Antibacterial Effects of Ramulus mori Oligosaccharides against Streptococcus mutans.

Ramulus mori has been widely used in traditional Chinese medicine because of its physiological activities, including antibacterial, anti-inflammatory, and antioxidant activities. Antimicrobial properties of Ramulus mori extract have been well described. However, no information is available regarding on Ramulus mori oligosaccharides (RMOS). The aim of this study was to investigate the effects of RMOS on the growth and virulence properties of the cariogenic bacterium Streptococcus mutans. The effects of RMOS on the biofilm structure and virulence gene expression of S. mutans were also evaluated, and the results were compared with the effects of commercial prebiotic galactooligosaccharides. RMOS were found to have an antibacterial effect against S. mutans, resulting in significant reductions in acid production, lactate dehydrogenase activity, adhesion, insoluble extracellular polysaccharide production, glucosyltransferase activity, and biofilm formation in a dose-dependent manner. Moreover, the biofilm structure was visibly damaged. A quantitative real-time PCR assay revealed downregulation of virulence gene-regulated acid production, polysaccharide production, adhesion, biofilm formation, and quorum sensing. These findings suggest that RMOS may be a promising natural product for the prevention of dental caries.

Ramulus mori (Sangzhi) alkaloids regulates gut microbiota disorder and its metabolism profiles in obese mice induced by a high-fat diet.

The imbalance of gut microbiota has been confirmed to have a close pathological and physiological correlation with obesity and metabolic syndrome. Ramulus Mori (Sangzhi) Alkaloids (SZ-A) derived from twigs of mulberry was approved by the National Medical Products Administration of China in 2020 for the treatment of type 2 diabetes mellitus. In addition to its hypoglycemic effect, previous studies have confirmed that SZ-A also alleviates high-fat diet-induced obesity and non-alcoholic fatty liver disease and ameliorates obesity-linked adipose tissue metabolism and inflammation, indicating the potential of SZ-A to regulate obesity and metabolic syndrome. However, whether SZ-A can improve obesity and metabolic syndrome by regulating gut microbiota and its metabolism profiles remains unclear. The purpose of this study was to assess the effect of SZ-A on gut microbiota in obese mice and to explore the association among changes in gut microbiota, obesity, and lipid metabolism. The results showed that oral administration of SZ-A could significantly reduce body weight, fat mass, and the level of total cholesterol and low-density lipoprotein in serum in obese mice induced by a high-fat diet. Interestingly, SZ-A also regulated gut microbiota and changed the fecal metabolite composition of obese mice. Compared with the high-fat diet group, the ratio of Firmicutes to Bacteroides changed at the phylum level and the abundance of Bifidobacterium and Akkermansia muciniphila significantly increased at the genus level in the SZ-A group. The gut microbiota of the SZ-A group was reshaped and the relative abundance of microbial genes in bile acid metabolism and fatty acid metabolism were altered, which was consistent with the metabolomics results. Additionally, SZ-A greatly enriched the number of goblet cells and reduced inflammatory colon injury and pro-inflammatory macrophage infiltration induced by a high-fat diet in obese mice. In conclusion, SZ-A can alleviate obesity and metabolic syndrome by improving the gut microbiota and its metabolism profiles of obese mice induced by a high-fat diet.

Pharmacokinetics and tissue distribution of Ramulus Mori (Sangzhi) alkaloids in rats and its effects on liver enzyme activity.

