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Kobayashi Y, Narita K, Chiba K, et al. Effects of L-citrulline diet on stress-induced cold hypersensitivity in mice. Pharmacognosy Res. 2014;6(4):297-302doi: 10.4103/0974-8490.138269.
Kobayashi, Y., Narita, K., Chiba, K., Takemoto, H., Morita, M., & Morishita, K. (2014). Effects of L-citrulline diet on stress-induced cold hypersensitivity in mice. Pharmacognosy research, 6(4), 297-302. https://doi.org/10.4103/0974-8490.138269
Kobayashi, Yoshinori, et al. "Effects of L-citrulline diet on stress-induced cold hypersensitivity in mice." Pharmacognosy research vol. 6,4 (2014): 297-302. doi: https://doi.org/10.4103/0974-8490.138269
Kobayashi Y, Narita K, Chiba K, Takemoto H, Morita M, Morishita K. Effects of L-citrulline diet on stress-induced cold hypersensitivity in mice. Pharmacognosy Res. 2014 Oct;6(4):297-302. doi: 10.4103/0974-8490.138269. PMID: 25276066; PMCID: PMC4166817.
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Pharmacognosy Res. 2014 Oct;6(4):297-302. doi: 10.4103/0974-8490.138269.

Effects of L-citrulline diet on stress-induced cold hypersensitivity in mice.

Pharmacognosy research

Yoshinori Kobayashi, Kazuki Narita, Kotaro Chiba, Hiroaki Takemoto, Masahiko Morita, Koji Morishita

Affiliations

  1. Laboratory of Pharmacognosy, School of Pharmaceutical Sciences, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-0861, Japan.
  2. Healthcare Products, Development Center, Kyowa Hakko Bio Co., Ltd, 2, Miyukigaoka, Tsukuba, Ibaraki, 305-0841, Japan.

PMID: 25276066 PMCID: PMC4166817 DOI: 10.4103/0974-8490.138269

Abstract

BACKGROUND: L-citrulline is an amino acid discovered in watermelon (Citrullus lanatus, Cucurbitaceae) and is a known component of the nitric oxide (NO) cycle that plays an important role in adjusting blood circulation and supplying NO and a key component of the endothelium-derived relaxing factor.

OBJECTIVE: The objective of this study is to evaluate the effect of L-citrulline on a newly established stress-induced cold hypersensitivity mouse model.

MATERIALS AND METHODS: When normal mice were forced to swim in water at 25°C for 15 min, their core body temperature dropped to 28.9°C, and then quickly recovered to normal temperature after the mice were transferred to a dry cage at room temperature (25°C). A 1-h immobilization before swimming caused the core body temperature to drop to ca. 24.1°C (4.8°C lower than normal mice), and the speed of core body temperature recovery dropped to 57% of the normal control. We considered this delay in recovery from hypothermia to be a sign of stress-induced cold hypersensitivity. Similar cold hypersensitivity was induced by administration of 50 mM L-NG-nitroarginine methyl ester, a NO synthesis inhibitor.

RESULTS: In this study, we showed that recovery speed from the stress-induced hypothermia remarkably improved in mice fed a 1% L-citrulline-containing diet for 20 days. Furthermore, the nonfasting blood level of L-arginine and L-citrulline increased significantly in the L-citrulline diet group, and higher serum nitrogen oxide levels were observed during recovery from the cold.

CONCLUSIONS: These results suggested that oral L-citrulline supplementation strengthens vascular endothelium function and attenuates stress-induced cold hypersensitivity by improving blood circulation.

Keywords: Citrullus lanatus; Cucurbitaceae; L-citrulline; cold hypersensitivity; nitric oxide

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