[Mechanism of Kaixin Powder in alleviating breast cancer chemotherapy-induced cognitive impairment by transcriptome association analysis].

The study aims to evaluate the effect of Kaixin Powder(KXP) on the behavior and brain tissue of chemotherapy-treated mice to explore its mechanism in alleviating chemotherapy-induced cognitive impairment in tumor-bearing mice. Thirty female BALB/c mice were inoculated with 4T1 breast cancer cells to establish a tumor-bearing mouse model and randomly divided into the tumor group, a doxorubicin group, and a KXP group. Behavioral tests, including open field test, elevated plus maze test, forced swimming test, tail suspension test, Morris water maze test, and novel object recognition test, were conducted. Pathological examinations, including hematoxylin-eosin staining, Nissl staining, toluidine blue staining, Fluoro-Jade B staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) assay, immunofluorescence staining, and transmission electron microscopy, were performed. Network pharmacology and whole transcriptome sequencing methods were used to analyze the mechanism of chemotherapy-induced cognitive impairment and the targets of KXP. The results showed that KXP prevented chemotherapy-induced behavioral changes(P<0.001), increased the total movement distance and central zone residence time in the open field test, increased exploration time in the open arm area in the elevated plus maze test, reduced immobility time in the forced swimming test and tail suspension test, reduced escape latency in the Morris water maze test and increased platform crossings, and improved cognitive index in the novel object recognition test. KXP also inhibited chemotherapy-induced neuroinflammation, apoptosis, and autophagy in the prefrontal cortex, and reshaped the RNA expression profile of the prefrontal cortex tissue during chemotherapy(P<0.05). In conclusion, KXP may alleviate chemotherapy-induced cognitive impairment in tumor-bearing mice by reshaping the RNA expression profile of prefrontal cortex tissue, thereby reducing neuronal tissue damage.

New insights into effects of Kaixin Powder on depression via lipid metabolism related adiponectin signaling pathway.

Objective: To clarify the anti-depressive potential mechanisms of Kaixin Powder (KP), a drug that helps to prevent and treat depression and other mentaldiseases, from genome-wide transcriptome profiling. Methods: Transcriptome and KEGG pathway analysis were conducted on the hippocampus of depressed rats, then the differentially expressed genes were validated and serum concentration of lipid parameters were identified by enzymatic assays. Furthermore, high-fat diets induced depression-like behaviors in Syrian golden hamsters were conducted to verify the predicted molecular mechanisms acquired from the transcriptome analysis. Results: Transcriptome results revealed that the 24 differentially expressed genes (DEGs) in chronic mild stress (CMS) rats could be reversed after two weeks of KP treatment. The mechanisms of KP in treating depression firstly involved the regulation of several pathology modules, including lipid metabolism, synapse function and inflammation. KP could regulate imbalances of lipid homeostasis in high-fat diet induced depressive symptoms. Furthermore, it was validated that cholesterol metabolism dysfunction can be ameliorated by KP, which was correlated with upregulation of the AdipoR1-BDNF (brain-derived neurotrophic factor) co-regulatory pathway. Conclusion: Taken together, our results demonstrated that KP not only alleviates depression via traditional mental illness targets, but it may also simulates the cholesterol metabolism and adiponectin signaling with multi-target characteristics.

[Research progress on chemical constituents and pharmacological effects of Kaixin Powder and predictive analysis of its Q-markers].

Kaixin Powder is a classic prescription for invigorating Qi, nourishing the mind, and calming the mind. It has pharmacological effects of improving learning and memory ability, resisting oxidation, delaying aging, and promoting the differentiation and regeneration of nerve cells. It is mainly used in the modern clinical treatment of amnesia, depression, dementia, and other diseases. The present paper reviewed the research progress on the chemical composition and pharmacological action of Kaixin Powder, predicted and analyzed its quality markers(Q-markers) according to the concept of Chinese medicine Q-markers, including transmission and traceability, specificity, effectiveness, measurability, and compound compatibility environment. The results suggested that sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3',6-disinapoylsucrose, tenuifoliside A, ginsenoside Rg_1, ginsenoside Re, ginsenoside Rb_1, pachymic acid, ß-asarone, and α-asarone could be used as Q-markers of Kaixin Powder. This study is expected to provide a scientific basis for establishing the quality control system and the whole process quality traceability system of Kaixin Powder compound preparations.

