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.

Yiyi Fuzi Baijiangsan in Treatment of Ulcerative Colitis： A Review / 中国实验方剂学杂志

Yiyi Fuzi Baijiangsan is scattered from the Essentials from the Golden Cabinet （《金匮要略》） for the treatment of intestinal carbuncles. The whole prescription is composed of Coicis Semen， Aconiti Lateralis Radix Praeparata， and Patrinia scabiosifolia， with the effect of invigorating spleen， warming Yang， clearing heat， removing dampness， and detoxification， which is a commonly used prescription for the clinical treatment of ulcerative colitis （UC）. UC is a chronic nonspecific inflammatory disease with lesions involving the colorectal mucosa， and the etiology is not yet very clear， which is mostly related to genetics， external and intestinal environment， immunity， infection， and other factors. Animal experiments and clinical studies have shown that Yiyi Fuzi Baijiangsan have the advantages of multi-target and multi-faceted treatment of UC. At present， the research mechanism of the treatment of UC is mainly focused on reducing intestinal inflammatory response， anti-colorectal cancer effect， alleviating oxidative stress， repairing the intestinal epithelial cell barrier， improving intestinal flora disorder， inhibiting apoptosis， maintaining intestinal immune balance， etc. Clinically， the combination of modified Yiyi Fuzi Baijiangsan and western medicine has a satisfactory effect， which can significantly improve the relevant clinical symptoms of patients with UC， delay the condition， and improve the quality of life of patients， with the advantages of high safety and small side effects. Its related research provides theoretical support and data support for the clinical prevention and treatment of UC and the follow-up exploration of the mechanism of Yiyi Fuzi Baijiangsan in the treatment of UC， and is also of great significance to the research on the treatment of UC with Chinese medicine. This paper reviewed the prevention and control mechanism of Yiyi Fuzi Baijiangsan in the treatment of UC.

Effect and Mechanism of Yiyi Fuzi Baijiangsan on Apoptosis of Human Colon Cancer HCT116 Cells / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Yiyi Fuzi Baijiangsan （YYFZBJ） on the apoptosis of colon cancer cell line HCT116. MethodYYFZBJ at different concentrations （0.5， 1， 2， 4， 6， 8， 10， 12， 14， 16 g·L-1） was used to intervene in HCT116 cells for 24， 48， 72 h. The cell counting kit-8 （CCK-8） method was used to determine the effect of YYFZBJ on cell proliferation in vitro. The cells were divided into a blank group， a capecitabine group（1.8 g·L-1）， and low-， medium-， and high-dose YYFZBJ groups （6， 10， and 14 g·L-1） and treated for 48 hours. Flow cytometry was used to detect the apoptosis. Hoechst 33342 staining was used to observe the apoptotic morphology of cells. Mitochondrial membrane potential （MMP） was analyzed by a mitochondrial-targeted deep-red fluorescent probe （Mito-Tracker Red CMXRos）. The expression of proteins related to the mitochondrial apoptosis pathway， such as B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cytochrome C （Cyt C）， cysteinyl aspartate-specific protease （Caspase）-9， Caspase-3， cleaved Caspase-9， and cleaved Caspase-3 was detected by Western blot. The mRNA levels of Bcl-2， Bax， Cyt C， Caspase-9， and Caspase-3 were determined by real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， YYFZBJ （8， 10， 12， 14， 16 g·L-1） significantly inhibited the proliferation of HCT116 cells in vitro （P<0.05） in a dose-dependent manner. Compared with the blank group， the medium- and high-dose YYFZBJ groups and the capecitabine group showed increased apoptosis rates of colon cancer cells （P<0.05）. The YYFZBJ groups and the capecitabine group showed reduced number of colon cancer cells with significantly changed cellular morphology and cell apoptosis manifestations， such as strong dark blue fluorescence， nucleus concentration， shrinkage， and fragmentation. With the increase in the mass concentration of YYFZBJ， the blue fluorescence intensity was significantly enhanced. Compared with the blank group， the YYFZBJ groups and the capecitabine group showed reduced MMP in a dose-dependent manner， decreased protein and mRNA levels of Bcl-2， and increased protein expression of Bax， Cyt C， Caspase-9， Caspase-3， cleaved Caspase-9， and cleaved Caspase-3 and mRNA expression of Bax， Cyt C， Caspase-9， and Caspase-3 （P<0.05）. ConclusionYYFZBJ can induce the apoptosis of colon cancer HCT116 cells through the mitochondrial apoptosis pathway.

