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The Anti-Inflammatory and Cytoprotective Efficiency of Curvularin, a Fungal Macrolactone against Lipopolysaccharide-Induced Inflammatory Response in Nucleus Pulposus Cells: An In Vitro Study

Asian Spine Journal 2021년 15권 2호 p.143 ~ 154
Banala Rajkiran Reddy, Vemuri Satish Kumar, Sherline E. V., Gurava Reddy A. V., Subbaiah G. P. V.,
소속 상세정보
 ( Banala Rajkiran Reddy ) - Sunshine Hospitals Sunshine Medical Academy of Research and Training
 ( Vemuri Satish Kumar ) - Sunshine Hospitals Sunshine Medical Academy of Research and Training
 ( Sherline E. V. ) - Star Hospitals Department of Spine Surgery
 ( Gurava Reddy A. V. ) - Sunshine Hospitals Sunshine Medical Academy of Research and Training
 ( Subbaiah G. P. V. ) - Sunshine Hospitals Sunshine Medical Academy of Research and Training

Abstract


Study Design: Developing an in vitro model for assessing the anti-inflammatory properties of curvularin.

Purpose: To evaluate the efficacy of natural fungal macrolactone as a therapeutic drug against lipopolysaccharide (LPS)-induced inflammation in primary human nucleus pulposus cells (NPCs) in vitro.

Overview of Literature: Lumbar disk disease is a common cause of lower back pain (LBP) and sciatica. It is an established fact that inflammation, rather than mechanical compression on the nerve root, plays a role in the cause of LBP and sciatica. Current treatment options for reducing inflammation are either nonsteroidal anti-inflammatory drugs or steroids, prolonged use of which can potentially lead to adverse effects such as gastrointestinal disturbances and renal and cardiac issues. Hence, there is a need for better antiinflammatory drugs with no or minimal complications for treating inflammation-induced LBP and sciatica. Curvularin (Cur), a fungal macrolactone, is known for its anti-inflammatory activity, but nothing is known about its impact on inflammation due to disk pathologies.

Methods: Primary NPCs were cultured and characterized by flow cytometry and immunocytochemistry using the CD24 antibody and treated with 10 μg/mL LPS for 36 hours and then treated with Cur, betamethasone, and dexamethasone (10 μg/mL) for 48 hours, after which cell cycle analysis, cell viability assay, and gene expression studies (quantitative polymerase chain reaction [PCR] and quantitative real-time-PCR) were conducted. The NPCs treated with Cur downregulated the expression of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1β, and IL-6); matrix metalloproteinases (MMPs; MMP-2 and MMP-3), ADAMTS; and apoptotic marker (cytochrome c).

Results: In our study, Cur-treated cells showed enhanced expression of collagen 9A1 and insulin-like growth factor receptor 1, indicating the recovery of NPCs from inflammatory assault.

Conclusions: Based on observations, the anti-inflammatory properties of Cur render it an excellent drug molecule for treating disk degeneration nonsurgically, by direct injection into spinal disks when treating LBP and sciatica.

키워드

Intervertebral disc degeneration; Macrolactone; Curvularin; Lipopolysaccharide; Inflammation; Cytokines; Nonsteroidal anti-inflammatory drugs

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