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Liquiritigenin, isoliquiritigenin rich extract of glycyrrhiza glabra roots attenuates inflammation in macrophages and collagen-induced arthritis in rats

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Abstract

Liquiritigenin (LTG) and its bioprecursor isoliquiritigenin(ISL), the main bioactives from roots of Glycyrrhiza genus are progressively documented as a potential pharmacological agent for the management of chronic diseases. The aim of this study was to evaluate the pharmacological potential of liquiritigenin, isoliquiritigenin rich extract of Glycyrrhiza glabra roots (IVT-21) against the production of pro-inflammatory cytokines from activated macrophages as well as further validated the efficacy in collagen-induced arthritis model in rats. We also performed the safety profile of IVT-21 using standard in-vitro and in-vivo assays. Results of this study revealed that the treatment of IVT-21 and its major bioactives (LTG, ISL) was able to reduce the production of pro-inflammatory cytokines (TNF-α, IL-6) in LPS-activated primary peritoneal macrophages in a dose-dependent manner compared with vehicle-alone treated cells without any cytotoxic effect on macrophages. In-vivo efficacy profile against collagen-induced arthritis in Rats revealed that oral administration of IVT-21 significantly reduced the arthritis index, arthritis score, inflammatory mediators level in serum. IVT-21 oral treatment is also able to reduce the NFкB-p65 expression as evidence of immunohistochemistry in knee joint tissue and mRNA level of pro-inflammatory cytokines in paw tissue in a dose-dependent manner when compared with vehicle treated rats. Acute oral toxicity profile of IVT-21 demonstrated that it is safe up to 2000 mg/kg body weight in experimental mice. This result suggests the suitability of IVT-21 for further study in the management of arthritis and related complications.

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Data availability

All data generated during this study are included in this article and the primary data for this study are available from the author on direct request.

Abbreviations

AI:

Arthritis index

CIA:

Collagen-induced arthritis

CMC:

Carboxymethyl cellulose

COX-2:

Cyclooxygenase-2

C-RP:

C-reactive protein

Dexa:

Dexamethasone

DMARDs:

Disease modifying anti-rheumatic drugs

DMEM:

Dulbecco’s modified eagle’s medium

G. glabra :

Glycyrrhiza glabra

GF:

Gram force

HRP:

Horseradish peroxidase

IHC:

Immunohistochemistry

IL:

Interleukin

ISL:

Isoliquiritigenin

LPS:

Lipopolysaccharides

LTG:

Liquiritigenin

LWT:

Limb withdrawal threshold

MMPs:

Matrix metalloproteinases

NO:

Nitric oxide

NSAIDs:

Non-steroidal anti-inflammatory drugs

PAM:

Pressure application measurement

PBS:

Phosphate-buffered saline

RA:

Rheumatoid arthritis

RT-PCR:

Reverse transcription–polymerase chain reaction

TNF-α:

Tumor necrosis factor α

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Acknowledgements

The study was financially supported by the CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow under project HCP-010 and CSIR- Emeritus Scientist project 21(1050)/18 EMR-II, respectively. The authors are grateful to the CSIR for providing fellowships to the first author and Director, CSIR-CIMAP, Lucknow, India for providing essential research facilities and support.

Funding

csir-cimap,HCP-010, Dnyaneshwar Umrao Bawankule, CSIR-Emeritus Scientist project 21(1050)/18 EMR-II, Rajendra S. Bhakuni.

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Authors and Affiliations

  1. Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Post Office-CIMAP, Near Kukrail Picnic Spot, Lucknow, Uttar Pradesh, 226015, India

    Vineet Babu, Monika Binwal & Dnyaneshwar U. Bawankule

  2. Phytochemistry Division, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow, 226015, India

    Deepak Singh Kapkoti & Rajendra S. Bhakuni

  3. Phytochemistry Division, Analytical Chemistry Lab, CSIR-Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow, 226015, India

    Karuna Shanker & Manju Singh

  4. Process Chemistry and Chemical Engineering Department, Central Institute of Medicinal and Aromatic Plants (CIMAP), Council of Scientific and Industrial Research (CSIR), PO CIMAP, Near Kukrail Picnic Spot, Lucknow, 226015, India

    Sudeep Tandon

  5. Department of Toxicology & Experimental Medicine, CSIR-Central Drug Research Institute (CDRI), Lucknow, Uttar Pradesh, 226031, India

    Madhav N. Mugale

  6. Botany and Pharmacognosy, CSIR-Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow, Uttar Pradesh, India

    Narendra Kumar

  7. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India

    Monika Binwal & Dnyaneshwar U. Bawankule

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  1. Vineet Babu
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  2. Deepak Singh Kapkoti
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  6. Manju Singh
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  10. Dnyaneshwar U. Bawankule
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Contributions

DUB: planning, manuscript preparation and supervised the experiment. VB: performed the biological experiments and manuscript preparation. DSK and RSB: enrich extract development and manuscript preparation. MB: contributed in in-vivo experiment. KS and MS: HPLC method development and quality standardization. ST: plant extraction. MNM: contributed in histopathology and Immunohistochemistry study. NK: Collection and identification of plant material.

Corresponding authors

Correspondence to Rajendra S. Bhakuni or Dnyaneshwar U. Bawankule.

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Babu, V., Kapkoti, D.S., Binwal, M. et al. Liquiritigenin, isoliquiritigenin rich extract of glycyrrhiza glabra roots attenuates inflammation in macrophages and collagen-induced arthritis in rats. Inflammopharmacol 31, 983–996 (2023). https://doi.org/10.1007/s10787-023-01152-w

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  • DOI: https://doi.org/10.1007/s10787-023-01152-w

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