Ixora parviflora Protects against UVB-Induced Photoaging by Inhibiting the Expression of MMPs, MAP Kinases, and COX-2 and by Promoting Type I Procollagen Synthesis

Kuo-Ching Wen, Pei-Ching Fan, Shang-Yuan Tsai, I-Chen Shih, Hsiu-Mei Chiang, Kuo-Ching Wen, Pei-Ching Fan, Shang-Yuan Tsai, I-Chen Shih, Hsiu-Mei Chiang

Abstract

Ixora parviflora with high polyphenol content exhibited antioxidant activity and reducing UVB-induced intracellular reactive oxygen species production. In this study, results of the photoaging screening experiments revealed that IPE at 1000 μg/mL reduced the activity of bacterial collagenase by 92.7 ± 4.2% and reduced the activity of elastase by 32.6 ± 1.4%. Therefore, we investigated the mechanisms by which IPE exerts its anti-photoaging activity. IPE at 1 μg/mL led to an increase in type I procollagen expression and increased total collagen synthesis in fibroblasts at 5 μg/mL. We found that IPE inhibited MMP-1, MMP-3, and MMP-9 expression at doses of 1, 5, and 10 μg/mL, respectively, in fibroblasts exposed to UV irradiation (40 mJ/cm(2)). Gelatin zymography assay showed that IPE at 50 μg/mL inhibited MMP-9 secretion/activity in cultured fibroblasts after UVB exposure. In addition, IPE inhibited the phosphorylation of p38, ERK, and JNK induced by UVB. Furthermore, IPE inhibited the UVB-induced expression of Smad7. In addition, IPE at 1 μg/mL inhibited NO production and COX-2 expression in UV-exposed fibroblasts. These findings show that IPE exhibits anti-inflammatory and anti-photoaging activities, indicating that IPE could be a potential anti-aging agent.

Figures

Figure 1
Figure 1
The inhibition of Ixora parviflora extract and its hydrolysates on collagenase activity (a, b) and bacterial collagenase activity by fluorometric assay (c). DC: doxycycline; PG: propylene glycol; IPH1: 85°C, 1.2 N HCl; IPH2: 85°C, 2.4 N HCl; IPH3: 100°C, 1.2 N HCl; IPH4: 100°C, 2.4 N HCl. (n = 4; **P < 0.01; ***P < 0.001).
Figure 2
Figure 2
The inhibition of Ixora parviflora extract on elastase activity in a dose-dependent manner. (n = 4; *P < 0.05; **P < 0.01; ***P < 0.001. PC: positive control, elastase inhibitor I).
Figure 3
Figure 3
Cell viability (%) of Ixora parviflora extract on human keratinocytes (HaCaT), mouse melanoma (B16) and human fibroblasts (Hs68). (n = 4).
Figure 4
Figure 4
Effect of Ixora parviflora extract on the UV-induced type I procollagen expression in human fibroblasts (a) and total collagen synthesis (b). IPE will upregulate type I procollagen expression and synthesis in a dose-dependent manner. (n = 4; significant difference versus control (non-UV-exposed): ***P < 0.001. Significant inhibition versus UV-exposed group: #P < 0.05; ##P < 0.01; ###P < 0.001. EGCG: (−)-epigallocatechin gallate.).
Figure 5
Figure 5
Effect of Ixora parviflora extract on the UV-induced Smad 3 and Smad 7 expression in human fibroblasts. (n = 4; significant difference versus control (non-UV-exposed): ***P < 0.001. Significant inhibition versus UV-exposed group: ###P < 0.001. EGCG: (−)-epigallocatechin gallate.).
Figure 6
Figure 6
Effect of Ixora parviflora extract on the UV-induced MMP-1 (a), MMP-3 (b), MMP-9 (c), and TIMP-1 (d) expression in human fibroblasts. (n = 4; significant difference versus control (non-UV-exposed): ***P < 0.001. Significant inhibition versus UV-exposed group: #P < 0.05; ###P < 0.001. EGCG: (−)-epigallocatechin gallate.).
Figure 7
Figure 7
Effect of Ixora parviflora extract on MMP-9 by gelatin zymography in the culture medium of human fibroblasts. (n = 3; significant difference versus control (non-UV-exposed): **P < 0.01. Significant inhibition versus UV-exposed group: #P < 0.05.).
Figure 8
Figure 8
Effect of Ixora parviflora extract on the UV-induced phosphorylation of MAP kinase in human fibroblasts. (n = 4; Significant difference versus control (non-UV-exposed): ***P < 0.001. significant inhibition versus UV-exposed group: #P < 0.05; ##P < 0.01; ###P < 0.001. EGCG: (−)-epigallocatechin gallate.).
Figure 9
Figure 9
Effect of Ixora parviflora extract on NO production in human fibroblasts (a) and the UV-induced expression of COX-2 (b). Human fibroblasts (Hs68) were treated with/without UV 40 mJ/cm2 and Ixora parviflora extract (IPE) of 1, 5, 10, and 50 μg/mL. (n = 3; Significant difference versus control (non-UV-exposed): ***P < 0.001. significant inhibition versus UV-exposed group: #P < 0.05; ##P < 0.01; ###P < 0.001; EGCG: (−)-epigallocatechin gallate.).

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