Antirheumatic Activity Research Articles

Comparison of chemical composition and biological activities of Seseli rigidum fruit essential oils from Serbia

Abstract Plants from genus Seseli, have been widely used in European traditional medicine, exhibiting antibacterial, antifungal, insect repellent, emmenogogue, antiflatulence, anti-inflammatory, antinociceptive, anti-tumor, antirheumatic activities and protective effect on human lymphocytes DNA. They usually grow on mountain rocky terrains. Part of their habitat on Vidlic Mountain, located in South-east Serbia, was struck with a large wildfire. Seseli rigidum fruit essential oils (from post fire and control areas) compositions were analyzed by GC and GC-MS, identifying monoterpenes α-pinene and sabinene as most abundant. Statistical tests showed a non-significant difference in chemical composition of these two oils, but a significant difference in comparison with the herb from a geographically different origin. Antimicrobial tests showed strong activities of the oils against tested bacteria, thus confirming its administration in various inflammation processes as a quite effective remedy. Applying DPPH. and ABTS+. radical scavenging and total reducing Fe(III) to Fe(II) power assays, antioxidant characteristics of both studied essential oils were estimated as weak, though of close values. Seseli rigidum fruit essential oil was proven as a potent inhibitor of human and horse serum cholinesterase, recognizing its possible application as neural protective agent

Synthesis, structural, optical and anti-rheumatic activity of metal complexes derived from (E)-2-amino-N-(1-(2-aminophenyl)ethylidene)benzohydrazide (2-AAB) with Ru(III), Pd(II) and Zr(IV)

Three new metal complexes derived from Pd(II), Ru(III) and Zr(IV) with (E)-2-amino-N-(1-(2-aminophenyl)ethylidene)benzohydrazide (2-AAB) have been synthesized. The isolated complexes were characterized by elemental analyses, FT-IR, UV–Vis, ES-MS, 1H NMR, XRD, thermal analyses (TGA and DTA) and conductance. The morphology and the particle size were determined by transmittance electron microscope (TEM). The results showed that, the ligand coordinates to Pd(II) in the enol form, while it coordinates to Ru(III) and Zr(IV) in the keto form. A square planar geometry is suggested for Pd(II) complex and octahedral geometries are suggested for Ru(III) and Zr(IV) complexes. The optical band gaps of the isolated complexes were measured and indicated the semi-conductivity nature of the complexes.The anti-inflammatory and analgesic activities of the ligand and its complexes showed that, Ru(III) complex has higher effect than the well known drug “meloxicam”.

Chemical and electrocatalytic cascade cyclization of salicylaldehyde with three molecules of malononitrile: ‘one-pot’ simple and efficient way to the chromeno[2,3-b]pyridine scaffold

А new type of catalytic cascade cyclization was found: the direct ‘one-pot’ simple and efficient transformation of salicylaldehyde and three molecules of malononitrile into the chromeno[2,3-b]pyridine systems. Chemical and electrochemical methods result in direct ‘one-pot’ formation of chromeno[2,3-b]pyridines in 60–90% yields. The implication of electrocatalysis in complex cascade cyclization reaction is an efficient approach to medicinally relevant chromeno[2,3-b]pyridines—the promising small-molecule ligands with pronounced antihistamic, antirheumatic and antiasthmatic activities. The electrocatalytic method is beneficial from the viewpoint of diversity-oriented large-scale processes and represents fast efficient and environmentally benign synthetic concept for cascade reactions strategy.

Characterization of an Ebosin derivative produced by heterologous gene replacement in Streptomyces sp. 139.

BackgroundEbosin is a novel exopolysaccharide (EPS) produced by Streptomyces sp. 139 and evidenced to possess an anti-rheumatic arthritis activity in vivo. The Ebosin biosynthesis gene cluster (ste) consists of 27 ORFs and ste7 has previously been demonstrated to code for a fucosyltransferase, which plays an essential role in the formation of repeating sugar units during Ebosin production. Aiming to generate derivatives of Ebosin for better activity, we replaced ste7 with a gene encoding for a glucosyltransferase (gtf) from Streptococcus thermophilus.ResultsThis alteration resulted in a novel Ebosin derivative (EPS-7 g) with its monosaccharide composition dramatically changed, especially in the proportion of glucose which increased from 1.1% (Ebosin) to 84.01% (EPS-7 g). In an ELISA analysis, EPS-7 g exhibited a higher binding activity for IL-1R, as a competitor of interleukin-1, than that of Ebosin. It also exhibited a higher inhibitory effect on the activity of IL-1β-converting enzyme and production of IL-1β in fibroblast-like synoviocytes (FLS). In addition, experiments with acute inflamed mice induced by croton oil showed a significantly higher anti-inflammatory activity of EPS-7 g compared with Ebosin.ConclusionsThe new Ebosin derivative EPS-7 g is more bioactive than Ebosin evaluated by a series of experiments. This is the first report demonstrating a modification of EPS structure via heterologous gene replacement in Streptomyces.

