Skip to content
2000
image of Recent Advancements in Pentacyclic and Other Terpenoid Derivatives as Anti-inflammatory Agents

Abstract

Inflammation is the body's defensive response to injury, infection, or external stimuli. While NSAIDs and corticosteroids are widely used to treat inflammatory diseases, their long-term application often leads to severe side effects, including gastrointestinal damage and cardiovascular toxicity, as well as drug resistance. This underscores the urgent need for developing safer and more effective anti-inflammatory agents. Natural products, particularly terpenoids, as the largest class of bioactive compounds, have garnered significant attention due to their potent anti-inflammatory properties and structural diversity. Through systematic structural modifications, researchers have developed numerous terpenoid derivatives with enhanced anti-inflammatory efficacy, providing valuable insights for drug discovery. This review comprehensively summarizes the anti-inflammatory mechanisms and therapeutic potential of terpenoids and their derivatives over the past decade, offering new perspectives for anti-inflammatory drug development and identifying promising candidates for further investigation.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/mrmc/10.2174/0113895575414767251013071926
2025-10-23
2025-12-25

  • From This Site

    /content/journals/mrmc/10.2174/0113895575414767251013071926
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Leuti A. Fazio D. Fava M. Piccoli A. Oddi S. Maccarrone M. Bioactive lipids, inflammation and chronic diseases. Adv. Drug Deliv. Rev. 2020 159 133 169 10.1016/j.addr.2020.06.028 32628989
    [Google Scholar]
  2. Scott A. Khan K.M. Cook J.L. Duronio V. What is “inflammation”? Are we ready to move beyond Celsus? Br. J. Sports Med. 2004 38 3 248 249 10.1136/bjsm.2003.011221 15155418
    [Google Scholar]
  3. Eltay E.G. Van Dyke T. Resolution of inflammation in oral diseases. Pharmacol. Ther. 2023 247 108453 10.1016/j.pharmthera.2023.108453 37244405
    [Google Scholar]
  4. Panigrahy D. Gilligan M.M. Serhan C.N. Kashfi K. Resolution of inflammation: An organizing principle in biology and medicine. Pharmacol. Ther. 2021 227 107879 10.1016/j.pharmthera.2021.107879 33915177
    [Google Scholar]
  5. Nasef N.A. Mehta S. Ferguson L.R. Susceptibility to chronic inflammation: An update. Arch. Toxicol. 2017 91 3 1131 1141 10.1007/s00204‑016‑1914‑5 28130581
    [Google Scholar]
  6. Aoki T. Narumiya S. Prostaglandins and chronic inflammation. Trends Pharmacol. Sci. 2012 33 6 304 311 10.1016/j.tips.2012.02.004 22464140
    [Google Scholar]
  7. Fullerton J.N. Gilroy D.W. Resolution of inflammation: A new therapeutic frontier. Nat. Rev. Drug Discov. 2016 15 8 551 567 10.1038/nrd.2016.39 27020098
    [Google Scholar]
  8. Hawiger J. Zienkiewicz J. Decoding inflammation, its causes, genomic responses, and emerging countermeasures. Scand. J. Immunol. 2019 90 6 12812 10.1111/sji.12812 31378956
    [Google Scholar]
  9. Calder P.C. Albers R. Antoine J.M. Blum S. Bourdet-Sicard R. Ferns G.A. Folkerts G. Friedmann P.S. Frost G.S. Guarner F. Løvik M. Macfarlane S. Meyer P.D. M’Rabet L. Serafini M. van Eden W. van Loo J. Vas Dias W. Vidry S. Winklhofer-Roob B.M. Zhao J. Inflammatory disease processes and interactions with nutrition. Br. J. Nutr. 2009 101 S1 1 45 10.1017/S0007114509377867 19586558
    [Google Scholar]
  10. Lutgendorf S.K. Positive affect and radiation-induced inflammation: Insights into inflammatory regulation? Brain Behav. Immun. 2009 23 8 1066 1067 10.1016/j.bbi.2009.08.011 19733231
    [Google Scholar]
  11. Wang B. Wu L. Chen J. Dong L. Chen C. Wen Z. Hu J. Fleming I. Wang D.W. Metabolism pathways of arachidonic acids: Mechanisms and potential therapeutic targets. Signal Transduct. Target. Ther. 2021 6 1 94 10.1038/s41392‑020‑00443‑w 33637672
    [Google Scholar]
  12. Piomelli D. Arachidonic acid in cell signaling. Curr. Opin. Cell Biol. 1993 5 2 274 280 10.1016/0955‑0674(93)90116‑8 7685181
    [Google Scholar]
  13. Garth J. Barnes J.W. Krick S. Targeting cytokines as evolving treatment strategies in chronic inflammatory airway diseases. Int. J. Mol. Sci. 2018 19 11 3402 10.3390/ijms19113402 30380761
    [Google Scholar]
  14. Habanjar O. Bingula R. Decombat C. Diab-Assaf M. Caldefie-Chezet F. Delort L. Crosstalk of inflammatory cytokines within the breast tumor microenvironment. Int. J. Mol. Sci. 2023 24 4 4002 10.3390/ijms24044002 36835413
    [Google Scholar]
  15. Souza D.G. Vieira A.T. Pinho V. Sousa L.P. Andrade A.A. Bonjardim C.A. McMillan M. Kahn M. Teixeira M.M. NF‐ κ B plays a major role during the systemic and local acute inflammatory response following intestinal reperfusion injury. Br. J. Pharmacol. 2005 145 2 246 254 10.1038/sj.bjp.0706190 15765103
    [Google Scholar]
  16. Qiu J. Jiang T. Yang G. Gong Y. Zhang W. Zheng X. Hong Z. Chen H. Neratinib exerts dual effects on cartilage degradation and osteoclast production in Osteoarthritis by inhibiting the activation of the MAPK/NF-κB signaling pathways. Biochem. Pharmacol. 2022 205 115155 10.1016/j.bcp.2022.115155 35820500
    [Google Scholar]
  17. Zhang N. Liu S. Shi S. Chen Y. Xu F. Wei X. Xu Y. Solubilization and delivery of Ursolic-acid for modulating tumor microenvironment and regulatory T cell activities in cancer immunotherapy. J. Control. Release 2020 320 168 178 10.1016/j.jconrel.2020.01.015 31926193
    [Google Scholar]
  18. Bjarnason I. Hayllar J. Macpherson A.N.J. Russell A.N.S. Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroenterology 1993 104 6 1832 1847 10.1016/0016‑5085(93)90667‑2 8500743
    [Google Scholar]
  19. Gallo K. Kemmler E. Goede A. Becker F. Dunkel M. Preissner R. Banerjee P. SuperNatural 3.0—a database of natural products and natural product-based derivatives. Nucleic Acids Res. 2023 51 D1 D654 D659 10.1093/nar/gkac1008 36399452
    [Google Scholar]
  20. de la Torre B.G. Albericio F. The Pharmaceutical Industry in 2020. An Analysis of FDA Drug Approvals from the Perspective of Molecules. Molecules 2021 26 3 627 10.3390/molecules26030627 33504104
    [Google Scholar]
  21. Bian G. Deng Z. Liu T. Strategies for terpenoid overproduction and new terpenoid discovery. Curr. Opin. Biotechnol. 2017 48 234 241 10.1016/j.copbio.2017.07.002 28779606
    [Google Scholar]
  22. Zhang X. Zheng M. Fu A. Li Q. Chen C. Zhu H. Zhang Y. Natural sesquiterpenoids, diterpenoids, sesterterpenoids, and triterpenoids with intriguing structures from 2017 to 2022. Chin. J. Chem. 2023 41 22 3115 3132 10.1002/cjoc.202300275
    [Google Scholar]
  23. Nguyen T.D. Riordan-Short S. Dang T.T.T. O’Brien R. Noestheden M. Quantitation of select terpenes/terpenoids and nicotine using gas chromatography–Mass spectrometry with high-temperature headspace sampling. ACS Omega 2020 5 10 5565 5573 10.1021/acsomega.0c00384 32201850
