Wogonin, a natural flavonoid, intercalates with genomic DNA and exhibits protective effects in IL-1beta stimulated osteoarthritis chondrocytes.

Title

Wogonin, a natural flavonoid, intercalates with genomic DNA and exhibits protective effects in IL-1beta stimulated osteoarthritis chondrocytes.

Creator

Khan Nazir M; Ahmad Imran; Ansari Mohammad Y; Haqqi Tariq M

Publisher

Chemico-biological interactions

Date

2017
2017-08

Description

Wogonin has recently been shown to possess anti-inflammatory and chondroprotective properties and is of considerable interest due to its broad pharmacological activities. The present study highlights that Wogonin binds DNA and exerts chondroprotective effects in vitro. Wogonin showed strong binding with chondrocytes genomic DNA in vitro. The mode of binding of Wogonin to genomic-DNA was assessed by competing Wogonin with EtBr or DAPI, known DNA intercalator and a minor groove binder, respectively. EtBr fluorescence reduced significantly with increase in Wogonin concentration suggesting possible DNA intercalation of Wogonin. Further, in silico molecular docking of Wogonin on mammalian DNA also indicated possible intercalation of Wogonin with DNA. The denaturation and FRET studies revealed that Wogonin prevents denaturation of DNA strands and provide stability to genomic DNA against a variety of chemical denaturants. The cellular uptake study showed that Wogonin enters osteoarthritis chondrocytes and was mainly localized in the nucleus. Wogonin treatment to OA chondrocytes protects the fragmentation of genomic DNA in response to IL-1beta as evaluated by DNA ladder and TUNEL assay. Treatment of chondrocytes with Wogonin resulted in significant suppression of IL-1beta-mediated induction of ROS. Further, Wogonin exhibited protective potential through potent suppression of extrinsic and intrinsic apoptotic pathways and induction of anti-apoptotic proteins in

Subject

Apoptosis/drug effects; Binding Sites; Cells; Chondrocytes/cytology/*drug effects/metabolism; Chondroprotective effects; Cultured; Denaturation; DNA binding; DNA/chemistry/*metabolism; Flavanones/chemistry/metabolism/*pharmacology; Flavonoids/chemistry/pharmacology; Fluorescence Resonance Energy Transfer; Humans; Intercalating Agents/chemistry/metabolism/*pharmacology; Interleukin-1beta/*pharmacology; Molecular Docking Simulation; Nucleic Acid Conformation; Osteoarthritis; Osteoarthritis/metabolism/pathology; Protective Agents/chemistry/metabolism/*pharmacology; Reactive Oxygen Species/metabolism; Up-Regulation/drug effects; Wogonin

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

13–23

Volume

274

Citation

Khan Nazir M; Ahmad Imran; Ansari Mohammad Y; Haqqi Tariq M, “Wogonin, a natural flavonoid, intercalates with genomic DNA and exhibits protective effects in IL-1beta stimulated osteoarthritis chondrocytes.,” NEOMED Bibliography Database, accessed August 6, 2021, https://neomed.omeka.net/items/show/3515.

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