OBJECTIVE Quanzhen Yiqi decoction (QZYQ) is a traditional Chinese medicine for treating chronic obstructive pulmonary disease. METHODS Mice were exposed to cigarette smoke (CS) 6 days/week (40 cigarettes/day) for 24 weeks and then intragastrically administered QZYQ (4.72, 9.45, or 18.89 g/kg) or dexamethasone (DEX, 0.6 mg/kg) for 6 weeks. We examined the lung function and collected bronchoalveolar lavage fluid for inflammatory cell and cytokine quantification. The pathological lung changes, ROS and oxidative biomarkers were measured. We used immunohistochemistry and western blotting to evaluate the levels of Nrf2/HO-1, NLRP3/ASC/Caspase1/IL-1β/IL-18. RESULTS The CS group showed significant increases in the forced vital capacity, lung resistance, and chord compliance and a lower FEV50/FVC compared with the control, and QZYQ improved these changes. In addition, QZYQ effectively reduced emphysema, immune cell infiltration, and airway remodeling. QZYQ stimulated HO-1 expression and reduced oxidative stress through the Nrf2 pathway. QZYQ inhibited the production of NLRP3/ASC/Caspase-1 to inhibit IL-1β and IL-18. CONCLUSION Our study suggested that QZYQ can improve the function and histology of the lungs and reduce inflammatory cell recruitment. QZYQ inhibits ROS production and NLRP3 inflammasome activation by upregulating Nrf2 to reduce lung injury. The anti-inflammatory effects of QZYQ are similar to those of DEX.
{"title":"Quanzhen Yiqi decoction attenuates inflammation in mice with smoking-induced COPD by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome.","authors":"Jiamin Zeng, Zhenqiu Li, Wanyan Li, Zhu Liang, Yuewen Luo, Caiping Li, Sida Liao, Kexin Wang, Yuanlong Hu, Yuanyuan Li, Qiuling Liang, Wenju Lu, Lu Li, Zhijuan Wu, Da-Peng Zhang, Zhiming Zhang","doi":"10.1093/jpp/rgae047","DOIUrl":"https://doi.org/10.1093/jpp/rgae047","url":null,"abstract":"OBJECTIVE\u0000Quanzhen Yiqi decoction (QZYQ) is a traditional Chinese medicine for treating chronic obstructive pulmonary disease.\u0000\u0000\u0000METHODS\u0000Mice were exposed to cigarette smoke (CS) 6 days/week (40 cigarettes/day) for 24 weeks and then intragastrically administered QZYQ (4.72, 9.45, or 18.89 g/kg) or dexamethasone (DEX, 0.6 mg/kg) for 6 weeks. We examined the lung function and collected bronchoalveolar lavage fluid for inflammatory cell and cytokine quantification. The pathological lung changes, ROS and oxidative biomarkers were measured. We used immunohistochemistry and western blotting to evaluate the levels of Nrf2/HO-1, NLRP3/ASC/Caspase1/IL-1β/IL-18.\u0000\u0000\u0000RESULTS\u0000The CS group showed significant increases in the forced vital capacity, lung resistance, and chord compliance and a lower FEV50/FVC compared with the control, and QZYQ improved these changes. In addition, QZYQ effectively reduced emphysema, immune cell infiltration, and airway remodeling. QZYQ stimulated HO-1 expression and reduced oxidative stress through the Nrf2 pathway. QZYQ inhibited the production of NLRP3/ASC/Caspase-1 to inhibit IL-1β and IL-18.\u0000\u0000\u0000CONCLUSION\u0000Our study suggested that QZYQ can improve the function and histology of the lungs and reduce inflammatory cell recruitment. QZYQ inhibits ROS production and NLRP3 inflammasome activation by upregulating Nrf2 to reduce lung injury. The anti-inflammatory effects of QZYQ are similar to those of DEX.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"9 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Bagde, Keb Mosley-Kellum, Shawn D Spencer, Mandip Singh
