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2.
J Nat Med ; 77(4): 721-734, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37353674

RESUMO

This study investigated the protective effect of lobetyolin (LBT), a Q-marker isolated from the roots of Platycodon grandiflorum (Radix Platycodi), against cisplatin-induced cytotoxicity in human embryonic kidney (HEK293) cells. Results showed that LBT at 20 µM significantly prevented cisplatin-induced cytotoxicity by improving the viability of HEK293 cells, decreasing levels of MDA, and decreasing GSH content triggered by cisplatin. It also suppressed reactive oxygen species (ROS) levels. Molecular docking analysis revealed a strong binding affinity between LBT and the NF-κB protein, with a docking fraction of - 6.5 kcal/mol. These results provide compelling evidence suggesting a potential link between the visualization analysis of LBT and its protective mechanism, specifically implicating the NF-κB signaling pathway. LBT also reduced the expression level of tumor necrosis factor-alpha (TNF-α), phosphorylation NF-κB and IκBα in HEK293 cells which were increased by cisplatin exposure, leading to inhibition of inflammation. Furthermore, western blotting showed that LBT antagonized the up-regulation of Bax, cleaved caspase 3, 8, and 9 expression and inhibited the MAPK signaling pathway by down-regulating phosphorylation JNK, ERK, and p38, partially ameliorating cisplatin-induced cytotoxicity in HEK293 cells. Therefore, these results indicate that LBT has potentially protected renal function by inhibiting inflammation and apoptosis.


Assuntos
Cisplatino , NF-kappa B , Humanos , Cisplatino/toxicidade , Células HEK293 , NF-kappa B/metabolismo , Simulação de Acoplamento Molecular , Fator de Necrose Tumoral alfa/metabolismo , Apoptose , Inflamação
3.
Phytother Res ; 37(7): 2827-2840, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37037488

RESUMO

Previous reports have confirmed that saponins (ginsenosides) derived from Panax ginseng. C. A. Meyer exerted obvious memory-enhancing and antiaging effects, and the simpler the structure of ginsenosides, the better the biological activity. In this work, we aimed to explore the therapeutic effect and underlying molecular mechanism of 20(S)-protopanaxatriol (PPT), the aglycone of panaxatriol-type ginsenosides, by establishing D-galactose (D-gal)-induced subacute brain aging model in mice. The results showed that PPT treatment (10 and 20 mg/kg) for 4 weeks could significantly restore the D-gal (800 mg/kg for 8 weeks)-induced impaired memory function, choline dysfunction, and redox system imbalance in mice. Meanwhile, PPT also significantly reduced the histopathological changes caused by D-gal exposure. Moreover, PPT could increase TFEB/LAMP2 protein expression to promote mitochondrial autophagic flow. Importantly, the results from molecular docking showed that PPT had good binding ability with LAMP2 and TFEB, suggesting that TFEB/LAMP2 might play an important role in PPT to alleviate D-gal-caused brain aging.


Assuntos
Ginsenosídeos , Panax , Camundongos , Animais , Ginsenosídeos/farmacologia , Galactose/efeitos adversos , Simulação de Acoplamento Molecular , Envelhecimento , Encéfalo/metabolismo , Panax/química
4.
Food Funct ; 13(21): 11283-11297, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36226633

RESUMO

Cisplatin-evoked profound gastrointestinal symptomatology is one of the most common side effects of chemotherapy drugs, further causing gastrointestinal cell damage, diarrhea and vomiting. Panax ginseng C. A. Meyer, a widely used medicinal and edible plant in China, shows many pharmacological activities. Nevertheless, the role of non-saponin is less known and has great potential in the treatment of severe toxic side effects related to the cisplatin treatment. The present work evaluates the efficiency of a major Maillard reaction product (MRP) of red ginseng, arginyl-fructosyl-glucose (AFG), against cisplatin-evoked intestinal toxicity in vivo and vitro, and the underlying possible mechanisms are also explored. The cisplatin-treated mice (a dose of 20 mg kg-1 for one time) showed serious intestinal mucosa damage accompanied by increased indicators of diamine oxidase (DAO) and decreased expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin. Moreover, cisplatin exposure increased intestinal cell apoptosis with decreased expression of Bcl-2 and increased expression of Bax and cleaved-caspase 3/9 as well as NF-κB related proteins. Interestingly, the supplements of AFG at doses of 40 and 80 mg kg-1 day-1 for 10 days significantly ameliorated these changes. It was also demonstrated in cultured IEC-6 cells that AFG enhanced the expression levels of apoptotic proteins during cisplatin exposure and reduced the sensitivity of IEC-6 cells to cisplatin by inhibiting the activation of GSK3ß and up-regulating the protein expression of ß-catenin. In conclusion, AFG exerted protective effects against cisplatin-induced intestinal toxicity, at least partially by the inhibition of NF-κB-mediated apoptosis, via regulating Wnt/ß-catenin signaling pathway.


Assuntos
Cisplatino , Panax , Camundongos , Animais , Cisplatino/toxicidade , Produtos Finais de Glicação Avançada/farmacologia , NF-kappa B/genética , NF-kappa B/metabolismo , Panax/metabolismo , Apoptose
5.
Int J Biol Macromol ; 209(Pt A): 871-884, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35439476

RESUMO

Many dietary polysaccharides have been shown to protect against various harmful external stimuli by protecting the integrity of the intestinal barrier. Arabinogalactan (AG) is a high molecular weight polysaccharide composed of arabinose and galactose, which has good immunomodulatory, antioxidant and intestinal conditioning activities. Gastrointestinal injury caused by cisplatin (CP) is an inevitable damage during CP chemotherapy. This research explored the ameliorative effect of AG on cisplatin-induced intestinal toxicity and its possible molecular targets and mechanisms. The results showed that AG (200, 400 mg/kg) could significantly reverse the intestinal histopathological changes and oxidative stress injury caused by CP. Meantime, AG could target the IRE1α/JNK axis to inhibit the expression of apoptosis-related proteins and block the apoptotic cascade, thus reducing intestinal damage. In vitro, AG (10, 20, and 40 µg/mL) could regulate the IRE1α/JNK axis, inhibit apoptosis, and restore the antioxidant defense system damaged by CP to play a protective role in the intestine. In addition, 4-phenylbutyrate (4-PBA), a specific inhibitor of endoplasmic reticulum stress, was used to verify that AG also affected protein expression levels by regulating the IRE1α/JNK pathway-mediated endoplasmic reticulum stress signaling pathway, thereby alleviating CP-induced gastrointestinal dysfunction. Therefore, AG may be a potential drug to prevent CP-induced intestinal damage.


Assuntos
Endorribonucleases , Larix , Antioxidantes/farmacologia , Apoptose , Cisplatino/efeitos adversos , Estresse do Retículo Endoplasmático , Endorribonucleases/metabolismo , Galactanos , Proteínas Serina-Treonina Quinases , Transdução de Sinais
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