Abstract：With continuous introduction of relevant national policies on famous classical formulas, the research of famous classical formulas is popular all over the country. Different from other new drugs, in the research and development process of famous classical formulas, substance benchmark is earlier than the product, suggesting that the research and development of substance benchmark is of great significance. Based on previous work of the authors, content of substance benchmark of famous classical formulas was analyzed, which was included in the document The Management Regulation of Simplified Registration and Approval over Chinese Herbal Medicine Compound Preparations of Ancient Famous Classical Formulas released by the National Medical Products Administration in May 2018. In this paper, the significance of substance benchmark development was described, a five-stage of research strategy was proposed, covering the prescription textual research and historical evolution, the collection and quality evaluation of medicinal materials, the processing method and quality evaluation of decoction pieces, the preparation and quality research of substance benchmark, the drafting and formulating of quality standard over substance benchmark. At the same time, some suggestions were put forward to the feasibility of compound preparations development over famous classical formulas, the implementation difficulty of resource evaluation over Chinese medicinal materials, and the irrationality on the quality correlation of Chinese medicinal materials. All of these are expected to provide reference and enlightenment for the development and policy officially landed over ancient famous classical formulas.
Keywords：traditional Chinese medicine;famous classical formulas;substance benchmark;research and development strategies;prescription textual research;resource evaluation;processing
Abstract：Objective:To explore the hepatoprotective effect and the mechanism of Buzhong Yiqitang (BZYQT) on mice with acute liver failure induced by Concanavalin A (ConA).Method:A total of 80 mice were randomly divided into normal group, model group, Cyclosporine A (CsA) group, BZYQT low and high dose group (10.5, 21 g·kg-1), 16 mice per group. All the mice except for normal group were injected intravenously with 15 mg·kg-1 ConA. The treatment group mice were orally administrated with BZYQT, or intravenously administrated with 50 mg·kg-1 CsA 30 min post ConA injection, normal and model group mice were orally administrated with ddH2O at the same time. Blood, liver and spleen were collected 3 and 10 h post ConA injection. Cytokine levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-12 (IL-12), interferon-gamma (IFN-γ) and monocyte chemoattractant protein-1 (MCP-1) in the serum were detected with cytometric bead array. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the serum were analyzed with fully automatic biochemical analyzer. The pathological changes of liver tissues were observed by hematoxylin-eosin (HE) staining. The activation of splenic CD4+ T lymphocytes was analyzed by flow cytometry. The expression and phosphorylation of extracellular regulated protein kinase 1/2(ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) was analyzed by Western blot.Result:Compared with normal group, model group showed higher levels of ALT and AST in the serum (P<0.01), obvious pathological damage of liver tissue, higher levels of TNF-α, IL-6, IL-12, IFN-γ and MCP-1 in the serum (P<0.01), higher expression of IL-2, IFN-γ and IL-4 CD4+ T lymphocytes in the spleen (P<0.01), and elevated levels of phosphorylation of ERK1/2 and p38 MAPK (P<0.01). Compared with the model group, BZYQT high dose group showed decreased levels of ALT and AST (P< 0.05, P<0.01), reduced liver injury, decreased levels of TNF-α, IL-6, IL-12, IFN-γ and MCP-1 in the serum (P<0.05, P<0.01), reduced level of IL-2 and IFN-γ CD4+ T lymphocytes in the spleen (P<0.05, P<0.01), and reduced levels of phosphorylation of ERK1/2 and p38 MAPK (P<0.05, P<0.01).Conclusion:BZYQT has a protective effect on mice with acute liver failure induced by ConA. The mechanism may be through inhibiting ERK1/2 and p38 MAPK signaling pathways, thereby reducing T lymphocyte activation and inflammatory cytokine secretion.
Abstract：Objective:To observe the effect of Youguiwan on the levels of cartilage transducers and activators of transcription 3 (STAT3) and interleukin-6 (IL-6) in rats with knee osteoarthritis (KOA).Method:Sixty SD rats were randomly divided into six groups: sham control group, model group, glucosamine sulfate group and Youguiwan (high, middle and low-dose) groups. The modified Hulth method was used to prepare KOA models for 6 weeks. The shame control group and the model group were treated with normal saline, Youguiwan high, middle, low-dose groups received Youguiwan 4.8, 2.4, 1.2 g·kg-1 by gavage respectively, and the glucosamine sulfate group was treated with glucosamine sulfate 0.17 g·kg-1. The rats were administrated for 8 weeks according to the dose. After intervention, each group was put to death by femoral artery blood collection, and the keen cartilages of the rats were collected. The pathological changes were observed by htoxylin eosin (HE) staining method, and Mankin score was evaluated. The expressions of STAT3, superoxide dismutase3(SOD3) and Wnt inhibitory factor 1(WIF1) in articular cartilage were detected by immunohistochemistry. The expressions of IL-6 mRNA in articular cartilage were detected by quantitative real-time fluorescence polymerase chain reaction (Real-time PCR). The expression of WIF1 in articular cartilage was detected by Western blot.Result:Compared with the sham control group, the Makin score was obviously increased in the model group, the protein expression of STAT3 was increased significantly, the mRNA of IL-6 was raised significantly, but the protein expression of WIF1 was decreased significantly (P<0.01), articular cartilage was seriously damaged, and chondrocytes were arranged in disorder. Compared with the model group, the Makin score was declined obviously in the high-dose Youguiwan group, the protein expression of STAT3 was significantly reduced, the mRNA expression of IL-6 was significantly reduced in Youguiwan treatment group, while the protein expression of WIF1 was significantly increased (P<0.05, P<0.01), the cartilage structure returned to be normal, the chondrocytes distribution was uneven, and articular cartilage surface was not smooth.Conclusion:Youguiwan could significantly improve the articular cartilage degeneration of KOA rats, and inhibit the inflammation of chondrocytes, which may be related to the suppression of STAT3 and IL-6 expression.
Keywords：knee osteoarthritis;Youguiwan;interleukin-6 (IL-6)/transducers and activators of transcription 3 (STAT3) signaling pathway;inflammatory cytokines
Abstract：Objective:To explore the mediating effect of Wutoutang (WTT) on brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) pathway in hippocampus and to clarify the mechanism of therapeutic action of WTD on pain-emotion comorbidity by inhibiting neuropathic pain (NP) preliminarily.Method:The mice were divided into sham group, spinal cord ligation (SNL) group, Wutoutang (WTT) group, Wutoutang-ANA12 antagonist (WTT-ANA12) group, pregabalin (PGB) group, Fluoxetine Hydrochloride (FLU) group randomly. Mice were fixed with the drug delivery cannula for hippocampal CA3.The L5 spinal cord of mice were tightly ligated but sham group (only exposed). During the 10-16th day after surgery, WTT, WTT-ANA12 groups were gavaged with 126 mg·kg-1 WTT, PGB and FLU groups were respectively given 25 mg·kg-1 PGB and 3 mg·kg-1 FLU, sham and SNL groups were given the physiological saline once a day. Then, 50 nmol·L-1 ANA12 were given to the hippoicampal CA3 of the WTT-ANA12 mice by drug delivery cannula, and physiological saline were given to the others on the 10-16th day after surgery. Mechanical pain were detected by Von Frey tests, anxiety and depression behaviors were separately detected by the open field and the tail tailing experiments, while the morphology of CA3 pyramidal neurons were qualified by the Golgi-staining.Result:Compared with sham group, significant decreases of the mechanical pain thresholds, decreases of the duration time in the open field, as well as the increases of the no-struggling time during the tail-suspension were detected in the SNL mice(P<0.01). In addition, as illustrated by the Golgi-staining, the atrophy of hippocampal pyramidal neurons were found in SNL mice as compared with sham(P<0.05, P<0.01). On the contrary, as compared to the SNL, significant increases of the mechanical pain thresholds, increases of the duration time in the open field, the decreases of the no-struggling time during the tail-suspension(P<0.01), as well as the morphological improvements of the hippocampal CA3 pyramidal neurons were detected in the WTT mice. Furthermore, after 7 d hippocampal injections, There is no significant distinction of the mechanical pain thresholds, the duration time in the open field, the no-struggling time during the tail-suspension, as well as the atrophy of hippocampal neurons were detected in the WTT-ANA12 groups as compared with SNL.Conclusion:The data suggested that the effective inhibition of WTT on SNL-induced vertebral neuron injury in hippocampus CA3 and pain-emotion disorder, which might attribute to it' s regulation of BDNF/TrkB pathway in hippocampus.
