Koumine Attenuates Lipopolysaccaride-Stimulated Inflammation in RAW264.7 Macrophages, Coincidentally Associated with Inhibition of NF-κB, ERK and p38 Pathways

Yuan, Zhihang; Matias, Froilan Bernard; Wu, Jing; Liang, Zengenni; Sun, Zhi-Liang

doi:10.3390/ijms17030430

Cited by 39 publications

(23 citation statements)

References 27 publications

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“…Induced NO synthesis was reported in inflammatory responses initiated by microbial products or autoimmune reactions also to be the major NO synthase involved in NO production during inflammatory conditions (Yuan et al, 2016). It was clear that the level of iNOS activity was significantly elevated in the acetic acid control group as Results are expressed as mean ± S.E.M of 6 observations.…”

Section: Resultsmentioning

confidence: 99%

Comparative pharmaceutical study on colon targeted micro-particles of celecoxib:in-vitro–in-vivoevaluation

et al. 2016

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In order to target celecoxib which is a COX2 inhibitor, with potentials in the prevention and treatment of colitis and colon cancer, it was formulated as microparticles using the solvent/ evaporation method and various pH-dependent Eudragit polymers. The in-vitro evaluation of the prepared microparticles showed spherical and smooth morphology. The encapsulation efficiency and yield were high, indicating that the method used is simple and efficient at this scale. The in-vitro release study showed no release in the acidic medium for 2 h followed by the release of the drug in pH 6.8 in case of Eudragit L100-55 and L100 and pH 7.4 in case of Eudragit S100. The pharmacokinetic parameters were calculated and method validation was performed to insure that it is suitable and reliable. Pharmacokinetic parameters were investigated by determining the C max , T max , AUC 0-t , K el , and t 1/2 of the drug as a suspension and as microparticles. There was a significant difference (p50.05) in T max between the drug as a suspension and as microparticles. The effect of celecoxib on the degree of inflammation was examined on acetic acid induced colitis rat model and the drug was given as a suspension and as microparticles. The evaluation was done using macroscopical, microscopical and biochemical examination. There was a significant difference between the acetic acid control group and the treatment groups regarding all examination criteria in the order microparticles formulated using Eudragit S100 followed by Eudragit L100-55 while microparticles using Eudragit L100 and drug suspension showed almost the same results.

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Section: Resultsmentioning

confidence: 99%

Comparative pharmaceutical study on colon targeted micro-particles of celecoxib:in-vitro–in-vivoevaluation

et al. 2016

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“…Koumine (KM), the most abundant alkaloid in Gelsemium elegans Benth. ( G. elegans ) has various pharmacological properties and is known to be effective in the treatment of numerous age-associated conditions including postoperative pain ( Xiong et al., 2017 ; Shoaib et al., 2019 ), inflammation ( Yuan et al., 2016 ; Wu et al., 2020 ), rheumatoid arthritis ( Yang et al., 2016 ), malignant tumors ( Yuan et al., 2019a ), nonalcoholic fatty liver disease ( Yue et al., 2019 ), oxidative stress ( Yuan et al., 2019b ), and neuropathic pain ( Jin et al., 2018a ; Jin et al., 2018b ). However, the pharmacokinetic profile of KM in the elderly or aged animals remains to be fully evaluated.…”

Section: Introductionmentioning

confidence: 99%

Orally Administered Koumine Persists Longer in the Plasma of Aged Rats Than That of Adult Rats as Assessed by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry

Zhang

et al. 2020

Front. Pharmacol.

