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Immunoassay methods are important for monitoring β-agonists illegally used for reducing animal fat deposition in livestock. However, there is no simultaneous screening surveillance immunoassay for detecting various β-agonist chemicals that are possibly present in food. In this study, through the use of an R-(−)-salbutamol derivative as the immunizing hapten, an antibody recognizing 31 β-agonists and analogues was generated for the first time. Three-dimensional quantitative structure–activity relationship (3D QSAR) revealed that strong steric and hydrophobic fields around the hapten spacer near C-2, as well as a chirality at C-1′, dominantly modulated the class specificity of the raised antibody. However, a hapten spacer linked at C-2′ or C-1 would lead to a narrow specificity, and the spacer charge at C-6 could affect the raised antibody specificity spectrum. A class specificity competitive indirect enzyme-linked immunosorbent assay (ciELISA) was established with an ideal recovery ranging from 81.8 to 118.3% based on the obtained antibody. With a good agreement to the HPLC/MS method, the proposed ciELISA was confirmed to be reliable for the rapid surveillance screening assay of β-agonists in urine. This investigation will contribute to the rational design and control of the immunoassay specificity.

Flavonoid dimer FD18is a new class of dimeric P-gp modulator that can reverse cancer drug resistance. FD18is a potent (EC50= 148 nM for paclitaxel), safe (selective index = 574), and selective P-glycoprotein (P-gp) modulator. FD18can modulate multidrug resistance toward paclitaxel, vinblastine, vincristine, doxorubicin, daunorubicin, and mitoxantrone in human breast cancer LCC6MDR in vitro. FD18(1 μM) can revert chemosensitivity of LCC6MDR back to parental LCC6 level. FD18was 11- to 46-fold more potent than verapamil. FD18(1 μM) can increase accumulation of doxorubicin by 2.7-fold, daunorubicin (2.1-fold), and rhodamine 123 (5.2-fold) in LCC6MDR. FD18inhibited P-gp-mediated doxorubicin efflux and has no effect on influx. FD18at 1 μM did not affect the protein expression level of P-gp. Pharmacokinetics studies indicated that intraperitoneal administration of 45 mg/kg FD18was enough to maintain a plasma level above EC50(148 nM) for more than 600 min. Toxicity studies with FD18(90 mg/kg, i.p. for 12 times in 22 days) with paclitaxel (12 mg/kg, i.v. for 12 times in 22 days) revealed no obvious toxicity or death in mice. In vivoefficacy studies indicated that FD18(45 mg/kg, i.p. for 12 times in 22 days) together with paclitaxel (12 mg/kg, i.v. for 12 times in 22 days) resulted in a 46% reduction in LCC6MDR xenograft volume (n= 11; 648 ± 84 mm3) compared to paclitaxel control (n= 8; 1201 ± 118 mm3). There were no animal deaths or significant drop in body weight and vital organ wet weight. FD18can increase paclitaxel accumulation in LCC6MDR xenograft by 1.8- to 2.2-fold. The present study suggests that FD18represents a new class of safe and potent P-gp modulator in vivo.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in postmenopausal women. Danshen, the dried root of Salvia miltiorrhizaBunge, has been used clinically in China to treat CVD and dyslipidemia in postmenopausal women, and its major active ingredients have been found to have an estrogenic effect. The aim of this study was to elucidate the underlying mechanism of danshen’s protective effects on vascular function in an ovariectomized (OVX) hyperlipidemic rat model.

Hypercholesterolemia is a major risk factor for the development and progression of cardiovascular diseases including atherosclerosis. A major active ingredient, scutellarin, from the plant Erigeron breviscapus was investigated for its hypocholesterolemic and atheroscleroprotective effects (30 and 100 mg/kg/day, p. o.). The serum lipid profile (total cholesterol, triglycerides, high density lipoprotein cholesterol and low density lipoprotein cholesterol) was monitored and aortic functions in Sprague-Dawley rats fed with normal diet, atherogenic diet or atherogenic diet plus oral administration of either scutellarin or simvastatin (a positive control) were tested. It was found that scutellarin markedly attenuated the increased serum total cholesterol induced by atherogenic diet. It caused a significant reduction in the atherogenic index. In addition, scutellarin administration could significantly enhance acetylcholine-induced nitrate/nitrite production, increase the gene expression of endothelial nitric oxide synthase and improve acetylcholine-induced endothelium-dependent vasorelaxation in rat isolated aortas. These data revealed that scutellarin could reduce the atherogenic properties of dietary cholesterol in rats. However, whether scutellarin's atheroscleroprotective potential targets endothelial function directly or indirectly on its antioxidative activity remains to be determined. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) is a chronic neurodegenerative disorder having close relationship with oxidative stress induced by reactive oxygen species (ROS). Cortex Fraxini (QP) is a kind of traditional Chinese medicinal herb with antioxidant properties. It may be a potential candidate for preventing the development of chronic neurodegenerative diseases. Thus, the key objective of the current study was to investigate the neuroprotective effect of QP water extract on 6-hydroxydopamine (6-OHDA) induced apoptosis in rat pheochromocytoma (PC12) cells. It was found that QP water extract possesses strong antioxidant property with SC50 = 0.15 mg/mL. Total phenolic content of QP water extract was found to be 200.78 ± 2.65 mg GAE/g. QP water extract’s free radical scavenging capacity was demonstrated by reversing the increased level of intracellular ROS induced by 6-OHDA, using 2′,7′-dichlorodihydrofluorescein diacetate. Moreover, QP water extract (0.5 mg/mL) could remarkably increase the viability of PC12 cells treated with 6-OHDA. The protective effect of QP water extract was found to be via inhibiting MEK/ERK pathway and reversing PI3-K/Akt/GSK3β pathway. The current results suggest that QP might be a potential candidate for preventing the development of neurodegenerative diseases, such as PD.