Browsing by Author "Donkor, P.O."
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Item Cetuximab enhances oridonin-induced apoptosis through mitochondrial pathway and endoplasmic reticulum stress in laryngeal squamous cell carcinoma cells(Toxicology in Vitro, 2020-05-12) Donkor, P.O.; Kang, N.; Cao, S.; Jiang, B.; Zhang, Q.; Zhu, Y.; Qiu, F.; Gao, X.Cetuximab plus oridonin showed a synergistic way to kill laryngeal squamous cell carcinoma (LSCC), as been reported previously. The present work further mechanistically extended action of the synergistic effects of combination treatment. Firstly, two LSCC cells displayed higher sensitivity to oridonin, whereas both low EGFR expression tumor cells and EGFR knockdown LSCC cells were less sensitive to oridonin. Next, cetuximab/oridonin significantly enhanced the mitochondrial apoptosis through NF-κB. Meanwhile, PI3K/Akt and JAK2/STAT3 pathways are associated with the nucleus translocation of NF-κB by combination treatment. Additionally, cetuximab enhanced oridonin-promoted ER stress-related apoptosis. Interestingly, both ER stress and mitochondrial apoptosis by combination treatment are abrogated by ROS scavenger. Furthermore, oridonin/cetuximab induced ROS production after 1.5 h, followed by G2/M arrest and apoptosis, indicating that ROS generation might be an early and key event. Taken together, cetuximab enhances oridonin-induced ER stress and mitochondrial apoptotic pathway, which contributes to the synergistic antitumor effects of cetuximab/oridonin.Item Eudesmane-Type Sesquiterpenes from Curcuma phaeocaulis and Their Inhibitory Activities on Nitric Oxide Production in RAW 264.7 Cells(European Journal of Organic Chemistry, 2014-09) Liu, Y.; Ma, J.; Wang, Y.; Donkor, P.O.; Li, Q.; Gao, S.; Hou, Y.; Xu, Y.; Cui, J.; Ding, L.; Zhao, F.; Kang, N.; Chen, L.; Qiu, F.Eight eudesmane-type sesquiterpenes - phaeusmanes A-H (1-8) - isolated for the first time in this work, and four others (9-12) isolated for the first time from plants in this work, together with fourteen known eudesmane derivatives, were isolated from the rhizomes of Curcuma phaeocaulis. Their structures were elucidated by 1D and 2D NMR and CD spectroscopy and HRMS. Compound 8 is the first example of a nitrogen-containing eudesmane-type sesquiterpene isolated from the genus Curcuma. Furthermore, inhibitory effects of the isolated compounds on NO production in lipopolysaccharide-activated macrophages were evaluated. Compounds 1, 6, 10, 19, 22, and 24 showed strong inhibitory activities on NO production with IC50 values of 3.2, 4.8, 1.2, 0.8, 3.8, and 0.8 μM, respectively. Preliminary structure-activity relationships for these compounds are proposed. A possible biogenetic pathway for nitrogen-containing eudesmane-type sesquiterpene 8 is postulated. Eight new sesquiterpenes (phaeusmanes A-H), together with eighteen known analogues, were isolated from the rhizomes of Curcuma phaeocaulis. Their complete structures were elucidated by NMR, MS, and CD spectroscopy. The NO inhibitory effects of the isolates are presented. A possible biogenetic pathway for N-containing eudesmane-type sesquiterpene 8 is postulated. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Item Metabolic profiles of corydaline in rats by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry(Xenobiotica, 2019-01) Chai, L.; Donkor, P.O.; Wang, K.; Sun, Y.; Oppong, M.B.; Wang, K.; Ding, L.; Qiu, F.1. Corydaline, an isoquinoline alkaloid obtained from the rhizomes of Corydalis yanhusuo, exhibits anti-acetylcholinesterase, anti-angiogenic, anti-allergic and gastric-emptying activities. In this study, a rapid and reliable ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) method was developed and employed for the comprehensive study of the metabolites of corydaline in rats. 2. Altogether, 43 metabolites were identified in the plasma (11), bile (9), urine (34) and feces (21) of rats after oral administration of corydaline at a dose of 4.5mg/kg. 3. It was demonstrated that demethylation, hydroxylation, sulfation and glucuronidation were the major metabolic transformation pathways. Among these, two metabolites were identified as tetrahydropalmatine and isocorybulbine, and 33 phase I and phase II products were inferred to be new metabolites arising from the in vivo metabolism of corydaline. 4. Importantly, this research provides scientific and reliable support for full understanding of the metabolic profiles of corydaline and the results could help to elucidate its safety and efficacy.Item Undescribed sesquiterpenoids with NO production inhibitory activity from oleo-gum resin of Commiphora myrrha(Phytochemistry, 2024) Zhang, B.; Chao, W.; Donkor, P.O.; et al.Six undescribed cadinane sesquiterpenoids (1− 6), two undescribed guaiane sesquiterpenoids (7− 8), and an undescribed germacrane sesquiterpenoid (9) were isolated from the oleo-gum resin of Commiphora myrrha. Their structures were determined by the analysis of 1D/2D NMR and HRESIMS data, as well as quantum chemical ECD and NMR calculations. All the sesquiterpenoids were evaluated for their NO production inhibitory activity in LPS-stimulated RAW 264.7 mouse monocyte-macrophages. The results revealed that commiphone A (1) and commipholide D (7) exhibited significant inhibitory effect on NO generation with IC50 values of 18.6 ± 2.0 and 37.5 ± 1.5 μM, respectively. Furthermore, 1 and 7 dose-dependently inhibited the mRNA expression of in flammatory cytokines IL-1β, IL-6 and TNF-α induced by LPS in the RAW264.7 cells, indicating that 1 and 7 possess potent anti-inflammatory activity in vitro.