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Glycyrrhizic acid alleviates bleomycin-induced pulmonary fibrosis in rats.

Gao L, Tang H, He H, Liu J, Mao J, Ji H, Lin H, Wu T - Front Pharmacol (2015)

Bottom Line: Idiopathic pulmonary fibrosis is a progressive and lethal form of interstitial lung disease that lacks effective therapies at present.Glycyrrhizic acid (GA), a natural compound extracted from a traditional Chinese herbal medicine Glycyrrhiza glabra, was recently reported to benefit lung injury and liver fibrosis in animal models, yet whether GA has a therapeutic effect on pulmonary fibrosis is unknown.The results indicated that GA treatment remarkably ameliorated BLM-induced pulmonary fibrosis and attenuated BLM-induced inflammation, oxidative stress, epithelial-mesenchymal transition, and activation of transforming growth factor-beta signaling pathway in the lungs.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian China.

ABSTRACT
Idiopathic pulmonary fibrosis is a progressive and lethal form of interstitial lung disease that lacks effective therapies at present. Glycyrrhizic acid (GA), a natural compound extracted from a traditional Chinese herbal medicine Glycyrrhiza glabra, was recently reported to benefit lung injury and liver fibrosis in animal models, yet whether GA has a therapeutic effect on pulmonary fibrosis is unknown. In this study, we investigated the potential therapeutic effect of GA on pulmonary fibrosis in a rat model with bleomycin (BLM)-induced pulmonary fibrosis. The results indicated that GA treatment remarkably ameliorated BLM-induced pulmonary fibrosis and attenuated BLM-induced inflammation, oxidative stress, epithelial-mesenchymal transition, and activation of transforming growth factor-beta signaling pathway in the lungs. Further, we demonstrated that GA treatment inhibited proliferation of 3T6 fibroblast cells, induced cell cycle arrest and promoted apoptosis in vitro, implying that GA-mediated suppression of fibroproliferation may contribute to the anti-fibrotic effect against BLM-induced pulmonary fibrosis. In summary, our study suggests a therapeutic potential of GA in the treatment of pulmonary fibrosis.

No MeSH data available.


Related in: MedlinePlus

Glycyrrhizic acid suppressed proliferation of 3T6 fibroblast cells. (A) Murine fibroblast cell line 3T6 was treated with various concentrations of GA for 24 h, and the cytotoxicity of GA was detected by the LDH activity in the conditioned culture medium. (B) The proliferation of 3T6 cells was assessed by MTT assay after 24 and 48 h GA treatment. The results are presented as the mean ± standard deviation of three independent experiments. Compared with the untreated cells, **p < 0.01, ***p < 0.001.
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Figure 4: Glycyrrhizic acid suppressed proliferation of 3T6 fibroblast cells. (A) Murine fibroblast cell line 3T6 was treated with various concentrations of GA for 24 h, and the cytotoxicity of GA was detected by the LDH activity in the conditioned culture medium. (B) The proliferation of 3T6 cells was assessed by MTT assay after 24 and 48 h GA treatment. The results are presented as the mean ± standard deviation of three independent experiments. Compared with the untreated cells, **p < 0.01, ***p < 0.001.

Mentions: Proliferation of fibroblasts takes place at the initial stage of tissue repair in response to injury, and the tightly regulated growth and apoptosis of fibroblasts are critical to restore normal tissue architecture (Lorena et al., 2002). The effect of GA on the proliferation and apoptosis of fibroblasts was investigated in vitro by employing a murine fibroblast cell line 3T6. The cytotoxicity of GA on 3T6 cells were examined by incubating the cells with different concentrations of GA ranging from 5 to 200 μM for 24 h, and the LDH activity assay indicated that GA of as high as 100 μM was non-cytotoxic to 3T6 cells (Figure 4A). Later on, the effect of GA on the proliferation of 3T6 cells was assessed by MTT assay. It was noted that GA treatment at the doses of 50 and 100 μM led to significant reduction of viable cell numbers after 24 and 48 h incubation as compared to the untreated cells, whereas 25 μM GA displayed the inhibitory effect on cell proliferation only at 48 h (Figure 4B). We further examined the cell cycle of 3T6 cells after 24 h treatment with GA. The results revealed that GA of 50 and 100 μM markedly increased the numbers of cells at G0/G1 phase and reduced the numbers of cells at S phase (Figures 5A,B), indicating that the cell cycle was slowed down by GA treatment. Consistently, GA of 50 and 100 μM led to downregulated expression of a number of cell cycle regulatory proteins such as Cyclin B1, Cyclin D1 and Cyclin E, and upregulated the G1 check-point proteins including P53 and P21 (Figures 5C,D). In addition, GA inhibited cell cycle and altered the expression of the cell cycle players in a dose-dependent manner.


