Tenuifolin

Acta Physiol (Oxf). 2009 Aug;196(4):419-25.

Tenuifolin, an extract derived from tenuigenin, inhibits amyloid-beta secretion in vitro.[Pubmed: 19208093]

Previous studies have shown that tenuigenin, a crude extract of Polygala tenuifolia Willd. that is commonly used in traditional Chinese herbal medicine for memory loss, can reduce the secretion of Abeta from cultured cells. However, the mechanism underlying this effect and the active compound derived from tenuigenin is unknown. In this study, a purified component of tenuigenin, Tenuifolin, was examined and revealed to be an effective compound in vitro.
METHODS AND RESULTS:
Abeta secretion from three sets of COS-7 cells, each carrying a plasmid expressing a different form of APP was examined following the treatment with Tenuifolin. Initially, Tenuifolin was determined to have no inherent toxicity to either the transfected or wild type cells at the effective concentrations. Cells were then treated with 0.5-2.0 microg mL(-1) Tenuifolin for 12 h and their media were examined via an ELISA for Abeta1-40 and Abeta-42. We found that treatment with 2.0 microg mL(-1) Tenuifolin significantly decreased Abeta secretion from COS-7 cells without altering the ratio of Abeta1-40 and Abeta-42. This effect is most probably due to inhibition of the beta-site APP cleaving enzyme as Abeta secretion was not inhibited from cells expressing the C99 fragment.
CONCLUSIONS:
Tenuifolin is an effective compound from tenuigenin. We believe that this finding should lead the way for future experiments to determine the exact mechanism for Tenuifolin's effect on Abeta secretion.

Molecules 2012, 17(3), 3524-3538

Terpenoids as Potential Anti-Alzheimer’s Disease Therapeutics[Pubmed: 17033524]

Alzheimer’s disease (AD) is one of the most well-known neurodegenerative diseases and explains 50–60% of dementia in patients. The prevalence rate of AD is positively correlated with age and AD affects ≥ 40% of those over 85 years old. The major AD therapeutics available on the market are acetylcholinesterase inhibitors, such as tacrine and donepezil. New therapeutic agents that can block the disease-inducing mechanisms are essential. Diverse efforts have been made to discover anti-AD agents from natural sources. In this review article, we describe some representative terpenoids such as ginsenosides, gingkolides, and canabinoids as potential anti-AD agents. These compounds exhibit promising in vitro and in vivo biological activities, but are still waiting clinical trials. Additionally, we also discuss some terpenoids including cornel iridoid glycoside, oleanolic acid, Tenuifolin, cryptotanshinone, and ursolic acid, which are under investigation for their in vitro and in vivo animal studies.

Pharmacol Biochem Behav. 2015 Jan;128:14-22.

Tenuifolin, a secondary saponin from hydrolysates of polygalasaponins, counteracts the neurotoxicity induced by Aβ25-35 peptides in vitro and in vivo.[Pubmed: 25444865]

Alzheimer's disease (AD) is associated with damage to hippocampal neurons and declines in cognitive functions. The accumulation of amyloid peptides is regarded as a crucial event in the initiation of AD. The neurotoxicity induced by Aβ25-35 peptides was used to screen for cytoprotective factors in vitro, and the cognitive deficits induced by the injection of Aβ25-35 into the hippocampus were used to evaluate effect on learning and memory. Our previous study revealed that hydrolysate of polygalasaponins (HPS) clearly improve the cognitive deficits induced by the injection of Aβ25-35 in mice, but the potential active constituent of HPS remains unclear. The purposes of this study were to separate and purify the secondary saponins of HPS, screen for neuroprotective effects of the constituents in vitro, and to evaluate the effect of cognition in vivo.
METHODS AND RESULTS:
Various chromatographic methods were used to separate and purify the HPS. The neuroprotective effects were examined in Aβ25-35-damage-induced PC12 cells. The protective effect of Tenuifolin on the cognitive impairments induced by Aβ25-35 injection was assessed using the Morris water maze and step-through passive avoidance tests. Tenuifolin and fallaxsaponin A were isolated from the HPS. Tenuifolin possessed neuroprotective effects against Aβ25-35-induced apoptosis in PC12 cells and significantly improved the cognitive deficits induced by the intrahippocampal injection of Aβ25-35 in mice.
CONCLUSIONS:
Thus, Tenuifolin is one of the active constituents of HPS against the neurotoxicity induced by Aβ25-35 peptides in vitro and in vivo.

Phytomedicine. 2008 Aug;15(8):587-94.

Effects of tenuifolin extracted from radix polygalae on learning and memory: a behavioral and biochemical study on aged and amnesic mice.[Pubmed: 18289838]

Although normal cognitive changes take place when a person becomes older, aging in humans is generally associated with deterioration of cognitive performance and, in particular, of learning and memory. These cognitive deficits can cause debilitating consequences due to aging. There are a number of herbal medicines which are reported to improve brain function including intelligence.
METHODS AND RESULTS:
In the present study, improving effects of Tenuifolin, extracted from Radix Polygalae (RP), on learning and memory in aged and dysmnesia mice were determined using step-down type passive avoidance test or Y type maze trial. Oral administration of Tenuifolin (0.02, 0.04, 0.08 g/kgd(-1), for 15 d) evidently improved the latency and number of errors in aged and dysmnesia mice. The levels of cortical acetylcholine esterase (AChE) activity and hippocampal neurotransmitters in aged mice given Tenuifolin (0.02, 0.04, 0.08 g/kgd(-1), for 15 d) were also investigated, and increased levels of norepinephrine (NE), dopamine (DA), decreased activity of AChE were found. However, serotonin (5-HT) had no significant difference from that of aged mice given distilled water.
CONCLUSIONS:
The evident improvement of learning and memory of aged mice is carried out by the effects of Tenuifolin on the three stages of memory process, that is, acquisition, consolidation and retrieval. This may do so by relatively increasing the levels of NE, DA in the hippocampus and by decreasing the activity of AChE in the cortex.