Ramulus Mori (Sangzhi) alkaloids (SZ-A) derived from twigs of mulberry (Morus alba L., genus Morus in the Moraceae family) was approved by the National Medical Products Administration in 2020 for the treatment of type 2 diabetes mellitus. In addition to excellent hypoglycemic effect, increasing evidence has confirmed that SZ-A exerts multiple pharmacological effects, such as protecting pancreatic ß-cell function, stimulating adiponectin expression, and alleviating hepatic steatosis. Importantly, a specific distribution of SZ-A in target tissues following oral absorption into the blood is essential for the induction of multiple pharmacological effects. However, there is a lack of studies thoroughly exploring the pharmacokinetic profiles and tissue distribution of SZ-A following oral absorption into the blood, particularly dose-linear pharmacokinetics and target tissue distribution associated with glycolipid metabolic diseases. In the present study, we systematically investigated the pharmacokinetics and tissue distribution of SZ-A and its metabolites in human and rat liver microsomes, and rat plasma, as well as its effects on the activity of hepatic cytochrome P450 enzymes (CYP450s). The results revealed that SZ-A was rapidly absorbed into the blood, exhibited linear pharmacokinetic characteristics in the dose range of 25-200 mg/kg, and was broadly distributed in glycolipid metabolism-related tissues. The highest SZ-A concentrations were observed in the kidney, liver, and aortic vessels, followed by the brown and subcutaneous adipose tissues, and the heart, spleen, lung, muscle, pancreas, and brain. Except for the trace oxidation products produced by fagomine, other phase I or phase II metabolites were not detected. SZ-A had no inhibitory or activating effects on major CYP450s. Conclusively, SZ-A is rapidly and widely distributed in target tissues, with good metabolic stability and a low risk of triggering drug-drug interactions. This study provides a framework for deciphering the material basis of the multiple pharmacological functions of SZ-A, its rational clinical use, and the expansion of its indications.

Ramulus Mori (Sangzhi) alkaloids tablets for diabetes mellitus: A regulatory perspective.

The reform of the review and approval system for Traditional Chinese Medicine (TCM) continues to advance with the introduction of a new registration classification and the establishment of a review and approval evidence system. This new registration process established a novel review and approval evidence system, which combines the TCM theory, human use experience and clinical trials. Ramulus Mori (Sangzhi) alkaloids Tablets are a brand new drug. It is the first botanical natural hypoglycemic drug, and a new model of TCM review and approval evidence system has gradually been developed through contemporary research. In this paper, we discuss the registration process of new Chinese medicine drugs under the "three integrated review and approval system", retrace the development process of Mulberry alkaloid tablets, and discuss the opportunities and challenges encountered under the "three integrated" evidence system to provide feasible strategies and reference models for the development of Chinese medicine and the development of botanical drugs in the world.

Pharmacokinetic effects of metformin hydrochloride, food and alcohol on Ramulus Mori (Sangzhi) alkaloids / 药学学报

Ramulus Mori (Sangzhi) alkaloids (SZ-A) are a group of polyhydroxy alkaloids extracted and isolated from the traditional Chinese medicine mulberry twig, which is mainly used for the treatment of type 2 diabetes mellitus (T2DM). In addition to acting as a glycosidase inhibitor in the small intestine after oral administration, SZ-A can also be absorbed into blood and widely distributed to target organs related to diabetes, exerting multiple pharmacological effects. It is important to elucidate the possible pharmacokinetic influences of SZ-A for its clinical rational applications, such as drug interactions, the effects of food and alcohol on the absorption of SZ-A. However, studies in this area are limited. Therefore, the pharmacokinetic interactions between orally administrated SZ-A (50 mg·kg-1) and metformin hydrochloride (Met, 200 mg·kg-1) in Sprague-Dawley (SD) rats were examined. Then, the effect of food (standard feed) on the pharmacokinetics of SZ-A was investigated using fasting administration of SZ-A (50 mg·kg-1) in rats as a control. Finally, we investigated the pharmacokinetic characteristics of SZ-A (50 mg·kg-1) in different concentrations alcohol solutions using aqueous solution of SZ-A administered to rats as a control to evaluate the effect of alcohol on the bioabsorption of SZ-A. The results showed no significant pharmacokinetic interactions between SZ-A and Met after combination treatment. The standard feed had little effect on the pharmacokinetic profile of SZ-A. Alcohol retarded the absorption of SZ-A, resulting in a significant decrease in the Cmax of SZ-A. The decrease was greater at higher alcohol concentrations; however, no significant difference was observed in the AUC0-t. These results support the clinical rational applications of SZ-A. All animal protocols were approved by the Ethics Committee of Kangtai Medical Laboratory Service Hebei Co., Ltd. (Hebei, China) (No. MDL2022-01-17-1).

