5F-Cumyl-PINACA in ‘e-liquids’ for electronic cigarettes: comprehensive characterization of a new type of synthetic cannabinoid in a trendy product including investigations on the in vitro and in vivo phase I metabolism of 5F-Cumyl-PINACA and its non-fluorinated analog Cumyl-PINACA

ABSTRACTA gene that codes for a novel intracellular poly-3-hydroxybutyrate (PHB) depolymerase has now been identified in the genome ofBacillus thuringiensissubsp.israelensisATCC 35646. This gene, previously annotated as a hypothetical 3-oxoadipate enol-lactonase (PcaD) gene and now designatedphaZ, encodes a protein that shows no significant similarity with any known PHB depolymerase. Purified His-tagged PhaZ could efficiently degrade trypsin-activated native PHB granules as well as artificial amorphous PHB granules and release 3-hydroxybutyrate monomer as a hydrolytic product, but it could not hydrolyze denatured semicrystalline PHB. In contrast, purified His-tagged PcaD ofPseudomonas putidawas unable to degrade trypsin-activated native PHB granules and artificial amorphous PHB granules. TheB. thuringiensisPhaZ was inactive againstp-nitrophenylpalmitate, tributyrin, and triolein. Sonication supernatants of the wild-typeB. thuringiensiscells exhibited a PHB-hydrolyzing activity in vitro, whereas those prepared from aphaZmutant lost this activity. ThephaZmutant showed a higher PHB content than the wild type at late stationary phase of growth in a nutrient-rich medium, indicating that this PhaZ can function as a PHB depolymerase in vivo. PhaZ contains a lipase box-like sequence (G-W-S102-M-G) but lacks a signal peptide. A purified His-tagged S102A variant had lost the PHB-hydrolyzing activity. Taken together, these results indicate thatB. thuringiensisharbors a new type of intracellular PHB depolymerase.

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Comprehensive characterization of the in vitro and in vivo metabolites of ziyuglycoside I in rat microsome, intestinal flora, excretion specimen and fresh tissues based on LC–Q-TOF/MS

Journal of Pharmaceutical and Biomedical Analysis ◽

10.1016/j.jpba.2016.05.032 ◽

2016 ◽

Vol 128 ◽

pp. 191-200 ◽

Cited By ~ 22

Author(s):

Guangji Wang ◽

Hanxu Fu ◽

Wei Ye ◽

Xiao Zheng ◽

Jingcheng Xiao ◽

...

Keyword(s):

Intestinal Flora ◽

Comprehensive Characterization ◽

Tof Ms

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Pharmacological characterization of repeated administration of the first generation abused synthetic cannabinoid CP47,497

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2015-0118 ◽

2016 ◽

Vol 27 (3) ◽

Cited By ~ 6

Author(s):

Travis W. Grim ◽

Kimberly L. Samano ◽

Bogna Ignatowska-Jankowska ◽

Qing Tao ◽

Laura J. Sim-Selly ◽

...

Keyword(s):

G Proteins ◽

First Generation ◽

Repeated Administration ◽

Synthetic Cannabinoid ◽

In Vitro Assays ◽

Pharmacological Effects ◽

Pharmacological Characterization

AbstractA series of in vivo and in vitro assays were conducted to characterize the pharmacological effects of the first generation abused synthetic cannabinoid CP47,497, a racemic bicyclic cannabinoid that is similar in structure to the potent, high-efficacy synthetic cannabinoid CP55,940. CP47,497 was less efficacious than CP55,940 in activating G-proteins and dose-dependently produced common CB

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Design and Comprehensive Characterization of Tetramethylpyrazine (TMP) for Targeted Lung Delivery as Inhalation Aerosols in Pulmonary Hypertension (PH): In Vitro Human Lung Cell Culture and In Vivo Efficacy

Antioxidants ◽

10.3390/antiox10030427 ◽

2021 ◽

Vol 10 (3) ◽

pp. 427

Author(s):

Priya Muralidharan ◽

Maria F. Acosta ◽

Alexan I. Gomez ◽

Carissa Grijalva ◽

Haiyang Tang ◽

...

Keyword(s):

Human Lung ◽

Antioxidant Properties ◽

Dry Powder Inhaler ◽

Chinese Herbs ◽

Dry Powder ◽

Comprehensive Characterization ◽

Spray Dried

This is the first study reporting on the design and development innovative inhaled formulations of the novel natural product antioxidant therapeutic, tetramethylpyrazine (TMP), also known as ligustrazine. TMP is obtained from Chinese herbs belonging to the class of Ligusticum. It is known to have antioxidant properties. It can act as a Nrf2/ARE activator and a Rho/ROCK inhibitor. The present study reports for the first time on the comprehensive characterization of raw TMP (non-spray dried) and spray dried TMP in a systematic manner using thermal analysis, electron microscopy, optical microscopy, and Raman spectroscopy. The in vitro aerosol dispersion performance of spray dried TMP was tested using three different FDA-approved unit-dose capsule-based human dry powder inhaler devices. In vitro human cellular studies were conducted on pulmonary cells from different regions of the human lung to examine the biocompatibility and non-cytotoxicity of TMP. Furthermore, the efficacy of inhaled TMP as both liquid and dry powder inhalation aerosols was tested in vivo using the monocrotaline (MCT)-induced PH rat model.

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