Chiisanoside, a triterpenoid saponin, exhibits anti-tumor activity by promoting apoptosis and inhibiting angiogenesis

Bian, Xingbo; Zhao, Yan; Guo, Xue; Zhang, Lianxue; Li, Pingya; Fu, Tianhua; Wang, Weidong; Yin, Yongxia; Chen, Guilin; Liu, Jinping

doi:10.1039/c7ra08041g

Cited by 20 publications

(18 citation statements)

References 36 publications

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“…Chiisanoside was extracted from the leaf of A. sessiliflorus in our laboratory. The purity of CSS was determined by high‐performance liquid chromatography (HPLC) (purity > 98%) . Lipopolysaccharide (LPS, 99% purity) and d ‐galactosamine hydrochloride (d‐GalN, 98% purity) were produced by Sigma (St Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

“…The purity of CSS was determined by high-performance liquid chromatography (HPLC) (purity > 98%). 21 Lipopolysaccharide (LPS, 99% purity) and D-galactosamine hydrochloride (d-GalN, 98% purity) were produced by Sigma (St Louis, MO, USA). The mice were randomly divided into four groups (n = 8): Control group, LPS/GalN group, LPS/GalN + CSS (30 mg kg −1 ) group, LPS/GalN + CSS (120 mg kg −1 ) group.…”

Section: Treatment Of Animalsmentioning

confidence: 99%

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Hepatoprotective effect of chiisanoside from Acanthopanax sessiliflorus against LPS/D‐GalN‐induced acute liver injury by inhibiting NF‐κB and activating Nrf2/HO‐1 signaling pathways

Bian

Liu

et al. 2019

J Sci Food Agric

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BACKGROUND In China, Acanthopanax sessiliflorus is a delicious wild vegetable. It is also used to treat inflammation and pain. Chiisanoside (CSS) is the main constituent of the leaf of A. sessiliflorus. Combined use of lipopolysaccharide and d‐galactosamine (LPS/D‐GalN) can induce acute liver failure in human beings, and there are no reports on the protective effect of CSS against LPS/D‐GalN‐induced acute liver injury in mice. RESULTS Chiisanoside pretreatment evidently reduced the activities of alanine transaminase (ALT) and aspartate transaminase (AST) in the changes induced by LPS/D‐GalN, and these histopathological changes induced by LPS/GalN were significantly weakened. Catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD) activities increased, and malondialdehyde (MDA) activity decreased after CSS treatment compared with LPS/D‐GalN treatment. Pretreatment with CSS also inhibited the expression levels of inflammatory factors. The administration of CSS prevented the phosphorylated expression of inhibitor kappa B (IκB) kinase, and led to a significant increase in heme oxygenase‐1 (HO‐1) expression and nuclear factor erythroid 2‐related factor2 (Nrf2) nuclear translocation. CONCLUSION The protective effects of CSS are attributed to its antioxidative effect and inflammatory suppression in Nuclear factor kappa beta (NF‐κB) and Nrf2/HO‐1 signaling pathways. Chiisanoside might therefore be a potential ingredient for drug and food development against acute liver injury in the future. © 2018 Society of Chemical Industry

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Section: Methodsmentioning

confidence: 99%

Section: Treatment Of Animalsmentioning

confidence: 99%

Hepatoprotective effect of chiisanoside from Acanthopanax sessiliflorus against LPS/D‐GalN‐induced acute liver injury by inhibiting NF‐κB and activating Nrf2/HO‐1 signaling pathways

Bian

Liu

et al. 2019

J Sci Food Agric

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“…Although the antiangiogenic properties and VEGF inhibition by several tetracyclic triterpene saponins from ginseng, Rhizoma paridis , Acanthopanax sessiliflorus etc. have been reported, the knowledge about the effect of pentacyclic triterpene saponins on cancer angiogenesis is still limited [ 43 , 44 , 45 , 46 ]. In the present study, the wound healing assay showed that TSE1 almost totally inhibited OVCAR-3 cell migration at 2 μM after 24 h treatment ( Figure 4 a).…”

Section: Discussionmentioning

confidence: 99%

Theasaponin E1 Inhibits Platinum-Resistant Ovarian Cancer Cells through Activating Apoptosis and Suppressing Angiogenesis

