• Journal of Life Science
• /
• v.26 no.5
• /
• pp.509-518
• /
• 2016

Asparagus cochinchinensis is a medical plant that has long been used to treat fever, cough, kidney disease, breast cancer, inflammatory disease and brain disease in northeast Asian countries. Although several studies have been conducted on the anti-neuroinflammatory effects of A. cochinchinensis, the correlation between these effects and nerve growth factor (NGF) has not yet been examined. In this study, we investigated the effects of an aqueous extract of A. cochinchinensis (AEAC) on the secretion and action mechanism of NGF in neuronal cells. The concentration of the NGF protein in the supernatant collected from cultured cells increased significantly in B35 cells treated with AEAC in comparison with the vehicle-treated group without any specific cytotoxicity. Furthermore, the mRNA expression of NGF showed a very similar pattern to its protein concentration. To examine the bioactivity of NGF secreted from B35 cells, undifferentiated PC12 cells were cultured in an AEAC-conditioned medium and neuritic outgrowth was observed. The dendrite length of PC12 cells in the AEAC-treated group was significantly higher than that in the vehicle-treated group. Moreover, the level of the downstream effectors p-TrkA and p-ERK of the high-affinity NGF receptor was significantly higher in the AEAC-treated group, while the expression of the downstream effectors of the low-affinity NGF receptor was significantly lower in the same group. These results suggest that AEAC may contribute to the regulation of NGF expression and secretion in neuronal cells; it is therefore an excellent candidate for further investigation as a therapeutic drug for neurodegenerative diseases.

• Journal of Life Science
• /
• v.30 no.6
• /
• pp.501-512
• /
• 2020

Sasa quelpaertensis Nakai leaf has been used as a folk medicine for the treatment of gastric ulcer, dipsosis, and hematemesis based on its anti-inflammatory, antipyretic, and diuretic characteristics. We have previously reported the procedure for deriving a phytochemical-rich extract (PRE) from S. quelpaertensis and how PRE and its ethyl acetate fraction (EPRE) exhibits an anticancer effect by inducing apoptosis in various gastric cancer cells. To explore the molecular targets involved in this apoptosis, we investigated the mRNA and microRNA profiles of EPRE-treated SNU-16 human gastric cancer cells. In total, 2,875 differentially expressed genes were identified by RNA sequencing, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that the EPRE-modulated genes are associated with apoptosis, mitogen-activated protein kinase, inflammatory response, tumor necrosis factor signaling, and cancer pathways. Subsequently, protein-protein interaction network analysis confirmed interactions among genes associated with cell death and apoptosis, and 27 differentially expressed microRNAs were identified by further sequencing. Here, GO and KEGG pathway analysis revealed that EPRE modified the expression of microRNAs associated with the cell cycle and cell death, as well as signaling of tropomyosin-receptor-kinase receptor, transforming growth factor-b, nuclear factor kB, and cancer pathways. Taken together, these results provide insight into the mechanisms underlying the anticancer effect of EPRE.

• Journal of Life Science
• /
• v.21 no.9
• /
• pp.1234-1243
• /
• 2011

Liriope platyphylla has been used in oriental medicine as an effective medical plant to improve symptoms of cough, sputum production, neurodegenerative disorders, obesity and diabetes for long time. In order to investigate the effects of novel extracts on nerve growth factors (NGF)-stimulated neuritic outgrowth, the alteration of NGF expression and NGF receptor signaling pathway were detected in neuroblastoma cells and C57BL/6 mice. Of a total of 13 novel extracts, 4 extracts (LP-E, LP-M, LP-M50, LP2E17PJ) showed high viability on MTT assay. Also, all of these extracts induced NGF secretion and NGF mRNA expression in neuroblastoma cells. However, the NGF-induced neuritic outgrowth from PC12 cells was only stimulated by LP-E, LP-M and LP-M50. Furthermore, we selected LP-M as a best candidate, based on method and amounts of extraction, in order to verify its effect in mice. C57BL/6 mice were treated with 50 mg/kg of LP-M for 2 weeks and the effects on NGF regulation were analyzed with various methods. The expression of NGF mRNA was significantly increased in LP-M treated mice compared to vehicle treated mice. Also, the signaling pathway of p75NTR was inhibited in the cortex by LP-M treatment, with no change in the hippocampus of brain. However, the signaling pathway of TrkA was dramatically activated in only hippocampus via LP-M treatment. Therefore, these results suggest that the novel four extracts of L. platyphylla may contribute to the regulation of NGF expression and secretion in neuronal cells. LP-M was especially considered to be an excellent candidate for a neurodegenerative disease-therapeutic drug.

