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image of Integrated Network Pharmacology, LC-MS/MS, and Experimental Validation of Fangji-astragalus in Hyperlipidemia

Abstract

Introduction

Hyperlipidemia is linked to multiple cardiovascular and cerebrovascular diseases. Traditional Chinese Medicine formulations show potential for managing this condition, but the underlying mechanisms remain unclear. This study investigates the therapeutic effects of the Fangji-Astragalus (FJ-HQ) on hyperlipidemia and explores its key components and molecular pathways.

Methods

Network pharmacology was applied to identify active ingredients in FJ-HQ and drug-disease co-targets. Transcriptomic analysis and HPLC-MS/MS were integrated to screen core components and associated targets. and experiments evaluated the effects of FJ-HQ in hyperlipidemic rat models and cell models.

Results

A total of 23 active ingredients and 109 drug–disease co-targets were identified, with enrichment in inflammatory and signaling pathways, notably the PI3K/AKT/mTOR and p53 pathways. Transcriptomic profiling revealed seven differentially expressed targets. Integrated chemical and serum analysis identified calycosin as the core component and highlighted CAMTA2 and RXRA as downstream targets. In hyperlipidemic rats, FJ-HQ lowered total cholesterol, triglycerides, and low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol and apolipoprotein A1. FJ-HQ also modulated the expression of P53, AKT1, and IL6, as well as mRNA levels within the PI3K/AKT/mTOR pathway. In cell models, serum containing FJ-HQ inhibited lipid droplet formation.

Discussion

These findings demonstrate that FJ-HQ alleviates hyperlipidemia by modulating the PI3K/AKT/mTOR and p53 pathways, reducing lipid levels, and suppressing lipid droplet formation, with calycosin as a pivotal active component.

Conclusion

In summary, our study confirms the therapeutic effects of FJ-HQ on hyperlipidemia and identifies calycosin as a crucial component. Furthermore, we have experimentally validated the influence of FJ-HQ on the PI3K/AKT/mTOR signaling pathway. These findings highlight the potential of FJ-HQ as an effective lipid-lowering agent and provide preclinical evidence for future treatments of hyperlipidemia.

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2026-01-12
2026-01-19
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References

