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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hassan, Loiy Elsir Ahmed Dahham, Saad S. Fadul, Samah M. Umar, Muhammad Ihtisham Majid, Aman Shah Abdul Khaw, Kooi Yeong Majid, Amin Malik Shah Abdul |
| Description | Author Affiliation: Hassan LE ( EMAN Testing & Research Laboratory, Department of Pharmacology, School of Pharmaceutical Sciences Universiti Sains, Malaysia); Dahham SS ( EMAN Testing & Research Laboratory, Department of Pharmacology, School of Pharmaceutical Sciences Universiti Sains, Malaysia.); Fadul SM ( School of Heath Sciences, Ahfad Univeristy for Women, P.O. Box 167, Omdurman, Sudan.); Umar MI ( Departments of Pharmacology, School of Pharmaceutical Sciences, 11800 Minden, Pulau Pinang, Malaysia.); Majid AS ( Department of Pharmacology, Quest International University, Perak, Malaysia.); Khaw KY ( Departments of Pharmacology, School of Pharmaceutical Sciences, 11800 Minden, Pulau Pinang, Malaysia.); Majid AM ( EMAN Testing & Research Laboratory, Department of Pharmacology, School of Pharmaceutical Sciences Universiti Sains, Malaysia.) |
| Abstract | ETHNOPHARMACOLOGICAL RELEVANCE: Tephrosia apollinea (Delile) DC (Leguminosae) has been used in folk medicine in Arabian countries to treat inflammatory disorders. The plant has been described to treat swelling, bone fracture, bronchitis, cough, earache and wounds. AIM OF THE STUDY: the current study aims to evaluate the anti-inflammatory properties of the major active phytoconstituent of T. apollinea and elucidate the mechanisms by which it inhibits inflammation in vitro and in vivo. MATERIAL AND METHODS: The compound, (-)-pseudosemiglabrin (SSG) was isolated as a major component from the aerial parts of T. apollinea using column chromatography techniques. Sub-chronic in vivo anti-inflammatory effect of SSG was assessed using cotton pellet granuloma assay in SD rats and serum levels of tumor necrosis factor- (TNF- ), interleukin-1 (IL-1) and nitric oxide (NO) were measured, whereas, tail flick assay was performed to assess the analgesic effect of SSG. Furthermore, the anti-inflammatory effects of SSG were confirmed by measuring the levels of IL-1, TNF- , and NO in vitro using human macrophage cell lines (U937). In addition COX inhibition assay was also conducted in cells-free system. In silico study was performed to dock SSG in cyclooxygenase enzymes and opioid receptor to predict its structure-activity and molecular mechanism. RESULTS: SSG displayed potential inhibition of granuloma tissue in rats and significantly (P<0.05) lowered the production of cytokines (TNF- and IL-1) in vivo as well as human macrophages. Further investigation revealed that, SSG selectively inhibited COX-2 by 60% with negligible effect on COX-1. The selectivity of SSG towards COX-2 was confirmed in silico wherein, SSG demonstrated significant binding affinity with binding energy (-9.42kcal/mol). The binding found to be through covalent energy with Ser-530 amino acid residue of the active pocket of COX-2. SSG was found to prolong the flick tail time in mice by two folds. Further computational studies reveal that SSG binds to opioid receptor (µ-OR) through Ile-144 and Thr-218 with affinity two folds compared to the reference compounds, codeine and aspirin. CONCLUSION: In the present study the major phytoconstituent (-)-pseudosemiglabrin (SSG) from the aerial parts of T. apollinea demonstrated potent anti-inflammatory effect by inhibiting of granuloma tissue in rats and prolonging the tail flick time in mice. Investigation of levels of pro-inflammatory cytokines in SSG-treated rats and human macrophages demonstrated that SSG significantly inhibited TNF- and IL-1. Also SSG showed selective inhibitory effect towards COX-2. In silico study exhibited pronounced binding affinity between SSG and µ-opioid receptor better than that of codeine and aspirin. The obtained results justify the use of aerial parts of T. apollinea to treat various inflammatory diseases and indicate that (-)-pseudosemiglabrin has a great potential to be further developed as a promising anti-inflammatory drug. |
| File Format | HTM / HTML |
| ISSN | 03788741 |
| Journal | Journal of Ethnopharmacology |
| Volume Number | 193 |
| e-ISSN | 18727573 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2016-12-04 |
| Publisher Place | Ireland |
| Access Restriction | One Nation One Subscription (ONOS) |
| Content Type | Text |
| Resource Type | Article |
| Subject | Drug Discovery Pharmacology |
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