Fruits Of Gardenia Jasminoides Research Articles

Genome-Wide Characterization and Analysis of bHLH Transcription Factors Related to Crocin Biosynthesis in Gardenia jasminoides Ellis (Rubiaceae).

Crocins, enriched in Gardenia jasminoides fruits, have a pharmacological activity against central nervous system diseases, cardiovascular diseases, and cancer cell growth. The biosynthesis of crocins has been widely explored, but its regulatory mechanism remains unknown. Here, the basic helix-loop-helix (bHLH) transcription factors related to crocin biosynthesis were systematically identified on the basis of the genome of G. jasminoides. A total of 95 GjbHLH transcription factor genes were identified, and their phylogenetic analysis indicated that they could be classified into 23 subfamilies. The combination of gene-specific bHLH expression patterns, the coexpression analysis of biosynthesis genes, and the analysis of promoter sequences in crocin biosynthesis pathways suggested that nine bHLHs in G. jasminoides might negatively regulate crocin biosynthesis. This study laid a foundation for understanding the regulatory mechanism of crocin biosynthesis and the improvement and breeding of G. jasminoides varieties.

Renoprotective Mono- and Triterpenoids from the Fruit of Gardenia jasminoides.

This paper describes the isolation and characterization of 17 new and 12 known terpenoids from the fruit of Gardenia jasminoides. The structures of eight new triterpenoids and nine new monoterpenoids, including their absolute configurations, were defined by spectroscopic analysis in combination of quantum chemical electronic circular dichroism (ECD), vibrational circular dichroism (VCD), and gauge-independent atomic orbital (GIAO) NMR calculations. The cytoprotective effects of the isolated compounds against lipopolysaccharide (LPS)-induced apoptosis in normal rat kidney tubule epithelioid (NRK 52e) cells were investigated in vitro. Compounds 10, 18, 20, 21, 24, and 26 exhibited significant protective effects with EC50 values from 14.2 nM to 1.6 μM.

Genipin as An Emergent Tool in the Design of Biocatalysts: Mechanism of Reaction and Applications

Genipin is a reagent isolated from the Gardenia jasminoides fruit extract, and whose low toxicity and good crosslinking properties have converted it into a reactive whose popularity is increasing by the day. These properties have made it widely used in many medical applications, mainly in the production of chitosan materials (crosslinked by this reactive), biological scaffolds for tissue engineering, and nanoparticles of chitosan and nanogels of proteins for controlled drug delivery, the genipin crosslinking being a key point to strengthen the stability of these materials. This review is focused on the mechanism of reaction of this reagent and its use in the design of biocatalysts, where genipin plays a double role, as a support activating agent and as inter- or intramolecular crosslinker. Its low toxicity makes this compound an ideal alterative to glutaraldehyde in these processes. Moreover, in some cases the features of the biocatalysts prepared using genipin surpassed those of the biocatalysts prepared using other standard crosslinkers, even disregarding toxicity. In this way, genipin is a very promising reagent in the design of biocatalysts.

Genipin Attachment of Conjugated Gold Nanoparticles to a Decellularized Tissue Scaffold

Decellularized allograft tissue is used for a wide array of tissue injuries and repair with tenons and ligament repair being among the most common. However, despite their frequent use there is concern over the lengthy inflammatory period and slow healing associated with allografts. One promising solution has been the use of nanoparticles. There is currently no easy, fast method to achieve consistent conjugation of nanoparticles to tissue. The available conjugation methods can be time-consuming and/or may create numerous cytotoxic byproducts. Genipin, a naturally derived crosslinking agent isolated from the fruits of Gardenia jasminoides was investigated as a conjugation agent to achieve fast, consistent crosslinking without cytotoxic byproducts. The rational of utilizing genipin is that is reacts spontaneously with amino-group-containing compounds such as proteins, collagens, and gelatins, and does not require extensive washing after conjugation. Porcine diaphragm tendons were decellularized and then immersed in cysteamine functionalized gold nanoparticles and genipin for various time points. Tissue scaffolds were tested for the degree of crosslinking, gold nanoparticle concentrations, and fibroblast attachment and biocompatibility. Results demonstrated that genipin can successfully and reproducibly attach gold nanoparticles to tissue in as little as 15 min. The genipin had no cytotoxic effects and improved fibroblast attachment and proliferation. Genipin can be used to attach gold nanoparticles to tissue in a fast, cell safe manner.