OBJECTIVE The objective of the present study was to enhance the bioavailability of cannabidiol (CBD) using 3D Digital Light Processing (DLP)-printed microneedle (MN) transdermal drug delivery system. METHODS CBD MN patch was fabricated and optimized using 3D DLP printing using CBD (8% w/v), Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) (0.49% w/v), distilled water (20% w/v), and poly (ethylene glycol) dimethacrylate 550 (PEGDAMA 550) (up to 100% w/v). CBD MNs were characterized for their morphology, mechanical strength, in vitro release study, ex vivo permeation study, and in vivo pharmacokinetic (PK) profile. KEY FINDINGS Microscopic images showed that sharp CBD MNs with a height of ~800 μm, base diameter of ~250 μm, and tip with a radius of curvature (RoC) of ~15 μm were successfully printed using optimized printing parameters. Mechanical strength studies showed no significant deformation in the morphology of CBD MNs even after applying 0.5N/needle force. Ex vivo permeation study showed significant (P < .0001) permeation of CBD in the receiving media as compared to CBD patch (control). In vivo PK study showed significantly (P < .05) enhanced bioavailability in the case of CBD MN patch as compared to CBD subcutaneous inj. (control). CONCLUSION Overall, systemic absorption of CBD was significantly enhanced using 3D-printed MN drug delivery system.
{"title":"3D DLP-printed cannabinoid microneedles patch and its pharmacokinetic evaluation in rats.","authors":"A. Bagde, Keb Mosley-Kellum, Shawn D Spencer, Mandip Singh","doi":"10.1093/jpp/rgae043","DOIUrl":"https://doi.org/10.1093/jpp/rgae043","url":null,"abstract":"OBJECTIVE\u0000The objective of the present study was to enhance the bioavailability of cannabidiol (CBD) using 3D Digital Light Processing (DLP)-printed microneedle (MN) transdermal drug delivery system.\u0000\u0000\u0000METHODS\u0000CBD MN patch was fabricated and optimized using 3D DLP printing using CBD (8% w/v), Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) (0.49% w/v), distilled water (20% w/v), and poly (ethylene glycol) dimethacrylate 550 (PEGDAMA 550) (up to 100% w/v). CBD MNs were characterized for their morphology, mechanical strength, in vitro release study, ex vivo permeation study, and in vivo pharmacokinetic (PK) profile.\u0000\u0000\u0000KEY FINDINGS\u0000Microscopic images showed that sharp CBD MNs with a height of ~800 μm, base diameter of ~250 μm, and tip with a radius of curvature (RoC) of ~15 μm were successfully printed using optimized printing parameters. Mechanical strength studies showed no significant deformation in the morphology of CBD MNs even after applying 0.5N/needle force. Ex vivo permeation study showed significant (P < .0001) permeation of CBD in the receiving media as compared to CBD patch (control). In vivo PK study showed significantly (P < .05) enhanced bioavailability in the case of CBD MN patch as compared to CBD subcutaneous inj. (control).\u0000\u0000\u0000CONCLUSION\u0000Overall, systemic absorption of CBD was significantly enhanced using 3D-printed MN drug delivery system.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"67 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140664152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OBJECTIVES Breast cancer is a prevalent disease that has a substantial impact on women's mortality rates. Shikonin, a naphthoquinone derived from Lithospermum erythrorhizon, has demonstrated substantial anticancer effects. This study aims to conduct a comprehensive review of the latest research findings regarding the therapeutic efficacy of shikonin in the context of breast cancer treatment, with a specific emphasis on elucidating the underlying molecular mechanisms. METHODS A comprehensive literature review was conducted on shikonin and breast cancer by searching PubMed, Scopus, Web of Science, and Google Scholar databases. KEY FINDINGS Shikonin significantly reduces tumor cell viability, proliferation, migration, invasion, and metastasis in both in vivo and in vitro across all breast cancer subtypes. Additionally, when combined with other pharmaceutical agents, it exhibits synergistic effects. Shikonin stimulates immunogenic cell death, resulting in apoptosis and necroptosis. The induction of immunogenic cell death by shikonin enhances the immunogenicity of breast cancer cells, leading to its involvement in the development of dendritic cell-based tumor vaccines against breast cancer. CONCLUSION Shikonin exhibits potent anti-breast cancer properties and shows significant potential for the advancement of immunotherapeutic approaches against breast cancer, as well as enhancing the efficacy of conventional treatment strategies.
