Effects of modified Buzhong Yiqi Decoction on intestinal microflora in a rat model of chronic obstructive pulmonary disease / 中国基层医药

Objective:To investigate the effects of modified Buzhong Yiqi Decoction on intestinal microflora in a rat model of chronic obstructive pulmonary disease. Methods:From April to June 2021, 60 specific pathogen-free Wistar rats were selected for this study. They were randomly divided into blank control, model, traditional Chinese medicine, and western medicine groups with 15 rats per group. Rat models of chronic obstructive pulmonary disease with lung and spleen deficiency were established in all groups except the blank control group. Rat models in the traditional Chinese medicine and western medicine groups were administered modified Buzhong Yiqi Decoction and synbiotics. Rat models in the model and blank control groups were identically administered 0.9% sodium chloride injection. After 7 days, the feces of rats in each group were collected for 16S rRNA sequencing of intestinal flora. Effective sequences were clustered to obtain operational taxonomic units for principal coordinate analysis, species composition analysis, and alpha diversity analysis. The effects of modified Buzhong Yiqi Decoction on the structure, diversity, and abundance changes of intestinal flora were analyzed. Results:The dominant bacteria in the traditional Chinese medicine and western medicine groups were Firmicutes, while the dominant bacteria in the blank control and model groups were Bacteroides. The dominant bacterial groups in each group were mainly Lactobacillus and Bacteroides. Alpha diversity analysis showed that the Shannon index in the community diversity indices of traditional Chinese medicine, western medicine, and blank control groups was (3.65 ± 0.35), (3.65 ± 0.36), and (3.59 ± 0.20), respectively, which were significantly higher than (3.37 ± 0.26) in the model group ( t = 2.49, 2.44, 2.60, all P < 0.05). There was no significant difference in the Shannon index among traditional Chinese medicine, western medicine, and blank control groups (all P > 0.05). The Sobs index of the traditional Chinese medicine, western medicine, and blank control group was (458.67 ± 73.11), (454.80 ± 95.13), and (525.93 ± 101.88), respectively, which were significantly higher than (337.40 ± 37.49) in the model group ( t = 5.72, 4.45, 6.73, all P < 0.05). The Sobs index in the blank control group was higher than that in the western medicine group. There was no significant difference in the Sobs index between blank control and traditional Chinese medicine groups and between western medicine and traditional Chinese medicine groups (both P > 0.05). Principal coordinate analysis revealed that compared with the blank control group, Actinomycetes decreased and Proteobacteria and Desulfurization bacteria increased at the phylum level in the model group, while compared with the blank control group, Bacteroides, Rombutzia,Trichospirillus, and Parabacteroides increased, and Prevotella, Clostridium, Brucella, and Ruminococcus decreased at the genus level. Compared with the western medicine group, Bacillus, Prevotella, Brucella, and Prevotellidae in the traditional Chinese medicine group increased, while Clostridium, Pectinobacter, Christensen, and Trichospirillus decreased in the traditional Chinese medicine group. There was a statistically significant difference in the composition of the bacterial population between groups (all P < 0.05). Conclusion:There is an imbalance in intestinal microecology in a rat model of chronic obstructive pulmonary disease. Modified Buzhong Yiqi Decoction can regulate the intestinal microecology environment, improve the structure of intestinal flora, and increase the diversity and abundance of intestinal flora.

[RhoA/ROCK pathway involved in effects of Sanjiao acupuncture on learning and memory and synaptic plasticity in Alzheimer's disease mice].

OBJECTIVE: To observe the effect of Sanjiao acupuncture(triple energizer acupuncture)on the small G protein guanosine triphosphate enzyme subfamily protein RhoA/Rho kinase (ROCK) pathway in Alzheimer's disease mice, and explore its effect on learning and memory function and neurosynaptic plasticity. METHODS: Forty SAMP8 senile dementia mice were randomly divided into model, Sanjiao acupuncture (acupuncture), non acupoint acupuncture (non-acupoint) and fasudil groups, with 10 mice in each group, another 10 SAMR normal aging mice were selected as normal aging group. Mice in the acupuncture group were treated with acupuncture intervention on "Danzhong"(CV18), "Zhongwan"(CV13), "Qihai"(BL24) and bilateral "Xuehai"(SP10) and "Zusanli" (ST36). Mice in the non-acupoint group were treated with acupuncture at each of the left and right non-acupoints under the ribs and mice in the fasudil group were intraperitoneally injected with fasudil (25 mg/kg). The mice in each group were given medicine or acupuncture on the second day after grouping for 28 continuously days, once a day. Morris water maze test was used to test the learning and memory ability of mice. HE staining was used to observe the pathological changes of neurons in hippocampus. The number of hippocampal neuron dendritic spine was detected by FD fast Golgi staining kit. The contents of ß-amyloid 42 (Aß42) and phosphorylated tau protein (p-tau) in hippocampus were detected by ELISA. Western blot was used to detect the protein relative expression levels of RhoA, ROCK, F-actin and p-cofilin in hippocampus. RESULTS: Compared with those in the normal aging group, the hippocampal neurons of the model group were disorderly arranged, the number of neuron was reduced, the escape latency, hippocampal Aß42 and p-tau contents, RhoA and ROCK protein expressions increased (P<0.05), the number of crossing the original platform, the number of neuronal dendritic spines, expressions of F-actin and p-cofilin decreased (P<0.05). After the interventions, there was no statistically significant difference in the above indicators in the non-acupoint group relevant to the model group (P>0.05). The acupuncture group and fasudil group improved the hippocampal pathological damage. The escape latency, hippocampal Aß42 and p-tau contents, the expressions of RhoA and ROCK protein decreased (P<0.05), and the number of crossing the original platform, the number of hippocampal neuron dendritic spines, expressions of F-actin and p-cofilin increased (P<0.05) in both of the acupuncture and fasudil groups in contrast to the model and non-acupoint groups. Compared with the acupuncture group, there was no significant difference in the above indicators in the fasudil group (P>0.05). CONCLUSION: Sanjiao acupuncture may inhibit the activation of the RhoA/ROCK pathway, so as to improve the learning and memory function of AD mice, increase the number of hippocampal neuron dendritic spines, and promote synaptic plasticity.

