α-Mangostin promotes apoptosis of human rheumatoid arthritis fibroblast-like synoviocytes by reactive oxygen species-dependent activation of ERK1/2 mitogen-activated protein kinase.

α-Mangostin (α-M) is a commonly used traditional medicine with various biological and pharmacological activities. Our study aimed to explore the effects and mechanism of α-M in regulating apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). α-M of 10 to 100 µM was used to treat RA-FLS for 24 hours, followed by measuring cell viability and apoptosis. The involvement of reactive oxygen species (ROS) and mitogen-activated protein kinases was detected. Treatment of α-M promoted apoptosis and reduced viability of RA-FLS in a dose-dependent manner. The mitochondrial membrane potential in RA-FLS was remarkably reduced by α-M treatment, accompanied by the cytochrome c accumulation in the cytosol and increased activities of caspase-3 and caspase-9. Moreover, we found that α-M treatment promoted ROS production and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. The proapoptotic activity of α-M in RA-FLS was markedly reversed by the co-induction with the ERK1/2 inhibitor LY3214996 or ROS scavenger N-acetyl-l-cysteine. In conclusion, our studies found that α-M had remarkable proapoptotic activities in RA-FLS, which is regulated by the induction of ROS accumulation and ERK1/2 phosphorylation. α-M may thus have potential therapeutic effects for rheumatoid arthritis.

Calycosin stimulates the osteogenic differentiation of rat calvarial osteoblasts by activating the IGF1R/PI3K/Akt signaling pathway.

Calycosin has been reported to have a strong osteogenic activity and a positive correlation with anti-osteoporosis effects. However, its precise mechanism of action remains unclear. Since insulin-like growth factor 1 receptor (IGF1R) signaling and phosphatidylinositol 3-kinase/Akt (PI3K/Akt) signaling have been shown to play a pivotal role in regulating osteogenesis, we hypothesized that the osteogenic activity of calycosin is mediated by these signaling pathways. Rat calvarial osteoblasts (ROBs) were cultured in osteogenic medium containing calycosin with or without GSK1904529A (GSK) or LY294002 (LY) (inhibitors of IGF1R and PI3K, respectively). The effects on cell proliferation, alkaline phosphatase (ALP) activity, calcified nodules, mRNA or protein expression of osteogenic genes [alkaline phosphatase (Alpl), collagen type I (Col1a1), runt-related transcription factor 2 (Runx2), Osterix, and bone morphogenetic protein 2 (Bmp2)], and phosphorylation of IGF1R and Akt were examined. The present results showed that calycosin enhanced cell proliferation, ALP activity and Alizarin Red-S staining in a dose-dependent manner in the range of 10-8 -10-6 M, while an inhibitory effect was observed at 10-5 M. Treatment at the optimal concentration (10-6 M, a physiologically achievable concentration) increased mRNA levels of osteogenic genes and phosphorylation of IGF1R and Akt. Furthermore, treatment with GSK or LY partly reversed the effects of calycosin on ROBs, as indicated by the decreases in calycosin-induced ALP activity, calcified nodules and osteogenic gene expression. These results suggest that the osteogenic effect of calycosin partly involves the IGF1R/PI3K/Akt signaling pathway.

[Complex enzyme combined with ultrasound extraction technology, physicochemical properties and antioxidant activity of Hedysarum polysaccharides].

In this study, complex enzymes combined with ultrasonic extraction technology（MC） were used, to select optimal extraction combinations by single factor and orthogonal test, with Hedysarum polysaccharides yield and content as the comprehensive indexes. The components, physicochemical properties and antioxidant activity of Hedysarum polysaccharides from complex enzyme combined with ultrasonic extraction（HPS-MC）and the Hedysarum polysaccharides from hot water extraction（HPS-R）were analyzed. The results showed that：complex enzymes had significant effect on the yield and content of Hedysarum polysaccharides, and the ultrasonic power could significantly improve the content of Hedysarum polysaccharides. The optimum technological parameters were as follows: complex enzyme ratio 1:1, ultrasonic power 105 W, ultrasonic time 60 min, and enzymatic hydrolysis pH 5, achieving （14.01±0.64）% and （92.45±1.47）% respectively for the yield and content of Polysaccharides. As compared with HPS-R, the molecular weight, absolute viscosity and protein content of HPS-MC were decreased, while the content of uronic acid was increased. In the antioxidant system, the concentration of polysaccharide was within the range of 1-7 g·L⁻¹; the antioxidant activity of HPS-MC was higher than that of HPS-R, and HPS-MC (80%) with the lowest molecular weight showed a significant dose effect relationship with the increase of the experimental concentration. In conclusion, MC is a simple, convenient, economical and environmentally friendly extraction technology, and the Hedysarum polysaccharides extracted by this method have obvious antioxidant activity.

