Ameliorative Effects of Scopoletin from Crossostephium chinensis against Inflammation Pain and Its Mechanisms in Mice.

Scopoletin exists in nature as an anti-oxidant, hepatoprotective, and anti-inflammatory activities reagent. In this study, we have investigated the analgesic effects of the scopoletin using the models of acetic acid-induced writhing response and the formalin test, the anti-inflammatory effects of scopoletin using model of λ-carrageenan (Carr)-induced paw edema. The treatment of ICR mice with scopoletin inhibited the numbers of writhing response and the formalin-induced pain in the late phase. This study demonstrated that the administration of scopoletin resulted in the reduction of Carr-induced mice edema, and it increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) after Carr injection. We also demonstrated scopoletin significantly attenuated the malondialdehyde (MDA) level in the edema paw after Carr injection. Scopoletin decreased the NO, tumor necrosis factor (TNF-α) and prostaglandin E2 (PGE(2)) levels on serum after Carr injection. Scopoletin decreased Carr-induced inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in the edema paw. These anti-inflammatory mechanisms of scopoletin might be related to the decrease in the level of MDA via increasing the activities of SOD, CAT, and GPx in the edema paw. Also, scopoletin could affect the production of NO, TNF-α, and PGE(2), and therefore affect the anti-inflammatory effects.

Antioxidant and antiproliferative activities of Crossostephium chinensis (L.) Makino.

Crossostephium chinensis (L.) (CC) Makino is a common traditional Chinese medicinal plant used to dehumidify and cure rheumatism and arthralgia. The water and methanol extracts of C. chinensis (CCW and CCM) were evaluated for their antioxidant and antiproliferative activities. The antioxidant activities of CC were evaluated by using ABTS radical scavenging, DPPH radical scavenging, nitric oxide scavenging and superoxide scavenging methods. Iron chelating activity, lipid peroxidation, total polyphenol contents, total flavonoid contents and total flavonol contents were also detected. In all the tested models, both CCW and CCM showed their ability to scavenge the free radicals in a does-dependent manner. CCW had higher antioxidant and antiproliferative activities than CCM. In LC-MS-MS analysis, the chromatograms of CCW with good antioxidant activities were established. Rutin might be an important bioactive compound in CCW. The antiproliferative activities of CCW and CCM were also studied in vitro by using human hepatoma HepG2 cells. CCW exhibited good antiproliferative activity. These results indicated that CCW might be used as a potential source of natural antioxidants and as an anti-tumor agent.

Anti-inflammatory activities of 6ß-acetoxy-7α-hydroxyroyleanone from Taiwania cryptomerioides Hayata ex vivo and in vivo.

Excess production of nitric oxide (NO) by inducible NO synthase (iNOS) in activated macrophages is linked to acute and chronic inflammation. Thus, it would be valuable to develop inhibitors of NO production and/or iNOS for potential therapeutic use. This study investigated the anti-inflammatory effects of 6ß-acetoxy-7α-hydroxyroyleanone (AHR), a compound isolated from the bark of Taiwania cryptomerioides Hayata, using lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW 264.7) ex vivo and carrageenan (Carr)-induced mouse paw edema model in vivo. When RAW 264.7 macrophages were treated with different concentrations of AHR (0, 0.31, 0.62, 1.25, and 2.50 µg/mL) together with LPS (100 ng/mL), a significant concentration-dependent inhibition of NO production was detected. Western blotting revealed that AHR blocked protein expression of iNOS and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophages, significantly. In the anti-inflammatory test, AHR (1.25 and 2.50 mg/kg) decreased paw edema at 4 and 5 h after λ-carrageenan (Carr) administration and increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the liver tissue. It was also demonstrated that AHR significantly attenuated the malondialdehyde (MDA) level in the edema paw at 5 h after Carr injection. AHR (0.62, 1.25, and 2.50 mg/kg) decreased the NO levels on both edema paw and serum at 5 h after Carr injection. Also, AHR diminished the serum tumor necrosis factor (TNF-α) at 5 h after Carr injection. Western blotting revealed that AHR (2.50 mg/kg) decreased Carr-induced iNOS and COX-2 expressions at 5 h in the edema paw. An intraperitoneal (ip) injection treatment with AHR also diminished neutrophil infiltration into sites of inflammation, as did indomethacin (Indo). The anti-inflammatory activities of AHR might be related to the decrease in the levels of MDA, iNOS, and COX-2 in the edema paw and to the increase in the activities of CAT, SOD, and GPx in the liver through the suppression of TNF-α and NO.

Hepatoprotective effect of Crossostephium chinensis (L.) Makino in rats.

The hepatoprotective potential of Crossostephium chinensis (L.) Makino water extract (CCW) on carbon tetrachloride (CCl(4)) induced liver damage was evaluated in preventive and curative rat models. Not only were indicators of hepatic damage including GPT, GOT, lipid peroxides and TBARS were examined, the activities of antioxidant enzymes (SOD, CAT, GPx) and GSH were examined as well. The results showed that CCW (0.1, 0.5 and 1.0 g/kg) significantly reduced the elevated levels of GPT and GOT by CCl(4) administration (p < 0.05). TBARS level was dramatically reduced, and SOD, CAT, GPx and GSH activities were significantly increased. In addition, CCW decreased NO production and TNF-α activation in CCl(4)-treated rats. Therefore, we speculate that CCW protects against acute liver damage through its radical scavenging ability. CCW inhibited the expression of MMP-9 protein, indicating that MMP-9 played an important role in the development of CCl(4)-induced chronic liver damage in rats. In LC-MS-MS analysis, the chromatograms of CCW with good hepatoprotective activities were established. Scopoletin may be an important bioactive compound in CCW.

Analgesic effects and mechanisms of anti-inflammation of taraxeren-3-one from Diospyros maritima in mice.

This study investigated the analgesic effects of taraxeren-3-one, which is an ingredient from Diospyros maritima (DM), using the models of acetic acid-induced writhing response and the formalin test, and its anti-inflammatory effects using the model of λ-carrageenan (Carr)-induced paw edema. Treatment of male ICR mice with taraxeren-3-one inhibited the numbers of writhing response and formalin-induced pain in the late phase, significantly. In the anti-inflammatory test, taraxeren-3-one decreased paw edema at 4 and 5 h after Carr administration and increased the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH) in the liver tissue at 5 h after Carr injection. Taraxeren-3-one affects malondialdehyde (MDA), nitric oxide (NO), and tumor necrosis factor-α (TNF-α) levels from both the edema paw and serum at 5 h after Carr injection. Western blotting revealed that taraxeren-3-one decreased Carr-induced inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions. These anti-inflammatory mechanisms of taraxeren-3-one might be related to the decrease in the level of MDA in the edema paw via increasing the activities of SOD, CAT, GPx, and GSH in the liver. Also, taraxeren-3-one could affect the production of NO and TNF-α and, therefore, affect the anti-inflammatory effects.