Timosaponin AIII, a saponin isolated from Anemarrhena asphodeloides, ameliorates learning and memory deficits in mice

Lee, Bomi; Jung, Kangsik; Kim, Dong Hyun

doi:10.1016/j.pbb.2009.04.021

Cited by 100 publications

(83 citation statements)

References 30 publications

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confidence: 99%

“…(9,10) Experimental evidence shows that purified timosaponins and fractions of A. asphodeloides extracts containing timosaponins show various pharmacological properties, including improvement of learning and memory in subjects with dementia. (9,10) Recently, timosaponin AIII was also shown to be preferentially toxic to breast cancer cell lines over non-transformed cells. (11) Therefore, we assessed the effects of timosaponin AIII on the migration potential of melanoma cells using in vitro assays and an in vivo metastasis model in mice, in which timosaponin AIII had not previously been evaluated.…”

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Timosaponin AIII inhibits melanoma cell migration by suppressing COX‐2 and in vivo tumor metastasis

Kim

et al. 2016

Cancer Science

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Melanoma is the leading cause of death from skin disease, due in large part to its propensity to metastasize. We examined the effects of timosaponin AIII, a compound isolated from Anemarrhena asphodeloides Bunge, on melanoma cancer cell migration and the molecular mechanisms underlying these effects using B16-F10 and WM-115 melanoma cells lines. Overexpression of COX-2, its metabolite prostaglandin E 2 (PGE 2 ), and PGE 2 receptors (EP2 and EP4) promoted cell migration in vitro. Exposure to timosaponin AIII resulted in concentration-dependent inhibition of cell migration, which was associated with reduced levels of COX-2, PGE 2 , and PGE 2 receptors. Transient transfection of COX-2 siRNA also inhibited cell migration. Exposure to 12-O-tetradecanoylphorbal-13-acetate enhanced cell migration, whereas timosaponin AIII inhibited 12-O-tetradecanoylphorbal-13-acetate-induced cell migration and reduced basal levels of EP2 and EP4. Moreover, timosaponin AIII inhibited activation of nuclear factor-kappa B (NF-jB), an upstream regulator of COX-2 in B16-F10 cells. Consistent with our in vitro findings, in vivo studies showed that timosaponin AIII treatment significantly reduced the total number of metastatic nodules in the mouse lung and improved histological alterations in B16-F10-injected C57BL ⁄ 6 mice. In addition, C57BL ⁄ 6 mice treated with timosaponin AIII showed reduced expression of COX-2 and NF-jB in the lung. Together, these results indicate that timosaponin AIII has the capacity to inhibit melanoma cell migration, an essential step in the process of metastasis, by inhibiting expression of COX-2, NF-jB, PGE 2, and PGE 2 receptors. M elanoma is the most deadly type of skin cancer, accounting for approximately 80% of deaths caused by skin cancer.(1) Melanoma is particularly deadly due to its propensity to metastasize; clinical trials indicate that melanoma shows preferential metastasis to the lung, brain, liver, and skin. Moreover, melanoma is highly resistant to conventional chemotherapeutics.(2) Given the rising incidence of melanoma and the lack of effective therapies, development of new chemicals targeting the complex genetic networks involved in melanoma metastasis should provide new treatment strategies for this devastating disease. (3,4) Two COX isoforms with distinct physiologic functions have been identified: COX-1 and COX-2. COX-1 is expressed constitutively in many tissues and has an important role in the maintenance of homeostasis. In contrast, COX-2 is an inducible enzyme that is activated by extracellular stimuli, such as UV radiation. Enhanced expression of COX-2 in skin exposed to UV radiation has been identified as a risk factor for the development of skin cancer. (5,6) Cyclooxygenase-2 generates prostaglandins that are thought to play a central role in orchestrating the events involved in cancer invasion and metastasis. Prostaglandin E 2 (PGE 2 ) exerts its effects through G-protein coupled receptors (EP1, EP2, EP3, and EP4) and has been implicated in angiogenesis, invasion, and metastasis. (7,8)...

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Timosaponin AIII inhibits melanoma cell migration by suppressing COX‐2 and in vivo tumor metastasis

Kim

et al. 2016

Cancer Science

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“…Generally, scopolamine is an anti-cholinergic agent and induces memory deficits. Recently, it was reported that scopolamine is increasingly disruptive with age and a declining cognitive status (Lee et al 2009). Therefore, scopolamine treatment provides a good model for investigating learning and memory studies with the involvement of cholinergic system.…”

Section: Discussionmentioning

confidence: 99%

The beneficial effects of Achyranthus bidentata Blume on scopolamine-induced memory impairment in mice

Ahn

Jung

2011

Orient Pharm Exp Med

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Achyranthus bidentata Blume has traditionally been used to treat a variety of diseases including cough, fever, and asthma. However, the anti-amnesic effects of A. bidentata and its molecular mechanisms have yet to be clearly elucidated. In this study, we attempted to evaluate the effects of A. bidentata on scopolamine-induced memory impairments in mice. The regulatory effect of A. bidentata on memory impairment was investigated using passive avoidance, Y-maze and the Morris water maze tasks. Acetylcholinesterase inhibition assay was performed to investigate the cholinergic antagonistic effect of A. bidentata in hippocampus. The result of this study demonstrated that A. bidentata significantly restored memory impairments induced by scopolamine. Increase of Acetylcholinesterase activity caused by scopolamine was significantly attenuated by A. bidentata. In addition, A. bidentata recovered the reduction of cAMP-responsive element-binding protein activation induced by scopolamine in the hippocampus. Taken together, the results provide experimental evidence that A. bidentata might be a useful agent against a deficit of learning and memory caused by Alzheimer's disease and aging.

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“…The passive avoidance test was performed as previously described (Lee et al, 2009). One hour before the acquisition trial, mice were orally administered TN-2 (10, 20, and 40 mg/kg), tacrine (10 mg/kg) as a positive control, and vehicle (2% Tween 80) (the scopolamine group) as a negative control.…”

Section: Passive Avoidance Taskmentioning

confidence: 99%

“…Scopolamine, an anticholinergic drug, not only causes memory impairments, but also reduces the expression of brain-derived neurotrophic factor (BDNF), a neurotrophin that plays a crucial role in memory plasticity and formation (Tariot et al, 1996), and which is regulated by the transcription factor CREB (cAMP response element-binding protein) (Tariot et al, 1996;Lu et al, 2005Lu et al, , 2008. Hence, scopolamine is frequently used to develop animal models of memory and learning deficiencies (Lee et al, 2009;Joh et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Gypenoside TN-2 ameliorates scopolamine-induced learning deficit in mice

Hong

Yang

Joh

et al. 2011

Journal of Ethnopharmacology

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Timosaponin AIII, a saponin isolated from Anemarrhena asphodeloides, ameliorates learning and memory deficits in mice

Cited by 100 publications

References 30 publications

Timosaponin AIII inhibits melanoma cell migration by suppressing COX‐2 and in vivo tumor metastasis

Timosaponin AIII inhibits melanoma cell migration by suppressing COX‐2 and in vivo tumor metastasis

The beneficial effects of Achyranthus bidentata Blume on scopolamine-induced memory impairment in mice

Gypenoside TN-2 ameliorates scopolamine-induced learning deficit in mice

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