    [Google Scholar]
  24. Yazaki K. Arimura G. Ohnishi T. ‘Hidden’ terpenoids in plants: Their biosynthesis, localization and ecological roles. Plant Cell Physiol. 2017 58 10 1615 1621 10.1093/pcp/pcx123 29016891
    [Google Scholar]
  25. Kiyama R. Estrogenic terpenes and terpenoids: Pathways, functions and applications. Eur. J. Pharmacol. 2017 815 405 415 10.1016/j.ejphar.2017.09.049 28970013
    [Google Scholar]
  26. Jaeger R. Cuny E. Terpenoids with special pharmacological significance: A review. Nat. Prod. Commun. 2016 11 9 1934578X1601100946. 10.1177/1934578X1601100946
    [Google Scholar]
  27. Wang Z. Tang S. Jin Y. Zhang Y. Hattori M. Zhang H. Zhang N. Two main metabolites of gentiopicroside detected in rat plasma by LC–TOF-MS following 2,4-dinitrophenylhydrazine derivatization. J. Pharm. Biomed. Anal. 2015 107 1 6 10.1016/j.jpba.2014.12.003 25556816
    [Google Scholar]
  28. Zhao L. Ye J. Wu G. Peng X. Xia P. Ren Y. Gentiopicroside prevents interleukin-1 beta induced inflammation response in rat articular chondrocyte. J. Ethnopharmacol. 2015 172 100 107 10.1016/j.jep.2015.06.031 26116164
    [Google Scholar]
  29. Zhang Q.L. Xia P.F. Peng X.J. Wu X.Y. Jin H. Zhang J. Zhao L. Synthesis, and anti-inflammatory activities of gentiopicroside derivatives. Chin. J. Nat. Med. 2022 20 4 309 320 10.1016/S1875‑5364(22)60187‑0 35487601
    [Google Scholar]
  30. Ren G. Zhang Q. Xia P. Wang J. Fang P. Jin X. Peng X. Xu Y. Zhang J. Zhao L. Synthesis and biological evaluation of gentiopicroside derivatives as novel cyclooxygenase-2 inhibitors with anti-inflammatory activity. Drug Des. Devel. Ther. 2023 17 919 935 10.2147/DDDT.S398861 36992901
    [Google Scholar]
  31. Wang C. Gong X. Bo A. Zhang L. Zhang M. Zang E. Zhang C. Li M. Iridoids: Research advances in their phytochemistry, biological activities, and pharmacokinetics. Molecules 2020 25 2 287 10.3390/molecules25020287 31936853
    [Google Scholar]
  32. Wang Q.S. Xiang Y. Cui Y.L. Lin K.M. Zhang X.F. Dietary blue pigments derived from genipin, attenuate inflammation by inhibiting LPS-induced iNOS and COX-2 expression via the NF-κB inactivation. PLoS One 2012 7 3 34122 10.1371/journal.pone.0034122 22479539
    [Google Scholar]
  33. Nam K.N. Choi Y.S. Jung H.J. Park G.H. Park J.M. Moon S.K. Cho K.H. Kang C. Kang I. Oh M.S. Lee E.H. Genipin inhibits the inflammatory response of rat brain microglial cells. Int. Immunopharmacol. 2010 10 4 493 499 10.1016/j.intimp.2010.01.011 20123040
    [Google Scholar]
  34. Li S.M. Chiang C.Y. Zeng W.Z. Chung C.Y. Tseng C.C. Hu Y.P. Lin Y.C. Huang G.J. Arai I. Lee D.Y. Tsai S.E. Wong F.F. Bioactivity study of tricyclic and tetracyclic genipin derivatives as anti-inflammatory agents. Bioorg. Chem. 2022 126 105881 10.1016/j.bioorg.2022.105881 35636127
    [Google Scholar]
  35. Wang H. Gao S. Li J. Ma X. Liu W. Qian S. Hybrids of aurantiamide acetate and isopropylated genipin as potential anti‐inflammatory agents: The design, synthesis, and biological evaluation. Chem. Biol. Drug Des. 2021 97 4 797 808 10.1111/cbdd.13809 33219736
    [Google Scholar]
  36. Lewinsohn E. Schalechet F. Wilkinson J. Matsui K. Tadmor Y. Nam K.H. Amar O. Lastochkin E. Larkov O. Ravid U. Hiatt W. Gepstein S. Pichersky E. Enhanced levels of the aroma and flavor compound S-linalool by metabolic engineering of the terpenoid pathway in tomato fruits. Plant Physiol. 2001 127 3 1256 1265 10.1104/pp.010293 11706204
    [Google Scholar]
  37. Kim M.G. Kim S.M. Min J.H. Kwon O.K. Park M.H. Park J.W. Ahn H.I. Hwang J.Y. Oh S.R. Lee J.W. Ahn K.S. Anti-inflammatory effects of linalool on ovalbumin-induced pulmonary inflammation. Int. Immunopharmacol. 2019 74 105706 10.1016/j.intimp.2019.105706 31254955
    [Google Scholar]
  38. Cicalău G. Babes P. Calniceanu H. Popa A. Ciavoi G. Iova G. Ganea M. Scrobotă I. Anti-inflammatory and antioxidant properties of carvacrol and magnolol, in periodontal disease and diabetes mellitus. Molecules 2021 26 22 6899 10.3390/molecules26226899 34833990
    [Google Scholar]
  39. Lima M.S. Quintans-Júnior L.J. de Santana W.A. Martins Kaneto C. Pereira Soares M.B. Villarreal C.F. Anti-inflammatory effects of carvacrol: Evidence for a key role of interleukin-10. Eur. J. Pharmacol. 2013 699 1-3 112 117 10.1016/j.ejphar.2012.11.040 23220159
    [Google Scholar]
  40. Xiao Y. Li B. Liu J. Ma X. Carvacrol ameliorates inflammatory response in interleukin 1β-stimulated human chondrocytes. Mol. Med. Rep. 2017 17 3 3987 3992 10.3892/mmr.2017.8308 29257341
    [Google Scholar]
  41. Gago C. Serralheiro A. Miguel M.G. Anti-inflammatory activity of thymol and thymol-rich essential oils: Mechanisms, applications, and recent findings. Molecules 2025 30 11 2450 10.3390/molecules30112450 40509336
    [Google Scholar]
  42. Lenardão E.J. Botteselle G.V. de Azambuja F. Perin G. Jacob R.G. Citronellal as key compound in organic synthesis. Tetrahedron 2007 63 29 6671 6712 10.1016/j.tet.2007.03.159
    [Google Scholar]
  43. Melo M.S. Guimarães A.G. Santana M.F. Siqueira R.S. De Lima A.D.C.B. Dias A.S. Santos M.R.V. Onofre A.S.C. Quintans J.S.S. De Sousa D.P. Almeida J.R.G.S. Estevam C.S. Araujo B.S. Quintans-Júnior L.J. Anti-inflammatory and redox-protective activities of citronellal. Biol. Res. 2011 44 4 363 368 10.4067/S0716‑97602011000400008 22446600
    [Google Scholar]
  44. Haffas M. Benkiki N. Chebrouk F. Maadadi R. Menacer R. Mouffouk C. Kabouche Z. Mendes R.F. Paz F.A.A. Saher L. Bachari K. Talhi O. Silva A.M.S. Sousa J.L.C. Hemisynthesis of monoterpene-containing pyridin-2-one, pyrano [2,3-c] pyrazole and dicarbamate derivatives: In vitro and in silico anti-inflammatory activity. J. Mol. Struct. 2025 1331 141565 10.1016/j.molstruc.2025.141565
    [Google Scholar]
  45. Gao S. Wang Q. Tian X.H. Li H.L. Shen Y.H. Xu X.K. Wu G.Z. Hu Z.L. Zhang W.D. Total sesquiterpene lactones prepared from Inula helenium L. has potentials in prevention and therapy of rheumatoid arthritis. J. Ethnopharmacol. 2017 196 39 46 10.1016/j.jep.2016.12.020 27988396
    [Google Scholar]
  46. Maryam A. Mehmood T. Zhang H. Li Y. Khan M. Ma T. Alantolactone induces apoptosis, promotes STAT3 glutathionylation and enhances chemosensitivity of A549 lung adenocarcinoma cells to doxorubicin via oxidative stress. Sci. Rep. 2017 7 1 6242 10.1038/s41598‑017‑06535‑y 28740138
    [Google Scholar]
  47. Chun J. Choi R.J. Khan S. Lee D.S. Kim Y.C. Nam Y.J. Lee D.U. Kim Y.S. Alantolactone suppresses inducible nitric oxide synthase and cyclooxygenase-2 expression by down-regulating NF-κB, MAPK and AP-1 via the MyD88 signaling pathway in LPS-activated RAW 264.7 cells. Int. Immunopharmacol. 2012 14 4 375 383 10.1016/j.intimp.2012.08.011 22940184
    [Google Scholar]