A Novel Organ Culture Model of Mouse Intervertebral Disc Tissues.

The intervertebral disc (IVD) is a fibrocartilaginous joint between two vertebral bodies. An IVD unit consists of a gelatinous central nucleus pulposus, encased by the annulus fibrosus, which is sandwiched between cartilaginous endplates (EPs). The IVD homeostasis can be disrupted by injuries, ageing and/or genetic predispositions, leading to degenerative disc disorders and subsequent lower back pain. The complex structure and distinct characteristics of IVDs warrant the establishment of robust in vitro IVD organ culture for studying the etiology and treatment of disc degeneration. Here, we isolate mouse lumbar IVDs and culture the minimal IVD units in submersion or suspension medium supplemented with 2% bovine serum or 10% fetal bovine serum (FBS). We find the minimal IVD units remain healthy for up to 14 days when cultured in submersion culture supplemented with 10% FBS. New bone formation in the EPs of the cultured IVDs can be assessed with calcein labeling. Furthermore, the cultured IVDs can be effectively transduced by recombinant adenovirus, and transgene expression lasts for 2 weeks. Thus, our findings demonstrate that the optimized IVD organ culture system can be used to study IVD biology and screen for biological factors that may prevent, alleviate and/or treat disc degeneration.

The Prodomain-Containing BMP9 Produced from a Stable Line Effectively Regulates the Differentiation of Mesenchymal Stem Cells.

BACKGROUND: BMPs play important roles in regulating stem cell proliferation and differentiation. Using adenovirus-mediated expression of the 14 types of BMPs we demonstrated that BMP9 is one of the most potent BMPs in inducing osteogenic differentiation of mesenchymal stem cells (MSCs), which was undetected in the early studies using recombinant BMP9 proteins. Endogenous BMPs are expressed as a precursor protein that contains an N-terminal signal peptide, a prodomain and a C-terminal mature peptide. Most commercially available recombinant BMP9 proteins are purified from the cells expressing the mature peptide. It is unclear how effectively these recombinant BMP9 proteins functionally recapitulate endogenous BMP9. METHODS: A stable cell line expressing the full coding region of mouse BMP9 was established in HEK-293 cells by using the piggyBac transposon system. The biological activities and stability of the conditioned medium generated from the stable line were analyzed. RESULTS: The stable HEK-293 line expresses a high level of mouse BMP9. BMP9 conditioned medium (BMP9-cm) was shown to effectively induce osteogenic differentiation of MSCs, to activate BMP-R specific Smad signaling, and to up-regulate downstream target genes in MSCs. The biological activity of BMP9-cm is at least comparable with that induced by AdBMP9 in vitro. Furthermore, BMP9-cm exhibits an excellent stability profile as its biological activity is not affected by long-term storage at -80ºC, repeated thawing cycles, and extended storage at 4ºC. CONCLUSIONS: We have established a producer line that stably expresses a high level of active BMP9 protein. Such producer line should be a valuable resource for generating biologically active BMP9 protein for studying BMP9 signaling mechanism and functions.

MRI analysis of tibial PCL attachment in a large population of adult patients: reference data for anatomic PCL reconstruction.

