Chiisanoside from the Leaves of Acanthopanax sessiliflorus Can Resist Cisplatin-Induced Ototoxicity by Maintaining Cytoskeletal Homeostasis and Inhibiting Ferroptosis DOI

Hongbo Teng,

Xialin Sun,

R. I. Eglitis

и другие.

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(46), С. 25720 - 25742

Опубликована: Ноя. 6, 2024

Ototoxicity is a common side effect of cisplatin cancer treatment, potentially leading to hearing loss. This study demonstrated the significant protective activity Acanthopanax sessiliflorus (A. sessiliflorus) leaves against cisplatin-induced ototoxicity (CIO), investigated active compounds, and elucidated their mechanisms in countering CIO. UPLC-Q/TOF-MS analysis identified 79 compounds. Network pharmacology screening determined that chiisanoside (CSS) plays crucial role combating Transcriptomics combined with network experiments revealed CSS activates Dock1/PIP5K1A pathway suppress actin-severing protein gelsolin, protecting hair cells from cytoskeleton damage. also SLC7A11/GPX4 via TGFBR2, reducing lipid peroxidation intracellular iron accumulation ferroptosis. discovers major component A. reverses CIO by regulating actin homeostasis Dock1 inhibiting ferroptosis through providing theoretical basis for expanding treatment targets related drug development.

Язык: Английский

Ginsenoside Rh2(S) maintains cytoskeleton homeostasis and inhibits pyroptosis to resist cisplatin-induced cardiotoxicity through FGFR1/HRAS axis DOI

Hongbo Teng,

Shuai Huang,

Xialin Sun

и другие.

Phytomedicine, Год журнала: 2025, Номер 138, С. 156425 - 156425

Опубликована: Янв. 24, 2025

Язык: Английский

Процитировано

1

Modulation of NLRP3 inflammasome-related-inflammation via RIPK1/RIPK3-DRP1 or HIF-1α signaling by phenothiazine in hypothermic and normothermic neuroprotection after acute ischemic stroke DOI Creative Commons

Qian Jiang,

Yuchuan Ding, Fengwu Li

и другие.

Redox Biology, Год журнала: 2024, Номер 73, С. 103169 - 103169

Опубликована: Апрель 26, 2024

Inflammation and subsequent mitochondrial dysfunction cell death worsen outcomes after revascularization in ischemic stroke. Receptor-interacting protein kinase 1 (RIPK1) activated dynamin-related (DRP1) a NLRPyrin domain containing 3 (NLRP3) inflammasome-dependent fashion Hypoxia-Inducible Factor (HIF)-1α play key roles the process. This study determined how phenothiazine drugs (chlorpromazine promethazine (C+P)) with hypothermic normothermic modality impacts RIPK1/RIPK3-DRP1 HIF-1α pathways providing neuroprotection. A total of 150 adult male Sprague-Dawley rats were subjected to 2 h middle cerebral artery occlusion (MCAO) followed by 24 reperfusion. 8mg/kg C+P was administered at onset Infarct volumes, mRNA expressions HIF-1α, RIPK1, RIPK3, DRP-1, NLRP3-inflammation cytochrome c-apoptosis assessed. Apoptotic death, infiltration neutrophils macrophages, function evaluated. Interaction between RIPK1/RIPK3 HIF-1α/NLRP3 determined. In SH-SY5Y cells oxygen/glucose deprivation (OGD), effect on inflammation apoptosis examined. significantly reduced infarct (ATP ROS concentration, citrate synthase ATPase activity), without induced hypothermia. Overexpression NLRP3-inflammasome all 33°C RIPK1 inhibitor (Nec1s), suggesting via RIPK1/RIPK3-DRP1pathway. When body temperature maintained 37°C, (YC-1) expression, leading reduction dysfunction, NLRP3 inflammasome c-apoptosis, as well interaction NLRP3. These also evidenced vitro, indicating HIF-1α. Hypothermic neuroprotection involve different pathways. The mediated while signaling. provides theoretical basis for future precise exploration

