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JOURNAL OF ETHNOPHARMACOLOGY · 2023 · IF 5.4

The Active Fraction of Polyrhachis vicina Roger (AFPR) activates ERK to cause necroptosis in colorectal cancer

Dong-mei Li,Fu-cui Zhu,Jie Wei,Jia-xiu Xie,Jun-hui He,Dong-mei Wei,Yi Li,Ke-dao Lai,Li-min Liu,Qi-biao Su,Gui-ning Wei,Bin Wang,Yan-cheng Liu

Ethnopharmacological relevance Polyrhachis vicina Roger ( P. vicina ), a traditional Chinese medicinal animal, has been used to treat rheumatoid arthritis , hepatitis, cancer, and other conditions. Due to its anti-inflammatory properties, our previous pharmacological investigations have demonstrated that it is effective against cancer, depression, and hyperuricemia . Nevertheless, the key active components and targets of P. vicina in cancers are still unexplored. Aim of the study The study aimed to evaluate the pharmacological treatment mechanism of the active fraction of P. vicina (AFPR) in treating colorectal cancer (CRC) and to further reveal its active ingredients and key targets. Methods To examine the inhibitory impact of AFPR on CRC growth, tumorigenesis assays, cck-8 assays, colony formation assays, and MMP detection were utilized. The primary components of AFPR were identified by GC-MS analysis. The network pharmacology , molecular docking, qRT-PCR, western blotting , CCK-8 assays, colony formation assay, Hoechst staining, Annexin V-FITC/PI double staining, and MMP detection were performed to pick out the active ingredients and potential key targets of AFPR. The function of Elaidic acid on necroptosis was investigated through siRNA interference and the utilization of inhibitors. Elaidic acid's effectiveness to suppress CRC growth in vivo was assessed using a tumorigenesis experiment. Results Studies confirmed that AFPR prevented CRC from growing and evoked cell death. Elaidic acid was the main bioactive ingredient in AFPR that targeted ERK. Elaidic acid greatly affected the ability of SW116 cells to form colonies, produce MMP, and undergo necroptosis. Additionally, Elaidic acid promoted necroptosis predominantly by activating ERK/RIPK1/RIPK3/MLKL. Conclusion According to our findings, Elaidic acid is the main active component of AFPR, which induced necroptosis in CRC through the activation of ERK. It represents a promising alternative therapeutic option for CRC. This work provided experimental support for the therapeutic application of P. vicina Roger in the treatment of CRC.

CAS / MDL: 51-21-8
研究领域: 药理学 · 肿瘤学 · 传统中药 · 分子生物学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY · 2017 · IF 3.505

Nerol triggers mitochondrial dysfunction and disruption via elevation of Ca2+ and ROS in Candida albicans

Jun Tian,Zhaoqun Lu,Yanzhen Wang,Man Zhang,Xueyan Wang,Xudong Tang,Xue Peng,Hong Zeng

The antifungal activity of Nerol (NEL) against Candida albicans , a pathogenic fungus, has a minimum inhibitory concentration (MIC) of 4.4   mM that causes noteworthy candidacidal activity through an apoptosis-like mechanism. Calcium (Ca 2+ ) levels and reactive oxygen species (ROS) production, which are the major causes of apoptosis, were determined in C. albicans cells treated with NEL and were found to increase, which related to mitochondrial dysfunction and disruption. A series of characteristic changes of apoptosis caused by NEL, including mitochondrial membrane depolarization, cytochrome c (cyt c) release, and metacaspase activation were examined using a flow cytometer and Western blot . The results showed that an increase in intracellular Ca 2+ and ROS led to dramatically decreased mitochondrial membrane potential (MMP); cyt c was also released from the mitochondria to the cytosol. Other early apoptotic features were also observed with the metacaspase activation. Finally, the morphological changes of the cells were observed, including phosphatidylserine (PS) externalization, nuclear condensation, and DNA fragmentation through Annexin V-FITC and PI double staining, TUNEL assay , and DAPI staining. The results supported the hypothesis that NEL was involved in the apoptosis of C. albicans cells not only at the early stages, but also at the late stages. In summary, NEL can trigger mitochondrial dysfunction and disruption via elevation of Ca 2+ and ROS leading to apoptosis in C. albicans . This research on the mechanism of cell death triggered by NEL against C. albicans has important significance for providing a novel treatment of C. albicans infections.

研究领域: 微生物学 · 药理学 · 细胞生物学
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