[Research advance in multi-component pharmacokinetics of Chinese herbal extracts in recent five years].

The multi-component pharmacokinetic study of Chinese herbal extracts elaborates the in vivo processes,including absorption,distribution,metabolism,and excretion,of multiple bioactive components,which is of significance in revealing pharmacodynamic material basis of Chinese herbal medicine. In recent years,with the innovation in ideas,and development of techniques and methods on traditional Chinese medicine( TCM) research,the pharmacokinetic studies of Chinese herbal extracts were extensively performed,and notable progress has been made. This paper reviewed the advancement of multi-component pharmacokinetics of Chinese herbal extracts in recent five years from analysis technology of biological sample,the pharmacokinetic characteristics of Chinese herbal medicine with complex system,and the impacts of processing and pathological state on pharmacokinetics of Chinese herbal extracts,aiming to provide a reference for quality control,product development and rational medication of Chinese herbal extracts.

[Advance on pharmacokinetics study of traditional Chinese medicine injections in recent ten years].

Traditional Chinese medicine(TCM) injections boast a definite efficacy and have been widely used in clinic. However, the problems in medication safety have been attracted increasing attention. Pharmacokinetics is of significance to guiding TCM injection administration regimen design and improving safety and effectiveness in clinical use. In recent years, with the improvement of ideas, technology and methods of TCM studies, the pharmacokinetic studies of TCM injections have been broadly performed, with a notable progress. This paper reviewed the advance in pharmacokinetics studies of TCM injections in recent ten years, which mainly focused on pre-clinical concentration-time course, distribution, metabolism and excretion in vivo based on analysis techniques, pharmacokinetic interactions of constitutes, impact of pathological state, pharmacokinetic interactions between TCM injection and chemical drugs, and clinical pharmacokinetics studies of TCM injections, in the expectation of providing reference for studies on quality control, product development and rational clinical use of TCM injections.

Research advance in multi-component pharmacokinetics of Chinese herbal extracts in recent five years / 中国中药杂志

The multi-component pharmacokinetic study of Chinese herbal extracts elaborates the in vivo processes,including absorption,distribution,metabolism,and excretion,of multiple bioactive components,which is of significance in revealing pharmacodynamic material basis of Chinese herbal medicine. In recent years,with the innovation in ideas,and development of techniques and methods on traditional Chinese medicine( TCM) research,the pharmacokinetic studies of Chinese herbal extracts were extensively performed,and notable progress has been made. This paper reviewed the advancement of multi-component pharmacokinetics of Chinese herbal extracts in recent five years from analysis technology of biological sample,the pharmacokinetic characteristics of Chinese herbal medicine with complex system,and the impacts of processing and pathological state on pharmacokinetics of Chinese herbal extracts,aiming to provide a reference for quality control,product development and rational medication of Chinese herbal extracts.

Advance on pharmacokinetics study of traditional Chinese medicine injections in recent ten years / 中国中药杂志

Traditional Chinese medicine(TCM) injections boast a definite efficacy and have been widely used in clinic. However, the problems in medication safety have been attracted increasing attention. Pharmacokinetics is of significance to guiding TCM injection administration regimen design and improving safety and effectiveness in clinical use. In recent years, with the improvement of ideas, technology and methods of TCM studies, the pharmacokinetic studies of TCM injections have been broadly performed, with a notable progress. This paper reviewed the advance in pharmacokinetics studies of TCM injections in recent ten years, which mainly focused on pre-clinical concentration-time course, distribution, metabolism and excretion in vivo based on analysis techniques, pharmacokinetic interactions of constitutes, impact of pathological state, pharmacokinetic interactions between TCM injection and chemical drugs, and clinical pharmacokinetics studies of TCM injections, in the expectation of providing reference for studies on quality control, product development and rational clinical use of TCM injections.

