Platycodin D alleviates liver fibrosis and activation of hepatic stellate cells by regulating JNK/c-JUN signal pathway

Liu, Yongmei; Cong, Shuo; Cheng, Zhuo; Hu, Yunfei; Zhu, Lili; Zhao, Xueke; Mu, Mao; Zhang, Bao-fang; Fan, Linda; Yu, Lei; Cheng, Mingliang

doi:10.1016/j.ejphar.2020.172946

Cited by 43 publications

(36 citation statements)

References 35 publications

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“…Reports have demonstrated previously that PD reverses pathological myocardial hypertrophy and fi brosis in spontaneous hypertension rats (16). Additionally, PD improves liver fi brosis and activates hepatic stellate cells by regulating JNK/c-JUN signal pathway (17). In the present study, the expression of α-SMA, Col I, Col III and E-cad was markedly downregulated after PD exposure, suggesting that PD treatment suppresses ECM accumulation in TGF-β1-induced MCR-5 cells.…”

Section: Discussionsupporting

confidence: 64%

“…It has been well reported that PD reverses pathological myocardial hypertrophy and fi brosis in spontaneous hypertension rats (16). A study mentioned that by regulating JNK/c-JUN signal pathway, PD improves liver fi brosis and activates hepatic stellate cells (17). However, there has been no clarifi cation made for the effects of PD on lung fi brosis.…”

Section: Introductionmentioning

confidence: 99%

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Platycodin D alleviates proliferation and extracellular matrix accumulation in TGF-beta1 induced pulmonary fibroblasts

Hou¹,

Su²,

Liang³

et al. 2021

BLL

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AIM: Platycodin D (PD), an oleanane kind of triterpenoid saponin, possesses various pharmacological activities. We aimed to investigate the effects of PD in pulmonary fi brosis. METHOD: MRC-5 cells were induced by transforming growth factor-beta1 (TGF-β1) to simulate the pulmonary fi brosis in vitro. Cell viability was determined using a CCK-8 kit in the absence or presence of PD. Then, the expression of proliferation-related proteins was detected using immunofl uorescence assay or western blot analysis. Moreover, the levels of infl ammatory factors were examined. Subsequently, the ability of cell migration was evaluated using wound healing assay. Additionally, western blot analysis was employed to determine migration-and extracellular matrix accumulation (ECM)-related proteins expression. RESULTS: Results indicated that PD exposure signifi cantly dose-dependently inhibited TGF-β1 induced proliferation in MRC-5 cells. Additionally, the contents of infl ammatory factors were notably inhibited with PD treatment. Furthermore, signifi cant decrease in migration of TGF-β1-stimulated MRC-5 cells was observed after PD intervention. Afterwards, PD remarkably suppressed the expression of alpha smooth muscle actin (α-SMA), collagen I (Col I), collagen III (Col III) and E-cadherin (E-cad). CONCLUSIONS: PD attenuated proliferation and ECM accumulation in TGF-β1 induced lung fi broblasts, providing experimental support for the clinical application of PD in the treatment of pulmonary fi brosis (Fig. 6, Ref. 33).

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Section: Discussionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Platycodin D alleviates proliferation and extracellular matrix accumulation in TGF-beta1 induced pulmonary fibroblasts

Hou¹,

Su²,

Liang³

et al. 2021

BLL

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“…Liver-directed gene transfer of TFEB attenuated hepatic fibrosis by accelerating the autophagy-dependent degradation of SERPINA1 polymer in autolysosomes and decreasing SERPINA1 monomer expression in SERPINA1 deficient mice 60 . Furthermore, Liu et al reported that platycodin D mediated the activation of autophagy and suppressed activation of HSCs by promoting phosphorylation of C-Jun NH2-terminal kinases (JNK) and C-Jun, which was reversed by JNK inhibitor P600125 61 .…”

