Publication on Citrulline in Journal of Novel Physiotherapies

KYOWA HAKKO BIO CO., LTD. (President and CEO: Chikakuni Kotani), published a research article titled ‘Effects of Citrulline^*1 Combined with Tadalafil^*2 on Monocrotaline-Induced Pulmonary Hypertension in Rats Compared with Arginine’ on Journal of Novel Physiotherapies.

Summary
Purpose: Tadalafil, phosphodiesterase5 (PDE5) inhibitor, was reported to have a therapeutic effect on pulmonary hypertension (PH) and citrulline is an amino acid to dilate arteries as an extracellular supplement to improve nitric oxide (NO) production. Therefore, it is expected that combination of tadalafil and citrulline exert a stronger effect for PH. The aim of this study is to evaluate the combination effects of tadalafil and citrulline on monocrotaline (MCT) -induced PH in rats compared with the combination effects of tadalafil and arginine.
Methods: We used 4-week-old male SD rats which developed PH by 5-times subcutaneous injection of MCT. We evaluated heart function by echocardiography and calculated the ratio of RV to LV weight of heart before and after 6-times administration per two weeks of saline, tadalafil alone, citrulline alone and tadalafil and citrulline or arginine.
Results: The survival rate of tadalafil and citrulline administration was 91.7%, which was higher than other groups. The ratio of RV to LV weight in a tadalafil group and a tadalafil+citrulline group were significantly lower than other 3 groups.
Conclusion: Combination therapy of tadalafil and citrulline is useful to prevent deterioration of pulmonary hypertension and improve survival rate compared with concomitant use of arginine.

Term
^*1 L-Citrulline: Amino acid presents in the body and is a potent endogenous precursor of L-arginine, which is a substrate for NO synthase. L-Citrulline supplementation has been shown to exhibit various beneficial effects such as improving arterial stiffness, erectile function, and memory deficit through up-regulation of NO synthesis.
^*2 Tadalafil: PDE inhibitor that is reported to have a therapeutic effect on PH and the first line to treat patients with PH.

Reference
Ishikura F. et al. Journal of Novel Physiotherapies. 5(4) 269,2015.

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