  48. Kumar C. Kumar A. Nalli Y. Lone W.I. Satti N.K. Verma M.K. Ahmed Z. Ali A. Design, synthesis and biological evaluation of alantolactone derivatives as potential anti-inflammatory agents. Med. Chem. Res. 2019 28 6 849 856 10.1007/s00044‑019‑02337‑1
    [Google Scholar]
  49. Akiyama K. Matsuzaki K. Hayashi H. Plant sesquiterpenes induce hyphal branching in arbuscular mycorrhizal fungi. Nature 2005 435 7043 824 827 10.1038/nature03608 15944706
    [Google Scholar]
  50. Pollock C.B. Koltai H. Kapulnik Y. Prandi C. Yarden R.I. Strigolactones: A novel class of phytohormones that inhibit the growth and survival of breast cancer cells and breast cancer stem-like enriched mammosphere cells. Breast Cancer Res. Treat. 2012 134 3 1041 1055 10.1007/s10549‑012‑1992‑x 22476848
    [Google Scholar]
  51. Zheng J.X. Han Y.S. Wang J.C. Yang H. Kong H. Liu K.J. Chen S.Y. Chen Y.R. Chang Y.Q. Chen W.M. Guo J.L. Sun P.H. Strigolactones: A plant phytohormone as novel anti-inflammatory agents. MedChemComm 2018 9 1 181 188 10.1039/C7MD00461C 30108912
    [Google Scholar]
  52. Hoffstrom B.G. Kaplan A. Letso R. Schmid R.S. Turmel G.J. Lo D.C. Stockwell B.R. Inhibitors of protein disulfide isomerase suppress apoptosis induced by misfolded proteins. Nat. Chem. Biol. 2010 6 12 900 906 10.1038/nchembio.467 21079601
    [Google Scholar]
  53. Lee S.K. Kim H. Park J. Kim H.J. Kim K.R. Son S.H. Park K.K. Chung W.Y. Artemisia annua extract prevents ovariectomy-induced bone loss by blocking receptor activator of nuclear factor kappa-B ligand-induced differentiation of osteoclasts. Sci. Rep. 2017 7 1 17332 10.1038/s41598‑017‑17427‑6 29230013
    [Google Scholar]
  54. Ur Rasool J. Sawhney G. Shaikh M. Nalli Y. Madishetti S. Ahmed Z. Ali A. Site selective synthesis and anti-inflammatory evaluation of Spiro-isoxazoline stitched adducts of arteannuin B. Bioorg. Chem. 2021 117 105408 10.1016/j.bioorg.2021.105408 34655840
    [Google Scholar]
  55. Khom S. Baburin I. Timin E. Hohaus A. Trauner G. Kopp B. Hering S. Valerenic acid potentiates and inhibits GABAA receptors: Molecular mechanism and subunit specificity. Neuropharmacology 2007 53 1 178 187 10.1016/j.neuropharm.2007.04.018 17585957
    [Google Scholar]
  56. Jacobo-Herrera N.J. Vartiainen N. Bremner P. Gibbons S. Koistinaho J. Heinrich M. F‐ κ B modulators from Valeriana officinalis. Phytother. Res. 2006 20 10 917 919 10.1002/ptr.1972 16909443
    [Google Scholar]
  57. Egbewande F.A. Nilsson N. White J.M. Coster M.J. Davis R.A. The design, synthesis, and anti-inflammatory evaluation of a drug-like library based on the natural product valerenic acid. Bioorg. Med. Chem. Lett. 2017 27 14 3185 3189 10.1016/j.bmcl.2017.05.021 28558967
    [Google Scholar]
  58. Bazzocchi I.L. Núñez M.J. Reyes., C.P. Bioactive diterpenoids from Celastraceae species. Phytochem. Rev. 2017 16 5 861 881 10.1007/s11101‑017‑9494‑4
    [Google Scholar]
  59. Perestelo N.R. Jiménez I.A. Tokuda H. Bazzocchi I.L. Structure-Activity relationship of sesquiterpenes dihydro-β-agarofuran as chemopreventive agents. Planta Med. 2008 74 9 PG78 10.1055/s‑0028‑1084830
    [Google Scholar]
  60. Alarcón-Enos J. Muñoz-Núñez E. Gutiérrez M. Quiroz-Carreño S. Pastene-Navarrete E. Céspedes Acuña C. Dyhidro-β-agarofurans natural and synthetic as acetylcholinesterase and COX inhibitors: Interaction with the peripheral anionic site (AChE-PAS), and anti-inflammatory potentials. J. Enzyme Inhib. Med. Chem. 2022 37 1 1845 1856 10.1080/14756366.2022.2091554 35815566
    [Google Scholar]
  61. Tran Q.T.N. Wong W.S.F. Chai C.L.L. The identification of naturally occurring labdane diterpenoid calcaratarin D as a potential anti-inflammatory agent. Eur. J. Med. Chem. 2019 174 33 44 10.1016/j.ejmech.2019.04.023 31022551
    [Google Scholar]
  62. Islam M.T. Ali E.S. Uddin S.J. Islam M.A. Shaw S. Khan I.N. Saravi S.S.S. Ahmad S. Rehman S. Gupta V.K. Găman M.A. Găman A.M. Yele S. Das A.K. de Castro e Sousa, J.M.; de Moura Dantas, S.M.M.; Rolim, H.M.L.; de Carvalho Melo-Cavalcante, A.A.; Mubarak, M.S.; Yarla, N.S.; Shilpi, J.A.; Mishra, S.K.; Atanasov, A.G.; Kamal, M.A. Andrographolide, a diterpene lactone from Andrographis paniculata and its therapeutic promises in cancer. Cancer Lett. 2018 420 129 145 10.1016/j.canlet.2018.01.074 29408515
    [Google Scholar]
  63. Lee J.C. Tseng C.K. Young K.C. Sun H.Y. Wang S.W. Chen W.C. Lin C.K. Wu Y.H. Andrographolide exerts anti‐hepatitis C virus activity by up‐regulating haeme oxygenase‐1 via the p38 MAPK/N rf2 pathway in human hepatoma cells. Br. J. Pharmacol. 2014 171 1 237 252 10.1111/bph.12440 24117426
    [Google Scholar]
  64. Mishra K. Dash A.P. Swain B.K. Dey N. Anti-malarial activities of Andrographis paniculata and Hedyotis corymbosa extracts and their combination with curcumin. Malar. J. 2009 8 1 26 10.1186/1475‑2875‑8‑26 19216765
    [Google Scholar]
  65. Chen H.W. Lin A.H. Chu H.C. Li C.C. Tsai C.W. Chao C.Y. Wang C.J. Lii C.K. Liu K.L. Inhibition of TNF-α-Induced Inflammation by andrographolide via down-regulation of the PI3K/Akt signaling pathway. J. Nat. Prod. 2011 74 11 2408 2413 10.1021/np200631v 22026410
    [Google Scholar]
  66. González-Trujano M.E. Uribe-Figueroa G. Hidalgo-Figueroa S. Martínez A.L. Déciga-Campos M. Navarrete-Vazquez G. Synthesis and antinociceptive evaluation of bioisosteres and hybrids of naproxen, ibuprofen and paracetamol. Biomed. Pharmacother. 2018 101 553 562 10.1016/j.biopha.2018.02.122 29514128
    [Google Scholar]
  67. Wang W. Wu Y. Chen X. Zhang P. Li H. Chen L. Synthesis of new ent-labdane diterpene derivatives from andrographolide and evaluation of their anti-inflammatory activities. Eur. J. Med. Chem. 2019 162 70 79 10.1016/j.ejmech.2018.11.002 30419492
    [Google Scholar]
  68. Masters S.L. Dunne A. Subramanian S.L. Hull R.L. Tannahill G.M. Sharp F.A. Becker C. Franchi L. Yoshihara E. Chen Z. Mullooly N. Mielke L.A. Harris J. Coll R.C. Mills K.H.G. Mok K.H. Newsholme P. Nuñez G. Yodoi J. Kahn S.E. Lavelle E.C. O’Neill L.A.J. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes. Nat. Immunol. 2010 11 10 897 904 10.1038/ni.1935 20835230
    [Google Scholar]
  69. Wang W. Wu Y. Yang K. Wu C. Tang R. Li H. Chen L. Synthesis of novel andrographolide beckmann rearrangement derivatives and evaluation of their HK2-related anti-inflammatory activities. Eur. J. Med. Chem. 2019 173 282 293 10.1016/j.ejmech.2019.04.022 31009914
    [Google Scholar]
  70. Tran Q.T.N. Tan D.W.S. Wong W.S.F. Chai C.L.L. From irreversible to reversible covalent inhibitors: Harnessing the andrographolide scaffold for anti-inflammatory action. Eur. J. Med. Chem. 2020 204 112481 10.1016/j.ejmech.2020.112481 32712435
    [Google Scholar]
  71. Liu L. Yan Y. Zheng L. Jia H. Han G. Synthesis and structure anti-inflammatory activity relationships studies of andrographolide derivatives. Nat. Prod. Res. 2020 34 6 782 789 10.1080/14786419.2018.1501689 30678497
