Platycodin D protects acetaminophen-induced hepatotoxicity by inhibiting hepatocyte MAPK pathway and apoptosis in C57BL/6J mice

Fu, Chenglin; Liu, Ying; Leng, Jing; Zhang, Jing; He, Yuhang; Chen, Chen; Wang, Zi; Li, Wei

doi:10.1016/j.biopha.2018.08.082

Cited by 36 publications

(14 citation statements)

References 84 publications

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“…However, these elevated phosphorylation levels were decreased by BAI pretreatment. The result confirmed that BAI might be a potential substance to attenuate on fulminant APAP- induced hepatotoxicity in mice by mediating MAPK signaling pathway [45].…”

Section: Discussionsupporting

confidence: 56%

Hepatoprotective Effect of Baicalein Against Acetaminophen-Induced Acute Liver Injury in Mice

et al. 2018

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Baicalein (BAI), one of the main components of Scutellaria baicalensis Georgi, possesses numerous pharmacological properties, including anti-cancer, anti-oxidative, anti-virus and anti-bacterial activities. The purpose of this study was to evaluate the hepatoprotective effect of baicalein against acetaminophen (APAP)-exposed liver injury in mice, and elucidate the underlying hepatoprotective mechanism. Baicalein pretreatment significantly alleviated the elevation of IL-6, IL-1β and TNF-α in serum and hepatic in a dose-dependent manner. It also dose-dependently reduced the hepatic malondialdehyde (MDA) concentration, as well as the depletion of hepatic superoxide dismutase (SOD), hepatic glutathione (GSH) and hepatic catalase (CAT). Moreover, pretreatment with baicalein significantly ameliorated APAP-exposed liver damage and histological hepatocyte changes. Baicalein also relieved APAP-induced autophagy by regulating AKT/mTOR pathway, LC3B and P62 expression. Furthermore, the hepatoprotective effect of baicalein to APAP-induced liver injury involved in Jak2/Stat3 and MAPK signaling pathway. Taken together, our findings suggested that baicalein exhibits the ability to prevent liver from APAP-induced liver injury and provided an underlying molecular basis for potential applications of baicalein to cure liver injuries.

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Section: Discussionsupporting

confidence: 56%

Hepatoprotective Effect of Baicalein Against Acetaminophen-Induced Acute Liver Injury in Mice

et al. 2018

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“…Several previous researchers have reported that activated nuclear factor-erythroid 2-related factor 2 (Nrf2) plays a key role in the antioxidant efficacy of platycodin D. Among them, Gao et al (2017) reported that platycodin D protected pulmonary inflammation due to cigarette smoke by inhibiting inflammatory and oxidative response through increased expression of heme oxygenase-1 (HO-1), a downstream gene of Nrf2. In addition, increased expression of HO-1 by platycodin D was associated with protecting hepatocytes against acetaminophen-induced hepatotoxicity and suppressing the development of atopic dermatitis-like skin symptoms (Choi et al 2014;Fu et al 2018a). However, whether platycodin D can weaken oxidative stress-induced injury in muscle cells has not been studied.…”

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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“…A.DC., which has been traditionally used for the treatment of various ailments diseases [8][9][10][11]. Several studies revealed that PD possesses various pharmacological properties due to its antioxidant [12][13][14], anti-inflammatory [15,16], hepatoprotective [17,18], anti-obesity [19,20], and immunological adjuvant activities [21]. In addition, some studies have described anticarcinogenic effects of PD against many types of cancers in vitro and in vivo [22,23].…”

Section: Introductionmentioning

confidence: 99%

Induction of ROS-dependent apoptotic cell death by platycodin D in human prostate cancer PC3 cells

Choi

2022

J. Mens. Health

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Background and objective: Platycodin D (PD), a triterpenoid saponin isolated from an edible and medicinal plant Platycodon grandiflorum, possesses multiple pharmacological properties. The purpose of this study is to investigate the effect of PD on the growth of PC3 human prostate cancer cells and the underlying molecular mechanisms. Materials and methods:Cell viability, apoptosis and mitochondrial membrane potential (MMP) were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, nuclear staining and flow cytometry analysis. To investigate the mechanism of anti-cancer activity of PD, expression of apoptosis regulatory protein, caspase activity, and generation of intracellular reactive oxygen species (ROS) were determined.Results: PD treatment reduced PC3 cell proliferation, which was associated with induction of apoptosis, and accompanied by increased expression of Fas, Fas-ligand (FasL) and pro-apoptotic Bax, and decreased expression of anti-apoptotic Bcl-2 and truncation of Bid. PD also inhibited expression of c-FLIP and members of inhibitor of apoptosis protein family, and activated caspases, resulting in an increase in poly (ADP-ribose) polymerase cleavage. However, in the presence of a pan-caspase inhibitor, PD-mediated growth inhibition and apoptosis were significantly protected. PD also destroyed the integrity of mitochondria due to the loss of MMP, leading to cytosolic release of cytochrome c. Moreover, the levels of ROS were markedly increased by PD treatment, which was significantly attenuated by the ROS scavenger N-acetyl-L-cysteine (NAC). Furthermore, NAC fully suppressed PDinduced apoptotic events and cytotoxicity. Conclusions:The results of this study show that PD had chemopreventive potential through the induction of ROS-dependent apoptosis in PC3 cells, and that this compound could be useful for developing an effective and selective natural source to inhibit cancer cell proliferation.

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Platycodin D protects acetaminophen-induced hepatotoxicity by inhibiting hepatocyte MAPK pathway and apoptosis in C57BL/6J mice

Cited by 36 publications

References 84 publications

Hepatoprotective Effect of Baicalein Against Acetaminophen-Induced Acute Liver Injury in Mice

Hepatoprotective Effect of Baicalein Against Acetaminophen-Induced Acute Liver Injury in Mice

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

Induction of ROS-dependent apoptotic cell death by platycodin D in human prostate cancer PC3 cells

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