{"title":"Shikonin in breast cancer treatment: a comprehensive review of molecular pathways and innovative strategies.","authors":"Saeid Iranzadeh, Davood Dalil, Soroush Kohansal, Mahdi Isakhani","doi":"10.1093/jpp/rgae041","DOIUrl":"https://doi.org/10.1093/jpp/rgae041","url":null,"abstract":"OBJECTIVES\u0000Breast cancer is a prevalent disease that has a substantial impact on women's mortality rates. Shikonin, a naphthoquinone derived from Lithospermum erythrorhizon, has demonstrated substantial anticancer effects. This study aims to conduct a comprehensive review of the latest research findings regarding the therapeutic efficacy of shikonin in the context of breast cancer treatment, with a specific emphasis on elucidating the underlying molecular mechanisms.\u0000\u0000\u0000METHODS\u0000A comprehensive literature review was conducted on shikonin and breast cancer by searching PubMed, Scopus, Web of Science, and Google Scholar databases.\u0000\u0000\u0000KEY FINDINGS\u0000Shikonin significantly reduces tumor cell viability, proliferation, migration, invasion, and metastasis in both in vivo and in vitro across all breast cancer subtypes. Additionally, when combined with other pharmaceutical agents, it exhibits synergistic effects. Shikonin stimulates immunogenic cell death, resulting in apoptosis and necroptosis. The induction of immunogenic cell death by shikonin enhances the immunogenicity of breast cancer cells, leading to its involvement in the development of dendritic cell-based tumor vaccines against breast cancer.\u0000\u0000\u0000CONCLUSION\u0000Shikonin exhibits potent anti-breast cancer properties and shows significant potential for the advancement of immunotherapeutic approaches against breast cancer, as well as enhancing the efficacy of conventional treatment strategies.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"26 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140671482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Sridhar, Peter R. Flatt, Matthew Draper, Andrei I Tarasov, R. Moffett, Nigel Irwin, D. Khan
OBJECTIVES Dopamine and related receptors are evidenced in pancreatic endocrine tissue, but the impact on islet β-cell stimulus-secretion as well as (patho)physiological role are unclear. METHODS The present study has evaluated islet cell signalling pathways and biological effects of dopamine, as well as alterations of islet dopamine in rodent models of diabetes of different aetiology. KEY FINDINGS The dopamine precursor L-DOPA partially impaired glucose tolerance in mice and attenuated glucose-, exendin-4, and alanine-induced insulin secretion. The latter effect was echoed by the attenuation of glucose-induced [Ca2+]i dynamics and elevation of ATP levels in individual mouse islet cells. L-DOPA significantly decreased β-cell proliferation rates, acting predominantly via the D2 receptor, which was most abundant at the mRNA level. The administration of streptozotocin (STZ) or high-fat diet (HFD) in mice significantly elevated numbers of dopamine-positive islet cells, with HFD also increasing colocalization of dopamine with insulin. At the same time, colocalization of dopamine with glucagon was increased in STZ-treated and pregnant mice, but unaffected by HFD. CONCLUSION These findings highlight a role for dopamine receptor signalling in islet cell biology adaptations to various forms of metabolic stress.