  1. Li J-J. Zhao S-P. Zhao D. Lu G-P. Peng D-Q. Liu J. Chen Z-Y. Guo Y-L. Wu N-Q. Yan S-K. 2023 Chinese guideline for lipid management. Front. Pharmacol. 2023 14 10.3389/fphar.2023.1190934
    [Google Scholar]
  2. Ward N.C. Watts G.F. Eckel R.H. Statin toxicity. Circ. Res. 2019 124 2 328 350 10.1161/CIRCRESAHA.118.312782 30653440
    [Google Scholar]
  3. Dong G. Lv L. Ding G. Li F. Zhao P. Liu J. Liu H. Total flavonoids from Rosa rugosa Thunb.: A comprehensive review of its extraction and purification process, chemical composition, biological effect and applications. Naunyn Schmiedebergs Arch. Pharmacol. 2025 398 3 2343 2363 10.1007/s00210‑024‑03504‑x 39432067
    [Google Scholar]
  4. Fan Q. Xu F. Liang B. Zou X. The anti-obesity effect of traditional chinese medicine on lipid metabolism. Front. Pharmacol. 2021 12 696603 10.3389/fphar.2021.696603 34234682
    [Google Scholar]
  5. Gao J. Hou T. Cardiovascular disease treatment using traditional Chinese medicine:Mitochondria as the Achilles’ heel. Biomed. Pharmacother. 2023 164 114999 10.1016/j.biopha.2023.114999 37311280
    [Google Scholar]
  6. Guo W. Shao T. Peng Y. Wang H. Chen Z.S. Su H. Chemical composition, biological activities, and quality standards of hawthorn leaves used in traditional Chinese medicine: A comprehensive review. Front. Pharmacol. 2023 14 1275244 10.3389/fphar.2023.1275244 37927599
    [Google Scholar]
  7. Li Z. Ouyang H. Zhu J. Traditional Chinese medicines and natural products targeting immune cells in the treatment of metabolic-related fatty liver disease. Front. Pharmacol. 2023 14 1195146 10.3389/fphar.2023.1195146 37361209
    [Google Scholar]
  8. Liu M. Shi W. Huang Y. Wu Y. Wu K. Intestinal flora: A new target for traditional Chinese medicine to improve lipid metabolism disorders. Front. Pharmacol. 2023 14 1134430 10.3389/fphar.2023.1134430 36937840
    [Google Scholar]
  9. Shao M. Lu Y. Xiang H. Wang J. Ji G. Wu T. Application of metabolomics in the diagnosis of non-alcoholic fatty liver disease and the treatment of traditional Chinese medicine. Front. Pharmacol. 2022 13 971561 10.3389/fphar.2022.971561 36091827
    [Google Scholar]
  10. Wu L. Wang X. Jiang J. Chen Y. Peng B. Jin W. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review. Open Med. 2023 18 1 20230812 10.1515/med‑2023‑0812 37808167
    [Google Scholar]
  11. Zhang H.Y. Tian J.X. Lian F.M. Li M. Liu W.K. Zhen Z. Liao J.Q. Tong X.L. Therapeutic mechanisms of traditional Chinese medicine to improve metabolic diseases via the gut microbiota. Biomed. Pharmacother. 2021 133 110857 10.1016/j.biopha.2020.110857 33197760
    [Google Scholar]
  12. Zhang S.Y. Sun X.L. Yang X.L. Shi P.L. Xu L.C. Guo Q.M. Botany, traditional uses, phytochemistry and pharmacological activity of Crataegus pinnatifida (Chinese hawthorn): A review. J. Pharm. Pharmacol. 2022 74 11 1507 1545 10.1093/jpp/rgac050 36179124
    [Google Scholar]
  13. Zhang Y. Su F. Zhu E. Sun Y. Kuang H. Wang Q. A systematical review on traditional Chinese medicine treating chronic diseases via regulating ferroptosis from the perspective of experimental evidence and clinical application. Chin. Herb. Med. 2025 17 2 246 260 10.1016/j.chmed.2025.01.003 40256717