BACKGROUND: Consistent reference data used for anatomic posterior cruciate ligament (PCL) reconstruction is not well defined. Quantitative guidelines defining the location of PCL attachment would aid in performing anatomic PCL reconstruction. The purpose was to characterize anatomic parameters of the PCL tibial attachment based on magnetic resonance imaging (MRI) in a large population of adult knees. METHODS: The PCL tibial attachment site was examined in 736 adult knees with an intact PCL using 3.0-T proton density-weighted sagittal MRI. The outcomes measured were the anterior-posterior diameter (APD) of the tibial plateau; angle between the tibial plateau and the posterior tibial 'shelf' (the slope where the PCL tibial attachment site was) (PTS); length of the PTS; proximal, central, and distal PCL attachment positions as well as the width of the PCL attachment site; and vertical dimension of the PCL attachment site inferior from the tibial plateau. RESULTS: The average APD of the tibia plateau was 33.6 ± 3.5 mm, yielding significant differences between males (35.5 ± 3.0 mm) and females (31.6 ± 2.7 mm), P <.05, and there was a significantly decreasing trend with increasing age in males (P <.05). Mean angle between the tibial plateau and the PTS was 122.4° ± 8.1°, and subgroup analysis showed that the young group had a differently smaller angle (120.9° ± 7.5°) than the middle-aged (123.7° ± 8.2°) and the old (123.4° ± 7.7°) in males population, while there were no significant differences between sexes (P >.05). The proximal, central positions and width of the PCL attachment site were 13.4 ± 3.0 mm, 17.8 ± 3.0 mm and 9.6 ± 2.4 mm along the PTS, with significant differences between males and females (P <.05), and accounted for 60.0 % ± 9.1 %, 80.0 % ± 4.6 % and 43.3 % ± 9.7 % of the PTS respectively, with no significant differences between sexes and among age groups (all P >.05). CONCLUSIONS: This study provides reference data of the tibial PCL attachment based on MRI in the sagittal orientation. In analysis of retrospective data from a large population of adult patients, the quantitative values can be used as references to define the inserted angle and depth of the drill guide, and the exact position and size of the tibial PCL tunnel for performing arthroscopic anatomic PCL reconstruction.

The Calcium-Binding Protein S100A6 Accelerates Human Osteosarcoma Growth by Promoting Cell Proliferation and Inhibiting Osteogenic Differentiation.

BACKGROUND/AIMS: Although osteosarcoma (OS) is the most common primary malignancy of bone, its molecular pathogenesis remains to be fully understood. We previously found the calcium-binding protein S100A6 was expressed in ∼80% of the analyzed OS primary and/or metastatic tumor samples. Here, we investigate the role of S100A6 in OS growth and progression. METHODS: S100A6 expression was assessed by qPCR and Western blotting. Overexpression or knockdown of S100A6 was carried out to determine S100A6's effect on proliferation, cell cycle, apoptosis, tumor growth, and osteogenic differentiation. RESULTS: S100A6 expression was readily detected in human OS cell lines. Exogenous S100A6 expression promoted cell proliferation in vitro and tumor growth in an orthotopic xenograft model of human OS. S100A6 overexpression reduced the numbers of OS cells in G1 phase and increased viable cells under serum starvation condition. Conversely, silencing S100A6 expression induced the production of cleaved caspase 3, and increased early stage apoptosis. S100A6 knockdown increased osteogenic differentiation activity of mesenchymal stem cells, while S100A6 overexpression inhibited osteogenic differentiation. BMP9-induced bone formation was augmented by S100A6 knockdown. CONCLUSION: Our findings strongly suggest that S100A6 may promote OS cell proliferation and OS tumor growth at least in part by facilitating cell cycle progression, preventing apoptosis, and inhibiting osteogenic differentiation. Thus, it is conceivable that targeting S100A6 may be exploited as a novel anti-OS therapy.

ERK5 signalling pathway is essential for fluid shear stress-induced COX-2 gene expression in MC3T3-E1 osteoblast.