Ramulus Mori (Sangzhi) Alkaloids Ameliorate Obesity-Linked Adipose Tissue Metabolism and Inflammation in Mice.

Obesity has become a global epidemic disease as it is closely associated with a chronic low-grade inflammatory state that results in metabolic dysfunction. Ramulus Mori (Sangzhi) alkaloids (SZ-A) derived from Morus alba L. were licensed to treat type 2 diabetes (T2DM) in 2020. In this study, we explored the effect of SZ-A on adipose tissue metabolism and inflammation using an obesity model induced by a high-fat diet (HFD). C57BL/6J mice were fed high fat for 14 weeks and followed by SZ-A 400 mg/kg treatment via gavage for another six weeks, during which they were still given the high-fat diet. The results showed that SZ-A notably reduced body weight and serum levels of lipid metabolism-related factors, such as triglycerides (TG) and total cholesterol (TC); and inflammation-related factors, namely tumor necrosis factor alpha (TNFα), interleukin 6 (IL6), fibrinogen activator inhibitor-1 (PAI-1), angiopoietin-2 (Ang-2), and leptin (LEP), in the HFD-induced mice. SZ-A increased the protein and mRNA expression of lipid metabolism-related factors, including phosphorylated acetyl coenzyme A carboxylase (p-ACC), phosphorylated hormone-sensitive triglyceride lipase (p-HSL), adipose triglyceride lipase (ATGL), and peroxisome proliferator-activated receptor-alpha (PPARα), in adipose tissue. Immunohistochemistry results demonstrated that SZ-A significantly reduced the infiltration of pro-inflammatory M1-type macrophages in epididymal fat. The data also suggested that SZ-A down-regulates the transcriptional levels of inflammatory factors Il6, Tnfα, monocyte chemoattractant protein-1 (Mcp1), and F4/80, and up-regulates interleukin 4 (Il4), interleukin 10 (Il10), and interleukin 13 (Il13) in adipose tissue. Overall, the results indicate that SZ-A exhibits potential in regulating lipid metabolism and ameliorating obesity-linked adipose inflammation.

Ramulus Mori (Sangzhi) Alkaloids Alleviate High-Fat Diet-Induced Obesity and Nonalcoholic Fatty Liver Disease in Mice.

Nonalcoholic fatty liver disease (NAFLD), obesity, and type 2 diabetes mellitus (T2DM) have highly related mechanisms. Ramulus Mori (Sangzhi) alkaloids (SZ-A) from Morus alba L. were approved in 2020 for the treatment of T2DM. In this study, we examined the therapeutic effects and mechanism of SZ-A on obesity and NAFLD in mice. Mice (C57BL/6J) fed a high-fat diet (HFD) for 14 weeks were treated with SZ-A for another 6 weeks. HFD-induced weight gain was reduced by SZ-A in a dose-dependent manner. SZ-A treatment significantly stimulated adiponectin expression and secretion in adipose tissue and 3T3-L1 adipocytes. Additionally, SZ-A markedly reduced hepatic steatosis (triglyceride, total cholesterol) and expression of pro-inflammatory and pro-fibrotic genes. SZ-A regulated lipid metabolism and oxidative stress (malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione (GSH)) in the liver. Palmitic acid-induced insulin resistance and lipid accumulation in HepG2 cells were also repressed by SZ-A. Collectively, SZ-A protected mice from HFD-induced NAFLD through an indirect effect of improved systemic metabolism reducing bodyweight, and a direct effect by enhancing the lipid metabolism of HepG2 cells. The weight-loss effect of SZ-A in mice was partly due to improved fatty oxidation instead of influencing food consumption.

