Diffusion Efficiency and Bioavailability of Resveratrol Administered to Rat Brain by Different Routes: Therapeutic Implications

• Published in: Neurotherapeutics Vol. 12; no. 2; pp. 491 - 501
• Main Authors: Shu, Xiao-Hong, Wang, Li-Li, Li, Hong, Song, Xue, Shi, Shun, Gu, Jia-Yao, Wu, Mo-Li, Chen, Xiao-Yan, Kong, Qing-You, Liu, Jia
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2015; Springer Nature B.V
• Subjects: Aluminum; Analysis of Variance; Animals; Anticarcinogenic Agents - administration & dosage; Bioavailability; Biomedical and Life Sciences; Biomedicine; Blood-brain barrier; Brain; Brain - drug effects; Brain - enzymology; Brain - pathology; Brain Neoplasms - drug therapy; Cancer therapies; Carotid arteries; Cell Line, Tumor; Cell Survival - drug effects; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Routes; Drug dosages; Female; Gene Expression Regulation, Neoplastic - drug effects; Glioblastoma - drug therapy; Glucuronosyltransferase - metabolism; Laboratory animals; Male; Nervous system; Neurobiology; Neurology; Neurosciences; Neurosurgery; Original; Original Article; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes - administration & dosage; Tumors; Veins & arteries; Grand Island; United States > US; China; blood brain barrier; drug administration; bioavailability; glioblastoma neurotherapeutics; Resveratrol
• ISSN: 1933-7213; 1878-7479; 1878-7479
• DOI: 10.1007/s13311-014-0334-6

Resveratrol possesses anti-tumor activities against central nervous system (CNS) tumors in vitro but has not yet been used clinically due to its low bioavailability, particularly in the CNS. This study thus aimed to elucidate brain bioavailability of trans-resveratrol by monitoring brain concentrations and dwell times following administration of resveratrol through intragastric, intraperitoneal, external carotid artery/ECA and intrathecal routes. In parallel, we evaluated the biological responses of rat RG2 glioblastoma cells as well as RG2-formed rat intracranial glioblastomas treated with resveratrol via intrathecal administration. The results revealed that resveratrol was detected in rat brains except when administered systemically. Intrathecal administration of reseveratrol led to abundant apoptotic foci and increased staining of the autophagy proteins, LC-3 and Beclin-1 and shrinkage of the intracranial tumors. In conclusion, the BBB penetrability of resveratrol is remarkably increased by intracthecal administration. Regular short-term resveratrol treatments suppress growth and enhance autophagic and apoptotic activities of rat RG2 glioblastoma cells in vitro and in vivo. Therefore, intrathecal administration of resveratrol could be an optimal intervention approach in the adjuvant management of brain malignancies.