Protective Effect of Ginsenoside Rg1 on Bleomycin-Induced Pulmonary Fibrosis in Rats: Involvement of Caveolin-1 and TGF-β1 Signal Pathway

Zhan, Hong; Huang, Feng; Ma, Wenzhuo; Zhao, Zhenghang; Zhang, Haifang; Zhang, Chong

doi:10.1248/bpb.b16-00046

Cited by 33 publications

(15 citation statements)

References 41 publications

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“…In terms of normal cells, Zhan et al reported that ginsenoside Rg1 exerted protective effect on bleomycin-induced pulmonary fibrosis in rats by increasing the expression of CAV1 mRNA and protein [168]. Nakaso et al reported that knockdown of Cav-1 and/or Cav-2 prevented the protective effects of tocotrienol in a cellular Parkinson's disease model [169].…”

Section: Cav-1 and Oxidative Stress Regulationmentioning

confidence: 99%

Caveolin‐1: An Oxidative Stress‐Related Target for Cancer Prevention

Wang

Zheng

et al. 2017

Oxidative Medicine and Cellular Longevity

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Aberrant oxidative metabolism is one of the hallmarks of cancer. Reactive species overproduction could promote carcinogenesis via inducing genetic mutations and activating oncogenic pathways, and thus, antioxidant therapy was considered as an important strategy for cancer prevention and treatment. Caveolin-1 (Cav-1), a constituent protein of caveolae, has been shown to mediate tumorigenesis and progression through oxidative stress modulation recently. Reactive species could modulate the expression, degradation, posttranslational modifications, and membrane trafficking of Cav-1, while Cav-1-targeted treatments could scavenge the reactive species. More importantly, emerging evidences have indicated that multiple antioxidants could exert antitumor activities in cancer cells and protective activities in normal cells by modulating the Cav-1 pathway. Altogether, these findings indicate that Cav-1 may be a promising oxidative stress-related target for cancer antioxidant prevention. Elucidating the underlying interaction mechanisms between oxidative stress and Cav-1 is helpful for enhancing the preventive effects of antioxidants on cancer, for improving clinical outcomes of antioxidant-related therapeutics in cancer patients, and for developing Cav-1 targeted drugs. Herein, we summarize the available evidence of the roles of Cav-1 and oxidative stress in tumorigenesis and development and shed novel light on designing strategies for cancer prevention or treatment by utilizing the interaction mode between Cav-1 and oxidative stress.

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Section: Cav-1 and Oxidative Stress Regulationmentioning

confidence: 99%

Caveolin‐1: An Oxidative Stress‐Related Target for Cancer Prevention

Wang

Zheng

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…HYP is a common index for collagen quantification (31). A previous study verified that BLM-induced fibrosis was associated with an increased lung coefficient and HYP content (32). CD4 + T (helper) cells have an important role in the immune system, which not only help macrophages respond to intracellular antigens but also help B cells form germinal centers (33).…”

Section: Discussionmentioning

confidence: 99%

Inï¿½vivo effects of the NLRP1/NLRP3 inflammasome pathway on latent respiratory virus infection

Wei

et al. 2018

Int J Mol Med

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The present study aimed to investigate the effects of nucleotide-binding domain leucine-rich repeat protein (NLRP)1/NLRP3 inflammasome pathways on latent viral infection of the respiratory tract. A total of 55 BALB/c mice were assigned to the control, bleomycin (BLM)-treated, murine cytomegalovirus (McMV), McMV+BLM and McMV+BLM+cd4 + T-cell groups. The viral loads were detected in the salivary glands, kidney, liver and lung tissues via polymerase chain reaction (PCR). The weight, lung coefficient and hydroxyproline (HYP) were detected. HE and Masson staining were performed to score for alveolitis and degree of pulmonary fibrosis. Reverse transcription-quantitative PcR and western blot were applied to assess the expression levels of the NLRP inflammasome components caspase-1, interleukin (IL)-1β and IL-18. ELISA was used to evaluate the expression levels of caspase-1, tumor necrosis factor (TNF)-α, IL-1β and IL-18. The weight of the mice decreased, and the lung coefficient and HYP content increased in the BLM, McMV, McMV+BLM and McMV+BLM+cd4 + T-cell groups compared with those in the control group. compared with the control group, mice in the BLM, McMV+BLM and McMV+BLM+cd4 + T-cell groups had obviously increased alveolitis and degrees of pulmonary fibrosis, increased mRNA expression levels of caspase-1, IL-1β and IL-18, and increased protein expression levels of caspase-1(p20), mature IL-1β and mature IL-18. The values in the McMV+BLM group were also higher than those in the BLM group and those in the McMV+BLM+cd4 + T-cell group. The serum levels of caspase-1, TNF-α, IL-1β and IL-18 in the serum of mice in the MCMV+BLM group were significantly higher than those in the BLM group. compared with the McMV+BLM group, the McMV+BLM+cd4 + T-cell group had decreased levels of caspase-1, TNF-α, IL-1β and IL-18 (all P<0.05). These results demonstrated that the activation of the NLRP1 and NLRP3 inflammasome pathways may contribute to pulmonary fibrosis caused by latent McMV infection in mice.