Bone cells respond to various mechanical stimuli including fluid shear stress (FSS) in vitro. Induction of cyclooxygenase-2 (COX-2) is thought to be important for the anabolic effects of mechanical loading. Recently, extracellular-signal-regulated kinase 5 (ERK5) has been found to be involved in multiple cellular processes. However, the relationship between ERK5 and the induction of COX-2 is still unknown. Here, we investigated the potential involvement of ERK5 in the response of pre-osteoblastic MC3T3-E1 cells upon FSS. MC3T3-E1 cells were subjected to 12 dyn/cm(2) FSS. Then, we established a ERK5 small interfering RNA (siRNA) transfected cell line using the MC3T3-E1 cells. After the successful transfection confirmed by real-time reverse transcription-polymerase chain reaction and Western blotting, the expression of COX-2, cAMP response element-binding protein (CREB), and nuclear factor kappa B cells (NF-κB) were assayed for downstream effectors of activated ERK5 under FSS by Western blotting. Our results showed that FSS could stimulate COX-2 activity, and induce the phosphorylation of ERK5, CREB, and NF-κB. When the MC3T3-E1 cells were transfected using siRNA before exposure to FSS, COX-2 activity was suppressed, and the phosphorylation of CREB and NF-κB was significantly downregulated. In summary, we demonstrated that ERK5 pathway is essential in the induction of COX-2 gene.

The MEK5/ERK5 pathway mediates fluid shear stress promoted osteoblast differentiation.

The aim of this study was to determine the role of the mitogen-activated protein kinase kinase (MEK) 5/extracellular signal-regulated kinase (ERK) 5 pathway in osteoblast differentiation promoted by intermittent fluid shear stress (FSS). MC3T3-E1 osteoblastic cells were subjected to 12 dyn/cm(2) intermittent FSS, and the phenotypic markers for osteoblast differentiation, such as alkaline phosphatase (ALP) activity and expression of osteopontin (OPN) and osteocalcin (OCN), were then examined. The results showed that intermittent FSS could stimulate ERK5 phosphorylation, ALP activity and the expression of OPN and OCN. When the MEK5/ERK5 pathway was selectively inhibited by BIX02189, ALP activity was suppressed, and the expression of OPN and OCN was downregulated. Intermittent FSS induce the expression of Runt-related transcription factor-2 (Runx-2), which is involved in osteoblast differentiation by promoting the transcription of the above genes. Furthermore, the expression of Runx-2 was also reduced after treatment with BIX02189. Finally, we found that intermittent FSS was a more intense stimulus than steady FSS for promoting osteoblast differentiation. In summary, our results suggest that the MEK5/ERK5 pathway mediates osteoblast differentiation promoted by intermittent FSS, which was more effective than steady FSS in the differentiation process. The MEK5/ERK5 pathway also mediates FSS-induced Runx-2 expression in osteoblast differentiation.

Periarticular multimodal drug injection in total knee arthroplasty.

PURPOSE: A systematic review and meta-analysis based on randomized controlled trials (RCTs) were conducted to evaluate the efficiency and safety of periarticular multimodal drug injection in total knee arthroplasty (TKA). METHODS: Periarticular injection with the use of multimodal drugs is an efficient alternative for postoperative analgesia in TKA. A systematical electronic search was performed to identify the eligible RCTs in the databases of PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science and the Chinese Biomedical Literature Database. Two independent reviewers completed data collection and assessment of methodological quality. The quality of evidence of outcomes was judged using GRADE criteria. Meta-analysis was performed for the outcomes of pain, straight leg raise, operating time, hospital stay and complications. RESULTS: Ten RCTs including eight studies with 1,216 TKAs in 835 patients met the inclusion criteria. Periarticular injection with multimodal drugs in TKA was associated with short-term benefits in terms of pain relief, straight leg raise, narcotic consumption, and the rates of nausea, vomiting, rash and pruritus. There were no statistically significant differences in operating time, hospital stay, wound complications and deep vein thrombosis between both groups. CONCLUSIONS: The current evidence suggests that periarticular multimodal drug injection in TKA provides short-term advantages in pain relief, straight leg raise and postoperative complications.

Structural characterization and antioxidant activity of a heteropolysaccharide isolated from Hedysarum polybotrys.

