PMID- 35011304
OWN - NLM
STAT- MEDLINE
DCOM- 20220211
LR  - 20220211
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 27
IP  - 1
DP  - 2021 Dec 23
TI  - Rosmanol and Carnosol Synergistically Alleviate Rheumatoid Arthritis through 
      Inhibiting TLR4/NF-kappaB/MAPK Pathway.
LID - 10.3390/molecules27010078 [doi]
LID - 78
AB  - Callicarpalongissima has been used as a Yao folk medicine to treat arthritis for 
      years in China, although its active anti-arthritic moieties have not been 
      clarified so far. In this study, two natural phenolic diterpenoids with 
      anti-rheumatoid arthritis (RA) effects, rosmanol and carnosol, isolated from the 
      medicinal plant were reported on for the first time. In type II collagen-induced 
      arthritis DBA/1 mice, both rosmanol (40 mg/kg/d) and carnosol (40 mg/kg/d) alone 
      alleviated the RA symptoms, such as swelling, redness, and synovitis; decreased 
      the arthritis index score; and downregulated the serum pro-inflammatory cytokine 
      levels of interleukin 6 (IL-6), monocyte chemotactic protein 1 (MCP-1), and tumor 
      necrosis factor alpha (TNF-alpha). Additionally, they blocked the activation of the 
      Toll-like receptor 4 (TLR4)/nuclear factor kappaB (NF-kappaB)/c-Jun N-terminal kinase 
      (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways. Of particular 
      interest was that when they were used in combination (20 mg/kg/d each), the 
      anti-RA effect and inhibitory activity on the TLR4/NF-kappaB/MAPK pathway were 
      significantly enhanced. The results demonstrated that rosmanol and carnosol 
      synergistically alleviated RA by inhibiting inflammation through regulating the 
      TLR4/NF-kappaB/MAPK pathway, meaning they have the potential to be developed into 
      novel, safe natural combinations for the treatment of RA.
FAU - Li, Lianchun
AU  - Li L
AUID- ORCID: 0000-0002-1186-5742
AD  - Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, 
      Guangxi Institute of Botany, Chinese Academy of Sciences, Guilin 541006, China.
FAU - Pan, Zhenghong
AU  - Pan Z
AD  - Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, 
      Guangxi Institute of Botany, Chinese Academy of Sciences, Guilin 541006, China.
FAU - Ning, Desheng
AU  - Ning D
AD  - Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, 
      Guangxi Institute of Botany, Chinese Academy of Sciences, Guilin 541006, China.
FAU - Fu, Yuxia
AU  - Fu Y
AD  - Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, 
      Guangxi Institute of Botany, Chinese Academy of Sciences, Guilin 541006, China.
LA  - eng
GR  - 2018GXNSFDA050016/Natural Science Foundation of Guangxi/
GR  - 2018GXNSFBA281094/Natural Science Foundation of Guangxi/
GR  - ZY20111010/Special Funds for Local Science and Technology Development Guided by 
      the Central Committee/
GR  - Guike AA18118015/Guangxi Innovation-driven Development Special Project/
PT  - Journal Article
DEP - 20211223
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Abietanes)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (Plant Extracts)
RN  - 0 (Toll-Like Receptor 4)
RN  - 483O455CKD (carnosol)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - F25TV383OC (rosmanol)
SB  - IM
MH  - Abietanes/chemistry/*pharmacology
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Arthritis, Rheumatoid/drug therapy/etiology/*metabolism/pathology
MH  - Biomarkers
MH  - Cytokines/blood/metabolism
MH  - Disease Management
MH  - Disease Models, Animal
MH  - Disease Susceptibility
MH  - Drug Synergism
MH  - Inflammation Mediators/blood/metabolism
MH  - Male
MH  - Mice
MH  - Molecular Structure
MH  - NF-kappa B/metabolism
MH  - Plant Extracts/chemistry/pharmacology
MH  - Signal Transduction/*drug effects
MH  - Toll-Like Receptor 4/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC8746366
OTO - NOTNLM
OT  - Callicarpa longissima
OT  - TLR4/NF-kappaB/MAPK
OT  - carnosol
OT  - rheumatoid arthritis
OT  - rosmanol
OT  - synergistic effect
COIS- The authors declare no conflict of interest.
EDAT- 2022/01/12 06:00
MHDA- 2022/02/12 06:00
PMCR- 2021/12/23
CRDT- 2022/01/11 01:14
PHST- 2021/11/07 00:00 [received]
PHST- 2021/12/16 00:00 [revised]
PHST- 2021/12/20 00:00 [accepted]
PHST- 2022/01/11 01:14 [entrez]
PHST- 2022/01/12 06:00 [pubmed]
PHST- 2022/02/12 06:00 [medline]
PHST- 2021/12/23 00:00 [pmc-release]
AID - molecules27010078 [pii]
AID - molecules-27-00078 [pii]
AID - 10.3390/molecules27010078 [doi]
PST - epublish
SO  - Molecules. 2021 Dec 23;27(1):78. doi: 10.3390/molecules27010078.