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. 2016 Jul;32(4):460-6.
doi: 10.6515/acs20150416a.

Gentiana scabra Reduces SR-A Expression and Oxidized-LDL Uptake in Human Macrophages

Chin-Sheng Lin  1 , Pang-Yen Liu  1 , Chen-Hao Lian  2 , Ching-Heng Lin  3 , Jenn-Haung Lai  4 , Ling-Jun Ho  5 , Shih-Ping Yang  1 , Shu-Meng Cheng  1
Affiliations

Gentiana scabra Reduces SR-A Expression and Oxidized-LDL Uptake in Human Macrophages

Chin-Sheng Lin et al. Acta Cardiol Sin. 2016 Jul.

Abstract

Background: Macrophages can imbibe low-density lipoprotein (LDL) through scavenger receptors to become foam cells, which is critical in the initiation and progression of atherosclerosis. Mounting evidence suggests that the anti-inflammatory nature of Chinese herbs have the capacity to halt the complex mechanisms underlying atherosclerosis. This study examined the effects of Chinese herbs on foam cell formation.

Methods: Chinese herbs were obtained from the Sun Ten pharmaceutic company. Using oxidized LDL (OxLDL) uptake and a cell toxicity assay, we screened more than 30 types of Chinese herbs. Western blotting was used to determine expressions of scavenger receptors (SRs) and extracellular-signal-regulated kinase (ERK) activities.

Results: We found that Gentiana scabra reduced oxidized LDL uptake effectively in THP-1 macrophages (p < 0.05 vs. OxLDL treated control). Moreover, treatment with Gentiana scabra in THP-1 macrophages resulted in decreased expression of scavenger receptor- A (SR-A) (p < 0.05 vs. control). Molecular investigation revealed that Gentiana scabra inhibited SR-A protein expression, possibly by regulating ERK signaling pathways (p < 0.05 vs. control).

Conclusions: By regulating SR-A expression, Gentiana scabra reduced oxidized LDL uptake in human macrophages. These results support the potential use of Gentiana scabra in treating atherosclerosis.

Keywords: Atherosclerosis; Foam cells; Gentiana scabra; Macrophage; Oxidized LDL.

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Figures

Figure 1
Figure 1
Gentiana scabra inhibited OxLDL uptake in THP-1 macrophages. (A) THP-1 macrophages were pretreated with Gentiana scabra at a concentration of 10 mg/ml for 2 h and were then incubated with 10 μg/ml Dii-OxLDL for another 24 h. The culture supernatants were collected to determine the possible cytotoxic effects of Gentiana scabra by using LDH release assays. Cells treated with 1% Triton X-100 were taken as the positive control (indicated as H). (B) THP-1 macrophages were pretreated with various doses of Gentiana scabra for 2 h, incubated with 10 μg/ml Dii-OxLDL for another 24 h, and then analyzed using flow cytometry. Representative and average percentages of Dii-OxLDL uptake from at least three independent experiments are presented. * p < 0.05 vs. OxLDL treated control. (B) After treatment, cells were observed using fluorescence microscopy. LDH, lactate dehydrogenase; OxLDL, oxidized low-density lipoprotein.
Figure 2
Figure 2
Gentiana scabra suppressed SR-A expression in THP-1 macrophages. THP-1 macrophages were treated with Gentiana scabra at indicated concentrations for 24 h. The expressions of SR-A, CD36, and actin were determined. Values representative and relative protein expressions of SR-A and CD36 from at least three independent experiments were presented after densitometric analysis. * p < 0.05 vs. control. SR-A, scavenger receptor-A.
Figure 3
Figure 3
ERK pathway is involved in Gentiana scabra regulating SR-A expression. (A) THP-1 macrophages were treated with Gentiana scabra at indicated concentrations for 24 h. The expressions of p-ERK, T-ERK, and actin were determined. Values representative and relative protein expressions of p-ERK from at least three independent experiments were presented after densitometric analysis. * p < 0.05 vs. control. (B) THP-1 macrophages were treated with various doses of an ERK inhibitor, PD98059, for 16 h. The cell lysates were collected to determine SR-A, CD36, p-ERK, T-ERK and actin expressions. “v.” indicates vehicle control. Relative protein expressions of SR-A from at least three independent experiments were presented. * p < 0.05 vs. control.
Figure 4
Figure 4
Proposed mechanisms of Gentiana scabra suppressing SR-A expression and OxLDL uptake. The results of this study suggested that Gentiana scabra inhibits OxLDL uptake by regulating SR-A expression. A possible underlying mechanism may be through ERK signaling pathways.
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