• 한국식품영양과학회지
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• 제27권5호
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• pp.1015-1018
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• 1998

Capsaicin(8-methyl-N-vanillyl-6-nonenamide: CAP) known well as a major compound of not taste in hot pepper, was investigated for the inhibition effect on in vitro nitrosation. CAP(100$\mu$mol) inhibited the formation of N-nitrosoproline(NPRO) and N-nitrosothioproline(NTPRO) by 56% and 26%, respectively. Vanillyl alcohol inhibited the nitrosation of proline by a concentration-dependent manner, and vanillic acid and vanillin were less effective in blocking the nitrosation of proline compared to CAP and anillyl alcohol. The inhibitory effect of NPRO formation by CAP was evaluated to similar with alpha-tocopherol, and vanillyl alcohol was more effective than alpha-tocopherol in blocking the nitrosation of proline. Our results suggested that CAP and its metabolites such as vanillyl alcohol could inhibit endogenous nitrosation in hydrophobic biological environment.

• 분석과학
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• 제33권2호
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• pp.59-67
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• 2020

Nadolol is a β-blocker drug, which effectively manages hypertension and angina pectoris. Its chemical structure allows the formation of four possible stereoisomers. A coupled column high-performance liquid chromatographic (HPLC) system with UV and fluorescence detection was investigated for simultaneously determining four nadolol enantiomers in human plasma. The plasma samples were prepared using a convenient liquid-liquid extraction process and passed through HPLC. Nadolol was initially separated from the endogenous compounds or other impurities in human plasma on a Phenomenex silica column, and its enantiomers were resolved and determined on a Chirapak AD-H column. The developed HPLC method achieved an effective chiral separation and significantly eliminated endogenous compound interference. This optimal HPLC method was validated following FDA guidelines. The results showed good selectivity, linearity, accuracy (90.50 % - 105.27 %), and precision (RSDs < 9.52 %) for each enantiomer. This method was also successfully applied to determine nadolol enantiomers in the plasma samples of a healthy male volunteer (after orally administering 80 mg racemic nadolol), proving its suitability for nadolol stereoselective pharmacokinetic studies.

• 대한약침학회지
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• 제13권3호
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• pp.47-62
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• 2010

Objectives: Colitis is an inflammatory bowel disease characterized by colonic mucosal inflammation and chronic relapsing events represents. The purpose of this study is to evaluate effects of pharmacopuncture of anti-inflammatory herbal compound (AiC) applied to the different acupoints in the acute colitis induced by trinitrobenzenesulphonic acid (TNBS) intracolonic injection in rats. Methods: In Male Sprague - Dawley rats, weighing 250~400g, TNBS (5 mg/kg) was infused intrarectally through a silicon rubber catheter into the anus under isoflurane anaesthesia. Acupoints of LI4 (Hapkok), ST25 (Cheonchu), ST36 (Joksamni), and BL25 (Daejangsu) were intramuscularly injected by AiC, respectively (injection volume & times: 0.2 ml / acupoint, twice times on the 2nd & 3rd day). Expressions of cFos protein in the periaqueductal gray (PAG), locus coeruleus (LC), nucleus of solitary tract (Sol), and the 6th lumbar spinal cord (L6 s.c.) were observed at 24 hr after TNBS induced colitis by immunohistochemistry. Results: The expression of c-Fos protein in the L6 s.c., Sol, LC and PAG increased 24 hr after TNBS injection into colorectum as compared to normal and 50% ethanol treated group. AiC to LI4 inhibited the expression of c-Fos protein in Sol and PAG but not L6 s.c. and LC. AiC to ST36 showed significant inhibition the c-Fos expression in L6 s.c., Sol and PAG. AiC to ST25 only showed the effects in L6 s.c. and PAG. AiC to BL25 inhibited significantly the expression of c-Fos protein all over the areas. To investigate whether or not endogenous opioids are involved, intrathecal injection of naltrexone (30ug/30ul) was applied before the 2nd pharmacopuncture treatment 24 hr after TNBS-induced colitis in rat. Naltrexone reversed the inhibition of c-Fos protein expression in the spinal cord and brainstem. Conclusions: These data show that pharmacopuncture of Aic potently inhibits signal pathways ascending hypersensitivity of colorectum after TNBS induced colitis and depends on the endogenous opioids according to acupoints.

