Curcumin and metformin synergistically modulate peripheral and central immune mechanisms of pain
Issued Date
2022-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85131828925
Pubmed ID
35690654
Journal Title
Scientific Reports
Volume
12
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.12 No.1 (2022)
Suggested Citation
Dasuni Wasana P.W., Hasriadi, Muangnoi C., Vajragupta O., Rojsitthisak P., Rojsitthisak P., Towiwat P. Curcumin and metformin synergistically modulate peripheral and central immune mechanisms of pain. Scientific Reports Vol.12 No.1 (2022). doi:10.1038/s41598-022-13647-7 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/86414
Title
Curcumin and metformin synergistically modulate peripheral and central immune mechanisms of pain
Other Contributor(s)
Abstract
Metformin is a well-tolerated antidiabetic drug and has recently been repurposed for numerous diseases, including pain. However, a higher dose of metformin is required for effective analgesia, which can potentiate its dose-dependent gastrointestinal side effects. Curcumin is a natural polyphenol and has beneficial therapeutic effects on pain. Curcumin has been used as an analgesic adjuvant with several analgesic drugs, allowing synergistic antinociceptive effects. Nevertheless, whether curcumin can exert synergistic analgesia with metformin is still unknown. In the present study, the nature of curcumin-metformin anti-inflammatory interaction was evaluated in in vitro using lipopolysaccharide-induced RAW 264.7 macrophage and BV-2 microglia cells. In both macrophage and microglia, curcumin effectively potentiates the anti-inflammatory effects of metformin, indicating potential synergistic effects in both peripheral and central pathways of pain. The nature of the interaction between curcumin and metformin was further recapitulated using a mouse model of formalin-induced pain. Coadministration of curcumin and metformin at a 1:1 fixed ratio of their ED50 doses significantly reduced the dose required to produce a 50% effect compared to the theoretically required dose in phase II of the formalin test with a combination index value of 0.24. Besides, the synergistic interaction does not appear to involve severe CNS side effects indicated by no motor alterations, no alterations in short-term and long-term locomotive behaviors, and the general well-being of mice. Our findings suggest that curcumin exerts synergistic anti-inflammation with metformin with no potential CNS adverse effects.