Research progress on material composition, pre-clinical pharmacokinetic, and pharmacodynamic studies of Shengmai Injection / 中草药

Shengmai Injection (SMI), is a traditional Chinese medicine (TCM) formula injection composed of Panax ginseng, Ophiopogon japonicas and Schisandra chinensis, which is widely used in clinic for the treatment of cardiovascular diseases as well as protecting against pulmonary disease and add-on therapy to cancer chemotherapy. In recent years, the pre-clinical basic research of SMI was widely performed. The studies, including chemical composition, in vivo process, and action mechanism and so on of SMI, helped to provide scientific foundation for revealing the material basis of formula. In this paper, the studies on material composition, pre-clinical pharmacokinetics and pharmacodynamics of this formula were summarized, so as to provide reference for the quality control, second development and rational clinical application of SMI.

Acupuncture accelerates neural regeneration and synaptophysin production after neural stem cells transplantation in mice.

BACKGROUND: Synaptophysin plays a key role in synaptic development and plasticity of neurons and is closely related to the cognitive process of Alzheimer's disease (AD) patients. Exogenous neural stem cells (NSCs) improve the damaged nerve function. The effects of Sanjiao acupuncture on cognitive impairment may be related to the regulation of the NSC microenvironment. AIM: To explore the anti-dementia mechanism of acupuncture by regulating the NSC microenvironment. METHODS: NSCs were isolated from pregnant senescence-accelerated mouse resistant 1 (SAMR1) mice, labeled with BrdU, and injected into the hippocampus of senescence-accelerated mouse prone 8 (SAMP8) mice. Eight-month-old senescence-accelerated mice (SAM) were randomly divided into six groups: SAMR1 (RC), SAMP8 (PC), sham transplantation (PS), NSC transplantation (PT), NSC transplantation with acupuncture (PTA), and NSC transplantation with non-acupoint acupuncture (PTN). Morris water maze test was used to study the learning and memory ability of mice after NSC transplantation. Hematoxylin-eosin staining and immunofluorescence were used to observe the his-topathological changes and NSC proliferation in mice. A co-culture model of hippocampal slices and NSCs was established in vitro, and the synaptophysin expression in the hippocampal microenvironment of mice was observed by flow cytometry after acupuncture treatment. RESULTS: Morris water maze test showed significant cognitive impairment of learning and memory in 8-mo-old SAMP8, which improved in all the NSC transplantation groups. The behavioral change in the PTA group was stronger than those in the other two groups (P < 0.05). Histopathologically, the hippocampal structure was clear, the cell arrangement was dense and orderly, and the necrosis of cells in CA1 and CA3 areas was significantly reduced in the PTA group when compared with the PC group. The BrdU-positive proliferating cells were found in NSC hippocampal transplantation groups, and the number increased significantly in the PTA group than in the PT and PTN groups (P < 0.05). Flow cytometry showed that after co-culture of NSCs with hippocampal slices in vitro, the synaptophysin expression in the PC group decreased in comparison to the RC group, that in PT, PTA, and PTN groups increased as compared to the PC group, and that in the PTA group increased significantly as compared to the PTN group with acupoint-related specificity (P < 0.05). CONCLUSION: Acupuncture may promote nerve regeneration and synaptogenesis in SAMP8 mice by regulating the microenvironment of NSC transplantation to improve the nerve activity and promote the recovery of AD-damaged cells.

Application value of ω-3 fish oil fat emulsion in the parenteral nutritional support treatment following radical gastrectomy for gastric cancer / 中华消化外科杂志

