LP-M, a Novel Butanol-Extracts Isolated from Liriope platyphylla, could Induce the Neuronal Cell Survival and Neuritic Outgrowth in Hippocampus of Mice through Akt/ERK Activation on NGF Signal Pathway

Abstract

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 p75 NTR 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.

Effects of an Aqueous Extract of Asparagus cochinchinensis on the Regulation of Nerve Growth Factor in Neuronal Cells

“…The neuritic outgrowth of PC12 cells was measured as previously described [3,24]. After incubation of PC12 cells treated with AEAC-conditioned medium for 24 hr, the mor- …”

“…Specifically, these effects and related mechanisms were observed in several models, including Lipopolysaccharide (LPS)/substance P-stimulated mouse astrocytes [10], LPS-stimulated BV-2 microglial cells [12] and cockroach allergen-induced mice [9]. However, the underlying mechanism by which A. cochinchinensis influences NGF secretion ability has not yet been clearly identified, even though the effects of Liriope platyphylla, another plant in the Liliaceae family, have been thoroughly investigated in neuronal cells and animal models [2,3,24].…”

Phytochemical and pharmacological overview on <i>Liriopes radix</i>

“…Moreover, B35 cells conditioned medium treated to PC12 cells showed significantly higher the levels of tropomyosin receptor kinase A (TrkA), ERK phosphorylation, and extracellular calcium levels with a significant decrease in the intracellular calcium levels [50]. LR extracts induced NGFsecretion and NGF mRNA expression with high cell viability in vitro and significantly increased the NGF mRNA and hippocampus TrkA and inhibited the p75 NTR signaling pathways in C57BL/6 mice [51]. Spicatoside A on PC12 cells induced neurite outgrowth similar to NGF and activated ERK and PI3K/Akt via TrkA, which is responsible for the induction of the neuritic process [52].…”

Toxicity of redLiriope platyphyllamanufactured by steaming process on liver and kidney organs of ICR mice

“…Especially, it effectively stimulates insulin secretion as well as the insulin receptor signaling pathway in some cell lines and animal models [3-6]. Also, the differentiation of naive PC12 cells as well as improvement of learning and memory in mice were induced LP through upregulation of NGF secretion [7-10]. Furthermore, it relieved symptoms of atopic dermatitis in NC/Nga mice after phthalic anhydride (PA) treatment [11].…”