1.Alternative Methods for Testing Botulinum Toxin: Current Status and Future Perspectives
Mahesh Raj NEPAL ; Tae Cheon JEONG
Biomolecules & Therapeutics 2020;28(4):302-310
Botulinum toxins are neurotoxic modular proteins composed of a heavy chain and a light chain connected by a disulfide bond and are produced by Clostridium botulinum. Although lethally toxic, botulinum toxin in low doses is clinically effective in numerous medical conditions, including muscle spasticity, strabismus, hyperactive urinary bladder, excessive sweating, and migraine. Globally, several companies are now producing products containing botulinum toxin for medical and cosmetic purposes, including the reduction of facial wrinkles. To test the efficacy and toxicity of botulinum toxin, animal tests have been solely and widely used, resulting in the inevitable sacrifice of hundreds of animals. Hence, alternative methods are urgently required to replace animals in botulinum toxin testing. Here, the various alternative methods developed to test the toxicity and efficacy of botulinum toxins have been briefly reviewed and future perspectives have been detailed.
2.Role of Intestinal Microbiota in Metabolism of Voglibose In Vitro and In Vivo
Mahesh Raj NEPAL ; Mi Jeong KANG ; Geon Ho KIM ; Dong Ho CHA ; Ju-Hyun KIM ; Tae Cheon JEONG
Diabetes & Metabolism Journal 2020;44(6):908-918
Voglibose, an α-glucosidase inhibitor, inhibits breakdown of complex carbohydrates into simple sugar units in intestine. Studies showed that voglibose metabolism in the liver might be negligible due to its poor intestinal absorption. Numerous microorganisms live in intestine and have several roles in metabolism and detoxification of various xenobiotics. Due to the limited information, the possible metabolism of voglibose by intestinal microbiota was investigated For the The The present results indicate that voglibose would be metabolized by the intestinal microbiota, and that this metabolism might be pharmacodynamically critical in lowering blood glucose levels in mice.
3.Pharmacokinetic Interaction of Chrysin with Caffeine in Rats.
Keumhan NOH ; Do Gyeong OH ; Mahesh Raj NEPAL ; Ki Sun JEONG ; Yongjoo CHOI ; Mi Jeong KANG ; Wonku KANG ; Hye Gwang JEONG ; Tae Cheon JEONG
Biomolecules & Therapeutics 2016;24(4):446-452
Pharmacokinetic interaction of chrysin, a flavone present in honey, propolis and herbs, with caffeine was investigated in male Sprague-Dawley rats. Because chrysin inhibited CYP1A-selective ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase activities in enriched rat liver microsomes, the pharmacokinetics of caffeine, a CYP 1A substrate, was studied following an intragastric administration with 100 mg/kg chrysin. In addition to the oral bioavailability of chrysin, its phase 2 metabolites, chrysin sulfate and chrysin glucuronide, were determined in rat plasma. As results, the pharmacokinetic parameters for caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) were not changed following chrysin treatment in vivo, despite of its inhibitory effect on CYP 1A in vitro. The bioavailability of chrysin was found to be almost zero, because chrysin was rapidly metabolized to its sulfate and glucuronide conjugates in rats. Taken together, it was concluded that the little interaction of chrysin with caffeine might be resulted from the rapid metabolism of chrysin to its phase 2 metabolites which would not have inhibitory effects on CYP enzymes responsible for caffeine metabolism.
Animals
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Biological Availability
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Caffeine*
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Cytochrome P-450 CYP1A1
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Drug Interactions
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Honey
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Humans
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In Vitro Techniques
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Male
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Metabolism
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Microsomes, Liver
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Pharmacokinetics
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Plasma
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Propolis
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Rats*
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Rats, Sprague-Dawley
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Theobromine
4.Effects of Baicalin on Oral Pharmacokinetics of Caffeine in Rats.
Keumhan NOH ; Mahesh Raj NEPAL ; Ki Sun JEONG ; Sun A KIM ; Yeon Ji UM ; Chae Shin SEO ; Mi Jeong KANG ; Pil Hoon PARK ; Wonku KANG ; Hye Gwang JEONG ; Tae Cheon JEONG
Biomolecules & Therapeutics 2015;23(2):201-206
Scutellaria baicalensis is one of the most widely used herbal medicines in East Asia. Because baicalein and baicalin are major components of this herb, it is important to understand the effects of these compounds on drug metabolizing enzymes, such as cytochrome P450 (CYP), for evaluating herb-drug interaction. The effects of baicalin and baicalein on activities of ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), benzyloxyresorufin O-debenzylase (BROD), p-nitrophenol hydroxylase and erythromycin N-demethylase were assessed in rat liver microsomes in the present study. In addition, the pharmacokinetics of caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) in baicalin-treated rats were compared with untreated control. As results, EROD, MROD and BROD activities were inhibited by both baicalin and baicalein. However, there were no significant differences in the pharmacokinetic parameters of oral caffeine and its three metabolites between control and baicalin-treated rats. When the plasma concentration of baicalin was determined, the maximum concentration of baicalin was below the estimated IC50 values observed in vitro. In conclusion, baicalin had no effects on the pharmacokinetics of caffeine and its metabolites in vivo, following single oral administration in rats.
Administration, Oral
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Animals
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Caffeine*
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Cytochrome P-450 CYP1A1
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Cytochrome P-450 CYP2B1
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Cytochrome P-450 CYP3A
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Cytochrome P-450 Enzyme System
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Drug Interactions
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Far East
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Herb-Drug Interactions
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Inhibitory Concentration 50
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Microsomes, Liver
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Pharmacokinetics*
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Plasma
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Rats*
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Scutellaria baicalensis
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Theobromine