Efficacy of bioactive compounds of Chaihu () on glaucomatous optic atrophy through interleukin-6/hypoxia inducible factor-1α signal pathway.

OBJECTIVE: To investigate the bioactive compounds of Chaihu (Radix Bupleuri Chinensis) (RB) on glaucomatous optic atrophy (GOA), and to study the pharmacological mechanism. METHODS: We collected information on the bioactive compounds of RB from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets related to bioactive compounds and GOA were also obtained. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and network analyses were performed to investigate the potential mechanism of RB against GOA. Subsequently, the main bioactive compounds of RB and targets of GOA were docked by Autodock software. Moreover, a GOA model of retinal ganglion cells (RGCs) induced by cobalt chloride was established to verify the effect of RB on GOA. RESULTS: There were 17 main bioactive compounds and 46 key targets were screened as potential players in GOA. The compound-target network mainly contained 17 compounds and 46 corresponding targets, and the key targets consisted of interleukin-6 (IL-6), hypoxia inducible factor-1α (HIF1A), Caspase-3, estrogen receptor alpha (ESR1), MYC proto-oncogene (MYC), and vascular endothelial growth factor A (VEGFA). Forty-nine significantly enriched GO terms, and 134 KEGG signaling pathways were identified (P < 0.05), including HIF-1, tumor necrosis factor, VEGF, prolaction, and other signaling pathways. Molecular docking results showed that the main bioactive compounds of RB exhibited the strongest binding activity with IL-6. Furthermore, experimental validation showed that the RB extract inhibited the activity and promoted apoptosis of RGCs in a dose-dependent manner. The RB extract also suppressed the expression of Bax, Caspase-3, and Caspase-9 and regulated malonaldehyde, superoxide dismutase, and glutathione peroxide by inhibiting the IL-6/HIF-1α signaling pathway. CONCLUSIONS: The present study provided insights into the mechanism of RB on GOA. RB mainly reverses GOA by inhibiting the IL-6/HIF-1α signaling pathway.

The autophagy in ischemic stroke: A regulatory role of non-coding-RNAs.

Ischemic stroke (IS) is a central nervous system neurological disorder ascribed to an acute focal trauma, with high mortality and disability, leading to a heavy burden on family and society. Autophagy is a self-digesting process by which damaged organelles and useless proteins are recycled to maintain cellular homeostasis, and plays a pivotal role in the process of IS. Non-coding RNAs (ncRNAs), mainly contains microRNA, long non-coding RNA and circular RNA, have been extensively investigated on regulation of autophagy in human diseases. Recent studies have implied that ncRNAs-regulating autophagy participates in pathophysiological process of IS, including cell apoptosis, inflammation, oxidative stress, blood-brain barrier damage and glial activation, which indicates that regulating autophagy by ncRNAs may be beneficial for IS treatment. This review summarizes the role of autophagy in IS, as well as focuses on the role of ncRNAs-mediated autophagy in IS, for the development of potential therapeutic strategies in this disease.

The antifibrotic role of natural killer cells in liver fibrosis.

Liver fibrosis is the common pathological change of chronic liver diseases characterized by increased deposition of extracellular matrix and reduced matrix degradation. In response to liver injury caused by a variety of pathogenic agents, such as virus and alcohol, hepatic stellate cells (HSCs) are differentiated into myofibroblast-like cells and produce excessive collagens, thus resulting in fibrogenesis. Natural killer (NK) cells are the essential innate immune cells in the liver and generally control fibrosis by killing activated HSCs. This review briefly describes the fibrogenesis process and the phenotypic features of hepatic NK cells. Besides, it focuses on the antifibrotic mechanisms of NK cells and explores the potential of activating NK cells as a therapeutic strategy for the disease.