Abstract：Objective:To study whether Sanhuang Xiexintang (SHXXT) can restore endothelial function by inhibiting the activation of NOD-like receptor protein 3 (NIRP3) induced by 7-ketocholesterol (7-keto) in vascular endothelial cells.Method:The aortic rings of mice were cultured in normal group, model (7-keto) group, SHXXT groups (1%, 2% and 5% drug-containing serum). Vasodilation function of mice was observed. Microvascular endothelial cells were cultured according to the above experimental groups, and NIRP3 inhibitor isoglycyrrhizin (ISO) group, was also set. Western blot was used to detect the expressions of endothelial nitric oxide synthase (eNOS), NIRP3, cysteinyl aspartate specific proteinase-1 (Caspase-1), interleukin-1β (IL-1β) protein. In addition, nitric oxide (NO) quantitative kit was used to detect the concentration of NO.Result:Compared with the normal group, the endothelium-dependent vasodilation function of vascular rings was significantly reduced in model group (P<0.01), and the drug group significantly restored the endothelium-dependent vasodilation function in a concentration-dependent manner (P<0.05, P<0.01). Meanwhile, microvascular endothelial cells were also studied. Compared with the normal group, the content of eNOS protein in the model group decreased (P<0.05), while the concentration of NO decreased significantly (P<0.01). After treatment with SHXXT serum, eNOS and NO could be restored, with significant differences in the concentration of NO with 5% (P<0.05) and 10% (P<0.01) SHXXT serum. At the same time, the expressions of NIRP3 (P<0.05), cle-Caspase-1 activation (P<0.01) and IL-1β production (P<0.01) in endothelium were significantly increased under 7-keto stimulation, and the SHXXT serum could significantly inhibit the expression and activation of relevant proteins. Subsequently, endothelial cells were treated with NIRP3 inhibitor ISO. Compared with the model group, eNOS expression increased, and NO concentration increased significantly (P<0.01) after treatment with ISO, but ISO had no synergistic effect on SHXXT serum.Conclusion:SHXXT can improve endothelium-dependent vascular dysfunction induced by 7-keto, which is achieved by NO signaling pathway mediated by inhibiting the activation of endothelial NIRP3-related proteins.
Keywords：hyperlipidemia;endothelium;Sanhuang Xiexintang;NOD-like receptor protein 3 (NIRP3);endothelial nitric oxide synthase (eNOS);vasodilation
Abstract：Objective:To investigate the effect of Houpu Mahuangtang on airway inflammation and expressions of gene and proteins of Transient receptor potential ankyrin 1, vanilloid 1 (TRPA1, TRPV1) in asthmatic mice.Method:Sixty female Balb/c mice were randomly divided into six groups: control group, model group, low, medium and high-dose Houpu Mahuangtang groups (7, 14, 28 g·kg-1) and dexamethasone group (0.002 4 g·kg-1), with 10 mice in each group. A mouse model of asthma was replicated by sensitizing and challenging with ovalbumin. The changes of enhanced pause (Penh) following acetylcholine chloride (ACh) inhalation were detected. The pathological changes of the lung tissues were observed. The number of eosinophils (EOS) in peripheral blood and the percentage of EOS in bronchoalveolar lavage fluid (BALF) were detected. Interleukin (IL)-4, IL-13, prostaglandin D2 (PGD2) and substance P (SP) were detected by enzyme-linked immuno sorbent assay (ELISA). The expressions of TRPA1 and TRPV1 gene and protein in lung tissues were detected by Quantitative Real-time polymerase chain reaction (Real-time PCR) and Western blot.Result:Compared with control group, mice of model group showed significantly increased in Penh following ACh inhalation (P<0.05, P<0.01), EOS in blood and the percentage of EOS in BALF (P<0.01). Histopathological changes in lungs showed inflammatory cell infiltration and bronchial mucosa damage. The levels of IL-4, IL-13, PGD2 and SP in BALF and the expressions of TRPA1, TRPV1 mRNA and protein in lung tissues significantly increased (P<0.05, P<0.01). Compared with model group, treatment groups had significant effects in decreasing Penh, relieving lung injury, reducing EOS count in blood and the percentage of EOS in BALF (P<0.05, P<0.01), reducing IL-4, IL-13, PGD2 and SP levels in BALF (P<0.05, P<0.01), as well as down-regulating TRPA1 and TRPV1 mRNA and protein expressions in lung tissues (P<0.05, P<0.01).Conclusion:Houpu Mahuangtang could reduce airway inflammation, airway responsiveness. In addition to the reduction of levels of Th2 related cytokines, the mechanism of Houpu Mahuangtang might be related to the regulation of TRPA1, TRPV1 mRNA and protein expressions, and the decrease of associated neurofactor levels.
Abstract：Objective:To investigate the mechanism of Buyang Huanwu Tang (BYHWT) in improving synaptic structural plasticity after cerebral ischemia-reperfusion in rats.Method:Middle cerebral artery occlusion and reperfusion model was established. SD rats were randomly divided into sham-operated group, model group, BYHWT group, BYHWT+ Gap26(connexin43 inhibitor)groups. BYHWT was given twice a day(16 g·kg-1), Gap26 was intraperitoneally injected once a day since the third day after surgery (25 g·kg-1). Brain was taken out at the 7th day. The changes of neuronal synaptic and gap junction ultrastructure were observed by transmission electron microscopy. Synaptophysin (SYN) and growth-associated protein-43 (GAP-43) protein expression were detected by Western blot and immunofluorescence.Result:The structure of synapses was integrated, and the gap junctions were clear in sham-operated group. In the hippocampus of model group, the structure was destroyed, and the gap junctions disappeared. Compared with the sham-operated group, model group up-regulated the expressions of SYN and GAP-43 (P<0.05, P<0.01). In the hippocampus of BYHWT group, the structure was close to the normal. Furthermore, BYHWT up-regulated the expressions of SYN and GAP-43 (P<0.05, P<0.01). However, after the combined administration with Cx43 inhibitor (Gap26), the damage of synaptic structural decreased, only a small number of gap junctions with the structural integrity can be seen, and the effect of BYHWT on SYN and GAP-43 was inhibited (P<0.05, P<0.01).Conclusion:BYHWT could improve the hippocampal synaptic structural plasticity obviously after the CIRI. The mechanism may be related to the increase of the expression of Cx43 and the promotion of the intervention of SYN and GAP-43.