Objective To investigate the application value of ω-3 fish oil fat emulsion in the parenteral nutritional support treatment following radical gastrectomy for gastric cancer.Methods The retrospective cohort study was conducted.The clinical data of 60 patients who underwent radical gastrectomy for gastric cancer in Nanjing Medical University Affiliated Wuxi Second Hospital between January 2018 and December 2018 were collected.There were 37 males and 23 females,aged from 28 to 78 years,with an average age of 64 years.Thirty patients who received parenteral nutrition containing 100 mL of ω-3 fish oil fat emulsion after radical gastrectomy and 30 patients who received parenteral nutrition containing routine fat emulsion after radical gastrectomy were allocated into experimental group and control group,respectively.Observation indicators:(1) nutritional indicators in the perioperative period;(2) inflammatory indicators in the perioperative period;(3) immune indicators in the perioperative period;(4) postoperative complications.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was evaluated using the independent-sample t test.Count data were described as absolute numbers and percentages,and comparison between groups was analyzed using the chi-square test.Repeated measurement data were analyzed by the repeated measures ANOVA.Results (1) Nutritional indicators in the perioperative period:the levels of total protein,albumin,prealbumin,and transferrin from preoperative day 1 to preoperative day 6 were respectively changed from (60.2±3.0)g/L to (57.2± 3.1)g/L,from (35.3±3.1)g/L to (37.0±1.8)g/L,from (186±24)mg/L to (172±17)mg/L,from (3.0± 0.7) g/L to (2.4 ± 0.4) g/L in the experimental group and from (60.6± 2.4) g/L to (55.7 ± 4.2) g/L,from (35.0±3.8)g/L to (36.0±3.8) g/L,from (184±18)mg/L to (173±25)mg/L,from (3.1±0.6)g/L to (2.2± 0.8)g/L in the control group,with no significant difference in the changing trends between the two groups (F=0.79,2.14,0.03,0.36,P＞0.05).(2) Inflammatory indicators in the perioperative period:the levels of white blood cells,C-reactive protein,interleukin 6,and tumor necrosis factor-α from preoperative day 1 to preoperative day 6 were respectively from (7.2±1.1) ×109/L to (10.2±0.9) ×109/L,from (7.2±2.3) mg/L to (25.5±6.3) mg/L,from (16± 3) ng/L to (24± 4) ng/L,from (17± 4) ng/L to (22± 5) ng/L in the experimental group and from (7.4±0.8) × 109/L to (13.0±1.3) × 109/L,from (6.9±2.4) mg/L to (41.6± 18.9) mg/L,from (17±4) ng/L to (45±8)ng/L,from (16±4)ng/L to (43±7)ng/L in the control group,respectively,with significant differences in the changing trends between the two groups (F=63.05,51.65,127.82,104.91,P＜0.05).(3) Immune indicators in the perioperative period:the levels of immunoglobulin A,immunoglobulin G,immunoglobulin M,CD4+,CD8+,and ratio of CD4+/CD8+ from preoperative day 1 to preoperative day 6 were respectively from (1.5±0.4)g/L to (2.8±0.5)g/L,from (11.1±1.7)g/L to (14.0±1.2)g/L,from (0.77± 0.28)g/L to (1.61±0.31)g/L,from 42％±6％ to 46％±5％,from 23％±4％ to 24％±3％,from 1.82±0.42 to 2.11±0.24 in the experimental group and from (1.4±0.4) g/L to (2.3±0.6) g/L,from (10.7± 1.8) g/L to (11.9± 1.4)g/L,from (0.69±0.23)g/L to (1.19±0.33)g/L,from 40％±5％ to 39％±4％,from 24％±3％ to 23％±3％,from 1.75±0.34 to 1.81±0.35 in the control group,respectively,showing significant differences in the changing trends of the levels of immunoglobulin A,immunoglobulin G,immunoglobulin M,CD4+,and ratio of CD4+/CD8+ between the two groups (F=18.39,15.20,38.42,9.55,5.50,P＜0.05),showing no significant difference in the changing trend of the levels of CD8+ between the two groups (F =0.89,P ＞ 0.05).(4)Postoperative complications:5 patients had postoperative complications,with a incidence rate of 16.7％ (5/30),including 1 of abdominal infection,1 of incisional infection,and 3 of pulmonary infection,and all the 5 patients were cured after symptomatic treatment.Nine patients had postoperative complications,with a incidence rate of 30.0％(9/30),including 2 of abdominal infection,2 of incisional infection,and 5 of pulmonary infection,and all the 9 patients were cured after symptomatic treatment.There was no significant difference in the incidence of postoperative complications between the two groups (x2 =1.491,P＞0.05).Conclusion For patients who receive gastric cancer surgery,ω-3 fish oil fat emulsion can reduce the inflammatory response,improve their immune function and not increase postoperative complications.

Application value of ω-3 fish oil fat emulsion in the parenteral nutritional support treatment following radical gastrectomy for gastric cancer / 中华消化外科杂志

