Paeoniflorin induces apoptosis of lymphocytes through a redox‐linked mechanism

Tsuboi, Hideo; Hossain, Khaled; Akhand, Anwarul A.; Takeda, Kazuhisa; Du, Jie; Rifa’i, Muhaimin; Dai, Yan; Hayakawa, Akihiro; Suzuki, Haruhiko; Nakashima, Izumi

doi:10.1002/jcb.20134

Cited by 70 publications

(49 citation statements)

References 38 publications

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“…In previous studies, paeoniflorin has been reported to show various pharmacological activities, including inhibiting apoptosis (15,16). In this study, paeoniflorin was set as a positive control, based on which to investigate the effects of acteoside on radiation-induced injury.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of acteoside against X-ray-induced damage in human skin fibroblasts

Yang

Yao

Liu

et al. 2015

Molecular Medicine Reports

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Abstract. To investigate the protective effects of acteoside against apoptosis induced by X-ray radiation in human skin fibroblasts (HSFs), the cells were divided into the following groups: Control group; X-ray radiation group; acteoside group, in which the confluent cells were preincubated with 50 µg/ml acteoside for 2 h followed by radiation; and positive control group, in which the cells were preincubated with 50 µg/ml paeoniflorin followed by radiation. For the radiation, HSF cells preincubated with acteoside or paeoniflorin were exposed to X-ray beams at a dose-rate of 3 Gy/min (16 Gy in total). Cell viability, apoptosis and intracellular alteration of redox were monitored by MTT and flow cytometry. Compared with the radiation group, the number of cells arrested at the G0/G1 phase was significantly reduced in the acteoside and paeoniflorin groups, respectively (P<0.05). X-ray radiation induced marked apoptosis in HSF cells and acteoside reversed this effect. Compared with the radiation group, the generation of intracellular reactive oxygen species (ROS) was abrogated by pre-incubation with acteoside or paeoniflorin (P<0.05). In addition, the upregulation of pro-caspase-3 induced by radiation was reversed by acteoside or paeoniflorin. Radiation could induce upregulation of Bax and downregulation of Bcl-2; however, it was reversed completely after administration of acteoside or paeoniflorin. Furthermore, the enhanced expression of ERK and JNK induced by radiation was reversed by acteoside or paeoniflorin. Acteoside could protect the cells from X-ray induced damage through enhancing the scavenging activity of ROS, decreasing the Bax/Bcl-2 ratio and downregulating the activity of procaspase-3, as well as modulating the mitogen-activated protein kinase signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Protective effects of acteoside against X-ray-induced damage in human skin fibroblasts

Yang

Yao

Liu

et al. 2015

Molecular Medicine Reports

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“…Previous studies have shown that paeoniflorin exhibits antispasmodic, analgesic, antipyretic, anti-inflammatory, anti-ulcer, anti-oxidation, anti-coagulation and regulatory effects; however, the mechanism remains unclear, and a number of receptors and ion channels have been implicated as major targets of paeoniflorin's pharmacological effects (13)(14)(15)(16). Paeoniflorin inhibited human pancreatic cancer apoptosis, and the mechanisms are considered to be involved with MMP-9 expression and ERK signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Paeoniflorin inhibits human pancreatic cancer cell apoptosis via suppression of MMP-9 and ERK signaling

et al. 2016

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Abstract. Paeoniflorin exhibits anticancer, anti-inflammatory and antioxidation effects, as well as specific pharmacological effects on smooth muscle and the immune, cardiovascular and central nervous systems. The present study aimed to investigate the anticancer effects of paeoniflorin on pancreatic cancer cells and to elucidate the mechanisms by which these effects occur. In the present study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays were performed to assess cell viability and cell cytotoxicity of BXPC-3 human pancreatic cancer cells, respectively. Cellular apoptosis and caspase-3/9 activities were analyzed using an Annexin V-fluorescein isothiocyanate/propidium iodide Apoptosis Detection kit, a DAPI staining assay and colorimetric kits, respectively. Matrix metalloproteinase-9 (MMP-9) and extracellular signal-regulated kinases (ERK) protein expression in BXPC-3 cells were also investigated using gelatin zymography assays and western blot analysis, respectively. In the present study, paeoniflorin was found to inhibit the cell viability and increase cell cytotoxicity of BXPC-3 cells in a dose-and time-dependent manner. In addition, cellular apoptosis, as well as caspase-3 and -9 activity of BXPC-3 cells was increased following paeoniflorin treatment. Notably, paeoniflorin reduced MMP-9 and ERK protein expression in BXPC-3 cells. These results indicate that paeoniflorin exhibits a potential anticancer effect by enhancing human pancreatic cancer cell apoptosis via the suppression of MMP-9 and ERK signaling.

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“…Paeoniflorin, a monoterpene glucoside, is the principal bioactive constituent of peony root (40). Paeoniflorin has reportedly exhibited anti-inflammation, immunoregulation, antiarthritis, antihepatitis, pain-relieving, neuromuscular blocking, and antihyperglycemia effects (15,32,40,41). Previous studies have shown that paeoniflorin suppresses TNF-␣ induced chemokine production in human dermal microvascular endothelial cells by blocking the NF-B and ERK pathway (2).…”

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confidence: 99%

Paeoniflorin abrogates DSS-induced colitis via a TLR4-dependent pathway

Zhang

Dou

Zhang

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

112

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Paeonia lactiflora Pall is one of the most well-known herbs in China, Korea, and Japan for more than 1,200 years. Paeoniflorin, the major bioactive component of peony root, has recently been reported to have anticolitic activity. However, the underlying molecular mechanism is unclear. The present study was to explore the possible mechanism of paeoniflorin in attenuating dextran sulfate sodium (DSS)-induced colitis. Pre- and coadministration of paeoniflorin significantly reduced the severity of colitis and resulted in downregulation of several inflammatory parameters in the colon, including the activity of myeloperoxidase (MPO), the levels of TNF-α and IL-6, and the mRNA expression of proinflammatory mediators (MCP-1, Cox2, IFN-γ, TNF-α, IL-6, and IL-17). The decline in the activation of NF-κB p65, ERK, JNK, and p38 MAPK correlated with a decrease in mucosal Toll-like receptor 4 (TLR4) but not TLR2 or TLR5 expression. In accordance with the in vivo results, paeoniflorin downregulated TLR4 expression, blocked nuclear translocation of NF-κB p65, and reduced the production of IL-6 in LPS-stimulated mouse macrophage RAW264.7 cells. Transient transfection assay performed in LPS-stimulated human colon cancer HT-29 cells indicated that paeoniflorin inhibits NF-κB transcriptional activity in a dose-dependent manner. TLR4 knockdown and overexpression experiments demonstrated a requirement for TLR4 in paeoniflorin-mediated downregulation of inflammatory cytokines. Thus, for the first time, the present study indicates that paeoniflorin abrogates DSS-induced colitis via decreasing the expression of TLR4 and suppressing the activation of NF-κB and MAPK pathways.

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Paeoniflorin induces apoptosis of lymphocytes through a redox‐linked mechanism

Cited by 70 publications

References 38 publications

Protective effects of acteoside against X-ray-induced damage in human skin fibroblasts

Protective effects of acteoside against X-ray-induced damage in human skin fibroblasts

Paeoniflorin inhibits human pancreatic cancer cell apoptosis via suppression of MMP-9 and ERK signaling

Paeoniflorin abrogates DSS-induced colitis via a TLR4-dependent pathway

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