Abstract:ObjectiveTo investigate the mechanism of Chaihu Qinggantang (CHQGT) in the treatment of granulomatous lobular mastitis (GLM) in the rat model.MethodSixty female rats were divided into a normal group, a model group, a prednisolone group (0.001 8 g·kg-1), and three CHQGT low-dose, medium-dose, and high-dose groups (4.5, 8.9, 17.8 g·kg-1). The tissue homogenates mixed with GLM lesion tissue and Fritner's reagent were used for modeling. After modeling, the treatment groups were given corresponding treatment factors, and the normal group and the model group were given the equal volume of normal saline. The changes in mammary gland of rats were observed after 14 d. Hematoxylin-eosin (HE) staining was used to observe the histopathological changes in breast samples. The mRNA expressions of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, Caspase-1, and interleukin-1β (IL-1β) were detected by real-time quantitative fluorescence polymerase chain reaction (Real-time PCR). The protein expressions of NLRP3, Caspase-1, IL-1β, and IL-18 were detected by Western bolt.ResultAs compared with the normal group, the breasts of rats in the model group were obviously swelling, and mammary gland inflammation index was significantly increased (P<0.01). Pathological changes included the formation of granuloma centered on the lobule of mammary gland with a large number of inflammatory cells such as lymphocytes and plasma cells. The mRNA expressions of NLRP3, Caspase-1, and IL-1β, and the protein expressions of NLRP3, Caspase-1, IL-1β, and IL18 in the model group were significantly increased (P<0.01). Compared with the model group, the treatment groups improved breast swelling, and the CHQGT medium and high-dose groups and the prednisolone group reduced inflammation index to some extent after treatment (P<0.05, P<0.01). The inflammation degree of mammary gland was significantly improved, and inflammatory cells such as macrophages, lymphocytes, and plasma cells were reduced to varying degrees in pathological aspects. The mRNA expressions of NLRP3, Caspase-1, and IL-1β, and the protein expressions of NLRP3, Caspase-1, IL-1β, and IL-18 in the CHQGT high-dose group and the prednisolone group were significantly down-regulated (P<0.05, P<0.01).ConclusionCHQGT inhibits inflammation and treats GLM in rats. The mechanism is possibly related to the inhibition of NLRP3/IL-1β signaling pathway, which provides a new target for the prevention and treatment of GLM by Qingxiao method.
Keywords:granulomatous lobular mastitis;animal model of granulomatous lobular mastitis;Chaihu Qinggantang;Qingxiao method;NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome;NLRP3/interleukin-1β (IL-1β) signaling pathway
Abstract:ObjectiveTo observe the clinical effect of governor meridian moxibustion combined with modified Youguiwan in treating erectile dysfunction of kidney Yang deficiency type and its influence on the level of sex hormones and penile hemodynamics.MethodA total of 120 patients were randomized into the control group (60 cases in total, 3 dropouts/lost to follow-ups, 57 finally included) and treatment group (60 cases in total, 2 dropouts/lost to follow-ups, 58 finally included) with the random number table method. Both groups received governor meridian moxibustion (1 time/w, a total of 4 times). In addition, the control group took oral compound Xuanju capsule (3 capsules/time, 3 times/d), and the treatment group was given Jiawei Youguiwan (Chinese medicine decoction, 1 dose/d). The administration lasted 4 weeks for both groups. The scores of 5th edition international index of erectile function (IIEF-5), erection quality scale (EQS), and erectile hardness score (EHS), traditional Chinese medicine (TCM) syndrome score, levels of sex hormones [testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL)], and parameters of penile hemodynamics [peak systolic velocity (PSV), end-diastolic volume (EDV), and resistance index (RI)] were recorded.ResultAfter treatment, the total effective rate was 87.93% (51/58) in the treatment group, higher than the 71.93% (41/57) in the control group (χ2=4.600 3, P<0.05). After treatment, compared with before treatment,the treatment group registered increase in the scores of IIEF-5, EQS, and EHS (P<0.01), decrease in TCM syndrome score (P<0.01), rise of serum T level (P<0.05), reduction in the levels of FSH, LH, and PRL (P<0.05), increase in the levels of PSV and RI (P<0.05), and down-regulation of EDV level (P<0.05).ConclusionGovernor meridian moxibustion combined with modified Youguiwan can effectively improve the penile erectile function, erectile hardness, and erection quality, and relieve the clinical symptoms of erectile dysfunction patients of kidney Yang deficiency type.
Keywords:erectile dysfunction;governor meridian moxibustion;modified Youguiwan;kidney Yang deficiency
Abstract:ObjectiveBased on the inhibitory activity of phosphodiesterase (PDE), a method for determining the anti-inflammatory activity of Qingjin Huatantang was established to supplement and improve the quality control system of this famous classical formula.MethodHigh performance liquid chromatography (HPLC) was used to determine the activity of PDE, and the dose-effect relationship of inhibiting PDE activity of Qingjin Huatantang was investigated. The mobile phase consisted of methanol-0.5% acetic acid aqueous solution (5∶95), and the detection wavelength was 254 nm. By measuring the PDE inhibition rate of multiple batches of Qingjin Huatantang water extract lyophilized powder, biological activity was marked with the activity of the neutralizing enzyme in the international unit U.ResultWhen the concentration of reaction substrate (cyclic adenosine monophosphate) was 50 μmol·L-1 and the reaction time was 60 min, the enzymatic reaction was stable with 4 U·mL-1 of PDE. In this reaction system, when the concentration of Qingjin Huatantang water extract lyophilized powder was 0.11-3.0 g·L-1, the inhibitory effect of PDE showed a concentration-dependent relationship. It was determined that the concentration of Qingjin Huatantang water extract lyophilized powder to be tested was 1 g·L-1, which showed a significant and stable inhibitory effect on PDE, and the inhibitory rate was >45%, that is, 1 mg of Qingjin Huatantang water extract lyophilized powder could neutralize the activity of 1.8 U PDE at least.ConclusionThis study establishes a biological activity evaluation method of Qingjin Huatantang based on the inhibitory activity of PDE, and the anti-inflammatory activity of Qingjin Huatantang is characterized by international unit U of PDE activity, which can provide a new method for the determination of biological activity of traditional Chinese medicine compounds.
Abstract:ObjectiveTo explore the effect of Youguiwan on the rats with adriamycin-induced nephrotic syndrome (NS) and its mechanism.MethodSD rats were randomly divided into a normal group, a model group, three Youguiwan low, medium, and high-dose groups, and a prednisone group. Rats in the model group were intravenously injected with adriamycin in the tail vein to induce the NS model. Rats in the Youguiwan low, medium, and high-dose groups were given 2.8, 5.6, 11.2 g·kg-1·d-1 of crude drugs, respectively, and rats in the prednisone group were given 6.3 mg·kg-1·d-1 of prednisone acetate. Each administration group was given continuous medicine for 6 weeks, and the normal group and model group were given an equal volume of normal saline. Bicinchoninic acid (BCA) assay was used to detect 24 h urine protein (24 h UP). Automatic biochemical analyzer was used to detect serum urea nitrogen (BUN), creatinine (SCr), albumin (ALB), total cholesterol (TC), and triglyceride (TG) levels. Hematoxylin-eosin (HE) staining was used to observe renal tissue morphology, and kit was used to detect serum advanced oxidized protein products (AOPPs) and reactive oxygen species (ROS). Western blot was used to detect the receptor of advanced glycation endproducts (RAGE) of renal tissue, nuclear factor-κB (NF-κB) phosphorylation levels, Wnt, and β-catenin protein expression.ResultAs compared with the normal group, 24 h UP, serum BUN, SCr, TC, TG, AOPPs, and ROS levels in the model group increased significantly (P<0.01), whereas ALB decreased (P<0.01). There were typical pathological injuries in the renal tissue, and the expressions of RAGE, phosphorylation(p)-NF-κB, Wnt1, and β-catenin protein were significantly increased (P<0.01). As compared with the model group, the 24 h UP, serum BUN, SCr, TC, TG, AOPPs, and ROS levels of rats in the Youguiwan low, medium, and high-dose groups significantly reduced (P<0.01), and ALB significantly increased (P<0.01). The renal tissue damage was reduced, and the expressions of RAGE, p-NF-κB, Wnt1, and β-catenin protein were significantly decreased (P<0.01) in a dose-dependent manner.ConclusionYouguiwan improves the kidney injury of rats with adriamycin-induced NS. The mechanism may be related to the reduction of AOPPs level, inhibition of RAGE/ROS/NF-κB axis, and activation of Wnt/β-catenin signal.
Keywords:Youguiwan;nephrotic syndrome;advanced oxidized protein products (AOPPs);receptor of advanced glycation endproducts (RAGE)/reactive oxygen species (ROS)/nuclear factor-κB (NF-κB);Wnt/β-catenin
Abstract:ObjectiveTo explore the mechanism of Si Junzitang in regulating the expression of NKG2A to affect the anti-colon cancer function of natural killer (NK) cells.MethodNK cells isolated from healthy honors were cultured and used to construct the three incubation models of NK cells, human colon cancer HCT116 cells, and NK cells + HCT116 cells (co-incubation). real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was conducted to determine the mRNA levels of natural killer group 2 member A (NKG2A) and interleukin (IL)-15 in NK cells, as well as the mRNA level of histocompatibility leucocyte antigen E (HLA-E) in HCT116 cells. The secretion of IL-15 was detected by enzyme-linked immunosorbent assay (ELISA). Methyl thiazolyl tetrazolium (MTT) assay was employed to determine the applicable concentration of IL-15 and test the effects of Si Junzitang and IL-15 on the activities of NK cells and the HCT116 cells in the co-incubation model. The effects of Si Junzitang and IL-15 on the mRNA levels of NKG2A in NK cells and HLA-E in HCT116 cells were detected by Real-time PCR. Monalizumab (M, anti-NKG2A mab) was used to block the NKG2A-HLA-E pathway in co-incubation model, and then the proliferation of HCT116 cells was detected by MTT assay.ResultThe interaction of NK cells and HCT116 cells up-regulated the mRNA levels of NKG2A in NK cells and HLA-E in HCT116 cells (P<0.05), as well as the expression level and secretion of IL-15 (P<0.05). Compared with the blank group, Si Junzitang and Si Junzitang + IL-15 promoted the proliferation and improved the anti-colon cancer function of NK cells (P<0.01). Furthermore, they down-regulated the mRNA levels of NKG2A in NK cells and HLA-E in the HCT116 cells co-incubated with NK cells (P<0.01). M and IL-15 + M inhibited the proliferation of HCT116 cells compared with the groups without M (P<0.01).ConclusionThe interaction of NK cells and HCT116 cells can induce activation of NKG2A-HLA-E pathway to impair NK cell function. Si Junzitang can inhibit the activation of NKG2A-HLA-E pathway to restore the anti-colon cancer function of NK cells.