• 한국식품영양과학회지
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• 제22권3호
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• pp.266-272
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• 1993

우리들의 식이중에 함유되어 있는 플라보노이드 화합물들이 니트로소화합물의 생성에 미치는 영향을 알아보기 위하여 생체내에서 일어나는 니트로소화 과정을 아질산염, 프로린과 시료를 동시에 투여하여 생성된 니트로소프로린 함량을 시험관 및 생체조건하에서 HPLC로서 측정하였다. 그 결과, 잘 알려진 ascorbic acid, KSCN과 더불어 catechin, chlorogenic acid, morin, luteolin, luteolin-7-O-glucoside, naringenin 등은 아질산염 소거에는 상당한 효과가 있는 것으로 나타났으나, 니트로소프로린 생성에 대해서는 ascorbic acid와 chlorogenic acid를 제외한 나머지 화합물들은 거의 영향을 미치지 않거나 오히려 그 생성을 촉진시키는 것으로 나타났다.

• Biomolecules & Therapeutics
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• 제30권1호
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• pp.48-54
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• 2022

GPR43 (also known as FFAR2), a metabolite-sensing G-protein-coupled receptor stimulated by short-chain fatty acid (SCFA) ligands is involved in innate immunity and metabolism. GPR43 couples with Gα_i/o and Gα_q/11 heterotrimeric proteins and is capable of decreasing cyclic AMP and inducing Ca²⁺ flux. The GPR43 receptor has additionally been shown to bind β-arrestin 2 and inhibit inflammatory pathways, such as NF-κB. However, GPR43 shares the same ligands as GPR41, including acetate, propionate, and butyrate, and determination of its precise functions in association with endogenous ligands, such as SCFAs alone, therefore remains a considerable challenge. In this study, we generated novel synthetic agonists that display allosteric modulatory effects on GPR43 and downregulate NF-κB activity. In particular, the potency of compound 187 was significantly superior to that of pre-existing compounds in vitro. However, in the colitis model in vivo, compound 110 induced more potent attenuation of inflammation. These novel allosteric agonists of GPR43 clearly display anti-inflammatory potential, supporting their clinical utility as therapeutic drugs.

• BMB Reports
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• 제42권11호
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• pp.737-742
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• 2009

Hypoxia-inducible factor-$1{\alpha}/{\beta}$ (HIF-$1{\alpha}/{\beta}$) is a heterodimeric transcriptional activator that mediates gene expression in response to hypoxia. HIF-$1{\alpha}$ has been noted as an effective therapeutic target for ischemic diseases such as myocardiac infarction, stroke and cancer. By using a yeast two-hybrid system and a random peptide library, we found a 16-mer peptide named F29 that directly interacts with the bHLH-PAS domain of HIF-$1{\alpha}$. We found that F29 facilitates the interaction of the HIF-$1{\alpha/\beta}$ heterodimer with its target DNA sequence, hypoxia-responsive element (HRE). The transient transfection of an F29-expressing plasmid increases the expression of both an HRE-driven luciferase gene and the endogenous HIF-1 target gene, vascular endothelial growth factor (VEGF). Taken together, we conclude that F29 increases the DNA-binding ability of HIF-$1{\alpha}$, leading to increased expression of its target gene VEGF. Our results suggest that F29 can be a lead compound that directly targets HIF-$1{\alpha}$ and increases its activity.

• The Plant Pathology Journal
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• 제24권3호
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• pp.245-268
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• 2008

The outcome of plant-pathogen interactions is influenced significantly by endogenous small molecules that coordinate plant defence responses. There is currently tremendous scientific and commercial interest in identifying chemicals whose exogenous application activates plant defences and affords protection from pathogen infection. In this review, we provide a survey of compounds known to induce disease resistance in plants, with particular emphasis on how each compound was originally identified, its putative or demonstrated mechanism of defence induction, and the known biological target(s) of each chemical. Larger polymeric structures and peptides/proteins are also discussed in this context. The quest for novel defence-inducing molecules would be aided by the capability for high-throughput analysis of candidate compounds, and we describe some issues associated with the development of these types of screens. Subsequent characterization of hits can be a formidable challenge, especially in terms of identifying chemical targets in plant cells. A variety of powerful molecular tools are available for this characterization, not only to provide insight into methods of plant defence activation, but also to probe fundamental biological processes. Furthermore, these investigations can reveal molecules with significant commercial potential as crop protectants, although a number of factors must be considered for this potential to be realized. By highlighting recent progress in the application of chemical biology techniques for the modulation of plant-pathogen interactions, we provide some perspective on the exciting opportunities for future progress in this field of research.

