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Four new steroids, chouchunsteride A-D (1-4), together with four known steroids (5-8), were isolated from the leaves of Ailanthus altissima (Mill.) Swingle. Their structures were elucidated based on spectroscopic data analysis, while the relative and absolute configurations were determined via acetonide analysis and quantum chemical ECD calculations. All isolated steroids were evaluated for their cytotoxic activity against two hepatoma carcinoma cell lines (HepG2, Hep3B). Among them, 1 exhibited the most potent cytotoxicity against HepG2 cells with an IC

Timosaponin AIII (TAIII), a steroidal saponin isolated from the rhizome of Anemarrhena asphodeloides, exerted cytotoxic effect in many cancer cell lines. However, the effect of TAIII on resistant tumor cancer cells was unclear. In this study, MTT assay showed that TAIII exhibited significant cytotoxicity against A549/Taxol and A2780/Taxol cells in vitro. Annexin V-FITC/PI staining revealed that TAIII induced apoptosis in A549/T and A2780/T cells. Furthermore, Western blot analysis demonstrated that TAIII inhibited the expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR) as well as Ras, Raf, mitogen-activated protein kinase (MEPK), extracellular regulated protein kinases (ERK) in two taxol-resistant cancer cell lines. Besides, in vivo studies demonstrated that TAIII inhibited tumor growth in a nude mouse xenograft model. Additionally, TAIII (2.5 and 5 mg/kg) also down-regulated the protein expressions of PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways in vivo. Taken together, these findings demonstrated that TAIII exhibited significant anti-tumor effect on taxol-resistant cells.

Timosaponin AIII, a major steroidal saponin found in Anemarrhena asphodeloides Bge., which has been widely used as anti-pyretic, anti-diabetic, anti-inflammatory, anti-platelet aggregator and anti-depressant agents in traditional Chinese medicine. Recent pharmacological study showed that timosaponin AIII had potent cytotoxicity, which was potential to be developed as an anticancer agent, however the molecular mechanism underlying the anticancer activity has not been fully elucidated. This review aims to give a systematic summary of the study of timosaponin AIII to reveal its anti-tumor activities by investigating invasion and migration, apoptosis, autophagy and reversing multi-drug resistance. Furthermore, we also make an overview of the mechanisms identified till now. These meaningful findings may provide novel insights on exploiting timosaponin AIII as a new anti-tumor agent.

Sarsasapogenin, a kind of mainly effective component of Anemarrhena asphodeloides Bunge, possesses good antitumor properties. Two series of new sarsasapogenin derivatives were synthesized and evaluated for their cytotoxicities against three human cancer cell lines (HepG2, A549, MCF-7) using the MTT assay. The structure-activity relationship revealed that the N, N-dimethylamino, pyrrolidinyl, and imidazolyl substituted at the C26 position could increase the antitumor efficacy of the 3-oxo sarsasapogenin series of compounds. Compound 4c with pyrrolidinyl substituted at the C26 position exhibited the greatest cytotoxic activity against MCF-7 cell line (IC50 = 10.66 μM), which was 4.3-fold more potent than sarsasapogenin. Action mechanism investigations showed that 4c could inhibit the colony formation and induce the apoptosis of MCF-7 cells. Further researches showed that a decrease in mitochondrial membrane potential and increases in the expression level of cleaved-PARP and the ratio of Bax/Bcl-2 were observed in MCF-7 cells after treatment with 4c, suggesting that the mitochondrial pathway was involved in the 4c-mediated apoptosis. These results show that compound 4c may serve as a lead for further optimization.

Sarsasapogenin, extracted from Anemarrhena asphodeloides Bunge., has been reported to protect neurons from H 2 O 2 -induced damage. In the current study, four series of 26-amino acid methyl ester substituted sarsasapogenin derivatives ( 5a – 5e , 5f – 5j , 6a – 6e and 7a – 7e ) were synthesized and tested for neuroprotective activity by evaluating their neuroprotective ratio against SH-SHY5Y cell lines. Studies showed that most of the target compounds displayed better neuroprotective effects than that of sarsasapogenin. Structure-activity relationship analysis suggested that 3-methoxy derivatives ( 5f – 5j ) were more potent than other series and the phenylalanine methyl ester moiety at C-26 was important for exhibiting apparent neuroprotective activity. It was worth noting that compound 5h exhibited optimal neuroprotective activity (102.2%) compared with sarsasapogenin (27.3%) and trolox (40.5%), and this encouraged us to investigate the cellular mechanism of 5h further. Our investigation revealed that 5h could attenuate H 2 O 2 -induced cell damage by inhibiting the expression of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspase-3 as well as rescuing the downregulation of brain-derived neurotrophic factor (BDNF) and its tyrosine receptor kinase B (TrkB). Taken together, these results suggest that the representative compound 5h is a profound lead compound for further investigation and the sarsasapogenin skeleton could be a promising structural template for the development of new anti-Alzheimer drug candidates.