Sung-Tae Hong

Although Atractylodes macrocephala Koidz. (AM) exhibits various pharmacological properties, its molecular effects and active constituents regarding anagen entry and physiological hair cycle progression remain uncharacterized. This study aimed to investigate the hair growth-promoting efficacy of AM and identify its bioactive compounds and underlying molecular mechanisms. We evaluated AM extract using human dermal papilla cells (DPCs) and a synchronized depilation-induced C57BL/6 mouse model, employing RT-PCR, Western blotting, immunofluorescence, and SwissADME-based pharmacokinetic profiling. AM significantly enhanced DPC proliferation and migration while upregulating paracrine factors (HGF, VEGF, and FGF7). Mechanistically, AM activated Akt, ERK, and p38 MAPKs, leading to GSK3β phosphorylation (Ser9) and subsequent β-catenin stabilization. In vivo, oral AM (60 mg/kg) markedly accelerated the telogen-to-anagen transition, increasing dermal thickness, follicle count, and hair shaft quality without systemic toxicity. Furthermore, cell-based screening and SwissADME prioritized atractylenolide I and III as the chief bioactive sesquiterpenoids driving DPC activation. In conclusion, AM and its key atractylenolides promote anagen entry and hair regrowth, in association with GSK3β phosphorylation and β-catenin stabilization, representing promising natural candidates for promoting physiological hair cycle progression.

Reprogramming tumor cells to a normal state is a central issue in cancer biology. Human translationally controlled tumor protein (TCTP) has emerged as a major player in tumor reversion. However, genetic networks linked to the family of TCTP proteins are complex, and the roles of TCTP in tumor formation and reversion are only partially understood. Genetic analysis in model organisms can provide clues to the biological functions of TCTP in vivo as well as deliver insights into its roles in normal and cancer cells. Studies in the Drosophila model have revealed a wide range of Tctp functions regulating tissue growth, cell death, genome stability, and chromatin organization. Silencing of Tctp suppresses tumorous growth in fly organs, consistent with the human TCTP role in tumor reversion. In this chapter, we focus on the genetic and molecular interactions of Tctp with specific partners involved in growth signaling, DNA repair, and epigenetic regulation in Drosophila. These studies highlight Drosophila as an efficient animal model for studying TCTP functions in growth control and tumor reversion.

Asthma is a chronic inflammatory lung disease that causes respiratory difficulties. Black ginseng extract (BGE) has preventative effects on respiratory inflammatory diseases such as asthma. However, the pharmacological mechanisms behind the anti-asthmatic activity of BGE remain unknown. To investigate the anti-asthmatic mechanism of BGE, phorbol 12-myristate 13-acetate plus ionomycin (PMA/Iono)-stimulated mouse EL4 cells and ovalbumin (OVA)-induced mice with allergic airway inflammation were used. Immune cells (eosinophils/macrophages), interleukin (IL)-4, -5, -13, and serum immunoglobulin E (IgE) levels were measured using an enzyme-linked immunosorbent assay. Inflammatory cell recruitment and mucus secretion in the lung tissue were estimated. Protein expression was analyzed via Western blotting, including that of inducible nitric oxide synthase (iNOS) and the activation of protein kinase C theta (PKCθ) and its downstream signaling molecules. BGE decreased T helper (Th)2 cytokines, serum IgE, mucus secretion, and iNOS expression in mice with allergic airway inflammation, thereby providing a protective effect. Moreover, BGE and its major ginsenosides inhibited the production of Th2 cytokines in PMA/Iono-stimulated EL4 cells. In EL4 cells, these outcomes were accompanied by the inactivation of PKCθ and its downstream transcription factors, such as nuclear factor of activated T cells (NFAT), nuclear factor kappa B (NF-κB), activator of transcription 6 (STAT6), and GATA binding protein 3 (GATA3), which are involved in allergic airway inflammation. BGE also inhibited the activation of PKCθ and the abovementioned transcriptional factors in the lung tissue of mice with allergic airway inflammation. These results highlight the potential of BGE as a useful therapeutic and preventative agent for allergic airway inflammatory diseases such as allergic asthma.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease which causes breathing problems. YPL-001, consisting of six iridoids, has potent inhibitory efficacy against COPD. Although YPL-001 has completed clinical trial phase 2a as a natural drug for COPD treatment, the most effective iridoid in YPL-001 and its mechanism for reducing airway inflammation remain unclear. To find an iridoid most effectively reducing airway inflammation, we examined the inhibitory effects of the six iridoids in YPL-001 on TNF or PMA-stimulated inflammation (IL-6, IL-8, or MUC5AC) in NCI-H292 cells. Here, we show that verproside among the six iridoids most strongly suppresses inflammation. Both TNF/NF-κB-induced MUC5AC expression and PMA/PKCδ/EGR-1-induced IL-6/-8 expression are successfully reduced by verproside. Verproside also shows anti-inflammatory effects on a broad range of airway stimulants in NCI-H292 cells. The inhibitory effect of verproside on the phosphorylation of PKC enzymes is specific to PKCδ. Finally, in vivo assay using the COPD-mouse model shows that verproside effectively reduces lung inflammation by suppressing PKCδ activation and mucus overproduction. Altogether, we propose YPL-001 and verproside as candidate drugs for treating inflammatory lung diseases that act by inhibiting PKCδ activation and its downstream pathways.

The recently defined type of cell death ferroptosis has garnered significant attention as a potential new approach to cancer treatment owing to its more immunogenic nature when compared with apoptosis. Ferroptosis is characterized by the depletion of glutathione (GSH)/glutathione peroxidase-4 (GPx4) and iron-dependent lipid peroxidation. Diplacone (DP), a geranylated flavonoid compound found in Paulownia tomentosa fruit, has been identified to have anti-inflammatory and anti-radical activity. In this study, the potential anticancer activity of DP was explored against A549 human lung cancer cells. It was found that DP induced a form of cytotoxicity distinct from apoptosis, which was accompanied by extensive mitochondrial-derived cytoplasmic vacuoles. DP was also shown to increase mitochondrial Ca²⁺ influx, reactive oxygen species (ROS) production, and mitochondrial permeability transition (MPT) pore-opening. These changes led to decreases in mitochondrial membrane potential and DP-induced cell death. DP also induced lipid peroxidation and ATF3 expression, which are hallmarks of ferroptosis. The ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 were effective in counteracting the DP-mediated ferroptosis-related features. Our results could contribute to the use of DP as a ferroptosis-inducing agent, enabling studies focusing on the relationship between ferroptosis and the immunogenic cell death of cancer cells.