Study on the mechanism of Yiyi Fuzi powder in the treatment of rheumatoid arthritis based on metabolomics and network pharmacology / 药学学报

In this study, a combination of metabolomics and network pharmacology was used to study the pharmacodynamic substances and mechanism of action of Yiyi Fuzi powder (YYFZ) on rheumatoid arthritis (RA) rats. The animal experiments were conducted in accordance with the requirements of the Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine (approval number: TCM-LAEC2021241). The metabolomic analysis using UPLC-Q-TOF/MS technique identified 22 metabolites, including arachidonic acid, tryptophan, linoleic acid, phenylalanine, as significant biomarkers for the treatment of RA with YYFZ, and they were significantly regressed after YYFZ treatment. The analysis of YYFZ blood components also revealed that 11 blood components, including hypaconitine, benzoylhypaconitine, and deoxyaconitine, may be the components that exert direct pharmacological effects in YYFZ in vivo, and further network pharmacological analysis of blood components obtained that YYFZ may exhibit anti-inflammatory effects through acting on PI3K/Akt signaling pathway, estrogen signaling pathway, vascular endothelial growth factor (VEGF) signaling pathway. The results of this study provide implications for the clinical application of YYFZ.

Research progress in clinical application and pharmacological effect of Yiyi Fuzi Baijiang Powder / 中国中药杂志

Yiyi Fuzi Baijiang Powder(YFBP), originating from Synopsis of the Golden Chamber, is a classic prescription composed of Coicis Semen, Aconiti Lateralis Radix Praeparata, and Patriniae Herba for the treatment of abscesses and pus discharge. This article presented a systematic analysis of the clinical application of YFBP, including the indicated diseases, the number of cases, efficacy, dosage, administration methods, and compatibility with other drugs. The analysis reveals that YFBP has a wide range of clinical applications. It is commonly used, often with modifications or in combination with western medicine, for diseases in the fields of gastroente-rology, gynecology, urology, dermatology, and others. And most of the Traditional Chinese Medicine(TCM) evidence involved in these diseases are damp-heat evudence. The prescription shows rich variations in clinical administration methods, and most of which are the treatment of aqueous decoction of it. The therapeutic effect is also significant, and the total effective rate of clinical treatment is re-latively high. Additionally, this article summarized the pharmacological research on YFBP and found that it possessed various pharmacological effects, including anti-inflammatory, antioxidant, anticancer, and immune-modulating properties. Finally, correlation analysis was conducted on the main diseases, TCM types, prescription doses, pharmacological effects and action targets of YFBP, which to show the relationship between these five aspects in a visual form, reflecting the relationship between its clinical application and modern pharmacological effects. These findings provide a reference basis for further development and research on YFBP.

