{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T03:03:48Z","timestamp":1779678228439,"version":"3.53.1"},"reference-count":101,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Military Medical Science and Technology Young Talent Cultivation Program","award":["202566"],"award-info":[{"award-number":["202566"]}]},{"name":"Deep Blue Advancing Talent Program of Naval Medical University","award":["202501"],"award-info":[{"award-number":["202501"]}]},{"name":"High-Level Key Discipline Project of the National Administration of Traditional Chinese Medicine","award":["316"],"award-info":[{"award-number":["316"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Shenfu Decoction (SFD) is a traditional Chinese herbal formula composed of Panax ginseng and Aconitum carmichaelii that can revive and counteract shock. However, how SFD can mitigate hypothermia caused by seawater immersion is poorly understood. Methods: Three commonly used ratios of SFD (Panax ginseng:Aconitum carmichaelii = 1:1, 1:2, 2:1) were prepared, and their chemical properties were analyzed with UPLC-Q-TOF-MS. A rat model of hypothermia caused by seawater immersion at 15 \u00b0C was utilized. Survival analysis was used to evaluate the prophylactic effect of single intragastric administration of SFD with different ratios and doses on the survival time of rats, and to identify the optimal intervention conditions. Network pharmacology analysis based on the absorbed constituents of SFD was performed to preliminarily predict the underlying mechanisms, which were subsequently validated using RT-PCR, Western blotting, ELISA, and H&amp;E staining. Results: SFD contained 54 compounds, including ginsenosides and aconitine alkaloids, whose relative concentrations varied across different ratios of SFD. Animal studies showed that pretreatment of SFD (1:1) administered at a dose of 1.35 g\/kg was very effective in increasing rats\u2019 survival time in hypothermia and slowed down core body temperature decline. Based on the 28 plasma-absorbed compounds of SFD, network pharmacology identified 503 targets, enriched in cAMP and MAPK signaling pathways. SFD (1:1, 1.35 g\/kg) resulted in larger lipid droplets in brown adipose tissue (BAT) and enhanced the respiratory metabolic rate in seawater-immersion-induced hypothermia rats. Furthermore, its thermogenic effect is likely associated with the upregulation of uncoupling protein 1 (UCP1) via activating p38 MAPK\/PGC1\u03b1\/PPAR\u03b3 and NE-(\u03b23-AR)-cAMP-PKA pathways. Conclusions: The results of this study demonstrate that a single prophylactic administration of the traditional Chinese medicine formula SFD prior to cold seawater exposure significantly prolongs the survival time of rats. This effect is associated with the upregulation of UCP1 and the subsequent enhancement of thermogenesis in BAT. These findings highlight the great potential of SFD as a promising intervention for the management of hypothermia.<\/jats:p>","DOI":"10.3390\/ph19050793","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T02:32:28Z","timestamp":1779676348000},"page":"793","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioactive Constituents and Therapeutic Mechanisms of Shenfu Decoction in a Rat Model of Seawater-Immersion-Induced Accidental Hypothermia"],"prefix":"10.3390","volume":"19","author":[{"given":"Yanrong","family":"Gong","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibo","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China"},{"name":"Basic Medicine College, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Ben","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China"},{"name":"Basic Medicine College, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzhi","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China"},{"name":"Basic Medicine College, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyue","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China"},{"name":"Basic Medicine College, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0643-1974","authenticated-orcid":false,"given":"Huifang","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zifei","family":"Yin","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7998-4510","authenticated-orcid":false,"given":"Wei","family":"Gu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.ajem.2025.01.079","article-title":"Electrocardiographic patterns of accidental hypothermia","volume":"90","author":"Okumura","year":"2025","journal-title":"Am. 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