[Key quality attributes of benchmark samples of famous classical formula Kaixin Powder].

We prepared 15 batches of Kaixin Powder benchmark samples with the decoction pieces of different batches. Further, we established the specific chromatograms and index component content determination method of Kaixin Powder benchmark samples and analyzed the peaks and similarity of the chromatograms. With sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3,6'-disinapoyl sucrose, ginsenoside Rb_1, ß-asarone, α-asarone, and dehydropachymic acid as index components, the index component content determination method was established and 70%-130% of the mean content of each component was set as the range. The chromatograms of 15 batches of Kaixin Powder benchmark samples had a total of 22 characteristic peaks, among which 8 peaks were identified, which represented sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3,6'-disinapoyl sucrose, ginsenoside Rb_1, ß-asarone, α-asarone, and dehydropachymic acid, respectively. The chromatograms shared the similarity of 0.992-0.999. The 15 batches of benchmark samples had sibiricose A5 of 0.34-0.55 mg·g~(-1), sibiricose A6 of 0.43-0.57 mg·g~(-1), polygalaxanthone Ⅲ of 0.12-0.19 mg·g~(-1), 3,6'-disinapoyl sucrose of 1.08-1.78 mg·g~(-1), ginsenoside Rb_1 of 0.33-0.62 mg·g~(-1), ß-asarone of 2.34-3.72 mg·g~(-1), α-asarone of 0.11-0.22 mg·g~(-1), and dehydropachymic acid of 0.053-0.079 mg·g~(-1). This study established the specific chromatograms and index component content determination method of Kaixin Powder benchmark samples, and the method was simple, feasible, reproducible, and stable. This study provides a scientific basis for further research on the key chemical properties of the benchmark samples and preparations of Kaixin Powder.

Key quality attributes of benchmark samples of famous classical formula Kaixin Powder / 中国中药杂志

We prepared 15 batches of Kaixin Powder benchmark samples with the decoction pieces of different batches. Further, we established the specific chromatograms and index component content determination method of Kaixin Powder benchmark samples and analyzed the peaks and similarity of the chromatograms. With sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3,6'-disinapoyl sucrose, ginsenoside Rb_1, β-asarone, α-asarone, and dehydropachymic acid as index components, the index component content determination method was established and 70%-130% of the mean content of each component was set as the range. The chromatograms of 15 batches of Kaixin Powder benchmark samples had a total of 22 characteristic peaks, among which 8 peaks were identified, which represented sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3,6'-disinapoyl sucrose, ginsenoside Rb_1, β-asarone, α-asarone, and dehydropachymic acid, respectively. The chromatograms shared the similarity of 0.992-0.999. The 15 batches of benchmark samples had sibiricose A5 of 0.34-0.55 mg·g~(-1), sibiricose A6 of 0.43-0.57 mg·g~(-1), polygalaxanthone Ⅲ of 0.12-0.19 mg·g~(-1), 3,6'-disinapoyl sucrose of 1.08-1.78 mg·g~(-1), ginsenoside Rb_1 of 0.33-0.62 mg·g~(-1), β-asarone of 2.34-3.72 mg·g~(-1), α-asarone of 0.11-0.22 mg·g~(-1), and dehydropachymic acid of 0.053-0.079 mg·g~(-1). This study established the specific chromatograms and index component content determination method of Kaixin Powder benchmark samples, and the method was simple, feasible, reproducible, and stable. This study provides a scientific basis for further research on the key chemical properties of the benchmark samples and preparations of Kaixin Powder.