Xanthone-rich dichloromethane fraction of Securidaca inappendiculata, the possible antirheumatic material base with anti-inflammatory, analgesic, and immunodepressive effects

Context: Securidaca inappendiculata Hassk. is an traditional Chinese medicine curing rheumatoid arthritis, but there is a lack of reports on material base research.Objective: To find the active fraction of S. inappendiculata contributing the most to antirheumatic activity.Materials and methods: Prior to assays in vivo, mice were treated with different fractions from S. inappendiculata for 5 d at doses relative to 10, 5, and 2.5 g/kg of crude drug. Hot plate test and carrageenan-induced paw edema test were used to investigate analgesic and anti-inflammatory activities. PGE2 levels in inflammatory paws were determined by a colorimetric method. Carbon clearance test in vivo and lymphocyte transformation test in vitro were employed to assess the immune regulation activity. HPLC was used to explore the main compounds in the active fraction.Results: All the fractions, especially the dichloromethane fraction (SID), alleviated inflammation. High dose of SID (112 mg/kg) inhibited paw swelling by 63.1%, and decreased PGE2 level to 38 ng/mL. The ethyl acetate fraction (SIE) and SID suppressed the carbon clearance rate (K = 0.044, 0.038 for high dose) efficiently. All fractions hindered the transformation and proliferation of lymphocyte, and prolonged the reaction time of rats in the hot plate test. The concentrations of two typical xanthones: 2-hydroxyl-1,7-dimethoxyl-xanthone and 1,7-dihydroxyl-xanthone in SID were 0.93% and 1.19%, respectively, by HPLC analysis.Conclusion: SID exhibited significant anti-inflammatory, analgesic, and immunodepressive effects in vivo and vitro, and deemed as the main material base for the antirheumatic activity.

Essential oil from Pterodon emarginatus seeds ameliorates experimental autoimmune encephalomyelitis by modulating Th1/Treg cell balance

Ethnopharmacological relevancePterodon emarginatus Vogel is a medicinal plant commonly used in Brazilian traditional medicine as a folk therapy due to its immunosuppressive, anti-inflammatory, anti-rheumatic, healing, tonic and depurative activities. The essential oil (EO) of Pterodon emarginatus is composed of volatile aromatic terpenes and phenyl propanoids, mainly, β-elemene and β-caryophyllene sesquiterpenes. Here we reported the effects and some underlying mechanisms of action of EO during murine model of MS, the experimental autoimmune encephalomyelitis (EAE). Materials and methodsEO (50 and 100mg/kg) was orally administered during the entire period of development of EAE (preventive treatment, day 0–25). In vitro and in vivo immunological responses were evaluated by ELISA, immunohistochemistry, immunofluorescence and flow cytometry. ResultsWe provide evidence that EO of Pterodon emarginatus (100mg/kg, p.o.) significantly attenuates neurological signs and also the development of EAE. Furthermore, at the same dose EO consistently inhibited Th1 cell-mediated immune response and upregulated Treg response in vitro. Moreover, the EO inhibited both microglial activation and expression of iNOS, associated with inhibition of axonal demyelization and neuronal death during the development of the disease. ConclusionThis is the first experimental evidence showing that oral administration of EO consistently reduces and limits the severity and development of EAE, mainly, through the modulation of Th1/Treg immune balance, and might represent a helpful new tool for control immunoinflammatory conditions, such as MS.