    [Google Scholar]
  14. He X. Wang J. Li M. Hao D. Yang Y. Zhang C. He R. Tao R. Eucommia ulmoides Oliv.: Ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine. J. Ethnopharmacol. 2014 151 1 78 92 10.1016/j.jep.2013.11.023 24296089
    [Google Scholar]
  15. Lan J. Zhao Y. Dong F. Yan Z. Zheng W. Fan J. Sun G. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J. Ethnopharmacol. 2015 161 69 81 10.1016/j.jep.2014.09.049 25498346
    [Google Scholar]
  16. Lin L. Ni B. Lin H. Zhang M. Li X. Yin X. Qu C. Ni J. Traditional usages, botany, phytochemistry, pharmacology and toxicology of Polygonum multiflorum Thunb.: A review. J. Ethnopharmacol. 2015 159 158 183 10.1016/j.jep.2014.11.009 25449462
    [Google Scholar]
  17. Ren J. Fu L. Nile S.H. Zhang J. Kai G. Salvia miltiorrhiza in treating cardiovascular diseases: A review on its pharmacological and clinical applications. Front. Pharmacol. 2019 10 753 10.3389/fphar.2019.00753 31338034
    [Google Scholar]
  18. Jiang X. Wang H. Nie K. Gao Y. Chen S. Tang Y. Wang Z. Su H. Dong H. Targeting lipid droplets and lipid droplet-associated proteins: A new perspective on natural compounds against metabolic diseases. Chin. Med. 2024 19 1 120 10.1186/s13020‑024‑00988‑w 39232826
    [Google Scholar]
  19. Jiang Y.Y. Jiang X.L. Yu H.N. Dysregulation of lipid metabolism in chronic kidney disease and the role of natural products. Naunyn Schmiedebergs Arch. Pharmacol. 2025 398 1 261 278 10.1007/s00210‑024‑03373‑4 39162795
    [Google Scholar]
  20. Palumbo M. Ugolotti M. Zimetti F. Adorni M.P. Anti-atherosclerotic effects of natural compounds targeting lipid metabolism and inflammation: Focus on PPARs, LXRs, and PCSK9. Atherosclerosis. Plus 2025 59 39 53 10.1016/j.athplu.2024.12.004 39877131
    [Google Scholar]
  21. Salazar-García M. Corona J.C. The use of natural compounds as a strategy to counteract oxidative stress in animal models of diabetes mellitus. Int. J. Mol. Sci. 2021 22 13 7009 10.3390/ijms22137009 34209800
    [Google Scholar]
  22. Yao P. Liu Y. Terpenoids: Natural compounds for non-alcoholic fatty liver disease (NAFLD) therapy. Molecules 2022 28 1 272 10.3390/molecules28010272 36615471
    [Google Scholar]
  23. Zhang Y. Zhang X.Y. Shi S.R. Ma C.N. Lin Y.P. Song W.G. Guo S.D. Natural products in atherosclerosis therapy by targeting PPARs: A review focusing on lipid metabolism and inflammation. Front. Cardiovasc. Med. 2024 11 1372055 10.3389/fcvm.2024.1372055 38699583
    [Google Scholar]
  24. Li L. Hou X. Xu R. Liu C. Tu M. Research review on the pharmacological effects of astragaloside IV. Fundam. Clin. Pharmacol. 2017 31 1 17 36 10.1111/fcp.12232 27567103
    [Google Scholar]
  25. Auyeung K.K. Han Q-B. Ko J.K. Astragalus membranaceus: A review of its protection against inflammation and gastrointestinal cancers. Am. J. Chin. Med. 2016 44 1 1 22 10.1142/S0192415X16500014 26916911
    [Google Scholar]
  26. Su H. Shaker S. Kuang Y. Zhang M. Ye M. Qiao X. Phytochemistry and cardiovascular protective effects of Huang-Qi (Astragali Radix). Med. Res. Rev. 2021 41 4 1999 2038 10.1002/med.21785 33464616
    [Google Scholar]