Objective@#To investigate the application value of ω-3 fish oil fat emulsion in the parenteral nutritional support treatment following radical gastrectomy for gastric cancer.@*Methods@#The retrospective cohort study was conducted. The clinical data of 60 patients who underwent radical gastrectomy for gastric cancer in Nanjing Medical University Affiliated Wuxi Second Hospital between January 2018 and December 2018 were collected. There were 37 males and 23 females, aged from 28 to 78 years, with an average age of 64 years. Thirty patients who received parenteral nutrition containing 100 mL of ω-3 fish oil fat emulsion after radical gastrectomy and 30 patients who received parenteral nutrition containing routine fat emulsion after radical gastrectomy were allocated into experimental group and control group, respectively. Observation indicators: (1) nutritional indicators in the perioperative period; (2) inflammatory indicators in the perioperative period; (3) immune indicators in the perioperative period; (4) postoperative complications. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was evaluated using the independent-sample t test. Count data were described as absolute numbers and percentages, and comparison between groups was analyzed using the chi-square test. Repeated measurement data were analyzed by the repeated measures ANOVA.@*Results@#(1) Nutritional indicators in the perioperative period: the levels of total protein, albumin, prealbumin, and transferrin from preoperative day 1 to preoperative day 6 were respectively changed from (60.2±3.0)g/L to (57.2±3.1)g/L, from (35.3±3.1)g/L to (37.0±1.8)g/L, from (186±24)mg/L to (172±17)mg/L, from (3.0±0.7)g/L to (2.4±0.4)g/L in the experimental group and from (60.6±2.4)g/L to (55.7±4.2)g/L, from (35.0±3.8)g/L to (36.0±3.8)g/L, from (184±18)mg/L to (173±25)mg/L, from (3.1±0.6)g/L to (2.2±0.8)g/L in the control group, with no significant difference in the changing trends between the two groups (F=0.79, 2.14, 0.03, 0.36, P>0.05). (2) Inflammatory indicators in the perioperative period: the levels of white blood cells, C-reactive protein, interleukin 6, and tumor necrosis factor-α from preoperative day 1 to preoperative day 6 were respectively from (7.2±1.1)×109/L to (10.2±0.9)×109/L, from (7.2±2.3)mg/L to (25.5±6.3)mg/L, from (16±3)ng/L to (24±4)ng/L, from (17±4)ng/L to (22±5)ng/L in the experimental group and from (7.4±0.8)×109/L to (13.0±1.3)×109/L, from (6.9±2.4)mg/L to (41.6±18.9)mg/L, from (17±4)ng/L to (45±8)ng/L, from (16±4)ng/L to (43±7)ng/L in the control group, respectively, with significant differences in the changing trends between the two groups (F=63.05, 51.65, 127.82, 104.91, P<0.05). (3) Immune indicators in the perioperative period: the levels of immunoglobulin A, immunoglobulin G, immunoglobulin M, CD4+, CD8+, and ratio of CD4+ /CD8+ from preoperative day 1 to preoperative day 6 were respectively from (1.5±0.4)g/L to (2.8±0.5)g/L, from (11.1±1.7)g/L to (14.0±1.2)g/L, from (0.77±0.28)g/L to (1.61±0.31)g/L, from 42%±6% to 46%±5%, from 23%±4% to 24%±3%, from 1.82±0.42 to 2.11±0.24 in the experimental group and from (1.4±0.4)g/L to (2.3±0.6)g/L, from (10.7±1.8)g/L to (11.9±1.4)g/L, from (0.69±0.23)g/L to (1.19±0.33)g/L, from 40%±5% to 39%±4%, from 24%±3% to 23%±3%, from 1.75±0.34 to 1.81±0.35 in the control group, respectively, showing significant differences in the changing trends of the levels of immunoglobulin A, immunoglobulin G, immunoglobulin M, CD4+, and ratio of CD4+ /CD8+ between the two groups (F=18.39, 15.20, 38.42, 9.55, 5.50, P<0.05), showing no significant difference in the changing trend of the levels of CD8+ between the two groups (F=0.89, P>0.05). (4) Postoperative complications: 5 patients had postoperative complications, with a incidence rate of 16.7%(5/30), including 1 of abdominal infection, 1 of incisional infection, and 3 of pulmonary infection, and all the 5 patients were cured after symptomatic treatment. Nine patients had postoperative complications, with a incidence rate of 30.0%(9/30), including 2 of abdominal infection, 2 of incisional infection, and 5 of pulmonary infection, and all the 9 patients were cured after symptomatic treatment. There was no significant difference in the incidence of postoperative complications between the two groups (χ2=1.491, P>0.05).@*Conclusion@#For patients who receive gastric cancer surgery, ω-3 fish oil fat emulsion can reduce the inflammatory response, improve their immune function and not increase postoperative complications.

Acupuncture improves dendritic structure and spatial learning and memory ability of Alzheimer's disease mice.

Acupuncture can improve the cognitive state of Alzheimer's disease, but its mechanism is not clear. Dendritic atrophy and synaptic loss in Alzheimer's disease brain are positively correlated with cognitive damage. Therefore, we speculated that the effect of acupuncture on improving cognitive function may be associated with reduced dendritic damage in the brain. Acupuncture at Qihai (CV6), Zhongwan (CV12), Danzhong (CV17), bilateral Zusanli (ST36), and bilateral Xuehai (SP10) acupoints was performed once a day (1-day rest after 6-day treatment) for 14 consecutive days. Senescence-accelerated mouse prone 8 (SAMP8) mice without acupuncture and senescence-accelerated mouse resistant 1 (SAMR1) mice were used as normal controls. After 14 days of treatment, spatial learning and memory ability of mice was assessed in each group using the Morris water maze. Dendritic changes of pyramidal cells in the hippocampal CA1 region were analyzed by quantitative Golgi staining. Our results showed that acupuncture shortened escape latency and lengthened retention time of the former platform quadrant in SAMP8 mice. Further, SAMP8 mice exhibited a significant increase in the number of apical and basal dendritic branches and total length of apical and basal dendrites after acupuncture. These results suggest that acupuncture improves spatial learning and memory ability of middle-aged SAMP8 mice by ameliorating dendritic structure.

Combined acupuncture and HuangDiSan treatment affects behavior and synaptophysin levels in the hippocampus of senescence-accelerated mouse prone 8 after neural stem cell transplantation.

