Inhibitory Effects of Glycyrrhetinic Acid on DNA Polymerase and Inflammatory Activities

Ishida, Tatsuro; Mizushina, Yoshiyuki; Yagi, Saori; Irino, Yasuhiro; Nishiumi, Shin; Miki, Ikuya; Kondo, Yasuyuki; Mizuno, Shigeto; Yoshida, Hiromi; Azuma, Takeshi; Yoshida, Masaru

doi:10.1155/2012/650514

Cited by 37 publications

(27 citation statements)

References 47 publications

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“…Glycyrrhizin (GL) is the bioactive component of licorice and it has recently been used as an herbal medicine due to its antiviral , anticancer , and anti‐inflammatory properties . However, very limited researches have focused on the anticancer efficacy of GL in human hepatocellular carcinoma (HCC), and the detailed molecular mechanism refers to the tumor inhibition of GL in HCC is not yet fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

The mTOR inhibition in concurrence with ERK1/2 activation is involved in excessive autophagy induced by glycyrrhizin in hepatocellular carcinoma

et al. 2017

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Autophagy is a life phenomenon in which autophagosomes remove damaged or aging organelles and long‐lived circulating proteins to maintain the cell's stability. However, disorders of excessive autophagy are a response of cancer cells to a variety of anticancer treatments which lead to cancer cell death. The Akt/mammalian target of rapamycin (mTOR) and the extracellular signal‐regulated kinase 1/2 (ERK1/2) pathways are both involved in nutrient‐induced autophagic phenomenon and exhibit vital relevance to oncogenesis in various cancer cell types, including hepatocellular carcinoma (HCC). However, the influence of autophagy for cancer cell death remains controversial and few scientists have investigated the variation of these two signaling pathways in cancer cell autophagic phenomenon induced by anticancer treatment simultaneously. Here, we explored the anticancer efficacy and mechanisms of glycyrrhizin (GL), a bioactive compound of licorice with little toxicity in normal cells. It is interesting that inhibition of Akt/mTOR signaling in concurrence with enhanced ERK1/2 activity exists in GL‐induced autophagy and cytotoxicity in HepG2 and MHCC97‐H hepatocellular carcinoma cells. These results imply that the GL‐related anticancer ability might correlate with the induction of autophagy. The influence of induced autophagic phenomenon on cell viability might depend on the severity of autophagy and be pathway specific. In the subsequent subcutaneous xenograft experiment in vivo with MHCC97‐H cells, GL obviously exhibited its inhibitory efficacy in tumor growth via inducing excess autophagy in MHCC97‐H cells (P < 0.05). Our data prompt that GL possesses a property of excess autophagic phenomenon induction in HCC and exerts high anticancer efficacy in vitro and in vivo. This warrants further investigation toward possible clinical applications in patients with HCC.

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Section: Introductionmentioning

confidence: 99%

The mTOR inhibition in concurrence with ERK1/2 activation is involved in excessive autophagy induced by glycyrrhizin in hepatocellular carcinoma

et al. 2017

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“…Accordingly, the addition of 18βGA, shown to exert an anti-inflammatory action in cultured cells [22, 23] and in a model of acute inflammation in the mouse ear [22], could contribute to the in vivo anti-inflammatory action observed in our study, in combination with CPO and ZP.…”

Section: Discussionmentioning

confidence: 76%

Clinical and Biochemical Assessment of Maintenance Treatment in Chronic Recurrent Seborrheic Dermatitis: Randomized Controlled Study

Turlier

Viodé

Durbise³

et al. 2014

Dermatol Ther (Heidelb)