Keywords:natural killer (NK) cells;natural killer group 2 member A (NKG2A);histocompatibility leucocyte antigen E (HLA-E);interleukin (IL)-15;colon cancer;Si Junzitang
Abstract:ObjectiveTo observe the therapeutic effect of Radix Paeoniae Rubra-Radix Aconiti Lateralis on acute-on-chronic liver failure (ACLF) rats and its effect on M1/M2 macrophage polarization.MethodMale SD rats were randomly divided into normal group, model group, positive group (lactulose, 1.8 g·kg-1) and traditional Chinese medicine (TCM) group (Radix Paeoniae Rubra-Radix Aconiti Lateralis, 5.85 g·kg-1), six in each group. The ACLF rat model was established by subcutaneous and tail vein injection of bovine serum albumin combined with intraperitoneal injection of D-galactosamine+lipopolysaccharide. Then the modeled rats were intervened with corresponding drugs for one week. The normal group and model group were given the same dose of distilled water. The histopathological changes of liver tissue were observed by hematoxylin-eosin (HE) staining. The mRNA and protein expression levels of CD86, inducible nitric oxide synthase (iNOS), CD206 and arginase 1 (Arg1) were detected by real-time polymerase chain reaction (Real-time PCR), Western blot and immunohistochemistry.ResultCompared with the conditions in the normal group, pseudolobule formation in liver tissue and morphological changes and necrosis of hepatocytes were observed in ACLF rats, accompanied by a large number of inflammatory cell infiltration. Moreover, the mRNA and protein expression levels of CD86, iNOS were up-regulated(P<0.01). Compared with the model group, the treatment groups had improved necrosis and inflammatory infiltration of hepatocytes, down-regulated mRNA and protein expression of CD86 and iNOS (P<0.01) and up-regulated mRNA and protein expression of CD206 and Arg1 (P<0.05, P<0.01), with the up regulation in the TCM group better than that in the positive group.ConclusionACLF rats had unbalanced M1/M2 macrophage polarization, and the imbalance shifted towards M1. Radix Paeoniae Rubra-Radix Aconiti Lateralis inhibited the activation of M1 macrophages and reduced the inflammatory response of liver failure by promoting the polarization of liver macrophages towards M2.
Abstract:ObjectiveThe pulmonary edema (PE) model where the disease was located in the viscera was established according to the treatment principle that patients with the disease location inside should be treated with descending and sinking medicine, combined with changes in the disease tendency, to verify the scientificity of descending and sinking properties of Descurainiae Semen Lepidii Semen (SD), and to preliminarily elucidate the scientific connotation of descending, ascending, floating and sinking of Chinese medicine.MethodSixty male SD rats were randomly divided into normal control group, model group (20 mg·kg-1), positive drug group (dexamethasone, 0.075 mg·kg-1) and SD low (1.167 g·kg-1), medium (2.334 g·kg-1)and high (4.668 g·kg-1) dose groups. The PE model was established by intrapleural injection of 1% carrageenan (2 mL·kg-1). The evaluation indexes (lung autopsy, amount of pleural effusion, number of white blood cells, lung wet/dry weight ratio, lung water content and lung permeability) were tested to determine the optimal dose of SD decoction for intervention of PE. The relevant indexes of the five major systems (central nervous system, respiratory system, circulatory system, digestive system and urinary system) closely related to the body's Qi movement were detected and changes in the disease tendency in PE rats were analyzed, to determine the descending, ascending, floating and sinking properties of SD. In addition, histopathological changes were investigated by hematoxylin-eosin (HE) staining, and types and numbers of inflammatory cells and mediators were detected to preliminarily explore the mechanism of SD in improving PE.ResultCompared with the conditions in the normal control group, the amount of pleural effusion, number of white blood cells in pleural effusion, lung wet/dry weight ratio, lung water content and lung permeability were increased (P<0.01) in the model group, where the rats presented cough, dyspnea, shortness of breath and arched back, and a small number of them had wet nose and bubble liquid in nostrils. In the autopsy of the rats in the model group, the lungs were enlarged or accompanied by congestion and plenty of pink bubble liquid appeared at the trachea. Compared with the conditions in the model group, SD reduced the amount of pleural effusion, number of white blood cells in pleural effusion, lung coefficient, lung wet/dry weight ratio and lung water content (P<0.01), and improved pulmonary edema symptoms such as damage, inflammation and infiltration around the lumen, thickening of the trachea, and accumulation of edema fluid, and the SD medium dose group had the best effect on the treatment of PE. In terms of respiratory system, compared with the normal control group, the model group had reduced latent time of cough and asthma (P<0.05, P<0.01) and elevated number of cough and wheezing (P<0.01). The three SD groups had increased latent time of cough and asthma and decreased number of cough and wheezing (P<0.01). In terms of urinary system, compared with the normal control group, the model group presented decreased urine volume. The SD low, medium and high dose groups had increased urine volume (P<0.05, P<0.01), but they had no effect on perspiration. In terms of digestive system, compared with the conditions in the normal control group, the gastric residual rate and gastrin (GT) level were increased (P<0.05, P<0.01), and the gastric emptying rate and small intestine transit rate were decreased (P<0.01). The SD low dose group had elevated small intestine transit rate (P<0.01), and the SD high and medium groups had enhanced gastric emptying rate and small intestine transit rate (P<0.01), reduced gastric residual rate, lowered GT level to promote gastrointestinal movement and transportation (P<0.01), and increased motilin (MTL) level to promote gastric emptying in rats (P<0.05, P<0.01). In terms of circulatory system, compared with the normal control group, the model group displayed reduced left ventricular ejection fraction (LVEF), left ventricular short axis shortening rate (LVFS) and cardiac output (CO) (P<0.01), and elevated tendency of heart rate, systolic blood pressure (SBP, P<0.01) and diastolic blood pressure (DBP, P<0.05). Compared with the model group, the SD low dose group increased LVEF and decreased DBP (P<0.05), while the SD medium dose group increased LVEF, LVFS, CO and SBP (P<0.01) and decreased DBP (P<0.05), and the SD high dose group increased LVFS (P<0.01) and decreased SBP (P<0.01) and DBP (P<0.05). In terms of central nervous system, compared with the conditions in the normal control group, the standing times dropped in the model group (P<0.01). SD reduced the movement distance, movement time, standing times and activity time in the center of the open field, and increased the rest time and activity time at the edge of the open field (P<0.05, P<0.01). Moreover, compared with the normal control group, the model group had serious inflammatory infiltration around the lung lumen, thickened trachea with accumulated edema fluid, seriously damaged lung tissue, increased number of white blood cells and percentage of neutrophils in blood (P<0.01), elevated percentage of monocytes, interleukin-4 (IL-4), immunoglobulin E (IgE) level and reactive oxygen species (ROS) level in lung tissue (P<0.05,P<0.01), and decreased IFN-γ in alveolar lavage fluid (P<0.01). Compared with the model group, SD decreased the number of white blood cells, neutrophil accumulation, pulmonary congestion and interstitial edema, IFN-γ and IL-4 levels in alveolar lavage fluid and ROS level in lung tissue, and increased IgE level (P<0.05, P<0.01).ConclusionSD had a significant improvement effect on PE model where the disease was located in the viscera. It could regulate the excretion of water by purgation, regulate Qi movement and expel Qi stagnation by descending and sinking lung Qi, and promote purification and descent of lung qi to make Qi movement downward. This indicated SD had the descending and sinking properties. The medium dose of SD decoction exerted the best effect, and its mechanism of action might be through regulating the neutrophil inflammatory response.