  27. Bhagya N. Chandrashekar K.R. Tetrandrine: A molecule of wide bioactivity. Phytochemistry 2016 125 5 13 [May;] 10.1016/j.phytochem.2016.02.005 26899361
    [Google Scholar]
  28. Kim D.E. Min J.S. Jang M.S. Lee J.Y. Shin Y.S. Park C.M. Song J.H. Kim H.R. Kim S. Jin Y-H. Natural bis-benzylisoquinoline alkaloids: Tetrandrine, fangchinoline, and cepharanthine, inhibit human coronavirus OC43 infection of MRC-5 human lung cells. Biomolecules 2019 9 11 696 10.3390/biom9110696 31690059
    [Google Scholar]
  29. Krycer J.R. Sharpe L.J. Luu W. Brown A.J. The Akt–SREBP nexus: Cell signaling meets lipid metabolism. Trends Endocrinol. Metab. 2010 21 5 268 276 10.1016/j.tem.2010.01.001 20117946
    [Google Scholar]
  30. Abraham A.G. O’Neill E. PI3K/Akt-mediated regulation of p53 in cancer. Biochem. Soc. Trans. 2014 42 4 798 803 10.1042/BST20140070 25109960
    [Google Scholar]
  31. Huang X. Liu G. Guo J. Su Z. The PI3K/AKT pathway in obesity and type 2 diabetes. Int. J. Biol. Sci. 2018 14 11 1483 1496 10.7150/ijbs.27173 30263000
    [Google Scholar]
  32. Chen L.L. Wang W.J. p53 regulates lipid metabolism in cancer. Int. J. Biol. Macromol. 2021 192 45 54 10.1016/j.ijbiomac.2021.09.188 34619274
    [Google Scholar]
  33. Zhao J. Zhou X. Chen B. Lu M. Wang G. Elumalai N. Tian C. Zhang J. Liu Y. Chen Z. Zhou X. Wu M. Li M. Prochownik E.V. Tavassoli A. Jiang C. Li Y. p53 promotes peroxisomal fatty acid β-oxidation to repress purine biosynthesis and mediate tumor suppression. Cell Death Dis. 2023 14 2 87 10.1038/s41419‑023‑05625‑2 36750554
    [Google Scholar]
  34. Han B. Lin X. Hu H. Regulation of PI3K signaling in cancer metabolism and PI3K-targeting therapy. Transl. Breast Cancer Res. 2024 5 33 10.21037/tbcr‑24‑29 39534586
    [Google Scholar]
  35. Shamsan E. Almezgagi M. Gamah M. Khan N. Qasem A. Chuanchuan L. Haining F. The role of PI3k/AKT signaling pathway in attenuating liver fibrosis: A comprehensive review. Front. Med. 2024 11 1389329 10.3389/fmed.2024.1389329 38590313
    [Google Scholar]
  36. Han Q. Shi J. Yu Y. Yuan H. Guo Y. Liu X. Xue Y. Li Y. Calycosin alleviates ferroptosis and attenuates doxorubicin-induced myocardial injury via the Nrf2/SLC7A11/GPX4 signaling pathway. Front. Pharmacol. 2024 15 1497733 10.3389/fphar.2024.1497733 39600362
    [Google Scholar]
  37. Wei X. Zeng Y. Meng F. Wang T. Wang H. Yuan Y. Li D. Zhao Y. Calycosin-7-glucoside promotes mitochondria-mediated apoptosis in hepatocellular carcinoma by targeting thioredoxin 1 to regulate oxidative stress. Chem. Biol. Interact. 2023 374 110411 10.1016/j.cbi.2023.110411 36812960
    [Google Scholar]
  38. Xiong X. Huang W. Yang X. Wang X. Wu B. Li D. Calycosin suppresses the activating effect of granulocyte-macrophage-colony-stimulating factor-producing T helper cells on macrophages in experimental atherosclerosis. Front. Pharmacol. 2025 16 1607349 10.3389/fphar.2025.1607349 40709089
    [Google Scholar]
  39. Xu H. Wu K. Guo C. Zhong G. Calycosin action against atherosclerosis: Integrating network pharmacology and in-silico investigation. Acta Cardiol. 2024 79 5 566 574 10.1080/00015385.2024.2356902 38771335
    [Google Scholar]