Research progress on chemical constituents and pharmacological effects of Kaixin Powder and predictive analysis of its Q-markers / 中国中药杂志

Kaixin Powder is a classic prescription for invigorating Qi, nourishing the mind, and calming the mind. It has pharmacological effects of improving learning and memory ability, resisting oxidation, delaying aging, and promoting the differentiation and regeneration of nerve cells. It is mainly used in the modern clinical treatment of amnesia, depression, dementia, and other diseases. The present paper reviewed the research progress on the chemical composition and pharmacological action of Kaixin Powder, predicted and analyzed its quality markers(Q-markers) according to the concept of Chinese medicine Q-markers, including transmission and traceability, specificity, effectiveness, measurability, and compound compatibility environment. The results suggested that sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3',6-disinapoylsucrose, tenuifoliside A, ginsenoside Rg_1, ginsenoside Re, ginsenoside Rb_1, pachymic acid, β-asarone, and α-asarone could be used as Q-markers of Kaixin Powder. This study is expected to provide a scientific basis for establishing the quality control system and the whole process quality traceability system of Kaixin Powder compound preparations.

New insights into effects of Kaixin Powder on depression via lipid metabolism related adiponectin signaling pathway / 中草药·英文版

OBJECTIVE@#To clarify the anti-depressive potential mechanisms of Kaixin Powder (KP), a drug that helps to prevent and treat depression and other mentaldiseases, from genome-wide transcriptome profiling.@*METHODS@#Transcriptome and KEGG pathway analysis were conducted on the hippocampus of depressed rats, then the differentially expressed genes were validated and serum concentration of lipid parameters were identified by enzymatic assays. Furthermore, high-fat diets induced depression-like behaviors in Syrian golden hamsters were conducted to verify the predicted molecular mechanisms acquired from the transcriptome analysis.@*RESULTS@#Transcriptome results revealed that the 24 differentially expressed genes (DEGs) in chronic mild stress (CMS) rats could be reversed after two weeks of KP treatment. The mechanisms of KP in treating depression firstly involved the regulation of several pathology modules, including lipid metabolism, synapse function and inflammation. KP could regulate imbalances of lipid homeostasis in high-fat diet induced depressive symptoms. Furthermore, it was validated that cholesterol metabolism dysfunction can be ameliorated by KP, which was correlated with upregulation of the AdipoR1-BDNF (brain-derived neurotrophic factor) co-regulatory pathway.@*CONCLUSION@#Taken together, our results demonstrated that KP not only alleviates depression via traditional mental illness targets, but it may also simulates the cholesterol metabolism and adiponectin signaling with multi-target characteristics.

[Mechanism of Kaixin Powder prescriptions Buxin Decoction regulating PI3K/AKT signaling pathway to protect cardiovascular system: based on network pharmacology and experimental verification].

This study established the EA.hy926 cell myocardial ischemia model to compare the effects of two Kaixin Powder prescriptions, Buxin Decoction(BXD) and Dingzhi Pills(DZP), at three dosages(500, 200, and 100 µg·mL~(-1)) on the cell viability. Further, the public databases(TCMSP, TCMID, SYMMAP, and STRING) and the network pharmacology methods such as KEGG pathway enrichment were employed to decipher the possible molecular mechanism of BXD in exerting the cardioprotective effect. The pharmacological effect of BXD was evaluated with the rat model of isoprenaline(ISO)-induced myocardial ischemia. The expression levels of proteins involved in the phosphatidylinositol-3-kinase/protein kinase B(PI3 K/AKT) signaling pathway were measured by Western blot. BXD significantly increased the viability of EA.hy926 cells, showing the performance superior to DZP. The network pharmacology analysis predicted that BXD might exert cardiac protection through the PI3 K/AKT signaling pathway. The in vivo experiment on rats showed that BXD treatment significantly increased the cardiac ejection fraction(EF), fractional shortening(FS), diastolic left ventricular anterior wall(LVAWd), systolic left ventricular anterior wall(LVAWs), and diastolic left ventricular posterior wall(LVPWd), significantly decreased the beat per minute(BPM) and diastolic left ventricular internal diameter(LVIDd), and significantly improved the ST segment in the electrocardiogram. The pathological results(Masson staining) showed that BXD restored the myocardial thickness, decreased the collagen fiber, increased the muscle fiber, and reduced the infarct area to alleviate myocardial ischemia. Furthermore, BXD lowered the serum levels of inflammatory cytokines [tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6)] and myocardial enzymes [creatine kinase(CK) and lactate dehydrogenase(LDH)], increased the p-AKT/AKT ratio, up-regulated the protein levels of PI3 K, NF-κB, IKK-α, and Bcl-xl, and down-regulated that of the apoptotic protein Bax. In conclusion, BXD may exert cardiac protection effect by regulating the PI3 K/AKT signaling pathway.