Keywords:ascending, descending, floating and sinking;Descurainiae Semen Lepidii Semen;pulmonary edema;alleviating edema;drug evaluation system
Abstract:ObjectiveTo explore the meridian tropism of components in Bupleuri Radix (Chaihu, CH) based on the model of nonalcoholic steatohepatitis (NASH) and clarify the substance basis of the meridian tropism of CH in Xiaoyaosan (XYS) by means of principal component analysis.MethodEighty SPF male C57BL/6 mice were randomly assigned into 8 groups, with 10 mice in each group. Except that the blank group was fed with the methionine choline-sufficient (MCS) diet, the other mice were fed with methionine choline-deficient (MCD) diet for 4 weeks to establish the nonalcoholic steatohepatitis (NASH) model. After the established model was confirmed by hematoxylin-eosin (HE) staining, the mice were administrated with corresponding drugs by gavage once a day for 4 weeks. Specifically, the 8 groups were XYS group (2.874 g·kg-1), XYS-CH group (2.445 g·kg-1), XYS-CH+volatile oils (Vol, 0.163 mg·kg-1) group, XYS-CH+polysaccharides (Pol, 24.067 mg·kg-1) group, XYS-CH+flavones (Fla, 2.241 mg·kg-1) group, and XYS-CH+saponins (Sap, 2.746 mg·kg-1) group. The model group and the blank group were administrated with the same volume of normal saline. After the last administration, the mice were sacrificed for the collection of blood and liver tissue. The pathological changes of liver were observed by HE staining and oil red O staining. Enzyme linked immunosorbent assay (ELISA) kits were used to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) in serum as well as malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in liver. SPSS Statistics 23 was used for principal component analysis and comprehensive evaluation to determine the substance basis of the meridian tropism of CH in NASH mice.ResultCompared with the blank control group, the modeling led to hepatocyte swelling, increased fat vacuoles, and appearance of inflammatory cells. Further, the modeling elevated the levels of ALT, AST, TG, TC, and LDL and lowered the HDL level in serum, and it increased the MDA level and decreased the SOD, CAT, and GSH-Px levels in liver. Compared with the model group, the administration of XYS and XYS-CH in combination with the components of CH alleviated the oxidative damage in liver (P<0.05). The comprehensive score of the pharmacological efficacy was in a descending order as follows: XYS > XYS-CH+Sap > XYS-CH+Fla > XYS-CH+Pol > XYS-CH+Vol > XYS-CH. Among the chemical components of CH, Sap had the best effect.ConclusionSap lowers the blood lipid level, regulates the abnormal lipid metabolism, and alleviates the oxidative damage of liver, which is the substance basis for CH to exert the meridian tropism in liver.
Abstract:ObjectiveTo investigate the medicinal effect of total flavonoids of mulberry leaves on regulating liver lipid metabolism disorder in diabetes mellitus type 2 (T2DM) rats, and the mechanism based on liver peroxidase proliferators activate receptors-α (PPAR-α) and carnitine palmityl transferase-1 (CPT-1) proteins.MethodTotal flavonoids of mulberry leaves were extracted and purified by ethanol extraction + macroporous resin purification and then identified. T2DM rat model was induced by high fat diet (HFD) + streptozocin(STZ)method. Rats with blood glucose ≥ 11.1 mmol·L-1 were divided into three administration groups with the high dose (300 mg·kg-1), medium dose (150 mg·kg-1), and low dose (75 mg·kg-1) of total flavonoids of mulberry leaves for 8 weeks, respectively, to observe the weight and blood glucose of the rats. The pathological changes of rat livers were observed by hematoxylin-eosin (HE) staining. Biochemical method was used to detect the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C) of blood lipid metabolism in rats. The messenger ribonucleic acid (mRNA) and protein expressions of PPAR-α and CPT-1 were determined by real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot.ResultAfter 8 weeks of intervention of total flavonoids of mulberry leaves, compared with the control group, the food intake, liver index, and fasting blood glucose of rats in the model group increased significantly (P<0.01). Compared with the model group, the food intake, fasting blood glucose, and liver index of rats in the administration groups decreased significantly (P<0.01). The results of HE staining showed that the liver tissue structure of rats in the control group was complete and there was no obvious abnormality. The model group showed vacuolar degeneration and inflammatory infiltration of hepatocytes of rats. There was no obvious abnormality in the liver structure of rats in the administration groups. The results of blood lipid showed that compared with the control group, the levels of TC, TG, and LDL-C increased significantly (P<0.01), but the level of HDL-C decreased significantly (P<0.01) in the model group. Compared with the model group, the levels of TC, TG, and LDL-C decreased significantly (P<0.05, P<0.01), whereas the level of HDL-C increased significantly (P<0.01) in the administration groups. The results of Real-time PCR showed that compared with the control group, the mRNA expression of PPAR-α and CPT-1 of rats in the model group decreased significantly (P<0.01). Compared with the model group, the mRNA expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly (P<0.01). The results of Western blot showed that compared with the control group, the protein expressions of PPAR-α and CPT-1 of rats in the model group decreased significantly (P<0.01). Compared with the model group, the protein expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly (P<0.05, P<0.01).ConclusionTotal flavonoids of mulberry leaves can effectively reduce blood glucose and improve liver lipid metabolism disorder in T2DM rats. The total flavonoids of mulberry leaves could regulate lipid metabolism and play a hypoglycemic role by activating and regulating PPAR-α and CPT-1 proteins and promoting oxidative decomposition of fatty acids.
Keywords:diabetes mellitus type 2 (T2DM);liver lipid metabolism;total flavonoids of mulberry leaves;peroxidase proliferators activate receptors-α (PPAR-α);carnitine palmityltransferase-1 (CPT-1)
Abstract:ObjectiveTo explore the mechanism of Yishen Huoxue prescription in renal interstitial fibrosis (RIF) from the perspective of endothelial cell and cell energy metabolism.MethodThe model was successfully established by unilateral ureteral obstruction (UUO). Seventy-five SPF C57BL/6 mice were randomly divided into a model group, a resveratrol group (50 mg·kg-1·d-1), three Yishen Huoxue prescription low, medium, and high-dose groups (7.1, 14.2, 28.4 g·kg-1·d-1), with 15 mice in each group. In addition, another 15 mice were used to prepare sham operation model. Mice in the sham operation group and the model group were gavaged with equal volume of normal saline. All mice were sacrificed on 7, 14, and 21 d after modeling. The protein expression of platelet endothelial cell adhesion molecule 31 (CD31) was detected by immunohistochemical S-P method. The expression of α-smooth muscle actin (α-SMA), collagen Ⅳ (Col-Ⅳ), angiopoietin 1(Ang-1) and tyrosine kinase receptors 2 (Tie-2), vascular endothelial growth factor (VEGF), vascular endothelial cadherin (VE-cadherin), and occludin in renal tissues was detected by Western blotting. The mRNA expressions of Ang-1/Tie-2, VEGF, VE-cadherin, and occludin in renal tissues were detected by Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR), and the levels of reactive oxygen species (ROS) in mice were detected by enzyme linked immunosorbent assay (ELISA).ResultAs compared with the sham operation group, the expression of CD31 in renal tissues of the model group was significantly decreased and worsened with the extension of modeling time (P<0.05), α-SAM and Col-Ⅳ protein expression levels were significantly increased (P<0.01), but the expression of CD31 was stable in 14-21 d. ROS levels were significantly increased (P<0.01), and the protein and mRNA expressions of Ang-1/Tie-2, VEGF, VE-cadherin, and occludin were significantly down-regulated (P<0.01). As compared with the model group, the expression of CD31 was increased (P<0.05), and α-SAM and Col-Ⅳ in the resveratrol group and the medium and high-dose Yishen Huoxue prescription groups were significantly decreased (P<0.01). The ROS content was significantly decreased (P<0.01), and the protein and mRNA expressions of Ang-1/Tie-2, VEGF, VE-cadherin, and occludin were up-regulated (P<0.01), As compared with the resveratrol group, the protein expressions of Ang-1/Tie-2, VEGF, VE-cadherin, and occludin in the medium and low-dose Yishen Huoxue prescription groups were significantly different (P<0.01). There was no significant difference in the mRNA expressions of CD31 and Ang-1/Tie-2 in the high-dose Yishen Huoxue prescription group, and no significant difference in the ROS level in the medium-dose Yishen Huoxue prescription group.ConclusionThe anti-RIF effect of Yishen Huoxue prescription may be related to promoting vascular endothelial repair, regulating mitochondrial ROS to reduce oxidative stress, protecting the integrity of renal endothelial structure, delaying cell apoptosis, and maintaining cell energy metabolism.
Abstract:ObjectiveTo observe the effects of five Huoxue Huayu prescriptions on blood lipid metabolism, liver tissue and adenosine triphosphate binding cassette transporter A1 (ABCA1) and peroxisome proliferator-activated receptor γ(PPARγ) expression in New Zealand rabbits with blood stasis syndrome, and to compare their differences in order to provide laboratory evidence for clinical selection of prescriptions and drugs.MethodSeventy New Zealand rabbits were randomly divided into normal group (n=10) and model group (n=60). The blood stasis syndrome was modeled by the method of starvation+high-fat feed+adrenaline. After the models were successfully established, they were randomly divided into Xuefu Zhuyutang(3.55 g·kg-1·d-1) group, Danshenyin(1.962 g·kg-1·d-1) group, Shixiaosan(0.56 g·kg-1·d-1) group, Huoluo Xiaolingdan(2.80 g·kg-1·d-1) group, and Taohong Siwutang(2.66 g·kg-1·d-1) group, and were given corresponding compound prescriptions by gavage. The normal group and model group were given the same dose of distilled water. After the treatment of 30 consecutive days, blood was taken from the abdominal aorta to detect the content of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol(LDL-C) and apolipoprotein A1 (ApoA1). Hematoxylin-eosin(HE) staining was used to observe the changes in liver tissue. Real-time polymerase chain reaction (Real-time PCR) and Western blot were used to detect the mRNA and protein expression of ABCA1 and PPARγ in liver tissue, respectively.ResultCompared with the conditions in the normal group, increased mRNA and protein levels of HDL-C, LDL-C, TG, TC, and PPARγ (P<0.01), decreased ApoA1 level (P<0.05) and decreased mRNA and protein levels of ABCA1 (P<0.01) were found in the model group. Compared with the conditions in the model group, the HDL-C level in the five Huoxue Huayu prescriptions was lowered (P<0.05), and lowered TG level in Xuefu Zhuyutang group and Shixiaosan group (P<0.05), decreased LDL-C and TC levels in Shixiaosan group (P<0.05), and increased ApoA1 level in the Huoluo Xiaolingdan group (P<0.01) and Taohong Siwutang group (P<0.05) were observed. Furthermore, the mRNA and protein levels of ABCA1 in Xuefu Zhuyutang group, Shixiaosan group, Huoluo Xiaolingdan group and Taohong Siwutang group were elevated (P<0.05, P<0.01), and the elevated levels were higher than that of Danshenyin group (P<0.05). The mRNA level of PPARγ in the five Huoxue Huayu prescriptions was reduced (P<0.01), and its protein level was also decreased in Xuefu Zhuyutang group, Shixiaosan group, Huoluo Xiaolingdan group and Taohong Siwutang group (P<0.01).ConclusionThe five Huoxue Huayu prescriptions had a certain therapeutic effect on dyslipidemia,which might be achieved by up-regulating the expression of ApoA1 and ABCA1 to promote the production of HDL-C and strengthen the excretion of dysfunctional HDL-C. And Xuefu Zhuyutang had the optimal effect in lowering lipid.