Mechanism of Fuzi Lizhongwan Improving Injury in Cisplatin-induced CIPN Mice by Regulating MAPK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Fuzi Lizhongwan alleviating the damage of chemotherapy-induced peripheral neuropathy （CIPN） mice caused by cisplatin based on mitogen-activated protein kinase （MAPK） signaling pathway. MethodA total of 40 female KM mice were randomized into blank group （distilled water， ig）， model group （distilled water， ig）， Fuzi Lizhongwan group （3.5 g·kg-1， ig）， and aspirin group （0.026 g·kg-1， ig）. Cisplatin （3 mg·kg-1， ip， 5 days） was used to induce CIPN in mice. Administration began while modeling and lasted 12 days. The general conditions and behaviors of mice were observed. After the last administration， samples were collected. Pathological changes of the soles were observed based on hematoxylin-eosin （HE） staining. Biochemical assay was employed to determine the levels of serum superoxide dismutase （SOD）， hydrogen peroxide （H2O2）， malondialdehyde （MDA）， and nitric oxide （NO）， enzyme-linked immunosorbent assay （ELISA） the content of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and glutathione peroxidase-3 （GPX-3） in kidney tissue， and Western blotting the expression of extracellular signal-regulated kinase1/2 （ERK1/2）， phosphorylated-ERK1/2 （p-ERK1/2）， p38 MAPK， and phosphorylated-p38 MAPK （p-p38 MAPK） in kidney tissue. ResultCompared with the blank group， model group demonstrated obvious pathological damage on the soles， hyperkeratosis of the epidermis with a basketweave pattern， atrophy of stratum spinosum， reduction of cells， and intracellular edema. Compared with the model group， Fuzi Lizhongwan significantly alleviated the pathological damage of the skin tissue of the soles. The model group showed lower body weight， mechanical pain threshold， thermal pain threshold （P<0.01）， and SOD activity （P<0.05）， higher content of H2O2， MDA， and NO （P<0.01）， and higher expression of IL-6， IL-1β， and TNF-α （P<0.01） than the blank group. Fuzi Lizhongwan group demonstrated higher body weight， mechanical pain threshold， thermal pain threshold （P<0.01）， and SOD activity （P<0.05）， lower content of H2O2， MDA， and NO （P<0.05）， and lower expression of IL-6， IL-1β， and TNF-α （P<0.01） than the model group. The expression of ERK1/2， p-ERK1/2， p38 MAPK， and p-p38 MAPK increased significantly （P<0.01） in the model group compared with that in the blank group， while the expression decreased significantly （P<0.01） in the Fuzi Lizhongwan group compared with that in the model group. ConclusionFuzi Lizhongwan can relieve the neurological injury of cisplatin-induced CIPN mice and increase the pain threshold of mice， possibly by regulating the MAPK signaling pathway and inhibiting inflammatory response and oxidative stress.

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 Gancao Fuzi Decoction on osteoarthritis and proteomics of articular cartilage in rats / 中国中药杂志

The rat osteoarthritis model was replicated by injection of sodium iodoacetate into the knee joint cavity, and the effects of Gancao Fuzi Decoction on rat osteoarthritis and the proteome of articular cartilage were investigated. Sixty SD rats weighing 230-250 g were randomly divided into normal group, model group, glucosamine sulfate group, and Gancao Fuzi Decoction high, medium and low dose groups. Osteoarthritis model was induced by intra-articular injection of sodium iodoacetate(3 mg on each leg) in all groups except the normal group. After modeling, each administration group was given intragastric administration for 1 month. During the administration period, joint pain test and joint width measurement were performed every week to observe the autonomous behavior of rats. Enzyme linked immunosorbent assay(ELISA) method was used to detect the contents of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), matrix metalloproteinase-3(MMP-3), and matrix metalloproteinase tissue inhibitor(TIMP-1) in rat joint lavage fluid. Hematoxylin-eosin(HE) staining was used to observe bone and joint morphology. Nano-LC-LTQ-Orbitrap system was used to detect arti-cular cartilage proteins. The results showed that, compared with the model group, Gancao Fuzi Decoction could significantly improve joint pain and joint swelling in osteoarthritis rats, significantly reduce the contents of TNF-α, IL-1β and MMP-3 in the joint cavity la-vage fluid, increase the content of TIMP-1, and relieve inflammatory diseases such as enlarged joint space, rough cartilage edge, different thickness of cartilage layer, and disordered arrangement of chondrocytes. After comparing the proteins between the groups, 273 differential proteins were screened out. KEGG analysis found that the above differential proteins involved 43 signaling pathways such as systemic lupus erythematosus, among which 11 signaling pathways were related to osteoarthritis. The above results indicated that Gancao Fuzi Decoction had a preventive effect on osteoarthritis, and its mechanism of action may be accomplished by regulating the protein expression of osteoarthritis-related signal pathways.

