The aim of this study was to extract and purify anthocyanins from Lycium ruthenicum Murr. and evaluate their tyrosinase inhibitory activity. Response surface methodology was devoted to optimize enzyme‐assisted extraction of anthocyanins from L. ruthenicum dried fruits. Extraction at 38 °C for 37 min using water‐containing pectinase (52.04 mg/100 g dried fruit) rendered an anthocyanin extraction yield of 19.51 ± 0.21 mg/g. The purified anthocyanins were separated from the extract by macroporous resin XDA‐6. Antioxidant tests in vitro suggested that the extract and the purified anthocyanins exhibited a potent 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical scavenging capacity, 2,2‐azino‐bis‐3‐ethylbenzothiazoline‐6‐sulfonic acid (ABTS) radical scavenging capacity, hydroxyl radical scavenging capacity, superoxide radical scavenging capacity, and total reducing power. Thirteen anthocyanins from L. ruthenicum dried fruits were analyzed by HPLC‐MS. Moreover, the purified anthocyanins had inhibitory effect on tyrosinase monophenolase (IC50 = 1.483 ± 0.058 mg/mL), and the type of inhibition was competitive inhibition (Ki = 39.83 ± 1.4 mg/mL). The maximum inhibitory activity of the purified anthocyanins (3.00 mg/mL) on tyrosinase diphenolase was 42.16 ± 0.77%, and the type of inhibition was anticompetitive inhibition (Kis = 2.387 ± 0.10 mg/mL). Practical Application The anthocyanins from L. ruthenicum dried fruits can be used as tyrosinase inhibitors in medicine, cosmetics, and food preservation industries.
Background Multiple studies have revealed that repeated or long-term exposure to ketamine causes neurodegeneration and cognitive dysfunction. Pyroptosis is an inflammatory form of programmed cell death that has been linked to various neurological diseases. However, the role of NLRP3/caspase-1 axis-related pyroptosis in ketamine-induced neurotoxicity and cognitive dysfunction remains uncertain. Methods To evaluate whether ketamine caused NLRP3/caspase1-dependent pyroptosis, flow cytometry analysis, western blotting, ELISA test, histopathological analysis, Morris water maze (MWM) test, cell viability assay, and lactate dehydrogenase release (LDH) assay were carried out on PC12 cells, HAPI cells, and 7-day-old rats. In addition, the NLRP3 inhibitor MCC950 or the caspase-1 inhibitor VX-765 was used to investigate the role of the NLRP3/caspase-1 axis in ketamine-induced neurotoxicity and cognitive dysfunction. Results Our findings demonstrated that ketamine exposure caused cell damage and increased the levels of pyroptosis in PC12 cells, HAPI cells, and the hippocampus of neonatal rats. After continuous exposure to ketamine, targeting NLRP3 and caspase-1 with MCC950 or VX765 improved pyroptosis, reduced neuropathological damages, and alleviated cognitive dysfunction. Conclusion NLRP3/Caspase-1 axis-dependent pyroptosis is involved in ketamine-induced neuroinflammation and cognitive dysfunction, and it provides a promising strategy to treat ketamine-related neurotoxicity.
The genus Saururus, belonging to Saururaceae, contains two species, S. cernuus L. and S. chinensis (Lour) Baill. with common utilization in traditional medicine from Asia to North America for the treatment of edema, beriberi, jaundice, leucorrhea, urinary tract infections, hypertension, hepatitis diseases, and tumors. An extensive review of literature was made on traditional uses, phytochemistry, and ethnopharmacology of Saururus using ethno-botanical books, published articles, and electronic databases. The 147 of chemical constituents have been isolated and identified from S. cernuus and S. chinensis, and lignans, flavonoids, alkaloids, anthraquinones, saponins, and phenols are the major constituents. Various pharmacological investigations in many in vitro and in vivo models have revealed the potential of the genus Saururus with anti-inflammatory, antitumor, anti-oxidant, hepatoprotective, antimelanogenic, lipid-lowering, and bone protective activities, supporting the rationale behind numerous of its traditional uses. Due to the noteworthy pharmacological properties, Saururus can be a better option for new drug discovery. Data regarding many aspects of this plant such as toxicology, pharmacokinetics, quality-control measures, and the clinical value of the active compounds is still limited which call for additional studies.
