Effect of timosaponin A-III, from Anemarrhenae asphodeloides Bunge (Liliaceae), on calcium mobilization in vascular endothelial and smooth muscle cells and on vascular tension

Wang, Guei Jane; Lin, Lie Chwen; Chen, Chieh Fu; Cheng, Jin; Lo, Yuk Keung; Chou, Kang Ju; Lee, Kam Chung; Liu, Chun Peng; Wu, Yu Yuan; Su, Warren; Chen, Wei‐Chung; Jan, Chung Ren

doi:10.1016/s0024-3205(02)01794-0

Cited by 23 publications

(17 citation statements)

References 13 publications

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“…In contrast, Anemarrhena rhizome, which is a component herbal medicine of Byakkokaninjinto and Byakkoto, improves "water retention." Anemarrhena rhizome contains timosaponin A II, which has an intracellular Ca concentration-increasing effect 46) ; however, it remains unknown why Anemarrhena rhizome and Gypsum fibrosum are used simultaneously. We propose that the mechanism that causes the increase in AQP3 expression by Gypsum fibrosum is induced by the increase in the Ca concentration to explain the significance of the combined formulation of Anemarrhena rhizome and Gypsum fibrosum in Byakkokaninjinto and Byakkoto.…”

Section: Discussionmentioning

confidence: 99%

Elucidating the Mechanism by Which <i>Gypsum fibrosum</i>, a Traditional Chinese Medicine, Maintains Cutaneous Water Content

Ikarashi

Ogiue

Toyoda

et al. 2013

Biological & Pharmaceutical Bulletin

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Aquaporin-3 (AQP3) plays an important role in maintaining the normal water content of the skin. Previously, we revealed that the expression of cutaneous AQP3 increased following oral administration of Gypsum fibrosum (main component: CaSO 4 ) to mice. The purpose of this study is to elucidate the mechanism by which Gypsum fibrosum increases the expression of cutaneous AQP3 in a keratinocyte cell line. Gypsum fibrosum or CaSO 4 was added to keratinocytes, and the expression level of AQP3, the Ca concentration, the activity of protein kinase C (PKC), and the degrees of phosphorylation of both extracellular signal-regulated kinase (ERK) and cAMP response element binding protein (CREB) were measured. The mRNA and protein expression levels of AQP3 increased significantly 6 h-post addition of Gypsum fibrosum. In keratinocytes treated with Gypsum fibrosum, increases in the concentration of intracellular Ca, PKC activity, and the phosphorylation of ERK and CREB were observed. Pre-treatment with GF109203X, a PKC inhibitor, suppressed the mRNA expression levels of AQP3. Similarly to treatment with Gypsum fibrosum, the addition of CaSO 4 led to the same observations in keratinocytes. It is hypothesized that Gypsum fibrosum causes an increase in the intracellular Ca concentration, PKC activity, and the phosphorylation levels of ERK and CREB, resulting in increased AQP3 expression in keratinocytes. In addition, it is possible that the effect of Gypsum fibrosum is attributable to CaSO 4 , based on the results demonstrating that the mechanisms of action of Gypsum fibrosum and CaSO 4 were nearly identical.

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Section: Discussionmentioning

confidence: 99%

Elucidating the Mechanism by Which <i>Gypsum fibrosum</i>, a Traditional Chinese Medicine, Maintains Cutaneous Water Content

Ikarashi

Ogiue

Toyoda

et al. 2013

Biological & Pharmaceutical Bulletin

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“…TAIII-induced Autophagy Is Associated with Cytosolic Calcium Mobilization-In literature, TAIII was shown to increase cytosolic calcium levels in vascular endothelial cells and smooth muscle cells in buffered salt medium (35). This lead us to investigate TAIII-induced calcium mobilization in relationship to autophagy.…”

Section: Taiii Induces Formation Of Large Autophagic Vacuoles Apparenmentioning

confidence: 99%

Activation of Autophagy of Aggregation-prone Ubiquitinated Proteins by Timosaponin A-III

