Peperomin E is a natural secolignan existing distributed in the plants of the genus Peperomia. Previous investigations demonstrated that peperomin E showed potential antitumor activity in some cancer lines, but it is unclear whether peperomin E has an effect on prostate cancer cell lines. The aim of the present study is to investigate its effects on proliferation inhibition, apoptosis-inducing and cell-cycle arrest activity using a prostate cancer PC-3 cell line. The proliferation inhibition was evaluated by MTT assay, apoptosis was detected by Annexin V/propidium iodide (PI) staining and Hoechst 33258 staining, cell cycle distributions were measured by flow cytometry, and western blot analysis was used to determine specific cellular apoptotic protein expressions of Bcl-2, Bax, caspase-3 and cleaved-caspase-3. According to the results of this study, peperomin E exhibited significant anti-proliferation activity on PC-3 cell lines in vitro in a dose-dependent manner. Peperomin E treatments lead to marked morphological changes. Apoptotic cell count and cell-cycle distribution at G2/M phase significantly increased with increasing concentrations of peperomin E. The down-regulated expression level of Bcl-2 and up-regulated expression level of Bax and cleaved-caspase-3 compared with the controls were also observed after peperomin E treatment. These data suggest that peperomin E exhibited proliferation inhabitation, apoptosis-inducing and cell-cycle arrest activity on PC-3 cell lines. The anti-proliferation effect of peperomin E on PC-3 cells should result partly from its cell-cycle arrest and apoptosis-inducing activity, whereas the increasing of the Bax/Bcl-2 ratio and activation of caspases-3 play an important role in the development of apoptosis.

The rhizomes of Atractylodes macrocephala are used as both a food source and traditional Chinese medicine in China. A phytochemical investigation was carried out on wild A. macrocephala grown in Qimen County in eastern China, and yielded a novel bisesquiterpenoid lactone, namely, biatractylenolide II (1), along with two known compounds, atractylenolide II (2) and taraxeryl acetate (3). The structure and relative configuration of the new compound were elucidated mainly by 1D and 2D NMR spectroscopic methods in combination with HRESIMS experiments. This paper describes the isolation and structural elucidation of the new bisesquiterpenoid lactone (1).

Aralia echinocaulis is used for the treatment of rheumatoid arthritis by Tujia Minority in China. A previous study demonstrated that A. echinocaulis had a significant anti-arthritic effect on adjuvant arthritis (AA) rats in vivo. However, it remains unclear whether A. echinocaulis can induce the apoptosis of fibroblast-like synoviocytes (FLS) from AA rats and the underlying mechanism is unknown. In this paper, CCK-8 assay, Hoechst staining and flow cytometry were used to evaluate the apoptotic effect of an A. echinocaulis ethanol extract (AEE) on AA FLS. Western blotting analysis was performed to measure the protein expression levels of Bcl-2, Bax, cleaved caspase-3, Akt, p-Akt, and Hif-1α. The results revealed that AEE could inhibit FLS proliferation in a dose and time-dependent manner. After treatment with AEE, AA FLS displayed the classical apoptotic morphology, and the apoptosis rates were significantly increased. Furthermore, we found that AEE increased the protein levels of Bax, cleaved caspase 3, and decreased the protein levels of Bcl-2, Hif-1α and p-Akt, without affecting total Akt levels. Collectively, these results suggested that the apoptosis inducing effect of AEE on AA FLS was related to the regulation of the expression of apoptosis-related proteins and the inhibition of the Akt/Hif-1α signaling pathway.

Screening the lead compounds which could interact both with PAS and CAS of acetylcholinesterase (AChE) is an important trend in finding innovative drugs for Alzheimer’s disease (AD). In this paper, four sesquiterpenes, i.e., atractylenolide III (1), atractylenolide IV (2), 3-acetyl-atractylon (3) and β-eudesmol (4), were obtained from the wild Atractylode macrocephala grown in Qimen for the first time. Their structures were elucidated mainly by NMR spectroscopy. To screen the potential dual site inhibitors of AChE, the compounds 1, 2, 3, as well as a novel and rare bisesquiterpenoid lactone, biatractylenolide II (5), which was also obtained from the tilted plant in our previous investigation, were evaluated their AChE inhibitory activities by using Ellman’s colorimetric method. The results showed that biatractylenolide II displayed moderate inhibitory activity (IC₅₀ = 19.61 ± 1.11 μg/mL) on AChE. A further molecular docking study revealed that biatractylenolide II can interact with both the peripheral anionic site (PAS) and the catalytic active site (CAS) of AChE. These data suggest that biatractylenolide II can be considered a new lead compound to research and develop more potential dual site inhibitors of AChE.