Modulation of the transport of valproic acid through the blood-brain barrier in rats by the Gastrodia elata extracts

Yang, Ling; Lin, I-Hsin; Ting, Chin-Tsung; Tsai, Tung Hu

doi:10.1016/j.jep.2021.114276

Cited by 9 publications

(3 citation statements)

References 34 publications

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“…Due to ABC transporters’ low expression level and hydrophobic properties in cells, the requirement for a lipid double-layer environment to maintain their correct conformation makes expression, extraction, and purification more difficult in the study of function and structure 25 . Therefore, pure ABC transporters are difficult to acquire, and the screening of their ligands is mainly based on cell bidirectional transport experiments and computer-assisted virtual screening 26 , 27 , 28 . Currently, researchers have applied SMA technology to extract and stabilize ABC transporters in insect cell membranes, and they have discovered that MPs can maintain their correct conformation and physiological functions when stabilized by SMA 18 .…”

Section: Introductionmentioning

confidence: 99%

Screening potential P-glycoprotein inhibitors by combination of a detergent-free membrane protein extraction with surface plasmon resonance biosensor

Cao

Fang

Shi

et al. 2022

Acta Pharmaceutica Sinica B

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Section: Introductionmentioning

confidence: 99%

Screening potential P-glycoprotein inhibitors by combination of a detergent-free membrane protein extraction with surface plasmon resonance biosensor

Cao

Fang

Shi

et al. 2022

Acta Pharmaceutica Sinica B

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“…Histological examination showed mild hepatocyte steatosis and cholestasis in the low-dose group and hepatocyte steatosis, cholestasis, inflammatory infiltration of hepatocytes, and bile duct hyperplasia in the high-dose group, which were significantly different from those in the control group. On the other hand, the decrease of DBIL and TBIL levels in bile is related to the impairment of bilirubin uptake by hepatocytes caused by hepatotoxicity [ 10 ]. It was found that when the OATP1B1 and OATP1B3 genes were deleted, the TBIL released into the blood by MRP3 on the basal membrane of hepatocytes could not be reuptake by these two transporters, resulting in the increase of DBIL and TBIL concentrations in serum [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

iTRAQ Quantitative Proteomic Analysis of Different Expressed Proteins and Signal Pathways in Bakuchiol-Induced Hepatotoxicity

Gao

Abulizi

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Bakuchiol (BAK) is an abundant natural compound. BAK has been reported to have several biological activities such as anticancer, antiaging, anti-inflammatory, and prevention of bone loss. However, it causes hepatotoxicity, the mechanism of which is not known. In this study, we explored the mechanism of BAK hepatotoxicity by treating rats with 52.5 mg/kg and 262.5 mg/kg of BAK, administered continuously for 6 weeks. We examined the liver pathology and biochemical composition of bile to determine toxicity. Mechanisms of BAK hepatotoxicity were analyzed based on relative and absolute quantification (iTRAQ) protein equivalent signatures and validated in vitro using LO2 cells. iTRAQ analysis revealed 281 differentially expressed proteins (DEPs) in liver tissue of the BAK-treated group, of which 215 were upregulated, and 66 were downregulated. GO and KEGG enrichment analysis revealed that bile secretion, lipid metabolism, and cytochrome P450 signaling pathways were enriched in DEPs. Among them, peroxisome proliferator-activated receptor α (PPARα), farnesoid X receptor (FXR), and cholesterol 7α-hydroxylase (CYP7a1) were closely associated with the development and progression of BAK-induced hepatic metabolic dysfunction and abnormal bile metabolism. This study shows that BAK can induce hepatotoxicity through multiple signaling pathways.

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“…Given the potential of VPA as an anti‐tumor agent, current studies are exploring the acceleration of VPA influx through BBB. One such study determined that pre‐treatment with Gastrodia elata extract substantially improved BBB penetration of VPA due to upregulation of influx transporters, specifically the OATP transporter 117 . The study found that rats treated with Gastrodia elata at oral doses of 1 and 3 g/kg for 5 days increased the BBB AUC penetration ratio from 0.36 to 1.47 and 1.02, respectively.…”

Section: Chemotherapeutic Treatment Of Pediatric Brain Tumors (Pbts)mentioning

confidence: 99%

Chemotherapy in pediatric brain tumor and the challenge of the blood–brain barrier

Malik,

Podany,

Khan

et al. 2023

Cancer Medicine

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BackgroundPediatric brain tumors (PBT) stand as the leading cause of cancer‐related deaths in children. Chemoradiation protocols have improved survival rates, even for non‐resectable tumors. Nonetheless, radiation therapy carries the risk of numerous adverse effects that can have long‐lasting, detrimental effects on the quality of life for survivors. The pursuit of chemotherapeutics that could obviate the need for radiotherapy remains ongoing. Several anti‐tumor agents, including sunitinib, valproic acid, carboplatin, and panobinostat, have shown effectiveness in various malignancies but have not proven effective in treating PBT. The presence of the blood–brain barrier (BBB) plays a pivotal role in maintaining suboptimal concentrations of anti‐cancer drugs in the central nervous system (CNS). Ongoing research aims to modulate the integrity of the BBB to attain clinically effective drug concentrations in the CNS. However, current findings on the interaction of exogenous chemical agents with the BBB remain limited and do not provide a comprehensive explanation for the ineffectiveness of established anti‐cancer drugs in PBT.MethodsWe conducted our search for chemotherapeutic agents associated with the blood–brain barrier (BBB) using the following keywords: Chemotherapy in Cancer, Chemotherapy in Brain Cancer, Chemotherapy in PBT, BBB Inhibition of Drugs into CNS, Suboptimal Concentration of CNS Drugs, PBT Drugs and BBB, and Potential PBT Drugs. We reviewed each relevant article before compiling the information in our manuscript. For the generation of figures, we utilized BioRender software.FocusWe focused our article search on chemical agents for PBT and subsequently investigated the role of the BBB in this context. Our search criteria included clinical trials, both randomized and non‐randomized studies, preclinical research, review articles, and research papers.FindingOur research suggests that, despite the availability of potent chemotherapeutic agents for several types of cancer, the effectiveness of these chemical agents in treating PBT has not been comprehensively explored. Additionally, there is a scarcity of studies examining the role of the BBB in the suboptimal outcomes of PBT treatment, despite the effectiveness of these drugs for other types of tumors.

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Modulation of the transport of valproic acid through the blood-brain barrier in rats by the Gastrodia elata extracts

Cited by 9 publications

References 34 publications

Screening potential P-glycoprotein inhibitors by combination of a detergent-free membrane protein extraction with surface plasmon resonance biosensor

Screening potential P-glycoprotein inhibitors by combination of a detergent-free membrane protein extraction with surface plasmon resonance biosensor

iTRAQ Quantitative Proteomic Analysis of Different Expressed Proteins and Signal Pathways in Bakuchiol-Induced Hepatotoxicity

Chemotherapy in pediatric brain tumor and the challenge of the blood–brain barrier

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