  40. Zhu L. Liu S. Liao Y.F. Sheng Y.M. He J.C. Cai Z.X. Man Q. Wu Y.Y. Calycosin suppresses colorectal cancer progression by targeting ERβ, upregulating PTEN, and inhibiting PI3K/Akt signal pathway. Cell Biol. Int. 2022 46 9 1367 1377 10.1002/cbin.11840 35842774
    [Google Scholar]
  41. Chan A.B. Parico G.C.G. Fribourgh J.L. Ibrahim L.H. Bollong M.J. Partch C.L. Lamia K.A. CRY2 missense mutations suppress P53 and enhance cell growth. Proc. Natl. Acad. Sci. USA 2021 118 27 e2101416118 10.1073/pnas.2101416118 34183418
    [Google Scholar]
  42. Mijit M. Caracciolo V. Melillo A. Amicarelli F. Giordano A. Role of p53 in the regulation of cellular senescence. Biomolecules 2020 10 3 420 10.3390/biom10030420 32182711
    [Google Scholar]
  43. Beverly J.K. Budoff M.J. Atherosclerosis: Pathophysiology of insulin resistance, hyperglycemia, hyperlipidemia, and inflammation. J. Diabetes 2020 12 2 102 104 10.1111/1753‑0407.12970 31411812
    [Google Scholar]
  44. Wang Z.Y. Jiang Z.M. Xiao P.T. Jiang Y.Q. Liu W.J. Liu E.H. The mechanisms of baicalin ameliorate obesity and hyperlipidemia through a network pharmacology approach. Eur. J. Pharmacol. 2020 878 173103 10.1016/j.ejphar.2020.173103 32278854
    [Google Scholar]
  45. Gulyaev S.M. Turtueva T.A. Nikolaeva G.G. Evaluation of the antioxidant activity and anti-inflammatory effect of root extracts of Astragalus Membranaceus, Scutellaria Baicalensis, and Phlojodicarpus Sibiricus. Pharm. Chem. J. 2023 57 3 378 381 10.1007/s11094‑023‑02893‑2
    [Google Scholar]
  46. Hsieh H.L. Liu S.H. Chen Y.L. Huang C.Y. Wu S.J. Astragaloside IV suppresses inflammatory response via suppression of NF-κB, and MAPK signalling in human bronchial epithelial cells. Arch. Physiol. Biochem. 2022 128 3 757 766 10.1080/13813455.2020.1727525 32057253
    [Google Scholar]
  47. Li H. Shao L. Chen X. Wang M. Qin Q. Yang Y. Zhang G. Hai Y. Tian Y. Anti-inflammatory and DNA repair effects of astragaloside IV on PC12 cells damaged by lipopolysaccharide. Curr. Med. Sci. 2024 44 4 854 863 10.1007/s11596‑024‑2912‑0 39112916
    [Google Scholar]
  48. Li L. Zhang Y. Luo Y. Meng X. Pan G. Zhang H. Li Y. Zhang B. The molecular basis of the anti-inflammatory property of astragaloside IV for the treatment of diabetes and its complications. Drug Des. Devel. Ther. 2023 17 771 790 10.2147/DDDT.S399423 36925998
    [Google Scholar]
  49. Li M. Li H. Fang F. Deng X. Ma S. Astragaloside IV attenuates cognitive impairments induced by transient cerebral ischemia and reperfusion in mice via anti-inflammatory mechanisms. Neurosci. Lett. 2017 639 114 119 10.1016/j.neulet.2016.12.046 28011393
    [Google Scholar]
  50. Li M. Jia J. Wang Y. Zhuang Y. Wang H. Lin Z. Lu Y. Li M. Wang Z. Zhao H. Astragaloside IV promotes cerebral tissue restoration through activating AMPK- mediated microglia polarization in ischemic stroke rats. J. Ethnopharmacol. 2024 334 118532 10.1016/j.jep.2024.118532 38972527
    [Google Scholar]
  51. Li R. Shi C. Wei C. Wang C. Du H. Hong Q. Chen X. Fufang shenhua tablet, astragali radix and its active component astragaloside IV: Research progress on anti-inflammatory and immunomodulatory mechanisms in the kidney. Front. Pharmacol. 2023 14 1131635 10.3389/fphar.2023.1131635 37089929