• Mass Spectrometry Letters
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• 제11권1호
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• pp.10-14
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• 2020

Riboflavin is a water-soluble vitamin, which serves as a precursor to flavin mononucleotide and flavin adenine dinucleotide. This study aimed to develop a simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for the quantification of riboflavin in the Beagle dog plasma. This method utilized simple protein precipitation with acetonitrile and ¹³C₄, ¹⁵N₂-riboflavin was used as an internal standard (IS). For chromatographic separation, a hydrophilic interaction liquid chromatography (HILIC) column was used with gradient elution. The mobile phase consisted of 0.1% (v/v) aqueous formic acid with 10 mM ammonium formate and acetonitrile with 0.1% (v/v) formic acid. Since riboflavin is an endogenous compound, 4% bovine serum albumin in phosphate buffered saline was used as a surrogate matrix to prepare the calibration curve. The quantification limit for riboflavin in the Beagle dog plasma was 5 ng/mL. The method was fully validated for its specificity, sensitivity, accuracy and precision, recovery, and stability according to the US FDA guidance. The developed LC-MS/MS method may be useful for the in vivo pharmacokinetic studies of riboflavin.

• 약학회지
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• 제26권4호
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• pp.223-229
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• 1982

Uremia is associated with defective protein binding of weakly acidic drugs, whereas the protein binding of basic drugs tends to be normal. The exact chemical nature of compound(s) and mechanism for these changes as yet is unknown, and has not been defined. Organic solvent extraction of pooled normal human urine following hydrolysis by hydrochloric acid produced an extract, which when added to normal human serum, was capable of inducing binding defects similar to those in uremia. Binding defects were observed with the weakly acidic drugs such as nafcillin, salicylate, sulfamethoxazole and phenytoin while the binding of the basic drugs such as trimethoprim and quinidine were unaffected. The binding defects induced by the hydrolyzed urine extract could readily be corrected by same organic solvent extraction of acidified serum and the defects could be transferred to the normal human serum using the organic solvent layer at the physiologic pH (7.4). Followed by reacidification ind extraction of the binding defects induced serum with the same solvent, separated several fractions were obtained on thin-layer chromatography. One of these fractions could reinduce the binding defects and this factor(s) is apparently weakly acidic compounds and tightly bound to serum at physiologic pH, but extractable at acidic pH, and its molecular weight range is approximately 500 or less similar to those seen in uremia. These findings strongly support the hypothesis that the drug binding defect in uremia is due to the accumulation of endogenous metabolic products which arc normally excreted by the kidneys but accumulate in renal failure.

• Asian-Australasian Journal of Animal Sciences
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• 제27권7호
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• pp.917-925
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• 2014

An accurate feed formulation is essential for optimizing feed efficiency and minimizing feed cost for swine and poultry production. Because energy and amino acid (AA) account for the major cost of swine and poultry diets, a precise determination of the availability of energy and AA in feedstuffs is essential for accurate diet formulations. Therefore, the methodology for determining the availability of energy and AA should be carefully selected. The total collection and index methods are 2 major procedures for estimating the availability of energy and AA in feedstuffs for swine and poultry diets. The total collection method is based on the laborious production of quantitative records of feed intake and output, whereas the index method can avoid the laborious work, but greatly relies on accurate chemical analysis of index compound. The direct method, in which the test feedstuff in a diet is the sole source of the component of interest, is widely used to determine the digestibility of nutritional components in feedstuffs. In some cases, however, it may be necessary to formulate a basal diet and a test diet in which a portion of the basal diet is replaced by the feed ingredient to be tested because of poor palatability and low level of the interested component in the test ingredients. For the digestibility of AA, due to the confounding effect on AA composition of protein in feces by microorganisms in the hind gut, ileal digestibility rather than fecal digestibility has been preferred as the reliable method for estimating AA digestibility. Depending on the contribution of ileal endogenous AA losses in the ileal digestibility calculation, ileal digestibility estimates can be expressed as apparent, standardized, and true ileal digestibility, and are usually determined using the ileal cannulation method for pigs and the slaughter method for poultry. Among these digestibility estimates, the standardized ileal AA digestibility that corrects apparent ileal digestibility for basal endogenous AA losses, provides appropriate information for the formulation of swine and poultry diets. The total quantity of energy in feedstuffs can be partitioned into different components including gross energy (GE), digestible energy (DE), metabolizable energy (ME), and net energy based on the consideration of sequential energy losses during digestion and metabolism from GE in feeds. For swine, the total collection method is suggested for determining DE and ME in feedstuffs whereas for poultry the classical ME assay and the precision-fed method are applicable. Further investigation for the utilization of ME may be conducted by measuring either heat production or energy retention using indirect calorimetry or comparative slaughter method, respectively. This review provides information on the methodology used to determine accurate estimates of AA and energy availability for formulating swine and poultry diets.