{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:58:42Z","timestamp":1785437922880,"version":"3.56.0"},"reference-count":42,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32473080"],"award-info":[{"award-number":["32473080"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32473080"],"award-info":[{"award-number":["32473080"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Modern Agricultural Industry Technology System","award":["CARS-37"],"award-info":[{"award-number":["CARS-37"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Sheng Mai San (SMS), a traditional Chinese medicine formula for treating qi and yin deficiency, is widely used in the management of conditions such as cardiovascular diseases and heatstroke. However, its role in mitigating heat stress (HS)-induced liver injury remains underexplored. In this study, a rat model of HS was established under high-temperature and high-humidity conditions, and SMS was administered as an intervention. The pharmacodynamic effects of SMS were comprehensively evaluated through histopathological examination, detection of heat shock protein 70 (HSP70) and heat shock protein 90(HSP90) expression, and analysis of liver function biomarkers (AST, ALT). Meanwhile, oxidative stress indicators were measured using biochemical assay kits (GSH, SOD, CAT, MDA, T-AOC), and transmission electron microscopy was employed to observe mitochondrial ultrastructure, thereby assessing the protective effects of SMS on hepatic oxidative stress and mitochondrial damage induced by HS. In vitro, BRL-3A cells were cultured, subjected to HS, and treated with SMS. Cell viability was assessed using the CCK-8 assay, and changes in mitochondrial reactive oxygen species (ROS) levels, mitochondrial permeability transition pore (MPTP) opening, and mitochondrial membrane potential (MMP) were evaluated using fluorescent probes. The results showed that SMS effectively restored HS-induced histopathological damage in rat liver tissues, reduced serum AST and ALT levels, and downregulated the mRNA expression of HSP70 and HSP90 in liver tissues. Meanwhile, SMS strengthened the hepatic antioxidant system by increasing the levels of GSH, SOD, T-AOC, and CAT, while decreasing MDA content. In vitro experiments confirmed that SMS increased the viability of BRL-3A cells, reduced ROS production, improved MPTP opening\/closing regulation, and stabilized MMP. This study provides a clinical reference for its application in treating HS-related conditions in humans and animals.<\/jats:p>","DOI":"10.3390\/ani16091391","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:15:02Z","timestamp":1777853702000},"page":"1391","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sheng Mai San Regulating the Oxidative Stress and Mitochondrial Damage to Alleviate Liver Injury in Heat Stress Rats"],"prefix":"10.3390","volume":"16","author":[{"given":"Qian","family":"Ma","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Dong","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9722-6959","authenticated-orcid":false,"given":"Xiaosong","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanming","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4321","DOI":"10.5194\/gmd-10-4321-2017","article-title":"Assessing the impacts of 1.5 \u00b0C global warming\u2014Simulation protocol of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP2b)","volume":"10","author":"Frieler","year":"2017","journal-title":"Geosci. Model Dev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1079\/WPS200568","article-title":"Nutritional interventions in alleviating the effects of high temperatures in broiler production","volume":"61","author":"Gous","year":"2005","journal-title":"World\u2019s Poult. Sci. J."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Han, Y., Li, X., Zeng, X., Shakweer, W.M.E., Liu, G., and Wang, J. (2025). High-Performance Automated Detection of Sheep Binocular Eye Temperatures and Their Correlation with Rectal Temperature. Animals, 15.","DOI":"10.3390\/ani15172475"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1017\/S175173111000090X","article-title":"Metabolic and hormonal acclimation to heat stress in domesticated ruminants","volume":"4","author":"Bernabucci","year":"2010","journal-title":"Animal"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"100488","DOI":"10.1016\/j.gfs.2020.100488","article-title":"Impacts of climate change on the livestock food supply chain; a review of the evidence","volume":"28","author":"Godde","year":"2021","journal-title":"Glob. Food Secur."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s00484-007-0103-x","article-title":"Livestock production system management responses to thermal challenges","volume":"52","author":"Nienaber","year":"2007","journal-title":"Int. J. Biometeorol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"E52","DOI":"10.3168\/jds.S0022-0302(03)74040-5","article-title":"Economic Losses from Heat Stress by US Livestock Industries","volume":"86","author":"Cobanov","year":"2003","journal-title":"J. Dairy Sci."