Sun Mingyue, Liu Cuiyan, Zhang Pengju, Zhang Hao, Zhang Hong, Zhang Tao, Han Chunyang
College of Veterinary Medicine, Anhui Agricultural University, Hefei, Anhui Province, 230036, China.
Anhui Vocational and Technical College of Forestry, Hefei, Anhui Province, 230031, China.
Poult Sci. 2025 Apr 3;104(6):105128. doi: 10.1016/j.psj.2025.105128.
Baihu Decoction (BHD) is a classic traditional Chinese medicine formula used clinically for febrile diseases. Previous studies have demonstrated that BHD can prevent and alleviate heat stress in mice, chickens, and beef cattle, although its mechanisms remain unclear. In this study, chicks were used as experimental animals, and a heat stress injury model was established by exposing them to high temperature and humidity. UHPLC-Q-Exactive Orbitrap MS was employed to analyze and identify the chemical components of BHD, while the SwissADME platform was utilized to screen for active components. Through network pharmacology, the core targets and core components associated with heat stress were identified. Subsequently, potential targets were further analyzed through GO functional and KEGG pathway enrichment analyses, followed by molecular docking and animal experiments to validate the finding. The result showed that 169 active substances were identified and screened in BHD. KEGG pathway analysis revealed a strong correlation between the MAPK pathway and the intersecting targets. Molecular docking further confirmed the high binding affinity between the core components of BHD and the key targets in the MAPK pathway. These findings indicate that the MAPK pathway is critically involved in heat stress-induced myocardial injury in chicks as well as the cardioprotective effects of BHD. Animal experiments demonstrated that administering BHD via drinking water significantly alleviated myocardial pathology injury in heat stressed chicks exposed to high temperature and humidity. BHD treatment improved cardiac function and enhanced antioxidant capacity. Furthermore, it regulated the phosphorylation levels of ERK1/2, p38, and JNK1/2 in myocardial tissues, thereby inhibiting MAPK pathway activation. Additionally, BHD decreased the levels of Bax and cleaved caspase-3 while increasing Bcl2 expression. In conclusion, BHD effectively alleviates heat stress-induced myocardial injury and cardiac dysfunction in chicks, and its mechanism is closely associated with the inhibition of MAPK signaling pathway-mediated apoptosis. This study identifies BHD as a potential therapeutic drug for heat stress in animals and offers experimental support for its application in heat stress prevention and treatment.
白虎汤（BHD）是临床上用于治疗发热性疾病的经典中药方剂。以往研究表明，白虎汤可预防和减轻小鼠、鸡和肉牛的热应激，但其作用机制尚不清楚。本研究以雏鸡为实验动物，通过高温高湿环境建立热应激损伤模型。采用超高效液相色谱-四极杆-静电场轨道阱质谱（UHPLC-Q-Exactive Orbitrap MS）分析鉴定白虎汤的化学成分，同时利用瑞士药物发现平台（SwissADME）筛选活性成分。通过网络药理学，确定与热应激相关的核心靶点和核心成分。随后，通过基因本体（GO）功能富集分析和京都基因与基因组百科全书（KEGG）通路富集分析进一步分析潜在靶点，接着进行分子对接和动物实验以验证研究结果。结果表明，在白虎汤中鉴定并筛选出169种活性物质。KEGG通路分析显示丝裂原活化蛋白激酶（MAPK）通路与交集靶点之间存在强相关性。分子对接进一步证实了白虎汤核心成分与MAPK通路关键靶点之间具有高结合亲和力。这些发现表明，MAPK通路在热应激诱导的雏鸡心肌损伤以及白虎汤的心脏保护作用中起关键作用。动物实验表明，通过饮水给予白虎汤可显著减轻高温高湿环境下热应激雏鸡的心肌病理损伤。白虎汤治疗改善了心脏功能，增强了抗氧化能力。此外，它调节了心肌组织中细胞外信号调节激酶1/2（ERK1/2）、p38和c-Jun氨基末端激酶1/2（JNK1/2）的磷酸化水平，从而抑制MAPK通路激活。此外，白虎汤降低了Bax和裂解的半胱天冬酶-3（cleaved caspase-3）的水平，同时增加了Bcl-2的表达。总之，白虎汤有效减轻了热应激诱导的雏鸡心肌损伤和心脏功能障碍，其机制与抑制MAPK信号通路介导的细胞凋亡密切相关。本研究确定白虎汤为动物热应激的潜在治疗药物，并为其在热应激防治中的应用提供了实验支持。
