title: Synergistic effect of (+)-pinitol from Saraca asoca with β-lactam antibiotics and studies on the in silico possible mechanism.
abstract: Saraca asoca bark has been used in the Ayurvedic system of medicine for female urino-genital disorders. We have recently reported the isolation and characterization of several compounds as markers to develop HPLC profiling of its methanol and aqueous methanol extracts. Now, a HPLC-PDA inactive compound, (+)-pinitol has been isolated and characterized from the bark of this medicinally important tree. Pinitol is a well known bioactive compound for a variety of biological activities, including hypoglycemic and anti-inflammatory activities. A process for the isolation of relatively good concentration of (+)-pinitol from S. asoca bark has been developed and its in vitro anti TNF-α and anti-inflammatory activities against carragenan-induced edema confirmed. While conducting experiments on the possible agonistic activity, it was found that (+)-pinitol showed up to eight fold reduction in the doses of β-lactam antibiotics. The mechanism of its agonistic activity was studied by docking experiments which showed that different conformations of (+)-pinitol and antibiotics were actually in the same binding site with no significant change in the binding energy. These docking simulations, thus predict the possible binding mode of studied compounds and probable reason behind the synergistic effect of (+)-pinitol along with β-lactam antibiotics.
authors.affiliation: a CSIR- Central Institute of Medicinal and Aromatic Plants , Lucknow 226015 , India.|b Academy of Scientific and Innovative Research, CIMAP Campus , Lucknow 226015 , India.
authors.forename: Furkan
authors.initials: F
authors.lastname: Ahmad
authors.affiliation: a CSIR- Central Institute of Medicinal and Aromatic Plants , Lucknow 226015 , India.
authors.forename: Laxminarain
authors.initials: L
authors.lastname: Misra
authors.affiliation: a CSIR- Central Institute of Medicinal and Aromatic Plants , Lucknow 226015 , India.
authors.forename: Vivek Kumar
authors.initials: VK
authors.lastname: Gupta
authors.affiliation: a CSIR- Central Institute of Medicinal and Aromatic Plants , Lucknow 226015 , India.
authors.forename: Mahendra Pandurang
authors.initials: MP
authors.lastname: Darokar
authors.affiliation: a CSIR- Central Institute of Medicinal and Aromatic Plants , Lucknow 226015 , India.
authors.forename: Om
authors.initials: O
authors.lastname: Prakash
authors.affiliation: a CSIR- Central Institute of Medicinal and Aromatic Plants , Lucknow 226015 , India.
authors.forename: Feroz
authors.initials: F
authors.lastname: Khan
authors.affiliation: c CSIR- Central Drug Research Institute , Lucknow 226020 , India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Shukla
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002351:Carrageenan / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D007887:Fabaceae / Q000737:chemistry*; D005260:Female; D006801:Humans; D007194:India; D007294:Inositol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008515:Medicine, Ayurvedic; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D024301:Plant Bark / Q000737:chemistry; D051381:Rats; D013237:Stereoisomerism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D047090:beta-Lactams / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D047090:beta-Lactams; C021730:pinitol; D007294:Inositol; D002351:Carrageenan
keywords: (+)-pinitol; Caesalpiniaceae; Saraca asoca; in silico mechanism; synergistic antibiotic activity; β-lactam antibiotics