• Biomolecules & Therapeutics
• /
• v.21 no.2
• /
• pp.132-137
• /
• 2013

Geniposide is an active product extracted from the gardenia fruit, and is one of the most widely used herbal preparations for liver disorders. This study examined the cytoprotective properties of geniposide and its metabolite, genipin, against hepatic ischemia/reperfusion (I/R) injury. C57BL/6 mice were subjected to 60 min of ischemia followed by 6 h of reperfusion. Geniposide (100 mg/kg) and genipin (50 mg/kg) were administered orally 30 min before ischemia. In the I/R mice, the levels of serum alanine aminotransferase and hepatic lipid peroxidation were elevated, whereas hepatic glutathione/glutathione disulfide ratio was decreased. These changes were attenuated by geniposide and genipin administration. On the other hand, increased hepatic heme oxygenase-1 protein expression was potentiated by geniposide and genipin administration. The increased levels of tBid, cytochrome c protein expression and caspase-3 activity were attenuated by geniposide and genipin. Increased apoptotic cells in the I/R mice were also significantly reduced by geniposide and genipin treatment. Our results suggest that geniposide and genipin offer significant hepatoprotection against I/R injury by reducing oxidative stress and apoptosis.

• Journal of Microbiology and Biotechnology
• /
• v.25 no.6
• /
• pp.814-819
• /
• 2015

The natural crosslinking agent genipin has been applied widely in biomedicines and foods nowadays. Because of the special hemiacetal ring structure in its molecule, it can only be prepared by hydrolysis of geniposide according to biocatalysis. In this research, strategies including aqueous-organic biphasic catalysis and substrate fed-batch mode were adopted to improve the biocatalysis process of genipin. A 10 L ethyl acetate-aqueous biphasic system with geniposide fed-batch led to a satisfying genipin yield. With Fusarium solani ACCC 36223, 15.7 g/l genipin in the ethyl acetate phase was obtained, corresponding to space-time yields of 0.654 g l^-1 h^-1.

• Biomolecules & Therapeutics
• /
• v.16 no.2
• /
• pp.82-86
• /
• 2008

The fruits of Gardenia jasminoides Ellis have been previously reported to possess anti-inflammatory activity. In this study, the constituents including geniposide, geniposidic acid, genipin and crocin were evaluated for their effects on prostaglandin and NO production in an attempt to establish anti-inflammatory cellular mechanisms. Among the constituents tested, only genipin significantly inhibited cyclooxygenase-2-mediated $PGE_2$ and inducible nitric oxide synthase-mediated NO production from lipopolysaccharide-treated RAW 264.7 cells at 10-100 ${\mu}$M. Genipin also inhibited nuclear transcription factor-${\kappa}B$ activation. Moreover, genipin showed in vivo antiinflammatory activity on ${\lambda}$-carrageenan-induced paw edema in mice (10.4-29.9% inhibition at 20-100 mg/kg, i.p.). All of these results suggest that genipin may contribute to anti-inflammatory activity of the fruits of G. jasminoides and an inhibitory action on prostaglandin and NO production is, at least, the part of anti-inflammatory mechanism of genipin.

• Food Science and Biotechnology
• /
• v.15 no.5
• /
• pp.735-738
• /
• 2006

We examined the neuroprotective and neurotrophic effects of genipin fractionated from gardenia (Gardenia jasminoides Ellis) originating from Korea. The neurotrophic effects of the genipin containing fraction was evaluated by microscopically monitoring its potency to induce neurite outgrowth in PC12h cells. The genipin containing fraction from Korean gardenia promoted neurite outgrowth in PC12h cells in this study, similar to previously reported effects by Wako Chemical, Japan. When cells were treated with the genipin containing fraction prior to ${\beta}$-amyloid peptide treatment (active domain of A peptide 25-35 treated), toxicity was significantly diminished (p<0.0l). These results suggest that genipin prepared from Korean gardenia might potentially be used as a precautionary agent in neurodegenerative disease, such as Alzheimer's disease, etc.

