Canscora lucidissima, a Chinese folk medicine, exerts anti-inflammatory activities by inhibiting the phosphorylation of ERK1/2 in LPS-activated macrophages.

BACKGROUND: Canscora lucidissima (Levl. & Vaniot) Hand.-Mazz. (C. lucidissima), mainly distributed in southern China, has been shown to be effective in the treatment of inflammatory diseases. However, the underlying mechanism of its anti-inflammatory effect is not fully understood. METHODS: In this study, we investigated the anti-inflammatory mechanism of ethanol extract of C. lucidissima (Cl-EE) in lipopolysaccharide (LPS)-induced inflammatory models. ELISA, real-time PCR, Western blot and luciferase reporter assay were used for the experiments in vitro, and ICR mouse endotoxemia model was used for in vivo test. RESULTS: Our data showed that Cl-EE reduced the production of NO by down-regulating the mRNA and protein expression of inducible nitric oxide synthase (iNOS) in LPS-activated RAW 264.7 cells. Meanwhile, it potently decreased other proinflammatory mediators, such as TNF-α, IL-6, MCP-1 and IL-1ß at the transcriptional and translational levels. Further study indicated that Cl-EE did not affect NF-κB signaling pathway but significantly suppressed the phosphorylation of ERK1/2, rather than JNK or p38. In a LPS-induced endotoxemia mouse model, a single intraperitoneal injection of Cl-EE (75-300 mg/kg) could lower circulatory TNF-α, IL-6 and MCP-1 levels. CONCLUSIONS: Collectively, our results indicated that Cl-EE suppressed the phosphorylation level of ERK1/2 thus reducing the transcription and translation of inflammatory genes, thereby exerted anti-inflammatory activity. This study reveals the anti-inflammatory mechanism of C. lucidissima and may provide an effective treatment option for a variety of inflammatory diseases.

Lipid-soluble extracts from Salvia miltiorrhiza inhibit production of LPS-induced inflammatory mediators via NF-κB modulation in RAW 264.7 cells and perform antiinflammatory effects in vivo.

Salvia miltiorrhiza, a traditional Chinese herbal medicine, is used to treat various inflammatory diseases. In the present study, the antiinflammatory effects of S. miltiorrhiza lipid-soluble extracts (SMLE) were demonstrated in vitro and in vivo, along with its underlying mechanism of action. SMLE significantly inhibited the production of NO, TNF-α, IL-1ß and IL-6 in lipopolysaccharides (LPS)-stimulated RAW 264.7 cells. SMLE also inhibited the LPS-induced degradation of IκB-α in the cytoplasm and the translocation of p65 to the nucleus in RAW 264.7 cells. In addition, SMLE inhibited the production of intracellular reactive oxygen species (ROS) and the surface expression of CD14 induced by LPS. In animal models, intraperitoneal administration of SMLE increased the survival rate of endotoxemia and sepsis in mice. The topical administration of SMLE significantly inhibited ear edema induced by PMA. It was found that SMLE inhibits the LPS-induced gene and protein expression of iNOS, TNF-α, IL-1ß and IL-6 in macrophages by blocking NF-κB activation, and these effects are mediated, at least in part, through the inhibition of intracellular ROS generation and the surface expression of CD14. The results suggest a possible therapeutic application of SMLE in inflammatory diseases and provide scientific evidence in support of the traditional Chinese medical practice of treatment with S. miltiorrhiza.

Antifatigue activity of phenylethanoid-rich extract from Cistanche deserticola.

A phenylethanoid-rich extract (ECD) of Cistanche deserticola Y.C. Ma, a holoparasitic plant and a valuable traditional Chinese medicine, was evaluated for antifatigue activity in ICR mice. ECD (0.25, 0.50, 1.00 g/kg) was administered orally to mice for 3 weeks. The swimming time to exhaustion was longer in the treatment groups (0.50, 1.00 g/kg) than in the control group (p < 0.01). The serum creatine kinase, lactate dehydrogenase and lactic acid levels were decreased significantly in the treatment groups compared with the control group, while the contents of hemoglobin and glucose were increased significantly. In conclusion, ECD appeared to enhance the swimming capacity of mice by decreasing muscle damage, delaying the accumulation of lactic acid and by improving the energy storage. These results provide scientific evidence for the traditional Chinese medical practice of C. deserticola.

Studies on antioxidant activities of breviscapine in the cell-free system.

Breviscapine is a commercially produced plant extract from the Chinese herb Erigeron breviscapus. (Vant.) Hand.-Mazz., which contains 2 main flavonoids. It is widely used in clinic to treat ischemic diseases in which free radicals are considered to be the main causal factor. Our study is aimed to examine the antioxidant activity of this extract. The following assays were employed: 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, superoxide anion radical scavenging, nitric oxide radical scavenging, total anti-oxidative capacity, and antilipid peroxidation assays. Breviscapine was demonstrated to show an effective activity on scavenging DPPH, superoxide anion radicals and nitric oxide. The total antioxidative capacity of breviscapine (7.8 microg/ml to 250 microg/ml) was 1.22 to 6.74 FRAP value (x 10(-5) mmol). At the highest concentration of breviscapine, the inhibition extent of lipid peroxidation induced by Fe(2+) in rat liver homogenates was 38.5%. Because of the antioxidant activity, the present study is therefore designed to investigate the therapeutic potential of breviscapine for treatment of ischemic diseases.

