Lily steroidal glycoalkaloid promotes early inflammatory resolution in wounded human fibroblasts

Rong Di; Anne F Murray; Jia Xiong; Debora Esposito; Slavko Komarnytsky; Thomas J Gianfagna; John P Munafo Jr

doi:10.1016/j.jep.2020.112766

Lily steroidal glycoalkaloid promotes early inflammatory resolution in wounded human fibroblasts

J Ethnopharmacol. 2020 Aug 10:258:112766. doi: 10.1016/j.jep.2020.112766. Epub 2020 Mar 17.

Authors

Rong Di¹, Anne F Murray², Jia Xiong³, Debora Esposito³, Slavko Komarnytsky⁴, Thomas J Gianfagna¹, John P Munafo Jr⁵

Affiliations

¹ Department of Plant Biology, Rutgers-The State University of New Jersey, 59 Dudley Rd, New Brunswick, NJ, 08901, USA.
² Department of Food Science, University of Tennessee Institute of Agriculture, Knoxville, TN, 37996, USA.
³ Plants for Human Health Institute, North Carolina State University, 600 Laureate Way, Kannapolis, NC, 28081, USA; Department of Animal Science, North Carolina State University, 400 Dan Allen Drive, Raleigh, NC, 27695, USA.
⁴ Plants for Human Health Institute, North Carolina State University, 600 Laureate Way, Kannapolis, NC, 28081, USA; Department of Food, Bioprocessing, and Nutrition Sciences, North Carolina State University, 400 Dan Allen Drive, Raleigh, NC, 27695, USA.
⁵ Department of Food Science, University of Tennessee Institute of Agriculture, Knoxville, TN, 37996, USA. Electronic address: jmunafo@utk.edu.

PMID: 32194231
DOI: 10.1016/j.jep.2020.112766

Abstract

Ethnopharmacological relevance: The bulbs and flowers of plants from the Lilium genus have historically been used in Asian and Greco-Roman medicine to treat burns and promote skin healing.

Aim of the study: To evaluate a steroidal glycoalkaloid isolated from Easter lily bulbs for its potential wound healing promoting properties.

Materials and methods: A lily-derived steroidal glycoalkaloid (LSGA), (22R, 25R)-spirosol-5-en-3β-yl O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)-β-D-glucopyranoside, was isolated from Easter lily bulbs, and its structure was confirmed by LC-MS and NMR spectrometry. LSGA effects on wound scratch closure were evaluated in a primary human dermal fibroblast cell culture, and the changes in gene expression profiles were quantitated using an 84 wound-related gene qPCR microarray.

Results: LSGA promoted migration of dermal fibroblasts into the wounded area. The treatment was associated with a rapid upregulation of early inflammatory (CD40LG, CXCL11, IFNG, IL10, IL2 and IL4), cell growth (CSF3 and TNF) and remodeling (CTSG, F13A1, FGA, MMP and PLG) genes both in the wounded and unwounded cells treated with LSGA. A selective decrease in gene expression profiles associated with inflammatory (CXCL2 and CCL7) and remodeling (MMP7 and PLAT) phases was observed in wounded cells treated with LSGA, in contrast to the wounded cells (control).

Conclusion: This study demonstrates that a glycoalkaloid present in lilies promoted fibroblast migration in vitro and affected inflammatory, remodeling and growth factor gene expression. The decreases in expression of key genes may impact the wound healing process, possibly contributing to an earlier end of the inflammatory response and shortening the early phases of model tissue reconstitution. The results of this preliminary investigation may provide a basis for the historical use of lily bulbs to promote dermal healing after injury.

Keywords: Easter lily; Gene expression; Human dermal fibroblast cells; Lilium longiflorum Thunb.; Scratch migration assay; Steroidal glycoalkaloid.

MeSH terms

Alkaloids / isolation & purification
Alkaloids / pharmacology*
Cell Movement / drug effects
Cells, Cultured
Chromatography, Liquid
Fibroblasts / drug effects
Fibroblasts / pathology
Flowers
Gene Expression Regulation / drug effects
Glycosides / isolation & purification
Glycosides / pharmacology*
Humans
Inflammation / drug therapy*
Inflammation / pathology
Lilium / chemistry*
Plant Roots
Wound Healing / drug effects

Substances

Alkaloids
Glycosides