Coffea arabica extracts and their chemical constituents in a murine model of gouty arthritis: How they modulate pain and inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Coffea arabica is commonly known for its cardiotonic and neurotonic activities, but in some places' folk medicine, like in Arabia and Africa, C. arabica is used to treat headache, migraine, the flu, anemia, oedema, asthenia, asthma, inflammation and wounds. AIMS OF THE STUDY: The aims were to evaluate if the aqueous extracts of Coffea arabica, prepared from beans with different degrees of roasting, and their main chemical constituents could exert an in vivo anti-gouty effect. MATERIALS AND METHODS: Coffea extracts were obtained from the beans of not roasted, light, medium and dark roasted coffee and from decaffeinated and traditional coffees and were prepared with water at 25°C and at 98°C. C57BL/6 mice were induced to gout by an injection of monosodium urate crystals and treated with coffee extracts at doses of 25, 75 and 225 mg/kg and their chemical constituents at a dose of 10 mg/kg. The antinociceptive and anti-inflammatory effects were evaluated. RESULTS: Treatments with Coffea extracts prepared with water at 98°C were more effective to exert antinociceptive and anti-inflammatory activities than the ones prepared with water at 25°C. Caffeic and chlorogenic acids reduced hypernociception in animals when compared with negative control group (7.79 and 5.69 vs 18.53; P < 0.05 and P < 0.001, respectively), inhibited neutrophil migration (1.59 × 104 and 0.38 × 104 vs 9.47 × 104; P < 0.0001 both) and decreased pro-inflammatory cytokines concentration (IL-1ß, IL-6 and TNF-α). CONCLUSIONS: We have demonstrated that our treatments attenuated gout, and this effect could be attributed to a reducement in hypernociception, neutrophil migration and cytokines concentration. These results suggest coffee as a potential candidate for studies in acute gout therapy.

Lychnophora pinaster's effects on inflammation and pain in acute gout.

ETHNOPHARMACOLOGICAL RELEVANCE: Ethanolic extract of aerial parts from Lychnophora pinaster Mart. are used in traditional Brazilian medicine for treating pain, rheumatism and inflammation. AIM OF THE STUDY: Drugs for the treatment of gout present severe adverse effects, justifying the need to search for new therapeutic options. The aim of the present study was to evaluate the effects of the ethanolic extract of L. pinaster and its main constituents in arthritis induced in mice by the injection of monosodium urate (MSU) crystals. MATERIALS AND METHODS: Antinociceptive effect was investigated using an electronic pressure-meter nociception paw test in C57BL/6 mice. Anti-gouty arthritis was investigated in mice induced with gout by the injection of MSU crystals into their femur-tibial tissue. Ethanolic extract of the aerial parts of Lychnophora pinaster and its main chemical constituents were evaluated as treatment. RESULTS: The ethanolic extract and their main chemical constituents inhibited neutrophil migration, reduced IL-1ß and TNF-α concentrations in the inflamed tissue and showed antinociceptive activity. CONCLUSIONS: Gouty arthritis effects of the ethanolic extract can be attached to a synergistic effect of terpenes, flavonoids and phenolic acids present in the extract. Results obtained support the use of this extract and its main chemical constituents in the treatment of gout, inflammation, and pain.

Sesquiterpene lactones from Lychnophora species: Antinociceptive, anti-inflammatory, and antioxidant pathways to treat acute gout.

