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Alzheimer's disease （AD） is one of the most common diseases in the elderly population. Its etiology involves multiple pathogenic factors and pathological links such as abnormal deposition of β amyloid protein （Aβ）， hyperphosphorylation of Tau protein， abnormalities of the cholinergic system， oxidative stress， and inflammatory response. However， its specific pathogenesis has not been clarified， and no specific therapeutic drugs have been found. In recent years， more and more studies have paid attention to the potential of chemical components of traditional Chinese medicine （TCM） in the treatment of AD. However， the diversity and complexity of the chemical components of TCM may have a positive impact on multiple pathological links of AD. Researchers have isolated many active components from TCMs， and the effects of treating AD have been confirmed by modern pharmacological studies. Through literature analysis， this article found that the main chemical components of TCM with anti-AD effects were saponins （31%）， flavonoids （24%）， polysaccharides （20%）， lactones （8%）， alkaloids （7%）， phenols （3%）， and other compounds （7%）. Among them， ginsenoside， notoginsenoside， epimedium flavones， puerarin， baicalein， schisandra polysaccharide， angelica polysaccharide， ganoderma lucidum polysaccharide， pachyman， huperzine A， berberine， andrographolide， curcumin， emodin， and gastrodin have been extensively studied in terms of their anti-AD effects， and their mechanisms of pharmacological action have been involved in many aspects of AD pathogenesis. This article reviews the anti-AD activities and possible mechanisms of chemical components of TCM， so as to provide a reference for the development of new drugs for the prevention and treatment of AD.
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ObjectiveTo analyze the clinical application hotspots， development trends， compatibility characteristics， application rules， and formulation mechanisms of the Chinese marine drug pair Haliotidis Concha-Oystreae Concha in order to provide references for its clinical medication and further research. MethodBy means of various modern literature databases such as China National Knowledge Infrastructure （CNKI）， modern clinical prescriptions containing Haliotidis Concha-Oystreae Concha， as well as the clinical application hotspots， were retrieved， followed by visualized analysis of hotspots and development trends of their clinical applications using Citespace. The drug composition， efficacy and indications， and drug dosages in the prescriptions were statistically analyzed. Additionally， various statistical software including SPSS Modeler 18.0 were employed to analyze the indications， syndromes， and formulation rules of Haliotidis Concha-Oystreae Concha. ResultThe visualized analysis included 90 articles， revealing a gradual decrease in publications in this field in recent years. Key clinical application keywords were identified as hypertension， collateral deficiency producing wind， insomnia， etc. Eighty clinical prescriptions were retrieved， involving 121 drugs. Frequency analysis of compatibility demonstrated that the top 10 drugs were Uncariae Ramulus cum Uncis， Gastrodiae Rhizoma， Os Draconis， Achyranthis Bidentatae Radix， Paeoniae Radix Alba， Chrysanthemi Flos， Scutellariae Radix， Gardeniae Frucuts， Glycyrrhizae Radix et Rhizoma， and Polygoni Multiflori Caulis. Association rule analysis showed that core combinations included "Uncariae Ramulus cum Uncis-Achyranthis Bidentatae Radix" and "Os Draconis-Pheretima-Chuanxiong Rhizoma". Through factor reliability analysis， new drug combinations were derived， such as "Gastrodiae Rhizoma-Polygoni Multiflori Caulis-Eucommiae Cortex-Taxilli Herba-Leonuri Herba"， "Achyranthis Bidentatae Radix-Uncariae Ramulus cum Uncis"， "Scutellariae Radix-Glycyrrhizae Radix et Rhizoma-Margarita-Prunellae Spica"， "Os Draconis-Pheretima-Bombyx Batryticatus"， "Chrysanthemi Flos-Chuanxiong Rhizoma"， "Poria-Acori Tatarinowii Rhizoma"， and "Paeoniae Radix Alba-Gardeniae Fructus-Sclerotium Poriae Pararadicis". The Haliotidis Concha-Oystreae Concha drug pair was mainly used to treat diseases with liver Yang hyperactivity syndrome， with hypertension accounting for 40.00%， migraines for 30.00%， and dizziness for 15.00%. In the treatment of liver Yang hyperactivity syndrome， the main categories of compatible drugs were liver-pacifying and wind-extinguishing ones （19.86%）， blood-activating and stasis-resolving ones （12.13%）， and spirit-calming ones （10.08%）. High-frequency drugs in the prescriptions function to reduce blood pressure through multiple pathways， such as increasing nitric oxide （NO） levels， downregulating angiotensin Ⅱ （Ang Ⅱ）， and inhibiting angiotensin-converting enzyme （ACE）. ConclusionThrough comprehensive analysis of the results， the Haliotidis Concha-Oystreae Concha drug pair is commonly used for hypertension with liver Yang hyperactivity syndrome， and is often combined with deficiency-tonifying， liver-pacifying and wind-extinguishing， heat-clearing， and spirit-calming drugs， aiming to simultaneously extinguish wind， relieve spasms， and pacify the liver to subdue Yang， while also clearing heat to relax bowels， stabilizing the mind， and enhancing the liver-pacifying and Yang-subduing effects of this drug pair.
