Abstract
Inflammation and oxidative stress are significant mechanisms that lead to various skin diseases. Controlling these mechanisms serves as therapeutic targets to treat these conditions. Topical corticosteroids and NSAIDs are used but are not ideal for long term usage and are also associated with serious side effects. Nuclear respiratory factor 2 (Nrf2), a master regulator of antioxidants and indirect regulator of inflammatory biomarkers, enables the body to control oxidative stress and inflammation. Targeting inflammation and oxidative stress via Nrf2 activation may prevent the onset of complex skin conditions. Several herbal ingredients are known to contain natural Nrf2 activators and exhibit anti-inflammatory and antioxidant activities. Furthermore, combining herbal ingredients using a synergistic approach may provide a multi-target and multi-therapeutic effect in reducing inflammation and oxidative stress. This study was in collaboration with Australian company NATIVE EXTRACTS (NE) Pty Ltd to investigate their nine herbal extract products of Australian native plants. These extracts are referred to as NE extracts throughout this study.This study aimed to (1) investigate anti-inflammatory and antioxidant activities of the NE extracts in vitro experimentation and their association with Nrf2 activation, (2) to develop synergistic combinations from the potent NE extracts, (3) investigate the optimal synergistic combination(s) for skin protection and wound healing recovery. Anti-inflammatory in vitro experiments include examining NE extracts for the inhibition of nitric oxide (NO), tumour necrosis factor-alpha (TNF-α) interleukin 6 (IL-6) in lipopolysaccharide (LPS)-induced murine macrophage cells (RAW 264.7). Antioxidant investigations include inhibition of reactive oxygen species (ROS) in LPS-stimulated RAW 264.7 cells and free scavenging activity using 2,2-Diphenyl-1-picrylhydrazyl assay. A luciferase assay determined Nrf2 activation using MC7 AREc32 cells. Mathematical models like combination index (CI) and Isobolograms determined synergism. The optimal combination(s) of the NE extracts with synergy was trialled on human dermal fibroblasts (HDF) to determine anti-inflammatory activity (IL-6 inhibitory effect) and wound healing ability. On the other hand, this study also investigated the anti-inflammatory and Nrf2 activation of selected phytochemicals that are present in the NE extracts to determine their contribution to the overall bioactivities of the NE extracts.
Findings show preliminary evidence that the NE extracts, including bitter orange (#2), mountain pepper berry (#6) and native river mint (#7), provided by NATIVE EXTRACTS Pty Ltd exhibited promising anti-inflammatory and antioxidant activities. Combining these three ingredients at a 1:1:1 (w/w) ratio exhibited synergistic activities as evidenced by the CI model. The synergistic mechanisms were at least partly associated with the increased Nrf2 activation. Furthermore, the combination continued to reduce IL-6 production and promote wound healing recovery on skin cells. These bioactivities may be attributed to the potent anti-inflammatory and antioxidant properties of the NE extracts.
| Date of Award | 2024 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Phoebe Zhou (Supervisor) |