Sang Jun Park

Network pharmacology is an emerging method for investigating the potential effects and mechanisms of natural products through system-level analyses of gene sets in herbs. Lonicera japonica Thunberg (LJ) is known to have anti-inflammatory, anti-bacterial, anti-oxidant, anti-tumor and neuroprotective effects. In the present study, network pharmacological analysis was performed to assess the potential efficacy and mechanisms of LJ. First of all, constituents of LJ were gathered from public databases: the Oriental Advanced Searching Integrated System (OASIS) database, PubChem and the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Then, a network was constructed using Cytoscape3.8.2, which visualizes biomedical interactions, and a functional enrichment analysis was conducted to uncover the pathways most relevant to LJ through Enrichr based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway 2021. Further, we performed a study of the literature to determine whether the results of our study were consistent with those of previous studies. The results showed that ‘Advanced glycation end products-Receptor for advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications’ was the pathway most relevant to LJ, especially through ‘Mitogen-activated protein kinase (MAPK) signaling pathway’, ‘Phosphatidylinositol 3 kinase-Protein kinase B (PI3K-AKT) signaling pathway’ and ‘Janus kinase-Signal transducers and activators of transcription (JAK-STAT) signaling pathway’. Based on the literature study, LJ showed relevance to MAPK, PI3K-AKT and JAK-STAT and was associated with therapeutic effects on diabetes and diabetic complications. This study shows that network pharmacology can be a suitable approach for analyzing LJ and suggests the potential efficacy and mechanisms of LJ.

Decursin, a pyranocoumarin compound from the root of Angelica gigas Nakai as a main constituent, has been reported to have various biological activities, including anti-inflammatory, anticancer, and antioxidant effects. This study aimed to predict and confirm the pharmacological relevance of Decursin on chemotherapy-induced alopecia (CIA) with the underlying molecular mechanisms. Decursin-targeted genes were compared with the gene set of alopecia and investigated through functional enrichment analysis. CIA was induced in C57BL/6J mice by injection of cyclophosphamide, and 1, 10, and 100 μM of Decursin were topically treated to depilated dorsal skin. KGF⁺ expression was detected in the dorsal skin tissues. Based on the predicted results, caspase, PIK3/AKT, and MAPKs protein expressions by Decursin were analyzed in the TNF-α-induced keratinocytes. The Decursin network had 60.20% overlapped genes with the network of alopecia. Biological processes, such as cellular response to chemical stimulus, apoptosis, PI3K-AKT signaling pathway, and MAPK signaling pathway, were derived from the Decursin network. In the Decursin-treated skin, there was morphological hair growth and histological restoration of hair follicles in the CIA mice. The KGF⁺ fluorescence and protein expressions were significantly increased by Decursin treatment. In addition, caspase-3, -7, and -8 expressions, induced by TNF-α, were dose-dependently decreased along with the inhibition of PI3K, AKT, ERK, and p38 expressions in Decursin-treated keratinocytes. These findings indicated that Decursin would be a potent therapeutic option for hair loss, in response to chemotherapy.

Fine particulate matter (PM) exposure exhibits a crucial risk factor to exacerbate airway epithelial remodeling, fibrosis, and pulmonary destruction in asthma. Based on the use of essential oils from aromatic plants on pain relief and anti-inflammatory properties, we investigated the inhibitory effects of essential oil derived from the Mentha species (MEO) against asthma exposed to PM10. The MEO (0.1 v/v %) was aerosolized by a nebulizer to ovalbumin and PM10-induced asthmatic mice. Histological changes were confirmed in the lung tissues. To define the mode of action of the MEO on asthma, a protein–protein interaction network was constructed using menthol and menthone as the major components of the MEO. Cytokine expression and the JAK2/STAT3 signaling pathway were analyzed in lung epithelial A549 cells co-treated with MEO and PM10. Inhalation of MEO by nebulization inhibited respiratory epithelium hyperplasia, collagen deposition, and goblet cell activation in asthmatic mice. Through a network pharmacological analysis, cytokine–cytokine receptor interaction and JAK/STAT was expected to be underlying mechanisms of MEO on asthma. Treatment with MEO significantly reduced the IL-6 levels with a decrease in pro-inflammatory and T helper 2-specific cytokines. PM10-induced phosphorylation of JAK2 and STAT3 was significantly decreased by MEO. Collectively, MEO may have an inhibitory effect on asthma under the condition of PM10 exposure through the IL-6/JAK2/STAT3 signaling pathway.