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.

The use of chitosan modified with glutaraldehyde and glyoxal as chromatographic support for the separation of flavonoids from Aleurites moluccana leaves.

This paper describes the preparation of chitosan modified with dialdehydes, glutaraldehyde (CH-Glu) and glyoxal (CH-Gly) and its application in the isolation of the flavonoids swertisin and 2"-O-rhamnosylswertisin from A. mollucana. The additional non-polar alkyl groups increase the hydrophobicity of the sorbent. The results show that the separation was mediated by hydrophobic interaction (CH-Glu), as well as hydrogen bonding, between phenolic OH or rhamnosil residues from the flavonoids, and the free amine groups (CH-Gly).

Analgesic potential of marrubiin derivatives, a bioactive diterpene present in Marrubium vulgare (Lamiaceae).

Marrubiin, a furane labdane diterpene, is the main analgesic compound present in Marrubium vulgare, a medicinal plant used in Brazil and other countries to treat several ailments. Considering its important pharmacological action, as well as its high yield, some structural modifications were performed in order to obtain more active compounds. Success was obtained in reducing the lactonic function, in the formation of marrubiinic acid and two esterified derivatives, which exhibited significant analgesic effect against the writhing test in mice. Marrubiinic acid showed better activity and excellent yield, and its analgesic effect was confirmed in other experimental models of pain in mice, suggesting its possible use as a model to obtain new and potent analgesic agents.

Isolation of flavonoids from Aleurites moluccana using chitosan modified with benzaldehyde (CH-Bz) as chromatographic support.

This paper describes the preparation, characterization and use of a derivative of chitosan as a chromatographic sorbent. Chitosan modified with benzenic ring (CH-Bz) was used to separate two flavonoids, swertisin and 2"-O-rhamnosylswertisin, from ethyl acetate fraction of Aleurites moluccana. The results showed that CH-Bz can be used as a sorbent for the separation of flavonoid compounds. The studies showed that CH-Bz in column chromatography produces goods results, separation of the flavonoid compounds.

Hypolipidaemic activity of methanol extract of Aleurites moluccana.

The lipid-lowering action of the leaves of the Aleurites moluccana methanol extract was studied in Triton W-1339 and high-fat-diet fed rats. The serum lipids (total cholesterol, LDL- and HDL-cholesterol and triglycerides) and body weight were found to be lowered by A. moluccana (300 mg/kg, b.w.) in rats with Triton-induced hypercholesterolaemia and on a hyperlipaemic diet. The results suggest that the lipid lowering action of this natural product is mediated through inhibition of hepatic cholesterol biosynthesis and reduction of lipid absorption in the intestine.

Phytochemical and pharmacological analysis of Bauhinia microstachya (Raddi) Macbr. (Leguminosae).

This paper describes the isolation of four phytoconstituents from the leaves of Bauhinia microstachya, a Brazilian medicinal plant used in folk medicine for the treatment of several ailments. Based on spectroscopic evidence, these compounds were identified as methyl gallate (1), kaempferol 3-O-rhamnosyl (2), quercitrin (3) and myricitrin (4). The crude methanolic extract and two compounds (3 and 4) were tested as analgesic using the writhing test in mice. The extract and compound 3 caused potent and dose-related analgesic effects, confirming the popular use of this plant for the treatment dolorous processes.

Preliminary phytochemical and pharmacological studies of Aleurites moluccana leaves [L.] Willd.

In the present work we have investigated the analgesic activity of various extracts prepared from Aleurites moluccana leaves by using the writhing test in mice. The results showed that the hydroalcoholic extract and the hexane fraction exhibit potent antinociceptive action. We have also isolated and identified some chemical constituents from the hexane fraction. In addition, the nature of substances present in ethyl acetate and butanol fractions were evaluated by TLC. Such fractions revealed the presence of phenolic compounds. Chromatographic procedures carried out with hexane fraction revealed the presence of n-hentriacontane, α-amyrin, ß-amyrin, stigmasterol, ß-sitosterol and campesterol, which were identified by spectroscopic data and HRGC or HRGC/MS techniques. The compounds considerably inhibited acetic acid-induced abdominal constrictions, being more efficacious than aspirin and paracetamol. In addition, preliminary HPLC analysis indicated, using a UV detector, one main constituent in alcoholic extract.