Abstract:ObjectiveTo explore the effect of sweroside on the protection of cardiac systolic/diastolic function during ischemia/reperfusion (I/R) injury.MethodTwenty-four healthy male SD rats were randomly divided into control group, model group, 10 μmol·L-1 sweroside group and 1 μmol·L-1 digoxin group. The I/R injury was modeled by Langendorff and ligation of the left anterior descending coronary artery. The infarct size in each group was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining and hemodynamic parameters such as left ventricular diastolic pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), left ventricular end-systolic pressure (LVESP), maximum rate of rising of left ventricular pressure (+dp/dtmax) and maximum rate of decreasing of left ventricular pressure (-dp/dtmax) of rat isolated heart were detected by Powerlab. In addition, neonatal rat cardiomyocytes (NRCMs) were isolated and randomly divided into control group, model group, 1 μmol·L-1 sweroside group and 10 μmol·L-1 sweroside group. Hypoxia/reoxygenation (H/R) injury model was established. Cardiac systolic function and calcium transients were examined by multi-functional cell imaging analyzer and laser confocal microscope. Furthermore, real-time polymerase chain reaction(Real-time PCR) was used to verify the mRNA expression of excitation-contraction coupling genes such as L-type calcium channel (Cacnb2), cytochrome c oxidase subunit 6A2 (Cox6a2), troponin (Tnnc1, Tnni3, Tnnt2), actin (Actc1), and myosin (Myh6, Myl2, Myl4) according to the results of previous transcriptome sequencing and literature investigation. Differentially expressed genes were subjected to cluster analysis.ResultCompared with the conditions in the control group, increased cardiac infarction size (P<0.01) and LVEDP (P<0.01) and decreased LVDP (P<0.01) and LVESP (P<0.05) were observed in the model group, with +dp/dtmax of increasing trend while -dp/dtmax decreasing. Moreover, the cell viability, heart rate and contraction amplitude of NRCMs was reduced (P<0.01), while the contraction duration, time to peak and relaxation time was elevated (P<0.01) in the model group. Interestingly, sweroside could reverse these indicators (P<0.05). In addition, the expression of Cacnb2, Cox6a2, Tnnc1, Tnni3, Tnnt2, Actc1, and Myh6, Myl2, and Myl4 was down-regulated in the model group (P<0.05, P<0.01), but sweroside could up-regulate the expression of the above genes (P<0.05).ConclusionSweroside effectively regulated Ca2+ level in NRCMs, enhanced cardiac systolic function, and protected against H/R injury by regulating excitation-contraction coupling.
Abstract:ObjectiveTo investigate the efficacy of Bushen Shengxue prescription and Yiqi Yangxue prescription in the treatment of chronic aplastic anemia and the effect on T cell subsets and the expression of T-box expressed in T cells (T-bet) and GATA binding protein 3 (GATA3).MethodA total of 585 patients with chronic aplastic anemia who were treated in 19 hospitals in China from May 2018 to June 2021 were enrolled. With the prospective, double-blind and randomized control methods, the patients were randomized into three groups: kidney deficiency group, Qi and blood deficiency group, and control group. The three groups were respectively treated with Bushen Shengxue prescription granule, Yiqi Yangxue prescription granule, and Placebo (half the dose of Bushen Shengxue formula granules). In addition, all of them were given oral cyclosporin and androgen. The treatment lasted 6 months, with 3 months as a course. The blood routine indexes, T cell subsets, and fusion genes T-bet and GATA3 before and after treatment were analyzed, and the safety indexes were monitored.ResultDuring the observation, a total of 75 cases dropped out and 18 were rejected. Finally, 161 cases in the kidney deficiency group, 164 in the Qi and blood deficiency group, and 167 in the control group were included. After 6 months of treatment, the total effective rate was 98.8% (159/161) in the kidney deficiency group, which was higher than the 79.9% (131/164) in the Qi and blood deficiency group (χ2=30.135, P<0.01) and the 61.7% (103/167) in the control group (χ2=70.126, P<0.01). The total effective rate was higher in the Qi and blood deficiency group than in the control group (χ2=13.232, P<0.01). After treatment, the hemoglobin (HGB) content increased significantly in three groups (P<0.05) as compared with that before treatment, particularly the kidney deficiency group (P<0.01). After treatment, the white blood cell (WBC) count and platelet (PLT) count in the kidney deficiency group and the control group increased compared with those in the Qi and blood deficiency group (P<0.01). There was no specific difference in neutrophils (ANC) after treatment among the three groups. At the same time point, the level of T helper type 1 (Th1) cells, Th1/Th2 ratio (P<0.05), level of CD4+, and CD4+/CD8+ ratio (P<0.05) were significantly low in the kidney deficiency group among three groups. There was no significant difference in CD19-, HLA/DR+, and CD25+ between the kidney deficiency group and the other two groups, but the T-bet of the kidney deficiency group and the control group was lower than that of the Qi and blood deficiency group (P<0.05).ConclusionBushen Shengxue prescription exerts therapeutic effect on the aplastic anemia by improving the immunoregulatory mechanism, inhibiting the activity of immune system, modulating T cell subsets, suppressing Th1 and CD4+, and promoting bone marrow hematopoiesis. Moreover, it is safe with little side effects, which is worthy of further promotion.
Keywords:Bushen Shengxue prescription;chronic aplastic anemia;immune regulation;T helper type 1 (Th1) cell;T helper type 2 (Th2) cell;T-box expressed in T cells (T-bet);GATA binding protein 3 (GATA3)
Abstract:ObjectiveTo further assess the safety of clinical application of Shujin Jianyao pills after marketing and find its potential risk factors as early as possible, to obtain the real world medication situation of Shujin Jianyao pills and its incidence of adverse reactions and clinical characteristics, and to explore the factors affecting the occurrence of adverse drug reactions (ADR).MethodIn this study, prospective, large-sample, multi-center and intensive whole-hospital monitoring with continuous registration was carried out, combined with telephone follow-up visits 2-4 weeks after the end of medication, for whole treatment course monitoring among patients. In addition, the three-level quality control was strictly implemented in the monitoring process. The study used a proprietary electronic data management system for data management, and SAS 9.4 and R software were used for statistical analysis.ResultFrom May 2018 to July 2020, the study completed the safety monitoring of 3 033 patients taking Shujin Jianyao pills in 30 clinical departments of 25 hospitals in China. A total of 36 ADR cases (49 times) were confirmed by expert assessment on data and supervision quality and expert interpretation of ADR.ConclusionAccording to the World Health Organization (WHO), the symptoms of adverse reactions were mainly classified into occasional adverse reactions (0.1%≤ADR<1%: abdominal distension, oral ulcer, dry mouth, constipation) and rare adverse reactions (0.01%≤ADR<0.1%: loss of appetite, rash, fatigue, increased ALT, increased creatinine, dizziness, stomachache, stomach distension, liver discomfort, pruritus, dysphoria, acid regurgitation, numbness in mouth, abdominal pain, sore throat, earache, tinnitus). Moreover, through the synthetic minority oversampling technique (SOMTE) combined with logistic regression, the following factors might affect ADR: taking Shujin Jianyao pills for 1-14 days, aged 46-65, 66-80 and 81 and above as well as combined use of atorvastatin, cobamamide, calcitriol capsules, Gushukang capsules, glucosamine, nifedipine, methylcobalamin, metformin, Tenghuang Jiangu pills, Bugu tablets, and diclofenac sodium sustained-release tablets. This study provided a real world basis for the safety and standardized use of Shujin Jianyao pills in clinical practice.
Keywords:Shujin Jianyao pills;real world study;active monitoring;safety;adverse reactions;intensive hospital monitoring
Abstract:ObjectiveBased on ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), the changes of endogenous markers in rat plasma at the different stage, namely modeling and administration of Shenling Baizhusan (SLBZS), and the mechanism of SLBZS in the treatment of ulcerative colitis (UC) were studied.MethodIn the modeling stage, rats were randomly divided into normal group, spleen deficiency with dampness retention-UC (SDDR-UC) and pure-UC (P-UC) model group. In the administration stage, SLBZS was given to the above two different model groups. After modeling and administration, rat plasma was collected and determined by UPLC-Q-TOF/MS. The mobile phase was 0.1% formic acid aqueous solution (A)-acetonitrile (B) for gradient elution (in positive ion mode:0-2 min, 99%A; 2-9 min, 99%-73%A; 9-10 min, 73%-44%A; 10-13 min, 44%-38%A; 13-19 min, 38%-28%A; 19-21 min, 28%-2%A; 21-23 min, 2%A; 23-25 min, 2%-10%A; 25-27 min, 10%-99%A; in negative ion mode:0-2 min, 85%A; 2-3 min, 85%-65%A; 3-5.5 min, 65%-44%A; 5.5-8 min, 44%-25%A; 8-10 min, 25%-2%A; 10-16 min, 2%-85%A). The electrospray ionization (ESI) temperature was 120 ℃ under the positive and negative ion modes, and the acquisition range was 50-1 000. Partial least squares-discriminant analysis (PLS-DA) was used to analyze the changes of endogenous metabolites in the above two different model rats from the different stage. MetaboAnalyst 5.0 was used to analyze the metabolic pathways of these identified metabolites.ResultSixteen potential biomarkers were screened and identified in the modeling stage, among which 11 potential biomarkers were common in the two model rats, which mainly affected the primary bile acid biosynthesis pathway. Twenty-three potential biomarkers were screened and identified during the administration stage, among which 3 potential biomarkers were shared by the two model rats, and SDDR-UC and P-UC model rats had 11 and 9 potential biomarkers, respectively. It mainly affected 6 pathways such as purine metabolism, pentose phosphate pathway, pyrimidine metabolism, retinol metabolism, primary bile acid biosynthesis and steroid hormone synthesis.ConclusionThe primary bile acid biosynthesis pathway appears in the different stage of modeling and administration of UC, showing a dynamic change process. The therapeutic effect of SLBZS on SDDR-UC rats may be related to inhibiting the expression of nuclear transcription factor -κB (NF-κB) signaling pathway, activating farnesoid X receptor (FXR) and enhancing the expression of cytochrome P450.