Abstract：Objective:To observe the effect of Guizhitang with different proportions of Cinnamomi Ramulus and Paeoniae Alba Radix on the expressions of transforming growth factor-β1(TGF-β1)/Smads signaling pathway and interleukin-10(IL-10), IL-6 and tumour necrosis factor-α(TNF-α)related inflammatory cytokines in salt-sensitive hypertensive rats, in order to explore the mechanism of Guizhitang in improving myocardial fibrosis in salt-sensitive hypertensive rats.Method:Totally 40 male 6-week-old salt-sensitive rats were randomly divided into 5 groups: the normal control group, the model group, the 1∶1(RC/peony)Guishao group, the 1∶2 Guishao group, and the 2∶1 Guishao group, with 8 in each group. The normal control group was fed with normal salt diet, while the other four groups were fed with high-salt diet. After 4 weeks of feeding, the rats were given intragastric administration, the normal control group and the model group were given the same amount of normal saline, and the 1∶1 Guishao group, the 1∶2 Guishao group and the 2∶1 Guishao group were given 4.0, 5.5, 5.5 g·kg-1 of Guizhitang by gavage for 4 weeks. Blood pressure was measured once a week, left ventricular end systolic diameter(LVESD), left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF) and left ventricular short axis shortening fraction (LVFS) were detected by using echocardiogram. The pathological changes of myocardial morphology were observed by htoxylin eosin(HE)and Masson staining. The expressions of type Ⅰ and Ⅲ collagen in myocardial tissue of each group was detected by immunohistochemistry. The mRNA expression levels of IL-10, IL-6 and TNF-α in myocardial tissue of each group were detected by quantitative real-time fluorescence polymerase chain reaction(Real-time PCR). The protein expression levels of TGF-β1, α-smooth muscle actin(α-SMA), Smad2, Smad3 and Smad7 in myocardial tissue of each group were detected by Western blot.Result:Compared with the normal control group, the blood pressure was increased in the model group at 8-15 weeks, LVESD, LVEDD were increased in the model group, while LVFS, LVEF were decreased in the model group. The collagen volume fraction was increased, immunohistochemistry showed the expression levels of type Ⅰ and Ⅲ collagen were increased, mRNA expression levels of IL-10, IL-6 and TNF-α were increased, the protein expression levels of TGF-β1, Smad2, Smad3 and α-SMA were increased, whereas the protein expression of Smad7 was decreased (P<0.01). Compared with the model group, the blood pressure rise of each group of Guizhitang was delayed in 12-15 weeks, LVESD and LVEDD were decreased in Guizhitang group (P<0.01), LVFS, LVEF were increased in Guizhitang group (P<0.01), the collagen volume fraction was decreased in Guizhitang group (P<0.01), and the expressions of type Ⅰ and Ⅲ collagen were decreased in Guizhitang group (P<0.01). At the same time, the mRNA expression of IL-10 was increased in Guizhitang group (P<0.05, P<0.01), the mRNA expressions of IL-6 and TNF-α were decreased in Guizhitang group (P<0.01), and the protein expressions of TGF-β1, Smad2, Smad3 and α-SMA were decreased in Guizhitang group (P<0.05, P<0.01), and the protein expression of Smad7 was increased in Guizhitang group (P<0.01). Compared with the 2∶1 Guishao group, the effect of the 1∶1 Guishao group in improving the above indicators was more obvious (P<0.05, P<0.01).Conclusion:Guizhitang with different proportions of Ramulus Cinnamomi and Poeny can alleviate the degree of myocardial fibrosis in salt-sensitive hypertensive rats. The mechanism may be related to the regulation of TGF-β1/Smads signaling pathway and the reduction of inflammatory response. Besides, the 1∶1 Guishao group showed the optimal effect in reducing inflammation and improving myocardial fibrosis.
Abstract：Objective:To investigate the effect of Aconiti Lateralis Praeparata Radix combined with Glycyrrhizae Radix et Rhizoma on mRNA expression of cytochrome P450 (CYP450) enzymes in rat' s heart.Method:Male Sprague Dawley rats were randomly divided into the control group, the inducer group (0.08 g·kg-1·d-1), the aconite group (0.5 g·kg-1·d-1), the licorice group (0.5 g·kg-1·d-1) and the compatibility group (aconite and licorice group 0.5 g·kg-1·d-1), with 6 rats in each group. In each group, the serum concentrations of aspartate transaminase (AST), creatine kinase (CK) andlactate dehydrogenase (LDH) were respectively measured. Hematoxylin-eosin(HE) staining was used to detect the pathologic changes in the heart tissue of the rats. The expression of several CYP genes were measured.Result:After combination, the contents of AST, CK and LDH were lower than those of the aconite group. At the same time, the pathological results showed cardiac injury in rats in the aconite group, and licorice could alleviate the cardiac injury caused by aconite. At the level of gene transcription, the glycyrrhizae group could up-regulate the expressions of CYP2C11 and CYP2J3 to different degrees (P<0.05), and the combination of licorice and aconite could up-regulate the expression of CYP2B1, CYP2C11 and CYP2J3 family (P<0.05). It suggested that the combination could promote the formation of EETs in arachidonic acid(AA) metabolism, and the aconite could up-regulate the expressions of CYP4A1, CYP4A3, CYP4F5 and CYP4F6 in CYP4 family (P<0.05), promote the formation of 20-hydroxyeicosatetraenoic acid(20-HETE). The combination of aconite and licorice can weaken the ability of aconite, down-regulate the expression of CYP4A3, CYP4F1, CYP4F5 and CYP4F6 family mRNA (P<0.05), inhibit the formation of 20-HETE and reduce the cardiotoxicity caused by aconite.Conclusion:The combination of licorice and aconite can regulate the expression of CYP450 enzyme in the heart, increase the production of EETs and the content of 20-HETE, and finally play a role in reducing toxicity.
Keywords：Radix Aconiti Lateralis Praeparata;Glycyrrhizae Radix et Rhizoma;heart;cytochrome P450;compatibility
Abstract：Objective:To study the protective effect and mechanism of Qidong Yixin oral liquid on doxorubicin-induced myocardial toxicity in mice.Method:Ninety male ICR mice were randomly divided into normal group, model(DOX) group, DOX+ Qidong Yixin oral liquid group (9.55, 23.88, 47.75 g·kg-1) and high dose group (47.75 g·kg-1) with 15 mice in each group. The normal group and model group were given pure water by gavage, and each dose group of Qidong Yixin oral liquid was given different doses of Qidong Yixin oral liquid once a day for 21 days. On the seventh day, normal saline was injected into the abdominal cavity of the normal group and the high dose group of Qidong Yixin oral liquid. Doxorubicin was injected into the abdominal cavity of the other groups (15 mg·kg-1). After 21 days, the weight and heart weight of mice were weighed and cardiac index was calculated. Serum was taken for the detection of lactate dehydrogenase (LDH), creatine kinase (CK), aspartate aminotransferase (AST). Heart was taken for hematoxylin-eosin (HE) staining, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) in myocardial tissue were detected. The expression of nuclear factor NF-E2 related factor (Nrf2) and heme oxygenase-1 (HO-1) were detected by Western blot.Result:Compared with normal group, adriamycin could significantly reduce the body weight of mice (P<0.01), increase the activities of LDH, CK and AST in serum(P<0.01), and decrease the activities of antioxidant enzymes (P<0.01). Compared with DOX group, high dose Qidong Yixin oral liquid could significantly increase the weight of mice (P<0.05, P<0.01), decrease the level of myocardial three enzymes(P<0.01), increase the activity of antioxidant enzymes(P<0.05, P<0.01), and increase the expression of Nrf2 and HO-1(P<0.01).Conclusion:Qidong Yixin oral liquid has a good protective effect on doxorubicin myocardial toxicity. Its mechanism may be related to activating Nrf2/HO-1 signaling pathway and alleviating oxidative stress injury.
Abstract：Objective:To explore the effect of Weichang' an (WCA) on the autophagy of human gastric cancer MKN45 cells and its possible anti-cancer mechanism.Method:MKN45 cells were cultured in vitro and incubated with different concentrations (250, 500, 1 000, 2 000 mg·L-1) of WCA for 24, 48, 72 h. Cell counting kit-8 (CCK-8) assay was used to detect the cell proliferation. AO/EB Dyeing (AO) staining and monodansylcadaverin (MDC) staining were used to observe the changes of the effect of WCA on autophagosome and autophagic vesicles in gastric cancer MKN45 cells at 48 h. Real-time polymerase chain reaction (Real-time PCR) and Western blot were used to detect microtubule-associated protein 1 light chain 3 (LC3), Beclin1, sequestosome 1 (p62), human autophagy-related gene 5 (ATG5), human autophagy-related gene 7 (ATG7) mRNA and protein expression levels.Result:WCA showed a dose-and-time-dependent growth inhibition at the concentration above 1 000 mg·L-1. Compared with the blank group, WCA (500, 1 000, 2 000 mg·L-1) significantly inhibited the proliferation of MKN45 cells (P<0.05, P<0.01). AO staining and MDC staining showed that autophagosomes and autophagic sacs increased with the rise of WCA concentration compared with the blank group. Real-time PCR and Western blot showed that the expressions of autophagy-related proteins LC3-Ⅱ, Beclin1, ATG5, ATG7, mRNA and protein increased gradually after WCA (1 000 mg·L-1) intervention, while p62 expression decreased (P<0.05, P<0.01).Conclusion:WCA induces the autophagy of human gastric cancer MKN45 cells in a time-and dose-dependent manner in vitro, which may be related to the up-regulation of LC3-Ⅱ, Beclin1, ATG5 and ATG7 as well as the down-regulation of p62 and LC3-Ⅰ.
