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Analysis of the anti-inflammatory and chemopreventive potential and description of the antimutagenic mode of action of the Annona crassiflora methanolic extract.

AbstractCONTEXT:
Annona crassiflora Mart. (Annonaceae) is a medicinal plant that is widely used in folk medicine, which leads to its investigation as a potential source of new pharmacological principles.
OBJECTIVE:
This study describes the anti-inflammatory, antiallodynic, and antimutagenic/chemopreventive activities of the leaves A. crassiflora methanolic extract. Its antimutagenic mode of action was analyzed in a plant or animal experimental model.
MATERIALS AND METHODS:
Total flavonoids were quantified by spectrophotometry at 415 nm and its composition was analyzed by (1)H NMR spectra. Animals received orally, 30, 100, and 300 mg/kg of extract in both tests, carrageenan-induced paw edema and myeloperoxidase activity. Animals were treated with 100 and 300 mg/kg, in all the analyzed tests, pleural cell migration and protein exudation, carrageenan-induced cell migration into the pouch, induction of joint inflammation and carrageenan-induced allodynia response in the mouse paw. To evaluate the antimutagenic/chemopreventive activity through the Allium cepa test, we used 5, 10, and 15 mg/L of extract, and for the micronucleus test in the peripheral blood, we used the dose of 15 mg/kg.
RESULTS:
The fractionation of the ethyl acetate (EA) fraction, resulting from the partition of the methanol extract of the A. crassiflora, afforded through chromatographic methods resulted in the isolation of kaempferol 3-O-β-glucoside and kaempferol 3-O-β-diglucoside. Oral treatment with 100 and 300 mg/kg of extract significantly inhibited the carrageenan-induced edema formation, with inhibitions of 53 ± 7% and 47 ± 10%; in MPO activity, the observed inhibitions were 60 ± 7% for 100 mg/kg treatment and 63 ± 7% for 300 mg/kg. The ACME reduced significantly the total leukocytes (an inhibition of 78 ± 9% with 100 mg/kg and 90 ± 7% with 300 mg/kg) and protein levels (approximately 100% inhibition with both doses) in the pleurisy model. In carrageenan-induced leukocyte migration into the pouch, the extract inhibited leukocyte migration only when administered 300 mg/kg per dose (the reduction was 43 ± 5%). Pretreatment with extract failed to reduce the zymosan-induced edema formation and did not inhibit the carrageenan-induced mechanical allodynia. Damage reduction in Allium cepa tested with different concentrations (5, 10, and 15 mg/L) was 66.17, 75.75, and 69.19% for the pre-treatment; 72.72, 33.33, and 22.22% for the simple simultaneous treatment; 100.50, 93.93, and 102.52% for the simultaneous treatment with pre-incubation; 89.39, 79.79, and 84.34%; for the post-treatment, and 86.36, 81.31, and 93.43% for the continuous treatment. The antimutagenic evaluation in the micronucleous test showed a damage reduction of 75.00 and 64.58% for the pre-treatment and simultaneous protocols, respectively. The post-treatment protocol increased the cyclophosphamide effects in 45.83%.
CONCLUSION:
These results suggest that this medicinal plant has chemopreventive and anti-inflammatory therapeutic potential.
AuthorsRoberta Schroder Rocha, Candida Aparecida Leite Kassuya, Anelise Samara Nazari Formagio, Mariana de Oliveira Mauro, Magaiver Andrade-Silva, Antonio Carlos Duenhas Monreal, Andréa Luiza Cunha-Laura, Maria do Carmo Vieira, Rodrigo Juliano Oliveira
JournalPharmaceutical biology (Pharm Biol) Vol. 54 Issue 1 Pg. 35-47 ( 2016) ISSN: 1744-5116 [Electronic] England
PMID25885939 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Analgesics
  • Anti-Inflammatory Agents
  • Anticarcinogenic Agents
  • Antimutagenic Agents
  • Plant Extracts
  • Solvents
  • Carrageenan
  • Methanol
Topics
  • Analgesics (chemistry, isolation & purification, pharmacology)
  • Animals
  • Annona (chemistry)
  • Anti-Inflammatory Agents (chemistry, isolation & purification, pharmacology)
  • Anticarcinogenic Agents (chemistry, isolation & purification, pharmacology)
  • Antimutagenic Agents (chemistry, isolation & purification, pharmacology)
  • Carrageenan
  • Chemotaxis, Leukocyte (drug effects)
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Hyperalgesia (chemically induced, prevention & control)
  • Inflammation (chemically induced, immunology, prevention & control)
  • Male
  • Methanol (chemistry)
  • Mice
  • Micronuclei, Chromosome-Defective (drug effects)
  • Micronucleus Tests
  • Phytotherapy
  • Plant Extracts (chemistry, isolation & purification, pharmacology)
  • Plant Leaves
  • Plants, Medicinal
  • Proton Magnetic Resonance Spectroscopy
  • Solvents (chemistry)
  • Time Factors

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