Effects of Xixin Decoction on Blood-brain Barrier Permeability and Expressions of P-gp,CB1 and CB2 Proteins in Hippocampal Tissue of SAMP8 mice / 中国中医药信息杂志

Objective To observe the effects of Xixin Decoction on the blood-brain barrier permeability and the expressions of P-glycoprotein(P-gp),cannabinoid receptor 1(CB1)and cannabinoid receptor 2(CB2)in hippocampal tissue of rapidly aging mice(SAMP8);To explore the possible mechanism of Xixin Decoction in the treatment of Alzheimer disease(AD).Methods Totally 60 SAMP8 mice were randomly divided into model group,probiotics group,and Xixin Decoction high-,medium-and low-dosage groups,with 12 mice in each group,another 12 SAMR1 mice were set as control group.The medicated groups received corresponding drugs by gavage for 10 weeks respectively,while the control group and model group were gavaged with equal volume of distilled water.Morris water maze test was used to detect the learning and memory ability of mice,the blood-brain barrier permeability was detected by Evans blue method,the contents of matrix metalloproteinase 9(MMP9),nuclear factor(NF)-κB and tumor necrosis factor-α(TNF-α)in serum were determined by ELISA,the expressions of P-gp,CB1 and CB2 in hippocampal tissue were detected by Western blot,P-gp expression in hippocampal tissue was detected by immunofluorescence staining.Results Compared with the control group,the learning and memory ability of mice in model group significantly decreased,Evans blue exudation in brain tissue significantly increased,the contents of MMP9,TNF-α and NF-κB in serum significantly increased,the expressions of P-gp and CB2 protein significantly decreased,the expression of CB1 protein significantly increased,with statistical significance(P<0.01,P<0.05).Compared with the model group,the learning and memory ability of mice in Xixin Decoction high-dosage group significantly increased,the Evans blue exudation in brain tissue significantly decreased,the contents of MMP9,TNF-α and NF-κB in serum significantly decreased,the protein expressions of P-gp and CB2 significantly increased,and the protein expression of CB1 significantly decreased,with statistical significance(P<0.01,P<0.05).Conclusion Xixin Decoction can improve the spatial learning and memory ability of AD model mice,and its mechanism is related to regulating the permeability of the blood-brain barrier and related protein expression,and inhibiting neuroinflammation.

Study on the toxic mechanism of Mahuang xixin fuzi decoction based on fecal metabolomics / 中国药房

OBJECTIVE To study the toxic mechanism of Mahuang xixin fuzi decoction （MXF） on normal mice. METHODS Totally 48 SPF grade BABL/C mice were randomly divided into blank group， MXF low-dose， medium-dose and high-dose groups， with 12 mice in each group. MXF low-dose， medium-dose and high-dose groups were given drug intragastrically at the dose of 11.262， 33.786， 45.050 g/kg， respectively. Blank group was administered with equal volume of normal saline， once a day， for consecutive 7 d. The body weight， anal temperature and survival rate were recorded， organ index and serum biochemical factors were detected. After the last administration， fecal samples of mice were collected and detected by UHPLC-QE/MS. RESULTS Compared with blank group， the body weight was decreased significantly from the 3rd to the 5th day after administration in MXF medium-dose group， and from the 2nd to the 7th day after administration in MXF high-dose group significantly （P＜0.05）. There was no significant difference in anal temperature among the treatment groups； the average survival rates of MXF medium-dose and high-dose groups were 58.33% and 50.00%， respectively. Compared with blank group， there were significant difference in the indexes of spleen， lung， thymus， adrenal gland and creatine kinase in MXF low-dose， medium-dose and high-dose groups， the testis index in MXF low-dose and high-dose groups， the creatine kinase isoenzyme/creatine kinase ratio in MXF low-dose group， the α-hydroxybutyrate dehydrogenase， lactate dehydrogenase and alkaline phosphatase in MXF medium-dose group， the urine and cystatin C in MXF medium-dose and high-dose groups （P＜0.05）. The fecal metabonomic analysis showed that 19 biomarkers such as phenylpyruvate， L-tyrosine， phosphatidylcholine， glycerol 3-phosphate in MXF low-dose， medium-dose and high-dose groups were significantly different from those in the blank group. CONCLUSIONS When MXF reaches a certain dose， it will have adverse effects on the body weight， multiple organs and serum biochemical indicators of mice， thus showing a certain toxic effect. Its mechanism may be related to disrupting the intestinal flora metabolism， causing inflammatory reaction and immune disorders.

