• Journal of Ginseng Research
• /
• v.44 no.1
• /
• pp.168-177
• /
• 2020

Background: Ginseng has been widely used as a health-promoting tonic. Gintonin present in ginseng acts as a lysophosphatidic acid (LPA) receptor ligand that activates six LPA receptor subtypes. The LPA6 subtype plays a key role in normal hair growth, and mutations in the LPA6 receptor impair normal human hair growth. Currently, human hair loss and alopecia are concerning issues that affect peoples' social and day-to-day lives. Objective: We investigated the in vitro and in vivo effects of a gintonin-enriched fraction (GEF) on mouse hair growth. Methods: Human hair follicle dermal papilla cells (HFDPCs) and six-week-old male C57BL/6 mice were used. The mice were divided into the four groups: control, 1% minoxidil, 0.75% GEF, and 1.5% GEF. The dorsal hair was removed to synchronize the telogen phase. Each group was treated topically, once a day, for 15 days. We analyzed hair growth activity and histological changes. Results: GEF induced transient [Ca²⁺]_i, which stimulated HFDPC proliferation and caused 5-bromo-2'-deoxyuridine (BrdU) incorporation in a concentration-dependent manner. GEF-mediated HFDPC proliferation was blocked by the LPA receptor antagonist and Ca²⁺ chelator. HFDPC treatment with GEF stimulated vascular endothelial growth factor release. Topical application of GEF and minoxidil promoted hair growth in a dose-dependent manner. Histological analysis showed that GEF and minoxidil increased the number of hair follicles and hair weight. Conclusion: Topical application of GEF promotes mouse hair growth through HFDPC proliferation. GEF could be one of the main components of ginseng that promote hair growth and could be used to treat human alopecia.

• The Journal of Korean Medicine
• /
• v.43 no.1
• /
• pp.18-32
• /
• 2022

Objectives: This study aimed to examine the safety, effects on proliferation of hair papilla cells, and anti-inflammatory and antioxidant mechanisms of Artemisia sieversiana Ehrh. ex Willd. (AS) extract. Methods: Safety tests through purity testing, acute toxicity tests, and repeated toxicity tests were performed using AS extract (ASE) which had been dried for over two years. Cell culture and proliferation tests were conducted; VEGF (vascular endothelial growth factor), bFGF (basic fibroblast growth factor), and EGF (epidermal growth factor) and protein expression analyses were performed for mechanistic evaluation; and inhibitory effects of ASE on the RNA expression of testosterone, 5𝛼-reductase, and aromatase was assessed. The anti-inflammatory and antioxidant efficacy of ASE was confirmed by measuring the levels of nitric oxide, inflammatory mediators (TNF-𝛼 and PGE2), inflammatory cytokines (IL-1𝛽, IL-6, and IL-8), and chemokine MCP-1. Results: The safety of ASE was confirmed. The mechanism of cell proliferation in human hair follicle dermal papilla cells involved the promotion of VEGF, bFGF, and EGF expression. ASE decreased mRNA expression of testosterone, 5𝛼-reductase, and aromatase-1 in a concentration-dependent manner. PGE2 and TNF-𝛼 production by inflammatory mediators was also significantly decreased in a concentration-dependent manner, and inflammatory cytokine and chemokine expression was inhibited. Conclusions: ASE is suggested to promote papillary cell growth at the cellular level, to suppress expression of various enzymes involved in hair cycle and cell death, and to inhibit hair loss through anti-androgen, anti-inflammatory, and antioxidant effects.

• Journal of Life Science
• /
• v.33 no.3
• /
• pp.234-241
• /
• 2023

At present, many countries around the world are legalizing cannabis and its products, and research on various treatments using cannabis is being actively conducted. However, the cannabis plant contains other compounds whose biological effects have not yet been established. We investigated the effect of cannabidiol (CBD) on hair growth in human dermal papilla cells (HDPCs). 2,2'-Azino-bis (3-ethylbenzothiazolin-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays were performed to determine the antioxidant activity of CBD. The HDPCs viability of CBD was examined via water-soluble tetrazolium salt (WST-1) assay. The expression of hair-loss-related markers in HDPCs by CBD treatment was analyzed by real-time PCR and western blotting. The DPPH, ABTS radical scavenging activity assay showed that CBD had superior antioxidant activities. In HDPCs, CBD increased cellular proliferation at concentrations without cytotoxicity. It also increased the expressions of fibroblast growth factor 1 (FGF1), fibroblast growth factor 7 (FGF7), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF). These results correlated with a decrease in the expression of inhibition-related factors, such as androgen receptor (AR) and transforming growth factor beta 1 (TGF-B1). Moreover, CBD resulted in a significant increase in the phosphorylation of AKT and extracellular signal-regulated kinase (ERK). Therefore, it is suggested that CBD may be a potential remedy for the treatment of alopecia.

