Japanese herbal medicine Inchin-ko-to as a therapeutic drug for liver fibrosis

Inao, Mie; Mochida, Satoshi; Matsui, Atsushi; Eguchi, Yuichiro; Yulutuz, Yusufu; Wang, Yanhong; Naiki, Kayoko; Kakinuma, Tohru; Fujimori, Kenji; Nagoshi, Sumiko; Fujiwara, Kenji

doi:10.1016/j.jhep.2004.06.033

Cited by 98 publications

(74 citation statements)

References 26 publications

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“…This decoction has long been used in Taiwan and China as an anti-inflammatory, antipyretic, and choleretic agent for liver disorders and jaundice. A variety of biological effects caused by YCHT have been described including potent effects on hepatic fibrosis (11,12) and hepatic apoptosis both in vitro (13) and in vivo (14,15). In addition, upregulation of ApoA-I in bile duct ligation rats after YCHT administration indicated enhanced triglyceride metabolism, which may link ApoA-I deficiency to the pathophysiology of liver fibrosis (15).…”

Section: Introductionmentioning

confidence: 99%

Alleviation of hepatic oxidative stress by Chinese herbal medicine Yin-Chen-Hao-Tang in obese mice with steatosis

Lee

Chang²,

Lo³

et al. 2010

Int J Mol Med

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Abstract. Obesity is associated with a complex systemic inflammatory state that has been implicated in the development of hepatic steatosis. This study was to test the efficacy of Yin-Chen-Hao-Tang (YCHT), an agent that improves hepatic triglyceride metabolism in its ability to modulate pathways implicated in hepatic steatosis. Mice were fed with high-fat diet for fifteen weeks. The therapeutic mechanism of YCHT likely enhanced adiponectin and endothelial progenitor cells, and up-regulation of peroxisome proliferator-activated receptor Á might be responsible for fatty liver diseases. In addition, YCHT anti-oxidative stress effect might be associated with inhibition of hepatic free fatty acid concentrations and elevation of the glutathione levels in hepatic tissues. Furthermore, YCHT action mechanisms might promote senescence marker protein-30 metabolism that increase resistance to hepatic oxidative stress. These findings suggest a novel therapeutic approach for fatty liver progression in obesity mice.

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Section: Introductionmentioning

confidence: 99%

Alleviation of hepatic oxidative stress by Chinese herbal medicine Yin-Chen-Hao-Tang in obese mice with steatosis

Lee

Chang²,

Lo³

et al. 2010

Int J Mol Med

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“…Geniposide is converted to genipin by bacterial enzymes in the digestive organs and then absorbed into the blood [14] . It has been recently reported that genipin is the component in Inchin-ko-to which suppresses hepatic fibrosis [15,16] . This notion prompted us to hypothesize that genipin or Inchin-ko-to inhibits bleb scarring.…”

mentioning

confidence: 99%

Genipin Suppresses Subconjunctival Fibroblast Migration, Proliferation and Myofibroblast Transdifferentiation

Kitano

Saika²,

Yamanaka³

et al. 2006

Ophthalmic Res

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Purpose: Inchin-ko-to is a herbal medicine which has therapeutic effects in ameliorating liver fibrosis or cholestatic liver diseases. Its main bioactive component is genipin, which is an intestinal bacterial metabolite of this medication. Accordingly, we determined whether or not Inchin-ko-to suppresses in a wound healing model subconjunctival fibroblast (SCF) migration proliferation and myofibroblast transdifferentiation since an inhibitory effect could be of value in improving trabeculotomy outcome. Methods: Effects of genipin on SCF cell migration were examined subsequent to wounding confluent monolayer cultures. Alamar blue staining evaluated the effects of genipin (0–50 µg/ml) on fibroblast cell proliferation. Immunostaining determined α-smooth muscle actin (αSMA) expression. Western blotting evaluated (αSMA) expression and phospho-Smad2 formation. Real-time RT-PCR evaluated TGFβ1 and collagen Iα2 mRNA expression. Enzyme-immunoassay determined culture medium collagen I content. Results: Genipin suppressed wound-induced cell migration and proliferation. It also decreased collagen type I TGFβ1 and αSMA mRNA and protein expression. Smad2 signaling was inhibited by genipin in a dose-dependent manner. Conclusion: Genipin suppresses injury-induced fibrogenic responses in SCFs. This result suggests that the herbal medicine Inchin-ko-to might have therapeutic value following trabeculotomy.

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“…Genipin is a natural derivative of Gardenia jasminoides . Its CXL effect has been used to induce CXL in collagen biospheres [24], of pericardium [25], of cardiac valves [26], and even to treat liver disease in traditional Japanese medicine [27]. Although the mechanism is not fully understood, it is known that genipin reacts with molecules that contain primary amines [10].…”

Section: Discussionmentioning

confidence: 99%

Optimizing Genipin Concentration for Corneal Collagen Cross-Linking: An ex vivo Study

et al. 2018

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Purpose: Studying genipin variable concentrations, treatment durations, and delivery methods as a substance to increase corneal stiffness by inducing corneal collagen cross-linking (CXL). Materials and Methods: 100 bovine corneas treated with different genipin concentrations (0.1, 0.5, and 1%) and treatment durations (15 min, 40 min, 2 h, and 3 days) through different delivery methods compared to 10 controls treated with riboflavin/UV. Histology examination, enzymatic digestion with collagenase and thermal differential scanning calorimetry were performed on the different samples. Results: Bovine corneas soaked in 0.5% genipin morphologically showed 4.7% CXL in comparison to 5.6% in controls (p < 0.05). Corneas treated with topical 0.5% genipin, by a 140-µL drop applied hourly for 2 h, showed 7% corneal CXL. Corneas treated with topical genipin 0.5% for 30 min, 1 and 2 h showed 54 ± 6, 40 ± 7, and 39 ± 9% enzymatic degradation, respectively, in comparison to controls (74%). Corneas treated with 0.5% genipin for 1, 2, and 8 h showed higher thermal denaturation resistance (Td values of 64.9 ± 0.3, 64.7 ± 0.0 and 67.3 ± 0.9), respectively, in comparison to the control group (64.6 ± 0.5) (p < 0.05). Conclusions: Genipin 0.5%, in a 140-µL drop applied hourly for 2 h, showed better potential to enhance corneal stiffness and stability through inducing CXL.

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Japanese herbal medicine Inchin-ko-to as a therapeutic drug for liver fibrosis

Cited by 98 publications

References 26 publications

Alleviation of hepatic oxidative stress by Chinese herbal medicine Yin-Chen-Hao-Tang in obese mice with steatosis

Alleviation of hepatic oxidative stress by Chinese herbal medicine Yin-Chen-Hao-Tang in obese mice with steatosis

Genipin Suppresses Subconjunctival Fibroblast Migration, Proliferation and Myofibroblast Transdifferentiation

Optimizing Genipin Concentration for Corneal Collagen Cross-Linking: An ex vivo Study

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