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Aging leads to changes in nearly all pharmacokinetic phases. Koumine (KM), an alkaloid derived from Gelsemium elegans Benth., is effective against age-associated chronic diseases, but its dose proportionality following oral administration in aged individuals remains unknown. Herein, we established and validated a simple method that requires low sample volumes to determine KM concentration in rats using ultra-performance liquid chromatography-tandem mass spectrometry. The maximum plasma concentration (C max) of 7 mg•kg −1 KM was~12-fold and~24-fold higher than that of 0.28 mg•kg −1 KM in adult and aged rats, respectively (P < 0.01). Time to reach C max (T max) for 7 mg•kg −1 KM was 4-fold longer in aged rats (P < 0.05). The area under the curve (AUC) of 7 mg•kg −1 KM was >17-fold and >43-fold higher than those of 0.28 mg•kg −1 KM in adult and aged rats, respectively (P < 0.01). The half-life (t 1/2) of 7 mg•kg −1 KM was over 4-fold longer than that of 0.28 mg•kg −1 KM in adult rats (P < 0.01). The t 1/2 of 1.4 and 7 mg•kg −1 KM were 1.5~2fold longer, than that of 0.28 mg•kg −1 KM in aged rats (P < 0.05). The clearance rate of 7 mg•kg −1 KM was significantly lower in aged than in adult rats (P < 0.05). For 7.0 mg•kg −1 KM, the C max in aged rats was higher than in adult rats during the T max period (P < 0.05). In aged rats, the AUC for KM was >2.5-fold higher (P < 0.05) and the t 1/2 was >60% longer than in adult rats (P < 0.05). These results help interpret the pharmacokinetics of KM in aging-associated diseases.

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“…It was widely used as a classic Chinese herbal medicine to treat malignant skin problems [ 1 ]. Recent years, its anti-tumor [ 2 ], anti-inflammatory [ 3 ], and anxiolytic [ 4 ] activities have also been well studied. On the other side, G. elegans was well-known for its toxicity.…”

Section: Introductionmentioning

confidence: 99%

Ultra-Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS)-Based Pharmacokinetics and Tissue Distribution Study of Koumine and the Detoxification Mechanism of Glycyrrhiza uralensis Fisch on Gelsemium elegans Benth.

et al. 2018

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Gelsemium elegans Benth. (G. elegans), which is a famous Chinese folk medicine, has been commonly used to treat certain types of skin ulcers and alleviate inflammation, headaches, and cancer pain. However, the extensive clinical use of G. elegans has been greatly hampered by its toxicity. As one of the most widely used herbal medicines, Glycyrrhiza uralensis Fisch, has a unique effect on detoxification of G. elegans. In the present study, a rapid and sensitive method using ultra-liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was established and validated for determination of koumine, the most abundant molecule among the alkaloids of G. elegans, in rat plasma, tissue, and liver microsome. The developed method was successfully applied to the pharmacokinetics, tissue distribution, and in vitro metabolism study in rat with or without pre-treated Glycyrrhiza uralensis Fisch extract. Meanwhile, the expression level of CYP3A1 mRNA was analyzed to explain the detoxification mechanism of Glycyrrhiza uralensis Fisch on G. elegans. As a result, our work demonstrated that Glycyrrhiza uralensis Fisch could significantly affect the pharmacokinetics and tissue distribution of koumine in rats. The detoxification mechanism of Glycyrrhiza uralensis Fisch on G. elegans may be its cytochrome enzyme up-regulation effect.

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Koumine Attenuates Lipopolysaccaride-Stimulated Inflammation in RAW264.7 Macrophages, Coincidentally Associated with Inhibition of NF-κB, ERK and p38 Pathways

Cited by 39 publications

References 27 publications

Comparative pharmaceutical study on colon targeted micro-particles of celecoxib:in-vitro–in-vivoevaluation

Comparative pharmaceutical study on colon targeted micro-particles of celecoxib:in-vitro–in-vivoevaluation

Orally Administered Koumine Persists Longer in the Plasma of Aged Rats Than That of Adult Rats as Assessed by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry

Ultra-Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS)-Based Pharmacokinetics and Tissue Distribution Study of Koumine and the Detoxification Mechanism of Glycyrrhiza uralensis Fisch on Gelsemium elegans Benth.

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