Sarsasapogenin

Int Immunopharmacol. 2015 Apr;25(2):493-503.

Timosaponin AIII and its metabolite sarsasapogenin ameliorate colitis in mice by inhibiting NF-κB and MAPK activation and restoring Th17/Treg cell balance.[Pubmed: 25698557]

The rhizome of Anemarrhena asphodeloides (AA, family Liliaceae), which contains furostanol and spirostanol saponins, is a typical herbal medicine that improves learning and memory in rats and inhibits inflammation.
METHODS AND RESULTS:
In a preliminary study, timosaponin AIII, one of AA main constituents, was metabolized to Sarsasapogenin by gut microbiota and inhibited NF-κB activation in lipopolysaccharide (LPS)-stimulated macrophages. Here we have investigated the anti-inflammatory effects of AIII and Sarsasapogenin in vitro and in vivo. Both AIII and Sarsasapogenin potently inhibited NF-κB and MAPK activation, as well as IRAK1, TAK1, and IκBα phosphorylation in LPS-stimulated macrophages. Further, AIII and Sarsasapogenin inhibited the binding of LPS to macrophage Toll-like receptor 4, as well as polarization of M2 to M1 macrophages. Oral administration of AIII and Sarsasapogenin inhibited 2,3,4-trinitrobenzene sulfonic acid (TNBS)-induced colon shortening and myeloperoxidase activity in mice, along with reducing NF-κB activation and interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 levels, while simultaneously increasing IL-10. Both compounds inhibited Th17 cell differentiation in colonic lamina propria, but induced Treg cell differentiation. Further, AIII and Sarsasapogenin inhibited the differentiation of splenic CD4(+) T cells into Th17 cells in vitro. The vitro and in vivo anti-inflammatory effects of Sarsasapogenin were more potent than AIII.
CONCLUSIONS:
These results suggest that orally administered AIII may be metabolized to Sarsasapogenin by gut microbiota, which may ameliorate inflammatory diseases such as colitis by inhibiting TLR4-NF-κB/MAPK signaling pathway and restoring Th17/Treg cell balance.

Cell Biol Int. 2007 Sep;31(9):887-92.

The apoptotic effect of sarsasapogenin from Anemarrhena asphodeloides on HepG2 human hepatoma cells.[Pubmed: 17400003 ]

Sarsasapogenin, a kind of mainly effective components of Anemarrhena asphodeloides Bunge (Liliaceae) has the effects of being anti-diabetes and improving memory. However, there are few reports focusing on its anti-tumor effects.
METHODS AND RESULTS:
In this study, the Sarsasapogenin was extracted from rhizomes of A. asphodeloides Bunge and applied to inhibit HepG2 human hepatoma cells. MTT assay showed that Sarsasapogenin induced a distinct dose- and time-dependent diminution of cell viability with IC(50) of 42.4+/-1.0microg/ml for 48h. Furthermore, Sarsasapogenin-induced apoptosis of HepG2 cells was verified by Hoechst 33258 staining, electron microscopy, DNA fragmentation and PI staining. Flow cytometry analysis showed that Sarsasapogenin-induced cell apoptosis was through arrest of cell cycle in G(2)/M phase.
CONCLUSIONS:
Hence we proposed that Sarsasapogenin could be used as an anti-liver cancer drug for future studies.

Biol Pharm Bull. 2006 Nov;29(11):2304-6.

Antidepressant-like effects of sarsasapogenin from Anemarrhena asphodeloides BUNGE (Liliaceae).[Pubmed: 17077534]

METHODS AND RESULTS:
The aim of this study was to investigate the effects of Sarsasapogenin from Anemarrhena asphodeloides BUNGE (Liliaceae) on the forced swimming test, and the central noradrenergic, dopaminergic and serotonergic activities in mice. Our results showed that Sarsasapogenin treatment at 12.5, 25 and 50 mg/kg (p.o.) for 14 d significantly reduced the duration of immobility in the forced swimming test. These doses that affected the immobile response did not affect locomotor activity. In addition, the neurochemical assays showed that Sarsasapogenin produced a marked increase of noradrenaline and serotonin levels at 50 mg/kg in both the hypothalamus and the hippocampus. Moreover, Sarsasapogenin showed a monoamine oxidase inhibitory activity in the mouse brain.
CONCLUSIONS:
These findings suggest that the antidepressant activity of Sarsasapogenin may involve the central monoaminergic neurotransmitter systems.

Neurosci Lett . 2017 Feb 3;639:173-178.

Sarsasapogenin reverses depressive-like behaviors and nicotinic acetylcholine receptors induced by olfactory bulbectomy[Pubmed: 27988349]

Abstract Cholinergic signalling in the hippocampus may contribute to the aetiology of mood regulation. Antidepressants can reverse the increase in acetylcholinesterase (AChE) activity induced by olfactory bulbectomy. The activation of nicotinic acetylcholine receptors (nAChRs) also alleviates the symptoms of depression. This study advances the development of Sarsasapogenin, which interacts with cholinergic signalling and has a favourable antidepressant profile in olfactory bulbectomised (OB) rats. We examined OB-induced changes in cholinergic signalling, as well as AChE, α4-nAChR, and α7-nAChR expression in the hippocampus. The results indicate that abnormal cholinergic signalling in the hippocampus contributes to the development of depression in the OB rat model. This depression may be alleviated following treatment with Sarsasapogenin. Keywords: Acetylcholinesterase; Depression; Olfactory bulbectomy; Sarsasapogenin; α4-nAChR; α7-nAChR.