Research on Transfer Rate of Heavy Metals and Harmful Elements in Traditional Chinese Medicine Extraction and Refining Processes and Product Health Risk Assessment.

Ramulus Mori alkaloids, also known as SangZhi alkaloids (SZ-A), is a natural medicine used for the treatment of type 2 diabetes mellitus in China. SZ-A is extracted from Morus alba L., which grows in the natural environment and may be contaminated by heavy metals and harmful elements. These contaminants can enter SZ-A products during the extraction of M. alba, thereby posing a threat to patient health. Therefore, it is necessary to formulate scientific and reasonable limits to ensure patient safety. For this purpose, in this study, we used the extraction process of SZ-A as the object of investigation and determined the content of five harmful elements: Cd, Pb, As, Hg, and Cu in the herb raw material, SZ-A product, and its intermediates obtained in different extraction steps. Next, the transfer rate of harmful elements in the extraction process was used as an indicator to evaluate the ability of different operations to remove harmful elements. Subsequently, the health risks of heavy metals and harmful elements in SZ-A were assessed. Our results demonstrated that M. alba has little risk of contamination by Hg. The cation and anion resin refining processes are the best effective method to remove Cd, Pb, and Cu from the products. However, As is not easily eliminated during the water extraction. There is as much as 87% of As transferred from the herb raw material to the water-extracted intermediate, while Cd, Pb, and Cu are rarely transferred (6% to 17%) under the same conditions. Overall, the results indicate that the regulatory standard limits for Cd, Pb, As, Hg, and Cu contained in natural medicine Ramulus Mori alkaloids are set to 1, 5, 2, 0.2, and 20 µg/g, respectively, which is the most scientific and it can guarantee the safety of patients.

Lowering energy consumption for fermentable sugar production from Ramulus mori: Engineered xylanase synergy and improved pretreatment strategy.

Biorefinery of Ramulus mori with lower energy consumption through improved enzyme and pretreatment strategies was reported. Directed evolution and saturation mutagenesis were used for the modification of xylanase, the yield of fermentable sugars and the degree of synergy (DS) were determined for different pretreatment (seawater/non-seawater) and enzyme treatment groups (xylanase/cellulase/co-treatment). The dominant mutant I133A/Q143Y of Bispora sp. xylanase XYL10C_ΔN was obtained with improved specific activity (1860 U/mg), catalytic efficiency (1150 mL/s∙mg) at 40 °C, and thermostability (T50 increased by 7 °C). With the pretreatment of seawater immersion, the highest yield of fermentable sugars for Ramulus mori at 40 °C reached 199 µmol/g when hydrolyzed with cellulase and I133A/Q143Y, with the highest DS of 2.6; this was 4.5-fold that of the group hydrolyzed by cellulase alone with non-seawater pretreatment. Thus, bioconversion of reducing sugar from Ramulus mori was improved significantly at lower temperatures, which provides an efficient and energy-saving wayfor biofuel production.

A Novel Nanomedicine Ameliorates Acute Inflammatory Bowel Disease by Regulating Macrophages and T-Cells.