Keywords:Shenling Baizhusan;spleen deficiency with dampness retention-ulcerative colitis;pure-ulcerative colitis;metabolomics;ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS);bile acid;biomarkers
Abstract:ObjectiveTo study the composition of volatile oil in Opisthopappus taihangensis (Taihangju), and provide a reference for comprehensive development of this medicine.MethodTaking Chrysanthemum morifolium (Xiaobaiju), C. morifolium (Xiaohuangju) and C. indicum (Yejuhua) as control, the qualitative and quantitative analysis of volatile oil in Taihangju and three control varieties were completed by gas chromatography-mass spectrometry (GC-MS) combined with retention index method. The GC conditions were as following:programmed temperature (initial temperature at 60 ℃, kept for 2 min; up to 120 ℃ with the heating rate of 5 ℃·min-1, still kept for 2 min; up to 180 ℃ with the heating rate of 2 ℃·min-1, kept for 3 min; and then up to 240 ℃ with the heating rate of 8 ℃·min-1, kept for 5 min; finally up to 280 ℃ with the heating rate of 10 ℃·min-1,kept it for 5 min and finished), high-purity helium as the carrier gas, the split ratio of 50∶1. MS conditions were as follows:electron impact ion source (EI), ion source temperature of 230 ℃, electron collision energy of 70 eV and scanning range of m/z 30-445. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to obtain the characteristic components between Taihangju and the three control varieties.ResultA total of 86, 96, 112 and 109 compounds including 73 common components were identified in Taihangju, Xiaobaiju, Xiaohuangju and Yejuhua, respectively. The contents of volatile components in Taihangju were significantly different from that of the control varieties. In which, the relative contents of α-thujone, eucalyptol and terpinen-4-ol were high in Taihangju, and eucalyptol, camphor and α-terpinyl acetate were the main compositions in the control varieties. In addition, 11 compounds were screened as characteristic components to distinguish Taihangju and the three control varieties by PCA and OPLS-DA, including main differential components of chamazulene and δ-cadinene.ConclusionThe main components of volatile oil in Taihangju includes alcohols, terpenes, ketones and esters with high medicinal value. The accuracy of qualitative analysis of volatile oil is improved by GC-MS combined with retention index method, which provides scientific reference for development and utilization of Taihangju.
Abstract:ObjectiveTo conduct genetic variation analysis of 11 cultivars and 7 wild populations of Angelica sinensis in Gansu province based on the chloroplast gene (cp DNA), and provide references for germplasm identification and breeding of new cultivars of A. sinensis.MethodThree pairs of cp DNA primers were used for polymerase chain reaction (PCR) amplification and sequencing of A. sinensis samples. MegaX was used to perform statistics on sequence characteristics and calculate mean genetic distances among A. sinensis populations. Unweighted pair-group method with arithmetic means (UPGMA) clustering tree based on genetic distance was constructed by NTSYS 2.10e. DanSP v6 was used to calculate sequence polymorphism and Tajima's D of A. sinensis. PERMUT was used to calculate the population structure of A. sinensis. Arlequin v3.5 was used to perform molecular variation analysis, and PopART1.7 was used to construct TCS haplotype network.ResultThree pairs of cp DNA primers were amplified, sequenced, compared, and combined to give a sequence length of 1 759 bp. One variable site was detected in the wild A. sinensis and 480 variable sites were detected in the cultivated A. sinensis, including 97 singleton variable sites, 383 parsimony informative sites, and 152 insertion-deletion sites. In the three regions of matK, psbA-trnH, and rbcL of cp DNA in the wild and cultivated A. sinensis, matK was the region with the highest polymorphism. Tajima’s D of all the combined sequences of A. sinensis were not significantly negative, but psbA-trnH and rbcL genes of the cultivated A. sinensis were significantly negative, indicating that the A. sinensis followed neutral evolution on a whole, while psbA-trnH and rbcL genes had undergone selection. The degree of genetic differentiation (Fst=0) among wild populations was lower than that among cultivated populations (Fst=0.114 19, P<0.05). The degree of genetic differentiation between wild and cultivated A. sinensis was relatively high (Fst=0.942 55, P<0.01). Genetic variation in the cultivated A. sinensis was mainly found within the populations (89%). UPGMA cluster tree based on genetic distance showed that the wild A. sinensis and the cultivated A. sinensis were clustered into one branch, respectively, with a distant genetic relationship, and the population 3 in the cultivated A. sinensis was far from other cultivated populations. The TCS haplotype network consisted of 15 haplotypes and 4 unknown haplotypes, which was divided into 3 parts, with a large number of variations among each part. Shared haplotypes were only found in the wild or cultivated groups, and there were no shared haplotypes between groups.ConclusionThe genetic diversity of A. sinensis was low at species level, and the population diversity of the wild was lower than that of the cultivated. The degree of genetic differentiation between the wild and the cultivated A. sinensis was high, but that in the wild and the cultivated populations were low. Genetic variation in the cultivated A. sinensis was mainly found within populations.
Abstract:ObjectiveTo investigate the quality of Amomi Fructus in the market, and to compare the difference between the seed mass and shell, so as to provide a basis for standardizing the usage of Amomi Fructus.MethodThe properties, thin layer identification, moisture, the content of bornyl acetate were determined by the methods in the 2020 edition of Chinese Pharmacopoeia, and the ash and extract content were determined according to the collection method of the 2020 edition of Chinese Pharmacopoeia.ResultAmong the 17 batches of samples, except the content of bornyl acetate in 2 batches of Amomum longiligulare, 2 batches of A. longiligulare and A. villosum mixture was lower than the standard, the quality of other samples all met the standard of the 2020 edition of Chinese Pharmacopoeia, but there were two specifications with shell and without shell. The husk rate, volatile oil, extract and bornyl acetate contents of the seed mass and shell were tested. It was found that the content of volatile oil in three kinds of Amomi Fructus seed mass was 1.8-5.3 times that of the corresponding shell, and the content of bornyl acetate in the seed mass was 8.8-62.1 times that of the corresponding shell, but there was little difference in the extract content.ConclusionBased on the above research, it is considered that the content of bornyl acetate in A. longiligulare contained in the 2020 edition of Chinese Pharmacopoeia remains to be discussed. It is tentatively determined that the total ash content of Amomi Fructus should not be more than 10.0%, and the extract content should not be less than 15.0%. At the same time, it is suggested that when Amomi Fructus is used as medicine, the dosage of Amomi Fructus should be calculated according to the removal rate of 20%-30% of shell, and it should be crushed regardless of whether it is used in shell or not.
Abstract:ObjectiveOn the basis of sensory evaluation, the changes of volatile components in gecko before and after processing were compared, and the odor correction effect of different processing methods of gecko was discussed.MethodRaw products, fried yellow products, vinegar processed products, wine processed products, talcum powder scalding products and white wine sprayed products after scalding talcum powder of gecko were prepared, and 10 odor assessors were invited to evaluate the 6 samples in turn by sensory evaluation. Headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and relative odor activity value (ROAV) were used to analyze the key odor components, and multivariate statistical methods were used to analyze the difference of volatile components between raw and processed products of gecko. Taking water-soluble extract and protein contents as internal indicators, sensory evaluation score and content ranking of differential components as external indicators, and assigning a weight of 0.25 to them respectively, the comprehensive scores of raw products and processed products of gecko were calculated to evaluate the odor correction effect of each processing method.ResultThe average sensory evaluation scores of the raw products, fried yellow products, vinegar processed products, wine processed products, talcum powder scalding products and white wine sprayed products after scalding talcum powder of gecko were 1.6, 5.2, 6.2, 6.1, 7.2 and 8.0, respectively. ROAV results showed that key components affecting odor of gecko were 2-ethyl-3,5-dimethylpyrazine, isovaleraldehyde, trimethylamine, 1-octen-3-ol, n-octanal, nonanal, 2-methylnaphthalene, γ-octanolide, 2-heptanone and phenol. Principal component analysis (PCA) significantly distinguished raw products from processed products. Orthogonal partial least squares-discriminant analysis (OPLS-DA) results showed that there were 16, 13, 16, 16, 16 differential components between raw products, fried yellow products, vinegar processed products, wine processed products, talcum powder scalding products and white wine sprayed products after scalding talcum powder of gecko. Among these differential components, there were 4 common components, namely, the contents of different odor components (2-methylnaphthalene and 2-ethyl-p-xylene) decreased, while the contents of different flavor components (2-decanone and 2,3,5-trimethylpyrazine) increased. The comprehensive scoring results showed that the odor correction effect of each processed products was in the order of talcum powder scalding products>wine processed products>vinegar processed products>fried yellow products>white wine sprayed products after scalding talcum powder.ConclusionTalcum powder scalding is a better method to improve the odor of gecko, and it can provide an experimental basis for the processing of gecko to correct the odor.