Abstract：Objective:To investigate the potential mechanism of astragaloside Ⅳ in protecting liver injury and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/forkheadbox transcription factor 1 (FoxO1), phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase) protein expressions in type 2 diabetic (T2DM) rats.Method:After 6 weeks of high-sugar and high-fat diet, a model of type 2 diabetes was established through intraperitoneal injection of streptozotocin (STZ, 0.035 g·kg-1). The rats were randomly divided into normal group, model group, low, medium and high-dose astragaloside Ⅳ groups and metformin group, 0.02, 0.04, 0.08 g·kg-1·d-1 astragaloside crude drug and 0.2 g·kg-1·d-1 metformin were administered in the low, middle and high-dose astragaloside Ⅳ and metformin groups. After 8 weeks of continuous administration, and 24 hours later after the last gavage, the rats were executed. Serum and liver tissues were collected to detect serum liver biochemical indexes, liver index HDL-C. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of liver tissue. Masson staining was used to observe the degree of liver fibrosis. The changes of glycogen, glycoprotein, or mucopolysaccharide in tissue cells were observed by periodic acid Schiff (PAS) reaction staining. Immunohistochemistry and Western blot analysis were used to detect the expression levels of PI3K/Akt/FoxO1 signaling protein and PEPCK and G6Pase in liver tissues of each group.Result:Compared with normal group, the liver index of the model group increased significantly (P<0.01), the levels of liver function indicators alanine aminotransferase(ALT), aspartate aminotransferase(AST), TC and TG were significantly increased (P<0.01), while HDL-C and body weight were significantly reduced (P<0.01). The results of immunohistochemistry and Western blot showed that the signal of PI3K/Akt/FoxO1 was weakened (P<0.01), and PEPCK and G6Pase were increased (P<0.01) in model group. Compared with model group, the contents of ALT, AST, TC and TG in middle and high-dose astragaloside Ⅳ groups were significantly decreased (P<0.05, P<0.01), while the body weight was significantly increased (P<0.05, P<0.01), the middle and high dose of astragaloside Ⅳ significantly inhibited the levels of FoxO1, PEPCK and G6Pase in liver tissue (P<0.05, P< 0.01), and enhanced the phosphorylation of FoxO1 (P<0.05, P<0.01).Conclusion:Astragaloside Ⅳ may inhibit T2DM hepatic gluconeogenesis by regulating PI3K/Akt/FoxO1 signaling pathway, and inhibiting high-fat, high-sugar and low-dose STZ, thereby protecting liver damage in T2DM rats.
Abstract：Objective:To detect the expression levels of leptin (LEP), acety-coenzyme A carboxylase(ACC) and malonyl-CoA (MCA)-related proteins and their genes in rat tissues, in order to explore the mechanism and dose-effect relationship of modified Wendantang in alleviating lipid metabolism disorder in female nutritional obese rats.Method:Totally 50 SD female rats were randomly divided into 5 groups according to body weight, namely the normal control group, the model control group, and high, medium and low-dose modified Wendantang groups (18.2, 9.1, 4.55 g·kg-1). Except the normal control group, the remaining rats were fed with " common feed + high fat emulsion + carbonated beverage" to establish the model of nutritional obesity, and then continuously given drugs by gavage for 5 weeks. After the last drug administration to animals in each group, the rats were anaesthetized to collect materials. The serum LEP, and liver and gastrocnemius ACC levels in each group were detected by enzyme-linked immunosorbent assay (ELISA). Quantitative real-time fluorescence polymerase chain reaction (Real-time PCR) was used to detect the expressions of LEP, MCA and ACC2 mRNA in the hypothalamus and liver tissues of each group.Result:Compared with the normal control group, the body weight and fat index of the model control group increased significantly (P<0.05). Compared with the model control group, the medium-dose modified Wendantang group could significantly down-regulate the expressions of LEP, MCA mRNA in rat hypothalamus (P<0.01). The low-dose group can significantly down-regulate the expression levels of serum LEP, hypothalamus tissue LEP, MCA mRNA and liver tissue ACC2 mRNA (P<0.05, P<0.01). Compared with the high-dose modified Wendantang group and the middle-dose modified Wendantang group had the best effect in down-regulating the expressions of LEP and MCA mRNA in the hypothalamus of rats, which were followed by the low-dose group (P<0.05, P<0.01).Conclusion:The mechanism of modified Wendantang against nutritional obesity in female rats is related to the intervention of LEP resistance and the decrease of the expression level of ACC2 mRNA in liver tissue and MCA mRNA in hypothalamus tissue. The middle and low-dose groups have a better effect.
Keywords：modified Wendantang;nutritional obesity;leptin;acety-coenzyme A carboxylase;malonyl-CoA;mechanism
Abstract：Objective:To investigate the clinical efficacy of modified Guizhi Jia Gegen Tang on cervical spondylotic radiculopathy (CSR) with Qi stagnation and blood stasis syndrome and its effect on cervical vertebral mobility, isometric muscle strength and pain-related factors.Method:Totally 162 CSR patients with Qi stagnation and blood stasis syndrome were randomly divided into observation group (81 cases) and control group (81 cases). The observation group was given modified Guizhi Jia Gegen Tang orally, 150 mL/time, twice a day, while the control group was given Jingshu granule orally for 6 g/time, twice a day. Both groups were treated for 8 weeks. The changes of median nerve F wave conduction velocity, cervical vertebral mobility, isometric muscle strength, CSR 20 subscale score and visual analogue score (VAS) were recorded before and after treatment. The total effective rate and the cure rate were counted after treatment. The levels of serum pain-related factors (5-HT), nerve growth factor (NGF) and prostaglandin E2 (PGE2) were measured before and after treatment.Result:The total effective rate of the observation group was 98.77%, and the cure rate was 40.74%, which were better than 83.95%and 7.41%of the control group (P<0.01). Compared with before treatment, the conduction velocity of median nerve F wave, cervical vertebral mobility, isometric muscle strength and CSR 20 score increased, whereas VAS score, pain related factors 5-HT, NGF and PGE2 content decreased in both groups (P<0.01). Compared with control group, median nerve F wave conduction velocity, cervical vertebral mobility, isometric muscle strength and CSR 20 subscale scores increased, while VAS score decreased, pain related factors 5-HT, NGF and PGE2 contents decreased in the observation group (P<0.01).Conclusion:Modified Guizhi Jia Gegen Tang is effective in treating CSR with Qi stagnation and blood stasis syndrome, and can significantly improve the neck and hand functions and relieve pain.
Keywords：modified Guizhi Jia Gegen Tang;cervical spondylotic radiculopathy;pain factor;electromyogram(EMG);cervical vertebral mobility
Abstract：Objective:To observe the clinical efficacy of modified Qingjin Huatan Tang on bronchiectasis with syndrome of phlegm-heat accumulating lung at acute exacerbation and its inhibitory effect on pro-inflammatory factors and proteolytic activity.Method:One hundred and thirty patients were randomly divided into control group and observation group by random number table. Patients in control group got tazobactam sodium and piperacillin sodium for injection, 3.375 g/time, 1 time/6 hours, and the types of antibiotics were regulated according to the bacterial culture results. And patients in control group also got Ambroxol Hydrochloride injection, 30 mg/time, 2 time/days, and postural drainage. In addition to the therapy of control group, patients in observation group were also given modified Qingjin Huatan Tang, 1 dose/day. Before and after treatment, symptoms and signs were scored. And levels of white blood cell count (WBC), neutrophile granulocyte (GRAN), C-reactive protein (CRP), procalcitonin (PCT) were detected. And scores of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR) and BODE were graded. And levels of tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6 and IL-8 in sputum, peripheral neutrophil elastase (NE) and cathepsin G were detected.Result:By rank sum test, the clinical efficacy in observation group was better than that in control group (Z=2.086, P<0.05), while scores of symptoms and signs in observation group were lower than those in control group (P<0.01). WBC, GRAN, CRP, PCT, airflow limitation (O), dyspnea (D), motor ability (E) score, BODE index, TNF-α, IL-4, IL-6, IL-8, plasma NE and cathepsin G were all lower than those in control group (P<0.01). And levels of FEV1, FVC, PEF and FEV1/FVC were higher than those in control group (P<0.01).Conclusion:In addition to routine anti-infection and expectoration western medicine therapy, modified Qingjin Huatan Tang can be added to control symptoms and signs, alleviate the degree of illness, improve pulmonary function and the quality of life of patients, and inhibit expression of airway pro-inflammatory factor and proteolysis, with a better clinical efficacy than pure western medicine.