{"title":"Dopamine signalling in pancreatic islet cells and role in adaptations to metabolic stress.","authors":"A. Sridhar, Peter R. Flatt, Matthew Draper, Andrei I Tarasov, R. Moffett, Nigel Irwin, D. Khan","doi":"10.1093/jpp/rgae049","DOIUrl":"https://doi.org/10.1093/jpp/rgae049","url":null,"abstract":"OBJECTIVES\u0000Dopamine and related receptors are evidenced in pancreatic endocrine tissue, but the impact on islet β-cell stimulus-secretion as well as (patho)physiological role are unclear.\u0000\u0000\u0000METHODS\u0000The present study has evaluated islet cell signalling pathways and biological effects of dopamine, as well as alterations of islet dopamine in rodent models of diabetes of different aetiology.\u0000\u0000\u0000KEY FINDINGS\u0000The dopamine precursor L-DOPA partially impaired glucose tolerance in mice and attenuated glucose-, exendin-4, and alanine-induced insulin secretion. The latter effect was echoed by the attenuation of glucose-induced [Ca2+]i dynamics and elevation of ATP levels in individual mouse islet cells. L-DOPA significantly decreased β-cell proliferation rates, acting predominantly via the D2 receptor, which was most abundant at the mRNA level. The administration of streptozotocin (STZ) or high-fat diet (HFD) in mice significantly elevated numbers of dopamine-positive islet cells, with HFD also increasing colocalization of dopamine with insulin. At the same time, colocalization of dopamine with glucagon was increased in STZ-treated and pregnant mice, but unaffected by HFD.\u0000\u0000\u0000CONCLUSION\u0000These findings highlight a role for dopamine receptor signalling in islet cell biology adaptations to various forms of metabolic stress.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"48 20","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140667047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yang Wang, Ge Bai, Shanshan Mu, Fenglian Zhang, Yan Wang
BACKGROUND Ischemic stroke (IS) is a detrimental neurological disease and IS lacks valuable methods to recover body function. Indobufen (IND) could alleviate IS. However, the possible mechanism remains undefined. METHODS SH-SY5Y cells were cultured under the oxygen-glucose deprivation/reoxygenation (OGD/R) environment and then were treated with small interfering RNA (siRNA) of NRF2 and ATG5. The influence of various concentrations of IND (50 μM, 100 μM, 200 μM, and 400 μM) was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide. Levels of superoxide dismutase (SOD) and malonaldehyde (MDA) were examined by ELISA. Reactive oxygen species (ROS) production was determined by DCFH-DA staining. The protein levels of LC3II/LC3I, Beclin1, p62, NRF2, and ATG5 were detected by western blot. RESULTS IND increased cell viability, while depressed the rate of apoptosis in SH-SY5Y cells of OGD/R environment. IND inhibited autophagy by suppressing the levels of LC3II/LC3I, Beclin1 protein, and increasing p62 protein expression in SH-SY5Y cells of OGD/R environment. IND limited the contents of ROS and MDA, while amplifying the activity of SOD in SH-SY5Y cells with OGD/R exposure. IND also promoted NRF2 expression in OGD/R environment. CONCLUSION IND could inhibit autophagy, oxidative stress, and apoptosis in SH-SY5Y cells with OGD/R exposure, further alleviating IS injury by regulating transcription factor NRF2 and inhibiting ATG5 expression.
