Abstract
Inflammation assists in the healing process as a part of the natural defensive mechanism. Apart from the healing process, inflammatory mechanisms contribute to the progression and development of a range of ailments, including asthma, rheumatoid arthritis, cancer, neurodegenerative diseases, and so on. A new anti-inflammatory medication that is safe, potent, non-toxic, or less toxic is now required as the existing anti-inflammatory and non-steroidal drugs are associated with various side effects. In this context, we have reviewed the genus Ilex for traditional uses related to inflammation and anti-inflammatory properties (in vitro and in vivo) by utilizing databases like PubMed, Google Scholar, and Science Direct. According to ethnomedicinal information, these plants have been used to treat various inflammatory conditions. A total of 12 species were found with anti-inflammatory potential, where some studies were conducted using crude extracts and others with pure compounds. Many chemical compounds have been reported from the Ilex species; however, the bioactive composition explored for anti-inflammatory effects include rotundarpene, triterpenoid saponins, chlorogenic acid, ursolic acid, ilexgenin A, isoquercetin, kaempferol, ilexchinenosides J-Q and salicifoneoliganol. The mechanistic insights into how Ilex species deal with inflammatory stimuli in the mitogen-activated protein kinase, nuclear factor-κB, PI3K/Akt/mTOR, Janus kinase-signal transducer and activator of transcription, and arachidonic acid pathways have also been highlighted. The toxicity profile of studies has also been discussed to assess safety. These plants can be developed as drug-developing candidates after detailed follow-up studies.
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Abbreviations
- 3,5-DCQA:
-
3,5-Dicaffeoylquinic acid
- 5-LOX:
-
5-Lipoxygenase
- AA:
-
Arachidonic acid
- AP-1:
-
Activator protein 1
- CAT:
-
Catalase
- CLP:
-
Cecal ligation and puncture
- COX-1:
-
Cyclooxygenase-1
- COX-2:
-
Cyclooxygenase-2
- CR:
-
Cytokine receptor
- DEX:
-
Dexamethasone
- ERK:
-
Extracellular signal-regulated kinase
- Fmlf:
-
N-formyl-L-Met-L-Leu-L-Phe
- GSH:
-
Glutathione
- GSH-Px:
-
Glutathione peroxidase
- GSSH:
-
Oxidized glutathione
- HN:
-
Human neutrophils
- iNOS:
-
Nitric oxide synthase
- Iκκcomplex:
-
I kappa B kinase 1 and I kappa B kinase 2
- JAK:
-
Janus kinase
- LPS:
-
Lipopolysaccharides
- MAPK:
-
Mitogen-activated protein kinase
- MMP:
-
Matrix metalloproteinases
- MMP-9:
-
Matrix metalloprotease-9
- MPO:
-
Myeloperoxidase
- mTOR:
-
Mammalian target of rapamycin
- MyD88:
-
Myeloid differentiation primary response gene 88
- NF-κB:
-
Nuclear factor kappa B
- NO:
-
Nitric oxide
- NSAIDs:
-
Non-steroidal anti-inflammatory drugs
- P and T:
-
Prostaglandins and thromboxanes
- p-Akt:
-
Phosphorylated akt
- PAMPs:
-
Pathogen-associated molecule patterns
- p-ERK ½:
-
Phosphorylated ERK-1/2
- PGE2 :
-
Prostaglandin-2
- PI3K:
-
Phosphatidylinositol-3-kinase
- p-IκBα:
-
Phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
- p-JAK:
-
Phosphorylated janus kinase
- PLA2:
-
Phospholipase A2
- PRRs:
-
Pattern recognition receptors
- p-SFKs:
-
Phosphorylated SRC family kinase
- p-STAT:
-
Phosphorylated signal transducer and activator of transcription
- ROS:
-
Reactive oxygen species
- SAIDs:
-
Steroids
- SHK:
-
Stimulated human keratinocytes
- SOD:
-
Superoxide dismutase
- STAT:
-
Signal transducer and activator of transcription
- STCSEI:
-
Short-term cigarette smoke exposure induced
- TBARS:
-
Thiobarbituric acid reactive substances
- TRIF:
-
TIR-domain-containing adapter-inducing interferon-β
- TLR:
-
Toll-like receptors
- TNF-α:
-
Tumour necrosis factor-alpha
- TRIF:
-
TIR-domain-containing adapter-inducing interferon-β
- HPLC:
-
High-performance liquid chromatography
- NMR:
-
Nuclear magnetic resonance
- MDCK:
-
Madin-Darby canine kidney
- OA:
-
Osteoarthritis
- NLRP3:
-
Human NACHT, LRR, and PYD domain-containing protein 3
- nCGA:
-
Neochlorogenic acid
- MTT:
-
3-(4, 5-Dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide
- AMPK:
-
AMP-activated protein kinase
- Nrf2:
-
Nuclear factor erythroid 2-related factor
- IL-1β:
-
Interleukin-1β
- IL-6:
-
Interleukin-6
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Acknowledgements
The authors (Acharya Balkrishna, Priyanka Rai, Rashmi Verma, Akansha Rohela, Ashwani Kumar, and Vedpriya Arya) are grateful to Revered Swami Ramdev, Patanjali Yogpeeth, Haridwar for providing all the necessary facilities. Further, the authors thank the Ministry of AYUSH under Grant-in-Aid for establishing the Centre of Excellence of Renovation and Upgradation of Patanjali Ayurveda Hospital, Haridwar, India.
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Balkrishna, A., Rai, P., Verma, R. et al. Mechanistic insight into anti-inflammatory potential, phytochemistry and ethnomedicinal status of Ilex species: a review. Phytochem Rev (2024). https://doi.org/10.1007/s11101-024-09968-2
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DOI: https://doi.org/10.1007/s11101-024-09968-2