Abstract
Lung injury was the common and serious complication of sepsis, a systemic inflammatory response syndrome caused by severe infections. Chinese medicine had unique advantages in attenuating inflammatory response, such as Zuojinfang (ZJF). ZJF was a classical compound herb formula composed of Coptidis Rhizoma and Euodiae Fructus in a ratio of 6 : 1. In this paper, 15 ingredients in ZJF were identified and 8 of them absorbed into rat's serum were quantified by HPLC-MS/MS. Subsequently, sepsis-induced lung injury model was replicated in rats by cecal ligation and puncture. 60 SD rats were randomly divided into 6 groups (n = 10): control group (CON), sham group (Sham), model group (MOD), ZJF low-dose group (ZJF-L), ZJF high-dose group (ZJF-H), and prednisolone group (PNSL). Within the next 24 h, the levels of inflammatory factors, correlation between active ingredients and inflammatory cytokines, the pathological changes of lung tissue, and protein expression of the JAK1/STAT3 signaling pathways were analyzed one by one. Finally, the concentration order of components absorbed in rat serum was berberine > palmatine > jatrorrhizine > coptisine > evodin > chlorogenic acid > evodiamine. Compared with the MOD group, the TNF-α, IL-6, and IFN-γ in the ZJF-H group were significantly reduced (p < 0.05). Moreover, the TNF-α decreased significantly accompanied by the increase of berberine, chlorogenic acid, jatrorrhizine, palmatine, evodin, and evodiamine in serum (negative correlation, p < 0.05). Compared with the MOD, the area of lung injury, the expressions of JAK1, p-JAK1, STAT3, and p-STAT3 were significantly decreased under the treatment of ZJF (p < 0.05). Therefore, downregulating the JAK1/STAT3 signaling pathways was a potential avenue of ZJF in reversing lung injury induced by sepsis.
Highlights
Sepsis was defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection [1]
60 SD rats were randomly divided into 6 groups (n = 10): control group (CON), sham group (Sham), model group (MOD), ZJF low-dose group (ZJF-L), ZJF high-dose group (ZJF-H), and prednisolone group (PNSL)
The results showed that the TNF-α was negatively correlated with berberine (p < 0:0001), chlorogenic acid (p < 0:01), jatrorrhizine (p < 0:01), palmatine (p < 0:01), evodin (p < 0:05), and evodiamine (p < 0:05)
Summary
Sepsis was defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection [1]. Sepsis was a leading cause of death and disability in intensive care units (ICU). Sepsis tended to induce lung injury, characterized by damaged alveolar capillary barrier, edema, pulmonary infiltrates, and hypoxemia [6]. Treatment of sepsisinduced lung injury includes antibiotic [7], glucocorticoids [8], corticosteroid [9], ketamine [10], simvastatin [11], and artesunate [12]. The use of antibiotics inevitably leads to the emergence of resistant bacteria, a series of adverse reactions [13, 14]. Other drugs were accompanied by some troubling side effects in osteoporosis and glaucoma [15], psychiatric adverse effect [16], cardiovascular diseases [17], liver and muscle injury [18], and cytotoxicity [19], respectively
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