[Therapeutic effect on mild perimenopausal depression treated with acupuncture at the "thirteen ghost points" and kaixin powder].

OBJECTIVE: To compare the clinical therapeutic effect on perimenopausal depression between the combined treatment with acupuncture at the "thirteen ghost points" and kaixin powder and the single application of kaixin powder. METHODS: A total of 60 patients with mild perimenopausal depression were randomized into a Chinese medication group (30 cases, 2 cases dropped off) and a combined treatment group (acupuncture and Chinese medication, 30 cases). In the Chinese medication group, the modified kaixin powder was administered, one dose a day, taking in the morning and the evening separately. In the combined treatment group, on the base of the treatment as the Chinese medication group, acupuncture was applied to the "thirteen ghost points" invented by SUN Si-miao, e.g. Shuigou (GV 26), Shaoshang (LU 11), Yinbai (SP 1), Daling (PC 7), Shenmai (BL 62), Jiache (ST 6), Chengjiang (CV 24), Laogong (PC 8), Shangxing (GV 23), etc. The needles were withdrawed after the qi was acquired, and acupuncture was given once every two days, 3 times a week. In both of the groups, the consecutive treatment for 12 weeks was required. Separately, before treatment, after treatment and in 1-month follow-up visit, the score of the Hamilton depression scale (HAMD), the score of the self-rating depression scale (SDS) and the score of the perimenopausal Kupperman were observed in the two groups. In 12 weeks of treatment, the clinical therapeutic effect was compared between the two groups. RESULTS: After treatment and during the follow-up, HAMD, SDS and Kupperman scores were all reduced obviously as compared with those before treatment in the two groups (P<0.05). These scores in the combined treatment group were all lower than those in the Chinese medication group (P<0.05). The total effective rate was 90.0% (27/30) in the combined treatment group, better than 78.6% (22/28) in the Chinese medication group (P<0.05). CONCLUSION: Either the combined treatment with acupuncture at the "thirteen ghost points" and kaixin powder or the single application of kaixin powder is effective on perimenopausal depression. The therapeutic effect of the combined treatment of acupuncture and Chinese medication is superior to the simple application of kaixin powder.

Review of anti-depression and improving learning and memory activities of Kaixin Powder and their mechanisms / 中草药

Kaixin Powder, an ancient Chinese herbal decoction and is composed of Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria Cocos. Its main active chemical components are ginseng ginsenosides, polygalae saponins, oligosaccharide esters, asarone, poria acid, and pachymaran, which have a variety of pharmacological effects such as anti-depression, anti-dementia, improving learning and memory, and anti-fatigue. This article mainly reviewed the literature related to Kaixin Powder published in domestic and foreign research journals, summarized the research on the pharmacological activity and their mechanisms of Kaixin Powder, and prospected the potential clinical application in the treatment of mental illness.