Geniposide protects against ox-LDL-induced foam cell formation through inhibition of MAPKs and NF-kB signaling pathways.

Atherosclerosis (AS) is characterized by the significant accumulation of low-density lipoprotein (LDL)-cholesterol in macrophages that reside in the vessel wall and the resultant inflammatory response. Therefore, inhibition of LDL-induced inflammation is a promising interference for AS. Many traditional Chinese medicine prescriptions have been developed for AS treatment. Geniposide (GEN) is an iridoid glycoside mainly found in Gardenia jasminoides fruit. Although GEN has previously been shown to possess anti-atherosclerotic activities, its effects on the formation of macrophage-derived foam cells remain poorly characterized. In our current study, we demonstrated that GEN could significantly inhibit oxidized light-density lipoprotein (ox-LDL) induced macrophage foam cell formation and the expression of pro-inflammatory cytokines in a dose-dependent manner. In addition, treatment of GEN in bone-marrow derived macrophages repressed iNOS expression and NO expression. GEN could also alleviate ox-LDL-dependent up-regulation of CD36 expression by blocking the phosphorylation of p38 MAPK, ERK, JNK and NF-kB p65. The results of our current study demonstrate that GEN exhibits significant therapeutic effects against ox-LDA-induced foam cell formation and inflammation. Therefore, GEN is promising agent for treating AS.

Evaluation on the antiviral activity of genipin against white spot syndrome virus in crayfish

White spot syndrome virus (WSSV) is a serious epidemic pathogen of crustaceans and cause severe economic losses to aquaculture. However, no commercial drugs presently available to control WSSV infection. Genipin (GN) is a bioactive compound extracted from the fruit of Gardenia jasminoides and exhibits potential antiviral activity. In the study, the antiviral activity of GN against WSSV was investigated in crayfish Procambarus clarkii and in shrimp Litopenaeus vannamei. In vitro antiviral test showed that GN could inhibit WSSV replication in crayfish and in shrimp, and the highest inhibition on WSSV was over 99% when treatment with 50 mg/kg of GN for 24 h. In vivo antiviral test proved that GN could be used to treat and prevent WSSV infection. GN could also effectively protect crayfish from WSSV infection by reducing the mortality rate of WSSV-infected crayfish. Moreover, GN attenuated the WSSV-induced oxidative stress and inflammatory by upregulation the expression of antioxidant-related genes and downregulation the expression of inflammatory-related genes, respectively. Mechanically, GN inhibited WSSV replication at least via decreasing STAT (signal transducer and activator of transcription) gene expression to block WSSV immediate-early gene ie1 transcription. Additionally, the inhibition of BI-1 (Bax inhibitor-1) gene expression also played an important role in the suppression of WSSV infection. In conclusion, GN represented a potential therapeutic and preventive agent to block WSSV infection.

Geniposide protected hepatocytes from acetaminophen hepatotoxicity by down-regulating CYP 2E1 expression and inhibiting TLR 4/NF-κB signaling pathway

Acetaminophen (APAP) is a widely used over-the-counter drug for antipyretic and analgesic, but an overdose will induce acute liver injury. APAP hepatotoxicity has been the most common cause of acute liver failure in western countries with high morbidity and mortality. Geniposide (GP), an iridoid glycoside extracted from the fruit of Gardenia jasminoides, has been reported to exert a profound anti-inflammatory activity on acute and chronic diseases. However, it is never demonstrated whether GP can protect hepatocytes from APAP hepatotoxicity. In this study, we investigated the protective effect and underlying mechanism of GP against AILI. The results showed that GP pretreatment reduced the levels of ALT and AST in a dose-dependent manner and alleviated hepatocyte necrosis and apoptosis in mice exposed at APAP. Moreover, it suppressed the expression of CYP 2E1 and attenuated the exhaustion of GSH and accumulation of MDA in the liver. Furthermore, GP remarkably inhibited inflammatory cells infiltration and mitigated the release of IL-1β and TNF-α, and inhibited Toll-like receptor 4 (TLR4) expression and nuclear factor kappa (NF-κB) activation. These data suggested that GP could effectively protect hepatocytes from APAP hepatotoxicity through the down-regulation of CYP 2E1 expression and the inhibition of TLR4/NF-κB signaling pathway.

