No abstract

Emerging evidence indicates important protective roles being played by autophagy in neurodegenerative disorders through clearance of aggregate-prone or mutant proteins. In the current study, we aimed to identify autophagy inducers from Chinese medicinal herbs as a potential neuroprotective agent that enhances the clearance of mutant huntingtin and α-synuclein in PC-12 cells. Through intensive screening using the green fluorescent protein-light chain 3 (GFP-LC3) autophagy detection platform, we found that the ethanol extracts of Radix Polygalae (Yuan Zhi) were capable of inducing autophagy. Further investigation showed that among three single components derived from Radix Polygalae—i.e., polygalacic acid, senegenin and onjisaponin B—onjisaponin B was able to induce autophagy and accelerate both the removal of mutant huntingtin and A53T α-synuclein, which are highly associated with Huntington disease and Parkinson disease, respectively. Our study further demonstrated that onjisaponin B induces autophagy via the AMPK-mTOR signaling pathway. Therefore, findings in the current study provide detailed insights into the protective mechanism of a novel autophagy inducer, which is valuable for further investigation as a new candidate agent for modulating neurodegenerative disorders through the reduction of toxicity and clearance of mutant proteins in the cellular level.

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Genus Sanguisorba (family: Rosaceae) comprises nearly 148 species, distributed widely across the temperate and subtropical regions of the Northern Hemisphere. Sanguisorba officinalis L. (S. officinalis) has been used as a hemostatic and scald treating medicine in China for a long time. Numerous studies have demonstrated that plant extracts or monomers from S. officinalis exhibit several pharmacological effects, such as anti-cancer, anti-virus, anti-inflammation, anti-bacteria, neuroprotective and hepatoprotective effects. The other species of genus Sanguisorba are also being studied by researchers worldwide. Sanguisorba minor Scop. (S. minor), as an edible wild plant, is a common ingredient of the Mediterranean diet, and its young shoots and leaves are often mixed with traditional vegetables and consumed as salad. Reports on genus Sanguisorba available in the current literature were collected from Google Scholar, Web of Science, Springer, and PubMed. The Plant List (http://www.theplantlist.org./tpl1.1/search?q=Sanguisorba), International Plant Name Index (https://www.ipni.org/?q=Sanguisorba) and Kew Botanical Garden (http://powo.science.kew.org/) were used for obtaining the scientific names and information on the subspecies and cultivars. In recent years, several in vivo and in vitro experiments have been conducted to reveal the active components and effective monomers of S. officinalis and S. minor. To date, more than 270 compounds have been isolated and identified so far from the species belonging to genus Sanguisorba. Numerous reports on the chemical constituents, pharmacologic effects, and toxicity of genus Sanguisorba are available in the literature. This review provides a comprehensive understanding of the current traditional applications of plants, which are supported by a large number of scientific experiments. Owing to these promising properties, this species is used in the treatment of various diseases, including influenza virus infection, inflammation, Alzheimer’s disease, type 2 diabetes and leukopenia caused by bone marrow suppression. Moreover, the rich contents and biological effects of S. officinalis and S. minor facilitate these applications in dietary supplements and cosmetics. Therefore, the purpose of this review is to summarize the recent advances in the traditional uses, chemical constituents, pharmacological effects and clinical applications of genus Sanguisorba. The present comprehensive review may provide new insights for the future research on genus Sanguisorba.

High levels of intracellular reactive oxygen species (ROS) in cells is recognized as one of the major causes of cancer cell apoptosis and has been developed into a promising therapeutic strategy for cancer therapy. However, whether apoptosis associated biophysical properties of cancer cells are related to intracellular ROS functions is still unclear. Here, for the first time, we determined the changes of biophysical properties associated with the ROS-mediated oesophageal cancer KYSE-150 cell apoptosis using high resolution atomic force microscopy (AFM). Oridonin was proved to induce ROS-mediated KYSE-150 cell apoptosis in a dose dependent manner, which could be reversed by N-acetylcysteine (NAC) pretreatment. Based on AFM imaging, the morphological damage and ultrastructural changes of KYSE-150 cells were found to be closely associated with ROS-mediated oridonin-induced KYSE-150 cell apoptosis. The changes of cell stiffness determined by AFM force measurement also demonstrated ROS-dependent changes in oridonin induced KYSE-150 cell apoptosis. Our findings not only provided new insights into the anticancer effects of oridonin, but also highlighted the use of AFM as a qualitative and quantitative nanotool to detect ROS-mediated cancer cell apoptosis based on cell biophysical properties, providing novel information of the roles of ROS in cancer cell apoptosis at nanoscale.