• The Korean Journal of Physiology and Pharmacology
• /
• v.22 no.2
• /
• pp.203-213
• /
• 2018

Tumor undergo uncontrolled, excessive proliferation leads to hypoxic microenvironment. To fulfill their demand for nutrient, and oxygen, tumor angiogenesis is required. Endothelial progenitor cells (EPCs) have been known to the main source of angiogenesis because of their potential to differentiation into endothelial cells. Therefore, understanding the mechanism of EPC-mediated angiogenesis in hypoxia is critical for development of cancer therapy. Recently, mitochondrial dynamics has emerged as a critical mechanism for cellular function and differentiation under hypoxic conditions. However, the role of mitochondrial dynamics in hypoxia-induced angiogenesis remains to be elucidated. In this study, we demonstrated that hypoxia-induced mitochondrial fission accelerates EPCs bioactivities. We first investigated the effect of hypoxia on EPC-mediated angiogenesis. Cell migration, invasion, and tube formation was significantly increased under hypoxic conditions; expression of EPC surface markers was unchanged. And mitochondrial fission was induced by hypoxia time-dependent manner. We found that hypoxia-induced mitochondrial fission was triggered by dynamin-related protein Drp1, specifically, phosphorylated DRP1 at Ser637, a suppression marker for mitochondrial fission, was impaired in hypoxia time-dependent manner. To confirm the role of DRP1 in EPC-mediated angiogenesis, we analyzed cell bioactivities using Mdivi-1, a selective DRP1 inhibitor, and DRP1 siRNA. DRP1 silencing or Mdivi-1 treatment dramatically reduced cell migration, invasion, and tube formation in EPCs, but the expression of EPC surface markers was unchanged. In conclusion, we uncovered a novel role of mitochondrial fission in hypoxia-induced angiogenesis. Therefore, we suggest that specific modulation of DRP1-mediated mitochondrial dynamics may be a potential therapeutic strategy in EPC-mediated tumor angiogenesis.

• Tuberculosis and Respiratory Diseases
• /
• v.50 no.6
• /
• pp.676-685
• /
• 2001

Background : Angiogenesis is an essential component of tumor growth and metastasis, and the vascular endothelial growth factor (VEGF) is one of the most important angiogenic factors. Several solid tumors produce substantial amounts of VEGF, which stimulates proliferation and the migration of endothelial cells, thereby inducing neovasculization by a paracrine mechanism. To evaluate the prognostic roles of angiogenesis and VEGF expression in patients with non-small cell lung cancer, the relationship between VEGF expression in tumor tissues, the clinicopathologic features and the overall survival rate were analysed. Methods : Sixty-nine resected primary non-small cell lung cancer specimens were evaluated. The paraffin-embedded tumor tissues were stained by anti-VEGF polyclonal antibodies using an immunohistochemical method to assess VEGF expression. Results : In Forty-one patients (59%), the VEGF antigen was expressed weakly in their tumor tissue, whereas in twenty-eight patients (41%) the VEGF antigen was expressed strongly. The median survival time of the weak VEGF expression group was 24 months, and that of the strong VEGF expression group was 19 months. The three year-survival rates were 35%, 33%, respectively. The survival difference between both groups was not statistically significant. Conclusion : Although results were not statistically significant, the strong expression group tended to poorer prognosis than the weak expression group.

• Molecules and Cells
• /
• v.38 no.6
• /
• pp.528-534
• /
• 2015

Hypoxia-inducible factor (HIF) is a key regulator of tumor growth and angiogenesis. Recent studies have shown that, BIX01294, a G9a histone methyltransferase (HMT)-specific inhibitor, induces apoptosis and inhibits the proliferation, migration, and invasion of cancer cells. However, not many studies have investigated whether inhibition of G9a HMT can modulate HIF-$1{\alpha}$ stability and angiogenesis. Here, we show that BIX01294 dose-dependently decreases levels of HIF-$1{\alpha}$ in HepG2 human hepatocellular carcinoma cells. The half-life of HIF-$1{\alpha}$, expression of proline hydroxylase 2 (PHD2), hydroxylated HIF-$1{\alpha}$ and von Hippel-Lindau protein (pVHL) under hypoxic conditions were decreased by BIX01294. The mRNA expression and secretion of vascular endothelial growth factor (VEGF) were also significantly reduced by BIX01294 under hypoxic conditions in HepG2 cells. BIX01294 remarkably decreased angiogenic activity induced by VEGF in vitro, ex vivo, and in vivo, as demonstrated by assays using human umbilical vein endothelial cells (HUVECs), mouse aortic rings, and chick chorioallantoic membranes (CAMs), respectively. Furthermore, BIX01294 suppressed VEGF-induced matrix metalloproteinase 2 (MMP2) activity and inhibited VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR-2), focal adhesion kinase (FAK), and paxillin in HUVECs. In addition, BIX01294 inhibited VEGF-induced formation of actin cytoskeletal stress fibers. In conclusion, we demonstrated that BIX01294 inhibits HIF-$1{\alpha}$ stability and VEGF-induced angiogenesis through the VEGFR-2 signaling pathway and actin cytoskeletal remodeling, indicating a promising approach for developing novel therapeutics to stop tumor progression.