Язык: Английский

Процитировано

4

The chiisanoside derivatives present in the leaves of Acanthopanax sessiliflorus activate autophagy through the LRP6/GSK3β axis and thereafter inhibit oxidative stress, thereby counteracting cisplatin-induced ototoxicity DOI Creative Commons

Wenxin Zhang,

Hongbo Teng,

Tianyi Zhao

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 15

Опубликована: Янв. 15, 2025

Cisplatin is extensively employed in the treatment of multiple solid malignant tumors. Nevertheless, side effects such as cisplatin-induced ototoxicity (CIO) pose obstacles to tumor therapy.The important natural product chiisanoside from Acanthopanax sessiliflorus has abundant activity against CIO. In this study, 26 derivatives were screened, and compound 19 demonstrated significant protective CIO damage. A HEI-OC1 cell injury model a mouse established. The regulatory revealed through transcriptome sequencing, protein expression levels analyzed by molecular docking, ELISA, Western blotting, immunofluorescence. It was found that inhibited apoptosis, alleviated abnormal hearing spiral ganglion Transcriptome sequencing its effects. Compound increased autophagy levels, thereby alleviating mitochondrial dysfunction reducing accumulation reactive oxygen species (ROS).In-depth studies have inhibitor 3-methyladenine (3-MA) weakens effect on inhibits clearance damaged cells, resulting oxidative stress damage, apoptosis necrosis. By knocking down LRP6, it eliminated, level significantly reduced, ROS production induced, after cisplatin exposure promoted. Finally, LiCl used suppress GSK3β. inhibiting GSK3β could protect cells damage activating autophagy. These findings suggest capable preventing via LRP6/GSK3β axis consequently stress, offering new approach for treating sensorineural loss.

Язык: Английский

Процитировано

0

Dexmedetomidine Promotes Angiogenesis After Ischemic Stroke Through the NRF2/HO-1/VEGF Pathway DOI
Zhenxing Tao,

Pengpeng Li,

Yushi Tang

и другие.

Neurochemical Research, Год журнала: 2025, Номер 50(2)

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0

Design and synthesis of matrine derivatives for anti myocardial ischemia–reperfusion injury by promoting angiogenesis DOI
Xiaofeng Liu, Bowen Fan, S. Huang

и другие.

Bioorganic & Medicinal Chemistry, Год журнала: 2024, Номер 108, С. 117776 - 117776

Опубликована: Май 30, 2024

Язык: Английский

Процитировано

1

Synthesis of furanotriterpenoids from betulin and evaluation of Tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibitory properties of new semi-synthetic triterpenoids DOI

И. А. Толмачева,

Daria V. Eroshenko, Irina A. Chernyshova

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 276, С. 116724 - 116724

Опубликована: Июль 27, 2024

Язык: Английский

Процитировано

1

Chiisanoside from the Leaves of Acanthopanax sessiliflorus Can Resist Cisplatin-Induced Ototoxicity by Maintaining Cytoskeletal Homeostasis and Inhibiting Ferroptosis DOI

Hongbo Teng,

Xialin Sun,

R. I. Eglitis

и другие.

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(46), С. 25720 - 25742

Опубликована: Ноя. 6, 2024

Ototoxicity is a common side effect of cisplatin cancer treatment, potentially leading to hearing loss. This study demonstrated the significant protective activity Acanthopanax sessiliflorus (A. sessiliflorus) leaves against cisplatin-induced ototoxicity (CIO), investigated active compounds, and elucidated their mechanisms in countering CIO. UPLC-Q/TOF-MS analysis identified 79 compounds. Network pharmacology screening determined that chiisanoside (CSS) plays crucial role combating Transcriptomics combined with network experiments revealed CSS activates Dock1/PIP5K1A pathway suppress actin-severing protein gelsolin, protecting hair cells from cytoskeleton damage. also SLC7A11/GPX4 via TGFBR2, reducing lipid peroxidation intracellular iron accumulation ferroptosis. discovers major component A. reverses CIO by regulating actin homeostasis Dock1 inhibiting ferroptosis through providing theoretical basis for expanding treatment targets related drug development.

Язык: Английский

Процитировано

1