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OBJECTIVE@#Phenolic acids widely exist in the human diet and exert beneficial effects such as improving glucose metabolism. It is not clear whether phenolic acids or their metabolites play a major role in vivo. In this study, caffeic acid (CA) and ferulic acid (FA), the two most ingested phenolic acids, and their glucuronic acid metabolites, caffeic-4'-O-glucuronide (CA4G) and ferulic-4'-O-glucuronide (FA4G), were investigated.@*METHODS@#Three insulin resistance models in vitro were established by using TNF-α, insulin and palmitic acid (PA) in HepG2 cells, respectively. We compared the effects of FA, FA4G, CA and CA4G on glucose metabolism in these models by measuring the glucose consumption levels. The potential targets and related pathways were predicted by network pharmacology. Fluorescence quenching measurement was used to analyze the binding between the compounds and the predicted target. To investigate the binding mode, molecular docking was performed. Then, we performed membrane recruitment assays of the AKT pleckstrin homology (PH) domain with the help of the PH-GFP plasmid. AKT enzymatic activity was determined to compare the effects between the metabolites with their parent compounds. Finally, the downstream signaling pathway of AKT was investigated by Western blot analysis.@*RESULTS@#The results showed that CA4G and FA4G were more potent than their parent compounds in increasing glucose consumption. AKT was predicted to be the key target of CA4G and FA4G by network pharmacology analysis. The fluorescence quenching test confirmed the more potent binding to AKT of the two metabolites compared to their parent compounds. The molecular docking results indicated that the carbonyl group in the glucuronic acid structure of CA4G and FA4G might bind to the PH domain of AKT at the key Arg-25 site. CA4G and FA4G inhibited the translocation of the AKT PH domain to the membrane, while increasing the activity of AKT. Western blot analysis demonstrated that the metabolites could increase the phosphorylation of AKT and downstream glycogen synthase kinase 3β in the AKT signaling pathway to increase glucose consumption.@*CONCLUSION@#In conclusion, our results suggested that the metabolites of phenolic acids, which contain glucuronic acid, are the key active substances and that they activate AKT by targeting the PH domain, thus improving glucose metabolism.
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Objective:By reviewing and analyzing the patent of Traditional Chinese Medicine compound for the prevention and treatment of chronic complications of diabetes, this paper aims to analize the patent of Traditional Chinese Medicine compound and medication rules for the prevention and treatment of diabetes complications with data mining technology.Methods:Based on data mining technology, this paper searched for the patent of Traditional Chinese Medicine compound that could prevent and treat chronic complications of diabetes with SOOIP (Intellectual Property Big Data Center) website, and analyzed the application trends, number , categories, etc. Then IBM SPSS Modeler 18.0 software was used for correlation analysis, and finally the medication and compatibility of the Chinese medicine prescriptions are summarized.Results:There were all together 307 patents, and the number of patent applications for the prevention and treatment of chronic complications of diabetes with Chinese medicines has increased before 2015. Most patents in classification belongs to A61P. China accounts for the majority of the global total applications, of which Shandong province accounts the most. The applicants are mostly individuals and enterprises. The categories commonly used in patent applications are mainly oral drug combinations; The Astragali Radix, Puerariae lobatae Radix, Rehmanniae Radix, Coptidis Rhizoma, Salviae miltiorrhizae Radix et Rhizoma are the most commonly used application. The Traditional Chinese Medicine patent mostly has sweet taste, warm in property, and channel-tropism of medicine is mostly liver, as well as the liver is most associated with bitterness in taste. The commonly used couplet medicines are Puerariae lobatae Radix-Astragali Radix, Puerariae lobatae Radix-Rehmanniae Radix, Astragali Radix-Coptidis Rhizoma. Conclusion:The number of such patents applied for in China is small, and the regional development is unbalanced; Data mining technology can be used to discover the compatibility rule of Chinese patent prescription prescription for diabetes prevention and treatment, so as to provide reference for clinical optimization of prescription, improvement of curative effect and development of new drugs for treatment of diabetic complications.
