Tian Chai

The occurrence and development of neurodegenerative diseases is related to a variety of physiological and pathological changes. Neuroinflammation is one of the major factors that induces and aggravates neurodegenerative diseases. The most important manifestation of neuroinflammation is the activation of microglia. Therefore, inhibiting the abnormal activation of microglia is an important way to alleviate the occurrence of neuroinflammatory diseases. In this research, the inhibitory effect of tabersonine (Tab) on neuroinflammation was evaluated by establishing the BV2 neuroinflammation model induced by lipopolysaccharide (LPS). It was found that Tab significantly inhibited the production and expression of nitric oxide (NO), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and reactive oxygen species (ROS) in BV-2 cells stimulated by LPS. In addition, Tab can also inhibit the activation of nuclear factor-κB (NF-κB) induced by LPS, thus regulating inflammatory mediators such as inducible nitric oxide synthase (iNOS). These results indicated that Tab regulated the release of inflammatory mediators such as NO, IL-1β, TNF-α, and IL-6 by inhibiting NF-κB signaling pathway, and exerting its anti-neuroinflammatory effect. This is the first report regarding the inhibition on LPS-induced neuroinflammation in BV2 microglia cells of Tab, which indicated the drug development potential of Tab for the treatment of neurodegenerative diseases.

Natural products (NPs) were a rich source of diverse bioactive molecules. Most anti-tumor agents were built on natural scaffolds. Nardostachys jatamansi DC. was an important plant used to process the traditional Chinese herbal medicines “gansong”. Pancreatic cancer was the fourth most common cause of cancer-related death in the world. Hence, there was an urgent need to develop novel agents for the treatment of pancreatic cancer. In this paper, nardoguaianone L (G-6) is isolated from N. jatamansi, which inhibited SW1990 cells colony formation and cell migration, and induced cell apoptosis. Furthermore, we analyzed the differential expression proteins after treatment with G-6 in SW1990 cells by using iTRAQ/TMT-based quantitative proteomics technology, and the results showed that G-6 regulated 143 proteins’ differential expression by GO annotation, including biological process, cellular component, and molecular function. Meanwhile, KEGG enrichment found that with Human T-cell leukemia virus, one infection was the most highly enhanced pathway. Furthermore, the MET/PTEN/TGF-β pathway was identified as a significant pathway that had important biological functions, including cell migration and motility by PPI network analysis in SW1990 cells. Taken together, our study found that G-6 is a potential anti-pancreatic cancer agent with regulation of MET/PTEN/TGF-β pathway.

Pancreatic cancer is the seventh leading cause of cancer-related death worldwide and is known as “the king of cancers”. Currently, gemcitabine (GEM) as the clinical drug of choice for chemotherapy of advanced pancreatic cancer has poor drug sensitivity and ineffective chemotherapy. Nardoguaianone L (G-6) is a novel guaiane-type sesquiterpenoid isolated from Nardostachys jatamansi DC., and it exhibits anti-tumor activity. Based on the newly discovered G-6 with anti-pancreatic cancer activity in our laboratory, this paper aimed to evaluate the potential value of the combination of G-6 and GEM in SW1990 cells, including cell viability, cell apoptosis, colony assay and tandem mass tags (TMT) marker-based proteomic technology. These results showed that G-6 combined with GEM significantly inhibited cell viability, and the effect was more obvious than that with single drug. In addition, the use of TMT marker-based proteomic technology demonstrated that the AGE-RAGE signaling pathway was activated after medication-combination. Furthermore, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) assays were used to validate the proteomic results. Finally, apoptosis was detected by flow cytometry. In conclusion, G-6 combined with GEM induced an increase in ROS level and a decrease in MMP in SW1990 cells through the AGE-RAGE signaling pathway, ultimately leading to apoptosis. G-6 improved the effect of GEM chemotherapy and may be used as a potential combination therapy for pancreatic cancer.