| Description: |
Genipin is an excellent natural cross-linker for proteins, collagen, gelatin, and chitosan cross-linking, can be used as a regulating agent for drug delivery, as the raw material for gardenia blue pigment preparation. It is a novel chemical activator of EBV lytic cycle and a cell permeable inhibitor of uncoupling protein 2 (UCP2). Genipin has antimicrobial,antiviral, antitumor, and anti-inflammatory effects, it is used for choleretic action for liver diseases control and could be used for the treatment of periodontal disease to prevent MMPs expression in periodontal lesion. It shows an antithrombotic effect in vivo due to the suppression of platelet aggregation. |
| Targets: |
ERK | TNF-α | MMP(e.g.TIMP) | JNK | AMPK | VEGFR | Phospholipase (e.g. PLA) | COX | NF-kB | PI3K | Akt | ROS | MAPK | AP-1 |
| In vitro: |
| J Microbiol. 2015 Feb;53(2):155-65. | | Genipin as a novel chemical activator of EBV lytic cycle.[Pubmed: 25626372] | Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that causes acute infection and establishes life-long latency. EBV causes several human cancers, including Burkitt's lymphoma, nasopharyngeal and gastric carcinoma. Antiviral agents can be categorized as virucides, antiviral chemotherapeutic agents, and immunomodulators. Most antiviral agents affect actively replicating viruses, but not their latent forms. Novel antiviral agents must be active on both the replicating and the latent forms of the virus. Gardenia jasminoides is an evergreen flowering plant belonging to the Rubiaceae family and is most commonly found growing wild in Vietnam, Southern China, Taiwan, Japan, Myanmar, and India. Genipin is an aglycone derived from an iridoid glycoside called geniposide, which is present in large quantities in the fruit of G. jasminoides.
METHODS AND RESULTS:
In this study, genipin was evaluated for its role as an antitumor and antiviral agent that produces inhibitory effects against EBV and EBV associated gastric carcinoma (EBVaGC). In SNU719 cells, one of EBVaGCs, genipin caused significant cytotoxicity (70 μM), induced methylation on EBV C promoter and tumor suppressor gene BCL7A, arrested cell-cycle progress (S phases), upregulated EBV latent/lytic genes in a dose-dependent manner, stimulated EBV progeny production, activated EBV F promoter for EBV lytic activation, and suppressed EBV infection.
CONCLUSIONS:
These results indicated that genipin could be a promising candidate for antiviral and antitumor agents against EBV and EBVaGC. | | Biomaterials. 2013 Oct;34(31):7754-65. | | Induction of angiogenesis using VEGF releasing genipin-crosslinked electrospun gelatin mats.[Pubmed: 23863451] | Rapid and controlled vascularization of engineered tissues remains one of the key limitations in tissue engineering applications.
METHODS AND RESULTS:
This study investigates the possible use of natural extracellular matrix-like scaffolds made of gelatin loaded with human vascular endothelial growth factor (VEGF), as a bioresorbable platform for long-term release and consequent angiogenic boosting. For this aim, gelatin was firstly electrospun and then cross-linked at two different concentrations (0.1% and 0.5% w/v) by using genipin, a low toxic agent, in order to fabricate a suitable substrate to be loaded with VEGF. Collected fibers were homogeneous and free of beads, the fibrous structure was retained after cross-linking. Mechanical properties were deeply affected by the chemical treatment showing a different behavior, depending on the testing conditions (i.e., dry or wet state). VEGF release was assessed by means of ELISA assay: a cumulative release of about 90% (0.1% w/v) and 60% (0.5% w/v) at 28 days was measured. Both VEGF loaded mats induced cell viability, endothelial differentiation and showed chemoattractive properties when tested on human mesenchymal stromal cells (hMSCs). In vitro and in vivo angiogenic assays demonstrated that the VEGF loaded mats induced an angiogenic potential in stimulating new vessel formation similar, if not superior, to fresh VEGF. VEGF retains bioactive and pro-angiogenic potential for up to 14 days.
CONCLUSIONS:
The results demonstrated that genipin cross-linked electrospun gelatin mats loaded with VEGF could be part of a useful strategy to stimulate and induce angiogenesis in tissue engineered applications. |
|
| In vivo: |
| Biochimie. 2014 Dec;107 Pt B:391-5. | | Genipin inhibits MMP-1 and MMP-3 release from TNF-a-stimulated human periodontal ligament cells.[Pubmed: 25457105] | Genipin, the aglycon of geniposide found in gardenia fruit has long been considered for treatment of inflammatory diseases in traditional oriental medicine. Genipin has recently been reported to have some pharmacological functions, such as antimicrobial, antitumor, and anti-inflammatory effects.
METHODS AND RESULTS:
The aim of this study was to examine whether genipin could modify matrix metalloproteinase (MMP)-1 and MMP-3, which are related to the destruction of periodontal tissues in periodontal lesion, expression in tumor necrosis factor (TNF)-α-stimulated human periodontal ligament cells (HPDLCs). Genipin prevented TNF-α-mediated MMP-1 and MMP-3 productions in HPDLCs. Moreover, genipin could suppress not only extracellular signal-regulated kinase (ERK) and Jun-N-terminal kinase (JNK) phosphorylations but also AMP-activated protein kinase (AMPK) phosphorylation in TNF-α-stimulated HPDLCs. Inhibitors of ERK and AMPK could inhibit both MMP-1 and MMP-3 productions. Moreover, we revealed the ERK inhibitor suppressed AMPK phosphorylation in TNF-α-stimulated HPDLCs.
CONCLUSIONS:
These data provide a new mechanism through which genipin could be used for the treatment of periodontal disease to prevent MMPs expression in periodontal lesion. | | Epigenetics . 2018;13(3):310-317. | | Genipin normalizes depression-like behavior induced by prenatal stress through inhibiting DNMT1[Pubmed: 29522357] | | Abstract
Synthetic antidepressants in current use for the complex etiopathogeneses of depression have slow response and remission as well as various unpleasant side effects. As a result, it is imperative to develop new antidepressants with more effectiveness and less severe side effects. Recent studies demonstrated that genipin, the aglycon of geniposide, extracted from Gardenia jasminoides Ellis has antidepressive effects. However, knowledge regarding the molecular mechanisms of its antidepressant effects remains limited. Employing a depression-like mouse model, we confirmed that genipin is capable of correcting depressions-like behaviors induced by prenatal stress in offspring from prenatally stressed dams (defined as PRS mice). In further experiments, we found that the effect of genipin on PRS mice occurs through DNA demethylation by inhibiting DNA methyltransferase 1 (DNMT1), normalizing the expression of reduced brain-derived neurotrophic factor (BDNF) in the hippocampus.
Keywords: BDNF; DNA methylation; DNMT1; Genipin; depression; mouse; prenatal stress. |
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