Ectopic expression of human acidic fibroblast growth factor 1 in the medicinal plant, Salvia miltiorrhiza, accelerates the healing of burn wounds

Abstract

BackgroundHealing of burns is a complex process and very few effective treatments exist to facilitate the burn recovery process. Human acidic fibroblast growth factor 1 (FGF-1) plays an important role in a variety of biological processes, including angiogenesis, and tissue repair. Salvia miltiorrhiza is widely used in traditional Chinese medicine as an herb for the treatment of various diseases, including cardiovascular and cerebrovascular diseases, and traumatic injuries. We present that expression of FGF-1 in S. miltiorrhiza significantly accelerates the healing of burn wounds.ResultsThe human fgf-1 gene was fused with a barley α-amylase signal peptide DNA sequence and driven by a 35S promoter for constitutive expression in transgenic S. miltiorrhiza plants. The highest yield of recombinant FGF-1 obtained from leaves of transgenic S. miltiorrhiza lines was 272 ng/fresh weight. Aqueous extracts from transgenic S. miltiorrhiza exhibited FGF-1 activity approximately 19.2-fold greater than that of the standard FGF-1. Compared to the standard FGF-1 or the extracts obtained from non-transgenic plants, it stimulated proliferation of Balb/c 3 T3 mouse fibroblast cells assessed with the standard MTT assay and promoted angiogenesis in the chicken embryo chorioallantoic membrane (CAM) assay. Topical application of the extract significantly accelerated the burn wound healing process.ConclusionsThe product appears to retain the biological activity of both FGF-1 as well as the medicinal properties of the plant. The extracts from transgenic S. miltiorrhiza combines the therapeutic functions of FGF-1 and the medicinal plant, S. miltiorrhiza. Topical application of the product can reduce the costs associated with extraction, purification, and recovery.

The effect of crude drugs on the angiogenic property and dynamic viscoelasticity of PEMA-based soft polymer materials

“…Huangqi contains glycosides and flavonoids as the main components, which have been shown to improve VEGF mRNA expression in vascular endothelial cells 8,14) . However, several researchers have reported that the activity of cyclooxygenase-2 (COX-2) may be inhibited by high concentrations of flavonoid [8][9][10]12,14) , which may explain for the diminished angiogenic activity in the specimens containing 10 wt% Huangqi in the present study. Similarly, diminished angiogenic activity in the specimens containing Danshen may be attributed to the high amounts of Salvianolic Acid B in this drug, which is known to inhibit the activities of TGF-β and COX-2 8,10,14,15) .…”

“…We performed an angiogenesis test in the group using PEMA-A polymer (powder form) due to the high tan δ values exhibited by this group. Several in vitro and in vivo method have been used to evaluate angiogenesis [8][9][10][11]26) . The various in vivo methods used include the Mile's assay, chicken embryo chorioallantoic membrane method, and the Matrigel subcutaneous implantation method; however, these methods have various limitations 26) .…”

“…It is possible to shorten the period of wound healing by promoting angiogenesis using various bioactive substances. Many researchers have reported that traditional Chinese drugs (crude drugs) have angiogenesis promoting effects, antimycotic properties, and antiangiogenic functions [8][9][10][11][12][13][14][15] . Yang et al 8) reported that several crude drugs such as Salvia miltiorrhiza Bunge (Danshen), Angelica sinensis (Danggui), Astragalus membranaceus Bunge (Huangqi), and Puerarin radix (Gegen) can promote angiogenesis by acting on proteins such as vascular endothelial growth factor (VEGF).…”

Effect of Topical Administration of Fractions and Isolated Molecules from Plant Extracts on Skin Wound Healing: A Systematic Review of Murine Experimental Models

“…The use of plant based strategies is opening a new perspective for the treatment of skin wounds, mainly in developing countries, once it represents a simple, low cost, and affordable therapy [1, 7, 56–58]. There are several studies indicating beneficial effects of herbal medicines in all phases of the healing process.…”

“…It has been demonstrated that flaws on the leukocyte recruitment and function can impair the healing process due to reductions in the synthesis of regulatory molecules that drives the extracellular matrix assembly [5–7] and neoangiogenesis [8]. In this way, the development of drugs and alternative treatments that favor the migration and cellular activity during the inflammatory and proliferation phases may enhance the skin wound repair.…”