Biochem Biophys Res Commun. 2013 Nov 15;441(2):519-24.

Sarsasapogenin induces apoptosis via the reactive oxygen species-mediated mitochondrial pathway and ER stress pathway in HeLa cells.[Pubmed: 24383086]

Sarsasapogenin is a sapogenin from the Chinese medical herb Anemarrhena asphodeloides Bunge.
METHODS AND RESULTS:
In the present study, we revealed that Sarsasapogenin exhibited antitumor activity by inducing apoptosis in vitro as determined by Hoechst staining analysis and double staining of Annexin V-FITC/PI. In addition, cell cycle arrest in G2/M phase was observed in Sarsasapogenin-treated HeLa cells. Moreover, the results revealed that perturbations in the mitochondrial membrane were associated with the deregulation of the Bax/Bcl-2 ratio which led to the upregulation of cytochrome c, followed by activation of caspases. Meanwhile, treatment of Sarsasapogenin also activated Unfolded Protein Response (UPR) signaling pathways and these changes were accompanied by increased expression of CHOP. Salubrinal (Sal), a selective inhibitor of endoplasmic reticulum (ER) stress, partially abrogated the Sarsasapogenin-related cell death. Furthermore, Sarsasapogenin provoked the generation of reactive oxygen species, while the antioxidant N-acetyl cysteine (NAC) effectively blocked the activation of ER stress and apoptosis, suggesting that Sarsasapogenin-induced reactive oxygen species is an early event that triggers ER stress mitochondrial apoptotic pathways.
CONCLUSIONS:
Taken together, the results demonstrate that Sarsasapogenin exerts its antitumor activity through both reactive oxygen species (ROS)-mediate mitochondrial dysfunction and ER stress cell death.

Journal of China Pharmaceutical University, 2009, 179(3):430-6.

Effects of sarsasapogenin on the activity of osteoblasts and the differentiation and the function of osteoclasts[Reference: WebLink]

To observe the effects of Sarsasapogenin(SAR) on osteoblasts and osteoclasts cultured in vitro.
METHODS AND RESULTS:
Colonal murine calvarial osteoblast-like cell line MC3T3-E1 cells were cultured in vitro.MTT,p-nitropheneye phosphate and tinctorial method of alizarin Bordeaux were used to investigate the effects of SAR on the proliferation,ALP expression,and mineralization tuberculation of MC3T3-E1 cells.Mature osteoclasts were isolated from the long bone of one-day rat.Meanwhile,marrow cells of mouse bone were cultured with induction of 1,25(OH)2VitD3.During the culturing of osteoclasts or marrow cells,SAR of different concentrations was added into the medium.The number of osteoclasts was recognized as tartrate resistant acid phosphatase(TRAP)(+) multinucleate cells and the resorption lacuna on bone slice were examined with toluidine blue staining.
CONCLUSIONS:
The results suggest that SAR can effectively promote the proliferation,differentiation and mineralization of osteoblasts cultured in vitro.Besides,SAR can inhibit the generation of osteoclasts from marrow cells.

Brain Res. 2005 Oct 26;1060(1-2):26-39.

A new approach to the pharmacological regulation of memory: Sarsasapogenin improves memory by elevating the low muscarinic acetylcholine receptor density in brains of memory-deficit rat models.[Pubmed: 16226729 ]

METHODS AND RESULTS:
The purpose of this paper is to study the basic pharmacological action of Sarsasapogenin, a sapogenin from the Chinese medicinal herb Rhizoma Anemarrhenae, (abbreviated as ZMS in this paper), on learning ability and memory of three animal models: aged rats and two neurodegeneration models produced either by single unilateral injection of beta-amyloid 1-40 (Abeta1-40) plus ibotenic acid (Ibot A) or by bilateral injection of Ibot A alone into nucleus basalis magnocellularis. Y-maze test and step-through test revealed that learning ability and memory were impaired in the three models and were improved by oral administration of ZMS. ZMS did not inhibit acetylcholinesterase nor did it occupy the binding sites of muscarinic acetylcholine receptor (M receptor), hence it is neither an cholinesterase inhibitor nor an agonist or antagonist of M receptors. On the other hand, the densities of total M receptor and its M1 subtype in the brain of the three models were significantly lower than control rats, and ZMS significantly raised the densities of total M receptors and its M1 subtype. Linear regression revealed significant correlation between the learning ability/memory and the density of either total M receptor or its M1 subtype. Autoradiographic study with 3H-pirenzipine showed that the M1 subtype density was significantly lowered in cortex, hippocampus and striatum of aged rats, and ZMS could reverse these changes towards normal control level. Interestingly, the M1 receptor density after ZMS administration only approached but did not exceed that of normal young control rats.
CONCLUSIONS:
Therefore, ZMS seems to represent a new approach to the pharmacological regulation of learning and memory and appears to be not simply palliative but may modify the progression of the disease.