Cucurbitacins: the antidiabetic compounds of “Wereque”

Cucurbitacins: the antidiabetic compounds of “Wereque”
Sonia H. Naviaa*, Miriam Rodríguez-Sosab, Mariano Martínez-Vázqueza
a Instituto de Química, UNAM, C. Exterior, C. Universitaria, Coyoacán 04510, México, CDMX.
* [email protected]
b Facultad de Estudios Superiores-Iztacala, UNAM, Unidad de Biomedicina, C.P. 54090 Tlalnepantla, Estado de México, México.

Diabetes mellitus type 2 (DMT2) is a metabolic disorder of indeterminate etiology, characterized by chronic hyperglycaemia, result of impaired production, secretion and / or use of insulin, causing an imbalance in glucose homeostasis. Skeletal muscle is the primary tissue responsible for insulin-stimulated whole-body glucose uptake in both humans and rodents (almost 90% of postprandial glucose)1. The glucose transporter 4 (GLUT4) mediates the transport of glucose to muscle this hormone2. This process is the limiting step in the use and storage of glucose, playing a key role in the maintenance of homeostasis. In the absence of insulin, GLUT4 is found in vesicles inside the cytoplasm, preventing the uptake of this hexose.3 Medicinal plants play an important role in the management and treatment of DMT2. Natural products are an important source of new pharmacological compounds. In Mexico, members of the Ibervillea genus locally known as "Wereque" have traditionally been used to treat the symptoms of this disease4. Considering the ethnobotanical use of Ibervillea lindheimeri and the importance of glucose transport, we establish the effect of this root over glycaemia and the translocation of GLUT4 to the plasma membrane in vivo.
We determined the effect of ethyl acetate extract and its major compounds (23, 24 dihydrocucurbitacin D and 2-O-β glucopyranosyl 23, 24 dihydrocucurbitacin D) over glycaemia acutely using streptozotocin induced CD1 diabetic mice. Additionally we evaluated the translocation of GLUT4 in plasma membrane by immunohistochemistry and the activation of second messengers involved in the GLUT4 translocation activation pathway AMPK, pAMPK, AKT and pAKT using Western Blot.

It was found that DHCD has a positive effect on the translocation of GLUT4 while the other products, although if they increase the presence of this membrane transporter, compared to diabetic control they do not do so in a statistically significant way. On the other hand, the WB results showed that only DHCD is able to statistically activate the signaling pathway that involves AMPK, while none of the compounds activate the AKT2 signaling pathway.

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