Spatial distribution and comparative analysis of Aconitum alkaloids in Fuzi using DESI-MSI and UHPLC-QTOF-MS.

Aconitum L. poisoning is a major type of poisoning caused by herbal medicines in many countries. However, despite its toxicity, Aconitum L. is still used because of its therapeutic value. Fuzi, the lateral root of Aconitum L., is one of the most important pharmacological parts. It is necessary for rational medication to figure out the types and contents of toxic Aconitum alkaloids (AAs) in Fuzi and its processed products. The present study aims to investigate the spatial distribution of toxic AAs in Fuzi and the quantification of AAs in various processing products through mass spectrometry methods. In this study, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was used to directly image the sections of raw Fuzi. The results showed a high content of diester alkaloids (DAs) and a relatively uniform distribution in the sections, while the content of monoester alkaloids (MAs) was low and uneven in the sections, distributed in the cortex, epidermis, vascular column, and other parts of the tissues. The content of non-ester alkaloids (NAs) was relatively minimum, and most of the NAs were distributed in the vascular column and the tightly connected cortex of the tissue. To further investigate the difference between raw and processed Fuzi, 60 known compounds were identified using UHPLC-QTOF-MS. The total contents of alkaloids in 7 processed Fuzi were lower than that in Shengfupian (SFP). Paofupian (PFP), Paotianxiong (PTX), Paofupian (PFP*), Danfupian (DFP), and Shufupian (SFP*) were the least similar. Zhengfupian (ZFP) and Chaofupian (CFP) had significantly reduced toxicity and increased efficacy compared with other processed products because the contents of active alkaloids in other processed products were also reduced. Understanding the distribution of metabolites and the composition changes after processing can guide users and herbal manufacturers to carefully choose the relatively safe and better therapeutic species of Fuzi. The information gathered from this study can contribute towards the improved and effective management of therapeutically important, nonetheless toxic, drugs such as Aconitum L.

Curcumin Ameliorates Copper-Induced Neurotoxicity Through Inhibiting Oxidative Stress and Mitochondrial Apoptosis in SH-SY5Y Cells.

Impaired homeostasis of copper has been linked to different pathophysiological mechanisms in neurodegenerative diseases and oxidative injury has been proposed as the main mechanism. This study aims to use curcumin, a widely used antioxidative and anti-apoptotic agent, to exert the neuroprotective effect against copper in vitro and illuminate the underlying mechanism. The effect of curcumin was examined by using a cell counting kit-8 assay, flow cytometry, immunofluorescence, spectrophotometer, and western blot. Results revealed that after pretreatment with curcumin for 3 h, copper-induced toxicity and apoptosis show a significant decline. Further experiments showed that curcumin not only decreased the production of ROS and MDA but also increased the activities of the ROS scavenging enzymes SOD and CAT. Moreover, curcumin treatment alleviated the decrease in mitochondrial membrane potential and the nuclear translocation of cytochrome c induced by copper. The protein levels of pro-caspase 3, pro-caspase 9, and PARP1 were up-regulated and the Bax/Bcl-2 ratio was down-regulated in the presence of curcumin. Taken together, our study demonstrates that curcumin has neuroprotective properties against copper in SH-SY5Y cells and the potential mechanisms might be related to oxidative stress and mitochondrial apoptosis.