Institute of Global Health and Human Ecology, School of Sciences and Engineering, The American University in Cairo (AUC), P.O. Box: 74, Cairo, 11835, Egypt.
Biochemical Engineering Department, Faculty of Energy and Environmental Engineering, The British University in Egypt, Suez Desert Road, P.O. Box: 43, El-Shorouk City, Cairo, 11837, Egypt.
BMC Biotechnol. 2024 Sep 18;24(1):62. doi: 10.1186/s12896-024-00890-1.
Inflammation serves as an intricate defense mechanism for tissue repair. However, overactivation of TLR4-mediated inflammation by lipopolysaccharide (LPS) can lead to detrimental outcomes such as sepsis, acute lung injury, and chronic inflammation, often associated with cancer and autoimmune diseases. This study delves into the anti-inflammatory properties of "Aspergillus unguis isolate SP51-EGY" on LPS-stimulated RAW 264.7 macrophages. Through real-time qPCR, we assessed the expression levels of pivotal inflammatory genes, including iNOS, COX-2, TNF-α, and IL-6. Remarkably, our fungal extracts significantly diminished NO production and showed noteworthy reductions in the mRNA expression levels of the aforementioned genes. Furthermore, while Nrf2 is typically associated with modulating inflammatory responses, our findings indicate that the anti-inflammatory effects of our extracts are not Nrf2-dependent. Moreover, the chemical diversity of the potent extract (B Sh F) was elucidated using Q-TOF LC-HRMS, identifying 54 compounds, some of which played vital roles in suppressing inflammation. Most notably, compounds like granisetron, fenofibrate, and umbelliprenin were found to downregulate TNF-α, IL-1β, and IL-6 through the NF-κB signaling pathway. In conclusion, "Aspergillus unguis isolate SP51-EGY", isolated from the Red Sea, Egypt, has been unveiled as a promising TLR4 inhibitor with significant anti-inflammatory potentials, presenting novel insights for their potential therapeutic use in inflammation.
炎症作为组织修复的一种复杂防御机制。然而，脂多糖（LPS）介导的 TLR4 过度激活可导致有害后果，如败血症、急性肺损伤和慢性炎症，这些常与癌症和自身免疫性疾病有关。本研究探讨了“埃及红海中分离的曲霉菌 SP51-EGY”对 LPS 刺激的 RAW 264.7 巨噬细胞的抗炎特性。通过实时 qPCR，我们评估了关键炎症基因（包括 iNOS、COX-2、TNF-α和 IL-6）的表达水平。值得注意的是，我们的真菌提取物显著降低了 NO 的产生，并显著降低了上述基因的 mRNA 表达水平。此外，尽管 Nrf2 通常与调节炎症反应有关，但我们的研究结果表明，我们提取物的抗炎作用不依赖于 Nrf2。此外，使用 Q-TOF LC-HRMS 阐明了有效提取物（B Sh F）的化学多样性，鉴定出 54 种化合物，其中一些在抑制炎症方面发挥了重要作用。最值得注意的是，化合物如格兰司琼、非诺贝特和 Umbelliprenin 被发现通过 NF-κB 信号通路下调 TNF-α、IL-1β 和 IL-6。总之，从埃及红海分离的“曲霉菌 SP51-EGY”被揭示为一种有前途的 TLR4 抑制剂，具有显著的抗炎潜力，为其在炎症中的潜在治疗用途提供了新的见解。