{"title":"Indobufen alleviates ischemic stroke injury by regulating transcription factor NRF2 and inhibiting ATG5 expression.","authors":"Yang Wang, Ge Bai, Shanshan Mu, Fenglian Zhang, Yan Wang","doi":"10.1093/jpp/rgae038","DOIUrl":"https://doi.org/10.1093/jpp/rgae038","url":null,"abstract":"BACKGROUND\u0000Ischemic stroke (IS) is a detrimental neurological disease and IS lacks valuable methods to recover body function. Indobufen (IND) could alleviate IS. However, the possible mechanism remains undefined.\u0000\u0000\u0000METHODS\u0000SH-SY5Y cells were cultured under the oxygen-glucose deprivation/reoxygenation (OGD/R) environment and then were treated with small interfering RNA (siRNA) of NRF2 and ATG5. The influence of various concentrations of IND (50 μM, 100 μM, 200 μM, and 400 μM) was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide. Levels of superoxide dismutase (SOD) and malonaldehyde (MDA) were examined by ELISA. Reactive oxygen species (ROS) production was determined by DCFH-DA staining. The protein levels of LC3II/LC3I, Beclin1, p62, NRF2, and ATG5 were detected by western blot.\u0000\u0000\u0000RESULTS\u0000IND increased cell viability, while depressed the rate of apoptosis in SH-SY5Y cells of OGD/R environment. IND inhibited autophagy by suppressing the levels of LC3II/LC3I, Beclin1 protein, and increasing p62 protein expression in SH-SY5Y cells of OGD/R environment. IND limited the contents of ROS and MDA, while amplifying the activity of SOD in SH-SY5Y cells with OGD/R exposure. IND also promoted NRF2 expression in OGD/R environment.\u0000\u0000\u0000CONCLUSION\u0000IND could inhibit autophagy, oxidative stress, and apoptosis in SH-SY5Y cells with OGD/R exposure, further alleviating IS injury by regulating transcription factor NRF2 and inhibiting ATG5 expression.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"5 6part2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140714141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. D. dos Santos, F. Veras, G. Netto, L. Elisei, C. Sorgi, L. Faccioli, G. Galdino
OBJECTIVES This study aimed to investigate the effect of cannabidiol (CBD) on type 4 Toll-like receptors (TLR4), glial cells and pro-inflammatory cytokines during the neuropathic pain induced by the chemotherapy agent paclitaxel (PTX), as well as the involvement of the endocannabinoid system in this process. METHODS Male C57BL6 mice were subjected to PTX-induced neuropathic pain. To evaluate the involvement of the TLR4, glial cells and cannabinoid CB2 receptor, specific inhibitors or antagonists were intrathecally administered. The western blotting and immunofluorescence assay was performed to evaluate the spinal expression of TLR4, microglia, astrocytes and cannabinoid CB2 receptor. The levels of spinal pro-inflammatory cytokines and endocannabinoids were determined by enzyme-linked immunosorbent assay and liquid chromatography-mass spectrometry analysis, respectively. KEY FINDINGS CBD prevented PTX-induced neuropathic pain, and the cannabinoid CB2 receptor antagonist AM630 reversed this effect. In addition, CBD treatment inhibited the spinal expression of TLR4 and Iba1 in mice with neuropathic pain. CBD also increased spinal levels of endocannabinoids anandamide and 2-arachidonoylglycerol, and reduced levels of cytokines in mice with neuropathic pain. CONCLUSIONS CBD was efficient in preventing PTX-induced neuropathic pain, and this effect may involve inhibition of the TLR4 on microglia spinal with activation of the endocannabinoid system.
{"title":"Cannabidiol prevents chemotherapy-induced neuropathic pain by modulating spinal TLR4 via endocannabinoid system activation.","authors":"R. D. dos Santos, F. Veras, G. Netto, L. Elisei, C. Sorgi, L. Faccioli, G. Galdino","doi":"10.2139/ssrn.4199529","DOIUrl":"https://doi.org/10.2139/ssrn.4199529","url":null,"abstract":"OBJECTIVES\u0000This study aimed to investigate the effect of cannabidiol (CBD) on type 4 Toll-like receptors (TLR4), glial cells and pro-inflammatory cytokines during the neuropathic pain induced by the chemotherapy agent paclitaxel (PTX), as well as the involvement of the endocannabinoid system in this process.