High levels of UV radiation in Okinawa contribute to skin damage, photoaging, and inflammation. Calophyllum inophyllum L. (Tamanu) trees are frequently cultivated along roadways in Okinawa. The oil isolated from Tamanu nuts is renowned for antioxidants, antibacterial, and anti-inflammatory properties. However, the specific UV-absorbing compounds responsible for its anti-inflammatory activity remain unidentified. This study aimed to isolate, characterize, and evaluate the anti-inflammatory activity of UV-absorbing components from Okinawan Tamanu oil. Clinical tests confirmed the UV-protective effects of Tamanu oil, with SPF and PA values of 6.3 ± 0.4 and 2.9 ± 0.6, respectively. UV-absorbing compounds were isolated based on absorbance at 300 nm and structurally characterized by mass spectrometry and NMR. The anti-inflammatory effects of calophyllolide (CAL), inocalophyllin A (ICA), and inocalophyllin B (ICB) were evaluated in LPS-stimulated RAW 264 macrophages and UVB-induced HaCaT keratinocytes. The specific absorbance at 300 nm of CAL, ICA, and ICB isolated from Tamanu oil (300 nm specific absorbance <InlineEquation ID="IEq1"> <EquationSource Format="TEX">$E_{1cm}^{1\% }$</EquationSource> <EquationSource Format="MATHML"><math> <msubsup> <mi>E</mi> <mrow> <mn>1</mn> <mi>c</mi> <mi>m</mi> </mrow> <mrow> <mn>1</mn> <mo>%</mo> </mrow> </msubsup> </math></EquationSource> </InlineEquation> = 28) were <InlineEquation ID="IEq2"> <EquationSource Format="TEX">$E_{1cm}^{1\% }$</EquationSource> <EquationSource Format="MATHML"><math> <msubsup> <mi>E</mi> <mrow> <mn>1</mn> <mi>c</mi> <mi>m</mi> </mrow> <mrow> <mn>1</mn> <mo>%</mo> </mrow> </msubsup> </math></EquationSource> </InlineEquation> = 695, 285, and 378, respectively. All three compounds significantly inhibited nitric oxide production in LPS-induced RAW 264 cells. CAL downregulated TNF-α, IL-1β, IL-6, and IL-1α, while ICA and ICB suppressed IL-1β, IL-6, and IL-1α. In UVB-stimulated HaCaT cells, all compounds reduced IL-1α production. ICA also suppressed TNF-α, HMGB1, and HDAC2, while ICB downregulated CASP1, BAX, NLRP3, HDAC1, and HDAC2 significantly. These findings suggest that CAL, ICA, and ICB have strong anti-inflammatory properties, with ICA and ICB providing additional protection against UVB-induced skin damage via inhibition of necroptosis and inflammatory signaling. Graphical abstract

Anti-inflammatory and UV-protective activities of isolated compounds from Calophyllum inophyllum L. in immune and skin cell models

期刊论文
发表日期：

2025年11月12日

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Takayuki Ogi,
Yasuhiro Kawano,
Toru Usami,
Idam Hermawan,
Hiroto Yokaryo,
Saori Yamamoto,
Papawee Saiki

摘要

High levels of UV radiation in Okinawa contribute to skin damage, photoaging, and inflammation. Calophyllum inophyllum L. (Tamanu) trees are frequently cultivated along roadways in Okinawa. The oil isolated from Tamanu nuts is renowned for antioxidants, antibacterial, and anti-inflammatory properties. However, the specific UV-absorbing compounds responsible for its anti-inflammatory activity remain unidentified. This study aimed to isolate, characterize, and evaluate the anti-inflammatory activity of UV-absorbing components from Okinawan Tamanu oil. Clinical tests confirmed the UV-protective effects of Tamanu oil, with SPF and PA values of 6.3 ± 0.4 and 2.9 ± 0.6, respectively. UV-absorbing compounds were isolated based on absorbance at 300 nm and structurally characterized by mass spectrometry and NMR. The anti-inflammatory effects of calophyllolide (CAL), inocalophyllin A (ICA), and inocalophyllin B (ICB) were evaluated in LPS-stimulated RAW 264 macrophages and UVB-induced HaCaT keratinocytes. The specific absorbance at 300 nm of CAL, ICA, and ICB isolated from Tamanu oil (300 nm specific absorbance $E_{1cm}^{1\% }$ $E_{1 c m}^{1 %}$ = 28) were $E_{1cm}^{1\% }$ $E_{1 c m}^{1 %}$ = 695, 285, and 378, respectively. All three compounds significantly inhibited nitric oxide production in LPS-induced RAW 264 cells. CAL downregulated TNF-α, IL-1β, IL-6, and IL-1α, while ICA and ICB suppressed IL-1β, IL-6, and IL-1α. In UVB-stimulated HaCaT cells, all compounds reduced IL-1α production. ICA also suppressed TNF-α, HMGB1, and HDAC2, while ICB downregulated CASP1, BAX, NLRP3, HDAC1, and HDAC2 significantly. These findings suggest that CAL, ICA, and ICB have strong anti-inflammatory properties, with ICA and ICB providing additional protection against UVB-induced skin damage via inhibition of necroptosis and inflammatory signaling.

Graphical abstract