Section: Liver Fibrosis and Autophagymentioning

confidence: 99%

Self-eating: friend or foe? The emerging role of autophagy in fibrotic diseases

Liu¹,

Wu²,

Li³

2020

Theranostics

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Fibrosis occurs in most human organs including the liver, lung, heart and kidney, and is crucial for the progression of most chronic diseases. As an indispensable catabolic process for intracellular quality control and homeostasis, autophagy occurs in most mammalian cells and is implicated in many biological processes including fibrogenesis. Although advances have been made in understanding autophagy process, the potential role of autophagy in fibrotic diseases remains controversial and has recently attracted a great deal of attention. In the current review, we summarize the commonalities of autophagy affecting different types of fibrosis in different organs, including the liver, lung, heart, and kidney as well as in cystic fibrosis, systematically outline the contradictory results and highlight the distinct role of autophagy during the various stages of fibrosis. In summary, the exact role autophagy plays in fibrogenesis depends on specific cell types and different stimuli, and identifying and evaluating the pathogenic contribution of autophagy in fibrogenesis will promote the discovery of novel therapeutic strategies for the clinical management of these fibrotic diseases.

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“…DC., of the Campanulaceae family, which has traditionally been used to treat a variety of diseases in Korea, China, and Japan (Zhang et al 2015;Ji et al 2020). Recently, platycodin D has been shown to have multiple pharmacological properties, including anti-inflammatory (Fu et al 2018b;Ye et al 2019), immunostimulatory (Xie et al 2008), anti-cancer (Seo et al 2018;Huang et al 2019), antioxidant (Cho et al 2018;Wang et al 2018;Shi et al 2020), and inhibitory effects against various cardiovascular and metabolic diseases (Lin et al 2018;Liu et al 2020). The antioxidant activity of platycodin D has been primarily attributed to increased ROS scavenging activity and involves the activation of oxidative stress defense systems.…”

Section: Introductionmentioning

confidence: 99%

Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of platycodin D against oxidative stress-induced DNA damage and apoptosis in C2C12 myoblasts

Choi¹

2020

gpb

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Myoblast damage by oxidative stress has been proposed as one of the main causes of skeletal muscle loss due to induction of muscle damage. Platycodin D, a triterpenoid saponin found in the root of Platycodon grandiflorum (Jacq.) A. DC., has been known to possess strong antioxidant activity. However, whether platycodin D can defend myoblasts against oxidative injury remains to be elucidated. Therefore, this study was conducted to investigate the potential protective effects of platycodin D against oxidative stress in mouse myoblast C2C12 cells. The results demonstrated that platycodin D inhibited hydrogen peroxide (H 2 O 2)-induced cytotoxicity and DNA damage by blocking abnormal reactive oxygen species (ROS) generation. Furthermore, platycodin D protected cells from the induction of mitochondria-mediated apoptosis by oxidative stress. In addition, platycodin D markedly promoted the activation of nuclear factor-erythroid-2-related factor 2 (Nrf2), which was associated with the enhanced expression of heme oxygenase-1 (HO-1) in the presence of H 2 O 2. However, inhibiting the expression of HO-1 by Nrf2 siRNA significantly attenuated the protective effect of platycodin D, indicating that platycodin D activates the Nrf2/HO-1 signaling pathway to protect against oxidative stress. Based on current data, platycodin D may be useful as a potential therapeutic agent against various oxidative stress-related muscle disorders.

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Platycodin D alleviates liver fibrosis and activation of hepatic stellate cells by regulating JNK/c-JUN signal pathway

Cited by 43 publications

References 35 publications

Platycodin D alleviates proliferation and extracellular matrix accumulation in TGF-beta1 induced pulmonary fibroblasts

Platycodin D alleviates proliferation and extracellular matrix accumulation in TGF-beta1 induced pulmonary fibroblasts

Self-eating: friend or foe? The emerging role of autophagy in fibrotic diseases

Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of platycodin D against oxidative stress-induced DNA damage and apoptosis in C2C12 myoblasts

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