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Zedoary tumeric (Curcumae Rhizoma, Ezhu in Chinese) has a long history of application and has great potential in the treatment of liver cancer. The antiliver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances. In order to clarify the specific mechanism of zedoary tumeric against liver cancer, this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer, and then verifies the joint anti liver cancer mechanism of its “pharmacodynamic group”. By searching the research on the antihepatoma effect of active components of zedoary tumeric in recent years, we found that pharmacodynamic substances, including curcumol, zedoarondiol, curcumenol, curzerenone, curdione, curcumin, germacrone, β-elemene, can act on multi-target and multi-channel to play an antihepatoma role. For example, curcumin can regulate miR, GLO1, CD133, VEGF, YAP, LIN28B, GPR81, HCAR-1, P53 and PI3K/Akt/mTOR, HSP70/TLR4 and NF-κB. Wnt/TGF/EMT, Nrf2/Keap1, JAK/STAT and other pathways play an antihepatoma role. Network pharmacological analysis showed that the core targets of the “pharmacodynamic group” for anti-life cancer are AKT1, EGFR, MAPK8, etc, and the core pathways are neuroactive live receiver interaction, nitrogen metabolism, HIF-1 signaling pathway, etc. At the same time, by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and “pharmacodynamic group”, it is found that they have great reference significance in target, pathway, biological function, determination of core pharmacodynamic components, formation of core target protein interaction, in-depth research of single pharmacodynamic substance, increasing curative effect and so on. By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and “pharmacodynamic group” in the treatment of liver cancer, this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and “pharmacodynamic group”.
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Glycyrrizae Radix et Rhizoma has high medicinal value and is widely used in compatibility. It is used most frequently in the compatibility of Chinese medicine prescriptions，and is known as ''Guolao''（national medicine） and "master of all medicines". The characteristic active ingredients are mainly liquitin，glycyrrizic acid，glycyrrizin，and licochalcone. In different compatibilities，based on traditional and modern pharmacological theories，the corresponding effect of Glycyrrizae Radix et Rhizoma are brought into play through different mechanisms. Based on the traditional pharmacology of Glycyrrizae Radix et Rhizoma for tonifying spleen，replenishing Qi，clearing heat，removing toxin，dispelling phlegm，relieving cough and pain，and harmonizing various medicines，this paper used herbal authentication to analyze its compatibility application and mechanism. It was found that Glycyrrizae Radix et Rhizoma played corresponding effect in compatibilities through "tonification"，"harmonization"，and "regulation". For example，Glycyrrizae Radix et Rhizoma was combined with tonics including Ginseng Radix et Rhizoma and Atractylodis Macrocephalae Rhizoma to tonify the five Zang-organs through its strong tonifying effect，combined with Paeoniae Radix Alba and Aconiti Lateralis Radix Praeparata to relieve emergencies and pains through harmonizing medicine power and properties，and combined with Rhei Radix et Rhizoma and Natrii Sulfas to reduce medicine intensity through regulating medicine properties and body characteristics. The application law and mechanism of the modern pharmacological compatibility of Glycyrrizae Radix et Rhizoma were analyzed by data mining and network pharmacology. It was found that the modern clinical formula was often compatible with Glycyrrizae Radix et Rhizoma for anti-inflammation，cardiovascular and cerebrovascular protection，anti-virus，and anti-tumor，Ephedrae Herba and Scutellariae Radix for anti-inflammation，Bambusae Caulis in Taenias，Salviae Miltiorrhizae Radix et Rhizoma，and Aurantii Fructus Immaturus for cardiovascular and cerebrovascular protection，and Ophiopogonis Radix and Chuanxiong Rhizoma for nerves protection. Meanwhile，the important targets of the characteristic ingredients were protein kinase B1 （Akt1），interleukin-6 （IL-6），tumor necrosis factor （TNF），and epidermal growth factor receptor （EGFR）. The important characteristic pathways such as tyrosine kinase inhibitor resistance pathway and cyclic guanosine monophosphate （cGMP）/protein kinase G （PKG） signal pathway played the role of cardiovascular and cerebrovascular protection，and proteoglycan pathway in cancer played a neuroprotective role. This study is expected to provide references for the rational compatibility and application of Glycyrrizae Radix et Rhizoma，as well as the compatibility application of Chinese medicine prescriptions.
