Anti-inflammatory activity of Odina wodier Roxb, an Indian folk remedy, through inhibition of toll-like receptor 4 signaling pathway
Authors: Bharti Malhotra
Amalesh Samanta
Durbadal Ojha
Supriya Mondal
Debprasad Chattopadhyay
Keshab C Mondal
Aditya Jena
Ved Prakash Dwivedi
Hemanta Mukherjee
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Inflammation; Chronic inflammatory diseases; Odina wodier; Methanol extract; Chlorogenic acid
Affiliations: ICMR Virus Unit, I.D. & B.G. Hospital, Beliaghata, Kolkata, India; Division of Microbiology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India., ICMR Virus Unit, I.D. & B.G. Hospital, Beliaghata, Kolkata, India., Department of Microbiology, Vidyasagar University, Midnapur, West Bengal, India., Department of Microbiology, SMS Medical College & Hospital, Jaipur, India., Division of Microbiology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.

Abstract:  Inflammation is part of self-limiting non-specific immune response, which occurs during bodily injury. In some disorders the inflammatory process becomes continuous, leading to the development of chronic inflammatory diseases including cardiovascular diseases, diabetes, cancer etc. Several Indian tribes used the bark of Odina wodier (OWB) for treating inflammatory disorders. Thus, we have evaluated the immunotherapeutic potential of OWB methanol extract and its major constituent chlorogenic acid (CA), using three popular in vivo antiinflammatory models: Carrageenan- and Dextran-induced paw edema, Cotton pellet granuloma, and Acetic acid-induced vascular permeability. To elucidate the possible anti-inflammatory mechanism of action we determine the level of major inflammatory mediators (NO, iNOS, COX-2-dependent prostaglandin E2 or PGE2), and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-12). Further, we determine the toll-like receptor 4 (TLR4), Myeloid differentiation primary response gene 88 (MyD88), c-Jun N-terminal kinases (JNK), nuclear factor kappa-B cells (NF-κB), and NF-kB inhibitor alpha (IK-Bα) by protein and mRNA expression, and Western blot analysis in drug treated LPS-induced murine macrophage model. Moreover, we determined the acute and sub-acute toxicity of OWB extract in BALB/c mice. Our study demonstrated a significant anti-inflammatory activity of OWB extract and CA along with the inhibition of TNF-α, IL-1β, IL-6 and IL-12 expressions. Further, the expression of TLR4, NF-κBp65, MyD88, iNOS and COX-2 molecules were reduced in drug-treated groups, but not in the LPS-stimulated untreated or control groups, Thus, our results collectively indicated that the OWB extract and CA can efficiently inhibit inflammation through the down regulation of TLR4/MyD88/NF-kB signaling pathway. 

Retracted: No

PubPeer comments:
 Above: Fig 2C.  The LPS-stimulated macrophages were treated with the OWB extract and CA, incubated for 24 h, following which RNA was isolated and subjected to the RTu2013PCR analysis for the expression of iNOS2 mRNA. Below: Fig 5.  The LPS-stimulated macrophages were treated with the OWB or CA and incubated for 24 h, following which RNA was isolated for RTu2013PCR analysis of the expression of MyD88 (A) and TLR4 (B) mRNA . iNOS2 and TLR8 bands are surprisingly similar. Could there have been an error during figure composition? ![file] ,