Abstract
Curcumol (Cur), a guaiane-type sesquiterpenoid hemiketal, is an important and representative bioactive component extracted from the essential oil of the rhizomes of Curcumae rhizoma which is also known as “Ezhu” in traditional Chinese medicine. Recently, Cur has received considerable attention from the research community due to its favorable pharmacological activities, including anti-cancer, hepatoprotective, anti-inflammatory, anti-viral, anti-convulsant, and other activities, and has also exerted therapeutic effect on various cancers, liver diseases, inflammatory diseases, and infectious diseases. Pharmacokinetic studies have shown that Cur is rapidly distributed in almost all organs of rats after intragastric administration with high concentrations in the small intestine and colon. Several studies focusing on structure–activity relationship (SAR) of Cur have shown that some Cur derivatives, chemically modified at C-8 or C-14, exhibited more potent anti-cancer activity and lower toxicity than Cur itself. This review aims to comprehensively summarize the latest advances in the pharmacological and pharmacokinetic properties of Cur in the last decade with a focus on its anti-cancer and hepatoprotective potentials, as well as the research progress in drug delivery system and potential applications of Cur to date, to provide researchers with the latest information, to highlighted the limitations of relevant research at the current stage and the aspects that should be addressed in future research. Our results indicate that Cur and its derivatives could serve as potential novel agents for the treatment of a variety of diseases, particularly cancer and liver diseases.
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Abbreviations
- ALT:
-
Alanine aminotransferase
- AST:
-
Aspartate transaminase
- ALP:
-
Alkaline phosphatase
- ACAT2:
-
Acetyl-CoA acetyltransferase: cytosolic
- ATF4:
-
Activating transcription factor 4
- ACE:
-
Acetaldehyde
- ACSL4:
-
Acyl-CoA synthetase 4
- ABCB1:
-
P-glycoprotein: P-gp
- ABCC1:
-
Multidrug-resistance protein 1
- ABCG2:
-
Mitoxantrone-resistance protein
- Bcl-2:
-
B-cell lymphoma-2
- Bax:
-
BCL2-associated X
- BIP:
-
Immunoglobulin heavy chain binding protein
- COX2:
-
Cyclooxygenase 2
- c-MET:
-
Cellular mesenchymal-epithelial transition factor
- CDK2:
-
Cyclin-dependent kinases
- COL1A1:
-
Collagen type 1 alpha 1 chain
- Cdh1:
-
Cadherin-1
- CXCR4:
-
C-X-C motif chemokine receptor 4
- DR5:
-
Death receptor 5
- EGFR:
-
Epidermal growth factor receptor
- ERK:
-
Extracellular signal-regulated kinase
- ECAR:
-
Extracellular acidification rate
- FTH1:
-
Ferritin heavy chain 1
- GSH:
-
Glutathione
- GOD:
-
Glucose oxidase
- GSDMD:
-
Gasdermin D
- GPX4:
-
Glutathione peroxidase 4
- GRP78:
-
Glucose regulated protein 78
- γ-GT:
-
γ-Glutamyl transferase
- HFD:
-
High fat diet
- HDL-C:
-
High-density lipoprotein cholesterol
- Hyp:
-
Hydroxyproline
- H3 Ser10:
-
Histone H3 Ser10
- HA:
-
Hyaluronic acid
- HK2:
-
Hexokinase 2
- HSP90:
-
Heat shock protein 90
- H3K27me3:
-
Trimethylation of histone 3 on lysine 27
- H3K9me3:
-
Trimethylation of histone 3 on lysine 9
- ICAM-1:
-
Intercellular cell adhesion molecule-1
- IV-C:
-
Collagen IV
- KLF5:
-
Krüppel-like factor 5
- α-KG:
-
α-Ketoglutaric acid
- LA:
-
Lactic acid
- LATS1:
-
Large tumor suppressor kinase 1
- LDL-C:
-
Low-density lipoprotein cholesterol
- MST‑1:
-
Mammalian STE20‑like protein kinase
- MST:
-