Effects of Kaixin Powder on Learning and Memory Function and ATP/AMP Ratio in Rats with Multiple Infarct Dementia / 世界科学技术-中医药现代化

Objective: To investigate the effects of Kaixin Powder on learning and memory, ATP/AMP ratio, GABA andiNOS levels in rats with multiple infarct dementia. Methods: The rat model of multi-infarct dementia was established bymicro-thromboembolism. Morris water maze and opening experiment were used to evaluate learning and memoryfunction. The pathological changes of hippocampal CA1 area were evaluated by HE staining. The contents of ATP andAMP in brain tissue were determined by HPLC. The content of γ-aminobutyric acid and iNOS in peripheral blood weredetected by ELISA kit. Results: Compared with the rats of model group, rats of Kaixin Powder group can significantlyshorten the escape latency, increase the number of crossing platforms, Results: Compared with the model group, increasethe standing times in the opening experiment, prolong the exercise time, shorten the resting time, improve the nerve celldamage in the hippocampal CA1 area, and significantly increase the ratio of ATP/AMP of brain tissue, decreased brainGABA content and serum iNOS content (P ＜ 0.05) . Conclusion: Kaixin Powder has the effect of improving learning andmemory function and abnormal motor behavior in rats with multiple infarct dementia. The mechanism is related toreducing GABA and i NOS content in brain tissue, increasing ATP/AMP ratio in brain tissue and improving energysupply in brain tissue.

Mechanism of network pharmacology of Xiaoyao Powder and Kaixin Powder in treating depression with “Same disease with different treatments” / 中草药

Objective: The network pharmacology method was used to predict the active components, targets, and mechanism of Xiaoyao Powder and Kaixin Powder, and to explore the molecular mechanism of depression “same disease with different treatments”. Methods: TCMID, Batman-TCM, and TCM database@Taiwan were used to predict the targets and ingredients of Xiaoyao Powder and Kaixin Powder. The prediction was made via screening out the antidepressive drug targets approved by TTD, PharmGkb, CTD, Genecard, OMIM, DrugBank database, and constructing protein interaction network (PPI). Through the Network Analyzer tool of Cytoscape, the topology of the target was analyzed, the MCODE algorithm of the plug-in ClusterViz was used for cluster analysis, and the DAVID biological molecular function software was used to perform enrichment analysis. Results: The network analysis indicated that two prescriptions may play antidepressant roles through INS, AKT1, TP53, IL6, and CREB1 targets, involving neuroactive ligand-receptor interaction, cAMP signaling pathway, serotonergic synapse, calcium signaling pathway, and cholinergic synapse pathways. The unique antidepressant mechanism for Xiaoyao Powder is that PIK3CA, BDNF, PIK3R1, and NGF target the PI3K-Akt, calcium, and other signal pathways, and CCND1, PRKACA, GCLM, GCLC targeting oxytocin signaling pathway, cholinergic synapses, and other pathways is considered as Kaixin Powder unique antidepressive mechanism. Conclusion: Xiaoyao Powder and Kaixin Powder have similarities and differences in antidepressant targets due to their differences in composition, and the scientific connotation of “same disease with different treatments” is preliminarily clarified by the analysis of the target and the pathway.

Effects of Kaixin Powder on LTP in vivo and expression of PSD-95 in APP/PS1 transgenic mice / 中成药

AIM To explore the effects of Kaixin Powder (Polygalae Radix,Ginseng Radix et Rhizoma,Poria and Acori tatarinowii Rhizoma) on hippocampal long-term potentiation (LTP) in vivo in APP/PS1 transgenic mice and expression of PSD-95 in hippocampus CA1 area and cerebral cortex.METHODS Thirty-two 3-monthold male APP/PS1 mice were randomly divided into model group,Donepezil [0.75 mg/(kg · d)] group,Kaixin Powder [1.5,3 g/(kg · d)] groups.C57/BL6 mice were used as the control group.Kaixin Powder and Donepezil were administered to the APP/PS1 mice for three months,respectively.Afterwards,the LTP in vivo was recorded in a perforant pathway-dentate gyrus in the hippocampus.Immunohistochemical method was used for measuring the expression of PSD-95 in hippocampus CA1 area and cerebral cortex.RESULTS The fEPSPs slopes were significantly decreased in the model group as compared with the control group.Kaixin Powder or Donepezil treatment significantly enhanced the fEPSPs slopes in the model group.The average optical density of PSD-95 positive cells in hippocampus CA1 area and cerebral cortex was obviously decreased in the model group.Donepezil increased the average optical density of PSD-95 positive cells in hippocampus CA1 area.Kaixin Powder [1.5 g/(kg · d)] increased the average optical density of PSD-95 positive cells in hippocampus CA1 area and cerebral cortex.Kaixin Powder [3 g/(kg · d)] increased the average optical density of PSD-95 positive cells in cerebral cortex.CONCLUSION Kaixin Powder can promote the LTP formation in APP/PS1 transgenic mice and enhance synaptic plasticity,which may be related to the regulation of protein expression of PSD-95.