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Liu, H., Li, F., and Luo, P. (2019). Effect of Carboxymethylation and Phosphorylation on the Properties of Polysaccharides from Sepia esculenta Ink: Antioxidation and Anticoagulation In Vitro. Mar. Drugs, 17.","DOI":"10.3390\/md17110626"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"306","DOI":"10.3748\/wjg.v13.i2.306","article-title":"Are heat stroke and physical exhaustion underestimated causes of acute hepatic failure?","volume":"13","author":"Weigand","year":"2007","journal-title":"World J. Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/liv.13373","article-title":"Heat stroke leading to acute liver injury & failure: A case series from the Acute Liver Failure Study Group","volume":"37","author":"Davis","year":"2017","journal-title":"Liver Int."},{"key":"ref_11","first-page":"1382","article-title":"Heatstroke: Its clinical and pathological presentation, with particular attention to the liver","volume":"87","author":"Hassanein","year":"1992","journal-title":"Am. J. Gastroenterol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"bcr2016214434","DOI":"10.1136\/bcr-2016-214434","article-title":"Exertional heat stroke and acute liver failure: A late dysfunction","volume":"2016","author":"Carvalho","year":"2016","journal-title":"BMJ Case Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.psj.2020.09.090","article-title":"Heat stress alters muscle protein and amino acid metabolism and accelerates liver gluconeogenesis for energy supply in broilers","volume":"100","author":"Ma","year":"2021","journal-title":"Poult. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"153920","DOI":"10.1016\/j.phymed.2021.153920","article-title":"Sheng Mai San ameliorated heat stress-induced liver injury via regulating energy metabolism and AMPK\/Drp1-dependent autophagy process","volume":"97","author":"Zhang","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"110697","DOI":"10.1016\/j.cbpa.2020.110697","article-title":"Changes in heat stress tolerance in a freshwater amphipod following starvation: The role of oxygen availability, metabolic rate, heat shock proteins and energy reserves","volume":"245","author":"Boerrigter","year":"2020","journal-title":"Comp. Biochem. Physiol. A Mol. Integr. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1007\/s00484-022-02351-w","article-title":"Effect of heat stress on DNA damage: A systematic literature review","volume":"66","author":"Habibi","year":"2022","journal-title":"Int. J. Biometeorol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1152\/physrev.00038.2020","article-title":"Exercise under heat stress: Thermoregulation, hydration, performance implications, and mitigation strategies","volume":"101","author":"Eijsvogels","year":"2021","journal-title":"Physiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41388-023-02907-z","article-title":"ROS production by mitochondria: Function or dysfunction?","volume":"43","author":"Palma","year":"2024","journal-title":"Oncogene"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1111\/j.0022-202X.2005.23667.x","article-title":"Less keratinocyte-derived factors related to more keratinocyte apoptosis in depigmented than normally pigmented suction-blistered epidermis may cause passive melanocyte death in vitiligo","volume":"124","author":"Lee","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Cheng, Y.Y., and Tsai, T.H. (2016). Analysis of Sheng-Mai-San, a Ginseng-Containing Multiple Components Traditional Chinese Herbal Medicine Using Liquid Chromatography Tandem Mass Spectrometry and Physical Examination by Electron and Light Microscopies. Molecules, 21.","DOI":"10.3390\/molecules21091159"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"154433","DOI":"10.1016\/j.phymed.2022.154433","article-title":"Shengmai san-derived compound prescriptions: A review on chemical constituents, pharmacokinetic studies, quality control, and pharmacological properties","volume":"107","author":"Ouyang","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Cheng, C., and Yu, X. (2021). Research Progress in Chinese Herbal Medicines for Treatment of Sepsis: Pharmacological Action, Phytochemistry, and Pharmacokinetics. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011078"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1254\/jphs.FP0040793","article-title":"Chinese herbal medicine, Shengmai San, is effective for improving circulatory shock and oxidative damage in the brain during heatstroke","volume":"97","author":"Wang","year":"2005","journal-title":"J. Pharmacol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"115212","DOI":"10.1016\/j.jep.2022.115212","article-title":"Huang Bai Jian Pi decoction alleviates diarrhea and represses inflammatory injury via PI3K\/Akt\/NF-\u03baB pathway: In vivo and in vitro studies","volume":"292","author":"Yan","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.7150\/ijbs.15992","article-title":"Ginsenoside Rg1 Protects against Oxidative Stress-induced Neuronal Apoptosis through Myosin IIA-actin Related Cytoskeletal Reorganization","volume":"12","author":"Wang","year":"2016","journal-title":"Int. J. Biol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.etap.2017.11.011","article-title":"N-acetyl-l-cysteine ameliorates the