\u0000\u0000\u0000METHODS\u0000Male C57BL6 mice were subjected to PTX-induced neuropathic pain. To evaluate the involvement of the TLR4, glial cells and cannabinoid CB2 receptor, specific inhibitors or antagonists were intrathecally administered. The western blotting and immunofluorescence assay was performed to evaluate the spinal expression of TLR4, microglia, astrocytes and cannabinoid CB2 receptor. The levels of spinal pro-inflammatory cytokines and endocannabinoids were determined by enzyme-linked immunosorbent assay and liquid chromatography-mass spectrometry analysis, respectively.\u0000\u0000\u0000KEY FINDINGS\u0000CBD prevented PTX-induced neuropathic pain, and the cannabinoid CB2 receptor antagonist AM630 reversed this effect. In addition, CBD treatment inhibited the spinal expression of TLR4 and Iba1 in mice with neuropathic pain. CBD also increased spinal levels of endocannabinoids anandamide and 2-arachidonoylglycerol, and reduced levels of cytokines in mice with neuropathic pain.\u0000\u0000\u0000CONCLUSIONS\u0000CBD was efficient in preventing PTX-induced neuropathic pain, and this effect may involve inhibition of the TLR4 on microglia spinal with activation of the endocannabinoid system.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128653145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Circ_UTRN ameliorates caerulein-induced acute pancreatitis in vitro via reducing inflammation and promoting apoptosis through miR-320-3p/PTK2 axis.","authors":"Q. Sun, Ran Liang, Mingdong Li, Hua Zhou","doi":"10.1093/jpp/rgac025","DOIUrl":"https://doi.org/10.1093/jpp/rgac025","url":null,"abstract":"","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115351194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Senggunprai, V. Kukongviriyapan, A. Prawan, S. Kongpetch
OBJECTIVES Strategies that induce apoptosis of malignant cells are recognized as effective cancer treatments. This study evaluated the apoptosis-inducing ability of momordin Ic against cholangiocarcinoma (CCA) cells and the respective underlying mechanisms. METHODS Quantification of apoptotic cells was performed using Annexin V/7-AAD double dye staining followed by flow cytometry. The effect of momordin Ic on the expression of epidermal growth factor receptor (EGFR) and its downstream signalling molecules was determined via Western blot analysis. The RT2 Profiler PCR Array was used to determine the expression of cell death-associated genes. Expression levels of apoptosis-related proteins were examined using an apoptosis antibody array. KEY FINDINGS Momordin Ic potently limited the ability of CCA cells to thrive by promoting apoptotic cell death. This apoptosis-inducing activity was accompanied with suppression of expression of EGFR, p-EGFR, c-Myc and other downstream EGFR signalling-related molecules. Additional molecular analyses demonstrated that momordin Ic modified the expression profile of cell death-associated genes in CCA cells. Moreover, significant upregulation of apoptosis-activating proteins and downregulation of apoptosis-inhibiting protein were also observed after exposure to momordin Ic. CONCLUSIONS These results suggest that momordin Ic has a potential therapeutic opportunity for CCA treatment by acting as an EGFR suppressant.
{"title":"Epidermal growth factor receptor as a potential target of momordin Ic to promote apoptosis of cholangiocarcinoma cells.","authors":"L. Senggunprai, V. Kukongviriyapan, A. Prawan, S. Kongpetch","doi":"10.1093/jpp/rgac033","DOIUrl":"https://doi.org/10.1093/jpp/rgac033","url":null,"abstract":"OBJECTIVES\u0000Strategies that induce apoptosis of malignant cells are recognized as effective cancer treatments. This study evaluated the apoptosis-inducing ability of momordin Ic against cholangiocarcinoma (CCA) cells and the respective underlying mechanisms.\u0000\u0000\u0000METHODS\u0000Quantification of apoptotic cells was performed using Annexin V/7-AAD double dye staining followed by flow cytometry. The effect of momordin Ic on the expression of epidermal growth factor receptor (EGFR) and its downstream signalling molecules was determined via Western blot analysis. The RT2 Profiler PCR Array was used to determine the expression of cell death-associated genes. Expression levels of apoptosis-related proteins were examined using an apoptosis antibody array.