Senkyunolide H protects PC12 cells from OGD/R-induced injury via cAMP-PI3K/AKT signaling pathway

Jiang, Yunyao; Luo, Yanyan; Chen, Xinyi; Liu, Nan; Hou, Jincai; Piao, Jingpei; Chen, Song; Si, Chuanling; Hu, Weicheng

doi:10.1016/j.jep.2021.114659

Cited by 12 publications

(7 citation statements)

References 29 publications

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“…cAMP reduces Akt kinase activity and inhibits Akt phosphorylation, and then modulates apoptosis ( Jiang et al, 2021 ; Wahlang et al, 2018 ). Adenosine A 2A receptor stimulation increases cAMP level and this increased cAMP level inhibits apoptotic cell death by secreting anti-apoptosis proteins, which in turn play a major role in the regulation of apoptosis ( Ahsan and Mehal, 2014 ; Ko et al, 2020a ).…”

Section: Discussionmentioning

confidence: 99%

Polydeoxyribonucleotide ameliorates alcoholic liver injury though suppressing phosphatidylinositol 3-kinase/protein kinase B signaling pathway in mice

Cho¹,

Ko²,

Jin³

et al. 2022

J Exerc Rehabil

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Polydeoxyribonucleotide (PDRN), which is adenosine A<sub>2A</sub> receptor agonist, facilitates healing and inhibits inflammation and apoptosis. The effect of PDRN on alcoholic liver injury (ALI) was evaluated focusing on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. The mice were given daily oral administration of 50% ethanol at a dose of 4 g/kg during 8 weeks. After 4 weeks of alcohol intake, 200 μL of normal saline containing 8-mg/kg PDRN was intraperitoneally administered 3 times a week for 4 weeks. To determine whether the action of PDRN occurs through the adenosine A<sub>2A</sub> receptor, 8-mg/kg 3,7-dimethyl-1-propargylxanthine (DMPX) with PDRN was treated. The concentration of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was detected. For liver histopathological score, hematoxylin and eosin staining was conducted. Enzyme-linked immunoassay was used to measure cyclic adenosine-3′,5′-monophosphate (cAMP) concentration. PI3K and Akt expression was determined using Western blot analysis. In the results, PDRN treatment suppressed AST and ALT level in serum and liver tissue, and improved damaged liver tissue and decreased histological score. PDRN application inhibited the expression of phosphorylated PI3K/Akt signaling pathway. The increasing effect of PDRN on cAMP level ats as a mechanism for ALI treatment. Co-treatment of DMPX with PDRN did not reduce apoptosis, causing no improvement in liver function. As a result of this experiment, PDRN has the potential to be selected as a therapeutic agent for ALI.

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Section: Discussionmentioning

confidence: 99%

Polydeoxyribonucleotide ameliorates alcoholic liver injury though suppressing phosphatidylinositol 3-kinase/protein kinase B signaling pathway in mice

Cho¹,

Ko²,

Jin³

et al. 2022

J Exerc Rehabil

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“…Among 11 traditional Chinese medicines, obvious therapeutic effects of Chuanxiong, Bupleurum, Licorice, and Poria on stroke have been observed [22]. The active ingredients senkyunolide A, Z-ligustilide [16], Ligusticum, Ligustrazine, Ligustylid [23], ferulic acid, and Senkyunolide H [24] in Chuanxiong can dramatically inhibit the production of pro-inflammatory mediators in mouse BV-2 microglia after lipopolysaccharide (LPS) stimulation, obviously impair the aggregation of thrombosis and platelet, as well as blood viscosity to improve cerebral microcirculation, significantly reduce injury after ICH. A network pharmacology analysis revealed that the anti-inflammatory effect of JFG is predominantly mediated by its activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway through Luteolin, (+)-Anomalin and Phaseol and their targeting of AKT1, tumor necrosis factorα (TNF-α), and interleukin-1β (IL-1β).…”

