New phenylethanoid from the flower of Osmanthus fragrans and their bioactivities on human dermal fibroblasts

Highlights

• The aqueous extracts of flower of Osmanthus fragrans were phenylethanoid-rich constituents.

• One new phenylethanoids were identified: glucooleoacteoside.

• Acteoside and osmanthuside B promote HDF cell proliferation.

• 4′′-O-acetylacteoside, acteoside and oleoacteoside increase the expression of type I collagen.

• 4′′-O-acetylacteoside and isoacteoside decrease MMP-1 expression.

Abstract

New phenylethanoid, glucooleoacteoside (2), along with 18 known compounds were isolated from the aqueous extract of Osmanthus fragrans. The structure of new compound was elucidated on the base of IR, HR-ESI-MS, 1D NMR, 2D NMR and DEPT analysis. Bioactivity investigation into human dermal fibroblasts (HDF) proliferation, type I collagen expression, and MMP-1 expression were examined with six phenylethanoids. We found that compounds 1, 3, 4, 7, and 9 showed moderate bioactivities. In conclusion, we demonstrated that the aqueous extract of flower of O. fragrans contained phenylethanoid-rich constituents which revealed bioactivities at the cellular level of HDFs.

Introduction

Although the cost of caring for wounds is increasing, the effective treatment of wounds remains a major global health challenge (Agyare et al., 2019). Wound healing is a dynamic and complicated process, can be divided into three overlapping phases—inflammation, proliferation, and remodeling. The inflammatory response is regarded as the first of series of complex processes that constitute wound healing. In addition to the sensitive balance between neutrophils and macrophages to achieving tissue homeostasis following injury, ROS plays a prominent role in multiple steps of the pathogenesis of wounds (Eming et al., 2007). Thus, the disturbed inflammation balance is considered a major factor of wound healing.

Fibroblasts are the key cells involved in the production of the extracellular matrix and collagen. Type I collagen is the most abundant collagen that is expressed in almost all tissues including skin and fibroblast cells. Preventing excessive matrix degradation is crucial in healing though abnormal degradation of the extracellular matrix probably results from the excessive proteinase activity in wounds (Harding et al., 2002). Once closure of the wound has been achieved, remodeling of the resulting scar takes places. At this stage, collagen synthesis plays a role in the setting to decrease scar fibrosis. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes responsible for the degradation of extracellular matrix proteins. Studies shown that MMPs play important roles in skin aging, inflammation and wound healing (Nagase et al., 2006). MMP-1, also known as fibroblast collagenase, is primarily implicated in degradation of type I collagen. Increased MMP-1 expression in skin fibroblast cells has been shown to associate with reduced collagen synthesis, which has been considered to be a cause of skin damages (Nagase et al., 2006). Taken together, proper regulation of fibroblasts proliferation, type I collagen expression, and MMP-1 expression in dermal fibroblasts can positively benefit the outcome of the wound healing process.

Recently, researchers have demonstrated that the presence of the phenylethanoids in herbs may play a role in wound healing effects of burns and scalds. The flower of Osmanthus fragrans is a traditional Chinese herb and edible flower widely consumed in Asian countries. Studies have revealed that the major phytochemicals presented in O. fragrans flower are phenylethanoids, including acteoside and isoacteoside (Lu et al., 2016). These phenylethanoids have been reported to possess several beneficial effects for human skin health, including prominent anti-inflammation (Hung et al., 2013), free radical scavenging (Lee et al., 2007), tyrosinase activity inhibition (Wu et al., 2009), and neuroprotection (Xiong et al., 2016). In addition, studies have elucidated that phenylethanoids can differentially affect cytoplasmic and nuclear components of the EGFR signaling pathway (Pastore et al., 2012). EGFR is an essential functional regulator of keratinocyte responses to a number of extracellular stimuli, including specific EGFR ligands and cytokine receptors, which regulate the inflammatory and repair-related processes in the skin. Moreover, phenylethanoids can also inhibit inflammation mediators and increase keratinocyte migration, thereby displaying a significant reduction in TNFα, IL-6, and IFNγ levels (de Moura Sperotto et al., 2018).

Above all, the phenylethanoids presented in O. fragrans flower may be an excellent strategy to fasten the wound healing process because it contains the prominent anti-inflammatory and cytoprotective effects. A relatively simple aqueous preparation, which is beneficial for formulation development, can be used to investigate the compounds that exhibit effective bioactivities. However, the chemical constituents of aqueous extract of O. fragrans are rarely reported. In this study, we identify the phenylethanoids of the aqueous extract of flowers of O. fragrans and screen their bioactivities on fibroblast proliferation, type I collagen, and MMP-1 expression. Our results suggest that O. fragrans is a promising botanical medicine that can exert positive bioactivities on HDFs.