Effects of Xixin Decoction （洗心汤） on the Diversity of Intestinal Flora and Levels of Aβ1-42，LPS，SAA，and ACH in Brain and Intestinal Tissues of Rapidly Aging Model Mice / 中医杂志

ObjectiveTo observe the possible mechanism of Xixin Decoction （洗心汤， XXD） in the prevention and treatment of Alzheimer 's disease（AD）. MethodsFifty rapid aging model mice （SAMP8） were randomly divided into model group， probiotic group， high-， moderate- and low-dose group of XXD， with 10 mice in each group. Another 10 homologous anti-rapid aging mice （SAMR1） were set as control group. After 10 weeks of feeding， the control group and the model group were given 10 ml·kg-1·d-1 of distilled water by gavage， while the probiotic group （0.39 g·kg-1·d-1）， the high-dose group of XXD （5.08 g·kg-1·d-1）， the moderate-dose group of XXD （2.54 g·kg-1·d-1）， and the low-dose group of XXD （1.27 g·kg-1·d-1） were given corresponding drugs or decoctions by gavage， once a day in all groups. After 10 weeks of intragastric administration， Morris water maze was used to detect the spatial learning and memory ability of mice in each group. HE staining was used to observe the pathological changes of hippocampal CA3 region and colon. The levels of β-amyloid 1-42 （Aβ1-42）， lipopolysaccharide （LPS）， serum amyloid A （SAA） and acetylcholine （ACH） in hippocampus and colon were detected by ELISA.The diversity of intestinal flora in mouse feces was detected by 16S rRNA sequencing. ResultsCompared to those in the control group， the levels of Aβ1-42，LPS， SAA increased， while the level of ACH decreased in the model group （P＜0.05 or P＜0.01）. Compared to those in the model group， the escape latency period of the probiotic group was significantly shortened on the 2nd and 5th days， while the escape latency period was shortened， and the residence time in the target platform quadrant increased in the high-dose XXD group during the 2nd to 5th days； the escape latency period was shortened significantly in the moderate-dose XXD group on the 5th day （P＜0.05 or P＜0.01）. Compared to those in the model group， the hippocampal neuron cells in the high- and moderate-dose XXD groups were arranged more closely， with decreased levels of SAA， Aβ1-42 and LPS， increased ACH level， Simpson and Shannon index （P＜0.05 or P＜0.01）； the arrangement of hippocampal neuron cells in the probiotic group and the low-dose XXD group was relatively loose； the proportions of Bacteroidetes and Prevotella were significantly reduced in the probiotic group and the high-dose XXD group， while that of Firmicutes and Lactobacillus significantly increased （P＜0.05 or P＜0.01）. Compared to those in the probiotic group and the high-dose XXD group， the number of goblet cells in the moderate-dose XXD group decreased， and the number of glands in the low-dose XXD group decreased with atrophy. The high-dose XXD group had decreased Aβ1-42 level in the hippocampus， increased ACH level in thehippocampus and colon tissue， and decreased SAA in the colon tissue than the moderate- and low-dose XXD groups （P＜0.05 or P＜0.01）； moreover， the SAA level in the hippocampus was significantly higher in the low-dose XXD group than the high- and moderate-dose groups （P＜0.01）. ConclusionXXD can improve the spatial learning and memory ability of SAMP8， reduce the production and deposition of LPS， SAA and Aβ1-42 in brain and intestine， and increase the content of ACH. The mechanism of its prevention and treatment of AD maybe related to regulating intestinal microecology， affecting flora diversity and improving inflammatory response.

Xixin Decoction improves learning and memory ability of SAMP8 by enhancing neuroprotective effect and inhibiting neuroinflammation / 中国中药杂志

This study aimed to explore the possible effect of Xixin Decoction(XXD) on the learning and memory ability of Alzheimer's disease(AD) model senescence-accelerated mouse-prone 8(SAMP8) and the related mechanism in enhancing neuroprotective effect and reducing neuroinflammation. Forty SAMP8 were randomly divided into a model group(10 mL·kg~(-1)·d~(-1)), a probiotics group(0.39 g·kg~(-1)·d~(-1)), a high-dose group of XXD granules(H-XXD, 5.07 g·kg~(-1)·d~(-1)), a medium-dose group of XXD granules(M-XXD, 2.535 g·kg~(-1)·d~(-1)), and a low-dose group of XXD granules(L-XXD, 1.267 5 g·kg~(-1)·d~(-1)). Eight senescence-accelerated mouse-resistant 1(SAMR1) of the same age and strain were assigned to the control group(10 mL·kg~(-1)·d~(-1)). After ten weeks of intragastric administration, the Morris water maze was used to test the changes in spatial learning and memory ability of mice after treatment. Meanwhile, immunofluorescence staining was used to detect the positive expression of receptor for advanced glycation end products(AGER), Toll-like receptor 1(TLR1), and Toll-like receptor 2(TLR2) in the hippocampal CA1 region of mice. Western blot was employed to test the protein expression levels of silencing information regulator 2 related enzyme 1(SIRT1), AGER, TLR1, and TLR2 in the hippocampus of mice. Enzyme linked immunosorbent assay(ELISA) was applied to assess the levels of Aβ_(1-42) in the hippocampus of mice and the levels of nuclear factor κB p65(NF-κB p65), NOD-like receptor protein 3(NLRP3), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) in the serum and hippocampus of mice. Compared with the model group, XXD significantly improved the spatial learning and memory ability of SAMP8, increased the expression of neuroprotective factors in the hippocampus, decreased the levels of neuroinflammatory factors, and inhibited the expression of Aβ_(1-42). In particular, H-XXD significantly increased the expression of SIRT1 in the hippocampus of mice, reduced the expression levels of NF-κB p65, NLRP3, TNF-α, and IL-1β in the serum and hippocampus of mice, and decreased the expression of AGER, TLR1, and TLR2 in the hippocampus of mice(P<0.05 or P<0.01). XXD may improve the spatial learning and memory ability of AD model SAMP8 by enhancing the neuroprotective effect and inhibiting neuroinflammation.