Ramulus mori polysaccharide (RMP), one of the most important active components of R. mori, has been attracting increasing interest because of its potent bioactive properties, including anti-inflammatory, antitumor, and antidiabetic effects. Despite the great therapeutic potential of RMP, its inherent properties of low bioavailability and brief biological half-life have limited its applications to the clinic. Thus, RMP was packaged by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to develop a novel anti-inflammatory nanomedicine (PLGA-RMP) in this study. The nanoparticles were synthesized via a double-emulsion solvent evaporation technique, and the average diameter of PLGA-RMP was about 202 nm. PLGA-RMP nanoparticles reduced the expression of inflammatory cytokines while promoting the production of IL-10, and boosted the phenotypic shift in macrophages in vitro. Furthermore, lipopolysaccharide (LPS)-induced inflammatory bowel disease (IBD) in mouse was used to examine the anti-inflammatory effect of PLGA-RMP in vivo. Oral administration of PLGA-RMP in LPS-induced IBD mice substantially mitigated the intestinal inflammation compared to treatment with LPS alone, as evidenced by attenuation of disease activity index scores and inflammatory damage in the intestine. Meanwhile, PLGA-RMP suppressed the expression and secretion of specific inflammatory cytokines including TNF-α, IL-6, IL-1ß, and PGE2 in the inflamed intestine while inhibiting the activation of CD3+CD8+ T-cells and increasing the number of activated Tregs in the intestine. These results indicated that PLGA-RMP deserves further consideration as a potential therapeutic nanomedicine to treat various inflammatory diseases, including IBD.

Ramulus mori polysaccharide-loaded PLGA nanoparticles and their anti-inflammatory effects in vivo.

In this study, ramulus mori polysaccharide (RMP) was encapsulated into Poly (lactic-co-glycolicacid) (PLGA) to form PLGA-RMP (PR). The aim of study is to investigate anti-inflammatory effects of PR. The particle size of PR nanoparticles was approximately 205.6 ± 1.86 nm. PR nanoparticles showed significant therapeutic effects on colitis mice model, evidenced by attenuation of the loss of body weight, reduction of the DAI score, and restoration of the colon length. From the histopathological analysis, alleviation of the histopathological damage, less production of IFN-γ and IL-6, and improvement of IL-10 were observed with the treatment of PR. Meanwhile, the treatment of PR not only promoted the expression of ZO-1 and occludin, but also improved the contents of acetate, propionate, and butyrate in the colitis colon. Furthermore, PR extenuated the reduction of the diversity and richness of gut microbiota induced by DSS, and decreased the ratio of Firmicutes to Bacteroidetes while increasing the proportion of Clostridium XIVa, Mucispirillum, and Paraprevotella in the gut microbiota. What's more, PR nanoparticles attenuated the metabolic disorders in the colitis colon induced by DSS. These results indicated that PR nanoparticles could serve as a potent nanomedicine to treat IBD and be used as potential prebiotics.

Ramulus Mori (Sangzhi) Alkaloids (SZ-A) Ameliorate Glucose Metabolism Accompanied by the Modulation of Gut Microbiota and Ileal Inflammatory Damage in Type 2 Diabetic KKAy Mice.

The novel Traditional Chinese Medicine Ramulus Mori (Sangzhi) alkaloid tablets (SZ-A) are approved by The China National Medical Products Administration for the treatment of type 2 diabetes mellitus (T2DM). However, the extensive pharmacological characteristics and the underlying mechanism are unknown. This study investigated the mechanisms by which SZ-A ameliorates glucose metabolism in KKAy mice, an animal model of T2DM. Diabetic KKAy mice were treated intragastrically with SZ-A once daily for 8 weeks, after which glucose levels, lipid metabolism, gut microbiome, systemic inflammatory factors, luminal concentrations of short-chain fatty acids (fecal samples), and ileal proteomic changes were evaluated. The ileum tissues were collected, and the effects of SZ-A on pathological inflammatory damage were evaluated by hematoxylin and eosin staining, immunofluorescence, and immunohistochemistry. The mRNA and protein expression levels of various inflammatory markers, including monocyte chemoattractant protein-1 and phosphorylated nuclear factor kappa B p65, were detected in the ileum tissues. SZ-A improved glucose metabolism with enhanced insulin response and elevated glucagon-like peptide 1 (GLP-1) nearly 2.7-fold during the glucose tolerance test in diabetic KKAy mice. Gut microbiota analysis demonstrated that SZ-A administration elevated the abundance of Bacteroidaceae and Verrucomicrobia, reduced the levels of Rikenellaceae and Desulfovibrionaceae; and increased the concentrations of fecal acetic and propionic acids compared to the diabetic model group. Additionally, SZ-A markedly improved ileal inflammatory injury and pro-inflammatory macrophage infiltration and improved intestinal mucosal barrier function in diabetic KKAy mice. SZ-A also attenuated the levels of circulating endotoxin, pro-inflammatory cytokines, and chemokines in the mice sera. Collectively, SZ-A ameliorated the overall metabolic profile including glucose and lipid metabolism in KKAy mice, which may be associated with an improvement in GLP-1 and insulin secretion, at least in part by modulating the gut microbiome and relieving the degree of ileal and systemic inflammation.

