Objective To investigate the protective effects of left ventricular myocardial perfusion after delivery of acidic fibroblast growth factor (aFGF) in rats with diabetic cardiomyopathy (DCM) by using ultrasound‐targeted microbubble destruction ( UTMD ) with real‐time myocardial contrast echocardiography( RT‐MCE) . Methods Among 64 male SD rats ,52 rats were randomly selected and were induced DCM by streptozotocin through intraperitoneal injecting ,the other rats as normal control group . DCM rats were randomly divided into the DCM model group ,aFGF only group ,SonoVue‐aFGF group and the SonoVue‐aFGF+ UTMD group in this study . The aFGF only group rats were injected with aFGF solution through tail vein ,the SonoVue‐aFGF group were injected with SonoVue‐aFGF solution through tail vein and SonoVue‐aFGF+ UTMD group rats were injected with SonoVue‐aFGF solution through tail vein and using UTMD simultaneously . All rats underwent conventional echocardiography and RT‐MCE exams before and 4 weeks after intervention . Left ventricular ejection fraction ( LVEF) and left ventricular fraction shortening( LVFS ) were measured by conventional echocardiography . The plateau intensity ( A ) ,initial slope of the curve (β) and myocardial blood flow ( A ×β) of left ventricular anterior wall at the papillary muscle level were measured in left ventricular short‐axis view by RT‐MCE . Results Before intervention , LVEF and LVFS in the DCM model group ,aFGF only group ,SonoVue‐aFGF group and the SonoVue‐aFGF+UTMD group were significantly lower than in the normal control group ( P <0 .01) .During 4 weeks after intervention ,LVEF and LVFS in the aFGF only group ,SonoVue‐aFGF group and the SonoVue‐aFGF+UTMD group were slightly increased than those in the DCM model group ,but no statistically significant differences were found ( P > 0 .05) ,however A and A × β in the SonoVue‐aFGF+ UTMD group were significantly increased than those in the DCM model group( P < 0 .01) . Compared with the same group before intervention ,A and A ×βin the SonoVue‐aFGF+UTMD group were higher ( P <0 .05) and these in the DCM model group were lower during four weeks after intervention ( P < 0 .05) . Conclusions Acidic fibroblast growth factor delivered by using UTMD can improve the left ventricular myocardial perfusion in diabetic cardiomyopathy rats .

Salviae Miltiorrhizae Radix et Rhizoma-Carthami Flos is a famous Chinese medicine pair (CMP). Salviae Miltiorrhizae Radix et Rhizoma can promote blood circulation for removing blood stasis, and Carthami Flos can promote blood circulation for removing meridian obstruction and remove blood stasis for relieving pain. The two herbs are important TCMs for activating blood. Danhong injection is the classic application of the two herbs compatibility, which was made from Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos with scientific formalation by extraction and refining. The CMP is used for treatement of organ flood insufficiency and ischemic infarction diseases. It can obviously relieving symptoms of angina pectoris, improve myocardial ischemia, regress atherosclerosis plaque, and inhibit thrombus. This paper elaberated the bio-active constituents, compatibility effects and action mechanism, and clinical applications of the CMP in order to further upgrade basic research and application levels of the CMP.
Animals ; Carthamus tinctorius ; chemistry ; Drug Compounding ; Drug Interactions ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Medicine, Chinese Traditional ; methods ; Salvia miltiorrhiza ; chemistry