• The Korean Journal of Physiology and Pharmacology
• /
• v.25 no.4
• /
• pp.281-296
• /
• 2021

The beneficial effects of hypoxic preconditioning are abolished in the diabetes. The present study was designed to investigate the protective effects and mechanisms of repeated episodes of whole body hypoxic preconditioning (WBHP) in db/db mice. The protective effects of preconditioning were explored on diabetes-induced vascular dysfunction, cognitive impairment and ischemia-reperfusion (IR)-induced increase in myocardial injury. Sixteen-week old db/db (diabetic) and C57BL/6 (non-diabetic) mice were employed. There was a significant impairment in cognitive function (Morris Water Maze test), endothelial function (acetylcholine-induced relaxation in aortic rings) and a significant increase in IR-induced heart injury (Langendorff apparatus) in db/db mice. WBHP stimulus was given by exposing mice to four alternate cycles of low (8%) and normal air O₂ for 10 min each. A single episode of WBHP failed to produce protection; however, two and three episodes of WBHP significantly produced beneficial effects on the heart, brain and blood vessels. There was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nitric oxide (NO) in response to 3 episodes of WBHP. Moreover, pretreatment with the BDNF receptor, TrkB antagonist (ANA-12) and NO synthase inhibitor (L-NAME) attenuated the protective effects imparted by three episodes of WBHP. These pharmacological agents abolished WBHP-induced restoration of p-GSK-3β/GSK-3β ratio and Nrf2 levels in IR-subjected hearts. It is concluded that repeated episodes of WHBP attenuate cognitive impairment, vascular dysfunction and enhancement in IR-induced myocardial injury in diabetic mice be due to increase in NO and BDNF levels that may eventually activate GSK-3β and Nrf2 signaling pathway to confer protection.

• The Korean Journal of Physiology and Pharmacology
• /
• v.14 no.1
• /
• pp.45-49
• /
• 2010

R-type $Ca_v2.3$ high voltage-activated $Ca^{2+}$ channels in peripheral sensory neurons contribute to pain transmission. Recently we have demonstrated that, among the six $Ca_v2.3$ isoforms ($Ca_v2.3a{\sim}Ca_v2.3e$), the $Ca_v2.3e$ isoform is primarily expressed in trigeminal ganglion (TG) nociceptive neurons. In the present study, we further investigated expression patterns of $Ca_v2.3$ isoforms in the dorsal root ganglion (DRG) neurons. As in TG neurons, whole tissue RT-PCR analyses revealed the presence of two isoforms, $Ca_v2.3a$ and $Ca_v2.3e$, in DRG neurons. Single-cell RT-PCR detected the expression of $Ca_v2.3e$ mRNA in 20% (n=14/70) of DRG neurons, relative to $Ca_v2.3a$ expression in 2.8% (n=2/70) of DRG neurons. $Ca_v2.3e$ mRNA was mainly detected in small-sized neurons (n=12/14), but in only a few medium-sized neurons (n=2/14) and not in large-sized neurons, indicating the prominence of $Ca_v2.3e$ in nociceptive DRG neurons. Moreover, $Ca_v2.3e$ was preferentially expressed in tyrosine-kinase A (trkA)-positive, isolectin B4 (IB4)-negative and transient receptor potential vanilloid 1 (TRPV1)-positive neurons. These results suggest that $Ca_v2.3e$ may be the main R-type $Ca^{2+}$ channel isoform in nociceptive DRG neurons and thereby a potential target for pain treatment, not only in the trigeminal system but also in the spinal system.