Tong

Ren

et al. 2021

Molecules

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Novel therapeutic strategies for ovarian cancer treatment are in critical need due to the chemoresistance and adverse side effects of platinum-based chemotherapy. Theasaponin E1 (TSE1) is an oleanane-type saponin from Camellia sinensis seeds. Its apoptosis-inducing, cell cycle arresting and antiangiogenesis activities against platinum-resistant ovarian cancer cells were elucidated in vitro and using the chicken chorioallantoic membrane (CAM) assay. The results showed that TSE1 had more potent cell growth inhibitory effects on ovarian cancer OVCAR-3 and A2780/CP70 cells than cisplatin and was lower in cytotoxicity to normal ovarian IOSE-364 cells. TSE1 significantly induced OVCAR-3 cell apoptosis via the intrinsic and extrinsic apoptotic pathways, slightly arresting cell cycle at the G2/M phase, and obviously inhibited OVCAR-3 cell migration and angiogenesis with reducing the protein secretion and expression of vascular endothelial growth factor (VEGF). Western bolt assay showed that Serine/threonine Kinase (Akt) signaling related proteins including Ataxia telangiectasia mutated kinase (ATM), Phosphatase and tensin homolog (PTEN), Akt, Mammalian target of rapamycin (mTOR), Ribosome S6 protein kinase (p70S6K) and e IF4E-binding protein 1(4E-BP1) were regulated, and Hypoxia inducible factor-1α (HIF-1α) protein expression was decreased by TSE1 in OVCAR-3 cells. Moreover, TSE1 treatment potently downregulated protein expression of the Notch ligands including Delta-like protein 4 (Dll4) and Jagged1, and reduced the protein level of the intracellular domain (NICD) of Notch1. Combination treatment of TSE1 with the Notch1 signaling inhibitor tert-butyl (2S)-2-[[(2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]propanoyl]amino]-2-phenylacetate (DAPT), or the Akt signaling inhibitor wortmannin, showed a stronger inhibition toward HIF-1α activation compared with single compound treatment. Taken together, TSE1 might be a potential candidate compound for improving platinum-resistant ovarian cancer treatment via Dll4/Jagged1-Notch1-Akt-HIF-1α axis.

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“…Lupane-type triterpenoids are distributed among many plant families. Previous studies have shown that several lupane triterpenes exhibit a wide range of pharmacological effects and engage in important biological activities, especially those involving anti-inflammation, liver protection, anti-tumor processes, and immune system regulation [26,27,28]. Based on our previous activity-guide isolation work, this work was undertaken to clarify the anti-inflammatory potential of HOA on LPS-stimulated RAW264.7 macrophages and its potential mechanisms.…”

Section: Discussionmentioning

confidence: 99%

20-Hydroxy-3-Oxolupan-28-Oic Acid Attenuates Inflammatory Responses by Regulating PI3K–Akt and MAPKs Signaling Pathways in LPS-Stimulated RAW264.7 Macrophages

Cao

Luo

et al. 2019

Molecules

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20-Hydroxy-3-oxolupan-28-oic acid (HOA), a lupane-type triterpene, was obtained from the leaves of Mahonia bealei, which is described in the Chinese Pharmacopeia as a remedy for inflammation and related diseases. The anti-inflammatory mechanisms of HOA, however, have not yet been fully elucidated. Therefore, the objective of this study was to characterize the molecular mechanisms of HOA in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. HOA suppressed the release of nitric oxide (NO), pro-inflammatory cytokine tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 macrophages without affecting cell viability. Quantitative real-time reverse-transcription polymerase chain reaction (RT-qPCR) analysis indicated that HOA also suppressed the gene expression of inducible NO synthase (iNOS), TNF-α, and IL-6. Further analyses demonstrated that HOA inhibited the phosphorylation of upstream signaling molecules, including p85, PDK1, Akt, IκBα, ERK, and JNK, as well as the nuclear translocation of nuclear factor κB (NF-κB) p65. Interestingly, HOA had no effect on the LPS-induced nuclear translocation of activator protein 1 (AP-1). Taken together, these results suggest that HOA inhibits the production of cytokine by downregulating iNOS, TNF-α, and IL-6 gene expression via the downregulation of phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinases (MAPKs), and the inhibition of NF-κB activation. Our findings indicate that HOA could potentially be used as an anti-inflammatory agent for medical use.

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Chiisanoside, a triterpenoid saponin, exhibits anti-tumor activity by promoting apoptosis and inhibiting angiogenesis

Abstract: Chissanoside from Acanthopanax species exhibits anti-tumor activity by protecting liver function, regulating immunity, promoting apoptosis and inhibiting angiogenesis.

Cited by 20 publications

References 36 publications

Hepatoprotective effect of chiisanoside from Acanthopanax sessiliflorus against LPS/D‐GalN‐induced acute liver injury by inhibiting NF‐κB and activating Nrf2/HO‐1 signaling pathways

Hepatoprotective effect of chiisanoside from Acanthopanax sessiliflorus against LPS/D‐GalN‐induced acute liver injury by inhibiting NF‐κB and activating Nrf2/HO‐1 signaling pathways

Theasaponin E1 Inhibits Platinum-Resistant Ovarian Cancer Cells through Activating Apoptosis and Suppressing Angiogenesis

20-Hydroxy-3-Oxolupan-28-Oic Acid Attenuates Inflammatory Responses by Regulating PI3K–Akt and MAPKs Signaling Pathways in LPS-Stimulated RAW264.7 Macrophages

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