Therapeutic Potential of Genipin in Central Neurodegenerative Diseases

Li, Yanwei; Li, Lin; Hölscher, Christian

doi:10.1007/s40263-016-0369-9

Cited by 39 publications

(31 citation statements)

References 80 publications

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“…Iridoids [e.g. geniposide (P5) and geniposidic acid (P2)] of Gardeniae Fructus and Eucommia Cortex are known to possess wide-ranging pharmacological actions in treating cardiovascular and cerebrovascular diseases and central nervous system diseases (He et al, 2014;Li, Li, & Holscher, 2016;Liu, Chen, Li, & Zhang, 2013). Similarly, pharmacological studies have proven that leonurine (P9), the main component of Leonuri Herba, is effective in treating cardiovascular diseases in various ways (Zhu, Wu, Zhu, & Liu, 2018).…”

Section: Analysis Of Plasmatic and Biliary Absorbed And Metabolic Pmentioning

confidence: 99%

Identification of the absorbed components and their metabolites of Tianma‐Gouteng granule in rat plasma and bile using ultra‐high‐performance liquid chromatography combined with quadrupole time‐of‐flight mass spectrometry

Zhang

Duan

Wang

et al. 2019

Biomedical Chromatography

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Tianma‐Gouteng granule (TGG), a Chinese herbal formula preparation, is clinically used for the treatment of cardio‐cerebrovascular diseases such as hypertension, cerebral ischaemia, acute ischaemic stroke and Parkinson's disease. Although few reports have been published concerning the absorbed prototype components of TGG, the possible metabolic pathways of TGG in vivo remain largely unclear. In this study, a method using UPLC–Q/TOF MS was established for the detection and identification of the absorbed prototype components and related metabolites in rat plasma and bile after oral administration of TGG at high and normal clinical dosages. A total of 68 components were identified or tentatively identified in plasma and bile samples, including absorbed prototypes and their metabolites. The major absorbed components were gastrodin, isorhynchophylline, rhynchophylline, isocorynoxeine, corynoxeine, geissoschizine methyl ether baicalin, baicalein, wogonoside, wogonin, geniposidic acid, leonurine, 2,3,5,4′‐tetrahydroxystilbene‐2‐O‐β‐d‐glucoside and emodin. The main metabolic pathways of these components involved phase I (isomerization, hydrolysis and reduction) and phase II (glucuronidation and sulfation) reaction, and the phase II biotransformation pathway was predominant. The present study provides rich information on the in vivo absorption and metabolism of TGG, and the results will be helpful for further studies on the pharmacokinetics and pharmacodynamics of TGG.

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Section: Analysis Of Plasmatic and Biliary Absorbed And Metabolic Pmentioning

confidence: 99%

Identification of the absorbed components and their metabolites of Tianma‐Gouteng granule in rat plasma and bile using ultra‐high‐performance liquid chromatography combined with quadrupole time‐of‐flight mass spectrometry

Zhang

Duan

Wang

et al. 2019

Biomedical Chromatography

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“…To stabilize ECM scaffolds, genipin crosslinking was used in myocardial matrix hydrogel 20 , decellularized spinal cord 21 or whole-liver decellularized grafts 22 , where it proved to have a lower cytotoxicity and in vivo immunogenicity than their glutaraldehyde-treated counterparts. In addition, genipin possesses a range of key pharmacological properties, such as anti-inflammatory, neuroprotective, neurogenic, and antidepressant effects which gives this compound therapeutic potential for diseases of the CNS 23 .…”

Section: Introductionmentioning

confidence: 99%

Genipin and EDC crosslinking of extracellular matrix hydrogel derived from human umbilical cord for neural tissue repair

