Astragalus polysaccharide improves diabetic ulcers by promoting M2-polarization of macrophages to reduce excessive inflammation via the ß-catenin/ NF-κB axis at the late phase of wound-healing.

Ethnopharmacological relevance: Astragalus polysaccharide (APS), the most biologically active ingredient of Astragali Radix, is used to treat diabetes mellitus (DM)-related chronic wounds in traditional Chinese medicine for several decades. This herb possesses an anti-inflammatory effect. Our study proved that APS can reduce excessive inflammation at the late phase of wound-healing in diabetic ulcers. Aim of the study: To clarify the molecular mechanism of APS in promoting wound-healing via reducing excessive inflammation in diabetic ulcers during the late stages of wound-healing. Methods and materials: The rat model of the diabetic ulcers was established via intraperitoneal injection of streptozocin (60 mg/kg). We detected the regulation of APS on diabetic ulcers by measuring wound-healing rates. Bioinformatics was used to predict the target genes of APS, and autodocking was used to predict the combination of APS and target genes. Immunohistochemistry, Enzyme-linked immunosorbent assay, Western blot, immunofluorescence staining, flow cytometry, and flow cytometric sorting were investigated. Results: The results demonstrated that APS promoted wound-healing and inhibited excessive inflammation at the late phase of wound-healing in diabetic rats. Mechanistic findings showed that APS promoted the expression of ß-catenin and Rspo3 while inhibiting the expression of NF-KB and GSK-3ß, which leads to the transformation of M1-type macrophages into M2-type macrophages and thus reducing excessive inflammation at the late phase of wound-healing in diabetic ulcers. Conclusion: We found an interesting finding that APS promoted the polarization of macrophages towards M2-type through the ß-catenin/NF-κB axis to reduce excessive inflammation at the late phase of wound-healing. Therefore, APS may be a promising drug for treating diabetic ulcers in clinic.

Pharmacological Mechanism of Xiaoyaosan in Treating Depression Due to Liver Stagnation and Spleen Deficiency / 中国实验方剂学杂志

Depression belongs to the category of "stagnation syndrome" in traditional Chinese medicine. There are many clinical types of depression in which liver stagnation and spleen deficiency syndrome is one of the main types. As a classic prescription for liver-soothing and spleen-strengthening, Xiaoyaosan has a definite curative effect in the treatment of depression due to liver stagnation and spleen deficiency. With fewer adverse reactions, a high safety and good patient compliance, it can be combined with western medicine to reduce the recurrence rate and adverse reactions of western medicine, and has become the focus and hotspot of research in recent years. Although many experts and scholars have conducted a lot of research on the pharmacological mechanism of Xiaoyaosan in the treatment of depression due to liver stagnation and spleen deficiency, its mechanism is still unclear. In addition, there are many types of animal models for depression due to liver stagnation and spleen deficiency but only a few systematic reports on Xiaoyaosan in treating depression of liver stagnation and spleen deficiency. Therefore, based on two classic models of chronic mild unpredictable stress depression model (CUMS) and chronic restraint stress depression model (CIS), a review was conducted on the pharmacological mechanisms of Xiaoyaosan in the treatment of depression due to liver stagnation and spleen deficiency by regulating neurotransmitter concentration, affecting the expression of neurotrophic factor, regulating hytothalamus-pitutary-adrenal(HPA)axis imbalance, improving intestinal micro-ecology and gastrointestinal function, regulating endogenous metabolite levels and immune inflammatory factor levels and improving synaptic structure and plasticity, so as to provide potential guidelines for basis study and clinical application of Xiaoyaosan in the treatment of depression due to liver stagnation and spleen deficiency.

Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis.

Tet is a type of alkaloid extracted from Stephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP). The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance.

