ABSTRACT
Nanozyme is novel nanoparticle with enzyme-like activity, which can be classified into peroxidase-like nanozyme, catalase-like nanozyme, superoxide dismutase-like nanozyme, oxidase-like nanozyme and hydrolase-like nanozyme according to the type of reaction they catalyze. Since researchers first discovered Fe3O4 nanoparticles with peroxidase-like activity in 2007, a variety of nanoparticles have been successively found to have catalytic activity and applied in bioassays, inflammation control, antioxidant damage and tumor therapy, playing a key role in disease diagnosis and treatment. We summarize the use of nanozymes with different classes of enzymatic activity in the diagnosis and treatment of diseases and describe the main factors influencing nanozyme activity. A Mn-based peroxidase-like nanozyme that induces the reduction of glutathione in tumors to produce glutathione disulfide and Mn2+, which induces the production of reative oxygen species (ROS) in tumor cells by breaking down H2O2 in physiological media through Fenton-like action, thereby inhibiting tumor cell growth. To address the limitation of tumor tissue hypoxia during photodynamic tumor therapy, the effect of photodynamic therapy is significantly enhanced by using hydrogen peroxide nanozymes to catalyze the production of oxygen from H2O2. In pathological states, where excess superoxide radicals are produced in the body, superoxide dismutase-like nanozymes are able to selectively regulate intracellular ROS levels, thereby protecting normal cells and slowing down the degradation of cellular function. Based on this principle, an engineered nanosponge has been designed to rapidly scavenge free radicals and deliver oxygen in time to save nerve cells before thrombolysis. Starvation therapy, in which glucose oxidase catalyzes the hydrolysis of glucose to gluconic acid and hydrogen peroxide in cancer cells with the involvement of oxygen, attenuates glycolysis and the production of intermediate metabolites such as nucleotides, lipids and amino acids, was used to synthesize an oxidase-like nanozyme that achieved effective inhibition of tumor growth. Furthermore, by fine-tuning the Lewis acidity of the metal cluster to improve the intrinsic activity of the hydrolase nanozyme and providing a shortened ligand length to increase the density of its active site, a hydrolase-like nanozyme was successfully synthesized that is capable of cleaving phosphate bonds, amide bonds, glycosidic bonds and even biofilms with high efficiency in hydrolyzing the substrate. All these effects depend on the size, morphology, composition, surface modification and environmental media of the nanozyme, which are important aspects to consider in order to improve the catalytic efficiency of the nanozyme and have important implications for the development of nanozyme. Although some progress has been made in the research of nanozymes in disease treatment and diagnosis, there are still some problems, for example, the catalytic rate of nanozymes is still difficult to reach the level of natural enzymes in vivo, and the toxic effects of some heavy metal nanozymes material itself. Therefore, the construction of nanozyme systems with multiple functions, good biocompatibility and high targeting efficiency, and their large-scale application in diagnosis and treatment is still an urgent problem to be solved. (1) To improve the selectivity and specificity of nanozymes. By using antibody coupling, the nanoparticles are able to specifically bind to antigens that are overexpressed in certain cancer cells. It also significantly improves cellular internalization through antigen-mediated endocytosis and enhances the enrichment of nanozymes in target tissues, thereby improving targeting during tumor therapy. Some exogenous stimuli such as laser and ultrasound are used as triggers to control the activation of nanozymes and achieve specific activation of nanozyme. (2) To explore more practical and safer nanozymes and their catalytic mechanisms: biocompatible, clinically proven material molecules can be used for the synthesis of nanoparticles. (3) To solve the problem of its standardization and promote the large-scale clinical application of nanozymes in biomonitoring. Thus, it can go out of the laboratory and face the market to serve human health in more fields, which is one of the future trends of nanozyme development.
ABSTRACT
Objective::To compare the pharmacodynamic effects of pith-nodecayed and pith-decayed products of Scutellariae Radix on rats with large intestine damp-heat syndrome, and to demonstrate the scientificness of dividing Scutellariae Radix into pith-nodecayed and pith-decayed products as medicines by modern pharmacological test. Method::Rats were randomly divided into blank group, model group, low-and high-dose group of pith-nodecayed products (0.9, 3.6 g·kg-1), low-and high-dose group of pith-decayed products (0.9, 3.6 g·kg-1), Scutellariae Radix group (0.9 g·kg-1), compound berberine tablets group (positive drug group, 0.045 g·kg-1), and 8 rats in each group. Taking model rats with large intestine damp-heat syndrome, the body temperature, thymus index, spleen index, pathological sections of colon and ileum, inflammatory factors and Secretory immunoglobulin (SIg) A content were selected as indexes to evaluate the therapeutic effect of pith-nodecayed and pith-decayed products on large intestine damp-heat syndrome, and make comprehensive evaluation of the difference in efficacy between them. Partial least squares-discriminant analysis (PLS-DA) was employed to analyze the pharmacological indexes of these two products against large intestine damp-heat syndrome. Result::Pith-nodecayed and pith-decayed products of Scutellariae Radix with different doses could reduce the body temperature, thymus index, spleen index, contents of interleukin (IL)-2, IL-6, IL-1β in serum and SIgA content in intestinal mucosa, and most of them had significant differences (P<0.05, P<0.01). Compared with the isodose group of pith-decayed products, the effect of corresponding dose group of pith-nodecayed products was better, and most of them had significant differences (P<0.05, P<0.01). PLS-DA results indicated that there were significant differences in the pharmacological effects of pith-nodecayed and pith-decayed products, and they were clustered on one side, respectively. Conclusion::Both of pith-nodecayed and pith-decayed products of Scutellariae Radix have therapeutic effect on large intestine damp-heat syndrome with distinctly different strength of action, and pith-nodecayed products is superior to pith-decayed products, which verify the scientific nature of pith-nodecayed products was specializedly used to treat bowel disease in ancient times.