UHPLC-Q-Exactive-Obitriap MS for quantification of ten components in Fuzi Lizhong Decoction / 中草药

Objective: To establish a method for quantifying ten components in Fuzi Lizhong Decoction (FLD). Methods: Ultra high performance liquid chromatography-Q-Exactive Obitriap mass spectrometry was used to detect components under optimized conditions as follows: Hypersil Gold C18 column (50 mm × 2.1 mm, 1.9 μm), column temperature: 30 ℃, mobile phase: methanol (A)-water (B), gradient elution conditions: 0-6 min, 25%-80% A, 6-7 min, 80%-95% A, 7-8 min, 95%-100% A, 8-9 min, 100% A, flow rate: 0.3 mL/min; Ion source: electrospray, scan mode: full scan (positive, negative), scan range: m/z 200-700 (positive), 200-500 (negative), resolution: 17 500, capillary temperature: 300 ℃, spray voltage: +4.0 kV, -3.5 kV, sheath gas flow rate: 35 L/h, S-lens voltage: 50 V. Results: Satisfactory linearity with correlation coefficient (r2) higher than 0.995 was achieved for each compound. The content of benzoyl aconitine, benzoylmesaconine, atractylenolide I, atractylenolide II and lobetyolin scanned under positive mode in FLD was 2.52, 0.11, 0.46, 1.75 and 5.8 μg/mL respectively, and that of emodin, glycyrrhizin, liguiritigenin, 8-gingerol, 10-gingerol scanned under negative mode in FLD was 0.35, 2.52, 0.98, 6.65 and 2.71 μg/mL, respectively. Conclusion: The developed liquid chromatography-mass spectrometry method was fastwith low limit of detection, which could provide methodological basis for quality control of FLD as well as quantification of these compounds.

Fuzi Polysaccharide Inhibits Vascular Smooth Muscle Cell Calcification via Ceramide Signaling / 中山大学学报(医学科学版)

@#【Objective】The aim of this study is to investigate whether Fuzi polysaccharide（FPS）inhibits calcification of vascular smooth muscle cells（VSMC）and its underlying mechanism involving ceramide signaling.【Methods】We used Ox- LDL to induce in vitro model of human VSMC calcification in this study. FPS at different concentrations was used to treat human VSMC. Cell calcification was assessed by alizarin red staining. The mRNA expressions of osteogenic differentiation markers including Msx2，Osterix and BMP2，and contractile marker SMA were analyzed by qRT- PCR. The protein expressions of Msx2 and BMP2 were analyzed by western blot. Cell apoptosis was examined by TUNEL. Additionally，we investigated the effect of FPS on ceramide levels and N- SMase activity in VSMC. 【Results】We found that FPS inhibits Ox- LDL- induced VSMC apoptosis and calcification. Ceramide participates in Ox- LDL- induced apoptosis and calcification of VSMC. FPS reduces N- SMase activity and ceramide levels in Ox- LDL- treated VSMC. Collectively ， reducing N-SMase activity and ceramide levels could become a promising strategy for the treatment of vascular calcification.【Conclusion】We demonstrate that FPS attenuates VSMC calcification via targeting ceramide signaling.

Exploring Mechanism of Modified Fuzi Lizhongtang in Intervening Inflammatory Response of Intestinal Mucosa in Rats with Ulcerative Colitis Based on mTOR/p-S6K1 / 中国实验方剂学杂志