    [Google Scholar]
  52. Liu T. Ai L. Jiang A. Wang Y. Jiang R. Liu L. Astragaloside IV suppresses the proliferation and inflammatory response of human epidermal keratinocytes and ameliorates imiquimod-induced psoriasis-like skin damage in mice. Allergol. Immunopathol 2024 52 5 44 50 10.15586/aei.v52i5.1140 39278850
    [Google Scholar]
  53. Luo C. Ye Y. Lv A. Zuo W. Yang Y. Jiang C. Ke J. The impact of Astragaloside IV on the inflammatory response and gut microbiota in cases of acute lung injury is examined through the utilization of the PI3K/AKT/mTOR pathway. PLoS One 2024 19 7 e0305058 10.1371/journal.pone.0305058 38954702
    [Google Scholar]
  54. Qu T. Suo S. Yan L. Wang L. Liang T. Anti‐inflammatory effects of astragaloside IV–chitosan nanoparticles and associated anti‐inflammatory mechanisms based on liquid chromatography‐mass spectrometry metabolomic analysis of RAW264.7 cells. Chem. Biodivers. 2025 22 6 e202402234 10.1002/cbdv.202402234 39891602
    [Google Scholar]
  55. Tan S. Wang G. Guo Y. Gui D. Wang N. Preventive effects of a natural anti-inflammatory agent, astragaloside IV, on ischemic acute kidney injury in rats. Evid. Based Complement. Alternat. Med. 2013 2013 1 12 10.1155/2013/284025 23853656
    [Google Scholar]
  56. Zhang Y. Huang O. Zhang W. Liu L. Xu C. Astragaloside IV exerts anti-inflammatory role in endometriosis by downregulating TLR4/NF-κB pathway. Trop. J. Pharm. Res. 2021 18 3 539 545 10.4314/tjpr.v18i3.14
    [Google Scholar]
  57. Page C. Lin H.J. Jin Y. Castle V.P. Nunez G. Huang M. Lin J. Overexpression of Akt/AKT can modulate chemotherapy-induced apoptosis. Anticancer Res. 2000 20 1A 407 416 [PMID: 10769688
    [Google Scholar]
  58. Franke T.F. PI3K/Akt: Getting it right matters. Oncogene 2008 27 50 6473 6488 10.1038/onc.2008.313 18955974
    [Google Scholar]
  59. Zhang M. Ma X. Xu H. Wu W. He X. Wang X. Jiang M. Hou Y. Bai G. A natural AKT inhibitor swertiamarin targets AKT‐PH domain, inhibits downstream signaling, and alleviates inflammation. FEBS J. 2020 287 9 1816 1829 10.1111/febs.15112 31665825
    [Google Scholar]
  60. Neurath M.F. Finotto S. IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer. Cytokine Growth Factor Rev. 2011 22 2 83 89 10.1016/j.cytogfr.2011.02.003 21377916
    [Google Scholar]
  61. Kostek M.C. Nagaraju K. Pistilli E. Sali A. Lai S.H. Gordon B. Chen Y.W. IL-6 signaling blockade increases inflammation but does not affect muscle function in the mdx mouse. BMC Musculoskelet. Disord. 2012 13 1 106 10.1186/1471‑2474‑13‑106 22716658
    [Google Scholar]
  62. Sueyoshi S. Mitsumata M. Kusumi Y. Niihashi M. Esumi M. Yamada T. Sakurai I. Increased expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ in human atherosclerosis. Pathol. Res. Pract. 2010 206 7 429 438 10.1016/j.prp.2010.01.010 20399568
    [Google Scholar]
  63. Wang L. Waltenberger B. Pferschy-Wenzig E.M. Blunder M. Liu X. Malainer C. Blazevic T. Schwaiger S. Rollinger J.M. Heiss E.H. Schuster D. Kopp B. Bauer R. Stuppner H. Dirsch V.M. Atanasov A.G. Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): A review. Biochem. Pharmacol. 2014 92 1 73 89 10.1016/j.bcp.2014.07.018 25083916
    [Google Scholar]
