Antinociceptive, anti-inflammatory and wound healing features in animal models treated with a semisolid herbal medicine based on Aleurites moluccana L. Willd. Euforbiaceae standardized leaf extract: semisolid herbal.

ETHNOPHARMACOLOGICAL RELEVANCE: Aleurites moluccana L. (Willd) Euforbiaceae is a native tree of Indonesia and India that has become acclimatized and well-adapted to the South and Southwest of Brazil. It is commonly used in traditional medicine to treat pain, fever, inflammation, asthma, hepatitis, headache, gastric ulcer, cuts, skin sores and other ailments. The oral antinociceptive effects of standardized 70:30 (v/v) ethanol:water spray dried extract of A. moluccana leaf, as well as its flavonoids 2"-O-rhamnosylswertisin (I) and swertisin (II), have previously been reported. AIM: The aim of this study was to develop a stable and effective semisolid herbal medicine for topical use in the treatment of pain, inflammation and wound healing, containing 0.5 and 1.0% of standardized dried extract of A. moluccana. MATERIALS AND METHODS: The chemical markers I and II were assayed by HPLC-UV analysis after extraction by matrix solid dispersion phase (MSDP) followed analytical validation as ICH Guidelines. The semisolid preparations of Hostacerin CG(®) vehicle containing 0.5 and 1.0% of dried extract of A. moluccana were submitted to stability studies (180 day of accelerated and long-term studies). The phytomedicine semisolid was analysed in croton oil-induced ear oedema model in mice, in the healing process, using the excisional wound model in rats, and to prevent mechanical sensitization following plantar incision in rats in the postoperative model of pain. RESULTS: The MSDP method showed average recovery of 101.6 and 105.7% for I and II, respectively, with good precision (RSD<2.0%) and selectivity, without interference of the excipients. The formulations were approved in the stability studies, maintaining conformity after 180 day of accelerated and long-term studies, with variation<10% in the analytical parameters. The phytomedicine reduced the ear oedema in 37.6±5.7% and 64.8±6.2%, for 0.5 and 1.0% of dried extract, respectively. The formulation also accelerated the healing process by up to 50.8±4.1% and 46.0±4.0% at 0.5 and 1.0% of extract, respectively, and both amounts were capable of preventing the development of mechanical sensitization following plantar incision in rats. CONCLUSIONS: The MSDP followed by HPLC-UV analytical method was appropriate for the quality control of the topical phytomedicine based on A. moluccana. The formulation developed at 0.5 and 1.0% of A. moluccana dried extract proved to be effective as an analgesic, anti-inflammatory and wound healing in the pre-clinical studies, which is in agreement with the ethnopharmacological data.

Filicene obtained from Adiantum cuneatum interacts with the cholinergic, dopaminergic, glutamatergic, GABAergic, and tachykinergic systems to exert antinociceptive effect in mice.

In the present study, we describe the antinociceptive effect of filicene, a triterpene isolated from Adiantum cuneatum (Adiantaceae) leaves, in several models of pain in mice. When evaluated against acetic acid-induced abdominal constrictions, filicene (10, 30 and 60 mg/kg, i.p.) produced dose-related inhibition of the number of constrictions, being several times more potent [ID(50)=9.17 (6.27-13.18) mg/kg] than acetaminophen [ID(50)=18.8 (15.7-22.6) mg/kg], diclofenac [ID(50)=12.1(9.40-15.6) mg/kg] and acetylsalicylic acid [ID(50)=24.0(13.1-43.8) mg/kg] in the same doses as those used for the standard drugs. Filicene also produced dose-related inhibition of the pain caused by capsaicin and glutamate, with mean ID(50) values of 11.7 (8.51-16.0) mg/kg and <10 mg/kg, respectively. Its antinociceptive action was significantly reversed by atropine, haloperidol, GABA(A) and GABA(B) antagonists (bicuculline and phaclofen, respectively), but was not affected by L-arginine-nitric oxide, serotonin, adrenergic and the opioid systems. Together, these results indicate that the mechanisms involved in its action are not completely understood, but seem to involve interaction with the cholinergic, dopaminergic, glutamatergic, GABAergic and tachykinergic systems.

Phytochemical analysis and analgesic properties of Curcuma zedoaria grown in Brazil.

The present study describes the phytochemical analysis and analgesic activity of Curcuma zedoaria rhizomes grown in Brazil. The results showed that the hydroalcoholic extract, fractions, specially dichloromethane, and a pure compound, denoted as curcumenol (1), exhibited potent and dose-related analgesic activity when evaluated in several models of pain in mice, including writhing, formalin and capsaicin. Compound (1), which seems to be the main active principle from this plant, presented promising analgesic effects, being several times more potent than different reference drugs evaluated in the same experimental models. The calculated ID50 values (micromol/kg, i.p) were 22 and 12 when evaluated in writhing and capsaicin tests, respectively, and 29 micromol/kg in relation to the second phase of the formalin model. The lack of effect in the hot plate test suggests that (1) act by a mechanism which do not involves the participation of the opioid system. The phytochemical analysis indicated that the chemical composition of the plant grown in Brazil is similar to that grown in other countries. The results confirm and justify the popular use of this plant for the treatment of dolorous processes.

Phytochemical and pharmacological investigations of Virola oleifera leaves.