Clinical Effect of Mahuang Xixin Fuzitang Combined with Acupuncture and Moxibustion in Treatment of Localized Scleroderma / 中国实验方剂学杂志

ObjectiveTo observe the clinical effect of Mahuang Xixin Fuzitang combined with acupuncture and moxibustion in the treatment of localized scleroderma. MethodA total of 95 patients with localized scleroderma treated in Wuhan No. 1 Hospital from September 2019 to October 2021 were assigned into a control group （47 patients） and an observation group （48 patients） by random number table method. The control group was treated with Centella triterpenes tablets and heparin sodium cream， and the observation group was additionally treated with Mahuang Xixin Fuzitang combined with acupuncture and moxibustion. Both groups were treated for 8 weeks， and the clinical effect was compared between groups. The traditional Chinese medicine（TCM） syndrome score （local skin sclerosis， loss of skin texture， darkening of skin pigment， scaly dry skin， etc.）， serum levels of soluble interleukin-2 receptor （sIL-2R） and tumor necrosis factor-alpha （TNF-α）， erythrocyte sedimentation rate （ESR）， and eosinophil count （EO） were compared between before and after treatment as well as between groups. Additionally， the adverse reactions were recorded. ResultThe observation group had higher total effective rate than the control group ［95.83% （46/48） vs. 82.98% （39/47）， χ2=4.166 4， P<0.05］. Before treatment， the TCM syndrome score， sIL-2R， TNF-α， ESR， and EO showed no significant differences between the two groups. The 8 weeks of treatment improved the TCM syndrome score， sIL-2R， TNF-α， ESR， and EO. Moreover， the observation group was superior to the control group in these indicators （P<0.05）. During the treatment， the observation group showed 1 case of abnormal liver function and 1 case of nausea and vomiting， and the control group had 1 case of nausea and vomiting， 1 case of abnormal renal function， and 1 case of abnormal liver function. The total adverse reactions of the observation group （4.17%） and the control group （6.38%） had no significant difference （χ2=0.233 9， P=0.062 86）. ConclusionMahuang Xixin Fuzitang combined with acupuncture and moxibustion is safe and effective in the treatment of localized scleroderma.

Clinical Effect of Mahuang Xixin Fuzitang Combined with Acupuncture and Moxibustion in Treatment of Localized Scleroderma / 中国实验方剂学杂志

ObjectiveTo observe the clinical effect of Mahuang Xixin Fuzitang combined with acupuncture and moxibustion in the treatment of localized scleroderma. MethodA total of 95 patients with localized scleroderma treated in Wuhan No. 1 Hospital from September 2019 to October 2021 were assigned into a control group （47 patients） and an observation group （48 patients） by random number table method. The control group was treated with Centella triterpenes tablets and heparin sodium cream， and the observation group was additionally treated with Mahuang Xixin Fuzitang combined with acupuncture and moxibustion. Both groups were treated for 8 weeks， and the clinical effect was compared between groups. The traditional Chinese medicine（TCM） syndrome score （local skin sclerosis， loss of skin texture， darkening of skin pigment， scaly dry skin， etc.）， serum levels of soluble interleukin-2 receptor （sIL-2R） and tumor necrosis factor-alpha （TNF-α）， erythrocyte sedimentation rate （ESR）， and eosinophil count （EO） were compared between before and after treatment as well as between groups. Additionally， the adverse reactions were recorded. ResultThe observation group had higher total effective rate than the control group ［95.83% （46/48） vs. 82.98% （39/47）， χ2=4.166 4， P<0.05］. Before treatment， the TCM syndrome score， sIL-2R， TNF-α， ESR， and EO showed no significant differences between the two groups. The 8 weeks of treatment improved the TCM syndrome score， sIL-2R， TNF-α， ESR， and EO. Moreover， the observation group was superior to the control group in these indicators （P<0.05）. During the treatment， the observation group showed 1 case of abnormal liver function and 1 case of nausea and vomiting， and the control group had 1 case of nausea and vomiting， 1 case of abnormal renal function， and 1 case of abnormal liver function. The total adverse reactions of the observation group （4.17%） and the control group （6.38%） had no significant difference （χ2=0.233 9， P=0.062 86）. ConclusionMahuang Xixin Fuzitang combined with acupuncture and moxibustion is safe and effective in the treatment of localized scleroderma.

Effects of Mahuang Xixin Fuzi Decoction on TLRs Response and Cyt-CO-mediated Apoptosis Regulation in Mice with Influenza Disease of Kidney-yang Deficiency / 中国药房