The combination of Danggui and Honghua (GH) is a popular herb pair commonly used in clinic for the treatment of blood stasis syndrome in China. To evaluate the activating blood circulation and dissipating blood stasis effects of the combination of different proportions of Danggui and Honghua on acute blood stasis rats, and optimize the proportion of GH to have the best activating blood circulation and dissipating blood stasis effect. Acute blood stasis rat model was induced by subcutaneous injection of adrenaline and ice water bath. The blood stasis rats were administrated intragastrically with GH (1 : 0, 4 : 1, 2 : 1, 3 : 2, 1 : 1, 2 : 3, 1: 2, 1 : 4 and 0 : 1) extracts. The whole blood viscosity (WBV), plasma viscosity (PV), and high shear whole blood relative index (HSWBRI), low shear whole blood relative index (LSWBRI), and erythrocyte aggregation index (EAI) were tested to observe the effects of GH on hemorheology of blood stasis rats. And the maximum aggregation induced by adenosine diphosphate (ADP) was tested to observe the effect of GH on platelet aggregation index of blood stasis rats. In addition, the prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT) and plasma fibrinogen (FIB) were tested to observe the effects of GH on blood coagulation function of blood stasis rats. Then principal component analysis and multi-attribute comprehensive index methods were both used to comprehensively evaluate the total activating blood circulation and dissipating blood stasis effects of GH. The results showed that the hemorheological indexes and coagulation parameters of model group both had significant differences with normal group. Compared with model group, GH (1 : 0, 4 : 1, 2: 1, 3 : 2, 1 : 1, 2 : 3, 1 : 2, 1 : 4 and 0 : 1) could improve all the blood hemorheology indexes and regulate part indexes of blood coagulation function and platelet aggregation in acute blood stasis rats. Based on principal component analysis and multi-attribute comprehensive index methods, GH 1 : 1 and GH 3 : 2 both had the best effect of blood circulation and dissipating blood stasis, and the effect of GH 1 : 1 was slightly better than GH 3 : 2. These results suggest that GH could obviously ameliorate the abnormality of hemorheology and blood coagulation function in acute blood stasis rats. The optimized proportion of GH was consistent with regulations of medicine usage that GH 1 : 1 had the highest frequency used in traditional Chinese formulae. It could provide scientific basis for more effective application of the compatibility between Danggui and Honghua in modern clinic medicine.
Animals ; Blood Coagulation ; Blood Viscosity ; Carthamus tinctorius ; China ; Drugs, Chinese Herbal ; pharmacology ; Erythrocyte Aggregation ; Hemorheology ; Partial Thromboplastin Time ; Platelet Aggregation ; Principal Component Analysis ; Prothrombin Time ; Rats ; Rats, Sprague-Dawley ; Thrombin Time

Chronic kidney disease (CKD) is a serious chronic disease with high incidence, poor prognosis, and a variety of complications. Indoxyl-sulfate (IS) and p-cresol sulfate (PCS) are two typical gut-derived uremic toxins, which are produced by the co-metabolism of intestinal microbes and the host. With the progression of CKD, gut-derived uremic toxins such as IS and PCS accumulate in patients with CKD and thereafter accelerate the progression of CKD. Gut microbiota is closely related with CKD, and targeting gut microbiota to regulate gut-derived uremic toxins synthesis and metabolic pathways may be a promising strategy to delay the progression of CKD. In this paper, the relationship between gut microbiota, gut-derived uremic toxins, and CKD was analyzed, and the strategy to delay the progression of CKD by targeting gut microbiota and uremic toxins metabolism pathway was proposed.

In this study, the ameliorative effects of Flos Abelmoschus manihot on mice with chronic inflammatory bowel disease (IBD) were investigated and its effects on the structure of the intestinal flora as well as the lipid profile in feces of IBD mice were analyzed. All animal welfare and experimental procedures followed the regulations of the Animal Ethics Committee of Nanjing University of Chinese medicine. A mouse model with chronic IBD induced by dextran sulfate sodium (DSS) was used to evaluate changes in body weight, disease activity index (DAI), colonic histopathological damage as well as gene expression levels of inflammatory factors in the colon. Fecal samples from mice in each group were collected and subjected to Illumina high-throughput sequencing to detect the abundance of intestinal flora; samples were analyzed by UHPLC-Q-Exactive^® HF Quadrupole-Orbitrap^® of untargeted lipidomics, which detects lipid content in feces. Administration of Flos Abelmoschus manihot could significantly restore the body weight and ameliorate colonic histopathological damage in IBD mice. Sequencing of the gut microbiota revealed that the species diversity and richness of the gut microbiota in IBD mice were decreased, with a significant increase in the abundance of Verrucomicrobia and a significant decrease in the abundance of Bacteroidetes; Flos Abelmoschus manihot significantly increased the richness and diversity of intestinal microbiota in IBD mice, increased the number of taxa species at each level, and restored the abundance of bacteria in the phylum Bacteroidetes. Analysis of fecal lipid profiles identified the most significant changes in sphingolipid and glycerophospholipid metabolic pathways in IBD mice, with Flos Abelmoschus manihot inhibiting ceramide and sphingomyelin synthesis in sphingolipid metabolism. In summary, Flos Abelmoschus manihot can effectively improve the disease condition of mice with chronic IBD, and it has the effect of regulating intestinal flora homeostasis and lipid metabolism, but the related mechanism between the two still needs to be deeply explored.

