1.Research progress of Lycium barbarum polysaccha-ride in preventing and treating Alzheimer's disease
Qiyuan HAN ; Beibei HU ; Danshen ZHANG ; Yongshuai JING
Chinese Journal of Pharmacology and Toxicology 2023;37(7):496-497
Alzheimer's disease(AD)is a neurode-generative disease with insidious onset and progressive development.In recent years,the prevalence of AD has shown a linear upward trend.At present,its pathogene-sis is not clear.Lycium barbarum polysaccharide(LBP)is one of the main effective components extracted from the dried ripe fruit of Lycium barbarum L.,a solanaceae plant.It has many pharmacological effects such as anti-aging,anti-oxidation,anti-fibrosis,anti-inflammation,neu-roprotection and immunomodulation.LBP has been widely studied in the field of prevention and treatment of AD because of its good anti-aging and neuroprotective effects.Its prevention and treatment mechanism mainly includes the following points:① Regulating the apoptosis of nerve cells.Studies have shown that the signal pathway com-posed of phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)participates in a series of processes such as the growth,proliferation and apoptosis of neurons and plays an important regulatory role.LBP can reduce the number of cell apoptosis,increase the expression levels of autophagy protein Beclin1 and microtubule-associated protein 1 light chain 3Ⅱ(LC3Ⅱ),and decrease the expres-sion levels of p-Akt and phosphorylated mammalian target protein of rapamycin(p-mTOR),which indicates that Lycium barbarum polysaccharide can prevent and treat AD by inhibiting PI3K/Akt/mTOR pathway and improv-ing the autophagy level of cells.②Inhibition of amyloid β-protein(Aβ)production.Aβ is the main component of senile plaque,which is regarded as the main biomarker of AD.It is found that the neurotoxicity of Aβ plays a role by increas-ing the influx of Ca2+ mediated by N-methyl-D-aspartate receptor in the process of signal transduction in the brain,and then generating reactive oxygen species(ROS)and apoptosis signals.LBP can promote autophagy of HT22 cells by inhibiting PI3K/Akt pathway,which has a protec-tive effect on Aβ-induced toxicity.③ Inhibit the produc-tion of inflammatory cytokines.In the pathogenesis of AD,microglia are activated when they feel pathological accumulation of Aβ,and then cell surface immune and adhesion molecules such as cluster of differentiation 45(CD45),CD40,CD36 and integrins are activated,thereby recruiting Src family kinases and activating MAPK path-way,leading to over-expression of proinflammatory fac-tors.A large number of cytokines and chemokines are produced,which may lead to synapse damage and loss.For example tumor necrosis factor-α(TNF-α)can induce neuronal apoptosis and injury.The production of interleu-kin,and other cytokines and chemokines may also lead to microglia activation,astrocyte proliferation,and further secretion of proinflammatory factors and amyloid deposi-tion,thus making the neuroinflammatory cascade perma-nent.LBP can down-regulate the expression of TNF-α and IL-1β genes,reduce the level of intracellular ROS,and improve the learning and memory ability of AD patients.In this paper,the mechanism of Lycium barbarum polysaccharide in preventing and treating AD is reviewed,in order to provide basis for drug development and clini-cal application.
2.Traditional Chinese medicine polysaccharides in the treatment of Parkinson's disease and its mechanism
Ziying WANG ; Xi CHEN ; Danshen ZHANG ; Yongshuai JING
Chinese Journal of Pharmacology and Toxicology 2023;37(7):499-499
Parkinson's disease(PD)is a degenera-tive disease of the central nervous system characterized by the loss of dopamine(DA)neurons in the dense sub-stantia nigra and the depletion of DA neurons.Clinically,the treatment of PD is mainly supplementing dopamine deficiency or using DA receptor agonists,but these drugs can only alleviate the symptoms of PD patients,but cannot prevent neuronal loss and delay disease progres-sion.Natural bioactive polysaccharides have the advan-tages of multi-target,low toxicity and synergistic effect,and have great potential in the prevention and treatment of PD.Numerous studies have shown that polysaccha-rides can be involved in neuronal protection and preven-tion of neurodegenerative diseases through mechanisms such as oxidative stress,reducing neuroinflammation,and inhibiting anti-apoptosis.①Anti-oxidative stress.Oxi-dative stress is caused by increased reactive oxygen spe-cies(ROS)products and weakened antioxidant capacity,resulting in destruction of lipids,proteins,and DNA.Oxi-dative stress-induced mitochondrial dysfunction is thought to be an important cause of DA neuronal loss in PD mice.Polysaccharides reduce the damage of DA neurons in the substantia nigra by increasing the activity of antioxidant enzymes and inhibiting the formation of reactive oxygen species.② Reduce neuroinflammation.Neuroinflamma-tory response is the main causative factor of neurodegener-ation,microglia are innate immune cells present in the central nervous system,and their continuous activation is a key link in central nervous system neuroinflammation.Polysaccharides can regulate the expression of inflamma-somes,reduce the levels of pro-inflammatory cytokines and cytotoxic factors,inhibit the excessive activation of microglia,reduce PD neuroinflammatory damage,and then exert neuroprotective effects.③ Inhibiting apopto-sis.Apoptosis(APO)is the process of cell death caused by the activation of cell death procedures by various fac-tors.During the pathogenesis of PD,due to changes in the internal and external environment of DA neurons,some apoptosis-related genes cause DA neuronal death by regulating cell death signaling pathways.Polysaccha-rides can reduce the Bax/Bcl2 ratio,weaken the activa-tion of caspase-related proteins,improve the viability of PC12 cells,reduce apoptosis,and protect the activity of dopamine neurons.In summary,traditional Chinese med-icine polysaccharides can effectively treat and improve PD,and its mechanism of action involves anti-oxidative stress,reducing neuroinflammation and apoptosis.There-fore,traditional Chinese medicine polysaccharides have great development potential in the field of medicine and health.
3.Therapeutic mechanism of Acorus tatarinowii on Alzheimer's disease
Meng YAN ; Beibei HU ; Danshen ZHANG ; Yongshuai JING
Chinese Journal of Pharmacology and Toxicology 2023;37(7):500-500
Acorus tatarinowii is the dried rhizome of the Araceae plant Acorus tatarinowii Schott.Acorus tata-rinowii was first recorded in Shennong's Classic of Mate-ria Medica.It was used for the treatment of epilepsy,amnesia,insomnia,tinnitus,deafness,silent diarrhea,and other diseases.Alzheimer's disease(AD),also known as senile dementia,is a degenerative disease of the central nervous system.It is mainly manifested as neuropsychiatric symptoms such as progressive memory impairment,cognitive dysfunction,personality changes and language disorders.Acorus tatarinowii mainly con-tains phenylpropylene,lignans,alkaloids,sugars,organic acids and amino acids,among which volatile compo-nents such as β-asarone are the main active compo-nents.The main mechanism of action of Acorus tatari-nowii in the prevention and treatment of AD is as follows:① Improve memory ability.Increasing the expression of brain-derived neurotrophic factor(BDNF),extracellular signal-regulated kinase(ERK)and adenosine cyclic phosphate response element binding protein(CREB)can improve cognitive dysfunction.Studies have shown that Acorus tatarinowii can increase the expression of BDNF,ERK,CREB and tyrosine receptor kinase B in the hippo-campus of mice to varying degrees.It can significantly improve the memory ability of memory-impaired mice,so as to achieve the purpose of prevention and treatment of AD.② Anti-oxidative stress.Studies have shown that Acorus tatarinowii can reduce the production of malondi-aldehyde in skeletal muscle,increase superoxide dis-mutase activity and total antioxidant capacity,and repair the balance of oxidative stress.③ Acetylcholinesterase inhibition.The loss of consciousness caused by deficiency of kidney essence in AD patients is related to the patho-logical changes of the cholinergic nervous system.The results showed that Acorus tatarinowii could significantly increase the contents of glutamate and acetylcholine in the cerebral cortex of AD model mice,and decrease the activity of acetylcholinesterase,to achieve the anti-AD effect.④ Anti-inflammatory and neuroprotective effects.The damage of neurons in the brain of AD patients is related to the excessive inflammatory immune response of nerve cells including microglia and astrocytes.The results showed that Acorus tatarinowii can inhibit the autophagy of microglia in rats with cerebral hemorrhage,and has neuroprotective effect,to achieve the effect of anti-AD.In this study,the effects of Acorus tatarinowii on AD were reviewed to further clarify its pharmacological ef-fects,and to provide a basis for clinical application and research.
