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Dendrobium nobile Lindl. alkaloids improve lipid metabolism by increasing LDL uptake through regulation of the LXRα/IDOL/LDLR pathway and inhibition of PCSK9 expression in HepG2 cells

  • Authors:
    • Jian Sun
    • Hao-Rui Liu
    • Ya-Xin Zhu
    • Wei Zhang
    • Jing-Shan Shi
    • Qin Wu
    • Rui-Xia Xu
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563006, P.R. China, Cardiometabolic Center, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, P.R. China
    Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 46
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    Published online on: January 9, 2025
       https://doi.org/10.3892/etm.2025.12796
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Abstract

Dendrobium nobile Lindl. alkaloids (DNLA) are active ingredients that can be extracted from the traditional Chinese herb Dendrobium Nobile Lindl. DNLA exhibits hypoglycemic and antihyperlipidemia effects. However, to the best of our knowledge, the specific molecular mechanism by which DNLA can regulate lipid metabolism remains unclear. The aim of the present study was to investigate the effect of DNLA on lipopolysaccharide (LPS)‑induced lipid metabolism in HepG2 cells and its potential mechanism. HepG2 cells were treated with LPS with or without different concentrations of DNLA (0, 0.035, 0.35 and 3.5 µg/ml) for 48 h. Cell viability was then detected using the Cell Counting Kit‑8 assay. The 1,1'‑dioctadecyl‑3,3,3',3'‑tetramethyl‑indocarbocyanideperchlorate‑low‑density lipoprotein (LDL) uptake assay was used to examine LDL uptake. In addition, possible mechanisms were explored using western blot analysis. The effect of the combination of DNLA with rosuvastatin calcium on the expression levels of the LDL receptor (LDLR) and proprotein convertase subtilisin/Kexin type 9 (PCSK9) was examined. The results indicated that LPS stimulation reduced the uptake of LDL by HepG2 cells, decreased the intracellular LDLR content, and increased the expression levels of inducible degrader of the LDLR (IDOL) and liver X receptor (LXR)α. DNLA intervention reversed all of the aforementioned LPS‑induced effects in HepG2 cells. Additional mechanistic experiments revealed that DNLA exerted its effects mainly by regulating the LXRα/IDOL/LDLR pathway. It was shown that DNLA also reduced the expression levels of PCSK9, sterol regulatory element binding protein 2 and hepatocyte nuclear factor 1α. In addition, DNLA decreased the expression levels of PCSK9 in rosuvastatin calcium‑induced HepG2 cells. Notably, DNLA was able to decrease 3‑hydroxy‑­3‑methylglutaryl‑coenzyme A reductase and increase cytochrome p450 7A1 expression at the protein level, which are rate‑limiting enzymes in cholesterol synthesis and metabolism. Collectively, these data suggested that DNLA could enhance LDL uptake of HepG2 cells by increasing LDLR expression through the LXRα/IDOL/LDLR pathway to alleviate the effects induced by LPS, suggesting the potential benefit of DNLA in improving lipid metabolism disorders.
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Copy and paste a formatted citation
Spandidos Publications style
Sun J, Liu H, Zhang W, Shi J, Wu Q, Xu R and Zhu Y: <em>Dendrobium nobile </em>Lindl. alkaloids improve lipid metabolism by increasing LDL uptake through regulation of the LXR&alpha;/IDOL/LDLR pathway and inhibition of PCSK9 expression in HepG2 cells. Exp Ther Med 29: 46, 2025.
APA
Sun, J., Liu, H., Zhang, W., Shi, J., Wu, Q., Xu, R., & Zhu, Y. (2025). <em>Dendrobium nobile </em>Lindl. alkaloids improve lipid metabolism by increasing LDL uptake through regulation of the LXR&alpha;/IDOL/LDLR pathway and inhibition of PCSK9 expression in HepG2 cells. Experimental and Therapeutic Medicine, 29, 46. https://doi.org/10.3892/etm.2025.12796
MLA
Sun, J., Liu, H., Zhang, W., Shi, J., Wu, Q., Xu, R., Zhu, Y."<em>Dendrobium nobile </em>Lindl. alkaloids improve lipid metabolism by increasing LDL uptake through regulation of the LXR&alpha;/IDOL/LDLR pathway and inhibition of PCSK9 expression in HepG2 cells". Experimental and Therapeutic Medicine 29.3 (2025): 46.
Chicago
Sun, J., Liu, H., Zhang, W., Shi, J., Wu, Q., Xu, R., Zhu, Y."<em>Dendrobium nobile </em>Lindl. alkaloids improve lipid metabolism by increasing LDL uptake through regulation of the LXR&alpha;/IDOL/LDLR pathway and inhibition of PCSK9 expression in HepG2 cells". Experimental and Therapeutic Medicine 29, no. 3 (2025): 46. https://doi.org/10.3892/etm.2025.12796
Copy and paste a formatted citation
x
Spandidos Publications style
Sun J, Liu H, Zhang W, Shi J, Wu Q, Xu R and Zhu Y: <em>Dendrobium nobile </em>Lindl. alkaloids improve lipid metabolism by increasing LDL uptake through regulation of the LXR&alpha;/IDOL/LDLR pathway and inhibition of PCSK9 expression in HepG2 cells. Exp Ther Med 29: 46, 2025.
APA
Sun, J., Liu, H., Zhang, W., Shi, J., Wu, Q., Xu, R., & Zhu, Y. (2025). <em>Dendrobium nobile </em>Lindl. alkaloids improve lipid metabolism by increasing LDL uptake through regulation of the LXR&alpha;/IDOL/LDLR pathway and inhibition of PCSK9 expression in HepG2 cells. Experimental and Therapeutic Medicine, 29, 46. https://doi.org/10.3892/etm.2025.12796
MLA
Sun, J., Liu, H., Zhang, W., Shi, J., Wu, Q., Xu, R., Zhu, Y."<em>Dendrobium nobile </em>Lindl. alkaloids improve lipid metabolism by increasing LDL uptake through regulation of the LXR&alpha;/IDOL/LDLR pathway and inhibition of PCSK9 expression in HepG2 cells". Experimental and Therapeutic Medicine 29.3 (2025): 46.
Chicago
Sun, J., Liu, H., Zhang, W., Shi, J., Wu, Q., Xu, R., Zhu, Y."<em>Dendrobium nobile </em>Lindl. alkaloids improve lipid metabolism by increasing LDL uptake through regulation of the LXR&alpha;/IDOL/LDLR pathway and inhibition of PCSK9 expression in HepG2 cells". Experimental and Therapeutic Medicine 29, no. 3 (2025): 46. https://doi.org/10.3892/etm.2025.12796
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