    [Google Scholar]
  72. Soliman A.F. Elimam D.M. El-Senduny F.F. Alossaimi M.A. Alamri M. Abdel Bar F.M. Design, biological evaluation, and molecular modelling insights of cupressic acid derivatives as promising anti-inflammatory agents. J. Enzyme Inhib. Med. Chem. 2023 38 1 2187327 10.1080/14756366.2023.2187327 36912259
    [Google Scholar]
  73. Teng Y.N. Wang Y. Hsu P.L. Xin G. Zhang Y. Morris-Natschke S.L. Goto M. Lee K.H. Mechanism of action of cytotoxic compounds from the seeds of Euphorbia lathyris. Phytomedicine 2018 41 62 66 10.1016/j.phymed.2018.02.001 29519320
    [Google Scholar]
  74. Jassbi A.R. Chemistry and biological activity of secondary metabolites in Euphorbia from Iran. Phytochemistry 2006 67 18 1977 1984 10.1016/j.phytochem.2006.06.030 16889806
    [Google Scholar]
  75. Zhang C.Y. Wu Y.L. Zhang P. Chen Z.Z. Li H. Chen L.X. Anti-inflammatory Lathyrane Diterpenoids from Euphorbia lathyris. J. Nat. Prod. 2019 82 4 756 764 10.1021/acs.jnatprod.8b00600 30817151
    [Google Scholar]
  76. Wang W. Wu Y. Li C. Yang Y. Li X. Li H. Chen L. Synthesis of new lathyrane diterpenoid derivatives from Euphorbia lathyris and evaluation of their anti‐inflammatory activities. Chem. Biodivers. 2020 17 2 1900531 10.1002/cbdv.201900531 31825561
    [Google Scholar]
  77. Wang W. Xiong L. Li Y. Song Z. Sun D. Li H. Chen L. Synthesis of lathyrane diterpenoid nitrogen-containing heterocyclic derivatives and evaluation of their anti-inflammatory activities. Bioorg. Med. Chem. 2022 56 116627 10.1016/j.bmc.2022.116627 35063896
    [Google Scholar]
  78. Chen X. Guo J. Bao J. Lu J. Wang Y. The anticancer properties of Salvia miltiorrhiza Bunge (Danshen): A systematic review. Med. Res. Rev. 2014 34 4 768 794 10.1002/med.21304 24123144
    [Google Scholar]
  79. Dong X. Dong J. Zhang R. Fan L. Liu L. Wu G. Anti-inflammatory effects of tanshinone IIA on radiation-induced microglia BV-2 cells inflammatory response. Cancer Biother. Radiopharm. 2009 24 6 681 687 10.1089/cbr.2009.0640 20025548
    [Google Scholar]
  80. Ma S. Zhang D. Lou H. Sun L. Ji J. Evaluation of the anti-inflammatory activities of tanshinones isolated from Salvia miltiorrhiza var. alba roots in THP-1 macrophages. J. Ethnopharmacol. 2016 188 193 199 10.1016/j.jep.2016.05.018 27178632
    [Google Scholar]
  81. Ranallo S. Amodio A. Idili A. Porchetta A. Ricci F. Electronic control of DNA-based nanoswitches and nanodevices. Chem. Sci. 2016 7 1 66 71 10.1039/C5SC03694A 28757998
    [Google Scholar]
  82. Jiang B. Yang H. Li M.L. Hou A.J. Han Q.B. Wang S.J. Li S.H. Sun H.D. Diterpenoids from Isodon a denantha. J. Nat. Prod. 2002 65 8 1111 1116 10.1021/np020084k 12193013
    [Google Scholar]
  83. Yin Q.Q. Liu C.X. Wu Y.L. Wu S.F. Wang Y. Zhang X. Hu X.J. Pu J.X. Lu Y. Zhou H.C. Wang H.L. Nie H. Sun H.D. Chen G.Q. Preventive and therapeutic effects of adenanthin on experimental autoimmune encephalomyelitis by inhibiting NF-κB signaling. J. Immunol. 2013 191 5 2115 2125 10.4049/jimmunol.1203546 23964105
    [Google Scholar]
  84. Hou J-K. Huang Y. He W. Yan Z-W. Fan L. Liu M-H. Xiao W-L. Sun H-D. Chen G-Q. Adenanthin targets peroxiredoxin I/II to kill hepatocellular carcinoma cells. Cell Death Dis. 2014 5 9 e1400 e1400 10.1038/cddis.2014.345 25188510
    [Google Scholar]
  85. dos Santos M.C. Tairum C.A. Cabrera V.I.M. Guimarães Cauz A.C. Ribeiro L.F. Toledo Junior J.C. Toyama M.H. Lago J.H.G. Brocchi M. Netto L.E.S. de Oliveira M.A. Adenanthin is an efficient inhibitor of peroxiredoxins from pathogens, inhibits bacterial growth, and potentiates antibiotic activities. Chem. Res. Toxicol. 2023 36 4 570 582 10.1021/acs.chemrestox.2c00049 35537067
    [Google Scholar]
  86. Tong L. Zha M.L. Hu J. Li H.Y. Kuai L. Li B. Dang Y. Zhao Q. Liao R. Lin G.Q. He Q.L. Adenanthin exhibits anti-inflammatory effects by covalently targeting the p65 subunit in the NF-κB signaling pathway. Eur. J. Med. Chem. 2024 280 116946 10.1016/j.ejmech.2024.116946 39383653
    [Google Scholar]
  87. Xiao Y. Chang Y. Liu Y.Y. Li T.T. Qu W.R. Yuan C. Chen L. Huang S. Zhou X.L. Biologically active franchetine-type diterpenoid alkaloids: Isolation, synthesis, anti-inflammatory, agalgesic activities, and molecular docking. Bioorg. Chem. 2024 153 107834 10.1016/j.bioorg.2024.107834 39332071
    [Google Scholar]
  88. Liang L.F. Kurtán T. Mándi A. Yao L.G. Li J. Zhang W. Guo Y.W. Unprecedented diterpenoids as a PTP1B inhibitor from the Hainan soft coral Sarcophyton trocheliophorum Marenzeller. Org. Lett. 2013 15 2 274 277 10.1021/ol303110d 23273218
    [Google Scholar]
  89. Ahmed A.F. Wen Z.H. Su J.H. Hsieh Y.T. Wu Y.C. Hu W.P. Sheu J.H. Oxygenated cembranoids from a Formosan soft coral Sinularia gibberosa. J. Nat. Prod. 2008 71 2 179 185 10.1021/np070356p 18198839
    [Google Scholar]
  90. Yang M. Li H. Zhang Q. Wu Q.H. Li G. Chen K.X. Guo Y.W. Tang W. Li X.W. Highly diverse cembranoids from the South China Sea soft coral Sinularia scabra as a new class of potential immunosuppressive agents. Bioorg. Med. Chem. 2019 27 15 3469 3476 10.1016/j.bmc.2019.06.030 31253536
    [Google Scholar]
  91. Zhao C. Xu J.J. Wang J. Li S.Y. Qiao W. Tang S.A. Five new cembrane diterpenoids from the South China Sea soft coral Sinularia flexibilis. Phytochem. Lett. 2018 25 180 183 10.1016/j.phytol.2018.04.012
    [Google Scholar]
  92. Zhang C. Li H. Liu J. Liu M. Zhang H. Chen K.X. Guo Y.W. Tang W. Li X.W. Diversity-oriented synthesis of cembranoid derivatives as potential anti-inflammatory agents. Bioorg. Chem. 2021 111 104887 10.1016/j.bioorg.2021.104887 33865055
    [Google Scholar]
  93. Shin J. Fenical W. Fuscosides A-D: Anti-inflammatory diterpenoid glycosides of new structural classes from the caribbean gorgonian Eunicea fusca. J. Org. Chem. 1991 56 9 3153 3158 10.1021/jo00009a042
    [Google Scholar]
  94. Marchbank D.H. Kerr R.G. Semisynthesis of fuscoside B analogues and eunicosides, and analysis of anti-inflammatory activity. Tetrahedron 2011 67 17 3053 3061 10.1016/j.tet.2011.03.006
    [Google Scholar]
  95. Kerr R.G. Brophy S. Derksen D.J. Synthesis and evaluation of anti-inflammatory activity of derivatives of the marine natural products fuscol and eunicol. Bioorg. Med. Chem. Lett. 2014 24 20 4804 4806 10.1016/j.bmcl.2014.09.008 25240256
    [Google Scholar]
  96. Sun M.L. Ao J.P. Wang Y.R. Huang Q. Li T.F. Li X.Y. Wang Y.X. Lappaconitine, a C18-diterpenoid alkaloid, exhibits antihypersensitivity in chronic pain through stimulation of spinal dynorphin A expression. Psychopharmacology 2018 235 9 2559 2571 10.1007/s00213‑018‑4948‑y 29926144
    [Google Scholar]
  97. Ahmad M. Ahmad W. Ahmad M. Zeeshan M. Norditerpenoid alkaloids from the roots of Aconitum heterophyllum wall with antibacterial activity. J. Enzyme Inhib. Med. Chem. 2008 23 6 1018 1022 10.1080/14756360701810140 18608773
    [Google Scholar]
