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Effect of Water Extract of Mangosteen Pericarp on Donepezil Pharmacokinetics in Mice.

ABSTRACT: The pharmacokinetic (PK) change in a drug by co-administered herbal products can alter the efficacy and toxicity. In the circumstances that herb-drug combinations have been increasingly attempted to alleviate Alzheimer's disease (AD), the PK evaluation of herb-drug interaction (HDI) is necessary. The change in systemic exposure as well as target tissue distribution of the drug have been issued in HDIs. Recently, the memory-enhancing effects of water extract of mangosteen pericarp (WMP) has been reported, suggesting a potential for the combination of WMP and donepezil (DNP) for AD treatment. Thus, it was evaluated how WMP affects the PK change of donepezil, including systemic exposure and tissue distribution in mice after simultaneous oral administration of DNP with WMP. Firstly, co-treatment of WMP and donepezil showed a stronger inhibitory effect (by 23.0%) on the neurotoxicity induced by Aβ_(25-35) in SH-SY5Y neuroblastoma cells than donepezil alone, suggesting that the combination of WMP and donepezil may be more effective in moderating neurotoxicity than donepezil alone. In PK interaction, WMP increased donepezil concentration in the brain at 4 h (by 63.6%) after administration without affecting systemic exposure of donepezil. Taken together, our results suggest that WMP might be used in combination with DNP as a therapy for AD.

SUBMITTER: Bae M

PROVIDER: S-EPMC8434012 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Memory-Enhancing Effects of Mangosteen Pericarp Water Extract through Antioxidative Neuroprotection and Anti-Apoptotic Action.

Project description:Mangosteen has long been utilized as a traditional medicine in Southeast Asia. Diverse extracts of mangosteen pericarp and its bioactive xanthones exhibit various bioactivities. However, the pharmacological potential of mangosteen pericarp water extract (MPW) has not been reported yet. This study used primary cultured rat cortical cells to investigate the effect of MPW on neurotoxicity. We found that MPW inhibited neurotoxicity and production of reactive oxygen species triggered by Aβ(25-35) or excitatory amino acids. MPW inhibited caspase 3 activation and DNA fragmentation in Aβ(25-35)- or N-methyl-D-aspartate-treated cells, suggesting an anti-apoptotic action. Additionally, MPW reduced lipid peroxidation and scavenged 1,1-diphenyl-2-picrylhydrazyl radicals, assuring its antioxidant property. Furthermore, MPW suppressed β-secretase and acetylcholinesterase activities. These findings prompted us to evaluate its effect on memory dysfunction in scopolamine-treated mice using Morris water maze test. Oral administration of MPW at the dosage of 50, 100, or 300 mg/kg for four days significantly decreased the latency time to find the platform and markedly increased the swimming time in the target quadrant. Taken together, our results suggest that MPW exerts memory-enhancing effect through antioxidative neuroprotection and anti-apoptotic action. Accordingly, MPW may have a potential to prevent or treat memory impairment associated with Alzheimer's disease.

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Mangosteen pericarp components alleviate progression of prostatic hyperplasia and mitochondrial dysfunction in rats.

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The Intestinal Efflux Transporter Inhibition Activity of Xanthones from Mangosteen Pericarp: An In Silico, In Vitro and Ex Vivo Approach.

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Project description:Donepezil (DNP) is the first-line drug used for Alzheimer's disease (AD). However, the therapeutic response rate of patients to DNP varies from 20 to 60%. The main reason for the large differences in the clinical efficacy of DNP therapy is genetic factors, some of which affect pharmacokinetics (PK), while others affect pharmacodynamics (PD). Thus, much emphasis has been placed on the investigation of an association between PK- and PD-related gene polymorphisms and therapeutic response to DNP, but a consistent view does not yet exist. In this review, we summarize recent findings regarding genetic factors influencing the clinical efficacy of DNP, including substantial differences in individual responses as a consequence of polymorphisms in Cytochrome P450 (CYP) 2D6, CY3A4, CY3A5, APOE, ABCA1, ABCB1, ESR1, BCHE, PON-1, CHRNA7, and CHAT. We also discuss possible strategies for the evaluation of the clinical efficacy of DNP, with a specific focus on possible biomarkers of PK/PD parameters, and provide perspectives and limitations within the field, which will also be beneficial for understanding the multiple mechanisms of DNP therapy in AD.

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