Artemisinin and deoxyartemisinin isolated from Artemisia annua L. promote distinct antinociceptive and anti-inflammatory effects in an animal model.

Artemisia annua L., known for antimalarial activity, has demonstrated evidence of anti-inflammatory potential. Previously our research group reported the anti-inflammatory and antinociceptive effect of a sesquiterpene lactone-enriched fraction (Lac-FR) obtained from plant, containing artemisinin and deoxyartemisinin. Both the isolated compounds and Lac-FR evaluated on experimental animal models, in the formalin test showed that deoxyartemisinin reduced both neurogenic pain (56.55 %) and inflammatory pain (45.43 %). These findings were superior to the effect of artemisinin (reduction of 28.66 % and 33.35 %, respectively). In the tail flick test, the antinociceptive effect reported as a percentage of the maximum possible effect (%MPE), deoxyartemisinin showed a lower antinociceptive effect (41.57 %) compared to morphine (75.94 %) in 0.5 h. After 1.5 h, the MPE of deoxyartemisinin (87.99 %) exceeded the effect of morphine (47.55 %), without reversal with naloxone. The MPE of artemisinin (23.3 %) observed after 2 h was lower than deoxiartemisinin, without reversal with the opioid antagonist. Lac-FR and artemisinin demonstrated reductions in ear edema of 43.37 % and 48.19 %, respectively, higher than the effect of deoxyartemisinin (33.64 %). Artemisinin reduced tumor necrosis factor alpha (TNF-α) (76.96 %) more selectively when compared to interleukin-1beta (IL-1ß) (48.23 %) and interleukin-6 (IL-6) (44.49 %). Lac-FR showed greater selectivity in IL-6 reduction (56.49 %) in relationship to TNF-α (46.71 %) and IL-1ß (45.12 %), whereas deoxyartemisinin selectively reduced TNF-α (37.37 %). The results of our study indicate that the lactones isolated did not have relationship with the opioid system. Deoxyartemisinin showed a higher antinociceptive potential than artemisinin. Whereas, artemisinin showed a higher reduction of inflammation and mediators, with a better anti-inflammatory activity outcome.

Artemisia annua L.: evidence of sesquiterpene lactones' fraction antinociceptive activity.

BACKGROUND: Artemisia annua L. has been used for many centuries in Chinese traditional medicine. Artemisinin, the active principle was first isolated and identified in the 1970s becoming the global back bone to the fight against malaria. Our research group previously developed an economic and ecological friendly process to obtain this compound. In the pursuit to also exploit the residue generated throughout the process we further evaluated the pharmacological potential of that extract. METHODS: The alcoholic crude extract after artemisinin precipitation maintained an enriched sesquiterpene lactones content with residue artemisinin (1.72%) and deoxyartemisinin (0.31%), used as chemical markers for this sample. This study evaluated the pharmacological potential of the enriched sesquiterpene lactone fraction (Lac-FR) on different nociceptive and inflammatory experimental animal models. Previous findings on the biological properties of lactones obtained from natural products permitted us to explore the antinociceptive activities of these compounds based on in vivo chemical-induced behavioral assays. RESULTS: The enriched sesquiterpene lactone fraction (Lac-FR) was administrated by intraperitoneal injection producing a relevant reduction in the reaction time of the animals in both phases of the formalin test, significantly reduced the sensitivity to mechanical allodynia stimulus, reduced the paw edema caused by carrageenan injection and promoted high antinociceptive activity in tail flick model suggesting relationship with the opioid system. Further studies are being undertaken to elucidate the active components involved with the antinociceptive activity as well as evaluation of synergy effect that is seen by combination of substances that is greater than would be expected from consideration of individual contributions. CONCLUSION: For the first time, results presented herein provided consistent data to support the potential use of these lactones for pain relief as revealed by chemical-induced nociception assays in mice.