Microscale thermophoresis
- Mcl-1:
-
Myeloid cell leukemia 1
- MDA:
-
Malondialdehyde
- mTOR:
-
Mammalian target of rapamycin
- NRAS:
-
GTPase NRas
- NF-κB:
-
Nuclear factor kappa-B
- NICD:
-
Intracellular domain of Notch
- NCOA4:
-
Nuclear receptor coactivator 4
- POSTN:
-
Periostin
- PPARγ:
-
Peroxisome proliferator activated receptor-γ
- PDGF-βR:
-
Platelet-derived growth factor β receptor
- PINP:
-
N-terminal pro-peptide for Type I collagen
- PIIINP:
-
N-terminal pro-peptide for Type III collagen
- PHD:
-
Prolyl-hydroxylase
- PCIII:
-
Procollagen type III
- PC-III:
-
Type III procollagen
- PROX1:
-
Prospero-related homeobox 1
- PFK1:
-
Phosphofructokinase 1
- PKM2:
-
Pyruvate Kinas type M2
- PCNA:
-
Proliferating cell nuclear antigen
- p-Akt:
-
Phosphorylated Akt
- p-H3 Ser10:
-
Phorylation of histone H3 Ser10
- PDI:
-
Proteindisulfide isomerase
- PTEN:
-
Phosphatase and tensin homolog deleted on chromosome ten
- PDK1:
-
Pyruvate dehydrogenase kinase 1
- RVSP:
-
Right ventricular systolic pressure
- RVHI:
-
Right ventricular hypertrophy index
- RIP:
-
Receptor-interacting protein kinase
- RhoA:
-
Ras homolog gene family A
- ROCK2:
-
Rho-associated kinase-2
- RELA:
-
RELA protooncogene: also known as p65
- Sirt1:
-
Sirtuin 1
- SOD:
-
Superoxide dismutase
- α-SMA:
-
α-Smooth muscle actin
- SLC7A11:
-
Light chain subunit
- Skp2:
-
S-phase kinase associated protein 2
- SDF-1α:
-
Stromal cell-derived factor-1
- SP1:
-
Specificity protein 1
- TGF-β1:
-
Transforming growth factor β1
- TGF-βRI:
-
Transforming growth factor-β receptor I
- TGF-βRII:
-
Transforming growth factor-β receptor II
- TIMP1/2:
-
Tissue inhibitor of metalloproteinase 1/2
- TG:
-
Triglyceride
- TBIL:
-
Total bilirubin
- TNF-α:
-
Tumor necrosis factor α
- TERT:
-
Telomerase reverse transcriptase
- TLR4:
-
Toll-like receptor 4
- TAK1:
-
Transforming growth factor-activated kinase 1
- TCHO:
-
Total cholesterol
- TCF4:
-
T-cell factor 4
- UUO:
-
Unilateral ureteral obstruction
- VCAM-1:
-
Vascular cell adhesion molecule-1
- VEGF:
-
Vascular endothelial growth factor
- VEGFR2:
-
VEGF receptor 2
- XBP1:
-
X box-binding protein-1
- YAP1:
-
Yes‑associated protein
- 4EBP1:
-
4E binding protein 1
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Funding
This study was supported by the 2020 Key Laboratory Project of Xianyang City (No. 2020K04-02), the Key Research & Development Project of Xianyang City (No. L2022ZDYFSF065), the Shaanxi Province Key subject of pharmacy engineering of Shaanxi Provincial Traditional Chinese Medicine administration (No. 2017001), and the Discipline Innovation Team Project of Shaanxi University of Chinese Medicine (No. 2019-YL11).
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SZ, YS, and XT conceived the idea and recommended a structure of this review. SZ, RW, and JW conducted literature searching and drafted the manuscript. XX and LN designed and created the figures. MG and YZ finished the tables. LN, YS, and XT helped to edited and revise the manuscript. All the authors listed have read and approved the final manuscript.
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Zhai, S., Wang, R., Wang, J. et al. Curcumol: a review of its pharmacology, pharmacokinetics, drug delivery systems, structure–activity relationships, and potential applications. Inflammopharmacol (2024). https://doi.org/10.1007/s10787-024-01447-6
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DOI: https://doi.org/10.1007/s10787-024-01447-6