Section: Introductionmentioning

confidence: 99%

“…Among 11 traditional Chinese medicines, obvious therapeutic effects of Chuanxiong, Bupleurum, Licorice, and Poria on stroke have been observed [ 22 ]. The active ingredients senkyunolide A, Z-ligustilide [ 16 ], Ligusticum, Ligustrazine, Ligustylid [ 23 ], ferulic acid, and Senkyunolide H [ 24 ] in Chuanxiong can dramatically inhibit the production of pro-inflammatory mediators in mouse BV-2 microglia after lipopolysaccharide (LPS) stimulation, obviously impair the aggregation of thrombosis and platelet, as well as blood viscosity to improve cerebral microcirculation, significantly reduce infarct volume, neurological dysfunction, BBB disruption, and cerebral edema [ 25 – 28 ]. The active ingredient Saikosaponin A in Bupleurum can significantly improve post-stroke depression (PSD)-like behavior, inhibit neuronal apoptosis, increased the levels of brain-derived neurotrophic factor and Bcl-2 in the hippocampus of PSD rats, and reduced the levels of Bax and caspase-3 [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Jingfang granules protects against intracerebral hemorrhage by inhibiting neuroinflammation and protecting blood-brain barrier damage

Li,

Yu,

Peng

et al. 2024

Aging

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Intracerebral hemorrhage (ICH) can induce intensive oxidative stress, neuroinflammation, and brain cell apoptosis. However, conventional methods for ICH treatment have many disadvantages. There is an urgent need for alternative, effective therapies with minimal side effects. Pharmacodynamics experiment, molecular docking, network pharmacology, and metabolomics were adopted to investigate the treatment and its mechanism of Jingfang Granules (JFG) in ICH. In this study, we investigated the therapeutic effects of JFG on ICH using behavioral, brain water content and Magnetic resonance imaging experiments. However, the key active component and targets of JFG remain unknown. Here we verified that JFG was beneficial to improve brain

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“…Yang et al demonstrated that SNH attenuates osteoclastogenesis and postmenopausal osteoporosis by regulating the NF‐κB, JNK, and ERK signal pathways 5 . In addition, SNH has been demonstrated to protect PC12 cells from OGD/R‐induced injury via cAMP‐PI3K/AKT signal pathway 6 …”

Section: Introductionmentioning

confidence: 99%

“…5 In addition, SNH has been demonstrated to protect PC12 cells from OGD/R-induced injury via cAMP-PI3K/AKT signal pathway. 6 Metabolite identification aims at identifying and quantifying metabolites, and such data are considered of critical value for understanding the elimination routes, efficacy, toxicological profiles of drugs, and for predicting drug-drug interaction in humans. 7 In particular, an early understanding of metabolite profiles in humans may increase drug safety that is of greatest regulatory and public health interest.…”

Section: Introductionmentioning

confidence: 99%

A high‐resolution mass spectrometric method for identification and characterization of the in vitro metabolites of senkyunolide H

Yan

Chen

Zou

et al. 2022

Rapid Comm Mass Spectrometry

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Rationale Ligusticum chuanxiong Hort is a well‐known herb medicine that has been widely prescribed to treat cardiovascular diseases in China for hundreds of years. Senkyunolide H (SNH) is one of the major bioactive ingredients extracted from L. chuanxiong, and it displayed neuroprotective effects. To fully understand its mechanism of action, the metabolism needs to be investigated. Methods In vitro studies were conducted by incubating SNH with rat and human hepatocytes, and the metabolites were identified and characterized using liquid chromatography in combination with hybrid quadrupole Orbitrap mass spectrometry (LC‐Orbitrap‐MS). The structures of the metabolites were proposed by accurate mass analysis of respective precursor ions, indicative product ions, and elemental compositions. Results Under the current conditions, a total of 10 metabolites were identified, and among these metabolites, M3 and M4 were the most abundant metabolites both in rat and human hepatocytes. Our results demonstrated that hydroxylation, hydration, glucuronidation, and GSH conjugation were the primary metabolic pathways of SNH. Conclusions The present study provides new information on the metabolism of SNH, which would help prospects of the disposition of SNH.

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Senkyunolide H protects PC12 cells from OGD/R-induced injury via cAMP-PI3K/AKT signaling pathway

Cited by 12 publications

References 29 publications

Polydeoxyribonucleotide ameliorates alcoholic liver injury though suppressing phosphatidylinositol 3-kinase/protein kinase B signaling pathway in mice

Polydeoxyribonucleotide ameliorates alcoholic liver injury though suppressing phosphatidylinositol 3-kinase/protein kinase B signaling pathway in mice

Jingfang granules protects against intracerebral hemorrhage by inhibiting neuroinflammation and protecting blood-brain barrier damage

A high‐resolution mass spectrometric method for identification and characterization of the in vitro metabolites of senkyunolide H

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