Keywords:Gecko;processed products;odor;sensory evaluation;headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS);relative odor activity value (ROAV);principal components analysis (PCA);orthogonal partial least squares-discriminant analysis (OPLS-DA)
Abstract:ObjectiveTo predict the potential targets and possible related signaling pathways of Salviae Miltiorrhizae Radix et Rhizoma against bladder cancer (BC) based on network pharmacology and verify the potential molecular mechanism through in vitro cell experiment.MethodActive components of Salviae Miltiorrhizae Radix et Rhizoma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and BC-related targets were searched from GeneCards and Online Mendelian Inheritance in Man (OMIM). Via Venny2.1, the potential targets of Salviae Miltiorrhizae Radix et Rhizoma against BC were screened out and the Venn diagram was plotted. Protein-protein interaction (PPI) network was constructed by STRING, followed by Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Gnomes (KEGG) pathway enrichment with DAVID. Cell Counting Kit-8 (CCK-8) assay was employed to detect the inhibitory effect of tanshinone ⅡA (Tan ⅡA), cryptotanshinone (CPT), and luteolin (LUT) at different concentration (0, 1, 2, 4, 8, 16, 32 μmol·L-1) on the proliferation of BC T24 and 5637 cells, propidium iodide (PI) staining to analyze the apoptosis of 5637 cells induced by Tan ⅡA, CPT, and LUT (0, 4, 8 μmol·L-1), and Western blotting to detect the regulatory effect of Tan ⅡA (0, 4, 8, 16 μmol·L-1) on the expression of key target proteins.ResultA total of 65 active components and 39 anti-BC targets of Salviae Miltiorrhizae Radix et Rhizoma were screened out. The anti-BC targets were mainly involved in the KEGG pathways of neuron-ligand-receptor interaction, phosphatidylinositol 3-kinases (PI3K)/protein kinase B (Akt) signaling pathway, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance, and hypoxia inducible factor (HIF)-1 signaling pathway. As for the CCK-8 assay, compared with the blank group, Tan ⅡA, CPT, and LUT significantly inhibited the proliferation of T24 and 5637 cells, particularly the 5637 cells. The half maximal inhibitory concentration (IC50) of Tan ⅡA on 5637 cells was significantly lower than that of CPT and LUT. Moreover, compared with the blank group, Tan ⅡA, CPT, and LUT all induced the apoptosis of 5637 cells, and the effect followed the order of Tan ⅡA>CPT>LUT (P<0.05). Western blot showed that Tan ⅡA significantly reduced the expression of EGFR, p-PI3K, and p-Akt in 5637 cells in a concentration-dependent manner compared with the blank group (P<0.05).ConclusionSalviae Miltiorrhizae Radix et Rhizoma exerts therapeutic effect on BC through multiple components, multiple targets, and multiple pathways. The mechanism is the likelihood that it down-regulates the expression of EGFR, p-PI3K, and p-Akt proteins, thus further inhibits cell proliferation, and induces apoptosis.
Keywords:Salviae Miltiorrhizae Radix et Rhizoma;bladder cancer (BC);network pharmacology;tanshinone ⅡA (Tan ⅡA);molecular docking
Abstract:ObjectiveTo explore the distribution mechanism of network modules in the combined treatment of liver cancer with Jiuwei Zhengxiao granules (JWZX) based on the analysis framework of module pharmacology.MethodThe cell experiment and the animal experiment were carried out to investigate the in vitro anti-liver cancer efficacy of JWZX of different concentrations and the effect on the survival time of H22 ascites tumor mice. By virtue of the analysis strategy of modular pharmacology,the distribution characteristics of nine Chinese drugs in the liver cancer disease network modules were investigated based on the constructed liver cancer disease network and module division by MCODE. In this study,the average degree (AD) of the nodes in the modules was used as an index to screen the main modules of the disease,and the intervention of the sovereign drugs,minister drugs,and assistant drugs on the main modules was explored. Finally,the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed on the drug-acted modules by Metascape.ResultAs revealed by the cell experiment,JWZX could significantly inhibit the proliferation of H22 cells. The animal experiment demonstrated that the medium- and high-dose JWZX could significantly prolong the survival time of mice with H22 ascites tumor (P<0.05,P<0.01). The distribution of targets of JWZX in the liver cancer disease network modules showed that JWZX interfered with tumor necrosis factor (TNF),epidermal growth factor receptor (EGFR),vascular endothelial growth factor A (VEGFA),transcription factor (JUN),tumor protein p53 (TP53),and other 26 targets and 8 modules. The sovereign drug Ginkgo Semen mainly intervened in modules 3 and 8,and the minister drugs such as Centipeda Herba jointly intervened in modules 1,3,5,8,10,and 12. Centipeda Herba and Phyllanthi Fructus intervened in module 7 and module 19 individually. Artemisiae Annuae Herba and other assistant drugs jointly intervened in modules 3,5,10,and 12. KEGG pathway enrichment analysis found that 135 pathways were enriched in 8 modules,and the pathway functions involved 12 categories including cancer,signal transduction,immune system,endocrine system,and amino acid metabolism. The functions of the four major modules involved cancer,signal transduction,and immune system. According to the results of literature verification,the key links of JWZX on the liver cancer disease network and the core mechanism were presumedly related to the inhibition of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and hypoxia-inducible factor-1 (HIF-1) signaling pathways,reduction of the immunosuppressive effect in the tumor microenvironment,and improvement of the anti-tumor immune response.ConclusionJWZX possesses pharmacological activity against liver cancer,and the therapeutic efficacy was achieved through the multiple targets,multiple modules,and multiple functions of drugs alone or in combination to intervene in the disease. The present study reduced the complexity of drug-disease target network analysis with module analysis strategy and explored the network module distribution mechanism of JWZX in the treatment of liver cancer,which provides a new idea for interpreting the complex mechanism of prescription compatibility.
Abstract:ObjectiveTo explore the syndrome and treatment rules of traditional Chinese medicine (TCM) in treating chronic obstructive pulmonary disease (COPD) based on the medical literature and cases with the help of TCM inheritance support system platform (V2.5), thus providing new ideas for TCM to treat COPD.MethodThe medical cases of TCM treating COPD were retrieved from China national knowledge infrastructure (CNKI), Wanfang Database, and VIP China Science and Technology Journal Database. The medical cases that met the inclusion literature were collected in a new Word document, and then input into the TCM inheritance support system platform (V2.5) after data standardization. With the help of the algorithm carried by this software, the frequency statistics of "symptoms, syndrome types of TCM, Chinese medicine, and meridians of Chinese medicine" in the included COPD medical cases were performed, and the correlation analysis of the "prescription rules" in the included medical cases was carried out, thus excavating the potential core drug pairs and new prescriptions for the treatment of COPD.ResultA total of 103 articles were included with 126 medical cases and 131 diagnoses and treatments. According to statistics, the common symptoms of COPD were cough, expectoration, chest tightness, and asthma, and the common TCM syndromes included phlegm-heat obstructing lung, phlegm and blood stasis blocking lung, and lung-spleen Qi deficiency. The common TCM treatment methods included clearing heat and resolving phlegm, banking up earth to generate metal, and descending adverse and relieving dyspnea, among which the high-frequency Chinese medicines for the treatment of COPD were Pinelliae Rhizoma, Armeniacae Semen Amarum, Ephedrae Herba, Citri Reticulatae Pericarpium, and so on. The commonly used drug pairs included Asari Radix et Rhizoma-Pinelliae Rhizoma, Pinelliae Rhizoma-Schisandrae Chinensis Fructus-Glycyrrhizae Radix et Rhizoma, etc. Twelve new prescriptions for the treatment of COPD were found.ConclusionTCM believes that COPD is a lung disease formed by external evil, phlegm, blood stasis, and other pathological factors, with cough, phlegm, and asthma as the main symptoms. The main syndromes of COPD are phlegm-heat obstructing lung, phlegm and blood stasis blocking lung, and lung-spleen qi deficiency. "Strengthening the upright and dispelling evil" is the basic principle of the treatment COPD. In clinical, TCM methods with dispelling phlegm and removing blood stasis, and tonifying lung, spleen, and kidney should be adopted to treat COPD.
Keywords:chronic obstructive pulmonary disease;medical cases;explore;syndrome and treatment rules
Abstract:ObjectiveTo explore the mechanism of hypericin against liver cancer using network pharmacology.MethodThe traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), Drug Gene Interaction Database (DGIdb), Comparative Toxicogenomics Database (CTD) and SwissTargetPrediction were used to predict the targets of hypericin. Five databases including GeneCards and Online Mendelian Inheritance in Man (OMIM) were employed to obtain liver cancer-related targets. The intersection was performed to obtain the targets of hypericin against liver cancer. The Database for Annotation, Visualization and Integrated Discovery (DAVID) v2021q4 was used for Gene Ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The protein-protein interaction (PPI) network of the targets was constructed by Cytoscape 3.6.1 to screen the core targets,and the affinity between hypericin and the core targets was verified by molecular docking. The effects of hypericin on liver cancer and the migration of liver cancer cells were observed by cell viability assay and would healing assay, respectively, and its effects on the mRNA and protein expression of key targets cysteinyl aspartate-specific protease-3(Caspase-3) and mitogen-activated protein kinase 3 (MAPK3) were detected by real-time polymerase chain reaction(Real-time PCR) and Western blot, respectively.ResultA total of 45 genes related to the anti-liver cancer effect of hypericin were obtained, and six core target genes were screened. The signal pathways enriched by KEGG pathway analysis included apoptosis,tumor necrosis factor (TNF) and cancer signal pathways. Molecular docking showed that the core target genes Caspase-3,TNF,estrogen receptor 1 (ESR1),MAPK3,catalase (CAT) and cyclooxygenase 2 (PTGS2) had good affinity with hypericin,especially Caspase-3 and MAPK3. In addition,compared with the conditions in control group, cell experiments demonstrated that hypericin could reduce the viability of liver cancer cells (P<0.05),inhibit their migration,increase the mRNA expression of Caspase-3 (P<0.05) and decrease that of MAPK3 (P<0.05).ConclusionHypericin exerted the anti-liver cancer effect by affecting the core targets such as Caspase-3,TNF,ESR1,MAPK3,CAT and PTGS2 and jointly interfering with apoptosis,TNF and cancer signal pathways.
