PMID- 37513606
OWN - NLM
STAT- MEDLINE
DCOM- 20230731
LR  - 20230801
IS  - 2072-6643 (Electronic)
IS  - 2072-6643 (Linking)
VI  - 15
IP  - 14
DP  - 2023 Jul 18
TI  - Glycyrrhizic Acid Inhibits High-Mobility Group Box-1 and Homocysteine-Induced 
      Vascular Dysfunction.
LID - 10.3390/nu15143186 [doi]
LID - 3186
AB  - Hyperhomocysteinemia (HHcy) worsens cardiovascular outcomes by impairing vascular 
      function and promoting chronic inflammation via release of danger-associated 
      molecular patterns, such as high-mobility group box-1 (HMGB-1). Elevated levels 
      of HMGB-1 have recently been reported in patients with HHcy. Therefore, targeting 
      HMGB-1 may be a potential therapy to improve HHcy-induced cardiovascular 
      pathologies. This study aimed to further elucidate HMGB-1's role during acute 
      HHcy and HHcy-induced atherogenesis and to determine if inhibiting HMGB-1 with 
      glycyrrhizic acid (Glyz) improved vascular function. Male New Zealand White 
      rabbits (n = 25) were placed on either a standard control chow (CD; n = 15) or 
      atherogenic diet (AD; n = 10) for 4 weeks. Rabbit serum and Krebs taken from 
      organ bath studies were collected to quantify HMGB-1 levels. Isometric tension 
      analysis was performed on abdominal aorta (AA) rings from CD and AD rabbits. 
      Rings were incubated with homocysteine (Hcy) [3 mM] for 60 min to induce acute 
      HHcy or rhHMGB-1 [100 nM]. Vascular function was assessed by relaxation to 
      cumulative doses of acetylcholine. Markers of vascular dysfunction and 
      inflammation were quantified in the endothelium, media, and adventitia of AA 
      rings. HMGB-1 was significantly upregulated in serum (p < 0.0001) and Krebs (p < 
      0.0001) after Hcy exposure or an AD. Incubation with Hcy (p < 0.0001) or rhHMGB-1 
      (p < 0.0001) and an AD (p < 0.0001) significantly reduced relaxation to 
      acetylcholine, which was markedly improved by Glyz. HMGB-1 expression was 
      elevated (p < 0.0001) after Hcy exposure and AD (p < 0.0001) and was normalized 
      after Glyz treatment. Moreover, markers of vascular function, cell stress and 
      inflammation were also reduced after Glyz. These results demonstrate that HMGB-1 
      has a central role during HHcy-induced vascular dysfunction and inhibiting it 
      with Glyz could be a potential treatment option for cardiovascular diseases.
FAU - Gadanec, Laura Kate
AU  - Gadanec LK
AUID- ORCID: 0000-0002-4801-8061
AD  - Institute of Health and Sport, Victoria University, Melbourne, VIC 3030, 
      Australia.
FAU - Andersson, Ulf
AU  - Andersson U
AUID- ORCID: 0000-0003-0316-3860
AD  - Department of Women's and Children's Health, Karolinska Institute, 17177 
      Stockholm, Sweden.
FAU - Apostolopoulos, Vasso
AU  - Apostolopoulos V
AUID- ORCID: 0000-0001-6788-2771
AD  - Institute of Health and Sport, Victoria University, Melbourne, VIC 3030, 
      Australia.
AD  - Immunology Program, Australian Institute for Musculoskeletal Science, Melbourne, 
      VIC 3021, Australia.
FAU - Zulli, Anthony
AU  - Zulli A
AD  - Institute of Health and Sport, Victoria University, Melbourne, VIC 3030, 
      Australia.
LA  - eng
PT  - Journal Article
DEP - 20230718
PL  - Switzerland
TA  - Nutrients
JT  - Nutrients
JID - 101521595
RN  - N9YNS0M02X (Acetylcholine)
RN  - 6FO62043WK (Glycyrrhizic Acid)
RN  - 0 (HMGB Proteins)
RN  - 0LVT1QZ0BA (Homocysteine)
SB  - IM
MH  - Male
MH  - Rabbits
MH  - Animals
MH  - Acetylcholine/pharmacology
MH  - Glycyrrhizic Acid/pharmacology
MH  - *Atherosclerosis
MH  - Inflammation/metabolism
MH  - HMGB Proteins
MH  - *Hyperhomocysteinemia/complications/drug therapy
MH  - Homocysteine
PMC - PMC10383373
OTO - NOTNLM
OT  - atherogenesis
OT  - cardiovascular diseases
OT  - glycyrrhizic acid
OT  - high-mobility group box-1
OT  - homocysteine
OT  - hyperhomocysteinemia
COIS- The authors declare no conflict of interest. Associate Professor Anthony Zulli 
      co-owns Zultek Engineering, the provider of product OB8 and OB16 bath systems.
EDAT- 2023/07/29 11:48
MHDA- 2023/07/31 06:43
PMCR- 2023/07/18
CRDT- 2023/07/29 01:36
PHST- 2023/06/02 00:00 [received]
PHST- 2023/07/04 00:00 [revised]
PHST- 2023/07/13 00:00 [accepted]
PHST- 2023/07/31 06:43 [medline]
PHST- 2023/07/29 11:48 [pubmed]
PHST- 2023/07/29 01:36 [entrez]
PHST- 2023/07/18 00:00 [pmc-release]
AID - nu15143186 [pii]
AID - nutrients-15-03186 [pii]
AID - 10.3390/nu15143186 [doi]
PST - epublish
SO  - Nutrients. 2023 Jul 18;15(14):3186. doi: 10.3390/nu15143186.