Objectives:To investigate the therapeutic effect and mechanism of modified Fuzi Lizhongtang on ulcerative colitis （UC） model rats. Method:The 72 male SD rats were randomly divided into normal group，model group，sulfasalazine group（0.5 g·kg-1），modified Fuzi Lizhongtang high，medium and low-dose group （23.62，11.81，5.91 g·kg-1）. These rats were used to replicate the UC rat model by 2，4，6-trinitrobenzene sulfonic acid （TNBS）-ethanol composite modeling and treated by gavage for 2 weeks. The general condition of rats in each group was observed. After anesthesia，blood was collected from abdominal aorta and colonic tissue was taken. Semi quantitative evaluation by the colon mucosa damage index （CMDI），the pathological changes of colonic tissue were observed by the hematoxylin and eosin （HE） staining. The contents of serum interleukin-4 （IL-4），IL-6，IL-10 and tumor necrosis factor-α （TNF-α） were detected by enzyme-linked immunosorbent assay （ELISA）. The expressions of mammalian target of rapamycin（mTOR） and phosphorylated ribosomal protein S6 kinase 1 （p-S6K1） in colonic mucosa were detected by immunohistochemistry （IHC） and Western blot. Result:Compared with normal group，the CMDI score of the model group rats was significantly increased （P<0.01）. The contents of IL-4 and IL-10 in serum were significantly decreased，the contents of IL-6 and TNF-α were significantly increased （P<0.01）. The expression levels of mTOR and p-S6K1 in colonic mucosa were up-regulated （P<0.01）. Compared with model group，the CMDI score of the modified Fuzi Lizhongtang high dose group was significantly decreased （P<0.05）. In modified Fuzi Lizhongtang high and medium dose group，the contents of IL-6 and TNF-α were significantly decreased （P<0.01） and the contents of IL-4 and IL-10 in serum were significantly increased （P<0.05，P<0.01）. In the modified Fuzi Lizhongtang high dose group，the expression level of mTOR and p-S6K1 protein was down-regulated significantly （P<0.05，P<0.01）. Conclusion:Modified Fuzi Lizhongtang high dose group can significantly reduce the congestion and edema，inflammatory cell infiltration，gland distortion，disorder of arrangement and other pathological manifestations of UC colon mucosa，and its mechanism may be related to its down-regulation of mTOR/p-S6K1 signal and the regulation of inflammatory factors secretion.

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.

The mechanism of action of Fuzi-Lizhong pill in treatment of ulcerative colitis based on network pharmacology-molecular docking / 药学学报

Network pharmacology and bioinformatics technology were used to predict the mechanism of action of Fuzi-Lizhong pill (FLP) in the treatment of ulcerative colitis (UC). 26 components (23 prototype compounds and 3 metabolites) in the blood of FLP were selected as the research objects. PharmMapper database, SwissTargetPrediction platform, GeneCards and OMIM database were used to screen and predict potential targets of FLP in blood. The protein-protein interaction network model was constructed by using String database and Cytoscape software. DAVID platform, KEGG and Reactome databases were used for GO analysis and pathway analysis of potential targets. Network of drug ingredients-targets-pathways was constructed by Cytoscape software. AutoDock vina software was used to dock the molecules of the absorbed ingredients of FLP in blood with the key targets. 82 potential targets of FLP for treatment of UC were obtained. Potential targets mainly involve biological processes such as response to organic substance, regulation of apoptosis, regulation of programmed cell death, which played roles in the treatment of UC by adjusting pathways in cancer, Colorectal cancer, Vascular endothelial growth factor signaling pathway, Mitogen-activated protein kinase signaling pathway, arachidonic acid metabolism and the other signal pathways. From the perspective of network pharmacology, this study predicted the mechanisms of action of FLP in treating UC, indicating that FLP in treating UC had the characteristics of multiple ingredients, multiple targets and multiple pathways, which laid a foundation for further research.