Keywords：bronchiectasis;acute exacerbation;phlegm-heat retention of lung syndrome;Qingjin Huatan Tang;quality of life;anti-inflammation;proteolytic activity
Abstract：Objective:To discuss the effect of Zhongfeng Xingnao liquid on neurological recovery of patients of ischemic stroke with Qi deficiency and blood stasis syndrome at early recovery, and the mechanisms of anti-inflammation, neuroprotection and improvement of microcirculation.Method:One hundred and twenty-eight patients were randomly divided into control group (64 cases) and observation group (64 cases) by random number table. Both groups’ patients got atorvastatin, 10 mg/days, aspirin enteric-coated tablets, 100 mg/days, and control of blood pressure and blood sugar, and modern rehabilitation training. Patients in control group orally got Zhongfeng Xingnao liquid, 25 mL/time, 3 times/days. The course of treatment was 90 days. And before and after treatment, national institutes of health neurological deficiency (NIHSS), Barthel index, improvement Rankin scale, brunel balance scale (BBA), Fugl-Meyer scale (FMA), Qi deficiency and blood stasis syndrome (SS-QOL) were scored. And levels of brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNF-alpha), homocysteine (Hcy), serum cystatin C (Cys-C), platelet aggregation rate (ADP) and fibrinogen (FIB) were detected.Result:The clinical efficacy in observation group was better than that in control group (Z=1.981, P<0.05). At different time points after treatment, scores of NIHSS and Qi deficiency and blood stasis syndrome were lower than those in control group (P<0.05), whereas scores of Barthel index, FMA, BBA and SS-QOL were higher than those in control group (P<0.01). Degrees of disability and dyskinesia in observation group was lighter than those in control group (Z=1.932, P<0.05). Degree of dyskinesia was lighter than that in control group (Z=2.149, P<0.05). And level of BDNF was higher than that in control group (P<0.01), while levels of TNF-α, Hcy, Cys-C, ADP and FIB were lower than those in control group (P<0.01).Conclusion:In addition to the routine comprehensive rehabilitation measures of western medicine, Zhongfeng Xingnao liquid can promote recovery of nerve function defect of patients of cerebral infarction with Qi deficiency and blood stasis syndrome at convalescence, is beneficial for rehabilitation of patients and improving the quality of life, with certain effects in resisting inflammation, improving microcirculation and protecting nerves, and better efficacy than simple western medicine treatment.
Keywords：ischemic stroke;recovery stage;Qi deficiency and blood stasis syndrome;Zhongfeng Xingnao liquid;quality of life;inflammatory factors;brain-derived neurotrophic factors
Abstract：Objective:To study on the plasma lipidomics characteristics of coronary heart disease (CHD) patients with syndrome of of intermingling of phlegm and static blood, and to find differential lipid metabolites between them and healthy volunteers.Method:The plasma samples from CHD patients with syndrome of intermingling of phlegm and static blood and healthy volunteers of the same age were collected. The plasma lipidomics was carried out by UPLC-Q/TOF-MS. The plasma samples were detected under positive and negative ion modes, and the primary and secondary mass spectrometry datas were collected simultaneously, and the m/z ranges were 100-2 000 and 50-2 000, respectively. The lipidomics model was established by orthogonal partial least squares discriminant analysis (OPLS-DA). Differential lipid metabolites were identified based on multivariate statistics.Result:OPLS-DA model could obviously distinguish CHD patients with syndrome of intermingling of phlegm and static blood and healthy volunteers. A total of 15 plasma differential lipid metabolites were identified, such as C16 sphinganine, phytosphingosine, N, N-dimethyl-safingol, 2-hydroxyphytanic acid, orotinichalcone, PC[18∶2(2E, 4E)/0∶0], PC(0∶0/16∶0), epitestosterone sulfate, etiocholanolone sulfate, PS[22∶1(11Z)/0∶0], PC[16∶0/20∶4(5E, 8E, 11E, 14E)], PC[19∶1(9Z)/17∶2(9Z, 12Z)], PC(16∶0/0∶0), PC(18∶0/0∶0), PS[15∶1(9Z)/22∶1(11Z)].Conclusion:There are significant differences in plasma lipid characteristics between CHD patients with syndrome of intermingling of phlegm and static blood and healthy volunteers. The plasma differential lipid metabolites are helpful for the accurate differentiation of CHD patients with syndrome of intermingling of phlegm and static blood.
Keywords：syndrome of intermingling of phlegm and static blood;coronary heart disease;plasma;lipidomics;differential lipid metabolites;phosphorylserine (PS);phosphatidylcholine (PC)
Abstract：Objective:To investigate the feasibility of near-infrared spectroscopy for detecting the coating film thickness of Tianshu tablets.Method:Nine batches of Tianshu tablets were taken during the coating process. Then, their near-infrared diffuse reflection spectra were collected. The sample set was divided into calibration set and validation set by Kennard-Stone algorithm. The preprocessing method was selected. The synergy interval partial least squares (siPLS) and moving window partial least squares (mwPLS) were employed to screen the optimal spectral interval. And the corresponding quantitative calibration model of partial least squares (PLS) were established. Some evaluation parameters were adopted to assess the performance of the model.Result:The method of first derivative and Norris Derivative smoothing combined with standard normal variate transformation was suitable for processing the spectra. The optimal PLS model was established in the preferred band interval of siPLS. The correlation coefficient between the predicted value and the measured value of calibration set was 0.966, and the correlation coefficient between the predicted value and the measured value of validation set was 0.991.Both root mean square error of calibration (RMSEC) and root mean square error of prediction (RMSEP) values were small, which showed the fitness and predictive performance of the model were favorable.Conclusion:The near-infrared spectroscopy technique can be used to determine coating film thickness of Tianshu tablets with high accuracy, which provides technical supports for the in-line determination of coating thickness in the production process of traditional Chinese medicine tablets.
Keywords：Tianshu tablets;near-infrared spectroscopy;film thickness;partial least squares;Kennard-Stone algorithm;synergy interval partial least squares (siPLS);coating weight gain
Abstract：Objective:To compare the protective effect of different bile (porcine bile, oxgall and sheep bile) and their Arisaema cum Bile on rats with acute lung injury, so as to provide reference for the selection of bile and the classification of decoction pieces of Arisaema cum Bile.Method:Wistar male rats were randomly divided into 8 groups (n=12), including blank group, model group, porcine bile group, oxgall group, sheep bile group, Arisaema cum Bile with porcine bile group, Arisaema cum Bile with oxgall group and Arisaema cum Bile with sheep bile group. Rats in each treatment group were given corresponding drug solution by gavage at 2.52 g·kg-1 every day, and rats in the model group and the blank group were given the same volume of normal saline by gavage every day for a total of 8 days. On the 8th day, after 1 h of administration, rats in the model group and each treatment group were intraperitoneally injected lipopolysaccharide (LPS, 2 mg·kg-1) to prepare rat lung injury model. Blood and lung tissues were collected from every four rats at 3, 6, 24 h after LPS injection, respectively. Lung coefficient, lung water content and wet weight/dry weight ratio of lung tissue (W/D) were measured, and the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and thromboxane B2 (TXB2) in serum and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the contents of malondialdehyde (MDA) and matrix metalloproteinase-9 (MMP-9) in lung tissue were determined by enzyme linked immunosorbent assay (ELISA). The pathological morphology of rat lung tissue was observed and the score of lung tissue injury was calculated.Result:Compared with the model group at the same time point, the lung coefficient, W/D, lung water content, contents of TNF-α, IL-6 and TXB2 in serum, contents of MDA and MMP-9 in lung tissue of rats in each treatment group were all decreased, and most of them had significant differences (P<0.05, P<0.01), but the activities of GSH-Px and SOD were all increased, and most of them had significant differences (P<0.05, P<0.01). The oxgall group and the sheep bile group were superior to the porcine bile group in most of the indexes, the Arisaema cum Bile with oxgall group and the Arisaema cum Bile with sheep bile group were superior to the Arisaema cum Bile with porcine bile group, and some of them had significant differences(P<0.05, P<0.01).Conclusion:Each bile group and each Arisaema cum Bile group all have protective effects on rats with acute lung injury induced by LPS, and the therapeutic effect of oxgall and sheep bile is better than that of porcine bile, the therapeutic effect of Arisaema cum Bile prepared by oxgall and sheep bile is better than that of Arisaema cum Bile prepared by porcine bile.
