<p>Glucose-coated Berberine Nanodrug for Glioma Therapy through Mitochondrial Pathway</p>

Abstract

Introduction: Glioma is the primary malignant brain tumor with poor prognosis. Berberine (BBR) was the potential drug for anti-tumor in glioma cells. Based on its limitation of poor aqueous solubility and instability, little information of BBR nanoparticles is reported in glioma. Methods: Different solutions including 5% glucose, 1*PBS, ddH 2 O, 0.9% NaCl, cell culture medium were selected, and only 5% glucose and ddH 2 O exhibited BBR-related nanoparticles. After heating for a longer time or adding a higher concentration of glucose solution, BBR nanoparticles were detected by TEM analysis. The uptake of BBR-Glu or BBR-Water nanoparticles were detected by immunofluorescence analysis for BBR autofluorescence. Cell viability was measured by MTT assay and Western blotting analysis. Apoptosis was performed with flow cytometric analysis and was detected by cleaved caspase-3 immuno-fluorescent staining. Cell cycle was used by flow cytometric analysis. Cytoskeleton was observed by confocal analysis using the neuron specific Class III ß-tubulin and ß-tubulin antibodies. Mitochondrial-related proteins were detected by Western blotting analyses and mito-tracker staining in live cells. Mitochondrion structures were observed by TEM analysis. ROS generation and ATP production were detected by related commercial kits. The tracking of BBR-Glu or BBR-Water nanoparticles into blood-brain barrier was observed in primary tumor-bearing models. The fluorescence of BBR was detected by confocal analyses in brains and gliomas. Results: BBR-Glu nanoparticles became more homogenized and smaller with dose-and time-dependent manners. BBR-Glu nanoparticles were easily absorbed in glioma cells. The IC 50 of BBR-Glu in U87 and U251 was far lower than that of BBR-Water. BBR-Glu performed better cytotoxicity, with higher G2/M phase arrest, decreased cell viability by targeting mitochondrion. In primary U87 glioma-bearing mice, BBR-Glu exhibited better imaging in brains and gliomas, indicating that more BBR moved across the blood-brain tumor barrier. Discussion: BBR-Glu nanoparticles have better solubility and stability, providing a promising strategy in glioma precision treatment.

Berberine and Oligomeric Proanthocyanidins Exhibit Synergistic Efficacy Through Regulation of PI3K-Akt Signaling Pathway in Colorectal Cancer

“…BBR emits a yellowish fluorescence (excitation: 488nm, emission: 564nm) ( 46 , 47 ), and its uptake was examined using the Infinite M1000 microplate reader (Tecan Trading AG, Männedorf, Switzerland) and confocal microscopy. The cells were treated with BBR, OPCs, or their combination for 24 hours, and washed two times with cold phosphate buffered solution (PBS) before measurement.…”

Activation of the GABA-alpha receptor by berberine rescues retinal ganglion cells to attenuate experimental diabetic retinopathy

“…It also was low cost, and had a long history of safe clinical application (Sandeep and Nandini, 2017 ; Ju et al, 2018 ; Imenshahidi and Hosseinzadeh, 2019 ; Suadoni and Atherton, 2021 ). In addition, BBR can penetrate the BBB successfully (Wang et al, 2005 , 2020 ; Simoes Pires et al, 2014 ; Abdel Moneim, 2015 ; Zhou et al, 2016 ) and may pass through the blood–retinal barrier which has similar structures.…”

Advances in mitophagy and mitochondrial apoptosis pathway-related drugs in glioblastoma treatment

“…Considering that silibinin has extremely high antioxidant and anti-tumor properties, it has drawn our attention to its potential use in the treatment of GBM.BNIP3, a member of the Bcl-2 family of pro-apoptotic proteins and a receptor for mitophagy, exhibits context-dependent roles in cancer (Gorbunova et al, 2020;Gorbunova et al, 2020;Vara-Perez et al, 2021).It targets mitochondria and could induce mitochondrial damage and nuclear translocation of AIF6 (Su et al, 2016). A study using GBM cell lines and nude mice with xenografted GBM has confirmed that silibinin could induce mitophagy in GBM, and that autophagy can promote silibinin-induced BNIP3 overexpression and its accumulation in the mitochondria, thereby triggering AIF-dependent death in GBM cells (Wang et al, 2020b). Moreover, silibinin has also been shown to inhibit GBM cell migration by inhibiting MMP-2 and -9 and improving TMZresistance in GBM cells (Zhai et al, 2021;Wong et al, 2023).…”