Microglia play an important role in the maintenance and neuroprotection of the central nervous system (CNS) by removing pathogens, damaged neurons, and plaques. Recent observations emphasize that the promotion and development of neurodegenerative diseases (NDs) are closely related to microglial activation. In this review, we summarize the contribution of microglial activation and its associated mechanisms in NDs, such as epilepsy, Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), based on recent observations. This review also briefly introduces experimental animal models of epilepsy, AD, PD, and HD. Thus, this review provides a better understanding of microglial functions in the development of NDs, suggesting that microglial targeting could be an effective therapeutic strategy for these diseases.

Cigarette smoke (CS) is considered a principal cause of chronic obstructive pulmonary disease (COPD) and is associated with mucus hypersecretion and airway inflammation. Ginsenoside compound K (CK), a product of ginsenoside metabolism, has various biological activities. Studies on the effects of CK for the treatment of COPD and mucus hypersecretion, including the underlying signaling mechanism, have not yet been conducted. To study the protective effects and molecular mechanism of CK, phorbol 12-myristate 13-acetate (PMA)-induced human airway epithelial (NCI–H292) cells were used as a cellular model of airway inflammation. An experimental mouse COPD model was also established via CS inhalation and intranasal administration of lipopolysaccharide. Mucin 5AC (MUC5AC), monocyte chemoattractant protein-1, tumor necrosis factor-α (TNF-α), and interleukin-6 secretion, as well as elastase activity and reactive oxygen species production, were determined through enzyme-linked immunosorbent assay. Inflammatory cell influx and mucus secretion in mouse lung tissues were estimated using hematoxylin and eosin and periodic acid–schiff staining, respectively. PKCδ and its downstream signaling molecules were analyzed via western blotting. CK prevented the secretion of MUC5AC and TNF-α in PMA-stimulated NCI–H292 cells and exhibited a protective effect in COPD mice via the suppression of inflammatory mediators and mucus secretion. These effects were accompanied by an inactivation of PKCδ and related signaling in vitro and in vivo. CK suppressed pulmonary inflammation and mucus secretion in COPD mouse model through PKC regulation, highlighting the compound's potential as a useful adjuvant in the prevention and treatment of COPD.

The extract tea of Dendropanax morbifera is popular beverages in Korea, and their preventive and therapeutic roles in metabolic disorders have been reported. However, the molecular mechanism has not been studied despite the known efficacy of D. morbifera. Eleven fractions (fr.1–fr.11) were divided by MPLC to find the active compound. Among them, Fr.5 was superior to others in that the inhibitory efficacy of de novo triglyceride (TG) biosynthesis. NMR analysis revealed that Fr.5 is composed 98% or more (9Z,16S)-16-hydroxy-9,17-octadecadiene-12,14-diynoic acid (HOD). Treatment of HOD diminished oleic acid (OA)-induced TG accumulation in HepG2 hepatocytes and differentiation of 3T3-L1 preadipocytes by activating LKB1/AMPK. In addition, we determined the effect of the oral administration of the extract of D. morbifera on obesity and hepatic steatosis in high-fat diet (HFD)-induced obese mice. This study proved that D. morbifera containing HOD, the active substance, can show preventive or therapeutic efficacy on obesity and hepatic steatosis through the targeting LKB1/AMPK axis.

Since long-term or high-dose use of COPD medication causes adverse effects in patients with COPD, more effective and safer ways to manage COPD symptoms are required. Daphne kiusiana Miquel is a medicinal plant, but its anti-COPD efficacy was little studied. We investigated the anti-COPD activity and molecular mechanism of action of active compounds isolated from D. kiusiana to find drug candidates for COPD. We isolated seven compounds (1-7) in an ethyl acetate (EtOAc) fraction from D. kiusiana, and determined that seven compounds effectively control the inflammatory responsiveness in both PMA-stimulated lung epithelial cells (in vitro) and/or in COPD model mice using cigarette smoke- and lipopolysaccharides-exposed animals in vivo. We show that the ethyl acetate (EtOAc) fraction from D. kiusiana. suppresses inflammatory response in both PMA-stimulated human lung epithelial cells (in vitro) and COPD model mice (in vivo). The EtOAc fraction effectively suppresses various inflammatory responses, such as mucus secretion, ROS production, bronchial recruitment of inflammatory cells, and release of proinflammatory cytokines. Additionally, we isolated three compounds with anti-inflammatory efficacy from the EtOAc fraction, out of which daphnodorin C was the most effective. Finally, we demonstrated that daphnodorin C negatively regulates inflammatory gene expression by suppressing NF-κB and specific MAPK signaling pathways (JNK and p38) in vitro and in vivo. These results suggest that daphnodorin C could be a promising therapeutic alternative for managing COPD symptoms.