Pterocephin A, a novel Triterpenoid Saponin from Pterocephalus hookeri induced liver injury by activation of necroptosis

Wang, Rui; Wei, Leilei; Dong, Zhaoyue; Meng, Fan-Cheng; Wang, Guowei; Zhou, Shaoyun; Lan, Xiaozhong; Liao, Zhihua; Chen, Min

doi:10.1016/j.phymed.2021.153548

Cited by 10 publications

(7 citation statements)

References 36 publications

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“…AC treatment partially reversed mitochondrial and cell membrane damage in RSV-infected mice (Figure 5A). LDH leakage can be used to verify the disruption of the cytoplasmic membrane, which is the main characteristic of necroptosis (Wang et al, 2021). As identified, the LDH content in BALF was remarkably reduced by AC administration (Figure 5B).…”

Section: Ac Decreased Rsv-induced Necroptosis Both In Vivo and In Vitromentioning

confidence: 78%

Acteoside attenuates RSV-induced lung injury by suppressing necroptosis and regulating metabolism

et al. 2022

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Background: Necroptosis and inflammation are closely related to the pathogenesis of respiratory syncytial virus (RSV). Acteoside (AC), a natural phenylpropanoid glycoside from Kuding Tea, has significant anti-RSV effect. However, the roles of AC on RSV-induced lung necroptosis and inflammation are yet to be elucidated.Methods: The effects of AC were investigated in BALB/c mice and A549 cells. Lung histopathology was observed through H&E staining. The viral titer was assessed via plaque assay. The RSV-F expression was determined by RT-qPCR and immunohistochemistry assay. The levels of cytokines were detected by ELISA and RT-qPCR. The necroptosis rate and mitochondrial membrane potential were evaluated via flow cytometry. The expressions of HMGB1/NF-κB and RIP1/RIP3/MLKL/PGAM5/DRP1 were detected by western blot. Additionally, untargeted metabolomics was conducted to investigate the metabolic profiles and related metabolic pathways via Gas Chromatography-Mass Spectrometry.Results: The results showed that compared with the RSV-infected group, AC treatment significantly attenuated lung pathological damage, virus replication, and cytokines levels. AC also alleviated RSV-induced necroptosis and mitochondrial dysfunction in vitro and in vivo. Moreover, AC treatment down-regulated the expression of HMGB1, p-Iκbα/Iκbα, p-p65/p65, RIP1, RIP3, MLKL, PGAM5, and DRP1. Furthermore, metabolomic analyses suggested that the perturbations in major metabolites of AC therapy were related to variations in amino acid and energy metabolism.Conclusion: Our findings validated the beneficial effects of AC in suppressing necroptosis and regulating metabolism, suggesting AC may be a new drug candidate for RSV infection.

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Section: Ac Decreased Rsv-induced Necroptosis Both In Vivo and In Vitromentioning

confidence: 78%

Acteoside attenuates RSV-induced lung injury by suppressing necroptosis and regulating metabolism

et al. 2022

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“…Accumulating documents have recognized necroptosis as a crucial downstream target of the inflammatory process during RA progression, suggesting that necroptosis acts as an important regulator for RA. 34,36 Meanwhile, RIPK3 and MLKL were discovered to be highly expressed in RA patients and have been suggested to be promising therapeutic targets for the treatment of RA. 37,38 As expected, a triggered necroptosis and high levels of RIPK3 and MLKL proteins were discovered in LPS-mediated C28/I2 cells in this study, while these elevations were greatly inhibited by BIRC2 knockdown, suggesting that BIRC2 knockdown could repress LPS-caused necroptosis in C28/I2 cells.…”

Section: Discussionmentioning

confidence: 99%

“…The activated TNFR1 mediates the activation of RIPK1 and RIPK3, promoting the phosphorylation of MLKL, which subsequently migrates towards the plasma membrane, causing changes in osmotic pressure and destroying the integrity of membrane structure, and eventually leading to the rupture of the plasma membrane. [33][34][35] Thus, the triggered RIPK3-MLKL is the critical downstream of the necroptotic pathway. Accumulating documents have recognized necroptosis as a crucial downstream target of the inflammatory process during RA progression, suggesting that necroptosis acts as an important regulator for RA.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of BIRC2 hinders the progression of rheumatoid arthritis through regulating TRADD

