A study of the influence of lead pollution on the anticoagulant activity of Whitmania pigra based on pharmacodynamics and metabolomics research

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2021-11, Vol.1185, p.122953-122953, Article 122953
• Main Authors: Chen, Xiufen, Luo, Xuemei, Yang, Chaojie, Meng, Jieqin, Cheng, Liangke, Gao, Luying, Xue, Miao, Yang, Yaojun
• Format: Article
• Language: English
• Subjects: Animals; Anticoagulants - administration & dosage; Anticoagulants - blood; Blood Coagulation - drug effects; Blood Coagulation Disorders - drug therapy; Blood Coagulation Disorders - physiopathology; Blood stasis syndrome; Chromatography, High Pressure Liquid; Coagulation function; Drug Contamination; Hemorheology; Humans; Lead - analysis; Lead - blood; Leeches - chemistry; Leeches - metabolism; Mass Spectrometry; Medicine, Chinese Traditional; Metabolomics; Plasma - chemistry; Principal Component Analysis; Rats; UPLC-Orbitrap-MS; Whitmania pigra Whitman (leech)
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2021.122953

•Lead pollution could reduce the anticoagulant activity of leech.•The mechanism of lead pollution on leech’s efficacy was studied by metabolomics.•Heavy metal pollution in planting and breeding of TCM should be taken seriously. Whitmania pigra Whitman (leech, also called Shuizhi in China, abbreviated as SZ), which has been used as a traditional Chinese medicine in the treatment of blood stasis syndrome (BSS) for a long time, is vulnerable to lead pollution in aquaculture environments. SZ has good anticoagulant activity. However, there are few studies on the influence of lead pollution on it. Therefore, we carried out the following researches to explore the influence of lead pollution on the anticoagulant activity of SZ and its mechanism. Firstly, the acute blood stasis model of rats was established by subcutaneous injection of adrenaline hydrochloride and ice water bath. Then unpolluted SZ (UPS) and lead-polluted SZ (LPS) were extracted. Next, the blood stasis model rats were administrated by gavage and the rats in normal control (NC) group and blood stasis model (BM) group were given the same amount of normal saline. Finally, the blood of the rats was collected to detect the coagulation function and hemorheology indexes. The metabolomics of rat plasma was studied by ultra-high-performance liquid chromatography coupled with orbitrap mass spectrometry (UPLC-Orbitrap-MS) technology. Principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA) and Hierarchical clustering analysis (HCA) were used to perform metabolomics analysis. MetPA analysis was used to search for related metabolic pathways. The results of coagulation function and hemorheology showed that lead pollution could decrease the anticoagulant activity of SZ. The OPLS-DA score plots indicated that the plasma metabolites of rats in LPS group were close to BM group, while UPS group tended to be close to NC group both in the positive and negative ion mode. Hierarchical cluster analysis (HCA) suggested that UPS group and NC group were clustered into a branch, while LPS group and BM group were clustered into a branch. To sum up, lead pollution will reduce the anticoagulant activity of SZ. And lead pollution reduces the anticoagulant activity of SZ probably by influencing the metabolic pathways such as sphingolipid metabolism, amino acid metabolism and energy metabolism in rats.