ABSTRACT
In order to establish a more perfect evaluation system for dryness effect of Atractylodis Rhizoma, determine the main dry parts of Atractylodis Rhizoma，and further define the mechanism of stir-baked Atractylodis Rhizoma in reducing the dryness. The healthy rats were given with different doses of water extract and volatile oil of raw Atractylodis Rhizoma and stir-baked Atractylodis Rhizoma for 21 days. Based on the theory of the dry-dry and dryness-induced Yin deficiency, the amount of drinking water, tissue morphology of submandibular glands, urine volume and the expression of aquaporin 2 (AQP2) in the kidneys, as well as blood rheology, ratio of cAMP/cGMP in serum and the content of Na⁺-K⁺-ATP enzyme were selected as the evaluation indexes. The results indicated that the rats with high dose volatile oil from raw Atractylodis Rhizoma had a significant increase in the amount of drinking water, urine volume, blood viscosity, ratio of cAMP/cGMP and content of Na⁺-K⁺-ATP enzyme in the serum（<0.05）as compared with the soybean oil group; meanwhile, atrophy of submandibular acinar gland was obvious，and the expression of aquaporin 2 was reduced significantly（<0.05）. There were significant differences between volatile oil high dose group of raw Atractylodis Rhizoma and volatile oil high dose group of stir-baked Atractylodis Rhizoma. There was no significant difference between the water extract groups of raw and stir-baked Atractylodis Rhizoma and the saline group. A comprehensive evaluation system for the dryness effect of Atractylodis Rhizoma was established. It was confirmed that the volatile oil part was the main dry part of Atractylodis Rhizoma. It revealed that the mechanism of dryness effect of Atractylodis Rhizoma was not only related to the decrease of the total content of the volatile oil, but also may be related to the transformation of dryness components in the volatile oil. It provides references for the study of material basis of Atractylodis Rhizoma dryness, provides an experimental basis for the clinical application of Atractylodis Rhizoma, further clarifies the mechanism of stir-baked Atractylodis Rhizoma in reducing the dryness, and provides thoughts for the evaluation of other dry traditional Chinese medicines.
ABSTRACT
Objective To compare the pharmacodynamic effects of Scutellaria baicalensis pith-nodecayed and S. baicalensis pith-decayed on pneumonia. Methods The minimal inhibitory concentration (MIC) of S. baicalensis pith-nodecayed and S. baicalensis pith-decayed on Streptococcus pneumoniae was determined by in vitro experiments with double dilution method. In vivo experiments, taking pneumonia rat as model, body temperature and lung weight coefficient, blood test and pathological section of lung in rats were used as evaluation index to evaluate the pharmacodynamic difference of the effect of S. baicalensis pith-nodecayed and S. baicalensis pith-decayed on pneumonia rats. S. baicalensis pith-nodecayed and S. baicalensis pith-decayed antibacterial activity and pathological indicators were analyzed with PLS-DA. Results The MIC of S. baicalensis pith-nodecayed to Streptococcus pneumoniae was 0.5 g/mL, and the MIC of S. baicalensis pith-decayed to Streptococcus pneumoniae was 0.25 g/mL. Both S.baicalensis pith-nodecayed and S. baicalensis pith-decayed could significantly reduce the inhibitory concentration body temperature, lung weight coefficient, white blood cell count, neutrophil number, and lymphocyte number in whole blood. PLS-DA showed that there were significant differences in the pharmacological effects of S. baicalensis pith-nodecayed and S. baicalensis pith-decayed. Conclusion S. baicalensis pith-nodecayed and S. baicalensis pith-decayed have a certain effect on the treatment of pneumonia, the role of the strength of the two have significant differences, the role of S. baicalensis pith-decayed is better.
ABSTRACT
Ankylosing spondylitis has become a common disease, whether early stage of the low back pain or disability of the late stage of the disease has a serious impact on life quality. There is an urgent need of safe and effective treatment to treat the disease. This article introduced two cases of ankylosing spondylitis treated by modified Jingang Pills, with significant efficacy.