Rao,

Xu,

et al. 2023

Immunity Inflam & Disease

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AimRheumatoid arthritis (RA) is a chronic inflammation mediated by an autoimmune response. Baculoviral IAP repeat‐containing 2 (BIRC2) and tumor necrosis factor receptor 1‐associated death domain protein (TRADD) have been reported to be highly expressed in RA, while their specific roles during RA progression remain unclear. This study aims to explore the specific regulation of BIRC2/TRADD during the progression of RA.MethodsC28/I2 cells were stimulated by lipopolysaccharide (LPS) to establish an in vitro RA cellular model. The expression level of BIRC2 and TRADD was examined by quantitative real‐time polymerase chain reaction and western blot. Cell Counting Kit‐8 and flow cytometry assays were performed to examine cell viability and necroptosis, respectively. The oxidative stress markers were detected using commercial kits, and the pro‐inflammatory cytokines were measured by ELISA assay. The interaction between BIRC2 and TRADD was verified by co‐immunoprecipitation assay.ResultsBIRC2 and TRADD were discovered to be highly expressed in LPS‐mediated C28/I2 cells. BIRC2 knockdown was demonstrated to inhibit LPS‐induced cell viability loss, necroptosis, oxidative stress, and inflammation in C28/I2 cells. BIRC2 could interact with TRADD and positively regulate TRADD expression. In addition, the protective role of BIRC2 knockdown against LPS‐mediated injuries in C28/I2 cells was partly weakened by TRADD overexpression.ConclusionIn summary, BIRC2 knockdown alleviated necroptosis, oxidative stress, and inflammation in LPS‐mediated C28/I2 cells, which might correlate to the regulatory role of TRADD, indicating a novel target for the treatment of RA.

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“…Lipid peroxidation, one of the primary reasons for CCl4induced liver damage, is generated by free radical derivatives of CCl4. (Wang et al 2021) indicated that triterpenoid saponins protect against liver injury by toxicants in mice via activation of necrosis and inflammation. An increase in MDA reflects increased lipid peroxidation after CC14 treatment and indicates oxidative stress (Botsoglou et al 2008).…”

Section: Effect Of Steroidal Saponins On Lipid Peroxidationmentioning

confidence: 99%

Steroidal Saponin as Antioxidant and Alleviator of CCl4-Induced Oxidative Damage in Albino Rats.

Eliwa

Ibrahim

El-Sayed

et al. 2022

Arab Universities Journal of Agricultural Sciences

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Liver toxicity is a common condition that can be induced by environmental pollutants. The present study explored the hepatoprotective activity of steroidal saponins extracted from the yam plant versus CC14-induced hepatotoxicity in albino rats. Twenty-five albino rats were classified into 5 groups. Rats of group (G1) were provided a basal diet and drinking water and served as un-treated controls. Other groups were administered CC14 orally twice a week at a dose of 400 mg/kg. The second group (G2) did not receive any further treatment and served as positive controls while rats in the groups G3, G4 and G5 were administered saponins (50,100 and 200 mg/kg body weight, respectively) for six weeks in the remaining groups. The hepatoprotective activity of saponins was assessed by measurement of liver enzymes, kidney function tests, malondialdehyde content, and antioxidant defense enzymes activities in serum of these rats. Saponins administration improved liver and renal function and significantly increased the activities of catalase, glutathione peroxidase (GSH-PX), glutathione reductase GSH-RD and superoxide dismutase SOD. These increases were linked to a considerable decrease in serum malondialdehyde levels, indicating that lipid peroxidation was being mitigated. Thus, the concentration of saponins (200 mg/kg) is the best concentration of protection against CC14-induced hepatic injury, improved liver and renal function, and reduced oxidative stress in rats.

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Pterocephin A, a novel Triterpenoid Saponin from Pterocephalus hookeri induced liver injury by activation of necroptosis

Cited by 10 publications

References 36 publications

Acteoside attenuates RSV-induced lung injury by suppressing necroptosis and regulating metabolism

Acteoside attenuates RSV-induced lung injury by suppressing necroptosis and regulating metabolism

Downregulation of BIRC2 hinders the progression of rheumatoid arthritis through regulating TRADD

Steroidal Saponin as Antioxidant and Alleviator of CCl4-Induced Oxidative Damage in Albino Rats.

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