Basic Study of Drug-Drug Interaction between Memantine and the Traditional Japanese Kampo Medicine Yokukansan

Mutoh, T.; Sekiguchi, Kyoji; Kawakami, Zenji; Watanabe, Junko; Mizoguchi, Kazuo; Ikarashi, Yasushi; Yamamoto, Masahiro

doi:10.3390/molecules24010115

Cited by 6 publications

(5 citation statements)

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“…Gai et al (2014) detected GM and its metabolite 18-hydroxy-GM in 8 h urine samples from mice orally administered YGS (9.1 g/kg). Matsumoto et al (2018) detected GM in urine samples collected during 24 h from mice orally administered YKS (1 g/kg) in a basic study of drug-drug interactions between memantine and YKS. Furthermore, Gai et al (2014) confirmed the urinary excretion of CX, ICX, RP, IRP, HTE, 11-hydroxy HTE, and 19-carbonyl HTI in addition to GM in mice orally treated with YGS.…”

Section: Urinary Excretionmentioning

confidence: 99%

“…Most pharmacokinetic studies of GM have been performed after the oral administration of crude drug products (Kushida et al, 2013;Matsumoto et al, 2018;Takiyama, et al, 2019) (Table 2). Although the absolute bioavailability of GM has not been verified, many studies revealed that GM in the intestinal lumen following oral administration is certainly absorbed into portal vein blood and transferred to circulating blood.…”

Section: Administration Of Uh-containing Crude Drug Productsmentioning

confidence: 99%

“…The area under the plasma concentration-time curve (AUC) increased dosedependently in the range of 0.441-6.79 ng h/mL. In male mice, GM was detected (approximately 2.5 ng/ml) in plasma 1 h after oral YKS administration (1 g/kg), and it had mostly disappeared after 8-24 h (Matsumoto et al, 2018). In addition to YKS, GM has also been detected in the plasma of rats orally administered Tianma-Gouteng Yin granules at doses of 2.5 and 5 g/kg (Zhang H. et al, 2019).…”

Section: Administration Of Uh-containing Crude Drug Productsmentioning

confidence: 99%

“…essential Uncaria alkaloids such as RP, IRP, CX, ICX, HTE, and HTI (Nakazawa et al, 2006;Wang et al, 2010a;Wang et al, 2010b;Wang et al, 2014a;Wang et al, 2014b;Wang et al, 2017;Zhang et al, 2017;Chen et al, 2020). However, as multiple and potent pharmacological activities of GM have become apparent, with breakthroughs of analytical technologies, pharmacokinetic information has also gradually been accumulated, such as its absorption (Ma et al, 2014;Han et al, 2019), exposure to circulation blood (Kushida et al, 2013;Gai et al, 2014;Kitagawa et al, 2015;Zhang H. et al, 2019), hepatic metabolism (Kushida et al, 2015;Matsumoto et al, 2016;Tian et al, 2018;Kushida et al, 2021), blood-brain barrier (BBB) permeability (Imamura et al, 2011), brain distribution (Mizoguchi et al, 2014;Matsumoto et al, 2020), and urinary excretion (Gai et al, 2014;Matsumoto et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Properties, Pharmacology, and Pharmacokinetics of Active Indole and Oxindole Alkaloids in Uncaria Hook

