Protective effects of Isofraxidin against lipopolysaccharide-induced acute lung injury in mice.

Acute lung injury (ALI) is a life-threatening disease characterized by serious lung inflammation and increased capillary permeability, which presents a high mortality worldwide. Isofraxidin (IF), a Coumarin compound isolated from the natural medicinal plants such as Sarcandra glabra and Acanthopanax senticosus, has been reported to have definite anti-bacterial, anti-oxidant, and anti-inflammatory activities. However, the effects of IF against lipopolysaccharide-induced ALI have not been clarified. The aim of the present study is to explore the protective effects and potential mechanism of IF against LPS-induced ALI in mice. In this study, We found that pretreatment with IF significantly lowered LPS-induced mortality and lung wet-to-dry weight (W/D) ratio and reduced the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in serum and bronchoalveolar lavage fluid (BALF). We also found that total cells, neutrophils and macrophages in BALF, MPO activity in lung tissues were markedly decreased. Besides, IF obviously inhibited lung histopathological changes and cyclooxygenase-2 (COX-2) protein expression. These results suggest that IF has a protective effect against LPS-induced ALI, and the protective effect of IF seems to result from the inhibition of COX-2 protein expression in the lung, which regulates the production of PGE2.

Protective effects of esculentic acid against endotoxic shock in Kunming mice.

Esculentic acid (EA), a triterpene compound extracted from the root of Phytolacca esculenta (the Chinese name Shang Lu), has been widely used to therapy a variety of inflammatory diseases such as rheumatoid arthritis, edema, hepatitis and bronchitis. The present study was designed to investigate the protective effects of EA against LPS-induced endotoxic shock by the intraperitoneal injection of EA (1, 5 and 10 mg/kg) prior to LPS stimulation (1 mg/kg, i.p.). We examined the effects of EA on the survival rate of mice, inflammatory cytokine and pro-inflammatory mediator production, histopathological changes and protein expression of COX-2 in tissue sections from lung, liver and kidney. The results indicate that EA not only increases the survival rate of mice, but decreases the levels of TNF-α, IL-6, NO and PGE2 in serum or tissues, histopathological changes and COX-2 protein expression also. Furthermore, EA also increases the levels of anti-inflammatory cytokine IL-10 in serum. Overall, these data suggest that the protective effects of EA against LPS-induced endotoxic shock may be mediated, at least in part, by regulation the release of inflammatory cytokines and mediators, and protein expression of COX-2 in mice.

Esculentic acid, a novel and selective COX-2 inhibitor with anti-inflammatory effect in vivo and in vitro.

Esculentic acid (EA), a pentacyclic triterpenoids compound extracted from the Chinese herb Phytolacca esculenta, has long been used in traditional Chinese medicine for the treatment of rheumatoid arthritis, edema, hepatitis and bronchitis disease. The present study aimed to investigate the anti-inflammatory effect of EA in vivo and in vitro and the effect of EA on cyclooxygenase (COX) protein expression. To gain insight into the anti-inflammatory effect of EA both in vivo and in vitro and its effect on COX-2 expression, we used animal inflammatory models and lipopolysaccharide (LPS)-induced mouse peritoneal macrophages to examine the anti-inflammatory action of EA. Our findings demonstrated that EA possessed potent anti-inflammatory activity both in vivo and in vitro, while the anti-inflammation action in vitro may be attributed to the inhibition of the level of TNF-α and IL-6 pro-inflammatory cytokines and PGE2 inflammatory mediator in macrophages. Meanwhile, the production of PGE2 was possibly associated with COX-2 protein expression which was similar to that of NSAIDS. The study extends our understanding of the anti-inflammatory effect of EA both in vivo and in vitro and provides clarification of the molecular mechanisms underlying the effect of EA on PGE2 production, extending a novel aspect to the pharmacological activity of EA.

Tetrahydrocoptisine protects rats from LPS-induced acute lung injury.

Recent studies show that nuclear factor-kappa B (NF-κB) signaling pathway plays a key role in contributing to the development of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Tetrahydrocoptisine is one of the main active components of Chelidonium majus L. and has been described to be effective in suppressing inflammation. The aim of the present study is to evaluate the protective effect of tetrahydrocoptisine on LPS-induced ALI in rats and clarify its underlying mechanisms of action. We found that in vivo pretreatment with tetrahydrocoptisine to rats 30 min before inducing ALI by LPS markedly decreased the mortality rate, lung wet weight to dry weight ratio, and ameliorated lung pathological changes. Meanwhile, tetrahydrocoptisine significantly inhibited the increase of the amounts of inflammatory cells, total protein content, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) secretion in the bronchoalveolar lavage fluids (BALFs). Furthermore, tetrahydrocoptisine inhibited myeloperoxidase (MPO) accumulation in lung tissue and alleviated TNF-α and IL-6 production in serum. Additionally, immunohistochemistry showed that tetrahydrocoptisine efficiently reduced nuclear factor-kappa B (NF-κB) activation by inhibiting the translocation of NF-κBp65. In conclusion, our results demonstrate that tetrahydrocoptisine possesses a protective effect on LPS-induced ALI through inhibiting of NF-κB signaling pathways, which may involve the inhibition of pulmonary inflammatory process.