Shuang-huang-lian attenuates lipopolysaccharide-induced acute lung injury in mice involving anti-inflammatory and antioxidative activities.

Shuang-Huang-Lian (SHL) is a common traditional Chinese preparation extracted from Lonicerae Japonicae Flos, Scutellariae Radix, and Fructus Forsythiae. In this study, we demonstrate the anti-inflammatory and antioxidative effects of SHL on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. SHL reduced the lung wet/dry weight ratio, lowered the number of total cells in the bronchoalveolar lavage fluid, and decreased the myeloperoxidase activity in lung tissues 6 h after LPS treatment. It also inhibited the overproduction of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) in the bronchoalveolar lavage fluid. Histological studies demonstrated that SHL attenuated LPS-induced interstitial edema, hemorrhage, and the infiltration of neutrophils into the lung tissue. Moreover, SHL could also enhance the superoxide dismutase and catalase activities, increase the reduced glutathione content, and decrease the malondialdehyde content. The present results suggest that SHL possesses anti-inflammatory and antioxidative properties that may protect mice against LPS-induced ALI.

Pharmacological basis for the medicinal use of muskmelon base (Pedicellus Melo.) for abdominal distention and constipation.

ETHNOPHARMACOLOGICAL RELEVANCE: Muskmelon base (Pedicellus Melo.) has a long history (Ming Dynasty) as a Chinese traditional medicine. According to traditional use, it was prepared as rectal suppositories for treating abdominal distention and constipation. The present study was carried out on the pharmacological basis for the medicinal use of muskmelon base. AIM OF THE STUDY: The objective of this study was to determine the pharmacological basis for the medicinal use of the ethanol extract from muskmelon base (EMB) for abdominal distention and constipation. MATERIALS AND METHODS: In this study, we report the gastrointestinal prokinetic action of EMB following single rectal or large intestinal administration. Laxative activity, gastric emptying and small intestinal transit tests were examined in ICR mice. SD rats were used to determine changes in large intestinal transit and contractile effects of the proximal colon in vivo. Guinea pigs were used to evaluate the contractile effects of the proximal colon and the possible mechanism or mechanisms on proximal colon activity ex vivo. Moreover, the acute toxicity of EMB was evaluated. RESULTS: In the in vivo experiments, the acute toxicity test showed that the maximum tolerated dose (MTD) of EMB was 400 mg/kg. A laxative effect was observed in mice at different dosages (6.5, 13 and 26 mg/kg). EMB showed a dose-dependent acceleration of gastric emptying (13 and 26 mg/kg). It also promoted both small intestinal (6.5, 13 and 26 mg/kg) and large intestinal (4, 8 and 16 mg/kg) transit activity. In the SD rat model, single rectal administration of EMB (8 and 16 mg/kg) showed a significant increase in both the frequency and amplitude of proximal colon smooth muscle contractility. These increases in amplitude and frequency peaked 30-60 min after EMB administration and corresponded with the results of the laxative activity test. The ex vivo experiments showed that varying doses of EMB (11.5, 23 and 46 mg/kg) had a direct prokinetic effect that was sensitive to atropine. CONCLUSIONS: Our results show that EMB is a low dosage, fast acting drug with a large therapeutic window (4-400 mg/kg) and shows significant gastrointestinal prokinetic action after single rectal or large intestinal administration. This gastrointestinal prokinetic effect was stronger in the intestines than in the stomach. This effect was sensitive to atropine, suggesting that EMB acts mainly through cholinergic mechanisms.

Antihypertensive effect of total flavone extracts from Puerariae Radix.

AIM OF THE STUDY: To evaluate the antihypertensive effect of total flavone extracts from Puerariae Radix (FEPR). To explore the hemodynamic profiles and pertinent mechanism of the extracts. MATERIALS AND METHODS: Acute and chronic antihypertensive effects of FEPR were examined in spontaneous hypertensive rats (SHRs) and reno-hypertensive rats (two kidneys one clip model, 2K1C). Anesthetized dogs were used to evaluate the hemodynamic effects of FEPR. The determination of angiotensin converting enzyme (ACE) activity in vitro and plasma renin activity (PRA) and endothelin (ET) in vivo were used to study the pilot mechanism of FEPR. Moreover, the toxicity study of FEPR was evaluated. RESULTS: FEPR (100, 200 and 400 mg/kg, i.v.) notably reduced the blood pressure of SHRs in a short time period. A two-week administration of FEPR (45, 90 and 180 mg/kg, p.o.) decreased the blood pressure of both 2K1C rats and SHRs. The results of hemodynamic study in anesthetized dogs showed that, left ventricular end systolic pressure and left ventricular dP/dt(max) had shown no significant difference between FEPR-treated dogs and those from the control group, while the cerebral blood flow increased significantly in FEPR-treated groups. FEPR significantly inhibited the ACE activities in vitro dose dependently, and inhibited the PRA in vivo, while the content of ET showed no difference in the FEPR treated group comparing with the control group. CONCLUSIONS: FEPR shows significantly blood pressure lowering and cerebral vascular resistance (CVR) decreasing effect, which can partly be explained by the involvement of the Renin-Angiotensin-System (RAS).