\u0000\u0000\u0000KEY FINDINGS\u0000Momordin Ic potently limited the ability of CCA cells to thrive by promoting apoptotic cell death. This apoptosis-inducing activity was accompanied with suppression of expression of EGFR, p-EGFR, c-Myc and other downstream EGFR signalling-related molecules. Additional molecular analyses demonstrated that momordin Ic modified the expression profile of cell death-associated genes in CCA cells. Moreover, significant upregulation of apoptosis-activating proteins and downregulation of apoptosis-inhibiting protein were also observed after exposure to momordin Ic.\u0000\u0000\u0000CONCLUSIONS\u0000These results suggest that momordin Ic has a potential therapeutic opportunity for CCA treatment by acting as an EGFR suppressant.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"100 6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123131646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OBJECTIVES Circular RNA (CircRNA) is a class of non-coding RNA transcripts, with multiple pathophysiological functions. Instead, the mechanism and function of circRNA in gastric cancer (GC) are not fully deciphered. METHODS CircRNA_0026344 (circ_0026344), microRNA (miR)-590-5p and programmed cell death 4 (PDCD4) mRNA expression levels in GC tissues and cells were probed by quantitative real-time PCR. Cell viability, migration and aggressiveness were examined by cell counting kit-8 and transwell assays. Additionally, the interplay among circ_0026344, miR-590-5p and PDCD4 was verified with bioinformatics and dual-luciferase reporter gene assay. Western blot was conducted to probe PDCD4 protein expression. KEY FINDINGS Circ_0026344 expression was underexpressed in GC tissues and cells, which was associated with clinicopathological characteristics such as tumour size, tumor-node-metastasis stage and lymph node metastasis. Circ_0026344 overexpression restrained the malignant biological behaviours of GC cells, while circ_0026344 knockdown functioned oppositely. Circ_0026344 could act as a competing endogenous RNA of miR-590-5p to negatively modulate its expression, and this miRNA could mitigate the impact of circ_0026344 on GC cells. In addition, PDCD4 was identified as the downstream target of miR-590-5p, and PDCD4 expression was positively modulated by circ_0026344. CONCLUSIONS Circ_0026344 up-regulates PDCD4 expression via sponging miR-590-5p, thus inhibiting the progression of GC. This study further expounds the underlying molecular mechanism in the GC progression.
{"title":"Circular RNA hsa_circ_0026344 suppresses gastric cancer cell proliferation, migration and invasion via the miR-590-5p/PDCD4 axis.","authors":"Long Lv, Jinghu Du, Daorong Wang, Zeqiang Yan","doi":"10.1093/jpp/rgac032","DOIUrl":"https://doi.org/10.1093/jpp/rgac032","url":null,"abstract":"OBJECTIVES\u0000Circular RNA (CircRNA) is a class of non-coding RNA transcripts, with multiple pathophysiological functions. Instead, the mechanism and function of circRNA in gastric cancer (GC) are not fully deciphered.\u0000\u0000\u0000METHODS\u0000CircRNA_0026344 (circ_0026344), microRNA (miR)-590-5p and programmed cell death 4 (PDCD4) mRNA expression levels in GC tissues and cells were probed by quantitative real-time PCR. Cell viability, migration and aggressiveness were examined by cell counting kit-8 and transwell assays. Additionally, the interplay among circ_0026344, miR-590-5p and PDCD4 was verified with bioinformatics and dual-luciferase reporter gene assay. Western blot was conducted to probe PDCD4 protein expression.\u0000\u0000\u0000KEY FINDINGS\u0000Circ_0026344 expression was underexpressed in GC tissues and cells, which was associated with clinicopathological characteristics such as tumour size, tumor-node-metastasis stage and lymph node metastasis. Circ_0026344 overexpression restrained the malignant biological behaviours of GC cells, while circ_0026344 knockdown functioned oppositely. Circ_0026344 could act as a competing endogenous RNA of miR-590-5p to negatively modulate its expression, and this miRNA could mitigate the impact of circ_0026344 on GC cells. In addition, PDCD4 was identified as the downstream target of miR-590-5p, and PDCD4 expression was positively modulated by circ_0026344.