Abstract:
Two main hypotheses have been accepted as the potential cause of eczema. The inside-out hypothesis states that eczema is caused by an immunological defect involving the overproduction of tumor necrosis factor-alpha (TNF-α), which further causes post-inflammatory hyperpigmentation. The outside-in hypothesis states that eczema is due to a skin barrier disruption including the skin becoming cracked. This promotes histamine production which could lead to wrinkle formation when overproduced. The aim of this study was to determine whether three South African plants namely Juncus lomatophyllus (JL), Elegia tectorum (ET) and Bulbine frutescens (BF) reduce symptoms associated with eczema and inhibit the production of either TNF-α or histamine. Furthermore, this study evaluated whether synthesized gold nanoparticles (AuNPs) using JL, ET and BF or fermenting the ethanolic extracts (Et-OH) of JL (JLF) and ET (ETF), using Bifidobacterium bifidum, would enhance biological activity. Bioassay-guided fractionation was conducted due to the limited information found on JL’s compound composition. Gas chromatography-mass spectrometry (GC-MS) of two semi-pure fractions, pooled from the butanol partition (JLB), indicated volatile compounds with a peak area above 5%. Furthermore, JLAuNP (50% inhibitory concentration (IC50): 268.8 ± 5.64 μg/mL) displayed enhanced anti-tyrosinase activity when compared to JL-EtOH and JLF (IC50 > 400 μg/mL). JLB, JLAuNP and JL-EtOH effect on TNF-α production using lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cells (PBMCs) was evaluated. None of the selected samples displayed antiproliferative activity against human keratinocytes (HaCaT) and PBMCs (IC50 > 400 μg/mL). JLAuNP (23.59 ± 1.95 pg/mL), compared to the untreated control (46.17 ± 9.51 pg/mL), significantly inhibited TNF-α production while JLB and JL-EtOH showed no effect at 200 μg/mL. ET-EtOH displayed anti-elastase activity (IC50: 28.27 ± 2.02 μg/mL), while ETF and ETAuNP displayed no inhibition (IC50 > 500 μg/mL). ET-EtOH was further evaluated on histamine production using phorbol 12-myristate 13-acetate (PMA) stimulated granulocytes. No antiproliferative activity was observed against HaCaT cells and granulocytes (IC50 > 400 μg/mL). Furthermore, ET-EtOH (0.10 ± 0.009 ng/mL) significantly inhibited histamine production at 6 μg/mL compared to the vehicle control (0.26 ± 0.02 ng/mL). BF samples (eight) were evaluated for their potential wound healing activity using HaCaT cells. The commercial spray (BFS) and BFSAuNP displayed antiproliferative activity (IC50 of 4.63 ± 0.05 and 3.50 ± 0.40%), while the ethanolic leaf juice (BFE), ethanolic whole leaf (BFE+), gel extract (BFG) and their AuNPs showed no activity (IC50 > 400 μg/mL and 10%). BFE (31.40 ± 0.88 %) and BFEAuNP (20.87 ± 0.69%) when compared to the controls showed significant closure at 100 μg/mL and were further evaluated. None of the samples displayed antiproliferative effects against granulocytes. Compared to the untreated control (0.30 ± 0.02 ng/mL), BFEAuNP at 100 μg/mL (0.12 ± 0.04 ng/mL) significantly inhibited histamine production. This study concluded that JLAuNP’s, ET-EtOH and BFEAuNPs potentially reduce eczema associated symptoms based on the in vitro results obtained. This is the first report of the synthesis of AuNPs from JL, ET and BF and their potential biological activity. Lastly, this study is the first to identify potential volatile compounds present in JL.