A water-soluble polysaccharide (HPS3aS) with a molecular mass of 1.22 × 10(4) Da was isolated from Hedysarum polybotrys using anion-exchange and gel-permeation chromatography. HPS3aS exhibits a globular-shaped conformation in 0.1 M NaNO3 by size exclusion chromatography with multi-angle laser light scattering (SEC-MALLS). The investigation of the structural features of this heteropolysaccharide through a combination of chemical and instrumental analyses revealed that the backbone of HPS3aS is composed of α-D-(1 → 4)-linked glucopyranose residues, which occasionally branched at O-6. The branches are composed of (1 → 4)-linked galactopyranose residues and terminated with glucopyranose residues. HPS3aS possesses good in vitro antioxidant activity, as evaluated by scavenging assays with 1,1-diphenyl-2-picrylhydrazyl, hydroxyl, and superoxide radicals, which suggests that HPS3aS could be a potential antioxidant.

Association of congestive heart failure with mortality in individuals with rheumatoid arthritis: a cohort study.

OBJECTIVE: Rheumatoid arthritis (RA) is a risk factor for congestive heart failure (CHF). Evidence is lacking regarding the relationship between CHF and mortality among American adults with RA. We aimed to investigate the relationship between CHF and mortality in patients with RA. METHODS: We extracted the corresponding data from the National Health and Nutrition Examination Survey (NHANES) database and calculated the hazard ratios (HR) and 95% CIs between CHF and mortality from all causes, cardiovascular disease (CVD), and cancer by using a Cox proportional risk model. RESULTS: A total of 2045 participants with a mean age of 60.32 ± 13.96 years were included; 57.60% were female. During a median follow-up period of 109 months, there were 602 deaths. After adjusting for potential confounders, compared with participants who are non-CHF, those with CHF had 60% (HR 1.60, 95% CI 1.27-2.01) and 110% (1.45, 1.45 to 3.06) higher all-cause mortality and CVD mortality, respectively. Furthermore, a significant association between CHF and all-cause mortality can also be observed in female individuals and those aged 65 and above. There was no significant association between CHF and cancer mortality. CONCLUSIONS: In this cohort study of US adults with RA, CHF was significantly associated with an increased risk of all-cause or CVD-related death. This finding underscores the importance of CHF in the management of patients with RA and may provide future information on maintaining the health status of patients with RA. Key messages • The study findings demonstrate a significant increase in overall mortality and cardiovascular mortality among individuals with RA who develop CHF. • This knowledge can assist healthcare professionals in identifying high-risk patients who could benefit from targeted monitoring and early intervention to prevent or manage CHF.

Biomechanical comparison of proximal, distal, and anatomic tibial tunnel for transtibial posterior cruciate ligament reconstruction.

No consensus has been reached on the optimal position of PCL tibial tunnel. The purpose of this study was to compare the biomechanical properties of proximal, distal and anatomic tibial tunnel in transtibial posterior cruciate ligament reconstruction. An in-vitro model of transtibial posterior cruciate ligament reconstruction was simulated using porcine tibias and bovine extensor tendons. Two models of biomechanical testing, load-to-failure loading, and cyclic loading, were performed in this study. The load-to-failure loading found that distal tibial tunnel resulted in greater ultimate load and yield load than the anatomic and proximal tunnel group (p < 0.05), whereas there were no significant differences in mean tensile stiffness among three groups (p > 0.05). The cyclic loading found no differences in the graft displacement at 250, 500, and 1000 cycles among three groups (p > 0.05). It was found that distal tibial tunnel showed superior ultimate load and yield load in load-to-failure loading testing compared with proximal and anatomic tibial tunnels, whereas no significant difference was found in terms of the mean displacement of the survived grafts in cyclic loading testing among three groups.

[Spectrum-effect relationship of reducing phlegm effect of Peucedanum harrysmithii var. subglabrum].

