Odisolane, a Novel Oxolane Derivative, and Antiangiogenic Constituents from the Fruits of Mulberry (Morus alba L.).
Mulberry, the fruit of Morus alba L., is known as an edible fruit and commonly used in Chinese medicines as a warming agent and as a sedative, tonic, laxative, odontalgic, expectorant, anthelmintic, and emetic. Systemic investigation of the chemical constituents of M. alba fruits led to the identification of a novel oxolane derivative, (R*)-2-((2S*,3R*)-tetrahydro-2-hydroxy-2-methylfuran-3-yl)propanoic acid (1), namely, odisolane, along with five known heterocyclic compounds (2-6). The structure of the new compound was elucidated on the basis of HR-MS, 1D and 2D NMR ((1)H-(1)H COSY, HSQC, HMBC, and NOESY) data analysis. Compound 1 has a novel skeleton that consists of 8 carbon units with an oxolane ring, which until now has never been identified in natural products. The isolated compounds were subjected to several activity tests to verify their biological function. Among them, compounds 1, 3, and 5 significantly inhibited cord formation in HUVECs. The action mechanism of compound 3, which had the strongest antiangiogenic activity, was mediated by decreasing VEGF, p-Akt, and p-ERK protein expression. These results suggest that compounds isolated from M. alba fruits might be beneficial in antiangiogenesis therapy for cancer treatment.
School of Pharmacy, Sungkyunkwan University , Suwon 440-746, Republic of Korea.
Seoung Rak
SR
Lee
College of Korean Medicine, Gachon University , Seongnam 461-701, Republic of Korea.
Jun Yeon
JY
Park
School of Pharmacy, Sungkyunkwan University , Suwon 440-746, Republic of Korea.
Jae Sik
JS
Yu
College of Life Sciences, Kyung Hee University , Yongin 17104, Republic of Korea.
Sung Ok
SO
Lee
Dong-A ST Research Center , Yongin 446-905, Republic of Korea.
Ja-Young
JY
Ryu
Dong-A ST Research Center , Yongin 446-905, Republic of Korea.
Sang-Zin
SZ
Choi
College of Korean Medicine, Gachon University , Seongnam 461-701, Republic of Korea.
Ki Sung
KS
Kang
College of Korean Medicine, Gachon University , Seongnam 461-701, Republic of Korea.
Noriko
N
Yamabe
School of Pharmacy, Sungkyunkwan University , Suwon 440-746, Republic of Korea.
Ki Hyun
KH
Kim
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D031625:Morus / Q000737:chemistry*
D020533:Angiogenesis Inhibitors
Moraceae; Morus alba; VEGF; angiogenesis; oxolane derivative