2021

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Uncaria Hook (UH) is a dry stem with hook of Ucaria plant and is contained in Traditional Japanese and Chinese medicine such as yokukansan, yokukansankachimpihange, chotosan, Gouteng-Baitouweng, and Tianma-Gouteng Yin. UH contains active indole and oxindole alkaloids and has the therapeutic effects on ailments of the cardiovascular and central nervous systems. The recent advances of analytical technology led to reports of detailed pharmacokinetics of UH alkaloids. These observations of pharmacokinetics are extremely important for understanding the treatment’s pharmacological activity, efficacy, and safety. This review describes properties, pharmacology, and the recently accumulated pharmacokinetic findings of UH alkaloids, and discusses challenges and future prospects. UH contains major indole and oxindole alkaloids such as corynoxeine, isocorynoxeine, rhynchophylline, isorhynchophylline, hirsuteine, hirsutine, and geissoschizine methyl ether (GM). These alkaloids exert neuroprotective effects against Alzheimer’s disease, Parkinson’s disease, and depression, and the mechanisms of these effects include anti-oxidant, anti-inflammatory, and neuromodulatory activities. Among the UH alkaloids, GM exhibits comparatively potent pharmacological activity (e.g., agonist activity at 5-HT1A receptors). UH alkaloids are absorbed into the blood circulation and rapidly eliminated when orally administered. UH alkaloids are predominantly metabolized by Cytochrome P450 (CYP) and converted into various metabolites, including oxidized and demethylated forms. Regarding GM metabolism by CYPs, a gender-dependent difference is observed in rats but not in humans. Several alkaloids are detected in the brain after passing through the blood–brain barrier in rats upon orally administered. GM is uniformly distributed in the brain and binds to various channels and receptors such as the 5-HT receptor. By reviewing the pharmacokinetics of UH alkaloids, challenges were found, such as differences in pharmacokinetics between pure drug and crude drug products administration, food-influenced absorption, metabolite excretion profile, and intestinal tissue metabolism of UH alkaloids. This review will provide readers with a better understanding of the pharmacokinetics of UH alkaloids and their future challenges, and will be helpful for further research on UH alkaloids and crude drug products containing UH.

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Section: Urinary Excretionmentioning

confidence: 99%

Section: Administration Of Uh-containing Crude Drug Productsmentioning

confidence: 99%

Section: Administration Of Uh-containing Crude Drug Productsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Properties, Pharmacology, and Pharmacokinetics of Active Indole and Oxindole Alkaloids in Uncaria Hook

2021

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“…Parts of the crude drugs used in the Kampo formulas are also used in health foods and supplements. Kampo formulas have traditionally been prescribed for a number of health conditions, including chronic hepatitis, bronchial asthma, allergic rhinitis, anemia, and gastric cancer, and gradually reemerged in Japan as alternatives to Western medicine [23,24,25,26,27,28]. In a recent survey, approximately 90% of Japanese doctors prescribe Kampo formulas in their daily medical practice [29].…”

Section: Introductionmentioning

confidence: 99%

Screening of Crude Drugs Used in Japanese Kampo Formulas for Autophagy-Mediated Cell Survival of the Human Hepatocellular Carcinoma Cell Line

et al. 2019

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Background: Autophagy is a catabolic process through which dysfunctional proteins and organelles are degraded, and that is associated with the proliferation of cancer cells. The aim of this study was to screen approximately 130 kinds of crude drugs used in Japanese Kampo formulas to identify crude drugs that would regulate the proliferation through autophagy of human hepatocellular carcinoma HepG2 cells. Methods: Extracts of each crude drug were prepared using methanol. Protein levels were determined using Western blotting. Cell viability was measured by MTT assay. Results: Among the 130 crude extracts, 24 of them increased LC3-II expression. Among these, Goboshi (burdock fruit), Soboku (sappan wood), Mokko (saussurea root), Rengyo (forsythia fruit), and Hikai (dioscorea) notably suppressed the proliferation of HepG2 cells and increased p62 expression levels, which suggested that these five extracts downregulate the autophagic activity resulting in the accumulation of p62. On the other hand, Hishinomi (water chestnut), Biwayo (loquat leaf), and Binroji (areca) induced cell growth and decreased or were uninvolved with p62 expression levels, which implied that these three extracts might induce autophagy modulators for cell growth. Conclusions: The results suggest that the compounds contained in the crude drugs selected for this study could control cell viability by regulating autophagic activity in HepG2 cells. The isolation and identification of the active compounds in these drugs might lead to the development of agents for autophagy research and cancer chemoprevention.

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Alzheimer's disease: Molecular aspects and treatment opportunities using herbal drugs

Thakral

Yadav

Singh

et al. 2023

Ageing Research Reviews

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Basic Study of Drug-Drug Interaction between Memantine and the Traditional Japanese Kampo Medicine Yokukansan

Cited by 6 publications

References 50 publications

Properties, Pharmacology, and Pharmacokinetics of Active Indole and Oxindole Alkaloids in Uncaria Hook

Properties, Pharmacology, and Pharmacokinetics of Active Indole and Oxindole Alkaloids in Uncaria Hook

Screening of Crude Drugs Used in Japanese Kampo Formulas for Autophagy-Mediated Cell Survival of the Human Hepatocellular Carcinoma Cell Line

Alzheimer's disease: Molecular aspects and treatment opportunities using herbal drugs

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