OBJECTIVE：To study the effects of Mahuang xixin fuzi decoction on Toll-like receptors （TLRs）response and cytochrome C oxidase （Cyt-CO）-mediated apoptosis regulation in mice with influenza disease of kidney-yang deficiency. METHODS：Totally 48 male Balb/c mice were randomly divided into normal group （n＝12）and modeling group （n＝36）. The modeling group was intraperitoneally injected with estradiol benzoate solution （8 mg/kg）and intranasally injected with influenza virus H 1N1（20 μL/mice）to establish the influenza disease compound model of kidney-yang deficiency. After modeling ，the mice were randomly divided into model group ，positive drug group （Oseltamivir phosphate capsules ，0.195 g/kg），Mahuang xixin fuzi decoction group （1.802 g/kg，by crude dru g），with 12 mice in each group. Each group was given relevant medicine intragastrically，normal group and model group were given， corresponding volume of normal saline intragastrically 20 mL/kg，once a day ，for consecutive 6 days. During admi-nistration，body weight and anal temperature of mice were mail：xsy407861520@163.com measured daily ；the percentage of initial body weight was calculated. After last medication ，the organ （spleen，thymus and lung ）indexes were calculated ；the pathological changes of lung tissue were observed. The viral load of influenza A virus H 1N1 in lung tissue was detected （reflected by M gene mRNA expression）；mRNA expressions of TLR3，TLR7，myeloid differentiation factor （MyD88）and Caspase- 3 in cardiac tissue as well as the activity of Cyt-CO and the content of cytochrome C （Cyt-C）were also determined. RESULTS ：Compared with normal group，initial body weight percentage and anal temperature of the model group continued to decrease （P＜0.05）；the spleen and thymus indexes were decreased significantly （P＜0.05），while lung index was increased significantly （P＜0.05）；the lung tissue lesions were serious. Viral load in lung tissue ，mRNA expressions of TLR 3，TLR7，MyD88 and Caspase- 3 in cardiac tissue as well as the content of Cyt-C were increased significantly （P＜0.05 or P＜0.01），while the activity of Cyt-CO in cardiac tissue was significantly decreased （P＜0.01）. Compared with model group ，initial body weight percentage and anal temperature of mice in Mahuang xixin fuzi decoction group showed an increasing trend from the fourth day of administration （P＜0.05 or P＜0.01）. The spleen and thymus indexes were increased significantly （P＜0.05），while the lung index was significantly decreased （P＜0.05）；the pathological injury of lung tissue was significantly improved ；viral load in lung tissue ，mRNA expressions of TLR 3 and Caspase- 3 as well as the content of Cyt-C in cardiac tissue were decreased significantly （P＜0.05 or P＜0.01），while the activity of Cyt-CO was increased significantly in cardiac tissue （P＜0.01）. CONCLUSIONS ：Mahuang xixin fuzi decoction can improve influenza disease of kidney-yang deficiency in mice ，the effect may related to inhibit TLRs response and apoptosis regulation pathway mediated by Cyt-CO.

Protective effect of Asarum polysaccharide on H1N1 influenza virus infection and expression of inflammatory factors / 中国中药杂志

In this paper, Asarum polysaccharides(AP) were extracted, and its composition was analyzed to study the activity against H1 N1 influenza virus in vitro and its intervention effect on mice with kidney Yang deficiency syndrome. AP was prepared by the strategy of water extraction and alcohol precipitation, the content was determined, and its monosaccharide composition was analyzed. The cell Real-time monitoring system and Reed-Muench model were adopted to evaluate the antiviral activity of AP in vitro. And the mouse model of kidney Yang deficiency syndrome was established in vivo to compare the efficacy of Mahuang Xixin Fuzi Decoction(MXF) and AP. MXF group and AP group were treated with clinical equivalent doses of 1.8 g·kg~(-1)·d~(-1) and 0.077 g·kg~(-1)·d~(-1) respectively, once a day for 6 consecutive days. Real-time PCR was used to detect the relative expression of M gene of H1 N1 influenza virus and cytokines in lung tissue. The content of AP in Asarum was 25.22%, and the protein content was 0.8%. And the monosaccharide composition was identified as L-rhamnose, D-arabinose, D-xylose, D-glucose, D-galactose and D-mannose. TI values of Tamiflu, MXF and AP were 30.00, 8.06 and 10.33, respectively. Three different doses of AP could significantly reduce the concentration of virus in supernatant. Compared with the model mice, lung indexes of MXF group and AP group decreased significantly(P<0.05), and the relative expression of M gene decreased significantly(P<0.05). The relative expressions of IL-10 and IFN-γ were up-regulated to varying degrees, while the relative gene expressions of IL-1β, IL-6 and MCP-1 were down-regulated to different degrees. In addition, AP could significantly enhance the expression of TNF-α(P<0.01). AP had a good anti-influenza virus activity in vitro, and could protect mice with kidney Yang deficiency syndrome by reducing the viral load in lung tissue, decreasing inflammation damage in lung tissue, and regulating the expression of inflammatory cytokines. Compared with the prescription of MXF, AP had a better antiviral activity.