Abstract:ObjectiveThis study aimed to predict the pharmacodynamic material basis and core targets of Bailing capsules in the treatment of chronic obstructive pulmonary disease (COPD) based on network pharmacology and molecular docking, which were further verified by cell experiments to explore the mechanism.MethodThe main active ingredients and related targets of Bailing capsules were screened in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction. The main COPD targets were searched from GeneCards, DrugBank, Online Mendelian Inheritance in Man (OMIM) and Therapeutic Target Database (TTD). The protein-protein interaction (PPI) network was constructed by STRING and Cytoscape 3.6.1. Gene Ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed by the Database for Annotation, Visualization and Integrated Discovery (DAVID). Molecular docking verification was carried out using AutoDock Vina. The cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, and the mRNA level of the targets was detected by real-time polymerase chain reaction (Real-time PCR).ResultA total of 11 active ingredients of Bailing capsules such as cerevisterol, 270 related drug targets, and 1 020 COPD target proteins were obtained, with 74 intersection targets. The visualization analysis of the PPI network showed that the core targets of Bailing capsules in the treatment of COPD were tumor protein P53 (TP53), catenin beta 1 (CTNNB1), tumor necrosis factor (TNF), interleukin-6 (IL-6) and insulin (INS). Further, 20 signaling pathways were screened by KEGG enrichment analysis as the main pathways for Bailing capsules to treat COPD, involving phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), cyclic adenosine monophosphate (cAMP), forkhead box O (FoxO), TNF, and hypoxia inducible factor-1 (HIF-1) signaling pathways. Molecular docking validation demonstrated that four active ingredients had stable binding to IL-6, with the lowest energy. Bailing capsules could reduce the mRNA level of IL-6 in RAW264.7 cells induced by lipopolysaccharide (LPS) (P<0.01) compared with the control group.ConclusionThe pharmacological mechanism of Bailing capsules in the treatment of COPD might be that its main active ingredients improved the inflammatory response by acting on TP53, CTNNB1, TNF, IL-6 and other targets and regulating PI3K/Akt, cAMP and other signaling pathways, thereby ameliorating COPD symptoms. This study provided experimental basis for subsequent in-depth research, and provided a diagnosis and treatment direction for disease-related clinical treatment.
Abstract:In recent years, as people's diets have changed and diversified, the incidence of dental arthritis has increased year by year, seriously affecting the quality of life of patients. Therefore, the prevention and treatment of dental arthritis should be emphasized. To further study the pathogenesis of dental arthritis and the development and screening of therapeutic drugs, this paper summarized and analyzed the modeling methods, mechanisms, as well as the advantages and disadvantages of the existing animal models of dental arthritis. The clinical diagnostic criteria of traditional Chinese medicine (TCM) and western medicine was established, and the compatibility of TCM and western medicine anastomosis in animal models was evaluated. The results showed that the gel perfusion model had a good match between TCM and western medicine, with simple operation and short cycle. By combining the pathogenic factors of TCM and western medicine, the models of kidney deficiency and stomach heat with kidney deficiency in TCM were obtained, which fully reflected the clinical syndrome characteristics of TCM and western medicine, thus simulating the pathogenesis of human natural dental arthritis. Besides, ligation line model, as the most commonly-used animal model of dental arthritis with a good match to western medicine, was mature and highly repeatable, and had a high success rate. Ligation line model was widely used in various periodontal disease studies, but it did not involve the pathogenic factors of TCM. The current animal model of dental arthritis is given priority to western medicine disease model, and the combination of disease and model is rare, which cannot meet the requirements of the syndrome characteristics of TCM. Only an animal model of dental arthritis with TCM syndrome that conforms to the clinical syndrome characteristics effectively assists to study the nature of TCM syndrome and develop innovative Chinese medicine. Therefore, the establishment of an accurate and standardized animal model of dental arthritis combined with TCM and western medicine is still the focus of future study on the pathogenesis of dental arthritis. This study is intended to provide a certain basis for the discovery, screening, and evaluation of medicines for the treatment of dental arthritis.
Keywords:dental arthritis;traditional Chinese medicine (TCM) and Western medicine;clinical syndrome characteristics;animal model
Abstract:Ulcerative colitis (UC) is one of the main manifestations of inflammatory bowel disease. Because of its lingering and refractory nature, it has become a major public health challenge worldwide. In the treatment of UC, traditional Chinese medicine (TCM) effectively relieves clinical syndromes, shortens the treatment period, reduces the frequency of recurrence, improves the quality of life, and reduces the occurrence of complications. To study the specific mechanism of TCM in the treatment of UC and screen out suitable drugs under the guidance of syndrome differentiation, the suitable UC animal model in the combination of disease and syndrome is used as an important method. This paper summarized and compared the UC animal model in the combination of disease and syndrome from five aspects, including selection of model animal species, sexual selection, preparation methods of UC animal model in the combination of disease and syndrome, indicators of model evaluation, and the main mechanism of TCM intervention in UC animal model in the combination of disease and syndrome. This paper aimed to provide references for the establishment of the optimal UC animal model in the combination of disease and syndrome. Research shows that UC syndrome mainly studied at present includes damp-heat syndrome, spleen deficiency syndrome, spleen-kidney Yang deficiency syndrome, spleen deficiency and dampness accumulation syndrome, liver depression and spleen deficiency syndrome, and cold-heat mixed syndrome.In the modeling method, the etiology simulation method is mainly used to first copy the syndrome type before the chemical agents or immune preparations were used to induce the disease model,and rats were often selected as the research objects,and the replication cycle was 7 to 28 days.The selected chemical reagents were mainly 5% dextran sulfate sodium(DSS) free drink, 2,4,6-trinitrobenzenesulfonic acid(TNBS) 100 mg·kg-1 and 50% ethanol 0.25 mL mixed reagent enema.This model replication method can take into account both UC pathogenesis characteristics of pathology of western medicine and TCM, syndrome type of traditional Chinese medicine and western medicine for interpretation pathological changes and TCM treatment of UC associated mechanism is of great significance, and help to help toestablish the optimal condition in combination with UC animal models for reference, for further research on prevention and treatment of UC specific mechanism of action of TCM model basis.
Keywords:ulcerative colitis (UC);animal model;combination of disease and syndrome;model establishment;model evaluation
Abstract:Stroke is the leading cause of death and disability. Therefore, it is critical to develop the approaches for improving recovery and neural repair after stroke. Recovery after stroke involves complex interrelated systems of neural repair. The whole process of neural repair requires a series of coordinated interactions, such as response of neuronal cell body to traumatic stimuli, neural stem cell proliferation and migration, axoplasmic transport of signaling molecules, construction of cytoskeleton, and formation of axonal growth cone, to achieve regeneration and growth. As a potential new target for the treatment of neurologic defects, neural remodeling has important research significance in both the specific mechanism of neural repair and the clinical treatment of neurologic defects. After brain injury, single therapy is often ineffective due to the complex mechanism of internal repair, and thus comprehensive therapy becomes the development direction to improve the brain repair. Invigorating qi and promoting blood can promote nerve function remodeling after injury through neural protection, angiogenesis, neurogenesis, loop reconstruction, and cytokine regulation, playing a key role in nerve repair after stroke. Its mechanism is associated with autophagy, immunomodulation, and microRNA regulation, which fully embodies the multi-pathway, multi-target, and overall regulation characteristics of invigorating Qi and activating blood. Therefore, it is of theoretical and guiding significance to study the brain function rehabilitation after stroke by invigorating qi and activating blood.
Keywords:ischemic stroke;neural repair;syndrome of Qi deficiency and blood stasis;invigorating qi and activating blood;biological basis
Abstract:Yunüjian (Jing Yue's Collected Works), composed of Gypsum Fibrosum, Rehmanniae Radix Praeparata, Anemarrhenae Rhizoma, Ophiopogonis Radix, and Achyranthis Bidentatae Radix, is used for the treatment of "headache, toothache, consumptive thirst, and other diseases caused by heat and Yin deficiency in the stomach". In modern clinical settings, it has definite hypoglycemic efficacy, as it improves insulin resistance, inhibits oxidative stress and inflammatory response, and down-regulates estrogen level. It is often directly used, modified before use, combined with other formulae (Liuwei Dihuangtang, Shashen Maidongtang, Shenqi Sanjingtang, Huangqi Guizhi Wuwutang, Zengyetang, Zengye Baihutang, etc.), or used together with western medicine (insulin, metformin, pioglitazone, glurenorm, etc.). Modified Yunüjian can be applied for the treatment of type 2 diabetes mellitus, gestational diabetes, polycystic ovary syndrome with insulin resistance, pruritus induced by diabetes mellitus, diabetic peripheral neuropathy, diabetic nephropathy, diabetic ketoacidosis, diabetic retinopathy, and diabetic periodontitis. According to previous experiment, the protection for pancreatic islet β-cells is an important way of Yunüjian to improve diabetes mellitus. The formula can remove damaged proteins and organelles by increasing the expression of autophagy-related 2B (Atg2B), ubiquitin-like-conjugating enzyme (Atg3), γ-aminobutyric acid type A receptor-associated protein (GABARAP), selective autophagy receptor (p62/SQSTM1), etc. Moreover, it plays an active role in islet cell proliferation and apoptosis by regulating the expression of mammalian target of rapamycin (mTOR) and reducing the expression of islet β-cell autophagy gene (Beclin). These are pivotal for maintaining the quantitative structure and functions of islet cells. The modulatory effect of Yunüjian on growth hormone-releasing peptide (ghrelin), gastrin, and growth hormone secretagogue receptor (GHSR) mRNA expression is also the underlying mechanism for the formula to protect pancreatic β-cells. In this study, we summarized the clinical and experimental studies on the therapeutic effect of this formula on diabetes mellitus, discussed the mechanisms, and proposed suggestions on the problems, hoping to provide a reference for the clinical application and further development of Yunüjian. This study is of practical significance for the scientific interpretation of the modern connotation of Yunüjian and the expansion of its clinical application.