Herbalogical study of Aconiti Lateralis Radix Praeparata(Fuzi) / 中国中药杂志

As a most important Chinese materia medica, Aconiti Lateralis Radix Praeparata(Fuzi) had been widely used in China for thousands of years. This herbalogical study was systematically performed based on variation characteristics of the naming, habitat, harvesting, processing and properties. The sharp toxicity of Fuzi had been well known since the spring and autumn period in the history, which was much earlier than that its medical properties was understood and applied. Sichuan province was regarded as the geo-authentic region of Fuzi all along, where the best quality goods could be provided for clinic use. The study showed the harvesting time of Fuzi was changing in different periods, and the possible effects were of climate change and artificial planting. The perishable characteris-tics of Fuzi severely limited its storage period; therefore, different kinds of storage methods were effectively used since Tang Dynasty. For thousands of years, Fuzi had been processed with various accessories to reduce toxicity, while simultaneously the study on processing mechanism was on going all the time. Fuzi was widely used in clinical practice to cure Yang depletion syndrome, which was based on its function of enhancing Yang and removing cold. Along with the further study on quality evaluation standard, Fuzi will probably get a much wider range of applications.

Comparison of Total Daily Doses of 16 Active Components in Three Dosage Forms of Fuzi Lizhongwan / 中国实验方剂学杂志

Objective:To compare the total daily doses of 16 active components in big honeyed pills, concentrated pills and tablets of Fuzi Lizhongwan. Method:Three dosage forms of Fuzi Lizhongwan were prepared according to the process described in the literature. RRLC-QqQ-MS was employed to analyze the contents of 16 active ingredients with mobile phase of 0.1%formic acid aqueous solution-0.1%formic acid acetonitrile solution for gradient elution,the separation was performed on a Accucore RP-MS column(2.1 mm×100 mm, 2.6 μm) with a flow rate of 0.3 mL·min-1 and the column temperature at 30℃, the mass spectrometry condition was electrospray ion source, positive and negative ion switching mode for detection, multi-reaction monitoring mode(MRM) for scanning. The contents of 16 active ingredients were calculated, and the normalization arithmetic method was used for comparing the total daily doses of these active ingredients in three dosage forms of Fuzi Lizhongwan. Result:Processed products of Aconiti Lateralis Radix Praeparata were used as raw powder in preparation process of the three dosage forms, so there was no significant difference in the contents of six alkaloids in the three dosage forms, while the contents of other 10 active ingredients from Zingiberis Rhizoma, Codonopsis Radix, Atractylodis Macrocephalae Rhizoma and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle were significantly higher in big honeyed pills than those in concentrated pills or tablets(PConclusion:The total daily doses of 16 active ingredients in the three dosage forms of Fuzi Lizhongwan are significantly different caused by preparation process, prescription and dosage.

Evaluation of Dosage form Characteristics of Fuzi Lizhongwan Based on Dissolution Behavior / 中国实验方剂学杂志

Objective:Based on the previous studies, to investigate the dissolution behavior of Fuzi Lizhongwan by simultaneously determining the dissolution of benzoylmesaconine, benzoylaconine and benzoylhypaconine in Aconiti Lateralis Radix Praeparata. Method:The simultaneous determination of benzoylmesaconine, benzoylaconine and benzoylhypaconine in Fuzi Lizhongwan was established by HPLC-QQQ-MS. The dissolution amounts of three compositions in 15 batches of Fuzi Lizhongwan from 5 manufacturers at different time points, the cumulative dissolution was calculated and the dissolution curve was drawn. The f2 similarity factor method was adopted to evaluate similarity of dissolution curves of index components in different batches of samples from the same manufacturer, and to evaluate similarity of dissolution curves of samples from different manufacturers based on the same index component. The dissolution model of Fuzi Lizhongwan was concluded by fitting with the dissolution data. Result:When hydrochloric acid solution with pH of 1.2 was used as the dissolution medium, the three alkaloids had the best dissolution effect. The dissolution behavior of three monoester alkaloids in Fuzi Lizhongwan was basically synchronous and the dissolution lasted for 24 h. Three batches of samples from the same manufacturer (manufacturer 1, 3, 4 and 5) appeared to be similar on dissolution behavior, indicating that the dissolution behavior of the majority of samples from different manufacturers was similar. The dissolution behavior of batch 1 sample was different from batch 2 and 3 samples in manufacturer 2, suggesting that the quality of different batches of samples in manufacturer 2 might be different. The fitting results of dissolution data of index components in samples from different manufacturers were consistent, and the Weibull model was the best. Conclusion:Index components in fifteen batches of samples from 5 manufacturers are continuously dissolved within 24 h, indicating that the samples have the characteristics of slow dissolution. The dissolution curves of samples from the same manufacturer are similar to each other, indicating that the quality of different batches of products from most manufacturers is stable. The dissolution behavior of benzoylmesaconine, benzoylaconine and benzoylhypaconine in samples form different manufacturers has some differences, which may be caused by the source of medicinal materials and preparation technology parameters.