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IntroductionFew studies have investigated the long-term effects of a maintenance regimen in the prevention of relapses in scalp seborrheic dermatitis (SD), in particular following biomarker changes.Materials and methodsA new shampoo containing beta-glycyrrhetinic acid (18βGA) in addition to cyclopiroxolamine (CPO) and zinc pyrithione (ZP) was tested in 67 subjects suffering from SD with moderate to severe erythema and itching in a biphasic study. After a first common intensive treatment phase (investigational product thrice a week × 2 weeks), subjects randomly received the investigational product once a week × 8 weeks (maintenance) or a neutral shampoo (discontinuation) in a comparative, parallel group maintenance phase. Efficacy was assessed clinically (overall clinical dandruff score, erythema, overall efficacy, self-evaluation), biochemically and microbiologically by quantitative polymerase chain reaction (qPCR), high performance liquid chromatography (HPLC) or enzyme-linked immunoabsorbent assay (ELISA) analysis of scale samples (Malassezia species (restricta and globosa), cohesion proteins (plakoglobins), inflammation (Interleukin (IL)-8, IL-1RA/IL-1α) and pruritus (histamine, cathepsin S) markers).ResultsDuring the intensive treatment phase, SD improved significantly (p < 0.0001) with a decrease in clinical signs as well as Malassezia species, cohesion proteins, inflammation and pruritus markers. During the maintenance phase, the improvement persisted in the ‘maintenance’ group only, with a significant intergroup difference. A consistently positive relationship was found between dandruff, itching, erythema and Malassezia populations, histamine levels and IL-1RA/IL-1α ratio.ConclusionThe effectiveness of this maintenance regimen was objectively demonstrated at the clinical, biochemical and microbiological level. Correlations between clinical signs and biomarkers could provide clues to explain the resolution of SD and confirm the interest of biomarkers for SD treatment assessment.Electronic supplementary materialThe online version of this article (doi:10.1007/s13555-014-0047-0) contains supplementary material, which is available to authorized users.

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“…Another study reported that hesperidin suppressed inflammatory cell accumulation and decreased inflammatory mediators in the BALF of an ovalbumin-induced chronic airway inflammation model (53). Glycyrrhizin and its metabolite, 18␤-glycyrrhetinic acid, have been reported to possess various pharmacological properties, including antiinflammatory activity (16), antioxidative activity (25), and antifibrotic effects (35). Both glycyrrhizin and 18␤-glycyrrhetinic acid exhibited anti-inflammatory activity through their inhibitory function against the conversion of hydrocortisone to its inactive metabolite cortisone (6,40).…”

Section: Discussionmentioning

confidence: 99%

Rikkunshito ameliorates bleomycin-induced acute lung injury in a ghrelin-independent manner

Tsubouchi

Yanagi

Miura

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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Acute lung injury (ALI) is a critical syndrome consisting of acute respiratory failure associated with extensive pulmonary infiltrates. The pathological characterization of ALI includes injuries of alveolar epithelial cells (AECs), alveolar neutrophilic infiltration, and increases in proinflammatory cytokines, which cause destruction of the alveolar capillary barrier and subsequent devastating lung fibrosis. Rikkunshito (RKT), a traditional Japanese herbal medicine, is widely used for the treatment of patients with gastrointestinal symptoms and is known to stimulate ghrelin secretion. The therapeutic effects of RKT on organ inflammation and fibrosis remain unknown. We investigated the pharmacological potential of RKT in the treatment of ALI by using a bleomycin-induced ALI model in mice. RKT or distilled water (DW) was given to mice daily starting 12 h after bleomycin administration. The RKT-treated mice showed a definitively higher survival rate than the DW-treated mice after injury. They also had smaller reductions in body weight and food intake. The amelioration of neutrophil alveolar infiltration, pulmonary vascular permeability, induction of proinflammatory cytokines, activation of the NF-κB pathway, apoptosis of AECs, and subsequent lung fibrosis were notable in the RKT-treated mice. RKT administration increased the plasma ghrelin levels in wild-type mice, and it also mitigated the ALI response in both ghrelin-deficient mice and growth hormone secretagogue receptor-deficient mice after lung injury. Our results indicate that RKT administration exerts protective effects against ALI by protecting the AECs and regulating lung inflammation independently of the ghrelin system, and they highlight RKT as a promising therapeutic agent for the management of this intractable disease.

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Inhibitory Effects of Glycyrrhetinic Acid on DNA Polymerase and Inflammatory Activities

Cited by 37 publications

References 47 publications

The mTOR inhibition in concurrence with ERK1/2 activation is involved in excessive autophagy induced by glycyrrhizin in hepatocellular carcinoma

The mTOR inhibition in concurrence with ERK1/2 activation is involved in excessive autophagy induced by glycyrrhizin in hepatocellular carcinoma

Clinical and Biochemical Assessment of Maintenance Treatment in Chronic Recurrent Seborrheic Dermatitis: Randomized Controlled Study

Rikkunshito ameliorates bleomycin-induced acute lung injury in a ghrelin-independent manner

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