Discrimination of patients with Xiao-Chaihu Tang syndrome using 1H NMR metabonomics and partial least square analysis / 药学学报

1H NMR metabonomics approach was used to reveal the chemical difference of urine between patients with Xiao-Chaihu Tang syndrome (XCHTS) and healthy participants (HP). The partial least square method was used to establish a model to distinguish the patients with Xiao-Chaihu-Tang syndrome from the healthy controls. Thirty-four endogenous metabolites were identified in the 1H NMR spectrum, and orthogonal partial least squares discriminant analysis showed the urine of patients with Xiao-Chaihu Tang syndrome and healthy participants could be separated clearly. It is indicated that the metabolic profiling of patients with Xiao-Chaihu Tang syndrome was changed obviously. Fifteen metabolites were found by S-pot of OPLS-DA and VIP value. The contents of leucine, formic acid, glycine, hippuric acid and uracil increased in the urine of patients, while threonine, 2-hydroxyisobutyrate, acetamide, 2-oxoglutarate, citric acid, dimethylamine, malonic acid, betaine, trimethylamine oxide, phenylacetyl glycine, and uridine decreased. These metabolites involve the intestinal microbial balance, energy metabolism and amino acid metabolism pathways, which is related with the major symptom of Xiao-Chaihu Tang syndrome. The patients with Xiao-Chaihu Tang syndrome could be identified and predicted correctly using the established partial least squares model. This study could be served as the basis for the accurate diagnostic and reasonable administration of Xiao-Chaihu-Tang syndrome.

1H NMR based metabolomics study of bu-zhong-yi-qi-tang in the spleen-qi deficiency rat model / 药学学报

The present study aimed to investigate the effect and the mechanisms of Bu-zhong-yi-qi-tang (BZYQ) on Spleen-Qi deficiency rat's model using nuclear magnetic resonance (NMR) metabolomics and multivariate statistical analysis methods. The rat Spleen-Qi deficiency model was established as follows: oral administration of Radix Rhei extract, loaded swimming and starvation for 24 h. The body weight and motor behavior of the rats were measured and recorded once a week. BZYQ could significantly improve body weight and behavioral of Spleen-Qi deficiency model rats compared with the model group (P < 0.05, 0.01). After drug administration, the changes in the levels of endogenous metabolites in the spleen including decreasing lactate, taurine and hypoxanthine, increasing glutamate and scyllo-inositol compared with the model group. The metabolomics approach is an effective tool for the investigation of the pharmacologic mechanism of BZYQ and it is helpful to further research.

1H NMR based metabolomics study of bu-zhong-yi-qi-tang in the spleen-qi deficiency rat model / 药学学报

The present study aimed to investigate the effect and the mechanisms of Bu-zhong-yi-qi-tang (BZYQ) on Spleen-Qi deficiency rat's model using nuclear magnetic resonance (NMR) metabolomics and multivariate statistical analysis methods. The rat Spleen-Qi deficiency model was established as follows: oral administration of Radix Rhei extract, loaded swimming and starvation for 24 h. The body weight and motor behavior of the rats were measured and recorded once a week. BZYQ could significantly improve body weight and behavioral of Spleen-Qi deficiency model rats compared with the model group (P < 0.05, 0.01). After drug administration, the changes in the levels of endogenous metabolites in the spleen including decreasing lactate, taurine and hypoxanthine, increasing glutamate and scyllo-inositol compared with the model group. The metabolomics approach is an effective tool for the investigation of the pharmacologic mechanism of BZYQ and it is helpful to further research.

LC-MS/MS method for the determination of a new puerarin derivative and its application in pharmacokinetic studies in rats / 中国天然药物

