Effects of an ethanol extract and the diterpene, xylopic acid, of Xylopia aethiopica fruits in murine models of musculoskeletal pain

Abstract

Context: Fruits of Xylopia aethiopica (Dunal) A. Rich. (Annonaceae) are used traditionally to manage arthritis, headache and other pain disorders. Objective: The analgesic properties of the X. aethiopica ethanol fruit extract (XAE) and xylopic acid (XA) were evaluated in musculoskeletal pain models. Materials and methods: Acute muscle pain was induced in gastrocnemius muscle of Sprague-Dawley rats with 3% carrageenan (i.m.). Rats received XAE (30-300 mg/kg), XA (10-100 mg/kg) or morphine (1-10 mg/ kg) after 12 h. Effects of XAE and XA on muscle pain were assessed by measuring post-treatment grip strength of the rats. Chronic muscle pain was similarly induced, but drug treatment was on the eighth day and effects of XAE and XA assessed with Randall-Selitto test for hyperlagesia. Acute-skeletal pain was induced in knee joints of rats with 3% carrageenan-kaolin mixture and effects determined 12-h later. Similar induction protocol was used for chronic knee pain with treatment and measurement as done for chronic muscle pain. Results: XAE and XA significantly and dose-dependently ameliorated both acute muscle (ED 50 mg/kg: XAE ¼ 22.9; XA ¼ 6.2) and skeletal hyperalgesia (XAE ¼ 39.9; XA ¼ 17.7) induced by 3% carrageenan. Similarly, chronic skeletal hyperalgesia was reduced by XAE and XA treatment similar to morphine (ED 50 : XAE ¼ 13.0; XA ¼ 4.6). This reduction was also seen in chronic muscle hyperalgesia (ED 50 : XAE¼ 79.1; XA ¼ 42.7). XAE and XA significantly reduced the spread of hyperalgesia to contralateral limbs in both models of chronic hyperalgesia. Conclusion: These findings establish analgesic properties of the ethanol fruit extract of X. aethiopica and xylopic acid in musculoskeletal pain. ARTICLE HISTORY

Xylopic Acid-Amodiaquine and Xylopic Acid-Artesunate Combinations are Effective in Managing Malaria in Plasmodium Berghei-infected Mice.

“…Although the XA monotherapy experiment did not significantly prevent weight loss, the combination therapy with ART and AQ showed significant reduction in weight loss in the 10.6 mg/kg and 12.1 mg/kg combination doses. This observation correlates with other studies where a combination of xylopic acid and cryptolepine prevented a loss in body weight in mice infected with P. berghei ANKA (12,16).…”

“…Xylopic acid was extracted from Xylopia aethiopica as previously described (14)(15)(16). Fresh unripe fruits of Xylopia aethiopica purchased from the Ho Central Market in Ghana were shadedried and pulverized with a hammer mill.…”

Isobolographic analysis of co-administration of two plant-derived antiplasmodial drug candidates, cryptolepine and xylopic acid, in Plasmodium berghei

“…Xylopic acid crystals formed after the concentrate had been allowed to stand for 72 h. This was washed with petroleum ether at 40–60 °C repeatedly to remove all unwanted materials. The resulting crude xylopic acid was finally purified in 96% ethanol by recrystallization as previously described [ 12 , 13 , 17 ]. The purity of xylopic acid (Fig.…”

Antiinflammatory properties of betulinic acid and xylopic acid in the carrageenan‐induced pleurisy model of lung inflammation in mice

“…Previous studies have shown that the major phytochemical constituent in the fruits and seeds is kaurene diterpenoid, xylopic acid (Figure ; Biney et al, ). Some authors have attributed the effects of the crude extract to this acid component with comparative studies, corroborating this hypothesis (Woode et al, ; Woode, Ameyaw, Boakye‐Gyasi, & Abotsi, ). In other pharmacological studies, the ethanolic fruit extract has been shown to reduce signs of inflammation in adjuvant‐induced arthritis and lipopolysaccharide‐induced systemic anaphylaxis (Obiri & Osafo, ; Obiri, Osafo, Oppong‐Sarfo, & Prah, ).…”