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LKB1-AMPK信号通路
PHARMAZIE · 2018 ·Vol. 73 ·期 10 ·594-597 · IF 1.016

Andrographolide inhibits proliferation and induces apoptosis of nasopharyngeal carcinoma cell line C666-1 through LKB1-AMPK-dependent signaling pathways

Wu Bo,Chen Xi,Zhou Ying,Hu Pingjun,Wu Dan,Zheng Guodong,Cai Yi

Background: Andrographolide (Andro) belongs to the main bioactive ingredients of Andrographis paniculata. Many studies have shown that andro has a variety of pharmacological activities such as anti-inflammatory, anti-bacterial, anti-virus, anti-oxidant, immune regulation and liver protective effects. Moreover andro has been reported to have anticancer activity in multiple types of cancer, including gastric cancer, breast cancer, lung cancer and so on. However, there is no report about the effect of andro on the human NPC cell line C666-1 and the molecular mechanisms of andro-mediated apoptosis in C666-1 cells remain to be clarified. Methods: Cell proliferation was measured by a CCK8 assay, cell apoptosis rate was evaluated by flow cytometric analysis, and the protein expression of LKB1/AMPK signaling pathways was detected by Western blotting. Results: Treatment with andro inhibited cell proliferation and induced apoptosis of C666-1 cells. Moreover, andro could activate LKB1-AMPK signaling. We also demonstrated that Ca2+/calmodulin-dependent protein kinase kinaseβ (CaMKKβ) was not involved in the regulation of andro on AMPK activation in C666-1 Cells. Conclusions: Andro suppressed proliferation and induced apoptosis of C666-1 cells through regulating the LKB1/AMPK/mTOR signal pathway.

研究领域: 肿瘤学 · 药理学 · 细胞生物学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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EUROPEAN JOURNAL OF PHARMACOLOGY · 2023 · IF 5

Alisol B blocks the development of HFD-induced obesity by triggering the LKB1-AMPK signaling in subcutaneous adipose tissue

Ling Yang,Linzi Li,Qian Lu,Lingfeng Li,Chun Xie,Fakun Jiang,Hongbing Li,Ai Zhao,Qian Wang,Wenyong Xiong

As a global epidemic disease, obesity causes dysfunction of glucose and lipid metabolism leading to persistently high morbidity and mortality. Given the difficulty to achieve and maintain weight loss through controlling diet and physical exercise, pharmacotherapy is considered an effective treatment for obesity. This investigation revealed that alisol B, a triterpene monomer isolated from the classical Chinese medicine Alisma orientale (Sam.) Juzep, functioned in suppressing adipogenesis and reducing the mass of subcutaneous adipose tissue, resulting in the reduction of weight gain, and improvements of hyperglycemia, hyperlipidemia, and insulin resistance in HFD-induced obese mice. In consistent to the results, alisol B also significantly inhibited adipocyte differentiation and maturation in vitro . Furthermore, our data revealed that the effects of alisol B on adipogenesis were mediated by LKB1-AMPK signaling pathway. In total, alisol B could be a potential lead compound which contributes to the improvement of obesity-related metabolic disorders.

CAS / MDL: 22978-25-2 28822-58-4
研究领域: 药理学 · 代谢学 · 内分泌学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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PHYTOMEDICINE · 2023 · IF 7.9

Baicalin inhibits pressure overload-induced cardiac hypertrophy by regulating the SIRT3-dependent signaling pathway

Yi Cai,Shisheng Jiang,Chaoming Huang,Ao Shen,Xuan Zhang,Wanling Yang,Yichuan Xiao,Shuhan Gao,Rong Du,Guodong Zheng,Tingdong Yan,Chunpeng (Craig) Wan

Background The conserved sirtuin protein sirtuin 3 (SIRT3) is a vital protective protein for cardiac hypertrophy. Inhibition of SIRT3 accelerated the development of heart hypertrophy. On the other hand, myocardial hypertrophy was prevented by overexpressing SIRT3. SIRT3 has been proposed as a potential therapeutic target for managing or averting heart hypertrophy. Baicalin, a flavonoid extracted from the Scutellaria baicalensis plant, has anti-cardiovascular properties, including protection against cardiac hypertrophy. However, the molecular mechanism of the anti-hypertrophic effect of baicalin is not well known. Purpose In this study, we aim to investigate the effect of baicalin on cardiac hypertrophy and explored its underlying molecular mechanisms. Study-design/methods Abdominal aortic constriction (AAC)-induced mouse cardiac hypertrophy and angiotensin II (Ang II)-induced cardiomyocyte hypertrophy models were established. After baicalin treatment, cardiac hypertrophy was monitored by detecting the expression of hypertrophic genes and cell surface area. Echocardiogram was performed to check the heart function in vivo . Moreover, the protein expression of the SIRT3-dependent pathway was detected by Western blotting. Results In this work, we demonstrated that baicalin might suppress the cell surface area and the expression of the Ang II -induced myosin heavy chain β (β-MHC), brain natriuretic polypeptide (BNP), and atrial natriuretic factor (ANF). Additionally, it reduced the AAC rats' hypertrophic impact. We also found that baicalin prevents cardiac hypertrophy by regulating SIRT3/LKB1/AMPK signaling pathway. Moreover, we showed that baicalin upregulated the SIRT3 protein expression by inhibiting proteasome and by the activation of 20 S proteasome subunit beta type-5 (PSMB5). Conclusion These results offer the first proof that baicalin inhibits cardiac hypertrophy due to its effect on the SIRT3-dependent signaling pathway, indicating its potential for treating cardiac hypertrophy and heart failure. The present study provides a preliminary experimental basis for the clinical application of baicalin and baicalin-like compounds.

CAS / MDL: 21967-41-9
研究领域: 心脏病学 · 药理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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