Sanjiao acupuncture and HuangDiSan can promote the proliferation, migration and differentiation of exogenous neural stem cells in senescence-accelerated mouse prone 8 (SAMP8) mice and can improve learning and memory impairment and behavioral function in dementia-model mice. Thus, we sought to determine whether Sanjiao acupuncture and HuangDiSan can elevate the effect of neural stem cell transplantation in Alzheimer's disease model mice. Sanjiao acupuncture was used to stimulate Danzhong (CV17), Zhongwan (CV12), Qihai (CV6), bilateral Xuehai (SP10) and bilateral Zusanli (ST36) 15 days before and after implantation of neural stem cells (5 × 105) into the hippocampal dentate gyrus of SAMP8 mice. Simultaneously, 0.2 mL HuangDiSan, containing Rehmannia Root and Chinese Angelica, was intragastrically administered. Our results demonstrated that compared with mice undergoing neural stem cell transplantation alone, learning ability was significantly improved and synaptophysin mRNA and protein levels were greatly increased in the hippocampus of mice undergoing both Sanjiao acupuncture and intragastric administration of HuangDiSan. We conclude that the combination of Sanjiao acupuncture and HuangDiSan can effectively improve dementia symptoms in mice, and the mechanism of this action might be related to the regulation of synaptophysin expression.

Multiple Effective Components Determination in Essential Oil from Curcuma phaeocaulis by GC-MS and Its Integrated Pharmacokinetic Study in Rats / 中国药房

OBJECTIVE:To develop the determination method for plasma concentration of effective components in essential oil from Curcuma phaeocaulis,and to study its integrated pharmacokinetics. METHODS:Sixteen rats were given the extract of essential oil from C. phaeocaulis 1.0 g/kg(by crude drug)intragastrically;blood samples 300-400 μL from orbit were collected 0, 0.17,0.5,1,2,2.5,3,4,6,8,10,12,24 h after medication. The plasma concentration of α-pinene,1,8-cineole,borneol, β-elemene,curcumol,germacrone and curdione in rats were determined by GC-MS. The determination was performed on DB-5 capillary column,using helium as carrier gas,at the flow rate of 1.2 mL/min. The injector temperature was 270 ℃,by temperature programming,and split ratio was 20∶1. The sample size was 1 μ L. The ion source was electrospray ion source. The selective reaction monitoring mode was used for the positive ion scanning in the range of m/z 20-500. Pharmacokinetic parameters of above effective components were calculated by using DAS 2.0 software. The weight coefficients were customized according to the proportion of AUC0-∞in the sum of AUC0-∞. The integrated pharmacokinetic parameters of multiple effective components in essential oil from C. phaeocaulis were calculated. RESULTS:The linear range of α-pinene,1,8-cineole,borneol,β-elemene, curcumol, germacrone, and curdione were 2.71-173.54, 7.76-496.88, 3.37-215.72, 21.68-1 387.50, 40.21-2 573.44, 24.84-3 179.69,47.78-3 057.81 ng/mL,respectively (r＞0.99). The lower limits of quantitation were 2.71,7.76, 3.37,21.68,40.21,24.84,47.78 ng/mL,respectively. The precision,accuracy and matrix effects were in line with related requirements of quantitative analysis of biological samples. The pharmacokinetic parameters of α-pinene,1,8-cineole,borneol, β-elemene,curcumol,germacrone,and curdione were as follows that cmaxwere (34.72 ± 9.97),(99.86 ± 5.54),(16.10 ± 3.37), (248.98±86.19),(673.75±104.15),(2 353.64±637.83),(2 420.04±708.51)ng/mL;tmaxwere(2.33±0.29),(0.67±0.29), (1.33±0.58),(1.83±0.76),(0.83±0.29),(0.89±0.18),(1.17±0.76)h;t1/2were(8.64±1.46),(8.98±1.63),(12.43± 2.88),(19.86 ± 4.05),(15.63 ± 5.50),(14.17 ± 4.13),(7.14 ± 0.67)h;AUC0-twere (189.78 ± 89.10),(454.74 ± 82.43), (100.55±8.27),(1 067.37±216.55),(3 154.16±405.94),(16 501.24±663.88),(12 524.92±3 222.10)ng·h/mL;AUC0-∞were(229.57±93.50),(524.32±81.67),(146.28±10.74),(2 092.70±416.18),(5 388.65±661.86),(28 198.87±4 102.62), (14 139.35 ± 3 109.19)ng·h/mL,respectively. After integration,the pharmacokinetic parameters were as follows that cmaxwas 1 880.94 ng/mL; tmaxwas 0.50 h; t1/2was 11.22 h;AUC0-twas 13 050.89 ng·h/mL;AUC0- ∞was 19 015.21 ng·h/mL. CONCLUSIONS: The method can be used for the detection of plasma concentration of effective components in rats;pharmacokinetic parameters of essential oil from C. phaeocaulis after integration are greatly different from single effective component,which can provide reference for characterization of its overall pharmacokinetics.