  98. Li X. Li N. Sui Z. Bi K. Li Z. An investigation on the quantitative structure-activity relationships of the anti-inflammatory activity of diterpenoid alkaloids. Molecules 2017 22 3 363 10.3390/molecules22030363 28264454
    [Google Scholar]
  99. Pang L. Liu C.Y. Gong G.H. Quan Z.S. Synthesis, in vitro and in vivo biological evaluation of novel lappaconitine derivatives as potential anti-inflammatory agents. Acta Pharm. Sin. B 2020 10 4 628 645 10.1016/j.apsb.2019.09.002 32322467
    [Google Scholar]
  100. Park S.Y. Park J.H. Kim H.S. Lee C.Y. Lee H.J. Kang K.S. Kim C.E. Systems-level mechanisms of action of Panax ginseng: A network pharmacological approach. J. Ginseng Res. 2018 42 1 98 106 10.1016/j.jgr.2017.09.001 29348728
    [Google Scholar]
  101. Ren H. Sun J. Wang G. A, J.; Xie, H.; Zha, W.; Yan, B.; Sun, F.; Hao, H.; Gu, S.; Sheng, L.; Shao, F.; Shi, J.; Zhou, F. Sensitive determination of 20(S)-protopanaxadiol in rat plasma using HPLC–APCI-MS: Application of pharmacokinetic study in rats. J. Pharm. Biomed. Anal. 2008 48 5 1476 1480 10.1016/j.jpba.2008.09.045 19022601
    [Google Scholar]
  102. Ruan J. Sun F. Zhang Y. Zheng D. Xiang G. Zhao W. Zhang Y. Wang T. New 20(S)-protopanaxadiol type saponins from the leaves of Panax notoginseng and their potential anti-inflammatory activities. Steroids 2020 162 108696 10.1016/j.steroids.2020.108696 32649999
    [Google Scholar]
  103. Karra A.G. Konstantinou M. Tzortziou M. Tsialtas I. Kalousi F.D. Garagounis C. Hayes J.M. Psarra A.M.G. Potential dissociative glucocorticoid receptor activity for protopanaxadiol and protopanaxatriol. Int. J. Mol. Sci. 2018 20 1 94 10.3390/ijms20010094 30591629
    [Google Scholar]
  104. Wang W. Wu X. Wang L. Meng Q. Liu W. Stereoselective property of 20(S)-protopanaxadiol ocotillol type epimers affects its absorption and also the inhibition of P-glycoprotein. PLoS One 2014 9 6 98887 10.1371/journal.pone.0098887 24887182
    [Google Scholar]
  105. Yang G. Gao M. Sun Y. Wang C. Fang X. Gao H. Diao W. Yu H. Design, synthesis and anti-inflammatory activity of 3-amino acid derivatives of ocotillol-type sapogenins. Eur. J. Med. Chem. 2020 202 112507 10.1016/j.ejmech.2020.112507 32650181
    [Google Scholar]
  106. Heller L. Schwarz S. Perl V. Köwitsch A. Siewert B. Csuk R. Incorporation of a Michael acceptor enhances the antitumor activity of triterpenoic acids. Eur. J. Med. Chem. 2015 101 391 399 10.1016/j.ejmech.2015.07.004 26177446
    [Google Scholar]
  107. Yang G. Mi X. Wang Y. Li S. Yu L. huang, X.; Tan, S.; Yu, H. Fusion of Michael-acceptors enhances the anti-inflammatory activity of ginsenosides as potential modulators of the NLRP3 signaling pathway. Bioorg. Chem. 2023 134 106467 10.1016/j.bioorg.2023.106467 36933337
    [Google Scholar]
  108. Wang Y. Mi X. Du Y. Li S. Yu L. Gao M. Yang X. Song Z. Yu H. Yang G. Design, synthesis, and anti-inflammatory activities of 12-dehydropyxinol derivatives. Molecules 2023 28 3 1307 10.3390/molecules28031307 36770974
    [Google Scholar]
  109. Matsuda H. Morikawa T. Ando S. Oominami H. Murakami T. Kimura I. Yoshikawa M. Absolute stereostructures of polypodane- and octanordammarane-type triterpenes with nitric oxide production inhibitory activity from guggul-gum resins. Bioorg. Med. Chem. 2004 12 11 3037 3046 10.1016/j.bmc.2004.03.020 15142562
    [Google Scholar]
  110. Mallavadhani U.V. Chandrashekhar M. Shailaja K. Ramakrishna S. Design, synthesis, anti-inflammatory, cytotoxic and cell based studies of some novel side chain analogues of myrrhanones A & B isolated from the gum resin of Commiphora mukul. Bioorg. Chem. 2019 82 306 323 10.1016/j.bioorg.2018.10.039 30399528
    [Google Scholar]
  111. Kim W. Fan Y.Y. Smith R. Patil B. Jayaprakasha G.K. McMurray D.N. Chapkin R.S. Dietary curcumin and limonin suppress CD4+ T-cell proliferation and interleukin-2 production in mice. J. Nutr. 2009 139 5 1042 1048 10.3945/jn.108.102772 19321585
    [Google Scholar]
  112. Yang X.B. Qian P. Yang X.W. Liu J.X. Gong N.B. Lv Y. Limonoid constituents of Euodia rutaecarpa var. bodinieri and their inhibition on NO production in lipopolysaccharide-activated RAW264.7 macrophages. J. Asian Nat. Prod. Res. 2013 15 10 1130 1138 10.1080/10286020.2013.817392 23869424
    [Google Scholar]
  113. Liang H. Liu G. Fan Q. Nie Z. Xie S. Zhang R. Limonin, a novel AMPK activator, protects against LPS-induced acute lung injury. Int. Immunopharmacol. 2023 122 110678 10.1016/j.intimp.2023.110678 37481848
    [Google Scholar]
  114. Yang Y. Wang X. Zhu Q. Gong G. Luo D. Jiang A. Yang L. Xu Y. Synthesis and pharmacological evaluation of novel limonin derivatives as anti-inflammatory and analgesic agents with high water solubility. Bioorg. Med. Chem. Lett. 2014 24 7 1851 1855 10.1016/j.bmcl.2014.02.003 24569111
    [Google Scholar]
  115. Wang S.C. Yang Y. Liu J. Jiang A.D. Chu Z.X. Chen S.Y. Gong G.Q. He G.W. Xu Y.G. Zhu Q.H. Discovery of novel limonin derivatives as potent anti-inflammatory and analgesic agents. Chin. J. Nat. Med. 2018 16 3 231 240 10.1016/S1875‑5364(18)30052‑9 29576060
    [Google Scholar]
  116. Bian M. Gong G. Lei P. Du H. Bai C. Wei C. Quan Z. Ma Q. Design, synthesis, and in vitro and in vivo biological evaluation of limonin derivatives for anti-inflammation therapy. J. Agric. Food Chem. 2021 69 45 13487 13499 10.1021/acs.jafc.1c04989 34713702
    [Google Scholar]
  117. Liang C.Q. Luo R.H. Yan J.M. Li Y. Li X.N. Shi Y.M. Shang S.Z. Gao Z.H. Yang L.M. Zheng Y.T. Xiao W.L. Zhang H.B. Sun H.D. Structure and bioactivity of triterpenoids from the stems of Schisandra sphenanthera. Arch. Pharm. Res. 2014 37 2 168 174 10.1007/s12272‑013‑0133‑3 23703254
    [Google Scholar]
  118. Yang X.W. Li S.M. Wu L. Li Y.L. Feng L. Shen Y.H. Tian J.M. Tang J. Wang N. Liu Y. Zhang W.D. Abiesatrines A–J: Anti-inflammatory and antitumor triterpenoids from Abies georgei Orr. Org. Biomol. Chem. 2010 8 11 2609 2616 10.1039/c001885f 20372737
    [Google Scholar]
  119. Ballestar E. Li T. New insights into the epigenetics of inflammatory rheumatic diseases. Nat. Rev. Rheumatol. 2017 13 10 593 605 10.1038/nrrheum.2017.147 28905855
    [Google Scholar]
  120. Ni D.X. Wang Q. Li Y.M. Cui Y.M. Shen T.Z. Li X.L. Sun H.D. Zhang X.J. Zhang R. Xiao W.L. Synthesis of nigranoic acid and manwuweizic acid derivatives as HDAC inhibitors and anti-inflammatory agents. Bioorg. Chem. 2021 109 104728 10.1016/j.bioorg.2021.104728 33636436
    [Google Scholar]
  121. Parra-Delgado H. Ramírez-Apan T. Martínez-Vázquez M. Synthesis of argentatin A derivatives as growth inhibitors of human cancer cell lines in vitro. Bioorg. Med. Chem. Lett. 2005 15 4 1005 1008 10.1016/j.bmcl.2004.12.038 15686901
    [Google Scholar]