4.Advances in chemical constituents of Areca catechu L.and their effects on nervous system
Hao ZHANG ; Xi CHEN ; Danshen ZHANG ; Yongshuai JING
Chinese Journal of Pharmacology and Toxicology 2023;37(7):501-501
Areca nut is the dried and mature seed of Areca catechu L.in the palm family,which is a medicinal and food resource.It tastes bitter,spicy and warm.It has the functions of killing insects,eliminating accumulation,activating qi and nourishing water.It contains alkaloids,polyphenols,polysaccharides,fatty acids,amino acids,flavonoids,triterpenes and steroids and other chemical components.It has a certain protective effect on the ner-vous system,and mainly includes:① Arecoline con-tained in areca nut can stimulate the sympathetic nerve and simultaneously stimulate M receptor and N receptor,which can be used for the treatment of Alzheimer's dis-ease.② Antidepressant effect.Arecoline can easily pass through the blood-brain barrier and stimulate nerve cell receptors,thus promoting the body's excitement.Total phenols increase the content of monoamine transmitters in the brain by decreasing the content of monoamine oxi-dase,thus exerting therapeutic effect on depression.③ Antioxidant effect.Polyphenols and flavonoids can reduce oxidative damage of nervous system,and their antioxidant capacity is related to their content.④ Anti-inflammatory effect.Areca polysaccharides can exert anti-inflammatory activity by inhibiting the production of NO in macrophages induced by lipopolysaccharide.⑤Improved digestion.Areca nut water extract has a pro-moting effect on gastrointestinal motility,which is not only related to M choline receptor,but also probably related to α-adrenalin receptor.⑥Other effects.Such as anti-throm-bosis,anti-atherosclerosis,hypoglycemia,blood lipid reg-ulation,anti-tumor,anti-allergy,bacteriostasis,etc.This review summarized the chemical composition and phar-macological action of Areca catechu in recent years.It was found that the mechanism of action of Areca cate-chu L.is still unclear and further research is needed to provide basis for scientific utilization of Areca catechu.
5.Advances in pharmacological effects of tanshi-none ⅡA on pain
Wenjing CHENG ; Xi CHEN ; Danshen ZHANG ; Yongshuai JING
Chinese Journal of Pharmacology and Toxicology 2023;37(7):524-525
Pain is one of the most serious problems plaguing human health today.Drug therapy is one of the main ways to treat pain in clinic.The analgesic drugs commonly used in clinical treatment of pain are often accompanied by many side effects,the analgesic effect is still not ideal.Salvia miltiorrhiza is a traditional medici-nal material with the same origin as food and medicine.It has the functions of promoting blood circulation and removing blood stasis,relieving pain through menstrual circulation,and contains many effective ingredients such as tanshinone and salvianolic acid.Tanshinone is a kind of rosin diterpenoid compound,which mainly consists of o-quinone type and p-quinone type parent nucleus,and tanshinone Ⅱ A is the representative compound.The pharmacological mechanism of tanshinone ⅡA in labor pain mainly includes:① Regulate inflammatory factors.Inflammatory cytokines played an important role in the occurrence and progression of pain.It was found that the analgesic effect of tanshinone ⅡA was related to the anti-inflammatory effect.Tanshinone ⅡA showed anti-injuri-ous activity in various pain models,such as bone cancer pain and sciatic nerve ligation,and related studies found that tanshinone ⅡA could inhibit the expression of inflammatory factors TNF-α,IL-1β and IL-6 in the spinal cord of model rats.In the spinal nerve ligation model,tanshinone ⅡA also promoted the release of anti-inflam-matory cytokine IL-10 in the spinal cord of rats.② Regu-late signal pathways related to regulating spinal cord oxi-dation and apoptosis.Apoptosis and oxidation played an important role in the process of pain.When nerve injury was caused by stimulation,oxidative stress and apopto-sis of nerve cells were involved in the mechanism of hyperalgesia.Tanshinone ⅡA sodium sulfonate could relieve pain by regulating apoptosis-related pathways.In neuralgia model,tanshinone ⅡA could reduce the apop-tosis of spinal cord neurons by inhibiting oxidative stress response in rat spinal cord tissue.In addition,tanshinone ⅡA also decreased the expression of pro-apoptotic protein in spinal dorsal horn of CCI rats.They included caspase-3,Bcl-2,Bax protein,and enhancer binding protein homologous protein,Increased the expres-sion of anti-apoptosis protein Bcl-2.③ Inhibit the activa-tion of spinal cord glial cells.tanshinone ⅡA could exert its labor pain effect by inhibiting the activation of astro-cytes,including inhibiting the expression of chemo-therapy-induced neuralgia,inflammatory pain and inflam-matory cytokines IL-6,IL-1β and TNF-α,and inhibiting the activation of inflammatory signaling pathways related to astrocyte activation.Such as NF-κB signaling path-way,c-Jun N-terminal kinase signaling pathway,etc.In addition,tanshinone ⅡA also inhibited the activation of microglia by inhibiting the expression of CX3CR1 receptor on the surface of microglia and inhibiting the phosphoryla-tion of ERK,JNK and p38 signaling pathways.④ Decr-ease the expression of glutamate receptors in spinal cord.NMDA is an ionic glutamate receptor in the central nervous system,and its subunit NR2B is closely related to pain.The overexpression of NR2B in spinal cord could lead to the decrease of pain threshold,which was an important mechanism of pain generation.The mechani-cal threshold and thermal threshold of CCI rats were increased by tanshinone ⅡA,and the expression of spi-nal dorsal horn 2B subunit was significantly decreased after tanshinone ⅡA treatment in CCI rats.Therefore,it was concluded that the analgesic effect of tanshinone ⅡA on CCI model may be related to the decreased expres-sion of NR2B in spinal dorsal horn.In conclusion,tanshi-none ⅡA can effectively play the role of labor pain,and has great potential for development in the field of medi-cine and health products.
