Biological Effects of Shikonin in Human Gingival Fibroblasts via ERK 1/2 Signaling Pathway

Abstract

Shikonin, an active ingredient of Lithospermum erythrorhizon, exerts anti-inflammatory and antibacterial effects, and promotes wound healing. We investigated whether shikonin stimulated gingival tissue wound healing in human gingival fibroblasts (hGF). In addition, we evaluated the effects of shikonin on the mitogen-activated protein kinase (MAPK) signaling pathway, which has an important role in wound healing. hGF were subjected to primary culture using gingiva collected from patients. The cells were exposed to/treated with Shikonin at concentrations ranging from 0.01 to 100 μM. The optimal concentration was determined by cell proliferation and migration assays. Type I collagen and fibronectin synthesis, the gene expression of vascular endothelial growth factor (VEGF) and FN, and the phosphorylation of Extracellular signal-regulated kinase (ERK) 1/2 were investigated. Identical experiments were performed in the presence of PD98059 our data suggest, a specific ERK 1/2 inhibitor. Shikonin significantly promoted hGF proliferation and migration. Shikonin (1 µM) was chosen as the optimal concentration. Shikonin promoted type I collagen and FN synthesis, increased VEGF and FN expression, and induced ERK 1/2 phosphorylation. These changes were partially suppressed by PD98059. In conclusion, Shikonin promoted the proliferation, migration, type I collagen and FN synthesis, and expression of VEGF and FN via ERK 1/2 signaling pathway in hGFs. Therefore, shikonin may promote periodontal tissue wound healing.

Electrospun wound dressings containing bioactive natural products: physico-chemical characterization and biological assessment

“…For A/S concentration of 1 wt.% suppression of cell motility was observed, as already witnessed by confocal microscopy analysis. In previous studies, where pure A/S compounds were tested (contained in low amounts in the A/S mixture that we applied in the scaffolds), it was found that shikonin (at 1 μΜ) and deoxy-shikonin (at 1.5 and 3 μΜ) enhanced the in vitro migration of human gingival fibroblasts and keratinocytes, respectively [ 39 , 40 ]. Added to that, shikonin and alkannin succeeded in accelerating (dose-dependently) the proliferation of granuloma tissue in Wistar rats with the same potency, therefore, suggesting that the absolute configuration of the hydroxyl group in the side chain of these molecules did not seem to play any important role on producing this accelerating effect.…”

“…Another group has reported that shikonin and alkannin showed non-selective toxicity towards normal cell lines (human skin fibroblasts), with the IC 50 values being 1.2 ± 0.1 μM and 1.5 ± 0.1 μM, respectively [ 42 ]. It had also been mentioned that a commercial sample of shikonin and lithospermi radix extract induced the proliferation of human fibroblasts [ 39 , 43 ]. The highest proliferation rate of Hs27 fibroblasts was achieved at day 3 by isovaleryl-shikonin (at 500 nM and 1 μM) and dimeric A/S (at 1 μM).…”

The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs

“…Future efforts towards uncovering the anti-inflammatory potential of shikonin may prove significant. Further promoting the importance of future investigations, shikonin has shown significant promise as an antimicrobial and antiviral agent, as well as a wound healing promoter [ 224 , 229 , 237 , 238 , 239 , 240 , 241 , 242 ] ( Figure 4 B ). Nevertheless, it remains to be determined whether these beneficial properties of shikonin are mediated through modulation of PKM2 activity.…”

Traditional Chinese Medicine is an Alternative Therapeutic Option for Treatment of Pseudomonas aeruginosa Infections

“…Shiunko ointment is a traditional botanic formula used for treatment of wounded skin without causing undesirable side effects in China and Japan (Higaki et al, 1999), and it has been found to accelerate the epithelization of wounded skin infected with P. aeruginosa (Huang et al, 2004). The mechanisms underlying the Shiunkomodulated epithelization possibly being through enhancing fibroblast proliferation and collagen production, and suppressing skin inflammation (Yan et al, 2015;Imai et al, 2019). In addition to inhibition of P. aeruginosa QS and biofilm formation, Qi Gui Yin decoction (9.9 g for every kg of body weight) was also identified to promote host immune response to P. aeruginosa infections by enhancing the antibody reactivity to β-lactamases, including VIM-1, SPM-1, and TEM-1, and manifested anti-inflammatory effects by reducing the levels of IL-1β and Th1/Th2 ratio in a rat model of abdominal infection (Kong et al, 2015).…”

“…Huang et al (2004);Yan et al (2015);Imai et al (2019) Qi Gui Yin Increase of B cell response and downregulation of inflammationEnhancement of antibody reactivity to β-lactamases and reduction of the levels of IL-1β and Th1/Th2 ratio Kong et al (2015) Qingre Baidu mixture Promotion of angiogenesis and wound healing Upregulation of the expression of HIF-1α, HIF-2α and VEGF Shan et al (2019) Frontiers in Pharmacology | www.frontiersin.org August 2021 | Volume 12 | Article 737252…”