Transcriptome analysis and targeted metabolic profiling for pathway elucidation and identification of a geraniol synthase involved in iridoid biosynthesis from Gardenia jasminoides

Iridoid compounds have been reported to be accumulated in the dried fruits of Gardenia jasminoides (Rubiaceae), which are used in traditional Chinese medicine. These compounds exhibit obvious pharmacological activities, including effective protective effects on the liver and therapeutic efficacy for cardiovascular diseases. However, the biosynthetic pathway of iridoid remains uninvestigated. In this study, 12 transcriptomes from four tissues (lower leaves, top leaves, flowers, and fruits) were analyzed to characterize the accumulation of active constituents and to identify the corresponding genes involved in iridoid biosynthesis. Almost all genes in the mevalonate (MVA) pathway and the 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway were found in our transcriptome database; these pathways comprise upstream pathways of iridoid compounds (monoterpene derivatives), most of which are abundant in flowers and fruits. Geraniol synthase (GES), which is involved in the first branch step in the iridoid biosynthetic pathway, was cloned, and quantitative real-time PCR (qRT-PCR) revealed that GjGES showed a similar expression pattern to that in the transcriptome in terms of reads per kilobase per million (RPKM) mapped reads. The recombinant GjGES protein efficiently converted geranyl diphosphate (GPP) to geraniol. Subsequently, the metabolic profiling of seven iridoids and iridoid glycosides, namely geniposide, gardenoside, genipin, geniposidic acid, genipin-1-β-gentiobioside, shanzhiside, and shanzhiside methyl ester, revealed that these compounds were highly accumulated in fruits. Consequently, the metabolites and speculated unigenes involved in iridoid metabolic pathways enabled the identification of glucosyltransferase, hydroxylase, and O-methyltransferase candidate genes responsible for the biosynthesis of iridoid and iridoid glycosides. The results of the present study can serve as a reference for the functional characterization of enzyme-coding genes and are beneficial for the engineering of biosynthetic pathways of iridoids and iridoid glycosides in the future.

Geniposide reduces Staphylococcus aureus internalization into bovine mammary epithelial cells by inhibiting NF-κB activation

Staphylococcus aureus (S.aureus), a Gram-positive organism, is a frequent cause of subclinical mastitis. Geniposide, an iridoid glucoside isolated from the fruits of Gardenia jasminoides, has been reported to exhibit antibacterial and anti-inflammatory properties. The ability of S. aureus internalizing into bovine mammary epithelial cells (bMEC) has been responsible for the establishment of the bovine mastitis. In this study, we evaluated the effect of geniposide on S. aureus internalization into bMEC and investigated the possible mechanism of action. The results revealed that geniposide (25–100 μg/ml) reduced S. aureus internalization by 17%–67% and down-regulated the mRNA expressions of TAP and BNBD5. Furthermore, geniposide inhibited S.aureus-induced NF-κB activation in a dose-dependent manner. In summary, the potential mechanism of geniposide reducing S. aureus internalization may be by inhibiting NF-κB activation.

Anti-TMV and Insecticidal Potential of Four Iridoid Glycosides from Gardenia Jasminoides Fruit

Anti-TMV and Insecticidal Potential of Four Iridoid Glycosides from Gardenia Jasminoides Fruit

Genipin inhibits the growth of human bladder cancer cells via inactivation of PI3K/Akt signaling.

