hepatoprotective effect of the ethanol extract of Vitis thunbergii on carbon tetrachloride-induced acute hepatotoxicity in rats through anti-oxidative activities

Ethnopharmacological relevance

Vitis thunbergii var. taiwaniana are traditionally used for the treatment of diarrhea, fracture and injury, jaundice, and hepatitis in Taiwan.

Aim of the study

The hepatoprotective activity of its plant extracts seems to be been associated with its antioxidant activity. This paper aims to investigate the in vitro and in vivo antioxidant effects of the ethanol extract of Vitis thunbergii (EVT).

Materials and methods

In HPLC analysis, the fingerprint chromatogram of EVT was established. Antioxidant ability of EVT was investigated by employing several established in vitro methods. In vivo antioxidant activity was tested against CCl₄-induced toxicity in mice. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected in the blood to indicate hepatic injury. Product of lipid peroxidation (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) contents were evaluated for oxidative stress in hepatic injury. Moreover, histopathological observation was assayed for the degree of hepatic injury.

Results

EVT exhibited strong antioxidant ability in vitro. After oral administration of EVT significantly decreased ALT and AST, and ameliorated the oxidative stress in hepatic tissue and increased the activity of CAT, SOD, GPx, and GSH. Serum tumor necrosis factor-alpha (TNF-α), interleukin−1β (IL-1β), and nitric oxide (NO) were decreased in the group treated with CCl₄ plus EVT. Western blotting revealed that EVT blocked protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in CCl₄-treated rats, significantly. Histopathological examination of livers showed that EVT reduced fatty degeneration, cytoplasmic vacuolization and necrosis in CCl₄-treated rats.

Conclusion

This study suggests that EVT possesses antioxidant effects in vitro and hepatoprotective effect on acute liver injuries induced by CCl₄in vivo, and the results suggested that the effect of EVT against CCl₄-induced liver damage is related to its antioxidant properties.