  122. Romero J.C. Martínez-Vázquez A. Herrera M.P. Martinez-Mayorga K. Parra-Delgado H. Pérez-Flores F.J. Martínez-Vázquez M. Synthesis, anti-inflammatory activity and modeling studies of cycloartane-type terpenes derivatives isolated from Parthenium argentatum. Bioorg. Med. Chem. 2014 22 24 6893 6898 10.1016/j.bmc.2014.10.028 25456078
    [Google Scholar]
  123. Debeleç-Bütüner B. Öztürk M.B. Tağ Ö. Akgün İ.H. Yetik-Anacak G. Bedir E. Korkmaz K.S. Cycloartane-type sapogenol derivatives inhibit NFκB activation as chemopreventive strategy for inflammation-induced prostate carcinogenesis. Steroids 2018 135 9 20 10.1016/j.steroids.2018.04.005 29678446
    [Google Scholar]
  124. liang, H.; Cheng, R.; Wang, J.; Xie, H.; Li, R.; Shimizu, K.; Zhang, C. Mogrol, an aglycone of mogrosides, attenuates ulcerative colitis by promoting AMPK activation. Phytomedicine 2021 81 153427 10.1016/j.phymed.2020.153427 33296813
    [Google Scholar]
  125. Liu B. Yang J. Hao J. Xie H. Shimizu K. Li R. Zhang C. Natural product mogrol attenuates bleomycin-induced pulmonary fibrosis development through promoting AMPK activation. J. Funct. Foods 2021 77 104280 10.1016/j.jff.2020.104280
    [Google Scholar]
  126. Song J.R. Li N. Wei Y.L. Lu F.L. Li D.P. Design and synthesis of mogrol derivatives modified on a ring with anti-inflammatory and anti-proliferative activities. Bioorg. Med. Chem. Lett. 2022 74 128924 10.1016/j.bmcl.2022.128924 35944853
    [Google Scholar]
  127. Wang H. Yang H. Tracey K.J. Extracellular role of HMGB1 in inflammation and sepsis. J. Intern. Med. 2004 255 3 320 331 10.1111/j.1365‑2796.2003.01302.x 14871456
    [Google Scholar]
  128. Kim S.W. Jin Y. Shin J.H. Kim I.D. Lee H.K. Park S. Han P.L. Lee J.K. Glycyrrhizic acid affords robust neuroprotection in the postischemic brain via anti-inflammatory effect by inhibiting HMGB1 phosphorylation and secretion. Neurobiol. Dis. 2012 46 1 147 156 10.1016/j.nbd.2011.12.056 22266336
    [Google Scholar]
  129. Zhu Y. Shen P. Wang J. Jiang X. Wang W. Raj R. Ge H. Wang W. Yu B. Zhang J. Microbial transformation of pentacyclic triterpenes for anti-inflammatory agents on the HMGB1 stimulated RAW 264.7 cells by Streptomyces olivaceus CICC 23628. Bioorg. Med. Chem. 2021 52 116494 10.1016/j.bmc.2021.116494 34800877
    [Google Scholar]
  130. Tailor N.K. Boon H.L. Sharma M. Synthesis and in vitro anticancer studies of novel C-2 arylidene congeners of lantadenes. Eur. J. Med. Chem. 2013 64 285 291 10.1016/j.ejmech.2013.04.009 23644211
    [Google Scholar]
  131. Sharma M. Sharma P.D. Bansal M.P. Lantadenes and their esters as potential antitumor agents. J. Nat. Prod. 2008 71 7 1222 1227 10.1021/np800167x 18553923
    [Google Scholar]
  132. Suthar S.K. Lee H.B. Sharma M. The synthesis of non-steroidal anti-inflammatory drug (NSAID)–lantadene prodrugs as novel lung adenocarcinoma inhibitors via the inhibition of cyclooxygenase-2 (COX-2), cyclin D1 and TNF-α-induced NF-κB activation. RSC Advances 2014 4 37 19283 10.1039/c4ra00280f
    [Google Scholar]
  133. Mahajan B. Taneja S.C. Sethi V.K. Dhar K.L. Two triterpenoids from Boswellia serrata gum resin. Phytochemistry 1995 39 2 453 455 10.1016/0031‑9422(95)99386‑3
    [Google Scholar]
  134. Sailer E.R. Subramanian L.R. Rall B. Hoernlein R.F. Ammon H.P.T. Safayhi H. Acetyl‐11‐keto‐β‐boswellic acid (AKBA): Structure requirements for binding and 5‐lipoxygenase inhibitory activity. Br. J. Pharmacol. 1996 117 4 615 618 10.1111/j.1476‑5381.1996.tb15235.x 8646405
    [Google Scholar]
  135. Shenvi S. Kiran K.R. Kumar K. Diwakar L. Reddy G.C. Synthesis and biological evaluation of boswellic acid-NSAID hybrid molecules as anti-inflammatory and anti-arthritic agents. Eur. J. Med. Chem. 2015 98 170 178 10.1016/j.ejmech.2015.05.001 26010018
    [Google Scholar]
  136. Han R. Highlight on the studies of anticancer drugs derived from plants in China. Stem Cells 1994 12 1 53 63 10.1002/stem.5530120110 8142920
    [Google Scholar]
  137. Meka B. Ravada S.R. Murali Krishna Kumar M. Purna Nagasree K. Golakoti T. Synthesis of new analogs of AKBA and evaluation of their anti-inflammatory activities. Bioorg. Med. Chem. 2017 25 4 1374 1388 10.1016/j.bmc.2016.12.045 28110820
    [Google Scholar]
  138. Pollier J. Goossens A. Oleanolic acid. Phytochemistry 2012 77 10 15 10.1016/j.phytochem.2011.12.022 22377690
    [Google Scholar]
  139. Lin C. Wen X. Sun H. Oleanolic acid derivatives for pharmaceutical use: A patent review. Expert Opin. Ther. Pat. 2016 26 6 643 655 10.1080/13543776.2016.1182988
    [Google Scholar]
  140. Lee W. Yang E.J. Ku S.K. Song K.S. Bae J.S. Anti-inflammatory effects of oleanolic acid on LPS-induced inflammation in vitro and in vivo. Inflammation 2013 36 1 94 102 10.1007/s10753‑012‑9523‑9 22875543
    [Google Scholar]
  141. Wang J.L. Ren C.H. Feng J. Ou C.H. Liu L. Oleanolic acid inhibits mouse spinal cord injury through suppressing inflammation and apoptosis via the blockage of p38 and JNK MAPKs. Biomed. Pharmacother. 2020 123 109752 10.1016/j.biopha.2019.109752 31924596
    [Google Scholar]
  142. Yang N. Tang Q. Qin W. Li Z. Wang D. Zhang W. Cao X. Lu Y. Ge X. Sun H. Shen P. Treatment of obesity-related inflammation with a novel synthetic pentacyclic oleanane triterpenoids via modulation of macrophage polarization. EBioMedicine 2019 45 473 486 10.1016/j.ebiom.2019.06.053 31285187
    [Google Scholar]
  143. Honda T. Rounds B.V. Bore L. Finlay H.J. Favaloro F.G. Suh N. Wang Y. Sporn M.B. Gribble G.W. Synthetic oleanane and ursane triterpenoids with modified rings A and C: A series of highly active inhibitors of nitric oxide production in mouse macrophages. J. Med. Chem. 2000 43 22 4233 4246 10.1021/jm0002230 11063620
    [Google Scholar]
  144. Liby K.T. Sporn M.B. Synthetic oleanane triterpenoids: Multifunctional drugs with a broad range of applications for prevention and treatment of chronic disease. Pharmacol. Rev. 2012 64 4 972 1003 10.1124/pr.111.004846 22966038
    [Google Scholar]
  145. Onyango E.O. Fu L. Cao M. Liby K.T. Sporn M.B. Gribble G.W. Synthesis and biological evaluation of amino acid methyl ester conjugates of 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid against the production of nitric oxide (NO). Bioorg. Med. Chem. Lett. 2014 24 2 532 534 10.1016/j.bmcl.2013.12.034 24388806
    [Google Scholar]
  146. Ikeda T. Masuda T. Takayama M. Adachi H. Haino T. Solvent-induced emission of organogels based on tris(phenylisoxazolyl)benzene. Org. Biomol. Chem. 2016 14 1 36 39 10.1039/C5OB01898F 26537424
    [Google Scholar]
  147. Nelson A.T. Camelio A.M. Claussen K.R. Cho J. Tremmel L. DiGiovanni J. Siegel D. Synthesis of oxygenated oleanolic and ursolic acid derivatives with anti-inflammatory properties. Bioorg. Med. Chem. Lett. 2015 25 19 4342 4346 10.1016/j.bmcl.2015.07.029 26259803
    [Google Scholar]
  148. Upadhyay K.D. Dodia N.M. Khunt R.C. Chaniara R.S. Shah A.K. Synthesis and biological screening of Pyrano[3,2-c]quinoline analogues as anti-inflammatory and anticancer agents. ACS Med. Chem. Lett. 2018 9 3 283 288 10.1021/acsmedchemlett.7b00545 29541375