• Journal of Pharmaceutical Investigation
• /
• v.35 no.1
• /
• pp.7-16
• /
• 2005

Gardeniae Fructus is consisted of geniposide and it's derivatives. For the purpose of treatment of skin disease, geniposide and hydrolyzed products (HP) of Gardeniae Fructus were studied on skin permeation and cross1inking with biological tissue. The hydrolyzed products (HP) and active ingredients of Gardeniae Fructus were identified and investigated about skin permeability. Genipin has provided low cytotoxic cross1inking reagents and formed stable and biocompatible crosslinked products. The permeation enhancing effects of geniposide and genipin under the hydrolyzed products of cream and hydrogel preparations were tested using Franz type diffusion cell and the skin of hairless mouse. The remaining proportions of geniposide and genipin were measured in the hydrolyzed products of cream and hydrogel preparations. The crosslinking of epidermic and endodermic tissue with genipin under the hydrolyzed prodcuts of cream and hydrogel preparation was observed using light microscopy. Increased absorption ratio of the skin of hairless mouse about genipin was higher than that of geniposide. Loads at break, tensile strengths and skin permeation rate of the hydrolyzed products (HP) of cream and hydrogel preparations were higher than the nonhydrolyzed products (NHP). The hydrolyzed products (HP) of cream and hydrogel of Gardeniae Fructus Extracts were proper preparations and crosslinking agents to increase the transdermal absorption with epidermic and endodermic tissue.

• Journal of Conservation Science
• /
• v.34 no.3
• /
• pp.157-166
• /
• 2018

In this study, gelatin binding ability was increased by adding cross linking agent to improve adhesive characteristic of animal glue. Animal glue added genipin measured gel strength and viscosity, the structural analysis, the color retention degree, elution degree, and rupture strength. And the water resistance and ultraviolet light resistance with the addition of genipin were compared. As a result of the study, the gel strength and viscosity increased with the amount of genipin. As a result of the structural analysis, in gelatin, the absorption peak of the triple structure of collagen structurally stabilized was observed. As a result of the color retention degree, the film was observed because of the lowered brightness. The amount of elution glue was increased with addition of genipin at $50^{\circ}C$ distilled water condition and rupture strength has increased with the amount of genipin. In the water resistance and light fastness, there was no appearance before and after deterioration due to the addition of genipin. Based on the results of this study, it confirmed the adhesive characteristics of animal glue added genipin and examined the experimental method applicable for animal glue. After the addition of genipin, flexibility, re-solving, adhesive force, and curing speed, which are unique characteristics of glue, can be improved without disappearing, so it is expected that it will be applicable to production of animal glue and conservation of cultural heritage when homogeneous glue is secured.

• Applied Biological Chemistry
• /
• v.41 no.5
• /
• pp.399-404
• /
• 1998

Genipin was obtained from hydrolysis of geniposide isolated from gardenia fruits with ${\beta}-glucosidase$. Reaction of genipin with glycine, alanine, histidine, lysine, phenylalanine and glutamate in aqueous buffer solution converted colorless starting materials to blue pigments. Effect of pH for the formation of blue pigments was tested using UV/Vis spectrophotometer. The optimum pH for the formation of blue pigments was 7.0. No pigment and trace amounts were formed at acidic (pH 3.0) and alkaline (pH 12.0) conditions, respectively. The amount and tincture of blue color were distinct with different amino acids. In contrast with lysine $({\lambda}_{max}=573\;nm)$, glycine $({\lambda}_{max}=595\;nm)$, phenylalanine $({\lambda}_{max}=602\;nm)$ and alanine $({\lambda}_{max}=595\;nm)$, the reaction of genipin with histidine $({\lambda}_{max}=601\;nm)$ and glutamate $({\lambda}_{max}=601\;nm)$ produced relatively small amounts of blue pigments. Rate constants for the formation of blue pigments from genipin with amino acids at various temperatures $(60,\;70,\;80,\;90^{\circ}C,\;pH\;7.0\;phosphate\;buffer)$ were obtained. Rate constants of genipin with basic amino acids were larger than neutral or acidic amino acids. Arrhenius activation energies of the formation of blue pigments indicated that activation energy of glycine $(E_A=9.8\;kcal/mol)$ was especially lower than those of other amino acids $(E_A=13.3{\sim}15.4\;kcal/mol)$.

• The Korean Journal of Physiology and Pharmacology
• /
• v.15 no.3
• /
• pp.157-162
• /
• 2011

Vascular inflammation process has been suggested to be an important risk factor in the development of atherosclerosis. Recently we reported that induction of peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$) selectively inhibits vascular cell adhesion molecule-1 (VCAM-1) but not intercellular cell adhesion molecule-1 (ICAM-1) in tumor necrosis factor (TNF)-${\alpha}$-activated human umbilical vein endothelial cells (HUVEC). In this study, we investigated whether genipin inhibits expression of cellular adhesion molecules, which is relevant to inflammation. Pretreatment with genipin reduced reactive oxygen species (ROS) production and expression of VCAM-1, but not ICAM-1 in TNF-${\alpha}$-activated HUVEC. Genipin dose- and time-dependently increased PPAR-${\gamma}$ expression and inhibited TNF-${\alpha}$-induced phosphorylation of Akt and PKC with different degrees. Finally, genipin prevented TNF-${\alpha}$-induced adhesion of U937 monocytic cells to HUVEC. Taken together, these results indicate that upregualtion of PPAR-${\gamma}$ by genipin selectively inhibits TNF-${\alpha}$-induced expression of VCAM-1, in which regulation of Akt and/or PKC play a key role. We concluded that genipin can be used for the treatment of cardiovascular disorders such as atherosclerosis.