PM(2.5)-induced oxidative stress by regulating SIRT-1 in rats","volume":"57","author":"Yang","year":"2018","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_27","first-page":"188","article-title":"Textual Research on Shengmaisan from Ancient Literature and Its Modern Clinical Application","volume":"31","author":"Lv","year":"2025","journal-title":"Chin. J. Exp. Tradit. Med. Formulae"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.jhep.2015.04.010","article-title":"Heatstroke induces liver injury via IL-1\u03b2 and HMGB1-induced pyroptosis","volume":"63","author":"Geng","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/j.freeradbiomed.2005.10.064","article-title":"Mechanism of cell death induction by nitroxide and hyperthermia","volume":"40","author":"Zhao","year":"2006","journal-title":"Free Radic. Biol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Yang, Y., Tian, Y., Hu, S., Bi, S., Li, S., Hu, Y., Kou, J., Qi, J., and Yu, B. (2017). Extract of Sheng-Mai-San Ameliorates Myocardial Ischemia-Induced Heart Failure by Modulating Ca(2+)-Calcineurin-Mediated Drp1 Signaling Pathways. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18091825"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lee, M.M.-L., Chan, B.D., Ng, Y.-W., Leung, T.-W., Shum, T.-Y., Lou, J.-S., Wong, W.-Y., and Tai, W.C.-S. (2024). Therapeutic effect of Sheng Mai San, a traditional Chinese medicine formula, on inflammatory bowel disease via inhibition of NF-\u03baB and NLRP3 inflammasome signaling. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1426803"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1007\/s11655-022-3620-x","article-title":"Shenmai Injection Attenuates Myocardial Ischemia\/Reperfusion Injury by Targeting Nrf2\/GPX4 Signalling-Mediated Ferroptosis","volume":"28","author":"Mei","year":"2022","journal-title":"Chin. J. Integr. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Feng, S., Li, T., Wei, X., Zheng, Y., Zhang, Y., Li, G., and Zhao, Y. (2024). The Antioxidant and Anti-Fatigue Effects of Rare Ginsenosides and \u03b3-Aminobutyric Acid in Fermented Ginseng and Germinated Brown Rice Puree. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251910359"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"22968","DOI":"10.1021\/acsnano.5c02492","article-title":"Biomimetic Ginsenoside Rb1 and Probucol Co-Assembled Nanoparticles for Targeted Atherosclerosis Therapy via Inhibition of Oxidative Stress, Inflammation, and Lipid Deposition","volume":"19","author":"Zeng","year":"2025","journal-title":"ACS Nano"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"155078","DOI":"10.1016\/j.phymed.2023.155078","article-title":"Multi-omics analysis reveals the mechanism of action of ophiopogonin D against pulmonary fibrosis","volume":"121","author":"Bao","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"513","DOI":"10.3109\/02656736.2014.971446","article-title":"Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage. A review","volume":"30","author":"Slimen","year":"2014","journal-title":"Int. J. Hyperth."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1089\/ars.2016.6855","article-title":"The Keap1-Nrf2 Stress Response Pathway Promotes Mitochondrial Hyperfusion Through Degradation of the Mitochondrial Fission Protein Drp1","volume":"27","author":"Sabouny","year":"2017","journal-title":"Antioxid. Redox Signal."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"103859","DOI":"10.1016\/j.redox.2025.103859","article-title":"Mitochondrial membrane potential and compartmentalized signaling: Calcium, ROS, and beyond","volume":"86","author":"Wojtovich","year":"2025","journal-title":"Redox Biol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Rehfeldt, S.C.H., Laufer, S., and Goettert, M.I. (2021). A Highly Selective In Vitro JNK3 Inhibitor, FMU200, Restores Mitochondrial Membrane Potential and Reduces Oxidative Stress and Apoptosis in SH-SY5Y Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073701"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e2403093","DOI":"10.1002\/advs.202403093","article-title":"CKB Promotes Mitochondrial ATP Production by Suppressing Permeability Transition Pore","volume":"11","author":"He","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e2303713120","DOI":"10.1073\/pnas.2303713120","article-title":"The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore","volume":"120","author":"Pekson","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Huo, H., Zhou, Z., Qin, J., Liu, W., Wang, B., and Gu, Y. (2016). Erastin Disrupts Mitochondrial Permeability Transition Pore (mPTP) and Induces Apoptotic Death of Colorectal Cancer Cells. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0154605"}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/9\/1391\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:28:08Z","timestamp":1777854488000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/9\/1391"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,2]]},"references-count":42,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ani16091391"],"URL":"https:\/\/doi.org\/10.3390\/ani16091391","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,2]]}}}