Výborný

Vallová

Kočí

et al. 2019

Sci Rep

106

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Extracellular matrix (ECM) hydrogels, produced by tissue decellularization are natural injectable materials suitable for neural tissue repair. However, the rapid biodegradation of these materials may disrupt neural tissue reconstruction in vivo . The aim of this study was to improve the stability of the previously described ECM hydrogel derived from human umbilical cord using genipin and N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC), crosslinking at concentration of 0.5–10 mM. The hydrogels, crosslinked by genipin (ECM/G) or EDC (ECM/D), were evaluated in vitro in terms of their mechanical properties, degradation stability and biocompatibility. ECM/G, unlike ECM/D, crosslinked hydrogels revealed improved rheological properties when compared to uncrosslinked ECM. Both ECM/G and ECM/D slowed down the gelation time and increased the resistance against in vitro enzymatic degradation, while genipin crosslinking was more effective than EDC. Crosslinkers concentration of 1 mM enhanced the in vitro bio-stability of both ECM/G and ECM/D without affecting mesenchymal stem cell proliferation, axonal sprouting or neural stem cell growth and differentiation. Moreover, when injected into cortical photochemical lesion, genipin allowed in situ gelation and improved the retention of ECM for up to 2 weeks without any adverse tissue response or enhanced inflammatory reaction. In summary, we demonstrated that genipin, rather than EDC, improved the bio-stability of injectable ECM hydrogel in biocompatible concentration, and that ECM/G has potential as a scaffold for neural tissue application.

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“…GP is a good crosslinking reagent for biological tissue fixation (Silva, Saint‐Jalmes, de Carvalho, & Gaucheron, ). GP possesses more potent pharmacological activities than GE, such as choleretic (Shoda et al, ), anti‐inflammatory (Li et al, ; Rajanbabu et al, ), antiapoptosis (Kim, Kim, Lee, Kwak, & Lee, ), antifibrosis (Inao et al, ), treatment of sprain (Chen et al, ), and neuroprotective effects (Li, Li, & Holscher, ). On the other hand, several studies demonstrate that GE causes acute liver injury after oral administration, and GP is responsible for GE‐induced hepatotoxicity (Khanal et al, ; Wei et al, ; Yamano et al, ).…”

Section: Introductionmentioning

confidence: 99%

A sensitive LC–MS/MS method for simultaneous quantification of geniposide and its active metabolite genipin in rat plasma and its application to a pharmacokinetic study

Shi

Pan

et al. 2017

Biomedical Chromatography

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Genipin (GP), an active metabolite of geniposide (GE), exhibits more potent pharmacological effects than its parent compound. In this paper, a sensitive LC-MS/MS method was developed and fully validated for the simultaneous determination of GE and GP in rat plasma. We found that GP degraded rapidly in rat plasma at room temperature as a result of irreversible binding with the endogenous nucleophiles in plasma. GP was stable when the sample's pH was ≤4.0. The degradation of GP in rat plasma was well prevented by immediate addition of 5% glacial acetic acid to the freshly collected plasma. The detection was performed on a tandem mass spectrometer coupled with electrospray ionization source in negative mode. Quantification was conducted by multiple reaction monitoring of the transitions [M + CH COO] m/z 447.3 → 225.3 for GE and [M - H] m/z 225.2 → 123.1 for GP. The method exhibited high sensitivity (LLOQ 1 ng/mL for GE and 0.2 ng/mL for GP) by selecting the acetate adduct ions as the precursor ions for GE. The robust developed method was successfully applied to a pharmacokinetic study in rats after oral administration of GE.

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Therapeutic Potential of Genipin in Central Neurodegenerative Diseases

Cited by 39 publications

References 80 publications

Identification of the absorbed components and their metabolites of Tianma‐Gouteng granule in rat plasma and bile using ultra‐high‐performance liquid chromatography combined with quadrupole time‐of‐flight mass spectrometry

Identification of the absorbed components and their metabolites of Tianma‐Gouteng granule in rat plasma and bile using ultra‐high‐performance liquid chromatography combined with quadrupole time‐of‐flight mass spectrometry

Genipin and EDC crosslinking of extracellular matrix hydrogel derived from human umbilical cord for neural tissue repair

A sensitive LC–MS/MS method for simultaneous quantification of geniposide and its active metabolite genipin in rat plasma and its application to a pharmacokinetic study

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