Genipin, a natural compound derived from the fruit of Gardenia jasminoides, possesses numerous biological properties. The aim of the present study was to investigate the anticancer effects of genipin in human bladder cancer. T24 and 5637 bladder cancer cells were treated with different concentrations of genipin (0-200 µM) and tested for cell viability, colony formation, cell cycle progression and apoptosis. A xenograft model of bladder cancer was established to determine the anticancer effect of genipin in vivo. The involvement of the phosphoinositide-3 kinase (PI3K)/Akt pathway in the action of genipin was examined. Genipin treatment significantly inhibited the viability and clonogenic growth of bladder cancer cells and inhibited the growth of T24 xenograft tumors, compared with vehicle controls (P<0.05). Genipin-treated cells exhibited a cell cycle arrest at the G0/G1-phase, which was accompanied by a deregulation of numerous cell cycle regulators. Genipin-treated cells demonstrated a significant increase in the percentage of apoptotic cells, loss of mitochondrial membrane potential, Bax translocation to the mitochondria and the release of cytochrome c to the cytosol. Additionally, genipin treatment significantly (P<0.05) reduced the phosphorylation levels of PI3K and Akt in bladder cancer cells. Importantly, genipin-mediated anticancer effects were reversed by the overexpression of constitutively active Akt. In conclusion, to the best of our knowledge, the present study demonstrates for the first time the growth inhibitory effects of genipin in bladder cancer cells, and indicates its potential as a natural anticancer agent for bladder cancer.

Gardenia jasminoides Encodes an Inhibitor-2 Protein for Protein Phosphatase Type 1

Protein phosphatase-1 (PP1) regulates diverse, essential cellular processes such as cell cycle progression, protein synthesis, muscle contraction, carbohydrate metabolism, transcription and neuronal signaling. Inhibitor-2 (I-2) can inhibit the activity of PP1 and has been found in diverse organisms. In this work, a Gardenia jasminoides fruit cDNA library was constructed, and the GjI-2 cDNA was isolated from the cDNA library by sequencing method. The GjI-2 cDNA contains a predicted 543 bp open reading frame that encodes 180 amino acids. The bioinformatics analysis suggested that the GjI-2 has conserved PP1c binding motif, and contains a conserved phosphorylation site, which is important in regulation of its activity. The three-dimensional model structure of GjI-2 was buite, its similar with the structure of I-2 from mouse. The results suggest that GjI-2 has relatively conserved RVxF, FxxR/KxR/K and HYNE motif, and these motifs are involved in interaction with PP1.

소교세포에서 heme oxygenase-1 발현 유도를 통한 치자(Gardenia jasminoides)의 항염증 효과

Died Gardenia jasminoides fruit is used as a dye in the food and clothes industries in Asia. The present study investigated the anti-inflammatory effects of aqueous extract of G. jasminoides fruits (GJ) in BV-2 microglial cells. GJ inhibited lipopolysaccharide-induced nitric oxide (NO) secretion, inducible nitric oxide synthase (iNOS) expression, and reactive oxygen species production, without affecting cell viability. Furthermore, GJ increased the expression of heme oxygenase-1 (HO-1) in a dose-dependent manner. Moreover, the inhibitory effect of GJ on iNOS expression was abrogated by small interfering RNA-mediated knock-down of HO-1. In addition, GJ induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. GJ-mediated expression of HO-1 was suppressed by LY294002, a phosphoinositide 3-kinase (PI-3K) inhibitor, and SB203580, a p38 kinase inhibitor, but not by the extracellular signal–regulated kinase (ERK) inhibitor PD98059 or c-Jun N-terminal kinase (JNK) inhibitor SP600125. GJ also enhanced the phosphorylation of Akt and p38. These results suggest that GJ suppresses the production of NO, a pro-inflammatory mediator, by inducing HO-1 expression via PI-3K/Akt/p38 signaling. These findings illustrate a novel molecular mechanism by which extract from G. jasminoides fruits inhibits neuroinflammation.