• Polymer(Korea)
• /
• v.38 no.6
• /
• pp.702-707
• /
• 2014

Corneal endothelium is mono-inner cell layer of cornea and lay on Descmet's membrane which comprised of various proteins called extracellular matrix such as fibronectin, collagen, laminin, and proteoglycan, etc. In this study, we fabricated transparent poly(lactic-co-glycolic acid) (PLGA) film because PLGA is widely used for tissue engineering based on their properties. We investigated the behaviors of rabbit corneal endothelial cells (rCEnCs) on PLGA film surfaces coated with various cell-adhesive molecules like fibronectin, laminin, collagen type I and IV and FNC coating mix. The morphologic images, proliferation and adhesion assay, immunofluorescence for ZO-1 and $Na^+/K^+-ATPase$ and RT-PCR for expression of specific markers were conducted. These results showed that PLGA film plays a role as CEnC carriers in vitro and the cell-adhesive molecules give positive effects on the behaviors of rCEnC.

• Journal of Life Science
• /
• v.23 no.12
• /
• pp.1532-1540
• /
• 2013

T-box transcription factor 2 (Tbr2) is a member of the T-box family of transcription factors and it plays an important role in brain development, progenitor cell proliferation, and the modulation of differentiation and function in immune cells, such as CD8+ T cells and natural killer cells. This study aims to elucidate the involvement of Tbr2 in the pathophysiological events following pilocarpine-induced status epilepticus in mice. Status epilepticus resulted in prominent neuronal cell death in discrete brain regions, such as CA3, the hilus, and the piriform cortex. Interestingly, when the immunoreactivity of Tbr2 was examined two days after status epilepticus, it was transiently increased in CA3 and in the piriform cortex. Tbr2-positive cells in CA3 and the piriform cortex were double-labeled with CD11b, a marker of microglia and a subset of white blood cells, such as monocytes, CD8+ T cells, and natural killer cells. Moreover, the double-labeled cells with Tbr2 and CD11b showed amoeboid morphology, and this data indicates that Tbr2-expressing cells may be reactive microglia or infiltrating white blood cells. Furthermore, clustered Tbr2-positive cells were observed in the platelet endothelial cell adhesion molecule-1 (PECAM-1)-positive blood vessels near the CA3 area, which suggests that Tbr2-positive cells may be infiltrating the white blood cells. Based on this data, this study is the first to indicate the involvement of Tbr2 in neuropathophysiology in status epilepticus.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.20 no.4
• /
• pp.825-829
• /
• 2006

Rhus verniciflua Stokes has been used for treatment of blood stasis and abdominal mass in Oriental medicine. Rhus verniciflua Stokes has been experimentally reported to exert antioxidant, antiproliferative, antithrombotic and apoptotic activities. In the present study, the antiangiogenic and in vivo antitumor activities of aqueous extract of processed Rhus verniciflua Stokes (Nexia) by heat were examined to elucidate its anticancer mechanism. Nexia showed weak cytotoxiicty against human umbilical vein endothelial cells (HUVEC) and Lewis lung carcinoma cells (LLC) with IC50 of${\sim}200\;{\mu}g/ml\;and\;>200\;{\mu}g/ml$, respectively. Nexia significantly inhibited the proliferation and migratory activity in vascular endothelial growth factor(VEGF) treated HUVEC. Furthermore, Nexia effectively suppressed the tumor volume in A549 nonsmall lung cancer bearing athymic nude mice, CanN. Cg-Foxn 1nu/CrljBgi up to 40.7% as well as tumor weight incised from LLC cells innoculated into the flank of C57BL/6 mice up to -50% compared with untreated control at a dose of 300 mg/kg. Taken together, these results suggest that processed Rhus verniciflua Stokes may inhibit the growth of Lewis lung carcinoma cells partly via inhibition of angiogenesis and can be potently applied to angiogenesis dependent cancers. However, it still needs a further research on molecular mechanism, angiogenesis animal study and clinical trial in future.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.31 no.4 s.54
• /
• pp.311-321
• /
• 2005

Tea (Camellia sinenis) is a popular beverage consumed worldwide. Since green tea, mainly consumed in Asia, has various biological activities, green tea components became one of the most favorite candidates as a functional materials for cosmetics and functional foods. The biological activities of green tea for skin cue have been ranged from protection of epidermal cells to the stimulation of extracellular matrix (ECM) biosynthesis. Green tea polyphenols (GTPs), which are active ingredients of green tea, possess anti-inflammatory, anti-carcinogenic and immune potentiation properties as well as antioxidant. They also modulate intracellular signal transduction pathways. GTPs decrease ultraviolet (UV)-induced oxidative stress, thus suppress mitogen-activated protein kinase (MAPK) pathway and apoptosis in keratinocytes. In addition, GTPs prevent the Induction of inflammatory mediators, such as cyclooxygenase-2 (COX-2), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) by tumor necrosis factor alpha $(TNF{\alpha})$ or chemical treatment in keratinocytes. GTPs treatment protects from chemical-or UV-induced skin tumor incidence in animal experiment. Besides, GTPs stimulate keratinocyte differentiation and proliferation of normal and aged epidermal cells, resectively, and suppress matrix metalloproteinases (MMPs) release. According to the progress of formulation study, green tea components will be guaranteed materials for the more effective skin cue products.