Keywords：porcine bile;oxgall;sheep bile;Arisaema cum Bile;acute lung injury;inflammatory factors;lipopolysaccharide
Abstract：Objective:To study the chemical constituents of pericarps of Zanthoxylum bungeanum.Method:The dried pericarps of Z. bungeanum were smashed, and then extracted and concentrated in 95%ethanol to obtain the total extract. The total extract was loaded on a silica gel CC, eluted with different polar solvents in sequence, and then concentrated to obtain corresponding parts. The methylene chloride fraction and the n-butanol fraction were separated and purified by silica gel column chromatography, Sephadex LH-20 gel column chromatography, ODS column chromatography, semi-preparative HPLC, etc. And their structures were identified based on physicochemical properties and various spectroscopic methods.Result:Fourteen compounds were isolated from the dichloromethane fraction and the n-butanol fraction of the Z. bungeanum and identified as(1S, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-β-carboline-3-carboxylic acid(1), (3S)-1, 2, 3, 4-tetrahydro-β-carboline-3-carboxylic acid(2), apigenin-7, 4′-dimethyl ether(3), genkwanin(4), lcariside F2(5), breyniaionoside A(6), 3-methoxyphenethyl alcohol-4-O-β-D-glucopynanoside(7), 1-O-β-D-glucopyranosyloxy-3-methoxy-5-hydroxybenzene(8), orcinol-O-β-D-glucopyranoside(9), syringin(10), 4-[(3S)-3-hydroxybutyl]-2-methoxyphenyl-β-D-glucopyranoside(11), (+ )-lyoniresinol-3a-O-β-D-glucopyranoside(12), 2-methylpropanyl-6-O-β-D-apiofuranosyl-β-D-glucopyranoside(13)and(E)-6-hydroxy-2, 6-dimethylocta-2, 7-dienoic acid(14).Conclusion:All compounds were isolated from Z. bungeanum for the first time, and compounds 1-4, 12 and 14 were isolated from this genus for the first time.
Abstract：Objective:To study the chemical constituents from n-butanol extract of Akebia trifoliata caulis.Method:The 100 kg caulis of A. trifoliata was extracted with 75% ethanol (EtOH) for three times by heating reflux. These 3 extracts were decompressed and concentrated, and then dissolved in water. The solvent was successively extracted with dichloromethane, ethyl acetate and n-butanol. The chemical constituents from the n-butanol fraction were isolated by macroporous, silica gel, sephadex LH-20 and ODS columns, and semi-preparative high performance liquid chromatography, and their chemical structures were determined through MS, NMR analysis (1H and 13C-NMR) and spectroscopic data from literatures.Result:Totally 14 compounds were isolated and identified as mutongsaponin B(1), mutongsaponin C(2), saponin PH(3), begoniifolide A(4), 2α, 3β, 23-trihydroxy-30-noroleana-12, 19-dien-28-oicacid-O-β-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl ester(5), akemisaponins D(6), akemisaponins E(7), asiaticoside(8), saponin PJ1(9), scheffoleoside A(10), symplocosneolignan A(11), kalopanax-saponins D(12), leonticin E(13), ciwujianoside A1(14).Conclusion:Compounds 1-4, 11, 13, 14 were isolated from this plant for the first time. The discovery of these compounds further enriched the chemical constituents of A. trifoliata, and provided experimental and scientific basis for the comprehensive development and utilization of A. trifoliata.
Abstract：Objective:To establish the HPLC fingerprint of aqueous extract of Citri Reticulatae Pericarpium, and research the spectrum-effect relationship in diabetic cognitive dysfunction rats.Method:The HPLC fingerprints of 21 batches of Citri Reticulatae Pericarpium were established, with acetonitrile (A)-0.1%of phosphoric acid (B) as the flow phase for gradient elution. The detection wavelength was 270 nm. Acomparative analysis was performed for the results based on similarity evaluation, SPSS 24.0 two-dimension clustering analysis and SIMCA 14.1 principal component analysis of fingerprint software. Thediabetic rat model wasduplicated by one-time intraperitoneal injection with streptozotocin (STZ) at the dose of 50 mg·kg-1. After successful replication of the model, thediabetic rats were given aqueous extract of Citri Reticulatae Pericarpium by gavage. The blood glucose value was determined at regular intervals. The cognitive function was analyzed with Morris water maze experiment at the 12 week. Grey relational analysis (GRA) and partial least squares regression analysis were used to study the spectrum-effect relationship.Result:Totally 16 common peaks of water extract of Citri Reticulatae Pericarpium were confirmed, five substances were identified, and 21 species of Citri Reticulatae Pericarpium of different varieties and origins were divided into 2 categories. Compared with the model group, the blood glucose of rats in each group treated with water extract of Citri Reticulatae Pericarpiumwere reduced, and their cognitive function was improved.According to the grey correlation analysis and the least partial square regression analysis, the peaks No. 19, 15, 4, 17 and 6 were significantly correlated with the cognitive function of diabetic rats.Conclusion:There were some differences in aqueous extract of Citri Reticulatae Pericarpium between different varieties and origins. It is convenient and fast to make a comprehensive quality evaluation of aqueous extract of Citri Reticulatae Pericarpium of different varieties and producing areas by stoichiometry, and aqueous extract of Citri Reticulatae Pericarpium can reduce the blood glucose level and improve the cognitive function of diabetic cognitive dysfunction rats, its mechanisms of action are resultedfrom the joint effects of multiple effective components, and peaks No. 19, 15, 4, 17 and 6 are components closely related to the cognitive function of diabetic rats.
Keywords：aqueous extract of Citri Reticulatae Pericarpium;fingerprints;chemometrics;diabetes;cognitive dysfunction;grey relational analysis;partial least squares regression analysis;spectrum-effect relationship
Abstract：Objective:To establish an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the simultaneous determination of 15 pyrrolidine alkaloids (PAs) and their nitrogen oxides, and determine the content of the 15 PAs in the 15 batches of Farfarae Flos samples obtained from different sources, in order to understand the distribution status of these 15 PAs in Farfarae Flos from different sources, and provide relevant references for the safe and rational use of this medicinal materials.Method:The method was achieved by Agilent Eclipse Plus C18 column (3.0 mm×150 mm, 1.8 μm) using a mobile phase made up of 0.05%formic acid and 2.5 mmol·L-1 ammonium formate in water (A)-0.05%formic acid and 2.5 mmol·L-1 ammonium formate in methanol(B). The flow rate and the injection volume were 0.4 mL·min-1 and 2 μL, respectively. The column temperature was 40 ℃. The instrument was Agilent 1290-6470 QQQ ultra high performance liquid chromatography-triple quaternary bar mass spectrometer. The components were detected in multiple reaction monitoring mode by mass spectrometry with ionizationmode of ESI+. The content of the components measured in the samples was calculated by using the external standard method, and the difference between samples was analyzed based on RSD of different components.Result:The established method had a high sensitivity and good separation degree. The results of methodological investigation met the requirements. The results showed that all of the 15 batches of Farfarae Flos contained PAs and their nitrogen oxides. These PAs had almost the same types of structure. There were significant differences in the content and distribution of PAs in Farfarae Flos obtained from different sources.Conclusion:In general, Farfarae Flos contains pyrrolidine alkaloids and their nitrogen oxides. Senkirkine with a significant hepatotoxicity is the main compound. The content determination of PAs will provide scientific fundaments for the safe and effective use of Farfarae Flos.
