Dihydrokaempferol attenuates LPS-induced inflammation and apoptosis in WI-38 cells

Abstract

Background: Globally, pneumonia has been associated as a primary cause of mortality in children aged less than 5 years. Dihydrokaempferol (DHK) has been proposed for being correlated with the process of various diseases. Nevertheless, whether DHK has a role in the progression of infantile pneumonia remains unclear. This study aimed at exploring whether DHK was involved in the progression of infantile pneumonia. Methods: Human fibroblast cells WI-38 were treated with lipopolysaccharide (LPS). The viability of WI-38 cells was measured via Cell counting kit-8. Reverse transcription-quantitative polymerase chain reaction was used to evaluate the levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). Western blot analysis revealed the protein levels of IL-1β, IL-6, TNF-α, Bax, and cleaved-caspase 3. Flow cytometry was applied for exploring the apoptosis of WI-38 cells. The concentrations of IL-1β, IL-6, and TNF-α were assessed via enzyme-linked-immunosorbent serologic assay. Results: DHK modulated the viability of WI-38 cells in infantile pneumonia. Furthermore, we identified that DHK treatment inversely changed LPS induction-mediated elevation on the levels of inflammation biomarkers. Besides, DHK counteracted LPS-induced production of reactive oxygen species (ROS) in WI-38 cells. DHK also decreased LPS-induced elevation of WI-38 cells apoptosis and mediated the levels of apoptosis-associated indexes. Moreover, modulating sirtuin-1 (SIRT1) protein level was lowered by the induction of LPS, and was reversed by DHK treatment. In addition, DHK counteracted LPS induction-mediated elevation of p-p65 and phosphorylated inhibitor of nuclear factor kappa-B kinase subunit alpha (p-IκBα) protein levels. Conclusion: DHK alleviated LPS-induced WI-38 cells inflammation injury in infantile pneumonia through SIRT1/NF-κB pathway. The results shed light on the implications of DHK on the prevention and treatment of infantile pneumonia.

Edgeworthia gardneri (Wall.) Meisn. Ethanolic Extract Attenuates Endothelial Activation and Alleviates Cardiac Ischemia-Reperfusion Injury

“…Similarly, astragalin [ 38 ], daidzein [ 39 ], and adenosine [ 40 ] have also been demonstrated to attenuate the endothelial inflammatory response. In addition, anti-inflammatory activity was observed for daphnoretin [ 41 ], dihydrokaempferol [ 42 ], jasmonic acid [ 43 ], and kaempferol 3- O -rutinoside [ 44 ], but their modes of action on endothelial activation remain largely unknown. Interestingly, among compounds mentioned above, previous studies have provided evidence that kaempferol [ 45 ], astragalin [ 46 ], apigenin [ 47 ], daidzein [ 48 ], adenosine [ 49 ], and salicylic acid [ 50 ] exerts protective effects on myocardial I/R injury in experimental animals, depending on the anti-inflammation and anti-oxidative stress activities of these natural molecules.…”

Functional Characterization of F3H Gene and Optimization of Dihydrokaempferol Biosynthesis in Saccharomyces cerevisiae

“…Studies have shown that DHK can ameliorate severe acute pancreatitis through the Keap1/Nrf2 pathway [11]. DHK also attenuates LPS-induced inflammation and apoptosis in Wl38 cells [12] and has apoptotic effects on synoviocytes. In addition, DHK detoxicates CCl4 by inhibiting RARP-1, thereby affecting multiple downstream pathways and cytokine-induced liver fibrosis [13].…”