Effect of Wenyang Huashi Prescription on Inflammatory Factors and Immune Function of Patients After Allergic Fungal Rhinosinusitis / 中国实验方剂学杂志

Objective::To assess the efficacy of Wenyang Huashi prescription on rehabilitation of patients after allergic fungal rhinosinusitis (AFRS) operation, and its effect on inflammatory factors and immune function. Method::One hundred and forty-four patients were randomly divided into control group and observation group by random number table, with 72 cases in each group. Patients in control group was treated with Messerklinger to remove lesions completely, and got anti-infective therapy for three days, prednisone acetate tablets, 10 mg/time, 2 times/days, fluticasone propionate inhaled aerosol for a continued 4 weeks, 2 sprays/time, 1 time/day, itraconazole capsules at the first, fifth and ninth week after treatment (one course of treatment was 7 days), 0.2 g/time, 1 time/day. In addition to the therapy of meloxicam tablets, patients in observation group were also given local rinsing and oral administration of Wenyang Huashi prescription. The courses of treatment of both groups were 12 weeks. Before the operation and at the fourth and 12th week after the operation, subjective conditions were assessed. And before the operation and at the 12th, 24th and 48th week after the operation, Lund-Kennedy detected by endoscopic sinus surgery and nasal and paranasal sinus outcomes test-20 (SNOT-20) were scored. And the relapse was recorded during 48 weeks after the operation. And levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1bet (IL-1bet), nuclear factor kappa B (NF-kappa B), intercellular adhesion molecule in peripheral blood-1 (ICAM-1), T lymphocyte subsets (CD3+, CD4+, CD8+ and CD4+ /CD8+) were detected. Result::By rank sum test, the clinical efficacy in observation group was better than that in control group (Z=2.016, P<0.05). At the fourth and 12th week after the operation, scores of nasal obstruction, dizziness, runny nose and dysosmia in observation group were lower than those in control group (P<0.01). And scores of lund-kennedy and SNOT-20 were lower than those in control group (P<0.01). And levels of TNF-α, IL-1β, NF-κB and ICAM-1 were lower than those in control group (P<0.01). After treatment, levels of CD3+, CD4+ /CD8+ and CD4+ were higher than those in control group, and level of CD8+ was lower than that in control group (P<0.05). During the one-year follow-up, the relapse rate in observation group was 7.81%(5/64), which was lower than 22.58%(14/62) in control group (χ2=5.363, P<0.05). Conclusion::Wenyang Huashi prescription can improve short-term and long-term symptoms, improve the comprehensive curative effect, the quality of life and the immune function of the body, alleviate inflammatory injury, reduce the recurrence rate and improve the prognosis, and so is worth further study and use.

Efficacy-toxicity Evaluation of Mahuang Xixin Fuzi Decoction on Mice with Kidney-yang Deficiency / 中国药学杂志

OBJECTIVE: To study the pharmacodynamic effects of Mahuang Xixin Fuzi Decoction (MXF) on mice with kidney-yang deficiency, its toxic effects on normal mice and effect-toxic mechanism. METHODS: BABL/C male mice were randomly divided into normal groups; normal groups with low, medium and high toxicity; kidney Yang deficiency model group. The low, medium and high dose groups were treated with infected Influenza virus of kidney-yang deficiency. After continuous gavage for 6 days, the body weight anal temperature and other pharmacological indicators were recorded, and the general signs, biochemical indicators and inflammatory factors of the mice were detected. RESULTS: Compared with the normal group, the biochemical parameters of the kidney yang deficiency model group, which means the creatine kinase (CK), creatine kinase-isoenzyme (CK-MB), alpha-hydroxybutyrate dehydrogenase (α-HBDH), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP) and urea (urea) were significantly increased (P<0.05), inflammatory factors interleukin-6 (IL-6), monocyte deproteinization protein (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-10 (IL- 10), interferon-γ (INF-γ) and interleukin 12 (IL-12p70) increased significantly (P<0.05). After administration, the levels of biochemical markers such as CK, ALT and urea in each administration groups were slightly reduced compared with the model group. The levels of inflammatory factors such as IL-6, IL-10 and IFN-γ in each administration groups showed different degrees of callback compared with the model group. In the toxicity study, the biochemical indicators of CK, urea, and cysteine (CYS-C) in each drug-administered group were significantly higher than those in the normal group (P<0.05), and the inflammatory factor interleukin-10 (IL-10) increased significantly, and the content of interleukin-12 (IL-12p70) decreased significantly (P<0.05). CONCLUSION: After treatment with MXF, the above biochemical indicators of mice with kidney yang deficiency and external sensation have different degrees of callback. MXF can achieve therapeutic effects by regulating IL-6, IL-10, IFN-γ, MCP-1, TNF-α and other factors on the body′s inflammatory response. While normal mice give different doses of MXF, the heart, liver and kidney function are dysfunctional, the balance of immune response of the body are broken through cell transfer, thus making normal mouse developed an inflammatory response.

Effects of Chinese herbal medicine of tonifying spleen and stomach on learning and memory ability and PKA/ERK/p-CREB pathway in hippocampus of SAMP8 mice / 中草药