Determining the effect of Huangqi on the pharmacokinetics of six different alkaloids from Fuzi in rats by LC-MS / 药学学报

This study aimed to investigate the influence of combinating Huangqi with Fuzi on the pharmacokinetics of six Aconitum alkaloids, i.e. aconitine (AC), hypaconitine (HA), mesaconitine (MA), benzoylaconine (BAC), benzoylhypaconine (BHA) and benzoylmesaconine (BMA). The plasma concentrations of the drugs were determined by LC-MS for dose response and time dependent curves. The pharmacokinetic parameters were calculated by DAS 3.3, and SPSS 12.0 was used to analyze the differences of main pharmacokinetic parameters between the two groups. Comparing with Fuzi group, the AUC0-t and AUC0-∞ of six alkaloids in Fuzi-Huangqi group was significantly decreased, the CLz/Fof six alkaloids except HA was significantly increased; the Cmax was decreased and the tmax was prolonged in 3 monoester alkaloids, and the apparent volume of distribution of BMA and MA (Vz/F) increases. These data indicated that Huangqi can inhibit the absorption of aconite alkaloids, induce the distribution of aconite alkaloids to the whole body, and accelerate the elimination of aconite alkaloids. The animal experiment scheme in this study has been approved by the Experimental Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine.

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.

Toxicity-efficacy converting of ginseng combined with Fuzi Banxia incompatibility in heart failure stage of cor pulmonale / 中草药·英文版

Objective: Fuzi Banxia is one of eighteen antagonisms, previous studies have shown that the incompatibility could play special effects in the specific condition of diseases and appropriate compatible environment. The present study aims to evaluate the toxicity-efficacy of ginseng combined with Fuzi Banxia incompatibility intervening in the heart failure stage of cor pulmonale and to explore its mechanism. Methods: Monocrotaline (MCT)-induced cor pulmonale were used in this study. Ultra high-resolution small animal ultrasound real-time imaging system and the right heart catheterization were used to estimate cardiac function. Semi automatic biochemical analyzer was used to test myocardial enzyme LDH, CK, and CK-MB in serum. The heart tissues were stained with HE, and TUNEL assay was used to assess the pathomorphological changes and myocardial apoptosis. The expression of hypertrophy and apoptosis associated genes: ANP, BNP, β-MHC, Bax, and Bcl-2 in the right ventricle were determined by RT-PCR. Results: Fuzi Banxia combined with ginseng obviously attenuated mortality, decreased RVHI, and increased cardiac index; RVSP and mPAP were significantly reduced, and EF and FS were raised obviously; Myocardial enzymes LDH, CK, and CK-MB were pronounced attenuated; heart diameter reduced, right ventricular dilatation was significantly decreased, inflammatory cell infiltration notably reduced, and cardiac apoptosis rate was decreased obviously. Meanwhile, the expression of hypertrophy-related ANP, BNP, and β-MHC mRNA were up-regulated, the expression of apoptosis-related Bax mRNA was down-regulated, and the expression of anti-apoptosis-related Bcl-2 mRNA and Bcl-2/Bax ratio were up-regulated. Conclusion: Ginseng compatible environment could attenuate cardiac toxicity of Fuzi Banxia incompatibility intervening in the heart failure stage of cor pulmonale, and improve cardiac function, which may be related to the expression of hypertrophy and apoptosis associated genes, and thus delay the occurrence and development of heart failure.