Abstract:Atherosclerotic cardiovascular disease is a common disease with high incidence rate and mortality worldwide. Atherosclerosis is an important pathological basis for the formation of ischemic cardiovascular diseases such as cardiovascular disease, which is related to inflammation, oxidative stress, apoptosis, vascular endothelial damage, foam cell formation, platelet activation, and so on, involving mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), cyclic adenosine monophosphate/protein kinase A (cAMP/PKA), Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil containing protein kinase (ROCK), nuclear factor-kappa B (NF-κB), and other signaling pathways. In the past few decades, high-intensity statins were mainly used to treat atherosclerosis by reducing blood lipid levels, which usually caused obvious side effects. Therefore, the development of safer and more effective drugs and treatment modes is the focus of research at this stage. In recent years, Chinese medicine has been playing an increasingly important role in the prevention and treatment of cardiovascular diseases in China. There are many studies on the mechanism of Chinese medicine in the prevention and treatment of atherosclerosis, and it is found that a variety of single Chinese medicine regulate the formation process of atherosclerosis by regulating targeted signal molecules. This paper reviewed the research results of related signaling pathways involved in the pathological formation of atherosclerosis and the mechanism of Chinese medicine in the prevention and treatment of cardiovascular diseases, thereby providing references for the clinical treatment of cardiovascular diseases.
Abstract:Diabetic nephropathy is one of the most common microvascular complications of diabetes. It is the main cause of end-stage renal disease and a cause of increased mortality of diabetes. Moreover, diabetic nephropathy has a complex pathogenesis, which is difficult to be detected in the early stage. Therefore, it is easy to miss the optimal intervention period in clinical treatment, which seriously endangers the life and health of patients. As an active ingredient of Chinese medicine, polysaccharides have biological activities such as anti-tumor, lowering blood sugar, immune regulation, anti-oxidation and anti-virus. In recent years, many studies have demonstrated that polysaccharides in Chinese medicine can effectively interfere with diabetic nephropathy, with multi-target and multi-channel characteristics and significant effect, showing great potential. Although there are many studies on the mechanism of Chinese medicine polysaccharides in the intervention of diabetic nephropathy, there is a lack of a systematic and detailed review on it. Therefore, based on the animal experiments on the intervention of Chinese medicine polysaccharides in diabetic nephropathy in recent years, we analyzed and summarized the mechanism of Chinese medicine polysaccharides in the intervention of diabetic nephropathy from five aspects of improving insulin resistance, improving oxidative stress, reducing inflammatory reaction, protecting kidney and improving intestinal flora. In addition, the signaling pathways and indicators involved in the mechanism were summarized, and the intervention effect and polysaccharide structure analysis were compared. The paper was expected to provide a theoretical basis for the basic research, new drug development and clinical application of Chinese medicine polysaccharides in the intervention of diabetic nephropathy.
Keywords:Chinese medicine polysaccharides;diabetic nephropathy;mechanism;signaling pathway
Abstract:Stroke is one of the major diseases threatening human health, with ischemic stroke accounting for about 70%. Ischemic stroke is characterized by complex pathological mechanism and high incidence, mobility and mortality. At present, the effective clinical treatment measures for ischemic stroke are limited, and it is urgent to develop new and effective treatment measures to improve the prognosis of patients. In recent years, bone marrow mesenchymal stem cells (BMSCs) transplantation has shown great therapeutic potential for a variety of diseases, including ischemic stroke, and has become a new research hotspot. However, due to the low homing and survival rate of BMSCs in human body after transplantation, their clinical effect on ischemic stroke needs to be further improved. With the characteristics of multi-components, multi-channels and multi-targets, Chinese medicine displays desirable curative effect on ischemic stroke, which has been widely concerned. Both Chinese medicine and BMSCs transplantation have good overall brain protection, and their combined effect on ischemic stroke is significantly better than that of single application. The mechanisms include improving the transplantation efficiency of BMSCs, promoting angiogenesis, enhancing neuroplasticity, ameliorating neuroinflammation, enhancing neuroprotection, and regulating the blood-brain barrier and exosomes. The combination of Chinese medicine and modern cutting-edge cell therapy reflects the advantages of integrative medicine, providing a new model and idea for preventing and treating ischemic stroke and improving the efficacy of BMSCs transplantation.
Keywords:traditional Chinese medicine;bone marrow mesenchymal stem cells (BMSCs);ischemic stroke;mechanism;exosomes
Abstract:Decoction is a traditional clinical way of traditional Chinese medicine (TCM) compound. A series of complex physical and chemical changes are often involved in the process of decoction, which presents a mixed-phase system. In most studies on the TCM compound decoction, it has always focused on the amounts of chemical substances in decoction, while the phase properties and existence forms of these components are neglected. Most of the chemical components exist in the mixed-phase system as molecules, ions or other particles. According to the particle size of the contained particles, the differences among the phases, including true solution phase, colloidal phase, suspended phase and precipitated phase, lead to their differences in pharmaceutical and biological effects. Based on the above research background, this paper takes the phase state differences of decoction as the breakthrough point, and systematically reviews the physicochemical properties, the physical structures of the active components and the biological effects of the decoction caused by the phase state differences. The phase state differences of TCM compound decoction have been found to be closely related to their efficacy, which might be a good perspective to investigate the possible mechanism. It might provide a beneficial reference for the exploration of related basic research on TCM compounds.
Keywords:traditional Chinese medicine compound;phase state differences;decoction;compatibility;colloidal phase;drug property delivery theory;material basis
Abstract:The cold congeal and blood stasis syndrome is a common clinical traditional Chinese medicine(TCM) syndrome. The animal model of cold ongeal and blood stasis syndrome is the basis for exploring the essence of TCM cold congeal and blood stasis syndrome,and the premise of follow-up TCM clinical research.This paper summarized the preparation method, theoretical support,and evaluation method of animal models of cold congeal and blood stasis syndrome in recent years and analysed the strengthens and weaknesses of different models. At present,the common animal models of cold congeal and blood stasis syndrome mainly include etiological model,etiological and pathological composite model and disease-syndrome combination model. The etiological model was mainly prepared by cold exposure,which could be divided into whole-body freezing, ice bath and local frostbite. The etiological and pathological composite model was mainly prepared by cold stimulation combined with epinephrine injection. The common disease-syndrome combination models included the coronary heart disease model of cold congeal and blood stasis syndrome,primary dysmenorrhea model of cold congeal and blood stasis syndrome,endometriosis model of cold congeal and blood stasis syndrome, and arteriosclerosis obliterans model of cold congeal and blood stasis syndrome. The three models have both advantages and disadvantages. Specifically, the disease-syndrome combination model had the highest consistency with clinical practice and was more reliable and practical. However, the disease types of this model were specific,and the combination method of disease and syndrome was controversial. The evaluation indicators of the animal models of cold congeal and blood stasis syndrome focused on the characterization of the syndrome and the physico-chemical indicators related to blood flow,such as blood rheology,coagulation function and microcirculation. In addition, some scholars explored the evaluation indicators from the aspects of vasomotor function,endocrine and energy metabolism. The objectivity and specificity of the current model evaluation methods needed to be further improved. The research of animal model of cold congeal and blood stasis syndrome should be based on clinical practice and oriented by clinical demand. Only by establishing animal models that are highly consistent with the characteristics of clinical disease and syndrome can we better reveal the essence of cold congeal and blood stasis syndrome and promote the modernization of TCM.
Abstract:Hederin is a natural active component of triterpenoid saponins extracted from many medicinal herbs, such as Lithospermum erythrorhizon, Pulsatilla chinensis, and Clematis florida. It has attracted much attention from doctors for its anti-inflammatory, anti-convulsive, anti-oxidation and anti-leishmaniasis activities. Hederin has significant anti-tumor bioactivity and is expected to be a potential drug for the treatment of malignant tumors. The available studies have demonstrated that hederin can promote the apoptosis, inhibit the proliferation, metastasis, and invasion, and induce the autophagy of tumor cells, exhibiting a promising prospect in the treatment of breast cancer, lung cancer, liver cancer, and pancreatic cancer. Specifically, hederin can regulate the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway, reactive oxygen species (ROS), and microRNA (miRNA) to trigger tumor cell apoptosis. Its anti-proliferation activity is mainly reflected in the regulation of cyclin and cyclin-dependent kinase (CDK). Hederin inhibits the metastasis and invasion of tumor cells by blocking epithelial-mesenchymal transformation (EMT). In addition, hederin can influence metabolic reprogramming to induce tumor cell autophagy. Hederin is involved in a variety of pathways to exert its anti-tumor activity and may become a novel anti-tumor drug in the future, which give new sights into the study of hederin in the anti-tumor field. There are few studies about hederin and no systematic review of its anti-tumor mechanisms. Therefore, this study reviewed the studies about the anti-tumor mechanism of hederin, aiming to provide reference and information for researchers and clinical staff.