    [Google Scholar]
  149. Walton I.M. Cox J.M. Benson C.A. Patel D.D.G. Chen Y-S. Benedict J.B. The role of atropisomers on the photo-reactivity and fatigue of diarylethene-based metal–organic frameworks. New J. Chem. 2016 40 1 101 106 10.1039/C5NJ01718A
    [Google Scholar]
  150. Krajka-Kuźniak V. Bednarczyk-Cwynar B. Paluszczak J. Szaefer H. Narożna M. Zaprutko L. Baer-Dubowska W. Oleanolic acid oxime derivatives and their conjugates with aspirin modulate the NF-κB-mediated transcription in HepG2 hepatoma cells. Bioorg. Chem. 2019 93 103326 10.1016/j.bioorg.2019.103326 31586705
    [Google Scholar]
  151. Wang X. Liu R. Zhang W. Zhang X. Liao N. Wang Z. Li W. Qin X. Hai C. Oleanolic acid improves hepatic insulin resistance via antioxidant, hypolipidemic and anti-inflammatory effects. Mol. Cell. Endocrinol. 2013 376 1-2 70 80 10.1016/j.mce.2013.06.014 23791844
    [Google Scholar]
  152. Liu L. Li H. Hu K. Xu Q. Wen X. Cheng K. Chen C. Yuan H. Dai L. Sun H. Synthesis and anti-inflammatory activity of saponin derivatives of δ-oleanolic acid. Eur. J. Med. Chem. 2021 209 112932 10.1016/j.ejmech.2020.112932 33131725
    [Google Scholar]
  153. Jin J. He H. Zhang X. Wu R. Gan L. Li D. Lu Y. Wu P. Wong W.L. Zhang K. The in vitro and in vivo study of oleanolic acid indole derivatives as novel anti-inflammatory agents: Synthesis, biological evaluation, and mechanistic analysis. Bioorg. Chem. 2021 113 104981 10.1016/j.bioorg.2021.104981 34020279
    [Google Scholar]
  154. Hassan Mir R. Godavari G. Siddiqui N.A. Ahmad B. Mothana R. Ullah R. Almarfadi O. Jachak S. Masoodi M. Design, synthesis, molecular modelling, and biological evaluation of oleanolic acid-arylidene derivatives as potential anti-inflammatory agents. Drug Des. Devel. Ther. 2021 15 385 397 10.2147/DDDT.S291784 33574657
    [Google Scholar]
  155. Asl M.N. Hosseinzadeh H. Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytother. Res. 2008 22 6 709 724 10.1002/ptr.2362 18446848
    [Google Scholar]
  156. Li B. Yang Y. Chen L. Chen S. Zhang J. Tang W. 18α-Glycyrrhetinic acid monoglucuronide as an anti-inflammatory agent through suppression of the NF-κB and MAPK signaling pathway. MedChemComm 2017 8 7 1498 1504 10.1039/C7MD00210F 30108861
    [Google Scholar]
  157. Kao T.C. Shyu M.H. Yen G.C. Glycyrrhizic acid and 18β-glycyrrhetinic acid inhibit inflammation via PI3K/Akt/GSK3β signaling and glucocorticoid receptor activation. J. Agric. Food Chem. 2010 58 15 8623 8629 10.1021/jf101841r 20681651
    [Google Scholar]
  158. You R. Long W. Lai Z. Sha L. Wu K. Yu X. Lai Y. Ji H. Huang Z. Zhang Y. Discovery of a potential anti-inflammatory agent: 3-Oxo-29-noroleana-1,9(11),12-trien-2,20-dicarbonitrile. J. Med. Chem. 2013 56 5 1984 1995 10.1021/jm301652t 23373965
    [Google Scholar]
  159. Li B. Cai S. Yang Y.A. Chen S.C. Chen R. Shi J.B. Liu X.H. Tang W.J. Novel unsaturated glycyrrhetic acids derivatives: Design, synthesis and anti-inflammatory activity. Eur. J. Med. Chem. 2017 139 337 348 10.1016/j.ejmech.2017.08.002 28803048
    [Google Scholar]
  160. Yang Y. Zhu Q. Zhong Y. Cui X. Jiang Z. Wu P. Zheng X. Zhang K. Zhao S. Synthesis, anti-microbial and anti-inflammatory activities of 18β-glycyrrhetinic acid derivatives. Bioorg. Chem. 2020 101 103985 10.1016/j.bioorg.2020.103985 32544739
    [Google Scholar]
  161. Bian M. Zhen D. Shen Q.K. Du H.H. Ma Q.Q. Quan Z.S. Structurally modified glycyrrhetinic acid derivatives as anti-inflammatory agents. Bioorg. Chem. 2021 107 104598 10.1016/j.bioorg.2020.104598 33450540
    [Google Scholar]
  162. Wang H. Zuo J. Zha L. Jiang X. Wu C. Yang Y.A. Tang W. Shi T. Design and synthesis of novel glycyrrhetin ureas as anti-inflammatory agents for the treatment of acute kidney injury. Bioorg. Chem. 2021 110 104755 10.1016/j.bioorg.2021.104755 33652342
    [Google Scholar]
  163. Zhang Q. Wang Y. Wang Z. Mohammed E.A.H. Zhao Q. He D. Wang Z. Synthesis and anti-inflammatory activities of glycyrrhetinic acid derivatives containing disulfide bond. Bioorg. Chem. 2022 119 105542 10.1016/j.bioorg.2021.105542 34902645
    [Google Scholar]
  164. Tu B. Liang J. Ou Y. Zhang X. Zheng W. Wu R. Gan L. Li D. Lu Y. Wu J. David Hong W. Zhang K. Wu P. Jin J. Wong W.L. Novel 18β-glycyrrhetinic acid derivatives as a Two-in-One agent with potent antimicrobial and anti-inflammatory activity. Bioorg. Chem. 2022 122 105714 10.1016/j.bioorg.2022.105714 35276603
    [Google Scholar]
  165. Wang B. Liu S. Huang W. Ma M. Chen X. Zeng W. Liang K. Wang H. Bi Y. Li X. Design, synthesis, and biological evaluation of hederagenin derivatives with improved aqueous solubility and tumor resistance reversal activity. Eur. J. Med. Chem. 2021 211 113107 10.1016/j.ejmech.2020.113107 33360797
    [Google Scholar]
  166. Kim G.J. Song D. Yoo H. Chung K.H. Lee K. An J. Hederagenin supplementation alleviates the pro-inflammatory and apoptotic response to alcohol in rats. Nutrients 2017 9 1 41 10.3390/nu9010041 28067819
    [Google Scholar]
  167. Li Y. Dong J. Shang Y. Zhao Q. Li P. Wu B. Anti-inflammatory effects of hederagenin on diabetic cardiomyopathy via inhibiting NF-κB and Smads signaling pathways in a type-2 diabetic mice model. RSC Advances 2019 9 45 26238 26247 10.1039/C9RA02043H 35531007
    [Google Scholar]
  168. Neha K. Wakode S. Contemporary advances of cyclic molecules proposed for inflammation. Eur. J. Med. Chem. 2021 221 113493 10.1016/j.ejmech.2021.113493 34029774
    [Google Scholar]
  169. Yu T. Cheng H. Li X. Huang W. Li H. Gao X. Zhao J. Zhang X. Gu X. Bi Y. Zhang L. Design and synthesis of hederagenin derivatives modulating STING/NF-κB signaling for the relief of acute liver injury in septic mice. Eur. J. Med. Chem. 2023 245 Pt 1 114911 10.1016/j.ejmech.2022.114911 36379106
    [Google Scholar]
  170. Duong T.H. Trung N.T. Phan C.T.D. Nguyen V.K. Musa V. Ruksilp T. Nguyen N.H. Nguyen H.H. Sichaem J. Manilkzapotane, a novel dimeric alkylresorcinol derivative from the stem bark of Manilkara zapota. J. Asian Nat. Prod. Res. 2021 23 11 1093 1099 10.1080/10286020.2020.1844189 33258704
    [Google Scholar]
  171. Li H. Xie W. Gao X. Geng Z. Gao J. Ma G. Liu X. Han S. Chen Y. Wen X. Bi Y. Zhang L. Design and synthesis of novel hederagonic acid analogs as potent anti-inflammatory compounds capable of protecting against LPS-induced acute lung injury. Eur. J. Med. Chem. 2024 263 115941 10.1016/j.ejmech.2023.115941 38000214
    [Google Scholar]
  172. Márquez Martín A. De La Puerta Vázquez R. Fernández-Arche A. Ruiz-Gutiérrez V. Supressive effect of maslinic acid from pomace olive oil on oxidative stress and cytokine production in stimulated murine macrophages. Free Radic. Res. 2006 40 3 295 302 10.1080/10715760500467935 16484046