6.Rubrofusarin glucosides of Berchemia polyphylla var. leioclada and their scavenging activities for DPPH radical.
Yongshuai JING ; Juan YANG ; Lanfang WU ; Zhendong ZHANG ; Li FANG
China Journal of Chinese Materia Medica 2011;36(15):2084-2087
OBJECTIVETo study the rubrofusarin glucosides from whole plants of Berchemia polyphylla var. leioclada, and their scavenging activities for 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical.
METHODThe chemical constituents were isolated and purified via repeated silica gel and Sephadex LH-20 column chromatography. Their structures were elucidated by spectral analysis and the compounds were tested for their scavenging activities on DPPH radical.
RESULTThree rubrofusarin glucosides compounds were isolated and identified as rubrofusarin-6-O-beta-D-glucopyranoside (1), rubrofusarin-6-O-beta-D-(6'-O-acetyl) glucopyranoside (2), rubrofusarin-6-O-alpha-L-rhamnosyl-(1-6) -O-beta-D-glucopyranside (3). Three isolated compounds showed strong scavenging activities on DPPH radical, the concentration of half elimination ratio( micromol x L(-1)) of VitC and Compounds 1-3 were 18.2, 40.5, 23.3 and 13.6, respectively.
CONCLUSIONCompounds 1-3 were isolated from this plant for the first time and compound 2 was a new compound. They showed significant antioxidant activity, and the scavenging activity of compound 3 was a little stronger than that of VitC.
Biphenyl Compounds ; metabolism ; Free Radical Scavengers ; chemistry ; pharmacology ; Glucosides ; chemistry ; pharmacology ; Nuclear Magnetic Resonance, Biomolecular ; Picrates ; metabolism ; Pyrones ; chemistry ; pharmacology ; Rhamnaceae ; chemistry
7.Effects of different formulations of high-fat diet on establishment of a non-alcoholic fatty liver model in rats
Zishuo ZHAO ; Yuguang ZHU ; Yanshan MA ; Zhiwei LI ; Yongshuai JING ; Yinghua XIE
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(5):543-553
AIM:To improve the success rate of experimental modeling of non-alcoholic fatty liver(NAFLD)in rats by high-fat diet through comparing three different formulations of high-fat diets in con-structing non-alcoholic fatty liver rats model,so as to provide a reliable animal model for the study of non-alcoholic fatty liver disease.METHODS:SPF-grade male SD rats were divided into four groups randomly:control group,high-fat diet group1(HFD1),high-fat diet group2(HFD2),high-fat diet group3(HFD3).Each group was given the corre-sponding feed for 8 weeks while modeling.The da-ta on general observation,body weight changes,and ingestion of the rats were recorded during the modeling period.After 8 weeks'feeding,liver ultra-sound,CT and MRI examination were performed for the rats of each group to check the status.Blood and liver samples were collected.Changes in liver function(ALT,AST),blood lipids(TC,TG,HDL-C,LDL-C),and inflammatory indexes(IL-1β,IL-6,TNF-α)were detected.The morphology of the liv-ers was observed with the naked eyes,and the liv-er index and Lee's index were calculated at the end of 8 weeks.The effects of different high-fat diets on the establishment of NAFLD model in SD rats were comprehensively evaluated by comparing the difference of above indexes among the groups.RE-SULTS:Compared with the control group,rats in the HFD1,HFD2 and HFD3 groups showed poor mental deterioration,decreased activity,severe hair loss,decreased food intake,increased body weights,and significantly increased liver index and Lee's in-dex,along with increased liver volume,blunt edge,steatosis and lipid deposition,and the trend was even more pronounced in the HFD3 group.Com-pared with the control group,the serum levels of ALT,AST,TC,TG,LDL-C,IL-1β,IL-6 and TNF-α were significantly increased,while the contents of HDL-C was significantly decreased in the HFD1,HFD2 and HFD3 group,especially in