Abstract
The aim of this study is to determine 18 elements in Tibetan medicine Qishiwei Zhenzhu pills (QSW) and their absorption, distribution, and excretion in rats with cerebral ischemia. Microwave digestion and inductively coupled plasma mass spectrometry (ICP-MS) were used to determine 18 elements of QSW in simulated gastrointestinal (GI) juice. Rats were given QSW (66.68 mg/kg) followed by middle cerebral artery occlusion (MCAO). Sham rats received saline and were not subjected to MCAO. ICP-MS was applied to determine the content of 18 elements in hepatic venous blood, abdominal aortic blood, brain, liver, kidney, hair, urine, and feces 24 h after MCAO. In vitro results showed that the extraction rate of Mn, Cu, Sr, Pb, Au, and Hg of QSW in gastric juice (1 h) was higher than that in water, and the contents of Cu, Au, Sr, and As were higher in intestinal juice (4 h) than in water. In vivo results showed that the contents of elements in the blood were quite low, and QSW increased Ni, Cr, Sr, Co, and V in artery blood and decreased V in venous blood. Elements in the tissues were also low, and QSW increased brain Li but decreased Cr and Cd; QSW increased kidney Ag and Cs and liver Mn but decreased liver Ni. QSW increased urinary excretion of Li, Sr, Hg, Cs, and V; QSW increased Hg content in hair but decreased Ni. Stool is the main excretion pathway of the elements in QSW, with Ba, Mn, Sr, Cd, V, Cu, Cs, Li, Pb, Ag, Hg, Cr, As, and Co the highest. In summary, this study examined the distribution of 18 elements in QSW-treated MCAO rats. The accumulation of these elements in blood and tissues was extremely low, and the majority was excreted in feces within 24 h, highlighting the importance of the gut-microbiota-brain axis in QSW-mediated brain protection.
Highlights
Cerebral ischemia is the commonest type of cerebral infarction [1]
On the basis of vascular wall lesions caused by cerebral atherosclerosis, vascular stenosis, occlusion, or thrombosis may result in ischemia and hypoxic necrosis of local brain tissues due to interruption of the blood supply, which result in corresponding symptoms and signs in the nervous system [2]
We have shown that Qishiwei Zhenzhu pills (QSW) are effective in the treatment of cerebral ischemia injury [20]. e disposition of 18 elements during the treatment of middle cerebral artery occlusion (MCAO) by QSW could add our understanding of the protection mechanisms of QSW against cerebral ischemia injury. e results clearly demonstrated that 24 h after QSW administration to MCAO rats, these elements’ accumulation in the blood and tissues were extremely low, and the amount found in feces were extremely high, implying these elements in the GI tract could modulate gut microbiota [21] to produce neuroprotection through the gut-microbiota-brain axis
Summary
Cerebral ischemia is the commonest type of cerebral infarction [1]. On the basis of vascular wall lesions caused by cerebral atherosclerosis, vascular stenosis, occlusion, or thrombosis may result in ischemia and hypoxic necrosis of local brain tissues due to interruption of the blood supply, which result in corresponding symptoms and signs in the nervous system [2]. Cerebral ischemia is equivalent to ischemic stroke in traditional Chinese medicine, “Baimai” disease in Tibetan medicine, and “Sa” disease in Mongolian medicine. Ey are mainly used to treat “Baimai” disease, “Longxue” disorder, stroke, paralysis, hemiplegia, epilepsy, Evidence-Based Complementary and Alternative Medicine cerebral hemorrhage, and other diseases [4]. According to the published literature, there should be 32 kinds of plant medicine, 8 kinds of animal medicine, more than 20 kinds of mineral and gem medicine, and a mineral mixture (Zuotai) in QSW. 12 plant medicines, 8 animal medicines, 8 mineral and gemstone medicines, 4 metal medicines, and Zuotai are known and are listed in Supplementary Table 1 [5]. Zuotai is obtained from mercury and other minerals by a complex processing procedure, and QSW contain a large amount of mercury. e high mercury content in QSW results in serious health problems [7,8,9]
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