A methanolic extract and two fractions (n-hexane and ethyl acetate) from Virola oleifera leaves and some compounds (one lignan and two flavonoids) were investigated to verify the analgesic activity by using the writhing test in mice. The crude methanolic extract showed a moderate analgesic effect (about 40% of inhibition in this test at 10 mg/kg), whereas n-hexane and ethyl acetate fractions caused inhibition of 51.3 +/- 5.9% and 50.5 +/- 6.3%, respectively. Oleiferin-C (1), a lignan isolated from the n-hexane fraction, showed an interesting analgesic potential in this model when compared to two standard drugs, paracetamol (4-acetamidophenol) and aspirin (acetylsalicylic acid). The ID50 calculated for this compound was 17.25 micromol/kg, with confidence interval between 13.7 and 21.3 micromol/kg, being about 8 times more potent than the standard drugs. The mixture of two glycoside-flavonoids, identified as astilbin (2) and quercitrin (3), also exhibited good analgesic activity, causing 63% of reduction of abdominal constriction in mice. These results suggest beneficial effect of this plant to treat dolorous processes.

I3-naringenin-II8--4'OMe-eriodictyol: a new potential analgesic agent isolated from Rheedia gardneriana leaves.

This paper describes the isolation, identification and analgesic activity of a new biflavonoid from Rheedia gardneriana leaves, which correspond to I3-naringenin-II8-4'-OMe-eriodictyol (GB-2a-II-4'-OMe) (1), with a methoxyl group in position 4 of ring-II. Its structure was determined by spectroscopic data and confirmed by an alkaline hydrolysis. Its analgesic effect was evaluated in a writhing test and a formalin test in mice. It was found that this compound exhibits potent and dose-related analgesic action in both experimental models, with ID50's values of 4.5 micromol/kg against the writhing test and 8.2 and 6.8 micromol/kg against the first and second phase of the formalin test, respectively. It was several times more potent than some well-known analgesic drugs used as reference.

Antinociceptive properties of morusin, a prenylflavonoid isolated from Morus nigra root bark.

The antinociceptive effects of morusin (1), the main prenylflavonoid present in the Morus nigra root barks have been investigated in classical models of pain in mice. The results showed that 1 exhibits a promising antinociceptive or analgesic profile by the intraperitoneal route, being more potent than some standard drugs used as reference. The mechanism by which the morusin exerts antinociceptive activity still remains undetermined, but our results strongly suggest that it involves the participation of the opioid system.

Antinociceptive activity of I3,II8-binaringenin, a biflavonoid present in plants of the guttiferae.

This paper describes the antinociceptive action of 13,118-binaringenin (GB-1a), a biflavonoid isolated from Clusia columnaris and present in several plants of the family Guttiferae, in a writhing test and a formalin test. It was found that it exhibits potent and dose-related antinociceptive action in both experimental models, with ID50 values of 22 mumol/kg against the writhing test and 28 mumol/kg against the second phase of the formalin test. It was more potent than some well-known analgesic drugs used as reference. Based on a hot-plate test its mechanism of action seems to be unrelated with the opioid receptors.

Antinociceptive properties of the methanolic extract obtained from Ipomoea pes-caprae (L.) R. Br.

Ipomoea pes-caprae is a medicinal plant used in many countries for the treatment of several ailments, including inflammatory and algesic processes. The present study describes the antinociceptive effects of the methanolic extract and two fractions obtained from aerial parts of this plant. The results indicated that both methanolic extract and two fractions (ethyl acetate and aqueous) exhibited considerable antinociceptive activity against two classical models of pain in mice. Methanolic extract presented a calculated ID50 value of 33.8 mg/kg, i.p. against writhing test and also inhibited both phases of pain (neurogenic and inflammatory) of the formalin test with ID50 of 37.7 and 12.5 mg/kg, i.p. for the first and second phase, respectively. Preliminary phytochemical analysis suggested the presence of steroids, terpenoids, alkaloids and flavonoids. These findings support, at least in part, the popular use of I. pes-caprae to treat dolorous processes.

Chemical and pharmacological examination of antinociceptive constituents of Wedelia paludosa.

The present work describes the antinociceptive effects of some fractions and two pure compounds obtained from the Wedelia paludosa, a Brazilian medicinal plant employed in folk medicine against a variety of diseases, including dolorous pathologies. It was found that such fractions as well as kaurenoic acid and luteolin exhibit marked antinociceptive action in mice using acetic acid-induced writhing. They were more active than some well-known analgesic drugs, such as acetyl salicylic acid, acetaminophen, dipyrone and indomethacin. The results confirm our previous studies conducted with this plant, suggesting that different chemical constituents are responsible for the antinociceptive activity shown by the extracts and fractions prepared from W. paludosa.

Analgesic profile of hydroalcoholic extract obtained from Marrubium vulgare.

Marrubium vulgare L. is a medicinal plant used in folk medicine to cure a variety of diseases. Recently we have demonstrated that a hydroalcoholic extract of this plant showed significant, nonspecific antispasmodic effects on isolated smooth muscle. In this report, we have investigated the possible analgesic effects of the same hydroalcoholic extract in different models of pain in mice. The results suggest that this extract exhibits significant analgesic activity, antagonizing chemically-induced acute pain. Such effects may be related to the presence of steroids and terpenes, which were detected by TLC analysis.