Improvement of Lentigines by Oral Crocetin Administration and Examination of Its Mechanism of Action

We investigated the effect of crocetin, a carotenoid present in the fruits of Gardenia jasminoides, on the improvement of lentigines in the skin and examined its mechanism of action. Subjects consumed an experimental meal consisting of a drink containing 7.5 mg of crocetin daily after dinner for 8 weeks. We examined the effects of oral ingestion of crocetin on the improvement of the size of lentigines on the skin. In an epidermis model in which crocetin was added at concentrations of 1 μg/mL and 2 μg/mL and cultured for 14 days, melanin was significantly suppressed compared with the control. Investigation of the mechanism of action via a cultured human epidermis model and cultured pigment cells revealed that crocetin decreased melanocortin receptor subtype 1 of melanocytes at the messenger ribonucleic acid level and inhibited the stimulatory action of melanocytes via melanocyte-stimulating hormone. The results of the study concluded that crocetin inhibits melanin synthesis by controlling the synthesis of tyrosinase and tyrosinase-related protein-1 via the suppression of melanocortin receptor subtype 1 expression.

Pharmacokinetics and Disposition of Circulating Iridoids and Organic Acids in Rats Intravenously Receiving ReDuNing Injection.

ReDuNing injection, prepared from a combination of Gardenia Jasminoides fruits, Lonicera japonica flower buds, and the Artemisia annua aerial part, is extensively used for treatment of viral upper respiratory tract infections in China. Iridoids, organic acids, and flavonoids are likely important compounds of the herbal injection because of their reported pharmacological properties. This study was designed to characterize pharmacokinetics and disposition of the major circulating herbal compounds in rats that received the injection intravenously. ReDuNing injection was found to contain 19 iridoids (content levels 0.01-27.93 mM), 16 organic acids (0.04-19.06 mM), and 11 flavonoids (<0.08 mM). After dosing the injection, the iridoids geniposide, secologanic acid, secoxyloganin, genipin-1-β-gentiobioside, geniposidic acid, sweroside, and shanzhiside and the organic acids chlorogenic acid, quinic acid, cryptochlorogenic acid, and neochlorogenic acid were found to be the major circulating compounds, with mean elimination half-lives of 0.2-0.9 hour; the other plasma compounds were at low exposure levels. These major circulating compounds exhibited small apparent volumes of distribution (0.03-0.34 l/kg). Most of the iridoids were eliminated predominantly via renal excretion of the unchanged compounds, whereas the organic acids were eliminated via methylation and sulfation and were excreted into urine as the unchanged and metabolized compounds. The methylated metabolites also underwent subsequent conjugations before hepatobiliary and renal excretion. In vitro data suggested that the metabolism of the organic acids in rats also occurred in humans. The current pharmacokinetic research could serve as a crucial step in identifying the chemical basis responsible for the therapeutic action of ReDuNing injection.

Therapeutic Potential of Genipin in Central Neurodegenerative Diseases.

Central neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are one of the biggest health problems worldwide. Currently, there is no cure for these diseases. The Gardenia jasminoides fruit is a common herbal medicine in traditional Chinese medicine (TCM), and a variety of preparations are used as treatments for central nervous system (CNS) diseases. Pharmacokinetic studies suggest genipin is one of the main effective ingredients of G. jasminoides fruit extract (GFE). Accumulated research data show that genipin possesses a range of key pharmacological properties, such as anti-inflammatory, neuroprotective, neurogenic, antidiabetic, and antidepressant effects. Thus, genipin shows therapeutic potential for central neurodegenerative diseases. We review the pharmacological actions of genipin for the treatment of neurodegenerative diseases of the CNS. We also describe the potential mechanisms underlying these effects.

A strategy for identification and structural characterization of compounds from Gardenia jasminoides by integrating macroporous resin column chromatography and liquid chromatography-tandem mass spectrometry combined with ion-mobility spectrometry

In this paper, an analysis strategy integrating macroporous resin (AB-8) column chromatography and high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) combined with ion mobility spectrometry (IMS) was proposed and applied for identification and structural characterization of compounds from the fruits of Gardenia jasminoides. The extracts of G. jasminoides were separated by AB-8 resin column chromatography combined with reversed phase liquid chromatography (C18 column) and detected by electrospray ionization tandem mass spectrometry. Additionally, ion mobility spectrometry (IMS) was employed as a supplementary separation technique to discover previously undetected isomers from the fruits of G. jasminoides. A total of 71 compounds, including iridoids, flavonoids, triterpenes, monoterpenoids, carotenoids and phenolic acids were identified by the characteristic high resolution mass spectrometry and the ESI-MS/MS fragmentations. In conclusion, the IMS-MS technique achieved the separation of isomers in crocin-3 and crocin-4 according to their acquired mobility drift times differing from classical analysis by mass spectrometry. The proposed strategy can be used as a highly sensitive and efficient procedure for identification and separation isomeric components in extracts of herbal medicines.