Objective: To study the effects of prescriptions including Ginseng Decoction, Xixin Decoction, and Dabuyuan Decoction for tonifying spleen and stomach on learning and memory ability and PKA/ERK/p-CREB pathway in hippocampus of SAMP8 mice, and explore the mechanism in the prevention and treatment of Alzheimer's disease (AD). Methods: Three-month-old SAMP8 mice were randomly divided into model group, Donepezil Hydrochloride group, prescription group of Tonifying Spleen and Stomach Yuanqi Prescription (Ginseng, Xixin Decoction, and Dabuyuan Decoction). Moreover, three-month-old SAMR1 mice were recruited as a normal control group, six groups in total. Related indices were detected after 10 weeks continuous gastrogavage. The spatial learning-memory deficit of mice was detected by Morris water maze test. The expression levels of PKA protein in hippocampal region of mice were detected by immunohistochemistry, and the expression levels of ERK and p-CREB protein in hippocampal region of mice were detected by immunofluorescence. The protein expression levels of PKA, ERK, and p-CREB in hippocampus were detected by Western blotting. Results: Compared with the model group, the escape latency of the prescription group of tonifying spleen and stomach was decreased (P < 0.05, P < 0.01), while the swimming time and the times of crossing the platform in the target quadrant were increased (P < 0.01). Results of immunohistochemistry showed that the protein expression of PKA was significantly increased and the expression of ERK and p-CREB in hippocampal region was significantly increased (P < 0.05, P < 0.01). The results of Western blotting were consistent with those of immunohistochemistry and immunofluorescence (P < 0.05, P < 0.01). Conclusion: The Tonifying Spleen and Stomach Yuanqi Prescription showed obvious improvement on the spatial learning-memory deficit in SAMP8 mice, which might be associated with affecting the PKA/ERK/p-CREB pathway in hippocampal region.

Exploration of Mahuang Fuzi Xixin Decoction formula syndromes based on severe cases of critical care and its application for nosocomial infection in critical care medicine including hyperpyrexia after tracheotomy and severe pain accompanied by acute myocardial infarction and diabetic peripheral neuropathy / 中国中药杂志

Mahuang Fuzi Xixin Decoction recorded in Treatise on Febrile Diseases by Zhang Zhongjing in the Han Dynasty have been widely used in treating Yang deficiency and exogenous wind-cold syndrome by traditional Chinese medicine physicians for thousands of years. The indications of Mahuang Fuzi Xixin Decoction include bradyarrhythmia,sinus bradycardia,sick sinus node syndrome,senile exogenous,asthmatic cold,rhinitis,bronchial asthma,optic neuritis,optic atrophy,sudden blindness,sudden onset of cough,laryngeal obstruction,migraine,joint pain,low back pain,insomnia,shock,heart failure,renal failure,accompanied by fever or nosocomial infection,and hyperpyrexia after tracheotomy; dark complexion,chills,cold limbs,listlessness,fatigue,insomnia,lack of thirst,liking hot drinks,slightly swollen limbs or whole body,pale fat tongue,greasy fur,and deep pulse. Mahuang Fuzi Xixin Decoction is a potential drug for Shaoyin disease complicated with fever and pain. Tracheal intubation is an artificial ephedrine syndrome. It is necessary to distinguish Yin and Yang syndrome in treating hyperpyrexia after tracheotomy. However,it belongs to Yin syndrome,which could be treated by Mahuang Fuzi Xixin Decoction. Mahuang Fuzi Xixin Decoction is effective in the treatment of sick sinus syndrome,second degree atrioventricular block and third degree atrioventricular block. It can significantly alleviate symptoms,improve heart rate,and heart rhythm in a short period of time. However,after one year of drug withdrawal,the diseases may recur,indicating that Mahuang Fuzi Xixin Decoction may not improve the long-term prognosis of slow arrhythmia. Mahuang Fuzi Xixin Decoction is often used for fever or nosocomial infection in critical care medicine. In the treatment of critical care medicine complicated with high fever,Mahuang Fuzi Xixin Decoction is often taken continuously by stomach tube.

Effectsofcerebrospinalfluidcontainingdrugsfortonifyingspleenandstomachonactivityandmigrationofrathippocampalneuralstemcells / 中草药

To study the effects of prescriptions including Ginseng, DabuyuanDecoction, and XixinDecoctionfor tonifying spleen and stomach on the activity and migration ability of neural stem/progenitor cells (NSPCs) induced by β-amyloid protein (β-amyloid),and investigate the effect of hippocampal neuronal repair and regeneration. Methods NSPCs were isolated from fetal rats of 14-16 d gestation and identified. It was randomly divided into seven groups: blank group, blank group treated with Aβ1-42, control group of normal cerebrospinal fluid, control group of Aricept, prescription of Tonifying Spleen and Stomach and Yuanqi (Ginseng, Dabu Yuan Decoction, and XixinDecoction) Protection groups. The third generation of neural stem cells were treated with 25 μmol/L Aβ1-42 for 48h. The activity of NSPCs in each group was detected bytranswell assay and CCK-8 assay and themigration was detected by scratch test. The content of reactive oxygen species (Ros) in the cells was detected by flow cytometry. ResultsBy immunofluorescence staining, NSPCs specific protein Sox2 staining was positive. The CCK-8 detection results showed that the activity of NSPCs in hippocampus was significantly increased in the groups of Tonifying Spleen and Stomach YuanqiPrescription (P< 0.01); The results of Transwell experiment and scratch test showed that the migration ability of NSPCs was significantly increased (P< 0.05, 0.01). The flow cytometryshowed that the content of ROS in the NSPCs of spleen and stomach prescription groups decreased significantly (P< 0.01). Conclusion The prescriptionsfor invigorating spleen and stomach promoted the activity and migration of NSPCs in rat hippocampal neural stem cells. The oxidative stress induced by Aβcan be antagonized and its active ingredients can easily penetrate the blood-brain barrier to exerta stronger neuroprotective effect.

