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Berberis lycium Royle fruit extract mitigates oxi-inflammatory stress by suppressing NF-κB/MAPK signalling cascade in activated macrophages and Treg proliferation in splenic lymphocytes

  • Anamika Sharma
  • Rohit Sharma
  • Dinesh Kumar
  • Yogendra Padwad
Original Article

Abstract

Although Berberis plant species have been advocated as immune modulators, information regarding their mechanism(s) of action is limited. Therefore, in the present study we assessed the efficacy of Berberis lycium Royle fruit extract (BLFE) in the attenuation of lipopolysaccharide (LPS)-induced oxi-inflammatory aggravation and concanavalin A (Con-A)-induced proliferation in murine peritoneal macrophages and lymphocytes, respectively. BLFE strongly suppressed production of the oxidative and inflammatory effector molecules nitric oxide (NO), reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), inflammatory cytokines (TNF-α/IL-6/IL-1β/IFN-γ) as well as chemokines (MCP-1 and RANTES), with a concomitant enhancement in heme oxygenase-1 (HO-1) and IL-10 levels. Subsequent mechanistic analysis revealed that BLFE strongly inhibited the phosphorylation of IκBα as well as MAPKs such as extracellular signal-regulated kinase (ERK), p38 MAPK, and c-Jun NH2-terminal kinase (JNK), thereby directly resulting in the suppression of nuclear factor-κB (NF-ĸB) and c-Jun activation, ultimately culminating in the observed attenuation of inflammatory molecules. Additionally, BLFE appeared to mitigate Con-A-induced proliferation of Tregs (CD3+ CD4+ CD25+) thereby suggesting its modulatory effects on adaptive immune cells. UPLC–DAD–ESI-QTOF-MS/MS of BLFE revealed the presence of major bioactive phenolics and alkaloids including chlorogenic acid, rutin, catechin and quercetin 3-d-galactoside, berberine and magnoflorine, which could have synergistically contributed to the above findings. Overall, this work provides evidence that BLFE may be effective in the mitigation of inflammatory disorders, especially those associated with NF-κB/MAPK activation.

Graphical abstract

Keywords

Berberis lycium Fruit extract Oxi-inflammation NF-κB c-Jun MAPKs Tregs 

Notes

Acknowledgements

We express our gratitude to the Director, CSIR-IHBT Palampur, for his support and encouragement. We acknowledge SEED, Department of Science and Technology, for providing financial assistance through project GAP-0193 and CSIR for project MLP-0204, respectively, along with Academy of Scientific and Innovative Research (AcSIR), Chennai, India, for Ph.D. registration. We are thankful to Mr. Pawan Kumar for his technical support. CSIR manuscript number for this work is 4327.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

Supplementary material

10787_2018_548_MOESM1_ESM.docx (560 kb)
Supplementary material 1 (DOCX 559 kb)

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Anamika Sharma
    • 1
    • 3
  • Rohit Sharma
    • 1
    • 3
  • Dinesh Kumar
    • 2
    • 3
  • Yogendra Padwad
    • 1
    • 3
  1. 1.Pharmacology and Toxicology Lab, Food and Nutraceutical DivisionCSIR-Institute of Himalayan Bioresource TechnologyPalampurIndia
  2. 2.Natural Product Chemistry and Product Development DivisionCSIR-Institute of Himalayan Bioresource TechnologyPalampurIndia
  3. 3.Academy of Scientific and Innovative ResearchCSIR-Institute of Himalayan Bioresource TechnologyPalampurIndia

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