\u0000\u0000\u0000CONCLUSIONS\u0000Circ_0026344 up-regulates PDCD4 expression via sponging miR-590-5p, thus inhibiting the progression of GC. This study further expounds the underlying molecular mechanism in the GC progression.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127277183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruhao Yang, Haizhen Yang, Wenqiang Li, F. Yue, Hao Chen, Yueying Hao, Ke Hu
BACKGROUND Our previous study found that Lianhuaqingwen reduces lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice by suppressing p53-mediated apoptosis. To identify the type of lung cells affected by Lianhuaqingwen, we conducted a cell experiment. METHODS C57/B6 mice and A549 cells were administered Lianhuaqingwen and LPS. A549 cells were transfected with p53 siRNA to inhibit p53. The degree of ALI in mice was validated by haematoxylin and eosin staining as well as measurement of IL-1β and MCP-1 levels. In A549 cells, Cell Counting Kit-8 (CCK-8), DHE and TUNEL assays were used to assess cell viability, reactive oxygen species (ROS) production and apoptosis, respectively. Western blot analysis was used to evaluate the protein expression of p53, Bcl-2, Bax, caspase-9 and caspase-3. Co-immunofluorescence was used to detect cytochrome C distribution. KEY FINDINGS Lianhuaqingwen alleviated LPS-induced ALI in vivo. Lianhuaqingwen at 300 μg/ml increased cell viability, lowered ROS production and reduced apoptotic cells in vitro. Lianhuaqingwen enhanced Bcl-2 expression and reduced Bax, caspase-9 and caspase-3 expression as well as blocked cytochrome C release under LPS stimulation. Treatment with a combination of Lianhuaqingwen and p53 siRNA was more effective than treatment with Lianhuaqingwen alone. CONCLUSION Lianhuaqingwen inhibits p53-mediated apoptosis in alveolar epithelial cells, thereby preventing LPS-induced ALI.
{"title":"Lianhuaqingwen alleviates p53-mediated apoptosis in alveolar epithelial cells to prevent LPS-induced ALI.","authors":"Ruhao Yang, Haizhen Yang, Wenqiang Li, F. Yue, Hao Chen, Yueying Hao, Ke Hu","doi":"10.1093/jpp/rgac035","DOIUrl":"https://doi.org/10.1093/jpp/rgac035","url":null,"abstract":"BACKGROUND\u0000Our previous study found that Lianhuaqingwen reduces lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice by suppressing p53-mediated apoptosis. To identify the type of lung cells affected by Lianhuaqingwen, we conducted a cell experiment.\u0000\u0000\u0000METHODS\u0000C57/B6 mice and A549 cells were administered Lianhuaqingwen and LPS. A549 cells were transfected with p53 siRNA to inhibit p53. The degree of ALI in mice was validated by haematoxylin and eosin staining as well as measurement of IL-1β and MCP-1 levels. In A549 cells, Cell Counting Kit-8 (CCK-8), DHE and TUNEL assays were used to assess cell viability, reactive oxygen species (ROS) production and apoptosis, respectively. Western blot analysis was used to evaluate the protein expression of p53, Bcl-2, Bax, caspase-9 and caspase-3. Co-immunofluorescence was used to detect cytochrome C distribution.\u0000\u0000\u0000KEY FINDINGS\u0000Lianhuaqingwen alleviated LPS-induced ALI in vivo. Lianhuaqingwen at 300 μg/ml increased cell viability, lowered ROS production and reduced apoptotic cells in vitro. Lianhuaqingwen enhanced Bcl-2 expression and reduced Bax, caspase-9 and caspase-3 expression as well as blocked cytochrome C release under LPS stimulation. Treatment with a combination of Lianhuaqingwen and p53 siRNA was more effective than treatment with Lianhuaqingwen alone.\u0000\u0000\u0000CONCLUSION\u0000Lianhuaqingwen inhibits p53-mediated apoptosis in alveolar epithelial cells, thereby preventing LPS-induced ALI.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"2017 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122217124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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