ABSTRACT
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment.
ABSTRACT
Objective: To determine the antibody titer in the serum of allergic rabbits after the injection of 1, 3-di-caffeoylquinic acid contained in Shuanghuanglian injection.Methods: The complete antigen was prepared by incubating the suspected small molecular hapten 1, 3-di-caffeoylquinic acid contained in Shuanghuanglian injection with the serum from the normal rabbits.The specific antibody was obtained in the immunized rabbits.The antibody titers of antiserum were measured by ELISA kits.Indirect competitive ELISA was used to determine serological specificity, and the obtained data was used to plot the inhibition curves.The content of IgE antibody in the antiserum of rabbits was detected by rabbit immunoglobulin E (IgE) ELISA kits.Results: The antibody titer (A) of 1,3-di-caffeoylquinic acid was 2 times higher than that of the negative control, which indicated its potential allergenicity.The regression equation was I=0.170 6 lg C + 0.317 5 , which was with the correlation coefficient of r=0.985 4 , the detection limit of IC 10 =57.40 μg·ml-1 and the half inhibitory concentration of IC 50 =8.732 0 mg·ml-1.Furthermore, the exogenous IgE antibody was produced in the rabbits.Conclusion: The results indicated that the hapten substance 1,3-di-caffeoylquinic acid in Shuanghuanglian injection was allergenic under the present experimental conditions.
ABSTRACT
AIM To investigate the effects of honokiol on ischemic neurological deficiency and on the scavenging ability of ischemia reperfusion (I-R) brain tissue for reactive oxygen species (ROS). METHODSCerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in rats. I-R in mice were induced by blood stream pause in bilateral common carotid arteries for 30 min and reperfusion for 30 min. The activities of ROS scavenging enzymes were determined with colorimetric methods. RESULTS Intravenous honokiol in 5-50 μg·kg-1 significantly decreased the neurological deficiency score, and diminished cerebral infarction volume in rats. In I-R brain tissue of mice, intravenous honokiol in 7-70 μg·kg-1 evidently enhanced the activities of superoxide dismutase, catalase, glutathione peroxidase and peroxidase, and markedly lowered lipid peroxidative product malondialdehyde content. Moreover honokiol significantly increased Na+-K+-ATPase activity in I-R brain tissue. CONCLUSION Honokiol ameliorates the neurological deficiency behavior and diminishes infarction volume in MCAO rats; and enhances cerebral scavenging ability for ROS and Na+-K+-ATPase activity in cerebral I-R mice. It is indicated that honokiol is a protective agent for cerebral ischemia and I-R.
ABSTRACT
Objective: To investigate the pharmacokinetics of honokiol in rats. Methods: Honokiol injection was delivered by vein injection to SD rats. The blood samples were gathered at a series of time lags. Honokiol in rat plasma was determined with an RP HPLC method and the data were analyzed with program 3P87. Results: After i v injection of honokiol, concentration time curves were fitted to a 3 compartment model: with halftime of 2.8 min, 11.9 min, and 56.8 min. Conclusion: Honokiol was quickly distributed in rats after i.v. and the concentration decreased rapidly. Our studies provided important referrence to the research on the pharmacodynamics and the pharmaceutics of Honokiol.
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Objective: To establish the quality standard of Yukuining Granules (Endoconcha Sepiae, Rhizoma Corydalis, Radix Astragali, Radix Paeoniae Alba, Radix Glycyrrhizae, etc.) .Methods: We have identified Rhizoma Corydalis, Radix Glycyrrhizae and Radix Astragali in Yukuining Granules by TLC and determined the paconiflorin by HPLC. The average recovery was 102.3%. RSD was 2.3%( n =5). Results: The methods were simple, sensitive, quick, accurate and specific. Conclusions: The methods can be used in the quality control of Yukuining Granules.
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Objective: To establish the qualification stadards of Jianwei Zhengchang Pills.Methods:The microscopical identification and quality identification were studied by TLC. And the contents of cinnamic aldehyde and menthol were determined synchronously by GC. Results: The corresponding microscopical characteristics and thin layer spots from the samples can be obtained. Conclusion: The qualitative and quantitative methods estabished were simple, sensitive, quick accurate and specific and can control the quality of the preparation validly.