|Pharm Biol. 2014 Nov;52(11):1478-86. |
|beta-Amyrin and alpha-amyrin acetate isolated from the stem bark of Alstonia boonei display profound anti-inflammatory activity.[Pubmed: 25026352]|
|Alstonia boonei De Wild (Apocyanaceae) is used in ethnomedicine for the management of malaria, ulcer, rhematic pain, toothache, and inflammatory disorders.To investigate the anti-inflammatory potential of beta-Amyrin and α-amyrin acetate isolated from the stem bark of Alstonia boonei using animal models.
METHODS AND RESULTS:
Chromatographic purification of the crude methanol extract led to the isolation and structure elucidation of beta-Amyrin and α-amyrin acetate. Their anti-inflammatory activities were evaluated in rodents using egg albumen-induced paw edema and xylene-induced ear edema models. The gastric ulcerogenic, in vivo leucocyte migration, and RBC membrane stabilization tests were also investigated.
α-Amyrin acetate at 100 mg/kg showed significant (p < 0.05) inhibition of egg albumen-induced paw edema with % inhibition of 40 at the 5th hour. Oral administration up to 100 mg/kg did not produce significant (p > 0.01) irritation of the gastric mucosa while significant (p < 0.01) ulceration was recorded for indomethacin at 40 mg/kg compared with the negative control. At 100 μg/mL, both beta-Amyrin and α-amyrin acetate inhibited heat-induced hemolysis to as much 47.2 and 61.5%, respectively, while diclofenac sodium (100 μg/mL) evoked only 40.5% inhibition. Both compounds at 100 µg/ear produced significant (p < 0.01) inhibition of ear edema in mice by 39.4 and 55.5%, respectively. Also at 100 mg/kg (p.o.) α-amyrin acetate evoked 60.3% reduction in total leucocyte count and significant (p < 0.05) suppression (47.9%) of neutrophil infiltration.
This study generally provided evidence of profound anti-inflammatory activity of β-amyrin and α-amyrin acetate isolated from the Alstonia boonei stem bark.
|J Pharmacol Exp Ther. 2005 Apr;313(1):310-8. |
|Antinociceptive properties of mixture of alpha-amyrin and beta-amyrin triterpenes: evidence for participation of protein kinase C and protein kinase A pathways.[Pubmed: 15626726 ]|
METHODS AND RESULTS:
The mixture of the two pentacyclic triterpenes alpha-amyrin and beta-Amyrin, isolated from the resin of Protium kleinii and given by intraperitoneal (i.p.) or oral (p.o.) routes, caused dose-related and significant antinociception against the visceral pain in mice produced by i.p. injection of acetic acid. Moreover, i.p., p.o., intracerebroventricular (i.c.v.), or intrathecal (i.t.) administration of alpha,beta-Amyrin inhibited both neurogenic and inflammatory phases of the overt nociception caused by intraplantar (i.pl.) injection of formalin.
Likewise, alpha,beta-Amyrin given by i.p., p.o., i.t., or i.c.v. routes inhibits the neurogenic nociception induced by capsaicin. Moreover, i.p. treatment with alpha,beta-Amyrin was able to reduce the nociception produced by 8-bromo-cAMP (8-Br-cAMP) and by 12-O-tetradecanoylphorbol-13-acetate (TPA) or the hyperalgesia caused by glutamate. On the other hand, in contrast to morphine, alpha,beta-Amyrin failed to cause analgesia in thermal models of pain. The antinociception caused by the mixture of compounds seems to involve mechanisms independent of opioid, alpha-adrenergic, serotoninergic, and nitrergic system mediation, since it was not affected by naloxone, prazosin, yohimbine, DL-p-chlorophenylalanine methyl ester, or L-arginine. Interestingly, the i.p. administration of alpha,beta-Amyrin reduced the mechanical hyperalgesia produced by i.pl. injection of carrageenan, capsaicin, bradykinin, substance P, prostaglandin E2, 8-Br-cAMP, and TPA in rats. However, the mixture of compounds failed to alter the binding sites of [3H]bradykinin, [3H]resiniferatoxin, or [3H]glutamate in vitro.
