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Labdane diterpenoids as potential anti-inflammatory agents.

Quy T N Tran1, W S Fred Wong2, Christina L L Chai1

  • 1Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4A, Level 3, 18 Science Drive 4, 117543, Singapore.

Pharmacological Research
|July 29, 2017
PubMed
Summary

Labdane diterpenoids show promise as anti-inflammatory agents by inhibiting nuclear factor-κB (NF-κB) and modulating nitric oxide (NO) and arachidonic acid (AA) pathways. This review covers natural compounds discovered between 1981-2016 with these activities.

Keywords:
Arachidonic acidInflammationLabdane diterpenoidMichael acceptorNF-κBNitric oxide

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Area of Science:

  • Natural Product Chemistry
  • Pharmacology
  • Medicinal Chemistry

Background:

  • Inflammation is a complex biological process crucial for host defense, but its dysregulation underlies many diseases.
  • Developing novel anti-inflammatory agents is challenging due to the intricate nature of inflammatory pathways.
  • Labdane diterpenoids have emerged as a significant class of compounds with potential therapeutic applications in inflammatory conditions.

Purpose of the Study:

  • To provide a comprehensive review of naturally occurring labdane diterpenes with anti-inflammatory properties.
  • To summarize labdane diterpenoids discovered between 1981 and 2016 that modulate nuclear factor-κB (NF-κB) activity, nitric oxide (NO) production, or arachidonic acid (AA) metabolism.
  • To explore the role of the Michael acceptor moiety in the anti-inflammatory activity of these compounds.

Main Methods:

  • Literature review of scientific publications from 1981 to 2016.
  • Identification and categorization of labdane diterpenoids with reported anti-inflammatory effects.
  • Analysis of mechanisms of action, including NF-κB inhibition, NO modulation, and AA metabolism.
  • Discussion of structure-activity relationships (SAR) and available clinical data.

Main Results:

  • Over 100 labdane diterpenoids exhibiting anti-inflammatory activities were identified.
  • Key mechanisms of action include inhibition of NF-κB signaling, reduction of NO production, and modulation of AA metabolism.
  • The presence of a Michael acceptor group was frequently correlated with NF-κB inhibitory activity.

Conclusions:

  • Labdane diterpenoids represent a valuable source of novel anti-inflammatory compounds.
  • Understanding their mechanisms of action and SAR can guide the development of more effective anti-inflammatory drugs.
  • Further research, including clinical studies, is warranted to fully exploit the therapeutic potential of these natural products.