Objective: To investigate the effects of asperuloside on cervical cancer based on endoplasmic reticulum(ER) stress and mitochondrial pathway. Methods: Different doses(12.5–800 μg/mL) of asperuloside were used to tre...Objective: To investigate the effects of asperuloside on cervical cancer based on endoplasmic reticulum(ER) stress and mitochondrial pathway. Methods: Different doses(12.5–800 μg/mL) of asperuloside were used to treat cervical cancer cell lines Hela and CaSki to calculate the half maximal inhibitory concentration(IC_(50)) of asperuloside. The cell proliferation was analyzed by clone formation assay. Cell apoptosis, intracellular reactive oxygen species(ROS) and mitochondrial membrane potential were determined by flow cytometry. The protein expressions of cleaved-caspase-3, Bcl-2, Bax, Cyt-c, cleaved-caspase-4 and glucose-regulated protein 78(GRP78) were analyzed by Western blot. And the inhibitor of ER stress, 4-phenyl butyric acid(4-PBA) was used to treat cervical cancer cells to further verify the role of ER stress in the apoptosis of cervical cancer cells induced by asperuloside. Results: Asperuloside of 325, 650, and 1300 μg/mL significantly inhibited the proliferation and promoted apoptosis of Hela and CaSki cells(P<0.01). All doses of asperuloside significantly increased intracellular ROS levels, reduced mitochondrial membrane potential, significantly reduced Bcl-2 protein expression level, and increased Bax, Cyt-c, GRP78 and cleaved-caspase-4 expressions(P<0.01). In addition, 10 mmol/L 4-PBA treatment significantly promoted cell proliferation and reduced apoptosis(P<0.05), and 650 μg/mL asperuloside could reverse 4-PBA-induced increased cell proliferation, decreased apoptosis and cleaved-caspase-3,-4 and GRP78 protein expressions(P<0.05). Conclusion: Our study revealed the role of asperuloside in cervical cancer, suggesting that asperuloside promotes apoptosis of cervical cancer cells through ER stress-mitochondrial pathway.展开更多
A new glycoside named 6β-O-β-D-glucosylpaederosidic acid(1) was isolated from Paederia scandens and its structure was elucidated on the basis of spectroscopic and chemical evidence,together with four known iridoids,...A new glycoside named 6β-O-β-D-glucosylpaederosidic acid(1) was isolated from Paederia scandens and its structure was elucidated on the basis of spectroscopic and chemical evidence,together with four known iridoids,paederoside(2),paederosidic acid(3),paederosidic acid methyl ester(4),and deacetyl asperulosidic acid methyl ester(5).Compound 5 was isolated from this plant for the first time.展开更多
基金Supported by Scientific Research Project of Hebei Provincial Administration of Traditional Chinese Medicine (No. 2021077)。
文摘Objective: To investigate the effects of asperuloside on cervical cancer based on endoplasmic reticulum(ER) stress and mitochondrial pathway. Methods: Different doses(12.5–800 μg/mL) of asperuloside were used to treat cervical cancer cell lines Hela and CaSki to calculate the half maximal inhibitory concentration(IC_(50)) of asperuloside. The cell proliferation was analyzed by clone formation assay. Cell apoptosis, intracellular reactive oxygen species(ROS) and mitochondrial membrane potential were determined by flow cytometry. The protein expressions of cleaved-caspase-3, Bcl-2, Bax, Cyt-c, cleaved-caspase-4 and glucose-regulated protein 78(GRP78) were analyzed by Western blot. And the inhibitor of ER stress, 4-phenyl butyric acid(4-PBA) was used to treat cervical cancer cells to further verify the role of ER stress in the apoptosis of cervical cancer cells induced by asperuloside. Results: Asperuloside of 325, 650, and 1300 μg/mL significantly inhibited the proliferation and promoted apoptosis of Hela and CaSki cells(P<0.01). All doses of asperuloside significantly increased intracellular ROS levels, reduced mitochondrial membrane potential, significantly reduced Bcl-2 protein expression level, and increased Bax, Cyt-c, GRP78 and cleaved-caspase-4 expressions(P<0.01). In addition, 10 mmol/L 4-PBA treatment significantly promoted cell proliferation and reduced apoptosis(P<0.05), and 650 μg/mL asperuloside could reverse 4-PBA-induced increased cell proliferation, decreased apoptosis and cleaved-caspase-3,-4 and GRP78 protein expressions(P<0.05). Conclusion: Our study revealed the role of asperuloside in cervical cancer, suggesting that asperuloside promotes apoptosis of cervical cancer cells through ER stress-mitochondrial pathway.
基金supported by the National Natural Sciences Foundation of China(No.20876126)Southwest University for Nationalities Foundation for doctors(No.26701001)
文摘A new glycoside named 6β-O-β-D-glucosylpaederosidic acid(1) was isolated from Paederia scandens and its structure was elucidated on the basis of spectroscopic and chemical evidence,together with four known iridoids,paederoside(2),paederosidic acid(3),paederosidic acid methyl ester(4),and deacetyl asperulosidic acid methyl ester(5).Compound 5 was isolated from this plant for the first time.