Absolute bioavailability, tissue distribution, and excretion of 2,4,5-trimethoxybenzaldehyde in rats

Schisandrol B, a lignan isolated from dried Schisandra chinensis fruits, has been shown to exhibit hepatoprotective, cardioprotective, renoprotective, and memory-enhancing properties. This study sought to design a sensitive and efficient HPLC-MS/MS approach to measuring Schisandrol B levels in rat plasma and tissues in order to assess the pharmacokinetics, oral bioavailability, and tissue distributions of this compound in vivo. For this analysis, bifendate was chosen as an internal standard (IS). A liquid-liquid extraction (LLE) approach was employed for the preparation of samples that were subsequently separated with an Agilent ZORBAX Eclipse XDB-C18 (4.6 × 150 mm, 5 μm) column with an isocratic mobile phase consisting of methanol and water containing 5 mM ammonium acetate and 0.1% formic acid (90 : 10, v/v). A linear calibration curve was obtained over the 5–2000 ng/mL and 1–1000 ng/mL ranges for plasma samples and tissue homogenates, respectively. This established method was then successfully applied to investigate the pharmacokinetics, oral bioavailability, and tissue distributions of Schisandrol B in Sprague-Dawley (SD) rats that were intravenously administered 2 mg/kg of Schisandrol B monomer, intragastrically administered Schisandrol B monomer (10 mg/kg), or intragastrically administered 6 mL/kg SCE (equivalent to 15 mg/kg Schisandrol B monomer). The oral absolute bioavailability of Schisandrol B following intragastric Schisandrol B monomer and SCE administration was approximately 18.73% and 68.12%, respectively. Tissue distribution studies revealed that Schisandrol B was distributed throughout several tested tissues, with particular accumulation in the liver and kidneys. Our data represent a valuable foundation for future studies of the pharmacologic and biological characteristics of Schisandrol B.

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Absolute Bioavailability, Tissue Distribution, and Excretion of Erinacine S in Hericium erinaceus Mycelia

Molecules ◽

10.3390/molecules24081624 ◽

2019 ◽

Vol 24 (8) ◽

pp. 1624 ◽

Cited By ~ 1

Author(s):

Jun-Hao Hu ◽

I-Chen Li ◽

Ting-Wei Lin ◽

Wan-Ping Chen ◽

Li-Ya Lee ◽

...

Keyword(s):

Body Weight ◽

Oral Administration ◽

Tissue Distribution ◽

Neurological Diseases ◽

Amyloid Plaque ◽

Oral Dosage ◽

Absolute Bioavailability ◽

Sprague Dawley ◽

Hericium Erinaceus ◽

The Absolute

Erinacine S, so far known to have been produced only in Hericium erinaceus mycelia, has just recently been discovered and is able to reduce amyloid plaque growth and improve neurogenesis in aged brain of rats. However, few investigations have been conducted on the absorption, distribution, and excretion study of Erinacine S. This study aimed to investigate the absolute bioavailability, tissue distribution, and excretion of Erinacine S in H. Erinaceus mycelia in eight-week old Sprague-Dawley rats. After oral administration and intravenous administration of 2.395 g/kg body weight of the H. erinaceus mycelia extract (equivalent to 50 mg/kg body weight Erinacine S) and 5 mg/kg of Erinacine S, respectively, the absolute bioavailability was estimated as 15.13%. In addition, Erinacine S was extensively distributed in organs such as brain, heart, lung, liver, kidney, stomach, small intestine, and large intestine. The maximum concentration of Erinacine S was observed in the stomach, 2 h after the oral administration of H. erinaceus mycelia extract, whereas the maximum amount of Erinacine S found in other tissues were seen after 8 h. Total amount of unconverted Erinacine S eliminated in feces and urine in 24 h was 0.1% of the oral dosage administrated. This study is the first to show that Erinacine S can penetrate the blood–brain barrier of rats and thus support the development of H. erinaceus mycelia, for the treatment of neurological diseases.

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Preclinical Bioavailability, Tissue Distribution, and Protein Binding Studies of Erinacine A, a Bioactive Compound from Hericium erinaceus Mycelia Using Validated LC-MS/MS Method

Molecules ◽

10.3390/molecules26154510 ◽

2021 ◽

Vol 26 (15) ◽

pp. 4510

Author(s):

Pei-Ching Tsai ◽

Yi-Kai Wu ◽

Jun-Hao Hu ◽

I-Chen Li ◽

Ting-Wei Lin ◽

...