Glycyrrhizic acid alleviates bleomycin-induced pulmonary fibrosis in rats.

Gao L, Tang H, He H, Liu J, Mao J, Ji H, Lin H, Wu T - Front Pharmacol (2015)

Glycyrrhizic acid suppressed proliferation of 3T6 fibroblast cells. (A) Murine fibroblast cell line 3T6 was treated with various concentrations of GA for 24 h, and the cytotoxicity of GA was detected by the LDH activity in the conditioned culture medium. (B) The proliferation of 3T6 cells was assessed by MTT assay after 24 and 48 h GA treatment. The results are presented as the mean ± standard deviation of three independent experiments. Compared with the untreated cells, **p < 0.01, ***p < 0.001.
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Figure 4: Glycyrrhizic acid suppressed proliferation of 3T6 fibroblast cells. (A) Murine fibroblast cell line 3T6 was treated with various concentrations of GA for 24 h, and the cytotoxicity of GA was detected by the LDH activity in the conditioned culture medium. (B) The proliferation of 3T6 cells was assessed by MTT assay after 24 and 48 h GA treatment. The results are presented as the mean ± standard deviation of three independent experiments. Compared with the untreated cells, **p < 0.01, ***p < 0.001.
Mentions: Proliferation of fibroblasts takes place at the initial stage of tissue repair in response to injury, and the tightly regulated growth and apoptosis of fibroblasts are critical to restore normal tissue architecture (Lorena et al., 2002). The effect of GA on the proliferation and apoptosis of fibroblasts was investigated in vitro by employing a murine fibroblast cell line 3T6. The cytotoxicity of GA on 3T6 cells were examined by incubating the cells with different concentrations of GA ranging from 5 to 200 μM for 24 h, and the LDH activity assay indicated that GA of as high as 100 μM was non-cytotoxic to 3T6 cells (Figure 4A). Later on, the effect of GA on the proliferation of 3T6 cells was assessed by MTT assay. It was noted that GA treatment at the doses of 50 and 100 μM led to significant reduction of viable cell numbers after 24 and 48 h incubation as compared to the untreated cells, whereas 25 μM GA displayed the inhibitory effect on cell proliferation only at 48 h (Figure 4B). We further examined the cell cycle of 3T6 cells after 24 h treatment with GA. The results revealed that GA of 50 and 100 μM markedly increased the numbers of cells at G0/G1 phase and reduced the numbers of cells at S phase (Figures 5A,B), indicating that the cell cycle was slowed down by GA treatment. Consistently, GA of 50 and 100 μM led to downregulated expression of a number of cell cycle regulatory proteins such as Cyclin B1, Cyclin D1 and Cyclin E, and upregulated the G1 check-point proteins including P53 and P21 (Figures 5C,D). In addition, GA inhibited cell cycle and altered the expression of the cell cycle players in a dose-dependent manner.

Bottom Line: Idiopathic pulmonary fibrosis is a progressive and lethal form of interstitial lung disease that lacks effective therapies at present.Glycyrrhizic acid (GA), a natural compound extracted from a traditional Chinese herbal medicine Glycyrrhiza glabra, was recently reported to benefit lung injury and liver fibrosis in animal models, yet whether GA has a therapeutic effect on pulmonary fibrosis is unknown.The results indicated that GA treatment remarkably ameliorated BLM-induced pulmonary fibrosis and attenuated BLM-induced inflammation, oxidative stress, epithelial-mesenchymal transition, and activation of transforming growth factor-beta signaling pathway in the lungs.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian China.

ABSTRACT
Idiopathic pulmonary fibrosis is a progressive and lethal form of interstitial lung disease that lacks effective therapies at present. Glycyrrhizic acid (GA), a natural compound extracted from a traditional Chinese herbal medicine Glycyrrhiza glabra, was recently reported to benefit lung injury and liver fibrosis in animal models, yet whether GA has a therapeutic effect on pulmonary fibrosis is unknown. In this study, we investigated the potential therapeutic effect of GA on pulmonary fibrosis in a rat model with bleomycin (BLM)-induced pulmonary fibrosis. The results indicated that GA treatment remarkably ameliorated BLM-induced pulmonary fibrosis and attenuated BLM-induced inflammation, oxidative stress, epithelial-mesenchymal transition, and activation of transforming growth factor-beta signaling pathway in the lungs. Further, we demonstrated that GA treatment inhibited proliferation of 3T6 fibroblast cells, induced cell cycle arrest and promoted apoptosis in vitro, implying that GA-mediated suppression of fibroproliferation may contribute to the anti-fibrotic effect against BLM-induced pulmonary fibrosis. In summary, our study suggests a therapeutic potential of GA in the treatment of pulmonary fibrosis.

No MeSH data available.


Related in: MedlinePlus