  64. Faghfouri A.H. Khajebishak Y. Payahoo L. Faghfuri E. Alivand M. PPAR-gamma agonists: Potential modulators of autophagy in obesity. Eur. J. Pharmacol. 2021 912 174562 10.1016/j.ejphar.2021.174562 34655597
    [Google Scholar]
  65. Maclaine N.J. Hupp T.R. The regulation of p53 by phosphorylation: A model for how distinct signals integrate into the p53 pathway. Aging (Albany NY) 2009 1 5 490 502 10.18632/aging.100047 20157532
    [Google Scholar]
  66. Nayak S. Panesar P. Kumar H. p53-Induced apoptosis and inhibitors of p53. Curr. Med. Chem. 2009 16 21 2627 2640 10.2174/092986709788681976 19601800
    [Google Scholar]
  67. Evans R.M. Mangelsdorf D.J. Nuclear receptors, RXR, and the big bang. Cell 2014 157 1 255 266 10.1016/j.cell.2014.03.012 24679540
    [Google Scholar]
  68. Chen Y. Zhang Z. Pan F. Li P. Yao W. Chen Y. Xiong L. Wang T. Li Y. Huang G. Pericytes recruited by CCL28 promote vascular normalization after anti-angiogenesis therapy through RA/RXRA/ANGPT1 pathway in lung adenocarcinoma. J. Exp. Clin. Cancer Res. 2024 43 1 210 10.1186/s13046‑024‑03135‑3 39075504
    [Google Scholar]
  69. Pan Z. Chen X. Wu D. Li X. Gao W. Li G. Du G. Zhang C. Jin S. Geng Z. A novel in duck myoblasts: The transcription factor retinoid X receptor alpha (RXRA) inhibits lipid accumulation by promoting CD36 expression. Int. J. Mol. Sci. 2023 24 2 1180 10.3390/ijms24021180 36674699
    [Google Scholar]
  70. Rajamani B.M. Illangeswaran R.S.S. Benjamin E.S.B. Balakrishnan B. Jebanesan D.Z.P. Das S. Pai A.A. Vidhyadharan R.T. Mohan A. Karathedath S. Abraham A. Mathews V. Velayudhan S.R. Balasubramanian P. Modulating retinoid-X-receptor alpha (RXRA) expression sensitizes chronic myeloid leukemia cells to imatinib in vitro and reduces disease burden in vivo. Front. Pharmacol. 2023 14 1187066 10.3389/fphar.2023.1187066 37324449
    [Google Scholar]
  71. Wang C. Gao Y. Luan C. Sun W. Ge S. Li Y. Xu L. Du Q. Liu W. Lu G. Gong W. Ma X. Zinc finger protein ZBTB17 controls cellular senescence via interacting with nuclear receptor RXRA and its downstream calcium signaling. FASEB J. 2023 37 10 e23193 10.1096/fj.202301050R 37698375
    [Google Scholar]
  72. Luan X.F. Wang L. Gai X.F. The miR‐28‐5p‐CAMTA2 axis regulates colon cancer progression via Wnt/β‐catenin signaling. J. Cell. Biochem. 2021 122 9 945 957 10.1002/jcb.29536 31709644
    [Google Scholar]
  73. Zhu X. Wang P. Bai Z. Herde M. Ma Y. Li N. Liu S. Huang C.F. Cui R. Ma H. Zhang M. Wang H. Wei T. Quan T. Zhang W. Liu C. Zhang T. Yang Z.B. Calmodulin‐like protein CML24 interacts with CAMTA2 and WRKY46 to regulate ALMT1‐dependent Al resistance in Arabidopsis thaliana. New Phytol. 2022 233 6 2471 2487 10.1111/nph.17812 34665465
    [Google Scholar]
  74. Galon Y. Snir O. Fromm H. How calmodulin binding transcription activators (CAMTAs) mediate auxin responses. Plant Signal. Behav. 2010 5 10 1311 1314 10.4161/psb.5.10.13158 20930517
    [Google Scholar]
  75. Zeng H. Wang G. Wang H. Lin J. Du L. Functions of Calmodulin-Binding Transcription Activators (CAMTAs) in Plants. Chih Wu Sheng Li Hsueh T’ung Hsun 2015 51 5 633 641
    [Google Scholar]
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