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Pro-inflammatory cytokine molecules from Boswellia serrate suppresses lipopolysaccharides induced inflammation demonstrated in an in-vivo zebrafish larval model

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A Correction to this article was published on 08 June 2023

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Abstract

Background

Boswellia serrate is an ancient and highly valued ayurvedic herb. Its extracts have been used in medicine for centuries to treat a wide variety of chronic inflammatory diseases. However, the mechanism by which B. serrata hydro alcoholic extract inhibited pro-inflammatory cytokines in zebrafish (Danio rerio) larvae with LPS-induced inflammation remained unknown.

Methods

LC–MS analysis was used to investigate the extract’s phytochemical components. To determine the toxicity of B. serrata extract, cytotoxicity and embryo toxicity tests were performed. The in-vivo zebrafish larvae model was used to evaluate the antioxidant and anti-inflammatory activity of B. serrata extract.

Results

According to an in silico study using molecular docking and ADMET, the compounds acetyl-11-keto-boswellic and 11-keto-beta-boswellic acid present in the extract had higher binding affinity for the inflammatory specific receptor, and it is predicted to be an orally active molecule. In both in-vitro L6 cells and in-vivo zebrafish larvae, 160 µg/mL concentration of extract caused a high rate of lethality. The extract was found to have a protective effect against LPS-induced inflammation at concentrations ranged between 10 and 80 µg/mL. In zebrafish larvae, 80 µg/mL of treatment significantly lowered the level of intracellular ROS, apoptosis, lipid peroxidation, and nitric oxide. Similarly, zebrafish larvae treated with B. serrata extract (80 µg/mL) showed an increased anti-inflammatory activity by lowering inflammatory specific gene expression (iNOS, TNF-α, COX-2, and IL-1).

Conclusions

Overall, our findings suggest that B. serrata can act as a potent redox scavenger against LPS-induced inflammation in zebrafish larvae and an inhibitor of specific inflammatory genes.

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Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

Code availability

Not applicable.

Change history

Abbreviations

LPS:

Lipopolysaccharide

iNOS:

inducible nitric oxide synthase

COX-2:

cyclooxygenase-2

TNF-α:

tumor necrosis factor-alpha

IL-1:

interleukin

ROS:

reactive oxygen species

LC-MS:

Liquid chromatography-mass spectrometry

ESI:

electrospray ionization

CDL:

curved desolation line

NO:

nitric oxide

DCFDA:

2’-7’-dichlorofluorescein diacetate

DPPP:

diphenyl-1-pyrenylphosphine

BBB:

blood-brain barrier

P-gp:

permeability glycoprotein

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Acknowledgements

We would like to thank SRM College of Pharmacy, Interdisciplinary Institute of Indian System of Medicine (IIISM), SRM Research Institute and the SRMIST management for providing support during the research work. The authors express their sincere appreciation to the Researchers Supporting Project Number (RSP2022R414), King Saud University, Riyadh, Saudi Arabia.

Funding

Researchers Supporting Project (Number: RSP2022R414), King Saud University, Riyadh, Saudi Arabia.

Author information

Authors and Affiliations

  1. Department of Pharmacy Practice, SRM College of Pharmacy, SRM Institute of Science and Technology, 603 203, Kattankulathur, Chennai, Tamil Nadu, India

    N. Sai Supra Siddhu & Thangavel Mahalingam Vijayakumar

  2. Department of Biotechnology, College of Science and Humanities, SRM Institute of Science and Technology, 603203, Kattankulathur, Chennai, Tamil Nadu, India

    Ajay Guru & Jesu Arockiaraj

  3. Interdisciplinary Institute of Indian System of Medicine, SRM Institute of Science and Technology, 603 203, Kattankulathur, Chennai, Tamil Nadu, India

    Rajappan Chandra Satish Kumar

  4. Department of Zoology, College of Science, King Saud University, P.O. Box 2455, 11451, Riyadh, Saudi Arabia

    Bader O. Almutairi & Mikhlid H. Almutairi

  5. Foundation for Aquaculture Innovations and Technology Transfer (FAITT), Thoraipakkam, 600 097, Chennai, Tamil Nadu, India

    Annie Juliet

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  1. N. Sai Supra Siddhu
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Contributions

NSSS, AG, TMV and JA contributed to the concept and design of the study; NSSS and AG performed the experiments; RCSK, BOA, MHA, AJ, TMV and JA contributed significantly to resources, data analysis, manuscript preparation and perform the analysis with constructive discussions; TMV and JA supervised and checked the manuscript; All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Thangavel Mahalingam Vijayakumar or Jesu Arockiaraj.

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Ethical approval

The experiments conducted with zebrafish is as per the guidelines of the Institute Animal Ethical Committee and approval (SAF/IAEC/211215/004). This research does not contain any studies with human participants by any of the authors.

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The original online version of this article was revised: The affiliation of the author “Annie Juliet” is corrected as “Foundation for Aquaculture Innovations and Technology Transfer (FAITT), Thoraipakkam, Chennai 600 097, Tamil Nadu, India”.

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Siddhu, N.S.S., Guru, A., Satish Kumar, R.C. et al. Pro-inflammatory cytokine molecules from Boswellia serrate suppresses lipopolysaccharides induced inflammation demonstrated in an in-vivo zebrafish larval model. Mol Biol Rep 49, 7425–7435 (2022). https://doi.org/10.1007/s11033-022-07544-5

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