Study on the Preventive and Therapeutic Effect and Its Mechanism of Medicine Pair Decoction Liquid of Curcuma phaeocaulis-Sparganium stoloniferum on Uterine Myoma in Rats / 中国药房

OBJECTIVE:To study the preventive and therapeutic effect and its mechanism of medicine pair decoction liquid of Curcuma phaeocaulis-Sparganium stoloniferum on rats with uterine myoma. METHODS:Rats were randomly divided into normal group,model group,positive group(mifepristone,2.25 mg/kg)and medicine pair decoction liquid group(C. phaeocaulis-S. stolon-iferum decoction liquid,6.0 g/kg),10 in each group. Except for the normal group,rats in other groups were injected Estradiol ben-zoate injection (0.5 mg/kg) intramuscularly every Monday,Wednesday and Friday,for 12 weeks. From the 13th week,rats in modeling group were added Progesterone injection(5 mg/kg)intramuscularly as well as relevant medicines intragastrically,once a day,until the 16th week. After administration,uterine coefficient of rats was detected. HE staining was used to observe the patho-logical changes of uterus and determine the thickness of smooth muscle;immunohistochemical staining was adopted to detect the transforming growth factor β3 (TGF-β3),matrix metalloproteinase 11 (MMP-11) protein expressions in uterus tissue of rats. RE-SULTS:Compared with normal group,uterine coefficient was increased in model group,pathological changes were obvious in uterus,thickness of smooth muscle was increased,TGF-β3 and MMP-11 protein expressions were enhanced(P<0.05 or P<0.01). Compared with model group,above-mentioned changes were improved significantly in positive group and medicine pair decoction liquid groups(P<0.05 or P<0.01). CONCLUSIONS:Medicine pair decoction liquid of C. phaeocaulis-S. stoloniferum shows cer-tain preventive and therapeutic effect on rats with uterine myoma. The mechanism may be associated with downregulating the TGF-β3,MMP-11 protein expressions in uterus tissue.

Renal protective effects of early continuous venovenous hemofiltration in rhabdomyolysis: improved renal mitochondrial dysfunction and inhibited apoptosis.

Rhabdomyolysis (RM) and subsequent myoglobin (Mb) deposition can lead to acute kidney injury. Continuous venovenous hemofiltration (CVVH) can remove Mb, but direct renal protection is unclear. We hypothesized that CVVH can improve renal mitochondrial dysfunction in its early stage. Twenty-four mongrel dogs were randomly divided into four groups: (A) control; (B) model; (C) model + CVVH (50 mL/kg/h); and (D) model + CVVH (30 mL/kg/h). RM was induced by glycerol via intramuscular injection. The dogs were closely monitored for urine flow and renal function. Mb, plasma tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. After 8 h of CVVH, the morphological changes of renal mitochondria were observed and mitochondrial function indicators (reactive oxygen species, malondialdehyde, and respiratory control index) were detected. Western blot analysis was used to detect the expression of Mb, TNF-α, and IL-6 in renal tubules. The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay method and Western blot analysis were used to detect apoptosis and apoptosis-related proteins. In group B, the dog urine output gradually decreased with increased blood creatinine. In groups C and D, the urine output was normal and stable. CVVH effectively eliminated Mb. High-dose CVVH was significantly better for removal efficiency than low-dose CVVH. CVVH significantly reduced the deposition of circulating Mb in the kidney in a dose-dependent manner. The impact of CVVH on TNF-α and IL-6 were not observed. The morphological changes of mitochondria and function indicators were significantly improved in group C compared with groups D and B. Compared with group B, renal apoptosis and apoptosis-related protein expression were inhibited in groups C and D. Group C was significantly better for mitochondrial improvement and apoptosis inhibition than group D. At the cellular and molecular level, CVVH can improve renal mitochondrial function and inhibit cell apoptosis. Early CVVH can protect from RM-caused renal injuries in a dose-dependent manner.

Andrographolide protects against LPS-induced acute lung injury by inactivation of NF-κB.

BACKGROUND: Nuclear factor-κB (NF-κB) is a central transcriptional factor and a pleiotropic regulator of many genes involved in acute lung injury. Andrographolide is found in the plant of Andrographis paniculata and widely used in Traditional Chinese Medicine, exhibiting potently anti-inflammatory property by inhibiting NF-κB activity. The purpose of our investigation was designed to reveal the effect of andrographolide on various aspects of LPS induced inflammation in vivo and in vitro. METHODS AND RESULTS: In vivo, BALB/C mice were subjected to LPS injection with or without andrographolide treatments to induce ALI model. In vitro, MLE-12 cells were stimulated with LPS in the presence and absence of andrographolide. In vivo, pulmonary inflammation, pulmonary edema, ultrastructure changes of type II alveolar epithelial cells, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6 and IL-1ß in BALF, along with the expression of VCAM-1 and VEGF were dose-dependently attenuated by andrographolide. Meanwhile, in vitro, the expression of VCAM-1 and VEGF was also reduced by andrographolide. Moreover, our data showed that andrographolide significantly inhibited the ratios of phospho-IKKß/total IKKß, phospho-IκBα/total IκBα and phospho-NF-κB p65/total NF-κB p65, and NF-κB p65 DNA binding activities, both in vivo and in vitro. CONCLUSIONS: These results indicate that andrographolide dose-dependently suppressed the severity of LPS-induced ALI, more likely by virtue of andrographolide-mediated NF-κB inhibition at the level of IKKß activation. These results suggest andrographolide may be considered as an effective and safe drug for the potential treatment of ALI.