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Cardiovascular diseases are the leading cause of death in the world today. Atherosclerosis （AS） is a chronic inflammatory disease characterized by thickening or functional degeneration of the arterial wall， and in the later stage of the disease， plaque ruptures to induce thrombosis， which in turn causes ischemia in tissues or organs. It is therefore the pathological basis for all types of cardiovascular diseases. Nuclear transcription factor kappa B （NF-κB）， an important nuclear transcription factor in the inflammatory response， is activated to mediate the transcription of inflammatory factors that can trigger or exacerbate the development of AS. Vascular endothelial cells are activated by inflammatory factors. NF-κB mediates related regulatory genes in endothelial cells to secrete adhesion molecules， chemokines， and coagulation factors， promotes selective aggregation of monocytes， up-regulates the expression of adhesion molecules to make adhesion molecules stick to the endothelium and move toward the intima， promotes the degradation of the extracellular matrix， and forms unstable plaques. In recent years， traditional Chinese medicine （TCM） has achieved certain results in the prevention and treatment of AS， and many Chinese medicines have been proved to be effective in resisting AS and can act on multiple targets in the human body， affecting the occurrence and development of AS in different links. This paper mainly introduced the NF-κB pathway and its relationship with AS， reviewed research progress on 75 components of different types in Chinese medicine monomers such as flavonoids， terpenoids， and alkaloids in AS resistance based on the NF-κB pathway， and found that Chinese medicine monomers mainly regulate cholesterol balance， inhibit the inflammatory response， reduce cell proliferation， inhibit intercellular adhesion， and suppress foam cell formation by regulating the NF-κB pathway to provide a reference for the prevention and treatment of AS.
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The animal models used in the experimental research of Traditional Chinese Medicine (TCM) to prevent and treat T2DM are mainly spontaneous and induced. The experimental research of TCM in the prevention and treatment of type 2 diabetes can be divided into Chinese medicine compound, Chinese medicine and its extract, Chinese medicine monomer. The mechanism is mainly through regulating intestinal flora, increasing insulin content, lowering blood sugar, lowering blood lipids, improving glucose tolerance, and improving gluconeogenesis, antioxidant, inhibit cell apoptosis, etc. play the role of preventing and treating T2DM in multiple links and multiple targets.
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OBJECTIVE： To screen the active part of Saccharum officinarum leaves against liver injury. METHODS： The S. officinarum leaves were extracted with 80％ ethanol to obtain ethanol extract， after dispersed with water， ethanol extract was respectively extracted with petroleum ether， ethyl acetate and n-butanol to obtain corresponding polar parts. The residual part was water part. Totally 108 mice were randomly divided into blank group A （0.5％ CMC-Na and 3.5％ polysorbate 80 solution）， blank group B （purified water）， model group （purified water）， biphenyl diester group （positive control， 0.2 g/kg）， S. officinarum leaves ethanol extract group， different polar parts of S. officinarum leaves group （petroleum ether， ethyl acetate， n-butanol， water， 22.92 g/kg crude drug， 0.5％ CMC-Na and 3.5％ polysorbate 80 solution as solvent）， with 12 mice in each group. They were given relevant medicine intragastrically once a day， for consecutive 12 d. 1 h after last medication， except for blank group A and blank group B， mice in other groups were given 0.15％ CCl4 peanut oil （0.1 mL/10 g） solution to induce acute liver injury model. 16 h later， general information of mice was observed， and the serum contents of ALT and AST were determined. The liver histopathological changes were observed and the Ishak scores were scored. RESULTS： Compared with blank group B， each index of blank group A had no significant difference （P＞0.05）. Compared with blank group A， model group had sparse hair and slow movement， and was emaciated. Serum contents of ALT and AST were increased significantly （P＜0.01）. The structure of hepatic lobule was severely damaged； the structure of hepatic cord and sinus was not clear； the arrangement of hepatic cord was disordered， and the Ishak score was significantly increased （P＜0.01）. Compared with model group， general information of mice was improved in administration groups. Serum contents of ALT and AST were decreased in biphenyl diester group， S. officinarum leaf ethanol extract group and S. officinarum leaf ethyl acetate group （P＜0.05 or P＜0.01）. The pathological damage of liver tissue was significantly relieved， and Ishak score was significantly reduced （P＜0.05 or P＜0.01）. CONCLUSIONS： The ethyl acetate part of ethanol extract from S. officinarum leaves is active part against CCl4-induced acute liver injury of mice.