Keyword(s):

Protein Binding ◽

Tissue Distribution ◽

Bioactive Compound ◽

Passive Diffusion ◽

Absolute Bioavailability ◽

Sprague Dawley ◽

Binding Studies ◽

Hericium Erinaceus ◽

Major Route ◽

Erinacine A

Erinacine A, derived from the mycelia of Hericium erinaceus, has attracted much attention due to its neuroprotective properties. However, very few studies have been conducted on the bioavailability, tissue distribution, and protein binding of erinacine A. This study aimed to investigate the bioavailability, tissue distribution, and protein binding of erinacine A in Sprague-Dawley rats. After oral administration (po) and intravenous administration (iv) of 2.381 g/kg BW of the H. erinaceus mycelia extract (equivalent to 50 mg/kg BW of erinacine A) and 5 mg/kg BW of erinacine A, respectively, the absolute bioavailability of erinacine A was estimated as 24.39%. Erinacine A was detected in brain at 1 h after oral dosing and reached the peak at 8 h. Protein binding assay showed unbound erinacine A fractions in brain to blood ratio is close to unity, supporting passive diffusion as the dominating transport. Feces was the major route for the elimination of erinacine A. This study is the first to show that erinacine A can penetrate the blood-brain barrier of rats by the means of passive diffusion and thus support the development of H. erinaceus mycelia for the improvement of neurohealth.

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A Novel Co-Crystal of Bexarotene and Ligustrazine Improves Pharmacokinetics and Tissue Distribution of Bexarotene in SD Rats

Pharmaceutics ◽

10.3390/pharmaceutics12100906 ◽

2020 ◽

Vol 12 (10) ◽

pp. 906

Author(s):

Shuyue Ren ◽

Lingtai Jiao ◽

Shiying Yang ◽

Li Zhang ◽

Junke Song ◽

...

Keyword(s):

Tissue Distribution ◽

Neurological Disorders ◽

Cell Lymphoma ◽

Neurological Diseases ◽

Absolute Bioavailability ◽

The Novel ◽

Pharmaceutical Ingredients ◽

Sd Rats ◽

Fda Approval ◽

Enhanced Solubility

Bexarotene (BEX), a specific retinoic acid X receptor (RXR) agonist granted by Food and Drug Administration (FDA) approval for the clinical treatment of T cell lymphoma, has now been found to exert pharmacological effects in the nervous system, with low bioavailability and poor cerebral distribution limiting its application in treatment on neurological disorders. Pharmaceutical co-crystal was a helpful method to improve the bioavailability and tissue distribution of active pharmaceutical ingredients (APIs). Here, 2bexarotene-ligustrazine (2BEX-LIG), a novel co-crystal system of BEX and ligustrazine (LIG) of which with BEX is an API, was constructed with satisfactory stability and enhanced solubility. The pharmacokinetics characteristics of BEX were detected, and the results showed that the absolute bioavailability and the cerebral concentration of BEX in rats administrated with 2BEX-LIG were enhanced from 22.89% to 42.86% and increased by 3.4-fold, respectively, compared with those in rats administrated an equivalent of BEX. Hence, our present study indicated that the novel co-crystal of 2BEX-LIG contributed to improving BEX oral bioavailability and cerebral distribution, thereby providing significant advantages for clinical application of brain tumors and other neurological diseases.

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Pharmacokinetics and Tissue Distribution of Anwuligan in Rats after Intravenous and Intragastric Administration by Liquid Chromatography-Mass Spectrometry

Molecules ◽

10.3390/molecules25010039 ◽

2019 ◽

Vol 25 (1) ◽

pp. 39

Author(s):

Yang Song ◽

Yuan Zhang ◽

Xiao-Yi Duan ◽

Dong-Wei Cui ◽

Xin Qiu ◽

...

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Tissue Distribution ◽

Enterohepatic Circulation ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Absolute Bioavailability ◽

Intragastric Administration ◽

High Concentration ◽

Tissue Samples

Anwuligan, a natural 2,3-dibenzylbutane lignan from the nutmeg mace of Myristica fragans, has been proved to possess a broad range of pharmacological effects. A rapid, simple, and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been established and successfully applied to the study of pharmacokinetics and tissue distribution of anwuligan after intravenous or intragastric administration. Sample preparation was carried out through a liquid-liquid extraction method with ethyl acetate as the extraction reagent. Arctigenin was used as the internal standard (IS). A gradient program was employed with a mobile phase consisting of 0.1% formic acid aqueous solution and acetonitrile. The mass spectrometer was operated in a positive ionization mode with multiple reaction monitoring. The transitions for quantification were m/z 329.0→205.0 for anwuligan and m/z 373.0→137.0 for IS, respectively. Calibration curves were linear over the ranges of 0.5–2000 ng/mL for both plasma samples and tissue samples (r > 0.996). The absolute bioavailability is 16.2%, which represented the existing of the obvious first-pass effect. An enterohepatic circulation was found after the intragastric administration. Anwuligan could be distributed rapidly and widely in different tissues and maintained a high concentration in the liver. The developed and validated LC-MS/MS method and the pharmacokinetic study of anwuligan would provide reference for the future investigation of the preclinical safety of anwuligan as a candidate drug.

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