Liposome-Encapsulated Baicalein Suppressed Lipogenesis and Extracellular Matrix Formation in Hs68 Human Dermal Fibroblasts

Abstract

The dermis of human skin contains large numbers of fibroblasts that are responsible for the production of the extracellular matrix (ECM) that supporting skin integrity, elasticity and wound healing. Previously, an in vivo study demonstrated that dermal fibroblasts siting in the lower dermis are capable to convert into skin adipose layer and hence fibroblast lipogenesis may vary the structure and elasticity of dermis. In the present study, Hs68 human dermal fibroblasts were utilized as an in vitro model to study the lipogenesis via using adipogenic differentiation medium (ADM). Baicalein, isolated from Scutellaria baicalensis, is one of the flavonoids to inhibit adipocyte differentiation due to high antioxidant activity in vitro. In order to develop a suitable formulation for baicalein (a poorly water-soluble drug), soybean phosphatidylcholine (SPC) was used to prepare baicalein-loaded liposomes to enhance drug bioavailability. Our results demonstrated that liposome-encapsulated baicalein protected cell viability and increased cellular uptake efficiency of Hs68 fibroblasts. Lipid accumulation, triglyceride synthesis and gene expressions of lipogenesis enzymes (FABP4 and LPL) were significantly increased in ADM-stimulated Hs68 fibroblasts but subsequently suppressed by liposome-encapsulated baicalein. In addition, ADM-induced TNF-α expression and related inflammatory factors was down-regulated by liposome-encapsulated baicalein. Through ADM-induced lipogenesis, the protein expression of elastin, type I and type III collagens increased remarkably, whereas liposome-encapsulated baicalein can down-regulate ADM-induced ECM protein synthesis. Taken together, we found that liposome-encapsulated baicalein can inhibit ADM-induced lipid accumulation and ECM formation in Hs68 fibroblasts through the suppression of lipogenesis enzymes and inflammatory responses. Liposome-encapsulated baicalein may have the potential to improve wound healing and restore skin structure after skin injury.

Novel Liposomal Formulation of Baicalein for the Treatment of Pancreatic Ductal Adenocarcinoma: Design, Characterization, and Evaluation

“…However, this group did not provide detailed size distribution graphs or PDI distribution values. Unfortunately, there are no data from this work about the EE% of BAI [ 60 ]. Another BAI loading procedure was reported by Fang et al [ 61 ].…”

Some Nanocarrier’s Properties and Chemical Interaction Mechanisms with Flavones

“…With respect to the characterization of the 5,6,7-trihydroxyflavone (baicalein) NPs, it has been found that the size of mesoporous silica NPs (MSNs) is considerably larger, 367 ± 94 nm [ 95 ], than the size of liposomes 135–154 nm [ 96 ] or NPs 82.5 ± 1.7 nm [ 97 ]. Regarding the variation of the size of NPs in the NP population that is PDI, it is observed that nanoemulsions (NE) and NPs are monodisperse, while liposomes vary in size.…”

“…The presence of baicalein does not alter the electrophoretic mobility of the liposomes. Fang et al (2018) [ 96 ] concluded that the reduction in particle size may be mainly due to strong interactions with baicalein via the H-bond but has no effect on the zeta potential.…”

“…Baicalein has low solubility in aqueous solution and low bioavailability in vivo, which limits its application; liposomal nanoencapsulation is recommended due to its high compatibility and easy incorporation efficiency [ 96 ]. Therefore, drugs encapsulated in NPs present a reduced dispersion of the drug, longer permanence time on the skin, and facilitate the internalization of the drug into the cells [ 99 ].…”

The potential of functionalized dressing releasing flavonoids facilitates scar-free healing

“…Flavonoids have been proven in studies to lower TGF-β1 and IL-1β production, limit extracellular matrix (ECM) secretion, and prevent excessive fibrous connective tissue deposition ( 97 ). For example, while maintaining the viability of fibroblasts, safranin inhibits TNF-α expression, reduces ECM protein synthesis and improves wound healing ( 98 ). Pinocembrin, the most abundant flavonoid compound in propolis, has anti-fibrotic properties, inhibiting TGF-β1 signaling and impairing TGF-β1-induced proliferation and activation of abnormal skin fibroblasts, effectively alleviating bleomycin (an antibiotic)-induced excessive skin fibrosis ( 99 ).…”