Aloe emodin shows high affinity to active site and low affinity to two other sites to result consummately reduced inhibition of lipoxygenase

• Published in: Prostaglandins & other lipid mediators 2020-10, Vol.150, p.106453-106453, Article 106453
• Main Authors: Sharanya, C.S., Arun, K.G., Sabu, A., Haridas, M.
• Format: Article
• Language: English
• Subjects: Cassia angustifolia (vahl.); Enzyme kinetics; Inflammation; Isotherma titration calorimetry; Lipoxygenase
• ISSN: 1098-8823
• DOI: 10.1016/j.prostaglandins.2020.106453

•Anthraquinone Aloe emodin, isolated from Cassia angustifolia (Vahl.).•It is a lipoxygenase inhibitor, comparable to known inhibitors.•Aloe emodin strongly bind at the active site.•It have a binding stoichiometry of three and these results validated through docking studies.•Molecular simulation shows high binding stability of Aloe emodin to LOX. Lipoxygenases (LOXs) are potential treatment targets in a variety of inflammatory conditions. It is assumed that blocking the arachidonic acid (AA) metabolism via COX inhibition by either traditional NSAIDs or selective cyclooxygenase-2 (COX-2) inhibitors could lead to the generation of pro-inflammatory leukotrienes and lipoxins via the LOX pathway, partly accounting for the side effects seen with traditional NSAIDs and selective COX-2 inhibitors. To counter this, several LOX, phospholipase A2 (PLA2) inhibitors have been reported nowadays from natural sources. Cassia angustifolia (Vahl.) is a medicinal herb belonging to the family Leguminosae and their LOX inhibitory profiles are reported in this study. Results indicate that ethyl acetate extract of Cassia leaves could inhibit LOX. MS and IR data revealed the presence of aloe emodin (270.2 m/z) in the isolated fraction. Enzyme kinetics showed that aloe emodin inhibit Lipoxygenase competitively with an IC50 of 29.49 μM. Interaction of aloe emodin with LOX was also studied using fluorescence quenching method. ITC results indicate that the interaction of LOX with aloe emodin is endothermic in nature with a stoichiometry of n = 3. In conclusion, anti-inflammatory property of the plant could be assigned to the presence of aloe emodin.