Abstract：Objective:To explore the feasibility of Photoshop image processing software in the micro-spherical diameter measurement and identification of medicinal materials, in order to provide a new method for the measurement and mapping of traditional Chinese medicine.Method:Photoshop (CS3 version and above) software was used to measure the diameter of 200 Notoginseng Radix et Rhizoma albumin microspheres in the same batch, digital microscopy and Photoshop image processing software was used to draw schematic diagrams of microstructures of Notoginseng Radix et Rhizoma medicinal powders and its four common pseudo-products and powders, namely Bletillae Radix, Alpiniae Officinarum Rhizoma, Curcumae Longae Rhizoma and Manihot esculenta, and make the identification table for classification and identification.Result:The average diameter of the microspheres was (30.62±4.21)μm, and the diameter was mainly distributed in 20-40 μm. The average diameter of the microspheres was verified by laser particle size analyzer (30.18±4.67)μm. The differences between the two methods were not statistically significant. There were many starch granules in Notoginseng Radix et Rhizoma powder, with no calcium oxalate needle, oil cell, brown pigment and stone cell. Microscopic identification could be made for Notoginseng Radix et Rhizoma powder and 4 common counterfeits.Conclusion:Photoshop image processing software measures the diameter of the microspheres with a high speed, high accuracy, simplicity, and low requirements for measuring instruments. It provides a new way to quickly measure the diameter of microspheres. Photoshop image processing software draws a schematic diagram of the microstructure, which is convenient and faster. The original morphology of the ground-reactive microstructure provides a new method for the microstructural drawing.
Abstract：Objective:To study the mechanism of modified Taohe Chengqitang in preventing and treating diabetic gastroparesis by regulating relative genes and signaling pathways based on network pharmacology.Method:Target genes of modified Taohe Chengqitang were obtained from Bioinformatics Analysis Tool for Molecular Mechanism of TCM (BATMAN-TCM) database, and target genes of diabetic gastroparesis were obtained from Comparative Toxicogenomics Database (CTD) database. The target genes of modified Taohe Chengqitang-diabetic gastroparesis intersection protein were obtained through the integration of two groups of genes. STRING was used to build the protein-protein interaction network and visualize the results. Cytospace software ClueGO, CluePedia plug-in were used for gene ontology (GO) analysis and enrichment analysis of KEGG pathway of modified Taohe Chengqitang-diabetic gastroparesis target genes intersection, and results were visualized. Finally, CTD database and literatures were used to obtain intersection genes in the treatment of diabetic gastroparesis.Result:Among 621 target genes in modified Taohe Chengqitang, 25 were related to diabetic gastroparesis. By regulating expressions of MLNR, SST, PTGS1, HRH2, HTR3A, HTR4, HTR7, NOS3 and other intersection genes, Taohe Chengqitang could improve the gastrointestinal hormone levels, affected the combination of serotonin and its receptors, activated adenylate cyclase (AC), and induced cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA), so as to activiate AC/cAMP/PKA signaling pathway, regulate Ca2+ /K+ channel, control ion balance, promote the adaptability of gastric smooth muscle, and contract gastric smooth muscle to regulate gastric volume. At the same time, gastric acid secretion was improved to protect gastric mucosa, which may help improve vasoconstriction and hemodynamics.Conclusion:Based on the network pharmacology, modified Taohe Chengqitang has multiple mechanisms in the prevention and treatment of diabetic gastroparesis. This study explored relevant signaling pathways, advantages and research directions of modified Taohe Chengqitang in treatment of diabetic gastroparesis.
Abstract：Objective:Evaluate the effects of Danhong injection for perioperative percutaneous coronary intervention (PCI) on cardiac function and thrombolysis in myocardial infarction (TIMI) in patients with acute myocardial infarction (AMI).Method:Computer retrieving CNKI, Wanfang database, VIP database, PubMed, CBM, Web of Science, The Cochrane Library, gathering Danhong injection in percutaneous coronary intervention perioperative application in the treatment of acute myocardial infarction clinic trials. The Cochrane risk evaluation is adopted to improve the quality of literature evaluation, with Revman 5.3 software for Meta-analysis.Result:Participants included in 12 clinic trials contains a total of 1 131 patients, including 569 patients in Danhong treatment and 562 patients in control group. The results showed that compared with conventional treatment, Danhong injection treated patients had LVEF increased obviously [mean difference (MD)=6.62, 95% confidence interval (CI) (4.91, 8.34), P<0.000 01], the number of TIMI class 3 patients significantly increased[relative risk (RR)=0.22, 95%CI(0.12, 0.41), P<0.000 01], and BNP levels significantly decreased [MD=151.86, 95%CI (-247.00, -56.72), P=0.002].Conclusion:Danhong injection can improve the function of acute myocardial infarction after percutaneous coronary intervention.
Keywords：acute myocardial infarction (AMI);percutaneous coronary intervention (PCI);Meta-analysis;left ventricular ejection fraction (LVEF);brain natriuretic peptide (BNP);thrombolysis in myocardial infarction (TIMI);cardiac function
Abstract：Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder among children. The theory of traditional Chinese medicine (TCM) does not have a special term of this disease, and classifies ADHD to the category of " forgetfulness" " dysphoria" " injudiciousness" according to its clinical manifestations. TCM theoretic and clinical systems for treating ADHD have been developed, but current pharmacodynamics studies of TCM on ADHD have mostly focused on neurotransmitter metabolic system and its receptor signaling pathway to reflect the advantages of multi-component and multi-target effect of TCM, but failed to demonstrate the scientific connotations of TCM theory, such as " coordination between kidney and brain" and " steady Yin and vexed Yang" , and ignored the delay in cortical maturation as the core neuropathology of ADHD. The symptoms relating to " restlessness of Yang" due to Yin deficiency that cannot inhibit hyperactivity of Yang, kidney-Yin deficiency and liver-Yang excess syndrome is the most common syndrome of ADHD, and TCMs with effect of invigorating kidney and filling sea of marrow are mostly used by TCM practitioners. According to anatomy basis of neuronal development disorder, the new theory of " energy metabolism dysfunction" , the pathogenesis hypothesis of sea of marrow development disorder and its relevant clinical practices and experimental studies, substantial basis studies of the therapy for " invigorating kidney and filling sea of marrow" , as well as pharmacodynamics study of Rehmannia glutinosa (Shudihuang) for treating ADHD, we put forward ADHD pathogenesis that " restlessness of Yang due to Yin deficiency" is related to the disorder of executive function due to the delay in cortical maturation, energy metabolism dysfunction and neurodevelopmental disorder, and regarded that TCMs with effect of invigorating kidney and filling sea of marrow are the most commonly used to treat ADHD, and improve delay in cortical maturation corresponding to sea of marrow insufficiency by regulating dysfunction of neurodevelopment and energy metabolism, so as to relieve the core symptoms of ADHD. The new treatment model of TCM with effect of invigorating kidney and filling sea of marrow for treating ADHD will provide a theoretical basis for improving the clinical efficacy of ADHD.
Keywords：attention deficit hyperactivity disorder;restlessness of Yang due to Yin deficiency;energy metabolism dysfunction;delay in cortical maturation;invigorating kidney and filling sea of marrow
Abstract：Traditional health preservation thoughts of four major schools (Confucianism, Buddhism, Taoism and medicine) were systematically summarized. The proposed health-preserving ideas of physical health maintenance by Confucianism (self-cultivation, moderation and harmony), mental health maintenance by Buddhism (keeping still and in deep meditation, insight, kindness and help), health preservation by Taoism (following the nature, enhancing spirit and energy) and life protecting by medicine (dredging collaterals, Qi and blood, possessing both the form and the spirit), and the health-preserving methods under the guidance of such ideas have important guiding value for current industry of traditional health care.
