Abstract | CONTEXT: Azadirachta indica A. Juss. (Meliaceaes) leaves have been used traditionally to treat swelling and rheumatism in Indian cultures. OBJECTIVE: To fractionate A. indica leaf extracts using bioactivity guided manner for identification of the active anti-inflammatory principles. MATERIALS AND METHODS: Polarity-gradient sequential extracts ( petroleum ether, chloroform, methanol, and water) of A. indica leaves were screened for their anti-inflammatory potential using the carrageenan-induced rat paw edema model (1 g/kg). The chloroform extract was sequentially fractionated to obtain n-hexane (F-1), n-hexane- chloroform (F-2), and chloroform (F-3) fractions and their inhibitory effect on rat paw edema was evaluated (500 mg/kg). Inhibitory effect of F-2 on granuloma formation, plasma interleukin (IL-1), and tumor necrosis factor (TNF-α) was assessed at the doses of 100, 200, and 400 mg/kg using the cotton pellet assay in rats. Three sub-fractions (SF-1, SF-2, and SF-3) were obtained upon chromatography of F-2, and their inhibitory effect on cyclooxygenase was assessed at 200 µg/mL concentration. The sub-fractions were subjected to gas chromatography-mass spectrometry (GC-MS). RESULTS: All the extracts showed significant anti-inflammatory effect; however, chloroform extract was the most effective against paw edema (53.25% inhibition). The three fractions of chloroform extract showed significant effect, while F-2 being the most potent (51.02%). F-2 demonstrated dose-dependent inhibition of granuloma and cytokines. Interestingly, all the sub-fractions of F-2 inhibited COX-1 and COX-2 with almost equal potential. GC-MS revealed that chemically the sub-fractions were totally different from each other. DISCUSSION AND CONCLUSION: Anti-inflammatory effect of A. indica is a result of cumulative and synergistic effects of diversified constituents with varying polarities that collectively exert the effect via suppression of cyclo- oxygenases and cytokines (IL-1 and TNF-α).
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Authors | Muhammad Ihtisham Umar, Mohd Zaini Asmawi, Amirin Sadikun, A M S Abdul Majid, Item Justin Atangwho, Mohamed B Khadeer Ahamed, Rabia Altaf, Ashfaq Ahmad |
Journal | Pharmaceutical biology
(Pharm Biol)
Vol. 52
Issue 11
Pg. 1411-22
(Nov 2014)
ISSN: 1744-5116 [Electronic] England |
PMID | 25026347
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents
- Plant Extracts
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Topics |
- Animals
- Anti-Inflammatory Agents
(isolation & purification, therapeutic use)
- Azadirachta
- Dose-Response Relationship, Drug
- Drug Synergism
- Edema
(blood, drug therapy, pathology)
- Female
- Humans
- Male
- Plant Extracts
(isolation & purification, therapeutic use)
- Plant Leaves
- Rats
- Rats, Sprague-Dawley
- Sheep
- Treatment Outcome
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