It is concluded that the mixture of triterpene alpha-amyrin and beta-Amyrin produced consistent peripheral, spinal, and supraspinal antinociception in rodents, especially when assessed in inflammatory models of pain. The mechanisms involved in their action are not completely understood but seem to involve the inhibition of protein kinase A- and protein kinase C-sensitive pathways.
|Inflammopharmacology. 2008 Feb;16(1):48-52. |
|Anti-inflammatory effect of alpha, beta-Amyrin, a pentacyclic triterpene from Protium heptaphyllum in rat model of acute periodontitis.[Pubmed: 18046512 ]|
|This study was aimed to evaluate the anti-inflammatory potential of triterpene alpha, beta-Amyrin in rats on acute phase periodontitis.
METHODS AND RESULTS:
Periodontitis was induced by ligature placement around the maxillary right second molar tooth. Rats (n = 8/group) were pretreated with alpha, beta-Amyrin (5 and 10 mg/kg, p. o.), two hours before the induction of periodontal inflammation. Sham-operated and positive controls (lumiracoxib and dexamethasone) were included. Six hours later, plasma levels of TNF-alpha were analysed. Rats were sacrificed at 24 h, and the gingival tissue analysed for myeloperoxidase (MPO) and thiobarbituric acid-reactive substances (TBARS), as measures of neutrophil influx and lipid-peroxidation, respectively alpha, beta-Amyrin as well as dexamethasone significantly inhibited the periodontitis-associated increases of TNF-alpha, and the gingival MPO and TBARS. alpha, beta-Amyrin effect was more prominent at 5 mg/kg. Lumiracoxib manifested varied influence on the studied parameters.
These results provide evidence to show that alpha, beta-Amyrin retards acute inflammation in rat model of periodontitis and warrant further study on its efficacy to prevent chronic periodontitis-associated bone loss.
|Pharmacol Biochem Behav. 2006 Dec;85(4):827-34. |
|A possible mechanism for anxiolytic and antidepressant effects of alpha- and beta-amyrin from Protium heptaphyllum (Aubl.) March.[Pubmed: 17207523 ]|
|In the present study, we examined the anxiolytic and antidepressant effects of the mixture of alpha- and beta-Amyrin (AMY), pentacyclic triterpenes isolated from the stem bark resin of Protium heptaphyllum.
METHODS AND RESULTS:
These effects of AMY were demonstrated by the open-field, elevated-plus-maze, rota rod, forced swimming, and pentobarbital-induced sleeping time tests, in mice. In the open-field test, AMY at the doses of 10, 25 and 50 mg/kg, after intraperitoneal or oral administrations, significantly decreased the number of crossings, grooming, and rearing. All these effects were reversed by the pre-treatment with flumazenil (2.5 mg/kg, i.p.), similarly to those observed with diazepam used as a positive standard. In the elevated-plus-maze test, AMY increased the time of permanence and the number of entrances in the open arms. On the contrary, the time of permanence and the number of entrances in the closed arms were decreased. All these effects were also completely reversed by flumazenil, an antagonist of benzodiazepine receptors. In the pentobarbital-induced sleeping time test, AMY at the same doses significantly increased the animals sleeping time duration. In the rota rod test, AMY did not alter motor coordination and, thus, was devoid of effects, as related to controls. Since AMY, at the doses of 10 and 25 mg/kg, showed a sedative effect in the open field test, lower doses (2.5 and 5.0 mg/kg) were used in the forced swimming test, producing a decrease in the immobility time, similarly to that of imipramine, the positive control. The effect of AMI was greater when it was administered 15 min after imipramine (10 mg/kg). However, the antidepressant AMY effects were not altered by the previous administration of paroxetine, a selective blocker of serotonin uptake. In addition, AMY effects in the forced swimming test were totally blocked by reserpine pretreatment, a drug known to induce depletion of biogenic amines.
In conclusion, the present work evidenced sedative and anxiolytic effects of AMY that might involve an action on benzodiazepine-type receptors, and also an antidepressant effect where noradrenergic mechanisms will probably play a role.