Epigenetic regulation of IL‐6 by pro‐inflammatory cytokines in rheumatoid arthritis synovial fibroblasts: role of HDAC inhibitors (1054.8)

Histone deacetylase inhibitors (HDACi) have gained significant attention in recent years due to their anti‐rheumatic activity and potential clinical application. However, the exact role of different HDAC classes in rheumatoid arthritis (RA) is not yet defined, which has limited our ability to target HDACs for therapeutic gain. In order to gain some insights on the epigenetic regulation of synovial inflammation and tissue destruction observed in RA, the present study was carried out to evaluate the role of HDACs in cytokine‐induced IL‐6 synthesis by RA synovial fibroblasts (RA‐FLS) and the influence of cytokine combination. Effect of class I HDACi (Largazole, LAR) or pan‐HDACi vorinostat (SAHA) was determined on TNF‐α (20 ng/ml), IFN‐γ (10 ng/ml), or IL‐1β (10 ng/ml)‐induced IL‐6 expression in RA‐FLS by Western blotting and qRT‐PCR. IL‐6 production under different treatment conditions was also compared with IL‐8 production. Results of the study showed that TNF‐α‐induced IL‐6 expression in RA‐FLS was further amplified in the presence of class I HDACi (LAR, 2‐5 μM) or pan‐HDACi (SAHA, 5 μM) (p<0.05). Surprisingly, we also observed that LAR downregulated TNF‐α/IL‐1β‐induced IL‐6 production by ~50%, but further enhanced TNF‐α/ IFN‐γ‐induced IL‐6 production by ~25%. Evaluation of the signaling pathways suggests that LAR effectively cooperated with TNF‐α to induce phosphorylation of AKT, which may partly be the reason for its IL‐6 increasing property in RA‐FLS. Results of the present study suggest that LAR may interact differently with TNF‐α, IL‐1β, and/or IFN‐γ to induce or inhibit IL‐6 production in RA‐FLS. Thus, our study highlights a need for validating the exact role of specific HDAC isoforms in RA pathogenesis before highly selective inhibitors could be designed and tested for the treatment of RA.Grant Funding Source: Supported by NIH/NIAMS grants (AR063104 and AR55741) and University of Toledo Start‐up funds to SA.

Anti-rheumatoid and anti-oxidant activity of homeopathic Guaiacum officinale in an animal model

Homeopathy is a popular form of complementary and alternative medicine. Guaiacum extract is said to be useful for pain and inflammation, but there appears to be no scientific evidence to support this. The aim of the present study was to evaluate the anti-rheumatic and anti-oxidant activity of homeopathic preparations of Guaiacum officinale (Gua) on experimental animal model. Rheumatoid arthritis (RA) was induced in male albino rats by Freund's complete adjuvant (FCA) at a dose of (0.25mg heat killed Mycobacterium tuberculosis/ml of emulsion). Gua mother tincture (MT) (prepared from the latex part of the plant) (MT), Gua 30cc and 200cc were purchased commercially from King Company, Kolkata, India. Male albino Wistar rats (130±10g) were divided into 6 groups: Sham control; Arthritis control; Standard treatment indomethacin(0.25mg100g(-1) p.o.×5 alternative days), Gua MT (1mlkg(-1) p.o.×5 days) treated; Gua (30c 1mlkg(-1) p.o.×5 days) treated; Gua (200c; 1mlkg(-1) p.o.×5 days) treated. Anti-rheumatic activity was examined through physical, urinary, serum parameters. All the results were expressed in terms of mean±SEM (statistical error of mean n=6) at each dose level. The level of significance was determined through one-way analysis of variance (ANOVA), p<0.05 was considered significant. It was observed that body weight, ankle and knee diameter, urinary parameters (hydroxyproline (OH-P), glucosamine, calcium (Ca(2)(+)), creatinine (CRE), phosphate (PO4(3)(-))), serum ACP (acid phosphatase)/ALP (alkaline phosphatase)/Ca(2+)/CRE/PO4(3-)/gamma-glutamyl transferase (GGT)/Lipid peroxidation (LPO)/Glutathione (GSH)/Superoxide dismutase (SOD)/Catalase, serum GGT, serum interleukins like IL-1β/CINC-1/PGE2/TNF-α/IL-6, IL-12/IL-4/IL-6 levels were significantly affected. After treatment with Guaiacum in all 3 regimes was associated with normalization of these parameters compared to control group. These findings suggest that homeopathic G. officinale possesses anti-rheumatic and anti-oxidant activity in experimental animal and these activities may be more significant in higher potencies.