Effects of Kaixin Powder on Expression of 5-HT Receptor in Hippocampus of Depressed Rats Induced by CUMS / 中草药·英文版

Objective: To observe the influence of Kaixin Powder on ethology, content of 5-HT in the hippocampus, expression of mRNA, and protein in 5-HT1A and 5-HT2A receptors in the hippocampus of depressed rats induced by chronic unpredictable mild stress (CUMS). Methods: Twenty-four male Wistar rats were randomly divided into blank, model, Trazodone, and Kaixin Powder groups, six rats in each group. In addition to the blank control group, other groups were established the depression model induced by CUMS combined with isolated feeding. At the same time, Trazodone group and Kaixin Powder group were treated with corresponding drugs for 3 weeks. After 3 weeks of administration, the rats were sacrificed, and a series of indexes were measured such as the contents of 5-HT, mRNA expression levels of 5-HT1A and 5-HT2A receptors, protein expression levels of 5-HT1A and 5-HT2A receptors, and so on. Results: A series of indexes in the model group were decreased significantly such as the body weight growth, the sugar water intake, the score of Open Field Test, the content of 5-HT in the hippocampus, expression of mRNA, and protein in 5-HT1A receptor, while the expression of mRNA and protein in 5-HT2A receptor were increased significantly. Compared with the model group, the indexes were ameliorated in Trazodone and Kaixin Powder groups. Kaixin Powder is better than Trazodone in decreasing the level of protein in 5-HT2A receptor. Conclusion: The result indicated that the depression performance of depressed rats induced by CUMS can be ameliorated by Kaixin Powder, and the mechanism maybe concerned with increasing the contents of 5-HT, exciting 5-HT1A receptor, and antagonising 5-HT2A receptor.

Establishment of computer-based image-processing system for animal's locomotor activity and sedative verification by Kaixin Powder / 中草药

Objective To set up a system for computer-based image-processing for animal's locomotor activity test in sedative Chinese materia medica(CMM),Kaixin Powder,one of traditional complex prescription. Methods Combining the advantage of computer sciences,information knowledge,and imaging analyzed technique into the open field test,the data of mice locomotor activities were collected and analyzed with technique of pattern-recognition,data mining,etc.The total distance,time and speed of movement, resting time and their ratios in the open field were developed;and those various indexes in central area and peripheral area in the open field were established.The system was also verified by using Kaixin Powder. Results Those indexes were sensitive and objective for judging animal's locomotor activity.The correlation coefficient of those indexes collected by computer and manpower was over 0.9,which indicated that the system had better reproducibility and stability.Conclusion The results show that the system could provide an automatic and intelligent method for studying sedative CMM with integration for monitor,collection, analysis,storage,statistics,and output of experimental data and results.

Effects of Kaixin Powder on learning and memory performance and acetylcholine esterase mRNA expressions in vascular dementia rats / 中成药

0.05. CONCLUSION:Kaixin Powder could enhance VD rats' memory; while Tacrine could enhance VD rats' learning; Kaixin Powder could enhance VD rats' learning and memory as well as Tacrine. Tacrine could down-regulate AChE mRNA expression in hippocampus of VD rats,further studies are needed to elucidate the effects of Kaixin Powder on memory performance in VD rats.