Osteoarthritis (OA) is characterized by progressive degeneration of cartilage, formation of cartilage at the cartilage edge, and remodeling of the subchondral bone. Pro-inflammatory cytokines [e.g., interleukin (IL)-1β] that induce inflammation and promote chondrocyte damage induce OA. Currently, the diagnosis of OA is commonly based on imaging examinations (e.g., X-ray) and evaluations of clinical symptoms; however, biomarkers that can effectively diagnose OA are currently not available. By studying the mechanism underlying OA cartilage injury and changes in the concentrations of the biomarkers procollagen type II carboxy-terminal propeptide (PIICP), collagen type-II C-telopeptide fragments (CTX-II), and type II collagen cleavage neoepitope (C2C) during pathogenesis, the present study established a theoretical basis for the evaluation and early diagnosis of OA. In an experiment, 10 ng/ml IL-1β was used to the treat chondrocyte-induced OA models in vitro for 0, 12, 24 and 48 h. Western blotting was used to detect the expression levels of matrix metalloproteinase (MMP)-3, MMP-13, and inducible nitric oxide synthase (iNOS) protein at each time-point. The concentrations of CTX-II, C2C, and PIICP in the cell culture supernatant were detected by ELISA kit. A biochemical kit was used to detect changes of nitric oxide (NO) in the cell culture supernatant. In addition, chondrocytes were treated with 10 ng/ml IL-1β for 0, 30, 60 and 90 min and the translocation and phosphorylation of the NF-κB pathway were investigated by western blotting. Following IL-1β stimulation, the NF-κB pathway was activated to increase the expression levels of MMPs and iNOS synthesis downstream of the pathway, resulting in an increased degradation of type II collagen (Col II). To sum up, pro-inflammatory IL-1β induced an OA chondrocyte model. During the development of OA, the expression of MMPs and NO increased and Col II was degraded.
The aim of the present study was to evaluate the anesthetic and cardiopulmonary effects of dexmedetomidine in combination with tiletamine (without zolazepam) as a general anesthetic. The study was divided into two phases. In Phase 1, 18 adult healthy mixed-breed dogs were randomly allocated into three groups: Group TD8 (4.5 mg kg−1 tiletamine and 8 μg kg−1 dexmedetomidine), Group TD10 (4.5 mg kg−1 tiletamine and 10 μg kg−1 dexmedetomidine), or Group TD12 (4.5 mg kg−1 tiletamine and 12 μg kg−1 dexmedetomidine). After drug administration, the heart rate (HR), respiratory rate (fR), mean arterial pressure (MAP), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), peripheral hemoglobin oxygen saturation (SpO2), behavioral score, quality of induction and recovery, extent of ataxia, the time taken for induction, and the duration of anesthesia were recorded. The recovery time and quality were recorded after administration of atipamezole (50 μg kg−1) after 60 min. In phase 2, the feasibility of combining dexmedetomidine (10 μg kg−1) and tiletamine (4.5 mg kg−1) as general anesthetics for orchiectomy was evaluated in dogs (n = 6). HR, fR, MAP, SAP, DAP, temperature, SpO2, behavioral scores, and adverse reactions were recorded during each surgical procedure. In phase 1, the dogs were anesthetized for 5 min after administration of drugs and achieved a maximum behavioral score in TD10 and TD12 after 10 min. Although HR, MAP, SAP, DAP, and NIBP decreased in all three groups, they still maintained within the normal range. In phase 2, orchiectomy was completed smoothly in all dogs with little fluctuation in the physiological variables. We found that a combination of tiletamine (4.5 mg kg−1) and dexmedetomidine (10 μg kg−1) intramuscularly induced moderate anesthesia in dogs and could be utilized for short-term anesthesia and minor surgery.
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