{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:09:49Z","timestamp":1772168989071,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/f1000research.40667.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000}}],"reference-count":40,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81560592"],"award-info":[{"award-number":["81560592"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060817"],"award-info":[{"award-number":["82060817"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002367","name":"Chinese Academy of Sciences","doi-asserted-by":"publisher","award":["2017-ZJ-Y08"],"award-info":[{"award-number":["2017-ZJ-Y08"]}],"id":[{"id":"10.13039\/501100002367","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    <ns3:bold>Background:<\/ns3:bold>\n                    Zuotai (mainly \u03b2-HgS)-containing 70 Wei-Zhen-Zhu-Wan (70W,\n                    <ns3:italic>Rannasangpei<\/ns3:italic>\n                    ) is a famous Tibetan medicine for treating cardiovascular and gastrointestinal diseases.\u00a0 We have shown that 70W protected against CCl\n                    <ns3:sub>4<\/ns3:sub>\n                    hepatotoxicity.\u00a0 CCl\n                    <ns3:sub>4<\/ns3:sub>\n                    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. \u00a0\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Methods:<\/ns3:bold>\n                    Mice were given clinical doses of 70W (0.15-1.5 g\/kg, po), Zuotai (30 mg\/kg, po), and compared to HgCl\n                    <ns3:sub>2<\/ns3:sub>\n                    (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.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Results:<\/ns3:bold>\n                    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-\u03b1 (PPAR\u03b1); farnesoid X receptor (FXR)]. In comparison, HgCl\n                    <ns3:sub>2<\/ns3:sub>\n                    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 HgCl\n                    <ns3:sub>2<\/ns3:sub>\n                    and MeHg only, and all treatments had no effects on CYP3A.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Conclusions:<\/ns3:bold>\n                    Zuotai and Zuotai-containing 70W at clinical doses had minimal influence on hepatic CYPs and corresponding nuclear receptors, while HgCl\n                    <ns3:sub>2<\/ns3:sub>\n                    and MeHg produced significant effects.\u00a0 Thus, the use of total Hg content to evaluate the safety of HgS-containing 70W is inappropriate.\n                  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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.58028.r88174, Xingguo Cheng, Department of Pharmaceutical Sciences, St. John's University, Queens, New York, NY, USA, 28 Jun 2021, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/10-203\/v2#referee-response-88174","order":0,"name":"referee-response-88174","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.43732.r81778, Xian-Ju Huang, College of Pharmaceutical Science, South-Central University for Nationalities, Wuhan, China, 30 Apr 2021, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/10-203\/v1#referee-response-81778","order":1,"name":"referee-response-81778","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by National Natural Science Foundation of China (81560592); Qinghai Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of Sciences (2017-ZJ-Y08). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}