Enhanced immune response induced by a potential influenza A vaccine based on branched M2e polypeptides linked to tuftsin.

Vaccination is the most effective means for preventing influenza-associated morbidity and mortality. Since the influenza virus mutates frequently, the virus strains for new vaccine production should be changed according to predicted epidemic strains. The extracellular domain of matrix protein 2 (M2e) is 24 amino acids long, which is highly conserved and therefore a good target for the development of a universal vaccine which may protect against a much wider range of influenza A virus strains. However its low antigenicity and immunogenicity, which are related to its small size, poses a big challenge for vaccine development. Multiple antigen peptide system (MAP) is based on an inert core molecule of radially branching lysine dendrites onto which a number of peptide antigens are anchored. Tuftsin is an immuno-stimulant molecule peptide. Here we developed a novel peptide vaccine by connecting a tuftsin to a branched, four-copy M2e. Not only did this increase the molecular mass, but also potentiate the immunogenicity. Two branched peptides, (M2e)4-tuftsin and (M2e)4-G4(tuftsin was replaced with four glycines), and a M2e monomer were synthesized using standard solid-phase methods. In vitro and in vivo studies were performed to compare their antigenicity and immunogenicity. Experiments in BALB/c mice demonstrated that the branched M2e could induce stronger humoral and cellular immune responses than the M2e monomer, and (M2e)4-tuftsin induced stronger humoral and cellular immune response than (M2e)4-G4. After lethal challenge with influenza virus PR8 strain, up to 80% of the animals in the (M2e)4-tuftsin vaccinated group still survived, in contrast to 44% in the (M2e)4-G4 group and 30% in the M2e monomer group. The combination of branched polypeptides and tuftsin in vaccine design is presented here for the first time, and the results show that the new construct is a promising candidate for a universal vaccine against the influenza A virus.

Chemical constituents of Rauvolfia verticillata / 药学学报

The study on the Rauvolfia verticillata (Lour.) Baill., which belongs to Apocynaceae, was carried out to look for its chemical constituents and pharmacological activity. The isolation and purification were performed by chromatography on silica gel, Sephadex LH-20 and ODS (octadecyl silane) open column. The structures of obtained compounds were elucidated on the basis of physicochemical properties and spectral analysis. Three indole alkaloids and one acridone alkaloid were isolated from chloroform layer extract and identified as ajmalicine B (1), sandwicine (2), raunescine (3) and 7-hydroxynoracronycine (4) separately. Ajmalicine B (1) is a new compound belonging to indole alkaloid. Compound 4 as an acridone alkaloid was a new type compound isolated from Rauvolfia genus for the first time. We also did some biological activity research on the new type compound (4) to explore other pharmacological activities in addition to antihypertensive activity.

[Combination of acupoints based on the theory of qi tonification, blood regulation and strengthening the primary source].

The acupuncture technique of tonifying qi, regulating blood and strengthening the primary source of human life is established on the base of the new pathology of dementia due to dysfunction of sanjiao by Prof. HAN Jing-xian. It is held that Tanzhong (CV 17), Zhongwan (CV 12), Qihai (CV 6), Xuehai (SP 10), Zusanli(ST 36) and Waiguan (TE 5) were the basic points for treatment of dementia. There are 3 characteristics of the point combination. Firstly, emphasis should be put on regulation of the stomach and the spleen so as to promote transportation, transformation and distribution; secondly, monarch, minister, assistant and guide points should be selected on the base of meridians, and more attention should be paid to the entity and connections among organs; and thirdly, treatment should be given according to physiological functions of the viscera.

Combination of acupoints based on the theory of qi tonification, blood regulation and strengthening the primary source / 中国针灸

The acupuncture technique of tonifying qi, regulating blood and strengthening the primary source of human life is established on the base of the new pathology of dementia due to dysfunction of sanjiao by Prof. HAN Jing-xian. It is held that Tanzhong (CV 17), Zhongwan (CV 12), Qihai (CV 6), Xuehai (SP 10), Zusanli(ST 36) and Waiguan (TE 5) were the basic points for treatment of dementia. There are 3 characteristics of the point combination. Firstly, emphasis should be put on regulation of the stomach and the spleen so as to promote transportation, transformation and distribution; secondly, monarch, minister, assistant and guide points should be selected on the base of meridians, and more attention should be paid to the entity and connections among organs; and thirdly, treatment should be given according to physiological functions of the viscera.