Mechanistic insights into dimethyl cardamonin-mediated pharmacological effects: A double control of the AMPK-HMGB1 signaling axis.
Life Sci
; 263: 118601, 2020 Dec 15.
Article
in English
| MEDLINE | ID: covidwho-866958
ABSTRACT
Dimethyl cardamonin (DMC) has been isolated from diverse plants, notably from Cleistocalyx operculatus. We have reviewed the pharmacological properties of this natural product which displays anti-inflammatory, anti-hyperglycemic and anti-cancer properties. The pharmacological activities essentially derive from the capacity of DMC to interact with the protein targets HMGB1 and AMPK. Upon binding to HMGB1, DMC inhibits the nucleocytoplasmic transfer of the protein and its extracellular secretion, thereby blocking its alarmin function. DMC also binds to the AMP site of AMPK to activate phospho-AMPK and then to trigger downstream signals leading to the anti-inflammatory and anti-hyperglycemic effects. AMPK activation by DMC reinforces inhibition of HMGB1, to further reduce the release of the alarmin protein, likely contributing to the anticancer effects. The characterization of a tight control of DMC over the AMPK-HMGB1 axis not only helps to explain the known activities of DMC but also suggests opportunities to use this chalcone to treat other pathological conditions such as the acute respiratory distress syndrome (which affects patients with COVID-19). DMC structural analogues are also evoked.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Chalcones
/
Anti-Inflammatory Agents
/
Antineoplastic Agents, Phytogenic
Type of study:
Experimental Studies
Topics:
Long Covid
Limits:
Animals
/
Humans
Language:
English
Journal:
Life Sci
Year:
2020
Document Type:
Article
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