A High‐Through Put Pro‐inflammatory screening of natural products using mouse RAW 264.7 macrophages indicate a more significant number of pro‐inflammatory natural herbal products than anti‐inflammatory

Abstract

When it comes to natural product research, there are an overarching plethora of studies focusing on and reporting “antioxidant” and “anti‐inflammatory properties,” with a relative void in the literature elucidating those that have pro‐inflammatory (immune stimulating) and pro‐oxidant properties. Furthermore, when it comes to cancer study, many anti‐cancer compounds induce apoptosis in the same cell lines (e.g., RAW 264.7 and BV‐2 cells) used to model inflammation, creating a confounding variable [cell death] leading to false positives for reported anti‐inflammatory compounds. We tested over 1,400 natural products in our past work and found only 29 confirmed natural anti‐inflammatory compounds effective against LPS treated RAW 264.7 viable cells. In the present study, we are reporting (without a confounding variable of cell death and with matrix controls run for every extract) an enormous number; 444 natural products to evoke pro‐inflammatory effects in RAW 264.7 cells producing nitric oxide at levels equal to LPS and IFN‐g, using the same library. We found these herbs' capacity to induce IFN‐g, whereas IFN‐g by itself can induce iNOS, defining the general mechanism of action. These findings suggest that many natural products trigger a massive elevation in IFN‐g by immune‐competent cells such as macrophages and could either worsen auto‐immune or inflammatory conditions or stimulate the immune system to fight infections when needed. In conclusion: there needs to be more work in the pro‐inflammatory/immune stimulation aspects of herbs and the specific influence of natural products on various immune cells and processes. It was concluded that in cancer cells, the anti‐inflammatory /antioxidant compounds might likely prevent cancer, but once cancer is established, pro‐inflammatory/ pro‐oxidant compounds may be required to re‐establish immunosurveillance.