Effects of different decocting methods on quality of Mahuang Xixin Fuzi decoction / 中国中药杂志

To compare the quality difference between Mahuang Xixin Fuzi decoction(MXF) prepared by traditional decocting method and that prepared by two commonly used decocting methods, and explore the scientific nature of the traditional decocting method. By taking effect-toxic components in MXF as the research object, this article investigated these three different decocting methods from the quantitative determination of effect-toxic components in MXF. By using multivariate statistical analysis methods, three characteristic constituents were identified as kakoul, mesaconitine (MA) and hypaconitine (HA) respectively. As compared with two commonly used decocting methods, MXF decoction prepared by traditional decocting method had the shortest boiling time, but with the lowest dissolution rates of MA and AC and the higher dissolution rates of mono-ester aconitum alkaloids. In addition, the traditional decocting method increased the dissolution of ephedra alkaloid and accelerated the hydrolysis of diester diterpenoid alkaloids. There were differences in the content of effect-toxic components in MXF decoctions prepared by three different decocting methods, which can provide a reference for use of the classical prescriptions.

Action mechanism of Mahuang Xixin Fuzi decoction for mice with influenza based on metabolomics information / 中国中药杂志

This study aimed to analyze the endogenous metabolite changes in the serum of mice infected with H1N1 virus after intervention by Mahuang-Xixin-Fuzi decoction (MXF) based on metabolomics method, investigate potential biomarkers and related metabolic pathways, and explore the therapeutic mechanism of MXF through metabolomics technology. Thirty-six Kunming (KM) mice were randomly divided into three groups: normal group, model group and MXF group. Influenza virus H1N1 was used by nasal drip to establish influenza mice model. The mice in MXF group were orally administrated with MXF for 6 consecutive days after inoculation, and the other two groups were given with equal volume of saline solution in the same way. Body weight, rectal temperature, morbidity and mortality were recorded daily. Serum samples were collected 24 hours after the last administration for HPLC-TOF-MS analysis. The results showed that as compared with the normal group, the body weight and rectal temperature were decreased in model group, and their lung index and mortality rate were significantly increased (P<0.05); MXF had good therapeutic effects on the abnormity of body weight, rectal temperature, lung index and high mortality rate of mice infected with H1N1 virus. The original data collected from the serum samples were analyzed with R language, MPP, SIMCA-P and other software, and significant changes were found in 14 kinds of endogenous substances from mice serum (P<0.05). As compared with model group, the potential metabolic markers in MXF group recovered to normal levels to a certain degree after being intervened by MXF. Further analysis with MetPA data platform showed that, the pathways involved in 14 metabolites included glucose metabolism, arachidonic acid metabolism, glycerophospholipids and sphingolipids metabolism etc. The metabolomics study and pharmacological experiment showed that MXF might play a role of efficacy by improving glucose metabolism, regulating arachidonic acid metabolism, glycerophospholipid and sphingolipid metabolic pathways.

Simultaneous determination of ten constituents in Dengzhan Xixin Injection by HPLC / 中成药

AIM To establish an HPLC method for the simultaneous content determination of 5-caffeoylquinic acid,chlorogenic acid,4-caffeoylquinic acid,caffeic acid,1,3-dicaffeoylquinic acid,scutellarin,isochlorogenic acid B,3,5-dicaffeoylquinic acid,apigenin-7-O-glucronide and 4,5-dicaffeoylquinic acid in Dengzhan Xixin Injection [Erigeron breviscapus (Vaniot.) Hand.-Mazz].METHODS The analysis of aqueous extract of this drug was performed on a 30 ℃ thermostatic Inertsil(R) ODS-3 column (250 mm × 4.6 mm,5 μm),with the mobile phase comprising of 0.4％ phosphoric acid-acetonitrile flowing at 0.9 mL/min in a gradient elution manner,and the detection wavelength was set at 327 nm.RESULTS Ten constituents showed good linear relationships within their own ranges (r≥0.999 0),whose average recoveries were 94.11％-100.64％ with the RSDs of 1.12％-2.77％.CONCLUSION This simple,accurate and reproducible method can be used for the quality control of Dengzhan Xixin Injection.

Study on the Effective Component Formula of Mahuang Fuzi Xixin Decoction for Anti-allergic Rhinitis / 中国药房

OBJECTIVE:To study the new formula of effective components in TCM for anti-allergic rhinitis (AR),and pro-vide reference for developing TCM preparations for anti-AR. METHODS:Using pseudoephedrine hydrochloride (0-13.5 mg/kg), total alkaloid extracts of Aconitum carmichaelii (0-21.18 mg/kg),volatile oil of asari radix (0-0.0092 mL/kg) in Mahuang Fuzi Xixin decoction as formula objects,uniform design method was used for drug grouping,and multiple regression analysis was con-ducted for the behavioral scores before and after administration,contents of histamine and immunoglobulin E (IgE) in serum of AR guinea pigs to obtain the best formula. Using Xinqin granule,Loratadine tablet,Mahuang Fuzi Xixin decoction respectively as positive control,efficacy of the best formula was verified from aspects of behavioral scores before and after administration,con-tents of histamine and IgE of AR guinea pigs. And the safety of the best formula was preliminarily observed through acute toxicity test in mice. RESULTS:The best formula was as follow as pseudoephedrine hydrochloride 11.25 mg/kg,total alkaloid extracts of A. carmichaelii 21.18 mg/kg,volatile oil of asari radix 0.0045 mL/kg. Compared with each positive drug group,there were no sig-nificant differences in behavioral scores before and after administration in the best formula group(P>0.05). While compared with Xinqin granule group and Mahuang Fuzi Xixin decoction group,histamine content in serum in the best formula group was signifi-cantly reduced (P<0.05);compared with Xinqin granule and Loratadine tablet group,IgE content in serum in the best formula group was significant decreased (P<0.05). Median lethal dose of the best formula was 1822.04 mg/kg. CONCLUSIONS:The screened best formula shows better effect than Xinqin granule and Mahuang Fuzi Xixin decoction in terms of reducing histamine content in serum,better than Loratadine tablet and Xinqin granule in terms of reducing IgE content in serum,with good safety, which indicates the feasibility of TCM effective component formula to a certain degree.