ETHNOPHARMACOLOGICAL RELEVANCE: Lychnophora trichocarpha and Lychnophora passerina are species used in folk medicine to treat inflammation, pain, and rheumatism. Previous studies have demonstrated the anti-inflammatory effect of ethanol extracts of these species and identified that sesquiterpene lactones contribute to this activity. AIM OF THE STUDY: Gout is an acute inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals in joints. Inflammation in joints induces oxidative stress in defense cells, releasing pro-inflammatory mediators. This study has three objectives: (1) to demonstrate the effects of sesquiterpene lactones lychnopholide and eremantholide C isolated from L. trichocarpha and goyazensolide isolated from L. passerina on arthritis induced by MSU crystals in C57BL6 mice; (2) to determine whether or not these compounds can inhibit the migration of neutrophils and the release of TNF-α and IL-1ß cytokines in the inflammation region; and (3) to evaluate the effects of sesquiterpene lactones on the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in the cartilage of C57BL/6 mice with gouty arthritis. MATERIALS AND METHODS: The anti-inflammatory, antinociceptive, and antioxidant activities of sesquiterpene lactones in C57BL/6 mice with MSU crystal-induced arthritis were evaluated. In our experimental model, the mice were injected with MSU crystals in the tibiofemoral joint to induce arthritis and then treated with indomethacin, vitamin C, and sesquiterpene lactones. Nociception was evaluated before and after inflammation induction and treatments, neutrophil migration, IL-1ß and TNF-α concentrations, and SOD and CAT activities. RESULTS: Sesquiterpene lactones exerted an anti-inflammatory effect by inhibiting neutrophil migration and TNF-α production. These compounds also demonstrated antinociceptive and antioxidant activities. CONCLUSION: Lychnopholide, eremantholide C, and goyazensolide improved the inflammation induced by MSU crystals by inhibiting the migration of neutrophils to the inflamed area and by blocking the release of the pro-inflammatory cytokine TNF-α. In addition, sesquiterpene lactones reduced oxidative stress by activating SOD and CAT. These results suggest that sesquiterpene lactones have anti-gout activity through the inflammation, pain, and oxidative stress pathways.

Effects of Pimenta pseudocaryophyllus extracts on gout: Anti-inflammatory activity and anti-hyperuricemic effect through xantine oxidase and uricosuric action.

ETHNOPHARMACOLOGICAL RELEVANCE: Leaves infusion of Pimenta pseudocaryophyllus (Gomes) Landrum is used in Brazilian folk medicine to treat the predisposition to arthritical and gouty affections of the joints, fever and other diseases. A refreshing drink prepared with the specie is also used due to its diuretic, sedative and aphrodisiac actions. AIM OF THE STUDY: The study was undertaken to investigate the mechanisms of anti-hyperuricemic effect and anti-inflammatory activity of P. pseudocaryophyllus extracts. MATERIALS AND METHODS: Anti-hyperuricemic effect was investigated using xanthine oxidase assay and uricosuric studies with rats in which hyperuricemia was induced by potassium oxonate and uric acid. Anti-inflammatory activity was investigated on MSU crystal-induced paw edema model. Ethyl acetate extracts of the leaves (EAL) and branches (EAB), ethanolic extracts of leaves (EEL) and branches (EEB) and aqueous extracts of leaves (AL) and branches (AB) were evaluated. RESULTS: The extracts of P. pseudocaryophyllus evaluated showed expressive results regarding the inhibition of xanthine oxidase enzyme in vitro and they were also able to reduce serum uric acid levels in hyperuricemic rats. The investigation of the mechanism of action, it was found that EAL, EAB, EEB, AB (125 and 250 mg/kg) and AL (250 mg/kg) promoted an increase on the urinary excretion of uric acid and EEL, EEB, AB (125 and 250 mg/kg) and EAB (250 mg/kg) were capable to inhibit liver xanthine oxidase. Treatments with EEL (125 and 250 mg/kg) and EEB (250 mg/kg) were able to reduce edema at 48 th h. EAL and EAB (125 and 250 mg/kg) showed significant anti-inflammatory activity on monosodium urate crystal-induced paw edema model at all evaluated times. CONCLUSIONS: The specie P. pseudocaryophyllus showed remarkable anti-hyperuricemic effects through uricosuric effects and inhibition of xanthine oxidase and therefore can be considered as a promise in the treatment of diseases related to hyperuricemia. Moreover, ethyl acetate extracts had significant anti-inflammatory activity.