Lok

Liu

et al. 2011

Journal of Biological Chemistry

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Chemical modulators of autophagy provide useful pharmacological tools for examination of autophagic processes, and also may lead to new therapeutic agents for diseases in which control of cellular sequestration and degradation capacity are beneficial. We have identified that timosaponin A-III (TAIII), a medicinal saponin reported to exhibit anticancer properties and improve brain function, is a pronounced activator of autophagy. In this work, the salient features and functional role of TAIIIinduced autophagy were investigated. In TAIII-treated cells, autophagic flux with increased formation of autophagosomes and conversion into autolysosomes is induced in association with inhibition of mammalian target of rapamycin activity and elevation of cytosolic free calcium. The TAIII-induced autophagy is distinct from conventional induction by rapamycin, exhibiting large autophagic vacuoles that appear to contain significant contents of endosomal membranes and multivesicular bodies. Furthermore, TAIII stimulates biosynthesis of cholesterol, which is incorporated to the autophagic vacuole membranes. The TAIII-induced autophagic vacuoles capture ubiquitinated proteins, and in proteasome-inhibited cells TAIII promotes autophagy of aggregation-prone ubiquitinated proteins. Our studies demonstrate that TAIII induced a distinct form of autophagy, and one of its pharmacological actions is likely to enhance the cellular quality control capacity via autophagic clearance of otherwise accumulated ubiquitinated protein aggregates.Autophagy, or precisely referred to macroautophagy, is a distinct lysosomal degradation pathway for intracellular materials (1, 2). Although the ubiquitin proteasome system (UPS) 2 usually degrades short-lived soluble proteins, autophagy complements UPS to degrade long-lived proteins, protein aggregates, or organelles (3-5). Autophagy is essentially a regulated intracellular vacuolization process consisting of two key steps: formation of autophagosomes that capture the cytosolic substrates, and fusion of autophagosomes and lysosomes to form autolysosomes in which the autophagic content is degraded. The membrane trafficking processes in autophagy are specifically controlled by proteins encoded by highly conserved autophagy related genes, ATGs, as well as the signaling lipid phosphatidylinositol 3-phosphate that recruits effector proteins to the membranes of autophagic vacuoles (6 -8).A major function of autophagy is to recycle free amino acids, lipids, and carbohydrates for resynthesis of biomolecules or energy production, particularly under starvation conditions. In this regard, autophagy was thought to be a nonspecific process involving random sequestration and degradation of cytoplasmic components, but it is now evident that cargo can also be selectively incorporated into autophagosomes (9). Emerging evidence has shown that autophagy may play a role in selective sequestration and degradation of aggregated protein complexes and/or damaged organelles, thereby serving as a cellular quality control system for ...

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“…Moreover, the alkaloids detected can significantly inhibit the progression of diabetes (Tang et al, 2006), suppress inflammatory agents-induced cytokine production in lung cells , exert an antidepressant-like effect and inhibit the replication of human cytomegalovirus (Hayashi et al, 2007), and the steroidal saponins have the function of lowering the blood glucose level in alloxandiabetic mice (Nakashima et al, 1993), improving memory and dysfunction induced by cerebral ischemia , antagonizing vessel contraction (Wang et al, 2002), inhibiting platelet aggregation and generating stimulus-induced superoxide in human neutrophils (Kaname et al, 2000;Zhang et al, 1999a,b).…”

Section: Identification Of Compoundmentioning

confidence: 99%

Identification of major alkaloids and steroidal saponins in rat serum by HPLC‐diode array detection‐MS/MS following oral administration of Huangbai‐Zhimu herb‐pair Extract

Fan

Tang

et al. 2008

Biomedical Chromatography

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Huangbai-Zhimu herb-pair (HBZMHP) is a widely used Chinese traditional medicine formula in treating various diseases; however, its active components have remained unknown. In this paper, serum chemistry and combined high-performance liquid chromatography (HPLC), diode-array detection and mass-spectrometry (MS) techniques were used to study the constituents of HBZMHP extract absorbed into rat serum after oral administration. A total of nine characteristic HPLC peaks in the TIC chromatograms were identified as magnoflorine (1), menisperine (2), palmatine (3), berberine (4), timosaponin N or timosaponin E1 (5), timosaponin D (6), timosaponin BIII, anemarsaponin C or xilingsaponin B (7) timosaponin BII (8) and timosaponin AIII (9). All of the identified peaks were constituents of HBZMHP extract. The results narrow the range of active compounds to be found in HBZMHP extract, and pave the way for the follow-up action mechanism research.

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Effect of timosaponin A-III, from Anemarrhenae asphodeloides Bunge (Liliaceae), on calcium mobilization in vascular endothelial and smooth muscle cells and on vascular tension

Cited by 23 publications

References 13 publications

Elucidating the Mechanism by Which <i>Gypsum fibrosum</i>, a Traditional Chinese Medicine, Maintains Cutaneous Water Content

Elucidating the Mechanism by Which <i>Gypsum fibrosum</i>, a Traditional Chinese Medicine, Maintains Cutaneous Water Content

Activation of Autophagy of Aggregation-prone Ubiquitinated Proteins by Timosaponin A-III

Identification of major alkaloids and steroidal saponins in rat serum by HPLC‐diode array detection‐MS/MS following oral administration of Huangbai‐Zhimu herb‐pair Extract

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