Effects of Mahuang-Xixin-Fuzi decoction on plasma levels of interlcukin-6 and tumor necrosis factor-α in allergic rhinitis in rats / 国际中医中药杂志

Objective To investigate the effects of Mahuang-Xixin-Fuzi decoction on the plasma levels of interlcukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in allergic rhinitis in rats. Methods Thirty-two Wistar rats were randomly divided into a control group, a model group, a chlorpheniramine group, and a Mahuang-Xixin-Fuzi decoction group, with 8 rats in each group. Allergic rhinitis was induced by ovalbumin sensitization. Rats in the chlorpheniramine and Mahuang-Xixin-Fuzi decoction groups received intragastric administration of 0.01%chlorpheniramine and Mahuang-Xixin-Fuzi decoction 0.4 g (twice daily for 21 days), respectively. The plasma levels of IL-6 and TNF-αwere measured with enzyme-linked immunosorbent assay. Results The frequencies of sneezing (2.4 ± 0.9/30 min vs.18.5 ± 3.6/30 min) and nasal rubbing (4.2 ± 1.5/30 min vs. 31.2 ± 3.7/30 min) in the Mahuang-Xixin-Fuzi decoction group were significantly lower than those in the model group (all P<0.05). The plasma levels of IL-6 (153.00 ± 13.87 pg/ml vs. 230.38 ± 33.92 pg/ml) and TNF-α(21.25 ± 4.62 pg/ml vs. 56.38 ± 7.93 pg/ml) in the Mahuang-Xixin-Fuzi decoction group were significantly lower than those in the model group (all P<0.05). Conclusions Mahuang-Xixin-Fuzi decoction can reduce the plasma levels of IL-6 and TNF-α, and alleviate symptoms in allergic rhinitis in rats.

Effect of Xixin Decoction Granule on Tau protein toxicity in brain of rats with sporadic Alzheimer's disease / 中草药

Objective: To establish sporadic Alzheimer's disease (SAD) rat model, to investigate the effects of Xixin Decoction Granule (XDG) on the phosphorylation of Thr231 and Ser422 sites as the important promoters of Tau protein toxicity in the brain of SAD rat, and to explore the possible mechanism of XDG on the prevention and treatment of SAD. Methods: The SPF male SD rats were randomly divided into Sham (S), model (M), donepezil (D, positive control), low-, mid-, and high-dose XDG (LX, MX, and HX, 7.61, 15.21, and 30.42 g/kg) groups, with ig administration once daily for two months. The immunohistochemistry and Western blotting were used to detect the phosphorylation levels of Thr231 and Ser422 sites in Tau protein in brain of rats with SAD. Results: Compared with M group, XDG could significantly decrease the expression of Thr231 and Ser422 sites in the hippocampus of SAD rats (P 0.05). Conclusion: The results suggest that XDG could inhibit the hyperphosphorylation of key sites in site protein and Tau toxicity, so as to prevent SAD pathological progress.

Influences of Dengzhan Xixin injection(灯盏细辛注射液) on vascular endothelial function in patients with(acute) cerebral infarction / 中国中西医结合急救杂志

Objective: To observe the influences of Dengzhan Xixin injection(灯盏细辛注射液) on(vascular) endothelial function and neurological deficit extent in patients with acute cerebral infarction.(Methods): Eightyseven patients with mild to moderate acute cerebral infarction were randomly(divided) into Dengzhan Xixin injection treatment group(treatment group,42 cases) and control group(45 cases) by the random method of envelope and card.The patients in both groups were treated with the same basic therapy.The treatment group was treated with 40 ml of Dengzhan Xixin injection,and the control group was treated with 16 ml of salvia miltiorrhiza injection.The therapeutic course was 14 days in both groups and 2 courses were applied.The changes of circulating endothelial cell count(CEC),the levels of endothelin(ET) and(calcitonin) generelated peptide(CGRP) in plasma as well as neurological deficit were measured and(compared).Results: The plasma CEC,ET in treatment group((8.0?3.6)cells/0.9 ?l and(52.92?(4.52)ng/L)) were significantly lower than those in control group((10.2?3.3)cells/0.9 ?l and(60.12?(3.23)ng/L)),but the plasma CGRP was higher than that in the(control) group on 14 th days((65.23?(1.52)ng/L) vs.(60.12?2.14)ng/L).The differences were significant between the two groups(P