• The Korean Journal of Physiology and Pharmacology
• /
• v.24 no.4
• /
• pp.363-372
• /
• 2020

Gardenia jasminoides (GJ) is a widely used herbal medicine with anti-inflammatory properties, but its effects on the ORAI1 channel, which is important in generating intracellular calcium signaling for T cell activation, remain unknown. In this study, we investigated whether 70% ethanolic GJ extract (GJ_EtOH) and its subsequent fractions inhibit ORAI1 and determined which constituents contributed to this effect. Whole-cell patch clamp analysis revealed that GJ_EtOH (64.7% ± 3.83% inhibition at 0.1 mg/ml) and all its fractions showed inhibitory effects on the ORAI1 channel. Among the GJ fractions, the hexane fraction (GJ_HEX, 66.8% ± 9.95% at 0.1 mg/ml) had the most potent inhibitory effects in hORAI1-hSTIM1 co-transfected HEK293T cells. Chemical constituent analysis revealed that the strong ORAI1 inhibitory effect of GJ_HEX was due to linoleic acid, and in other fractions, we found that genipin inhibited ORAI1. Genipin significantly inhibited I_ORAI1 and interleukin-2 production in CD3/CD28-stimulated Jurkat T lymphocytes by 35.9% ± 3.02% and 54.7% ± 1.32% at 30 μM, respectively. Furthermore, the same genipin concentration inhibited the proliferation of human primary CD4⁺ T lymphocytes stimulated with CD3/CD28 antibodies by 54.9% ± 8.22%, as evaluated by carboxyfluorescein succinimidyl ester assay. Our findings suggest that genipin may be one of the active components of GJ responsible for T cell suppression, which is partially mediated by activation of the ORAI1 channel. This study helps us understand the mechanisms of GJ in the treatment of inflammatory diseases.

• Journal of Pharmaceutical Investigation
• /
• v.34 no.2
• /
• pp.115-123
• /
• 2004

Geniposide and its related iridoid compounds have been used in traditional herbal medicine for thε treatment of Jaundice hepatic diseases and various inflammatorys. For the purpose to increase trandsdermal absorption, the hydrolyzed products of Gardeniae Furctus were identified and assayed of active ingredients and investigated trandsdermal absorption and anti-inflammatory effects. Geniposide was hydrolyzed to genipin by ${\beta}-glucosidase$ and it was suggested that genipin was more suitable form than geniposide for transdermal absorption by its lipophilic property. Using Franz type diffusion cell and the skin of hairless mouse, the permeation rate of hydrolyzed products and their emulsion preparation were determined. Genipin have more increased absorption ratio through the skin of hairless mouse than geniposide. Also, the emulsion of hydrolyzed products of extracts showed higher permeability than that of nonhydrolyzed preparations. After 9 hours $280.85\;{\mu}g/cm^2$ of genipin was absorbed and $193.52\;{\mu}g/cm^2$ in case of geniposide. The Js of geniposide and genipin were $26.27{\pm}4.11\;{\mu}g/cm^2/hr$ and $40.35{\pm}5.04\;{\mu}g/cm^2/hr$ respectively. After carrageenan injection, the swelling was increased repidly to 24 hr and maintained as plateau. but emulsion group weer reached about 2.5 mL and the swelling decreased successively form 24 hr to 72 hr. The anti-inflammation effects of extracts and hydrolyzed products emulsion were increased with significant difference with control group after 24 hr, 48 hr and 72 hr. In carrageenan induced edema, inhibition of swelling was increased in case of hydrolyzed product emulsion compare with nonhydrolyzed group at 24 hr, 48 hr and 72 hr after swelling. In histological study, the anti-inflammatory effects of hydrolyzed products were remarkable at 48 hr and 72 hr compare with nonhydrolyzed. Hydrolyzed products of Gardeniae Fructus extracts containing genipin would be a suitable preparation to increase the transdermal absorption and anti-inflammatory effects.