Protective effect and mechanism of Qishiwei Zhenzhu pills on cerebral ischemia-reperfusion injury via blood-brain barrier and metabonomics

Xu, Min; Wu, Ruixia; Liang, Yuan; Fu, Ke; Li, Xiaoli; Wu, Lei; Wang, Zhang

doi:10.1016/j.biopha.2020.110723

“…The present study confirmed and extended our prior study of the protective effect of QSW on I/R through the blood-brain barrier and metabolomics in the early stage [ 20 ]. QSW can protect against lipopolysaccharide plus 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity and disturbance of gut microbiota in mice [ 27 ].…”

Section: Discussionsupporting

confidence: 90%

“…SD rats weighing 250 to 280 g were randomly divided into four groups as follows ( n = 6/group; Figure 1 ): Sham, I/R, Nmdp (30 mg/kg, po) + I/R group, and QSW (66.68 mg/kg, po) + I/R group. The selected dose refers to the dose used in the previous experiment of the research group [ 20 – 22 ]. The experiment was conducted in the National Medicine Resource Evaluation Laboratory of Chengdu University of Traditional Chinese Medicine (the third-level scientific research laboratory of the State Administration of Traditional Chinese Medicine, NO.…”

Section: Methodsmentioning

confidence: 99%

Tibetan Medicine Qishiwei Zhenzhu Pills Can Reduce Cerebral Ischemia-Reperfusion Injury by Regulating Gut Microbiota and Inhibiting Inflammation

Fu

¹

,

Zhang

²

,

Song

³

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Cerebral ischemia is a series of harmful reactions, such as acute necrosis of tissue, inflammation, apoptosis, autophagy, and blood-brain barrier injury, due to the insufficient blood supply to the brain. Inflammatory response and gut microbiota imbalance are important concomitant factors of cerebral ischemia and may increase the severity of cerebral ischemia through the gut-brain axis. Qishiwei Zhenzhu pills (QSW) contain more than 70 kinds of medicinal materials, which have the effects of anti-cerebral infarction, anti-convulsion, anti-dementia, and so on. It is a treasure of Tibetan medicine commonly used in the treatment of cerebral ischemia in Tibetan areas. In this study, we gave rats QSW (66.68 mg/kg) once by gavage in advance and then immediately established the rat middle cerebral artery occlusion (MCAO) model. After 24 hours of treatment, the neuroprotection, intestinal pathology, and gut microbiota were examined. The results showed that QSW could significantly reduce the neurobehavioral abnormalities and cerebral infarction rate in MCAO rats. Furthermore, qPCR, western blot, and immunohistochemistry results showed that QSW could effectively inhibit IL-6, IL-1β, and other inflammatory factors so as to effectively reduce the inflammatory response of MCAO rats. Furthermore, QSW could improve intestinal integrity and reduce intestinal injury. 16S rRNA sequencing showed that QSW could significantly improve the gut microbiota disorder of MCAO rats. Specifically, at the phylum level, it can regulate the abundance of Firmicutes and Proteobacteria in the gut microbiota of rats with MCAO. At the genus level, it can adjust the abundance of Escherichia and Shigella. At the species level, it can adjust the abundance of Lactobacillus johnsonii and Lactobacillus reuteri. All in all, this study is the first to show that QSW can reduce the severity of cerebral ischemia-reperfusion injury by regulating gut microbiota and inhibiting the inflammatory response.

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“…70W is a famous Tibetan medicine listed in the 2015 Edition of Chinese Pharmacopoeia for the treatment of various diseases 3,10 . The major ingredients in 70W and the mode of the protection against cerebral ischemia-reperfusion injury has recently been demonstrated 11 . We have shown that 70W is effective against CCl 4 -induced liver injury, protected LPS plus MPTP-induced neurotoxicity 8 , and modulated gut microbiota 8,12 .…”

Section: W and Zuotai In Tibetan Medicinesmentioning

confidence: 99%

Zuotai (β-HgS)-containing 70 Wei Zhen-Zhu-Wan differs from mercury chloride and methylmercury on hepatic cytochrome P450 in mice

Nie

¹

,

Xu

²

,

Lu

³

et al. 2021

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Background: Zuotai (mainly β-HgS)-containing 70 Wei-Zhen-Zhu-Wan (70W, Rannasangpei) is a famous Tibetan medicine for treating cardiovascular and gastrointestinal diseases. We have shown that 70W protected against CCl4 hepatotoxicity. CCl4 is metabolized via cytochrome P450 (CYP) to produce reactive metabolites. Whether 70W has any effect on CYPs is unknown and such effects should be compared with mercury compounds for safety evaluation. Methods: Mice were given clinical doses of 70W (0.15-1.5 g/kg, po), Zuotai (30 mg/kg, po), and compared to HgCl2 (33.6 mg/kg, po) and MeHg (3.1 mg/kg, po) for seven days. Liver RNA and protein were isolated for qPCR and Western-blot analysis. Results: 70W and Zuotai had no effects on hepatic mRNA expression of Cyp1a2, Cyp2b10, Cyp3a11, Cyp4a10 and Cyp7a1, and corresponding nuclear receptors [aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor-α (PPARα); farnesoid X receptor (FXR)]. In comparison, HgCl2 and MeHg increased mRNA expression of Cyp1a2, Cyp2b10, Cyp4a10 and Cyp7a1 except for Cyp3a11, and corresponding nuclear receptors except for PXR. Western-blot confirmed mRNA results, showing increases in CYP1A2, CYP2B1, CYP2E1, CYP4A and CYP7A1 by HgCl2 and MeHg only, and all treatments had no effects on CYP3A. Conclusions: Zuotai and Zuotai-containing 70W at clinical doses had minimal influence on hepatic CYPs and corresponding nuclear receptors, while HgCl2 and MeHg produced significant effects. Thus, the use of total Hg content to evaluate the safety of HgS-containing 70W is inappropriate.