OBJECTIVE: To analyze the relationship between high-performance liquid chromatography (HPLC) fingerprints of the chloroform extract fractions of Peucedanum harrysmithii var. subglabrum (PHS) and its phlegm-reducing effect, in order to establish "active component group for reducing phlegm". METHOD: HPLC was adopted to determine and analyze HPLC fingerprints of chloroform extract fractions of PHS. Phenol red expectorant experiment was used to observe the phlegm-reducing effect in mice. Mice were administered intragastrically with chloroform extract fractions for 6 days (1.4 g x kg(-1)), with acute bronchitis syrup as the positive control drug (12 mL x kg(-1)). The phenol red secretion in mice was determined by spectrophotometer. Then the grey relational analysis was used to study the spectrum-effect relationship. RESULT: The phlegm-reducing effect of the chloroform extract fractions of PHS were resulted from the combined effect of all of its chemical components. Its various characteristic peaks represented different chemical components, and the order of their contributions to the phlegm-reducing effect was (number of peaks) 13 > 12 > 16 > 18 > 19 > 6 > 20 > 14 > 1 > 11 > 15 > 10 > 17 > 2 > 5 > 4 > 7 > 3 > 8 > 9, in No. 1, 3, 4, 10, 13 and 16 characteristic peaks were identified as marmesin, psoralen, xanthotoxin, Pd-Ib, pteryxin and peuformosin. CONCLUSION: The chloroform extract fractions of PHS show strongly phlegm-reducing effect. There may be certain relationship between their HPLC fingerprint and phlegm-reducing effect.

Hepatoprotective effect and structural analysis of Hedysarum polysaccharides in vivo and in vitro.

The crude Hedysarum polysaccharides (HPS: HPS-50 and HPS-80) obtained from Radix Hedysari exhibited great pharmacological activities in our previous research. This study investigated the effects of HPS on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury (ALI) in mice and LPS-induced injury in LO2 cells, as well as the relationship between structural characteristics and hepatoprotective activities. The in vivo results showed that compared with HPS-80, HPS-50 showed stronger hepatoprotection, which improved histopathological changes to normal levels. HPS-50 significantly decreased the levels of ALT, AST, MPO, and MDA, increased the activities of SOD, CAT, and GSH, and suppressed the LPS/D-GalN-triggered production of TNF-α, IL-1ß, and IL-6 (p < .05). The results in vitro showed that HPS-50-P (HPS-50-1, HPS-50-2, and HPS-50-3) purified from HPS-50 played significant protective roles against LPS-induced injury in LO2 cells by reducing cell apoptosis and relieving cell cycle arrest. HPS-50-2 restored the percentage of normal cells from 54.8% to 94.7%, and reduced the S phase cells from 59.40% to 47.05% (p < .01). By analyzing the structure of HPS-50-P, including monosaccharide composition, molecular weight, chain conformation, and surface morphology, we speculated that the best protective effect of HPS-50-2 might be attributed to its beta configuration, highest molecular weight, and high glucose and galactose contents. These findings indicate that HPS-50 might be a promising source of functional foods for the protection and prevention of ALI. PRACTICAL APPLICATIONS: In this study, the protective effect of HPS on ALI was evaluated from multiple perspectives, and HPS-50-2 was screened as a potential active ingredient. This study has two practical applications. First, it provides a new way to improve ALI, and a new option for patients to prevent and treat ALI. Second, this work also complements the pharmacological activity of Radix Hedysari and provides a basis for the development of Radix Hedysari as a functional food.

Correction: Formononetin in Radix Hedysari extract-mediated green synthesis of gold nanoparticles for colorimetric detection of ferrous ions in tap water.

[This corrects the article DOI: 10.1039/D0RA05660J.].

Structural characterization of a polysaccharide from Radix Hedysari and its protective effects against H2O2-induced injury in human gastric epithelium cells.

