Page 5 - H. Cell signaling

Hispidin, an extract of Phellinus Linteus, can alleviate
endothelial dysfunction by inhibiting arginase

Byeongjun Yoon and Sungwoo Ryoo
Department of Biology, College of Natural Sciences, Kangwon National University, Chuncheon 200-701, Republic of Korea

ABSTRACTS INTRODUCTIONS
● Hispidin effectively inhibited arginase, which induced phosphorylation CaMKll ● Endothelial nitric oxide synthase (eNOS) produces nitric oxide (NO) by
2+
thr 286 and eNOS ser1177 residues in a Ca -dependent manner. using L-arginine as a substrate.
● The activity of eNOS induced by cytosolic Ca 2+ increased NO production, which ● The reduction of NO production due to decrease of eNOS activity is
increased the endothelium-dependent relaxation acetylcholine (Ach) response, considered an indicator of almost all cardiovascular diseases.
but the contraction of phenylephrine (PE) was reduced.
● Arginase hydrolyzes L-arginine to L-ornithine, a precursor for spermine,
● In ApoE -/- mice fed HCD, an arteriosclerosis model, eNOS activity was which has two isoforms for arginase, arginase l in the cytosol, and
decreased due to a decrease in cytosol Ca 2+ levels, which caused endothelial arginase ll in the mitochondria.
dysfunction
● Intracellular Ca level are associated with the activity of Ca /calmodulin-
2+
2+
-/-
● Treatment of hispidin in ApoE mice fed HCD restored cytosolic Ca 2+ levels and dependent protein kinase ll (CaMK ll) and eNOS, and Arginase ll can
increased vascular reactivity. regulate cytosolic Ca 2+ level.
● In conclusion, arginase inhibition with hispidin can increase eNOS activity in a ● Therefore, we investigated whether arginase inhibition with hispidin can
Ca -dependent manner, which can alleviate endothelial dysfunction. alleviate endothelial dysfunction.
2+
RESULTS
Materials & methods

Hispidin Structure
Week 0 1 2 3 4 5 6 7 8

ApoE -/- mice,
39 weeks old, Start experiments
fed HCD
• Hispidin is a phenol compound in Phellinus
Linteus (Sang-hwang mushroom) that is known to
be effective in anti-inflammatory and anti-cancer.
• The experiment was conducted after feeding HCD
to ApoE -/- mice for 8 weeks

Fig. 1. Hispidin inhibited arginase I,II in an uncompetitive Fig. 2. Arginase inhibition with hispidin incuced
manner, which induced eNOS and CaMKII activity. an increase cytosolic Ca 2+ level.

Fig. 3. Arginase inhibition with hispidin incuced an increase Fig. 4. In arteriosclerosis mice model, Hispidin increases Fig. 5. In arteriosclerosis mice model, the relaxation
cytosolic Ca 2+ level. cytosolic Ca 2+ and the production of NO. rate of blood vessels increases with the
treatment of Hispidin.
CONCLUSION REFERENCES
● Hispidin can act as an arginase inhibitor, which induces eNOS activity in a ● Hye Mi Hwang, Jeong Hyung Lee, Byung Sun Min, Byeong Hwa Jeon,
2+-
Ca dependent manner. Kwang Lae Hoe, Young Myeong Kim and Sungwoo Ryoo, A Novel Arginase
Inhibitor Derived from Scutellavia indica Restored Endothelial Function in
● Arginase inhibition with hispidin can increase NO production and restore ApoE Null Mice Fed a High-Cholesterol Diet Journal of Pharmacology and
vascular reactivity. Experimental Therapeutics (2015) 355 (1) 57-65
● Yoon J, Park M, Lee Jh, Min BS, Ryoo S, Endothelial nitric oxide synthase
● In ApoE -/- mice fed HCD, an arteriosclerosis model, hispidin can alleviate activation through obacunone-dependent arginase inhibition restored
endothelial dysfunction impaired endothelial function in ApoE-null mice. Vascul Pharmacol (2014)
102-9.