δ-Amyrone, a specific inhibitor of cyclooxygenase-2, exhibits anti-inflammatory effects in vitro and in vivo of mice.

The whole plant of Sedum lineare Thunb has been used as traditional folk medicines for the treatment of sore throat, persistent hepatitis, jaundice and dysentery. δ-Amyrone (13(18)-Oleanen-3-one), a pentacyclic triterpene compound from S. lineare Thunb, was found to possess a potent anti-inflammatory effect in different inflammation model animals. Pretreatment with δ-Amyrone (i.p.) inhibited the ear edema in xylene-induced mouse ear edema. δ-Amyrone also decreased the level of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6) and leukocyte numbers in acetic acid-induced peritonitis in vivo. To clarify the possible mechanism of δ-Amyrone, we investigated the effect of δ-Amyrone in lipopolysaccharide (LPS) induced peritoneal macrophages. The data indicated that δ-Amyrone notably inhibited IL-6, TNF-α and NO production. In addition, the result showed that δ-Amyrone may control the cyclooxygenase-2 (COX-2) regulation and not the cyclooxygenase-1 (COX-1) at protein levels. These results suggest that δ-Amyrone is a bioactive agent which possesses anti-inflammatory effects, which may be relevant to the regulation of COX-2.

Protective effect of total alkaloids on lipopolysaccharide-induced acute lung injury.

BACKGROUND: Corydalis denticulato-bracteata Fedde is used as a traditional herbal medicine for the treatment of pneumonia. However, there is no scientific evidence, which validate the use of total alkaloids of denticulato-bracteata Fedde in the literature. MATERIALS AND METHODS: Male Kunming mice were randomly divided into seven groups (n = 12, each): control group, total alkaloids alone (200 mg/kg, intragastric gavage), LPS group, and three different doses (50, 100, and 200 mg/kg, intragastric gavage) for total alkaloids-treated groups, Dexamethasone (5 mg/kg, intraperitoneally) group. Corresponding drugs or vehicles were given 24 and 1 h before lipopolysaccharide (LPS) administration (5 mg/kg, intraperitoneally). The severity of pulmonary injury was evaluated 6 h after LPS challenge. RESULTS: As revealed by survival study, pretreatment with total alkaloids significantly reduced LPS-induced death. We also found that total alkaloids pretreatment markedly decreased the lung wet-to-dry weight ratios and significantly attenuated histopathologic changes. Moreover, total alkaloids decreased the production of the tumor necrosis factor α and nitric oxide in the serum and bronchoalveolar lavage fluid. Total alkaloids pretreatment also reduced LPS-induced inducible nitric oxide synthase and p65 nuclear factor kappa B protein expression in the lung. CONCLUSIONS: This study indicates that total alkaloids may have a protective effect against LPS-induced acute lung injury. This protective effect of total alkaloids seems to result from inhibition of nuclear factor kappa B activation, which causes the reduction of inflammatory markers such as tumor necrosis factor α and inducible nitric oxide synthase.

The anti-inflammatory effects of Caragana tangutica ethyl acetate extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Caragana tangutica KOM has been used to treat arthritis, wounds, fever and other disease conditions in traditional Chinese medicine (TMC). To support the application of the plant in traditional Chinese medicine by investigating the anti-inflammatory effects of the ethyl acetate extract of Caragana tangutica. MATERIALS AND METHODS: The anti-inflammatory activity was evaluated by animal models including xylene-induced ear edema in mice, carrageenan-induced paw edema in rats, acetic acid induced writhing in mice and LPS-induced acute lung injury (ALI). The anti-inflammatory mechanism was evaluated by detecting prostaglandin E2 and immunohistochemistry expression of cyclooxygenase-2 (COX-2) using an EIA assay kit and immunohistochemistry, respectively. RESULTS: The results showed that the xylene-induced ear edema in mice was significantly reduced by the ethyl acetate extract at dosages of 100, 200 and 400mg/kg, and the carrageenan-induced paw edema in rats was monitored to be reduced by the ethyl acetate extract 3h after carrageenan injection. The ethyl acetate extract was also found to reduce the inflammation pain of acetic acid-induced writhing model in a dose-dependent manner and cause reduction of the ALI in mice through the inhibition of the release of PGE2 and the LPS-induced COX-2 expression in the lung. CONCLUSION: Our study demonstrates that the ethyl acetate extract of the plant can help to reduce inflammations by inhibiting the expression of COX-2.

Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice.

Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5ml/100g) were pre-treated with THC (10 or 20mg/kg, ip), cimetidine (100mg/kg, ip) or saline in different experimental sets for a period of 3days, and animals were euthanized 4h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-α and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-κB (NF-κB) in the ethanol group. Pretreatment of THC at doses of 10 and 20mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-κB expression.