Gastroprotective effect of palmatine against acetic acid-induced gastric ulcers in rats.

Gastric ulcers are one of the most common gastrointestinal disorders. The aim of this study was to investigate the gastroprotective activity and possible underlying mechanisms of palmatine against acetic acid-induced gastric ulcers in rats. Palmatine was administered orally for 7 consecutive days to treat ulcers. The ulcer area, ulcer inhibition rate, histological section, platelet-activating factor (PAF) level in serum, prostaglandin E2 (PGE2) level in gastric tissue, 5-hydroxytryptamine (5-HT) level in the brain and norepinephrine (NE) level in the adrenal glands were analyzed. Histological results showed that the ulcer areas were significantly decreased by both doses of palmatine (10 and 20 mg/kg/day) compared with the model group, and the ulcer inhibition rates were 51.42% and 60.92%, respectively. Palmatine treatment markedly increased the level of PGE2 and decreased PAF, compared with the model group; however, it had no significant effect on 5-HT and NE levels. The results indicated that palmatine may exert a gastroprotective effect against gastric ulcers, and the mechanisms might be associated with the anti-inflammatory status and the protection of gastric mucosa via increasing PGE2 and decreasing PAF rather than neurohumoral regulation through 5-HT and NE. Thus, palmatine is a potential drug for treatment of gastric ulcers.

Antioxidative Activity of Flavonoids from Abrus cantoniensis against Ethanol-Induced Gastric Ulcer in Mice.

The present study investigated the flavonoids from Abrus cantoniensis against ethanol-induced gastric ulcers in mice. The flavonoids from A. cantoniensis were extracted with ethanol and purified by macroporous resin and polyamide. The 2,2-diphenyl-1-picrylhydrazyl assay was used to measure the antioxidative activities in vitro. The ethanol-induced ulcer mouse model was used to evaluate the gastroprotective activities of the flavonoids from A. cantoniensis. In addition, a method was established to ensure accuracy for animal ulcer evaluation. The flavonoids from A. cantoniensis showed a strong free radical scavenging capacity with an IC50 of 43.83 µg/mL in the 2,2-diphenyl-1-picrylhydrazyl assay. At doses between 28.16-112.67 mg/kg, the flavonoids conspicuously reduced the ulcer index in ethanol-induced mice (p<0.001). Significant differences were found in the levels of superoxide dismutase, catalase, glutathione, and myeloperoxidase in the stomach tissues between the flavonoids from the A. cantoniensis groups and the ethanol control group. The gastroprotective effect of the flavonoids from A. cantoniensis could be due to its antioxidative activity of the defensive mechanism. The data revealed that the flavonoids from A. cantoniensis could be a potential therapeutic agent for gastric ulcer prevention and treatment.

Alkaloids from Mahonia bealei posses anti-H⁺/K⁺-ATPase and anti-gastrin effects on pyloric ligation-induced gastric ulcer in rats.

The purpose of this study was to investigate the underlying mechanism(s) of the total alkaloids (TA) from Mahonia bealei in treating pyloric ligation-induced gastric ulcers in rats. Animals were sacrificed after 19 h of the ligation. Gastric acid, peptic activities, mucin levels, H(+)/K(+)-ATPase activities and the gastrin level were analyzed. To improve the accuracy of the observations, IPP 6.0 software was introduced to measure the area of ulcer. TA (18.56 mg/kg/day, i.g.) showed an antiulcer effect by significantly decreasing the gastric ulcer areas (11.28 mm(2)) compared with model group (26.36 mm(2)). The TA ulcer inhibition ratio was 57.2%, compared with the effect of the positive control, omeprazole (62.96%). The results also showed that TA had a significant effect in inhibiting the release of H(+)/K(+)-ATPase, reducing the content of gastrin and decreasing gastric acidity on experimental animals. However, the TA had no significant effects on gastric mucus secretion and pepsin activity. Data indicated that TA had gastric ulcer protective effects by modulating the H(+)/K(+)-ATPase activity and gastrin level. TA has a potential to be developed as a pharmacological agent for the treatment of gastric ulcers.