AIM@#To establish a sensitive and rapid liquid chromatographic-tandem mass spectrometry (LC-MS/MS) method for the quantitative analysis of dehydrated puerarin in rat plasma, and its application for pharmacokinetic studies.@*METHODS@#A plasma sample was pretreated by one-step protein precipitation by the addition of five volumes of methanol. The chromatographic separation was achieved on a Zorbax SB-C18 column (4.6 mm × 150 mm I.D. 5.0 μm, Agilent, USA) at 40 °C at a flow rate of 0.6 mL·min(-1) by an isocratic elution consisting of 10 mmol·L(-1) ammonium acetate in methanol and water containing 0.1% formic acid in a ratio of 20 : 80 (V/V). Detection was performed on a triple quadrupole mass spectrometer in multiple-reaction monitoring (MRM) mode. An atmospheric pressure chemical ionization (APCI) interface in positive ionization mode was used by monitoring the transitions from m/z 399.1→281.0 (dehydrated puerarin) and m/z 271.0→215.0 (internal standard, IS).@*RESULTS@#Calibration curves were linear in the concentration range from 1.50 to 5400 ng·mL(-1), and the lower limit of quantification (LLOQ) was 1.50 ng·mL(-1) in rat plasma. The accuracy and precision values, which were calculated from three different sets of quality control samples analyzed in sextuplicate on three different days, ranged from 95.73% to 103.18%, and from 4.33% to 7.86%, respectively.@*CONCLUSION@#The method was successfully applied to assess the pharmacokinetics of dehydrated puerarin after oral administration in rats.

Assessment of external methods of traditional Chinese medicine in patients with chronic ulcer of the lower extremities: study protocol of a multicenter, randomized, parallel-group, prospective trial / 中西医结合学报

Chronic ulcer of the lower extremities amounts for a grave and serious problem for public health. Western medicine focuses on controlling infection, improving blood circulation, surgical debridement, skin grafting, etc, but there are bottlenecks in the treatment. Traditional Chinese medicine (TCM) has a long history and a legacy of sound clinical efficacy in this area. TCM has developed a unique, effective external theory, and a large number of topical prescriptions and external technology. Through this research, a safe and effective treatment protocol of TCM for chronic ulcer of the lower extremities can be formed. To this end, during China's "Eleventh Five-Year" Plan, special research committees and projects on TCM external treatments and external technologies were established. This study on ulcer of the lower extremities constitutes one of the major research topics.

Effects of Shenmai Injection on serum concentration and pharmacokinetics of digoxin in dogs with heart failure / 中西医结合学报

To explore the effects of Shenmai Injection (SMI), a compound traditional Chinese herbal medicine, on pharmacokinetics and serum concentration of digoxin when applied together with digoxin.

Applying collateral disease theory to treat chronic dermal ulcer / 中西医结合学报

Collateral disease theory has been applied to investigate the pathogenesis of chronic dermal ulcer in traditional Chinese medicine. It is suggested that deficiency of vital qi is the pathological basis of chronic dermal ulcer with collaterals stagnation as the major pathological factor, and collaterals impairment by toxin evil is the main pathological change. The important principle in treatment of chronic dermal ulcer is established as strengthening the body resistance, dredging collaterals and removing toxins, and this enriched the theory of wound healing in traditional Chinese medicine, and has practical value.

Effects of reinforcing qi and nourishing blood recipes on vascular endothelial growth factor and microvessel count in granulation tissue in rats with chronic skin ulcers / 中西医结合学报

OBJECTIVE: To explore the effects of reinforcing qi and nourishing blood recipes on vascular endothelial growth factor (VEGF) and the microvessel count (MVC)in granulation tissue in rats with chronic skin ulcers. METHODS: A total of 90 male SD rats with back full-thickness skin lesion were used in this study. Except for the normal control group, the rats were injected with hydrocortisone for inducing chronic skin ulcers, and were randomly divided into untreated group, Sijunzi Decoction group, Siwu Decoction group and Bazhen Decoction group. The time of wound healing was observed; immunohistochemical method and image analytical method were used to test the expressions of VEGF and MVC in granulation tissue of dermal chronic ulcers in the rats. RESULTS: In the untreated group, the time of wound healing was significantly longer than that in the normal group (P<0.01). The time of wound healing was obviously shortened in the three treated groups as compared with the untreated group (P<0.01, P<0.05). In the Sijunzi Decoction group, the time of wound healing was obviously shorter than those in Siwu Decoction group and Bazhen Decoction group (P<0.05, P<0.01). In the untreated group, the expression of VEGF and MVC were significantly lower than those in the normal control group (P<0.01). The expression of VEGF and MVC were obviously increased in the three treated groups as compared with those in the untreated group (P<0.01, P<0.05). In the Sijunzi Decoction group, the expression of VEGF and MVC were obviously lower than those in Siwu Decoction group and Bazhen Decoction group (P<0.05, P<0.01). CONCLUSION: Reinforcing qi and nourishing blood recipes can promote wound healing in rats through up-regulating the expression of VEGF in granulation tissue of dermal chronic ulcers, and inducing angiogenesis.

Effects of Chinese herbs for replenishing qi and resolving stagnation on hypoxia-inducible factor-1alpha and vascular endothelial growth factor in granulation tissue of skin ulcers in rats with diabetes / 中西医结合学报

OBJECTIVE: To explore the effects of Chinese herbs for replenishing qi and resolving stagnation on hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in granulation tissue of skin ulcers in rats with syndrome of blood stasis and qi deficiency. METHODS: Diabetic rats with back full-thickness skin lesion and syndrome of blood stasis and qi deficiency were divided in to five groups: untreated group, basic fibroblast growth factor (bFGF)-treated group, Yiqi Huayu Recipe (a recipe for replenishing qi and resolving stagnation)-treated group, Yiqi Recipe (a recipe for replenishing qi)-treated group and Huayu Recipe (a recipe for resolving stagnation)-treated group, and another eight normal rats served as normal control group. Immunohistochemical method and image analysis were used to test the expressions of HIF-1alpha and VEGF in granulation tissue of skin ulcers in rats with diabetes. RESULTS: In the untreated group, the expression of HIF-1alpha was significantly increased and the expression of VEGF was significantly decreased as compared with those in the normal control group (P<0.01). The expression of HIF-1alpha was obviously lower (P<0.01) and the expression of VEGF was significantly higher in the four drug treated groups as compared with those in the untreated group. In the Yiqi Huayu Recipe-treated group, the expression of HIF-1alpha was obviously lower than those in the bFGF-treated, Yiqi Recipe-treated and Huayu Recipe-treated groups (P<0.05 or P<0.01), and the expression of VEGF was significantly higher than that in the bFGF-treated group (P<0.01). CONCLUSION: Chinese herbs for replenishing qi and resolving stagnation can promote the wound healing in rats through reducing the expression of HIF-1alpha, accelerating the expression of VEGF in granulation tissue of skin ulcers in rats with diabetes and ameliorating the status of ischemia and hypoxia.

The tissue distribution in mice and pharmacokinetics in rabbits of oridonin-solid lipid nanoparticles / 药学学报

<p><b>AIM</b>To investigate the tissue distribution and pharmacokinetics of oridonin-solid lipid nanoparticles in animals.</p><p><b>METHODS</b>HPLC method was established to determine the concentration of oridonin in serum of rabbits and in different tissues of mice. The results after tail iv administration of oridonin and oridonin solid lipid nanoparticles were compared.</p><p><b>RESULTS</b>The relative tissue content of oridonin of solid lipid nanoparticles in the liver, spleen, lung, heart and kidney were 4.25%, 3.44%, 1.19%, 0.52% and 0.60%, respectively. The concentration-time curves of oridonin and oridonin solid lipid nanoparticles were both fitted to the three-compartment model. T(1/2)pi = 0.087 h, T(1/2)alpha = 1.65 h, T(1/2)beta = 32.36 h, V(C) = 0.66 mL.kg(-1).</p><p><b>CONCLUSION</b>Solid lipid nanoparticles could increase the hepatic and lienic targeting efficiency of oridonin in mice and improve its bioavailability. Solid lipid nanoparticles were helpful for oridonin to reach a long circulation time and were hopeful to be its novel drug carrier.</p>