Novel greener approached synthesis of polyacrylic nanoparticles for therapy and care of gestational diabetes.

In the present medical diagnostic method for the therapeutic of gestational diabetes mellitus (GDM), it is problematic and difficult to release successful and secure release of drugs to the exact site. Hence, many researchers have been carried out to bring antidiabetic using modern method to release of drugs for their production. This research work focusses on to provide an assemblage to the recent growth in the field of Ramulus mori extract (RME) loaded on polyacrylic gold nanoparticle for antidiabetics with special highlighting on nursing of GDM. Keynote of gold nanoparticle: diabetes mellitus, nursing, insulin, antidiabetic, drugs, and new system for drug delivery. Rat is used to test the drug delivery system. In vivo examination was not prepared seldom including in this research paper. This research investigation could be a new avenue for the development of drug delivery system of GDM.

Antiobesity effect of ethanolic extract of Ramulus mori in differentiated 3T3-L1 adipocytes and high-fat diet-induced obese mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The mulberry (Morus alba L.) is a plant that mainly grows in East Asian countries such as Korea and China and has been used as a folk remedy for improving inflammation, cancer, and diabetes. Ramulus mori, the twig of Morus alba L., is known as "sangzhi" or "ppongnamugazhi" in Korea and used as a traditional medicine. Moreover, its effective compounds show some health benefits such as cholesterol reduction and attenuation of acute colitis. AIM OF THE STUDY: As the number of obese people is increasing worldwide, the demand for diet drugs or products to treat obesity is also increasing. In this study, we investigated the antiobesity effect of the ethanolic extract of Ramulus mori (ERM) using differentiated 3T3-L1 adipocytes and a high-fat diet (HFD)-induced obese mouse model. METHODS: The expression levels of genes and proteins related to adipogenesis, lipogenesis, and lipolysis were analyzed by quantitative real-time PCR (qPCR) and western blot, respectively. Oil red O staining was carried out to determine the amount of neutral lipids deposited in the liver. RESULTS: Compared with the ERM-untreated group, the ERM-treated groups exhibited reduced expression levels of genes involved in adipogenesis and lipogenesis in differentiated adipocytes and in HFD-induced obese mice, while the expression levels of genes involved in lipolysis increased. The administration of ERM to HFD-induced obese mice reduced the body weight, liver weight, and epididymal adipose tissue weight. Compared with the untreated HFD-induced obese mice, the ERM-treated mice exhibited decreased serum lipid levels. ERM treatment also reduced lipid accumulation in the liver, which was confirmed by oil red O staining. CONCLUSION: ERM has the potential to be an effective natural material for reducing obesity.

Preparation of Polysaccharides from Ramulus mori, and Their Antioxidant, Anti-Inflammatory and Antibacterial Activities.

The extraction of Ramulus mori polysaccharides (RMPs) was optimized using response surface methodology (RSM). The optimal process conditions, which gave the highest yield of RMPs (6.25%) were 80 °C, 50 min, and a solid⁻liquid ratio of 1:40 (g/mL), with the extraction performed twice. The RMPs contained seven monosaccharides, namely, mannose, rhamnose; glucuronic acid, glucose, xylose, galactose, and arabinose, in a 1.36:2.68:0.46:328.17:1.53:21.80:6.16 molar ratio. The glass transition and melting temperatures of RMPs were 83 and 473 °C, respectively. RMPs were α-polysaccharides and had surfaces that resembled a porous sponge, as observed by scanning electron microscopy. RMPs inhibited the proliferation of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa and showed antioxidant activity (assessed by three different methods), although it was generally weaker than that of vitamin C. RMPs showed anti-inflammatory activity in a concentration-dependent manner. This study provides a basis for exploring the potential uses of RMPs.