Intestinal absorptive transport of Genkwanin from Flos genkwa using a single-pass intestinal perfusion rat model.

To investigate the absorptive transport behavior of genkwanin and the beneficial effects of monoterpene enhancers with different functional groups, the single-pass intestinal perfusion (SPIP) of rats was used. The results showed that genkwanin was segmentally-dependent and the best absorptive site was the duodenum. The effective permeability coefficient (P eff ) was 1.97 × 10(-4) cm/s and the absorption rate constant (Ka) was 0.62 × 10(-2) s(-1). Transepithelial transportation descended with increasing concentrations of genkwanin. This was a 1.4-fold increase in P eff by probenecid, whereas a 1.4-fold or 1.6-fold decrease was observed by verapamil and pantoprazole, respectively. Furthermore, among the absorption enhancers, the enhancement with carbonyl (camphor and menthone) was higher than that with hydroxyl (borneol and menthol). The concentration-independent permeability and enhancement by coperfusion of probenecid indicated that genkwanin was transported by both passive diffusion and multidrug resistance protein (MDR)-mediated efflux mechanisms.

Antioxidant effects of Genkwa flos flavonoids on Freund׳s adjuvant-induced rheumatoid arthritis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Genkwa flos (Daphne genkwa Sieb. et Zucc.), a Chinese herbal medicine, has been traditionally used for over two thousand years in China for inflammation related symptoms, including joint pain. To evaluate the antioxidative effects of flavonoid aglycones (FA) isolated from Genkwa flos on adjuvant arthritis in rats and to identify the relationship between antioxidant potential and whole blood viscosity (WBV). MATERIALS AND METHODS: FA compounds were identified using LC-MS and the content was assayed by HPLC. Arthritis was induced by an intradermal injection of Freund׳s complete adjuvant in the footpad. The effects of FA on paw volumes, secondary arthritis scores, histopathology of joints, and body and organ weights were measured. The antioxidant effects of FA and WBV were determined. RESULTS: LC-MS analysis showed that the FA contained four major compounds: luteolin, apigenin, hydroxygenkwanin and genkwanin. FA significantly decreased paw edema, arthritis scores, and weight loss. These observations were consistent with the reduction of oxidative stress and the improvement of the WBV. CONCLUSION: FA significantly decreased arthritis in a rat model through antioxidant and hemorheological modulatory mechanisms. The Genkwa flos flavonoids may have clinical potential for the treatment of rheumatoid arthritis.

Anti-rheumatoid arthritic activity of flavonoids from Daphne genkwa.

The aim of the study was to investigate the anti-rheumatoid arthritic activity of four flavonoids from Daphne genkwa (FFD) in vivo and in vitro. Flavonoids of D. genkwa were extracted by refluxing with ethanol and purified by polyamide resin. An in vivo carrageenan-induced paw edema model, tampon-granuloma model and Freund's complete adjuvant (FCA)-induced arthritis mouse model were used to evaluate the anti-rheumatoid arthritic activities of FFD. Moreover, nitric oxide (NO) release and neutral red uptake (NRU) in lipopolysaccharide (LPS)-induced murine macrophage RAW264.7 cells were used to evaluate the anti-inflammatory effect in vitro. In addition, antioxidant effect of FFD was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. A high dose of FFD significantly reduced the degree of acute inflammatory paw edema in mice as a response to carrageenan administration (p<0.01). FFD displayed a dose-dependent inhibition of granuloma formation in mice (p<0.05). FFD also inhibited chronic inflammation in adjuvant-induced arthritis rats when administered orally at the dose of 50mg/kg/day (p<0.001). In addition, FFD suppressed the production of NO and exhibited immunoregulatory function in LPS-activated RAW264.7 cells in a dose-related manner. Simultaneously, FFD revealed conspicuous antioxidant activity with IC50 values of 18.20µg/ml. FFD possesses significant anti-inflammatory and antioxidant activity, which could be a potential therapeutic agent for chronic inflammatory disorders such as rheumatoid arthritis.