    [Google Scholar]
  173. Chouaïb K. Delemasure S. Dutartre P. Jannet H. B. Microwave-assisted synthesis, anti-inflammatory and antiproliferative activities of new maslinic acid derivatives bearing 1,5- and 1,4-disubstituted triazoles. J. Enzym Inhib Med. Chem. 2016 31 sup2 130 147 10.1080/14756366.2016.1193733
    [Google Scholar]
  174. Chen X. Wan Y. Zhou T. Li J. Wei Y. Ursolic acid attenuates lipopolysaccharide-induced acute lung injury in a mouse model. Immunotherapy 2013 5 1 39 47 10.2217/imt.12.144 23256797
    [Google Scholar]
  175. Shanmugam M.K. Dai X. Kumar A.P. Tan B.K.H. Sethi G. Bishayee A. Ursolic acid in cancer prevention and treatment: Molecular targets, pharmacokinetics and clinical studies. Biochem. Pharmacol. 2013 85 11 1579 1587 10.1016/j.bcp.2013.03.006 23499879
    [Google Scholar]
  176. Wei Z.Y. Chi K.Q. Wang K.S. Wu J. Liu L.P. Piao H.R. Design, synthesis, evaluation, and molecular docking of ursolic acid derivatives containing a nitrogen heterocycle as anti-inflammatory agents. Bioorg. Med. Chem. Lett. 2018 28 10 1797 1803 10.1016/j.bmcl.2018.04.021 29678461
    [Google Scholar]
  177. Zhang T.Y. Li C.S. Li P. Bai X.Q. Guo S.Y. Jin Y. Piao S.J. Synthesis and evaluation of ursolic acid-based 1,2,4-triazolo[1,5-a]pyrimidines derivatives as anti-inflammatory agents. Mol. Divers. 2022 26 1 27 38 10.1007/s11030‑020‑10154‑7 33200293
    [Google Scholar]
  178. Zhang T.Y. Li C.S. Cao L.T. Bai X.Q. Zhao D.H. Sun S.M. New ursolic acid derivatives bearing 1,2,3-triazole moieties: Design, synthesis and anti-inflammatory activity in vitro and in vivo. Mol. Divers. 2022 26 2 1129 1139 10.1007/s11030‑021‑10236‑0 34080112
    [Google Scholar]
  179. Radtke O.A. Kiderlen A.F. Kayser O. Kolodziej H. Gene expression profiles of inducible nitric oxide synthase and cytokines in Leishmania major-infected macrophage-like RAW 264.7 cells treated with gallic acid. Planta Med. 2004 70 10 924 928 10.1055/s‑2004‑832618 15490320
    [Google Scholar]
  180. Gonzaga D.T.G. Ferreira L.B.G. Moreira Maramaldo Costa T.E. von Ranke N.L. Anastácio Furtado Pacheco P. Sposito Simões A.P. Arruda J.C. Dantas L.P. de Freitas H.R. de Melo Reis R.A. Penido C. Bello M.L. Castro H.C. Rodrigues C.R. Ferreira V.F. Faria R.X. da Silva F.C. 1-Aryl-1 H - and 2-aryl-2 H -1,2,3-triazole derivatives blockade P2X7 receptor in vitro and inflammatory response in vivo. Eur. J. Med. Chem. 2017 139 698 717 10.1016/j.ejmech.2017.08.034 28858765
    [Google Scholar]
  181. Qi Z. Xie P. Wang Z. Zhou H. Tao R. Popov S.A. Yang G. Shults E.E. Wang C. Synthesis of novel ursolic acid-gallate hybrids via 1,2,3-triazole linkage and its anti-oxidant and anti-inflammatory activity study. Arab. J. Chem. 2024 17 5 105762 10.1016/j.arabjc.2024.105762
    [Google Scholar]
  182. Sylla B. Lavoie S. Legault J. Gauthier C. Pichette A. Synthesis, cytotoxicity and anti-inflammatory activity of rhamnose-containing ursolic and betulinic acid saponins. RSC Advances 2019 9 68 39743 39757 10.1039/C9RA09389C 35541393
    [Google Scholar]
  183. Ríos J.L. Effects of triterpenes on the immune system. J. Ethnopharmacol. 2010 128 1 1 14 10.1016/j.jep.2009.12.045 20079412
    [Google Scholar]
  184. Hsu C.L. Fang S.C. Huang H.W. Yen G.C. Anti-inflammatory effects of triterpenes and steroid compounds isolated from the stem bark of Hiptage benghalensis. J. Funct. Foods 2015 12 420 427 10.1016/j.jff.2014.12.009
    [Google Scholar]
  185. Kahnt M. Fischer Née Heller L. Al-Harrasi A. Csuk R. Ethylenediamine derived carboxamides of betulinic and ursolic acid as potential cytotoxic agents. Molecules 2018 23 10 2558 10.3390/molecules23102558 30297604
    [Google Scholar]
  186. Popov S.A. Semenova M.D. Baev D.S. Sorokina I.V. Zhukova N.A. Frolova T.S. Tolstikova T.G. Shults E.E. Turks M. Lupane-type conjugates with aminoacids, 1,3,4- oxadiazole and 1,2,5-oxadiazole-2-oxide derivatives: Synthesis, anti-inflammatory activity and in silico evaluation of target affinity. Steroids 2019 150 108443 10.1016/j.steroids.2019.108443 31295462
    [Google Scholar]
  187. Khlebnicova T.S. Piven Y.A. Lakhvich F.A. Sorokina I.V. Frolova T.S. Baev D.S. Tolstikova T.G. Betulinic acid-azaprostanoid hybrids: Synthesis and pharmacological evaluation as anti-inflammatory agents. Antiinflamm. Antiallergy Agents Med. Chem. 2020 19 3 254 267 10.2174/1871523018666190426152049 33001006
    [Google Scholar]
  188. Luo Z. He H. Tang T. Zhou J. Li H. Seeram N.P. Li D. Zhang K. Ma H. Wu P. Synthesis and biological evaluations of betulinic acid derivatives with inhibitory activity on hyaluronidase and anti-inflammatory effects against hyaluronic acid fragment induced inflammation. Front Chem. 2022 10 892554 10.3389/fchem.2022.892554 35601554
    [Google Scholar]
  189. Lipeeva A.V. Dolgikh M.P. Tolstikova T.G. Shults E.E. A study of plant Coumarins. 18. Conjugates of coumarins with lupane Triterpenoids and 1,2,3-Triazoles: Synthesis and anti-inflammatory activity. Russ. J. Bioorganic Chem. 2020 46 2 125 132 10.1134/S1068162020010161
    [Google Scholar]
  190. Semenova M.D. Popov S.A. Sorokina I.V. Meshkova Y.V. Baev D.S. Tolstikova T.G. Shults E.E. Conjugates of lupane triterpenoids with arylpyrimidines: Synthesis and anti-inflammatory activity. Steroids 2022 184 109042 10.1016/j.steroids.2022.109042 35580647
    [Google Scholar]
  191. Fernández A. Álvarez A. García M.D. Sáenz M.T. Anti-inflammatory effect of Pimenta racemosa var. ozua and isolation of the triterpene lupeol. Farmaco 2001 56 4 335 338 10.1016/S0014‑827X(01)01080‑1 11421264
    [Google Scholar]
  192. Bhandari P. Patel N.K. Bhutani K.K. Synthesis of new heterocyclic lupeol derivatives as nitric oxide and pro-inflammatory cytokine inhibitors. Bioorg. Med. Chem. Lett. 2014 24 15 3596 3599 10.1016/j.bmcl.2014.05.032 24909081
    [Google Scholar]
  193. Bindu S. Mazumder S. Bandyopadhyay U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochem. Pharmacol. 2020 180 114147 10.1016/j.bcp.2020.114147 32653589
    [Google Scholar]
  194. Pofi R. Caratti G. Ray D.W. Tomlinson J.W. Treating the side effects of exogenous glucocorticoids; Can we separate the good from the bad? Endocr. Rev. 2023 44 6 975 1011 10.1210/endrev/bnad016 37253115
    [Google Scholar]
/content/journals/mrmc/10.2174/0113895575414767251013071926
Loading
Recent Advancements in Pentacyclic and Other Terpenoid Derivatives as Anti-inflammatory Agents
Bentham Science Publishers ; https://doi.org/10.2174/0113895575414767251013071926
/content/journals/mrmc/10.2174/0113895575414767251013071926
/content/journals/mrmc/10.2174/0113895575414767251013071926
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: inflammation ; Natural products ; mechanism of action ; structural modification ; anti-inflammatory activity ; terpenoids

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test