Study on the Effects of Prophylactic Administration of Ramulus mori Polysaccharides on Inflammatory Responses of Renal Ischemia Reperfusion Injury Model Mice and Its Mechanism / 中国药房

OBJECTIVE： To study on the effects of prophylactic administration of Ramulus mori polysaccharides （RMP） on inflammatory response of renal ischemia reperfusion injury （RIRI） model mice and to explore its possible mechanism. METHODS： Totally 60 C57BL/6 mice were randomly divided to sham operation group， model group， atorvastatin group （positive control， 15 mg/kg）， RMP low-dose， medium-dose and high-dose groups （300， 600， 1 200 mg/kg）. Except for sham operation group， RIRI model was induced in other 5 groups. 24 h before surgery， they were given relevant medicine intragastrically， once a day， for consecutive one week. 24 h after reperfusion， the mice were sacrificed. The serum levels of Scr and BUN were detected. The morphological changes of renal tissue were observed under optical microscope. The serum levels of IL-1β， IL-6， IL-10 and TNF-α were determined by ELISA. Western blot assay was used to determine the protein expressions of Toll-like receptor 4 （TLR4）， p38 mitogen-activation protein kinase （p38MAPK） and p-p38MAPK. RESULTS： Compared with sham operation group， the serum levels of Scr and BUN were significantly elevated in model group  （P＜0.01）. RIRI led to typical inflammatory response of renal tissue， widespread renal tubular epithelial cell degeneration and necrosis， and inflammatory cells infiltration. Serum levels of IL-1β， IL-6， IL-10 and TNF-α were increased significantly （P＜0.01）. The protein expressions of TLR4， p38MAPK and p-p38MAPK were increased significantly in renal cortex （P＜0.01）. Compared with model group， serum levels of Scr and BUN were decreased significantly in administration groups （P＜0.05 or P＜0.01）. The pathological damage of renal tissue was improved in varying degrees， especially in the RMP medium-dose and high-dose groups. Serum levels of IL-1β and IL-6 were decreased significantly in administration groups （P＜0.05 or P＜0.01）. Serum levels of IL-10 were further increased in atorvastatin group and RMP high-dose group （P＜0.01）， and serum level of TNF-α was decreased significantly in atorvastatin group and RMP medium-dose and high-dose groups （P＜0.05 or P＜0.01）. The protein expressions of TLR4 and p-p38MAPK in renal cortex were decreased significantly in administration groups （P＜0.05 or P＜0.01）. CONCLUSIONS： RMP prophylactic administration can improve RIRI of mice， the mechanism of which may be associated with relieving the inflammatory response through inhibition of TLR4/p38MAPK signaling pathway.

Structural characterization and antitumor activity of a polysaccharide from ramulus mori.

This study investigated the chemical characterization and antitumor effects of a polysaccharide from ramulus mori. A water-soluble polysaccharide, RMP1 with the estimated molecular weight of 137 kDa, was isolated and purified from ramulus mori through gel permeation chromatography. RMP1 is mainly composed of arabinose, xylose, glucose, galactose and rhamnose in a ratio of 0.56:0.37:0.17:1.00:0.08. Methylation and NMR analysis revealed that RMP1 had a backbone composed of 1,6-ß-d-Galp, 1,3,6-ß-d-Galp and 1,3-ß-d-Galp residues, two main branches of 1,2-α-l-Araf, 1,3,6-ß-d-Galp and 1,4-ß-d-Xylp; it also had α-l-Araf and ß-d-Glcp as terminals. In the MTT assay, RMP1 showed significant anticancer effects against the SGC-7901 and HeLa cells. In addition, no cytotoxicity was observed on the HEK-293 and RAW 264.7 cells. Flow cytometry showed that RMP1 exerted a stimulatory effect on the SGC-7901 cells apoptosis and induced the cell cycle arrest at the S phases. These findings suggest that RMP1 may serve as a potential novel antitumor agent.