The gastroprotective effects of polysaccharides had become a hot topic in the field of functional polysaccharides research. Three polysaccharides, namely HPS-80-1, HPS-80-2, and HPS-80-3 were purified by DEAE-52 column chromatography. The thermodynamic characteristics, scanning electron microscopy, and Congo red experimental results of the above polysaccharides were greatly distinctive. Then a mature GES-1 oxidative stress cell model induced by H2O2 was established to screen out subsequent research subjects. It turned out that HPS-80-1 had a desirable protective effect, which was confirmed by analyses of cell cycle & apoptosis, and oxidative stress-related factors in the cell culture media, and so on. Furthermore, Structural features demonstrated that the backbone of HPS-80-1 appeared to mainly consist of →4)-α-D-Glcp-(1→, →4,6)-ß-L-Glcp-(1→, and →6)-α-D-Galp-(1→, with branches at O-1, O-4, and O-6 position consisting of →2,4)-ß-D-Rhap-(1→, →1)-α-D-Galp-(4→, and →3,4)-α-D-Manp-(1→. It was speculated that the excellent gastric mucosal protective activity of HPS-80-1 may be due to the high amount of glucose in the backbone. In addition, it was also related to the anti-inflammatory activity and antioxidant bases such as (1 â†’ 4)-Glcp and (1 â†’ 6)-Galp in the structure of HPS-80-1. These findings provide a scientific basis for further utilization of polysaccharides from Radix Hedysari.

Antidiabetic properties of purified polysaccharide from Hedysarum polybotrys.

Hedysarum polybotrys polysaccharide (HPS) is the principal active fraction responsible for the antidiabetic properties of this species. The aim of this study was to determine the antidiabetic properties of 4 purified fractions of different molecular weight range HPSs (HPS1, HPS2, HPS3, HPS4). HPS3 was selected for examination of its hypoglycemic mechanism because of its significant hypoglycemic effect in alloxan-induced diabetic mice. The changes in blood glucose levels and oral glucose tolerance tests (OGTT) showed that hypoglycemia was more pronounced in HPS3-treated groups than in the diabetes mellitus model (DM) control group. The interleukin-6, tumor necrosis factor-alpha, leptin, and free fatty acid levels were significantly lower in the HPS3-treated groups and HPS3 + metformin (HPS3+MET) group than in the DM control group, while plasma insulin, hepatic glycogen, superoxide dismutase, and nitric oxide synthetase activity were significantly higher. Treatment with HPS3 or HPS3+MET also significantly lowered malonaldehyde levels compared with the DM control group, while it elevated the nitric oxide and total antioxidant capacity. HPS3 altered the plasma lipid levels by lowering cholesterol and triglyceride concentrations, while elevating the plasma high-density lipoprotein cholesterol level. Therefore, these results suggest that HPS3 may partly ameliorate hyperglycemia and hyperlipidemia associated with type 2 diabetes through increased insulin secretion, inhibition of lipid peroxidation, promotion of sensitivity to insulin, suppression of gluconeogenesis and reduction in the biosynthesis fatty acid, cholesterol and cell cytokines related to insulin resistance, and it could be a useful adjunct therapy to a proven first-line therapy for type 2 diabetes using metformin.

The amelioration of ulcerative colitis induced by Dinitrobenzenesulfonic acid with Radix Hedysari.

Ulcerative colitis (UC) is a chronic inflammatory disease with an unknown precise etiology. This study proves that Radix Hedysari (RH) ameliorates UC. Four RH extracts were used to ameliorate UC induced by 2,4-Dinitrobenzenesulfonic acid by 7 days intervention in agreement to preliminary studies. Compared to treatment with RH extracts, the RH ethanol extract (EE) was found to be more effective in ameliorating UC. With EE, the DAI were significantly decreased. Macroscopic and histopathological assessments suggest that the colon mucosa was repaired, the organizational structure of the colon had been rebuilt. The levels of MPO, TNF-α, IL-1ß, and MDA were significantly decreased (p < .01), the levels of T-SOD and CAT were significantly increased (p < .01). Moreover, the compounds in EE were analyzed by HPLC. The results show that EE can ameliorate UC, and its anti-inflammatory capability probably plays an important role. RH can act as a functional food and ameliorate UC. PRACTICAL APPLICATIONS: In this work, the ameliorative effect of RH on UC was evaluated from multiple angles. There are two practical applications of this work. On the one hand, a new approach to ameliorating UC is provided by this work. In addition, UC patients have a new option for improving their symptoms. On the other hand, this work also provides information on how best to process RH for therapeutic use. In addition, we can utilize some compounds of RH that were once considered useless and reduce the waste of natural resources.