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“…In the present study, SML reduced the expression of both TGF-β1 and SMAD4. Similar to SML, many natural compounds including berberine [ 13 ], daidzein [ 30 ], and ginsenoside Rg1 [ 31 ] exerted protective effect by intervening the TGF-β/SMAD signalling pathway. The advantage of using natural products, including SML, is that they usually do not induce significant side effects in body even with a long-term application.…”

Section: Discussionmentioning

confidence: 99%

Combination of Salvia miltiorrhiza and ligustrazine attenuates bleomycin-induced pulmonary fibrosis in rats via modulating TNF-α and TGF-β

Huang

Wang

et al. 2018

Chin Med

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BackgroundIdiopathic pulmonary fibrosis (IPF), a chronic, progressive, fibrosing interstitial lung disease, is associated with extremely poor prognosis, and lacks effective treatment. The frequently used immunosuppressive therapies such as dexamethasone (DEX) are often associated with side effects. Recently, combination of two Chinese herbal medicine preparations, Salvia miltiorrhiza and ligustrazine (SML), serves as an alternative medicine for treatment of IPF in clinical practices in China. The aim of this study is to compare the anti-fibrotic effect of SML with that of DEX and to investigate the underlying mechanisms.MethodsA rat model of bleomycin (BLM) induced pulmonary fibrosis was used in this study. Ninety rats were assigned to six groups: control group; BLM-group; BLM and dexamethasone group (BLM + DEX); BLM + low-dose SML; BLM + medium-dose SML and BLM + high-dose SML. Rats were sacrificed on day 7, 14 and 28 after treatment. The extent of alveolitis and fibrosis was observed by H&E and Masson’s trichrome staining. The expressions of TNF-α, TGF-β1 and SMAD4 were determined and quantified by immunohistochemical analysis. The serum levels of TNF-α and TGF-β1 were further quantified by ELISA kits.ResultsBoth DEX and SML treatment attenuated BLM-induced lung injury and pathological collagen deposition in rats, showing improved alveolitis and fibrosis scores on day 7, 14, 28, compared to the BLM group (p < 0.05). The anti-fibrotic effect of SML was in a dose-dependent manner, and the medium- and high-dose SML showed comparable effect with DEX on day 14 and 28. Expressions of TNF-α, TGF-β1 and SMAD4 were significantly decreased in the DEX- and SML-treated groups compared with BLM groups (p < 0.05). Medium- and high-dose SML showed better repression of TNF-α, TGF-β1 and SMAD4 expression compared to DEX at all time points (p < 0.05). Notably, SML at different dosages did not affect serum levels of alanine aminotransferase, aspartate aminotransferase and creatinine.ConclusionsSML is safe and effective in repressing BLM-induced pulmonary fibrosis, which might be through modulating the expression of TNF-α and TGF-β1. Our findings advocate the use of SML for IPF, which might serve as a better treatment option over DEX.Electronic supplementary materialThe online version of this article (10.1186/s13020-018-0194-9) contains supplementary material, which is available to authorized users.

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Protective Effect of Ginsenoside Rg1 on Bleomycin-Induced Pulmonary Fibrosis in Rats: Involvement of Caveolin-1 and TGF-β1 Signal Pathway

Cited by 33 publications

References 41 publications

Caveolin‐1: An Oxidative Stress‐Related Target for Cancer Prevention

Caveolin‐1: An Oxidative Stress‐Related Target for Cancer Prevention

Inï¿½vivo effects of the NLRP1/NLRP3 inflammasome pathway on latent respiratory virus infection

Combination of Salvia miltiorrhiza and ligustrazine attenuates bleomycin-induced pulmonary fibrosis in rats via modulating TNF-α and TGF-β

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