Pharmacokinetics, Tissue Distribution, and Elimination of Three Active Alkaloids in Rats after Oral Administration of the Effective Fraction of Alkaloids from Ramulus Mori, an Innovative Hypoglycemic Agent.

In this study, we systematically investigated the plasma pharmacokinetics, tissue distribution, and elimination of three active alkaloids after oral administration of the effective fraction of alkaloids from Ramulus Mori (SZ-A)-an innovative hypoglycemic agent-in rats. Moreover, the influences of other components in SZ-A on dynamic process of alkaloids were explored for the first time. The results showed that 1-deoxynojirimycin (DNJ), fagomine (FGM) and 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) exhibited nonlinear pharmacokinetics following oral administration of SZ-A (40-1000 mg/kg). The prolonged t1/2 and greater area under concentration-time curve (AUC) versus time (AUC0-t) of DNJ for SZ-A than for purified DNJ has been observed after both oral and intravenous administration. It was found that other components in SZ-A could enhance the absorption of DNJ through the intestinal barrier. The major distribution tissues of DNJ, FGM, and DAB were the gastrointestinal tract, liver, and kidney. Three alkaloids were mainly excreted into urine and feces, but less into bile. Interestingly, the excess excretion of FGM was revealed to be partly due to the biotransformation of other components in SZ-A via gut microbiota. These information provide a rational basis for the use of SZ-A in clinical practice.

Analysis of chemical composition of volatile oil in Ramulus Mori by GC-MS / 国际药学研究杂志

Objective To extract the volatile oil of Ramulus Mori and analyze the chemical composition of the volatile oil. Methods The volatile oil of Ramulus Mori was extracted by simultaneous distillation extraction(SDE)and direct distillation extraction(DDE)method, and the chemical composition was identified by GC-MS. Results Nineteen compounds were identified in the volatile oil extracted by SDE, which accounted for 94.49% of the total amount of detection. There were alkyl, acids, aldehydes, ketones, esters, alcohols and other substances in the volatile oil. And 16 compounds were determined in the volatile oil extracted by DDE, accounting for 97.12% of the total amount detected. There were furan, carboxylic acids, esters, aldehydes, alcohols, phenols, ketones, alkene and acyl halide. The chemical compositions of the volatile oil extracted by SDE were more than those extracted by DDE. Conclusion The chemical constituents of volatile oil of Ramulus Mori can be more fully identified by the combination of the two extraction methods.

Analysis of chemical composition of volatile oil in Ramulus Mori by GC-MS / 国际药学研究杂志

Objective To extract the volatile oil of Ramulus Mori and analyze the chemical composition of the volatile oil. Methods The volatile oil of Ramulus Mori was extracted by simultaneous distillation extraction(SDE)and direct distillation extrac?tion(DDE)method,and the chemical composition was identified by GC-MS. Results Nineteen compounds were identified in the vol?atile oil extracted by SDE,which accounted for 94.49%of the total amount of detection. There were alkyl,acids,aldehydes,ketones, esters,alcohols and other substances in the volatile oil. And 16 compounds were determined in the volatile oil extracted by DDE,ac?counting for 97.12 % of the total amount detected. There were furan,carboxylic acids,esters,aldehydes,alcohols,phenols,ke?tones,alkene and acyl halide. The chemical compositions of the volatile oil extracted by SDE were more than those extracted by DDE. Conclusion The chemical constituents of volatile oil of Ramulus Mori can be more fully identified by the combination of the two ex?traction methods.