Chinese medicine pairs (CMP) are specific compatibility with traditional Chinese medicine (TCM) theory as principle, which was formed on basis of effect and treatment theory of TCM. The compatibility of CMP can enhance the effect, or reduce the toxicity. So, compatibility effects of CMP were studied from different pharmacology levels including animals, tissues and organs, cell and molecular levels, their synergy and compatibility attenuation were also evaluated with monomer component-component (group) compatibility-single herb-CMP-formulae as the main line, and the action mechanisms were investigated, all of which can provide scientific basis for the clinical applications of CMP and creation of TCM new drugs.
Animals ; Drug Interactions ; Drug Synergism ; Drug-Related Side Effects and Adverse Reactions ; prevention & control ; Humans ; Medicine, Chinese Traditional ; adverse effects ; methods

Aging can cause degenerative changes in the function of multiple tissues and organs in the body. Gastrointestinal diseases and intestinal dysfunction are very common in the elderly people. The purpose of this study is to explore the effect of the total extract of Astragalus membranaceus (Fisch.) Bge. on intestinal function and gut microbiota homeostasis in natural aging mice, which will provide clues for further mechanism study. The natural aging mice model is established and animal experiments follow the regulations of the Animal Ethics Committee of Nanjing University of Traditional Chinese Medicine. The overall health of the mice was evaluated by the "frailty index" scoring method. The intestinal absorption and transport function were measured by detecting intestinal glucose absorption capacity, transport time, lipase and amylase activities of aging mice. Intestinal inflammation was assessed by detecting inflammatory cytokines by enzyme-linked immunosorbent assay (ELISA). The pathological changes in the intestines of aging mice were tested by hematoxylin-eosin (H&E) staining and alizarin blue (AB) staining. The qRT-PCR method was used to explore the gene transcription level related with the proliferation and differentiation of intestinal stem cells. Microbiota analysis based on 16S rDNA were used to evaluate the composition of gut microbiota. The results showed that Astragalus had a tendency to reduce the "frailty index" of aging mice, but did not show a significant difference. In some indicators of aging phenotype, Astragalus has the most significant effect on hair loss and physical fitness. In terms of intestinal function, Astragalus could increase intestinal glucose absorption capacity, shorten intestinal transportation time and promote lipase secretion in aging mice. The levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-‍α) in the aging intestinal tissue were reduced after Astragalus administration. Astragalus also ameliorated the pathological degeneration of the intestinal tissue of aging mice by increasing the length of small intestinal villi, the thickness of colonic mucosa and goblet cell number. In addition, Astragalus elevated the expression of genes associated with the proliferation and differentiation in jejunum and modulated gut microbiota, especially restoring the abundance of Lachnospiraceae. Taken together, the above research results demonstrate the total extract of Astragalus as a key factor improving the intestinal function and gut microbiota homeostasis of aging mice.

Acetylcholine ; metabolism ; Animals ; Arcuate Nucleus of Hypothalamus ; metabolism ; Dopamine ; metabolism ; Epinephrine ; metabolism ; Female ; Neurotransmitter Agents ; metabolism ; Norepinephrine ; metabolism ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Synaptic Transmission

Along with progress of modern science and technology, human is utilizing natural resources and their inherent law more effectively and more efficiently according to their own purposes. Chinese medicine pair (CMP) is relatively fixed combination of two TCMs which was proven to be effective in clinical application. CMP has its inner specification, and it is an intermediate point between single herb and many TCM formulae. With the aid of modern science and technology, and by means of choosing appropriate strategies and approaches, the compatibility rules of CMP might be revealed, which will be significant to develop the compatibility theory of TCM formulae and create modern TCM new drugs.
Animals ; Clinical Trials as Topic ; Drug Interactions ; Humans ; Medicine, Chinese Traditional ; methods ; Research Design ; Systems Biology

To analyze naringin, naringenin and its metabolites in rat urine and feces after intragastric administration of alcohol extract of Exocarpium Citri Grandis, healthy SD rats were fed with alcohol extract of Exocarpium Citri Grandis for 3 days. On the last day, 0-24 h feces and 0-4 h, 4-8 h, 8-24 h urine were collected and analyzed by UPLC-Q-TOF/MS. The post-acquisition data were processed using Metabolynx The result is that naringin and its 6 metabolites, naringenin and its 4 metabolites were detected in the urine of rat. Meanwhile, naringin and its 3 metabolites, naringenin and its 2 metabolites were detected in the feces of rat.
Administration, Oral ; Animals ; Chromatography, High Pressure Liquid ; Citrus ; chemistry ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacokinetics ; Feces ; chemistry ; Flavanones ; metabolism ; urine ; Male ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization