Genipin inhibits lipopolysaccharide-induced acute systemic inflammation in mice as evidenced by nuclear factor-κB bioluminescent imaging-guided transcriptomic analysis

Li, Chia-Cheng; Hsiang, Chien-Yun; Lo, Hsin-Yi; Pai, Fu-Tzu; Wu, Shih-Lu; Ho, Tin-Yun

doi:10.1016/j.fct.2012.05.054

Cited by 45 publications

(37 citation statements)

References 36 publications

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“…Several studies have reported that genipin has antiinflammatory effects. Genipin inhibits NO production and iNOS expression upon stimu lation by lipopolysaccharide/interferongamma (IFNg) in RAW 264.7 cells, a murine macrophage cell line (16), and shows antiinflammatory effects in a model of LPSinduced acute systemic inflammation (9,17). We examined the effects of genipin on RANKLinduced osteoclastogenesis to investigate the possibility that it could be a candidate for treating osteoporosis through the regulation of osteoclast differentiation.…”

Section: Discussionmentioning

confidence: 99%

Genipin Inhibits RANKL-Induced Osteoclast Differentiation Through Proteasome-Mediated Degradation of c-Fos Protein and Suppression of NF-κB Activation

et al. 2014

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Abstract. People over the age of 50 are at risk of osteoporotic fracture, which may lead to increased morbidity and mortality. Osteoclasts are responsible for bone resorption in bonerelated disorders. Genipin is a wellknown geniposide aglycon derived from Gardenia jasminoides, which has long been used in oriental medicine for controlling diverse conditions such as inflammation and infection. We aimed to evaluate the effects of genipin on RANKLinduced osteoclast differen tiation and its mechanism of action. Genipin dosedependently inhibited early stage RANKL induced osteoclast differentiation in bone marrow macrophages (BMMs) during culture. Genipin inhibited RANKLinduced IkB degradation and suppressed the mRNA expression of osteoclastic markers such as NFATc1, TRAP, and OSCAR in RANKLtreated BMMs, but did not affect c-Fos mRNA expression. Interestingly, genipin markedly inhibited cFos protein expression in BMMs, which was reversed in the presence of the proteosome inhibitor MG132. Furthermore, genipin inhibited RANKLmediated osteoclast differentiation, which was also rescued by overexpression of c-Fos and NFATc1 in BMMs. Taken together, our findings indicate that genipin downregulated RANKLinduced osteoclast differentiation through inhibition of cFos protein proteolysis as well as inhibition of IkB degradation. Our findings indicate that genipin could be a useful drug candidate that lacks toxic side effects for the treatment of osteoporosis.

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Section: Discussionmentioning

confidence: 99%

Genipin Inhibits RANKL-Induced Osteoclast Differentiation Through Proteasome-Mediated Degradation of c-Fos Protein and Suppression of NF-κB Activation

et al. 2014

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“…Previous reports demonstrated that genipin treatment could inhibit NF-κB activation in LPS-stimulated cells [21,24]. It is known that IL-1β stimulation could induce the NF-κB pathway activation in HPDLCs [23].…”

Section: Discussionmentioning

confidence: 99%

“…Nam et al reported that genipin was effective at inhibiting LPS-induced nitric oxide (NO) release from cultured rat brain microglial cells [20]. Li et al reported that genipin had anti-inflammatory effects in a model of LPS-induced acute systemic inflammation via downregulation of IL-1β and TNF-α productions [21]. However the effect of genipin on Th17 cells related proteins, such as CCL20 and IL-6, productions is unknown.…”

Section: Introductionmentioning

confidence: 99%

Genipin Inhibits IL-1�-Induced CCL20 and IL-6 Production from Human Periodontal Ligament Cells

Shindo

Hosokawa

et al. 2014

Cell Physiol Biochem

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Background/Aims: Genipin, the aglycon of geniposide found in gardenia fruit has long been considered for treatment of various diseases in traditional oriental medicine. Genipin has been used as a blue colorant in food industry. Genipin has recently been reported to have some pharmacological functions, such as antimicrobial, antitumor, and anti-inflammatory effects. The aim of this study was to examine whether genipin could modify CCL20 and IL-6, which are related to bone resorption in periodontal disease, expression in human periodontal ligament cells (HPDLCs). Methods: CCL20 and IL-6 productions from HPDLCs were determined by ELISA. Western blot analysis was used for the detection of signal transduction molecules expressions in HPDLCs. Results: Genipin prevented IL-1ß-mediated CCL20 and IL-6 production in HPDLCs. Moreover, genipin could suppress nuclear factor kappa B (NF-κB) p65, extracellular signalregulated kinase (ERK) and MAPK/ERK kinase (MEK) phosphorylations in IL-1ß-stimulated HPDLCs. NF-κB inhibitor and ERK inhibitor significantly inhibited IL-6 and CCL20 productions from IL-1ß-stimulated HPDLCs. Conclusions: These data provide a novel mechanism through which genipin could be used to provide direct benefits in periodontal disease to inhibit IL-6 and CCL20 productions in periodontal lesions.

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“…59 Genipin exhibited anti-inflammatory effects via downregulation of chemokine ligand, chemokine receptor, and IFN-induced protein productions in LPS-induced acute systemic inflammation. 60 Genipin prevented IL-1β-mediated CCL20 and IL-6 production in HPDLCs through suppressing nuclear factor kappa B (NF-κB) p65, extracellular signal regulated kinase (ERK) and MAPK/ERK kinase (MEK) phosphorylations. 61 Both genipin and geniposide inhibited production of exudate and nitric oxide (NO).…”

Section: Anti-inflammatory Activitymentioning

confidence: 99%

Phytochemistry, Pharmacological Activities and Intellectual Property Landscape of Gardenia jasminoides Ellis: a Review

Phatak¹

2015

Phcog J

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Genipin inhibits lipopolysaccharide-induced acute systemic inflammation in mice as evidenced by nuclear factor-κB bioluminescent imaging-guided transcriptomic analysis

Cited by 45 publications

References 36 publications

Genipin Inhibits RANKL-Induced Osteoclast Differentiation Through Proteasome-Mediated Degradation of c-Fos Protein and Suppression of NF-κB Activation

Genipin Inhibits RANKL-Induced Osteoclast Differentiation Through Proteasome-Mediated Degradation of c-Fos Protein and Suppression of NF-κB Activation

Genipin Inhibits IL-1�-Induced CCL20 and IL-6 Production from Human Periodontal Ligament Cells

Phytochemistry, Pharmacological Activities and Intellectual Property Landscape of Gardenia jasminoides Ellis: a Review

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