Original ArticleAllicin Inhibits Proliferation and Promotes Apoptosis of Human Epidural Scar Fibroblasts
Introduction
Lumbar epidural fibrosis represents a consequence of the histopathologic wound healing process after laminectomy and discectomy. Normal epidural fibrosis helps to repair the surgical incision, whereas extensive fibrosis may compress and irritate the nerve roots, thereby inducing recurrent radicular pain.1 Up to 95.6% of patients had extensive epidural fibrosis under epiduroscopy, and concordant pain was present in 84.3% of these patients and depended on the severity of fibrosis.2 As the outcome of current treatment options, including conservative treatment and scar excision, for such patients remains poor, biological therapies are increasingly being investigated.3
Fibroblasts are the main cells affecting the process of epidural fibrosis, and their proliferation is regulated by growth factors. The extensive epidural fibrosis is primarily produced by excessive fibroblast proliferation, which extends into the neural canal and causes pressure and stimulation to spinal marrow and nerve roots.4 Allicin (diallyl thiosulfinate) is a biomolecule produced during mashing of garlic. It has a variety of active biological functions for microbial, plant, and mammalian cells. In mammalian cell lines, allicin can induce apoptosis and inhibits cell proliferation.5 Intriguingly, allicin can suppress liver fibrosis via inhibition of transforming growth factor-β16 and suppress cardiac fibrosis by blocking nuclear factor-κB and Smad 2/3 signaling pathway.7 Notably, allicin is the main ingredient of garlic extract, the phytochemicals of which have never been associated with negative side effects.6 Thus, we hypothesized that allicin can inhibit proliferation and promote apoptosis of human epidural scar fibroblasts, thereby attenuating the epidural fibrosis and partly avoiding failed back surgery syndrome.
Section snippets
Cell Isolation and Culture
This study was approved by the Ethics Committee of the Clinical Medical College of Yangzhou University, and the patient provided informed written consent. Human epidural scar fibroblasts were obtained from epidural fibrous scars formed after laminectomy in a patient from Clinical Medical College of Yangzhou University in China. The patient was a 51-year-old man who had undergone a microendoscopic discectomy 4 years ago. He came to the clinic at the present time owing to a recurrent disc
Cell Viability and Migration Rate
After being treated with allicin at a concentration gradient of 0 mg/L, 12.5 mg/L, 25 mg/L, 50 mg/L, 100 mg/L, 200 mg/L, and 400 mg/L for 24 hours, the viability of fibroblasts in each group significantly decreased compared with the control group (P < 0.05) (Figure 2E), and it decreased in a concentration-dependent manner (r = 0.772, P = 0.042) (Figure 2E). The 50% inhibitory concentration of allicin for fibroblasts was 58.18 mg/L. After being treated with allicin at a concentration gradient of
Discussion
The healing process of an incision includes local inflammation reaction; fibroblast proliferation, differentiation, and immigration; extracellular matrix synthesis; and tissue reconstruction.3 The hyperplasia of fibrous scar tissue, which mainly originates from the sacrospinalis, annulus fibrosus, posterior longitudinal ligament, and lumbospinal region, into the neural canal is considered to be the main cause of leg pain after laminectomy and discectomy.8 In the present study, we found that
Conclusions
Allicin can block fibroblast proliferation at S phase and G2 phase, suppress cell migration, and induce cell apoptosis. Therefore, allicin has potential application value in clinical prevention and treatment of epidural adhesion. The underlying molecular biological mechanisms are still to be determined. Our next step is to apply allicin on all laminectomy rat models to observe if it can prevent the scar tissue from excessive fibrosis.
CRediT authorship contribution statement
Hui-Hui Sun: Methodology, Software, Writing - review & editing. Jing-Cheng Wang: Data curation, Software, Writing - original draft. Xin-Min Feng: Visualization, Investigation, Writing - review & editing. Shou-Lei Zhu: Data curation, Visualization, Writing - review & editing. Jun Cai: Conceptualization, Supervision, Validation.
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Conflict of interest statement: This study was funded by Jiangsu Provincial Health and Family Planning Commission (CXTDB2017004).