the HFD3 group.Com-pared with the control group,the B ultrasonogra-phy showed an enlarged liver with enhanced paren-chymal echo and pipe unsharpness,CT showed that the liver and spleen CT ratio decreased obvi-ously,and the MRI images showed obvious differ-ence of liver signal intensity between in/out of phase image in the HFD1,HFD2 and HFD3 group,and the most significant imaging changes was ob-served in the HFD3 group.CONCLUSION:The above three kinds of high-fat diets can establish NAFLD model in SD rats after 8 weeks'feeding,the models induced by HFD3 was better than those in-duced by the other two groups.NAFLD lesion is rel-atively serious and expected to last longer in HFD3 group,which are more suitable for investigating the underlying mechanisms of non-alcoholic fatty liver disease and development of lipid-lowering drugs.
8. Research progress on extraction methods and pharmacological activities of polysaccharide from traditional Chinese herb compound
Yongshuai JING ; Yuwei ZHANG ; Ruijuan ZHANG ; Yunfeng MA ; Danshen ZHANG ; Lanfang WU
Chinese Journal of Clinical Pharmacology and Therapeutics 2021;26(4):462-468
Traditional Chinese herb compound is a prescription formulated according to the theory of Chinese medicine, and it is a commonly used method of Chinese medicine. As one of the main active ingredients, the extraction methods of polysaccharides from traditional Chinese herb compound include solvent extraction, ultrasonic assisted extraction, microwave assisted extraction and microbial fermentation extraction. The traditional Chinese herb compound polysaccharide has antitumor, immunoregulatory, intestinal mucosa repair, hypoglycemic, antiviral, antioxidant and other pharmacological activities. In this paper, the extraction methods of polysaccharides from traditional Chinese herb compound and its pharmacological activities were summarized, so as to provide scientific evidence for a better development and utilization of traditional Chinese herb compound polysaccharide.
9.Optimization of Preparation Technology of Tetracaine Hydrochloride Ethosomes
Nan ZHANG ; Danshen ZHANG ; Yongshuai JING ; Xiaomei SU ; Jianmei ZHANG
China Pharmacy 2019;30(24):3369-3374
OBJECTIVE: To establish a method for determining the content of tetracaine hydrochloride (TCH) ethosomes, and to optimize the preparation technology. METHODS: The content of TCH was determined by HPLC. TCH ethosomes were prepared with injection-ultrasonic method. Using drug-loading amount, egg lecithin concentration and ethanol volume fraction as factor, encapsulation efficiency as index, central composite design-response surface methodology was used to optimize the prescription based on the single factor test. The prepared ethosomes were characterized and the stability was evaluated. RESULTS: The linear range of TCH was 10-100 μg/mL (r=0.999 5); the limit of quantification was 0.045 μg/mL, and detection limit was 0.021 μg/mL. RSD of precision, stability and repeatability tests were less than 2%. The recoveries ranged 97.80%-103.20% (RSD=0.36%, n=9). The optimal preparation technology included that the adding amount of TCH control was 1 mg; the concentration of egg lecithin was 7 mg/mL, and ethanol volume fraction was 33%. Under this technology, the average encapsulation efficiency was 64.50% (n=3), the relative error of which from the predicted value (64.92%) was 0.64%. TCH ethosome was a clear blue liquid with a blue opalescence. Its appearance was spherical, its shape was round, smooth, uniform in size; the average particle size was (80.33±2.24) nm, and the average Zeta potential was (-22.6±1.33) mV. TCH ethosome was stable during 10 days under 4 ℃, sealed and protected from light. CONCLUSIONS: The optimal preparation process is stable and feasible. Established method is simple and rapid.