Optimization of supercritical fluid extraction of oil from the fruit of Gardenia jasminoides and its antidepressant activity.

A response surface methodology was applied to optimize the variables affecting the supercritical fluid carbon dioxide extraction of oil from the fruit of Gardenia jasminoides using the Box–Behnken design. The optimum extraction parameters were an extraction temperature of 49.94 °C, an extraction pressure of 29.89 MPa and an extraction time of 93.82 min. Through a GC/MS analysis, we revealed 16 major components of the oil extract, which showed potent antidepressant effects in both of two behavior despair models in mice: tail suspension test and forced swimming test. Our results suggest that the oil extract of Gardenia jasminoides prepared using the supercritical fluid carbon dioxide extraction may contain effective constituents to be used for depression therapy.

Genipin attenuates lipopolysaccharide-induced persistent changes of emotional behaviors and neural activation in the hypothalamic paraventricular nucleus and the central amygdala nucleus

Sickness behavior is a series of behavioral and psychological changes that develop in inflammatory disease, including infections and cancers. Administration of the bacterial endotoxin lipopolysaccharide (LPS) induces sickness behavior in rodents. Genipin, an aglycon derived from an iridoid glycoside geniposide extracted from the fruit of Gardenia jasminoides, has anti-inflammatory and antidepressant activities. However, the effects of genipin on inflammation-induced changes in emotional behaviors are unknown. In this study, we examined the effects of genipin on LPS-induced inflammation in BV-2 cells and sickness behavior in mice. Pretreatment with genipin inhibited LPS-induced increases in NO production and reduced the mRNA levels of inflammation-related genes (iNOS, COX-2, IL-1β and IL-6) in BV-2 cells. Oral administration of genipin ameliorated LPS-induced depressive-like behavior in the forced swim test and social behavior deficits 24h after LPS administration in mice. LPS-induced expression of mRNAs for inflammation-related genes and the number of c-fos immunopositive cells decreased in the paraventricular nucleus (PVN) of the hypothalamus and the central nucleus of the amygdala (CeA), suggesting that genipin attenuates LPS-induced changes of emotional behaviors through inhibition of neural activation and inflammatory responses in the PVN and CeA. These novel pharmacological effects of genipin may be useful for treatment of patients with sickness behavior.

Simultaneous quantification of sixteen bioactive constituents in Zhi-zi-chi decoction: Application to the optimization of Zhi-zi-chi decoction in ratio of dosage

A simple and robust method of liquid chromatography-mass spectrometry coupled with an electrospray ionization interface was developed for the simultaneous determination of sixteen representative ingredients including seven iridoids, four soy isoflavones, two flavonoids, one gardenia yellow pigment, one monoterpene glycoside, and one organic acid in different composition of Gardenia jasminoides fruit (GJF) and Fermented Soybean (FS) (4 : 0, 2 : 1, 1 : 1, 1 : 2, 0 : 4), which are two component herbs of Zhi-zi-chi decoction. Chromatographic separation was accomplished on a Gemini C18 reversed-phase column (250 mm × 4.6 mm, 5 μm) using gradient elution with the mobile phase consisting of methanol and 0.1% aqueous formic acid. The analytes were quantified without interference in the selected ion monitoring mode with positive electrospray ionization. All calibration curves show good linearity (r > 0.9994) within test ranges. The precisions and repeatability were evaluated and relative standard deviation values were less than 3.0%. The recoveries were between 96.5 and 103.7%. The validated method was successfully applied to a comparative analysis of sixteen constituents. The results demonstrate that there are significant differences in the contents of compounds in different proportions, and the combination of GJF and FS (2 : 1) was considered as the optimum ratio of dosage of Zhi-zi-chi decoction.