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“…70W is a famous Tibetan medicine listed in the 2015 Edition of Chinese Pharmacopoeia for the treatment of various diseases 3,10 . The major ingredients in 70W and the mode of the protection against cerebral ischemia-reperfusion injury has recently been demonstrated 11 .…”

Section: W and Zuotai In Tibetan Medicinesmentioning

confidence: 99%

“…70W was developed in the middle of fifteenth century and is composed of herbo-metallic mixtures, mainly from pearl, Hong-sik, Albergia odorifera, Nine stone, Saffron, Bezoar, Musk and Zuotai (a mineral mixture) in the treatment of cardiovascular, gastrointestinal, and neurodegenerative diseases 8 , and is listed in the 2015 edition of Pharmacopoeia of China 9 . 70W is effective experimentally against vascular dementia in rats 10 , and protects cerebral ischemia-reperfusion injury via blood-brain barrier and metabonomics with 18 identified active ingredients 11 . We have recently demonstrated that 70W is effective in protecting against LPS plus MPTP-induced chronic neuroinflammation and dopaminergic neuron loss 8 and could modulate gut microbiota as a means of protection 8,12 .…”

Section: Introductionmentioning

confidence: 99%

Zuotai (β-HgS)-containing 70 Wei Zhen-Zhu-Wan differs from mercury chloride and methylmercury on hepatic cytochrome P450 in mice

Nie

¹

,

Xu

²

,

Lu

³

et al. 2021

View full text Add to dashboard Cite

Background: Zuotai (mainly β-HgS)-containing 70 Wei-Zhen-Zhu-Wan (70W, Rannasangpei) is a famous Tibetan medicine for treating cardiovascular and gastrointestinal diseases. We have shown that 70W protected against CCl4 hepatotoxicity. CCl4 is metabolized via cytochrome P450 (CYP) to produce reactive metabolites. Whether 70W has any effect on CYPs is unknown and such effects should be compared with mercury compounds for safety evaluation. Methods: Mice were given clinical doses of 70W (0.15-1.5 g/kg, po), Zuotai (30 mg/kg, po), and compared to HgCl2 (33.6 mg/kg, po) and MeHg (3.1 mg/kg, po) for seven days. Liver RNA and protein were isolated for qPCR and Western-blot analysis. Results: 70W and Zuotai had no effects on hepatic mRNA expression of Cyp1a2, Cyp2b10, Cyp3a11, Cyp4a10 and Cyp7a1, and corresponding nuclear receptors [aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor-α (PPARα); farnesoid X receptor (FXR)]. In comparison, HgCl2 and MeHg increased mRNA expression of Cyp1a2, Cyp2b10, Cyp4a10 and Cyp7a1 except for Cyp3a11, and corresponding nuclear receptors except for PXR. Western-blot confirmed mRNA results, showing increases in CYP1A2, CYP2B1, CYP2E1, CYP4A and CYP7A1 by HgCl2 and MeHg only, and all treatments had no effects on CYP3A. Conclusions: Zuotai and Zuotai-containing 70W at clinical doses had minimal influence on hepatic CYPs and corresponding nuclear receptors, while HgCl2 and MeHg produced significant effects. Thus, the use of total Hg content to evaluate the safety of HgS-containing 70W is inappropriate.

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Protective effect and mechanism of Qishiwei Zhenzhu pills on cerebral ischemia-reperfusion injury via blood-brain barrier and metabonomics

Cited by 24 publications

References 35 publications

Tibetan Medicine Qishiwei Zhenzhu Pills Can Reduce Cerebral Ischemia-Reperfusion Injury by Regulating Gut Microbiota and Inhibiting Inflammation

Tibetan Medicine Qishiwei Zhenzhu Pills Can Reduce Cerebral Ischemia-Reperfusion Injury by Regulating Gut Microbiota and Inhibiting Inflammation

Zuotai (β-HgS)-containing 70 Wei Zhen-Zhu-Wan differs from mercury chloride and methylmercury on hepatic cytochrome P450 in mice

Zuotai (β-HgS)-containing 70 Wei Zhen-Zhu-Wan differs from mercury chloride and methylmercury on hepatic cytochrome P450 in mice

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