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Abstract: Ethnopharmacological relevance: The lateral root of Aconitum has been popularly used in traditional Chinese medicine (TMC) known as Fuzi which is beneficial for the treatment of various diseases, such as rheumatism, painful joints, syncope and bronchial asthma. However, it has a potential carditoxicity with a relatively narrow margin of safety. Aim of the study: This paper was designed to explore the mechanisms of Fuzi's toxicity and find out potential tissue-specific biomarkers of toxic effects. Material and methods: A myocardial lipidomics based on ultraperformance lipid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC/Q-TOF MS) was developed to compare three cardiac lipid extraction methods and investigate the changes of lipids in mice heart of three different dosage groups. In addition, we concurrently inspected the biochemical parameters in plasma, observed the histology of the heart and recorded the electrocardiogram (ECG). Results: The cardiotoxicity of Fuzi was dose-dependent, and the high-dose group obviously manifested the heart damage in histology and a certain degree of arrhythmia. Significant changes of 14 lipid metabolites which primarily involved in phospholipid metabolism, sphingolipid metabolism, saturated fatty acid oxidation and unsaturated fatty acid peroxidation were identified and considered as the potential biomarkers of Fuzi toxicity. Conclusion: The lipidomics approach is helpful to search potential tissue-specific biomarkers and understand the underlying mechanisms of Fuzi toxicity on the heart. [Copyright &y& Elsevier]

Abstract: Aim of the study: Lizhong Pill, composed of Radix Ginseng (Panax ginseng C.A. Meyer), Rhizoma Zingiberis (Zingiber officinale Roscoe), Rhizoma Atractylodis Macrocephalae (Atractylodes macrocephala Koidz.) and Radix Glycytthizae (Glycyrrhiza uralensis Fisch.), is a classical herbal product for curing spleen deficiency in traditional Chinese medicine (TCM), and reserpine treated rats show similar signs to TCM spleen deficiency pattern. This paper is aimed to explore the regulatory effect on neuroendocrinoimmune network by Lizhong Pill in reserpine induced TCM spleen deficiency rats. Materials and methods: 100 healthy adult male SD rats, with a mean weight of 200g, were randomly divided into five groups in average: control group, reserpine treated group, atropine treated group, treatment groups with Lizhong Pill at high dose and low dose (equal to the dosage of crude drugs for 4g/kg/d and 8g/kg/d). Rats in reserpine treated group were induced by intraperitoneal injection of reserpine at 0.5mg/kgd for 4 weeks. The levels of IL-1, IL-6 and gastrin were measured with radioimmunoassay, TNF-α and IFN-γ in serum were measured with ELISA, the level of vasoactive intestinal peptide (VIP) and substance P (SP) in small intestine were determined with radioimmunoassay, and the TNF-α and TGF-β positive cells in small intestine were detected by immunohistological staining. Data were analyzed with SAS 9.1 software package. Results: The rats in reserpine treated group, body weight, concentrations of IFN-γ, IL-1 and TNF-α in serum, expression of TGF-β in small intestine, VIP in small intestine decreased (P <0.05), and the level of IL-6 in serum, expression of TNF-α, SP in small intestine and gastrin were increased (P <0.05). Administration of Lizhong Pill at high dose could increase the body weights at day 21, and the weights of rats in Lizhong Pill groups were much higher compared to reserpine treated group. At high dose of Lizhong Pill could increase the level of TNF-α in serum. Lizhong Pill at high dose and low dose could reverse the changes of IL-1, IL-6 and IFN-γ, gastrin, expression of TGF-β and TNF-α, VIP and SP in small intestine. Conclusions: The rats treated with reserpine, with similar signs to TCM spleen deficiency, show neuroendocrinoimmune disorders, and the restoration of the neuroendocrinoimmune disorders might be the part of mechanism of Lizhong Pill for reinforcing TCM spleen deficiency. [Copyright &y& Elsevier]