Abstract：In recent years, Tripterygii Radix et Rhizoma polyglycosides have been used more and more widely in clinic, mostly in the treatment of rheumatoid arthritis. Besides, it is also used as a basic immunosuppressive drug to treat various kidney diseases, such as nephrotic syndrome. However, there are many adverse reactions in clinic, as well as controversies over its medication regimen, especially its dosage and time. To make rational use of Tripterygii Radix et Rhizoma polyglycosides in clinic and further study, the pharmacological and toxicological research progress of Tripterygii Radix et Rhizoma polyglycosides was reviewed. The author collected pharmacological and toxicological research literatures of Tripterygii Radix et Rhizoma polyglycosides at home and abroad in recent years, finding that Tripterygii Radix et Rhizoma polyglycosides have the pharmacological effects of anti-inflammation, anti-tumor, kidney protection and immunosuppression, and mainly plays a pharmacological role by regulating the expression of cytokines in NF-κB signaling pathway, mTOR signaling pathway and apoptosis-related signaling pathway. And the toxicological effects of Tripterygii Radix et Rhizoma polyglycosides mostly focused on hepatotoxicity, nephrotoxicity and reproductive system toxicity, which are mostly related to oxidative stress response and expression of inflammatory factors. The main components of Tripterygii Radix et Rhizoma polyglycosides are triptolide and celastrol. The pharmacological and toxicological studies of Tripterygii Radix et Rhizoma polyglycosides are in-depth, the results showed that the efficacy and toxicity were dose-dependent and time-dependent, with no toxicity study of Tripterygii Radix et Rhizoma polyglycosides varying with dosage and time in the context of efficacy, indicating dose-effect, time-effect, dose-toxicity, time-toxicity relationships. Relevant mechanisms still need further study.
Keywords：Tripterygii Radix et Rhizoma polyglycosides;pharmacology;toxicology
Abstract：By reviewing the 2015 edition of Chinese Pharmacopoeia, the author collected 37 neutral blood-activating and stasis-removing traditional Chinese medicines. And by retrieving literatures on relevant material basis and pharmacological effects on CNKI, the author organized and summarized their chemical composition and pharmacological effects. Neutral blood-activating and stasis-removing traditional Chinese medicines are rich in chemical components, such as flavonoids, steroids and sugars. At the same time, it has a variety of pharmacological effects, including anti-platelet aggregation and anti-thrombotic mechanism, anti-atherosclerosis, inhibition of ischemia-perfusion injury, anti-tumor, anti-fibrosis, liver protection, anti-inflammatory analgesia, blood pressure reduction and immune regulation. It is widely used in the treatment of liver fibrosis, cardiovascular disease, liver cancer, uterine cancer, hypertension, hyperlipidemia and other diseases. Nowadays, as people has paid increasing attention to neutral herbs, studies on traditional Chinese medicines for activating blood circulation and removing blood stasis have been further deepened, which provides a better development prospect for neutral blood-activating and stasis-removing traditional Chinese medicines. From the perspective of medicinal properties, the authors systematically collected and summarized the pharmacological effects and material basis of neutral blood-activating and stasis-removing traditional Chinese medicines. This article provides theoretical guidance for the clinical application of neutral blood-activating and stasis-removing traditional Chinese medicines and new medicine research ideas for neutral blood-activating and stasis-removing traditional Chinese medicines.
Keywords：blood-activating and stasis-removing Chinese medicine;neutral herb;material basis;pharmacological effect;research progress
Abstract：Zhenwutang is the classic formula of Wenyang Lishui in " Treatise on Febrile Diseases" . It consists of five kinds of medicines, namely Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma Recens, Atractylodis Macrocephalae Rhizoma, Poria, Paeoniae Radix Alba or Paeoniae Radix Rubra. It has been included in the Catalogue of Ancient Classics (The First Batch) issued by the State Administration of Traditional Chinese Medicine in 2018.There are two articles in the " Treatise on Febrile Diseases" about the syndromes of Zhenwutang. On the basis of Article 82 of the Chapter of Taiyang disease, the Taiyang disease is demonstrated by sweating, but after that the patient still suffers from fever, epigastric throb, dizziness and shiver, this shall be treated with Zhenwutang. According to Article 316 of the chapter of Shaoyin disease, Shaoyin disease lasts for two or three days, until the fourth and fifth days, and is demonstrated by abdominal pain, difficult urination, severe pain in the limbs and diarrhea, the patient have a cough, diuresis, diarrhea and vomit, this shall be treated with Zhenwutang. The original texts discuss the basic pathogenesis is edema syndrome due to Yin and Yang deficiency, with symptoms of unfavorable urination, heavy limbs or edema, pale tongue, white moss and heavy pulse as dialectical points. In terms of the compatibility of prescriptions, usage and dosage, and the interpretation of prescriptions, this paper examines Zhenwutang syndromes in " Treatise on Febrilediseases" , summarizes the material basic research of Zhenwutang, and provides the basis for the quality control of its compound pharmacodynamics. This study summarizes the progress of pharmacological research for Zhenwutang in recent years, finds that Zhenwutang has many efficacies, such as cardiotonic, diuretic, lowering lipid, anti-oxidation, improving renal function and balancing of water and liquid metabolism, lists traditional Chinese medicine(TCM) syndromes treated with Zhenwutang, such as heart palpitations, edema, cough, abdominal pain, sipping, dizziness, and Western medicine diseases, like congestive heart failure, pulmonary heart disease, bronchial asthma, chronic colitis, cirrhosis, ascites, chronic glomerulonephritis, chronic renal failure, benign prostatic hyperplasia and Meniere's syndrome, expounds the principle of Zhenwutang for " treating different diseases with the same therapy" , in order to provide useful reference for the research and development and clinical application of Zhenwutang and more classic prescriptions.
Keywords：Zhenwutang;Treatise on Febrile Diseases;Fangzheng analysis;treat different diseases with the same therapy;modern research
Abstract：Cinnamomi Ramulus is a dry tender branch of Cinnamomum cassia Presl, which is a multifunctional traditional Chinese medicine(TCM). Cinnamomi Ramulus has different efficacy under different compatibility environment. Complet medicine is a commonly used and relatively fixed compatibility form of two drugs, and it is the smallest unit in the compatibility of TCM. The four kinds of complet medicine commonly used in Cinnamomi Ramulus were as follows: the diaphoretics pungent in flavour and warm in property pairs include Cinnamomi Ramulus Ephedrae Herba and Cinnamomi Ramulus Bupleuri Radix complet medicine. The stasis dredge collaterals pairs involve Cinnamomi Ramulus Poria and Cinnamomi Ramulus Persicae Semen complet medicine. The regulation Qi and Blood Cinnamomi Ramulus Paeoniae Radix Alba complet medicine. Wenda Tongyang pairs consist of Cinnamomi Ramulus Aconiti Lateralis Radix Praeparaia, Cinnamomi Ramulus Astragali Radix, and Cinnamomi Ramulus Glycyrrhizae Radix et Rhizoma complet medicine. After compatibility, some changes have taken place in the chemical composition of complet medicines. For example, after compatibility of Cinnamomi Ramulus and Ephedrae Herba, the content of effective components of both herbs decreases, and the chemical constituents that are not found in single herbs are produced. After compatibility of Cinnamomi Ramulus and Bupleuri Radix, the dissolution of active ingredients is related to compatibility ratio. The active ingredients of Cinnamomi Ramulus Poria, Cinnamomi Ramulus Paeoniae Radix Alba pair and Cinnamomi Ramulus Aconiti Lateralis Radix Praeparaia have also changed to some extent.The content of active ingredients in Astragali Radix and Glycyrrhizae Radix et Rhizoma both increase after compatibility with Cinnamomi Ramulus. Different complet medicine have different pharmacological effects, Cinnamomi Ramulus Ephedrae Herba complet medicine have the effect of transpiration and antipyretic, Cinnamomi Ramulus Bupleuri Radix complet medicine can analgesia. Cinnamomi Ramulus Poria complet medicine have the effect of diuretic, improve myocardial ischemia and so on. Cinnamomi Ramulus Persicae Semen complet medicine have the anti-coagulation action.Cinnamomi Ramulus Paeoniae Radix Alba complet medicine have the anti-inflammatory and analgesic activities. Cinnamomi Ramulus Aconiti Lateralis Radix Praeparaia complet medicine have the effect of dispelling cold to relieve pain. Cinnamomi Ramulus Astragali Radix complet medicine have the many effects in relieving anti-coagulation, antioxidation and anti-myocardial ischemia. Cinnamomi Ramulus Glycyrrhizae Radix et Rhizoma complet medicine displays diverse activities, including antiarrhythmic, antithrombosis. In this paper, the chemical constituents and pharmacology of four kinds of complet medicine of Cinnamomi Ramulus were reviewed, which provided a reference for the better open utilization of Cinnamomi Ramulus complet medicine.