Anti-toxoplasmosis effect of Dictamnus dasycarpus extract against Toxoplasma Gondii

Toxoplasma gondii (T. gondii) causes a life-threatening opportunistic infection. Despite its clinical importance, very few therapeutic drugs against T. gondii are available. Furthermore, these therapeutic regimens are not always suitable for prolonged treatment due to adverse side effects as well as the potential of clinical failure by selecting drug-resistant parasite variants. Dictamnus dasycarpus is known to have many medicinal properties, including anti-inflammatory, anti-fever, and anti-rheumatic activities. In this study, 70% ethanol extract of Dictamnus dasycarpus showed anti-T. gondii effects. Ethanolic extracts of Dictamnus dasycarpus used to treat T. gondii were tested in vitro for their anti-T. gondii activity and cytotoxicity. The selectivity of Dictamnus dasycarpus extract was 7.52, which was higher than that of Sulfadiazine (2.08). We conducted an in vivo animal test to evaluate the anti-T. gondii activity of Dictamnus dasycarpus extract as compared with that of Sulfadiazine. In T. gondii-infected mice, the inhibition rate of Dictamnus dasycarpus extract was high, similar to that of Sulfadiazine. This indicates that Dictamnus dasycarpus extract may be a source of new anti-T. gondii compounds.

Chemical constituents of the stem bark of Fraxinus rhynchophylla

Fraxinus rhynchophylla Hance belongs to the Oleaceae family and is widely distributed in China. It is one of the sources of the traditional Chinese herbal drug “Qinpi” and has been used as an anti-inflammatory agent for many years. The traditional Chinese herbal drug “Qinpi” was reported to have diuretic, antifebrile, analgesic, and antirheumatic activities [1]. Coumarins, lignans, secoiridoid glucosides, and other compounds have been isolated from plants of the genus Fraxinus [2, 3]. In order to find more bioactive compounds, an investigation of the chemical constituents of Fraxinus rhynchophylla was carried out. The fresh stem barks of F. rhynchophylla (3 kg) were cut into pieces and extracted with methanol three times under reflux. The solvent was removed under reduced pressure to give a crude extract (100 g). The crude extract was subjected to 200–300 mesh silica gel column chromatography eluting with a gradient of chloroform–methanol (20:1 to 1:1) to yield 20 fractions. Subfractions 7–10 were then purified by Sephadex LH-20 and semipreparative HPLC to yield compounds 1–9. Their structures were identified to be 2,5-dimethoxy-3-O-D-grucopyranosyl cinnamic alcohol (1) [4], ligstroside (2) [5], 10-hydroxyligstroside (3) [6], (+)-1-hydroxypinoresinol 4 -O-D-glucopyranoside (4) [7], (+)-1-hydroxypinoresinol 4 -O-D-glucopyranoside (5) [7], oleuropein (6) [6], adenosine (7) [8], dopaol (8) [9], and salidroside (9) [9] on the basis of spectral data and by comparison with published data. Compounds 1 and 7 were isolated from the genus Fraxinus for the first time, and compounds 3–5 were isolated from this plant for the first time. 2,5-Dimethoxy-3-O-D-grucopyranosyl Cinnamic Alcohol (1). C17H24O9, colorless needles. UV spectrum (MeOH, max, nm): 263, 220. 1H NMR (600 MHz, DMSO-d6, , ppm, J/Hz): 3.04 (1H, m, H-5 ), 3.14 (1H, m, H-4 ), 3.20 (1H, m, H-3 ), 3.21 (1H, m, H-2 ), 3.41 (1H, dd, J = 5.4, 12, H-6 b), 3.59 (1H, dd, J = 1.8, 12, H-6 a), 3.77 (6H, s, 2, 5-OCH3), 4.11 (2H, d, J = 4.8, H-9), 4.97 (1H, d, J = 6.6, H-1 ), 6.34 (1H, dt, J = 4.8, 15.6, H-8), 6.47 (1H, d, J = 15.6, H-7), 6.73 (2H, s, H-4, 6). 13C NMR (150 MHz, DMSO-d6, , ppm): 152.8 (C-2, 5), 104.5 (C-4, 6), 132.8 (C-3), 133.9 (C-1), 128.6 (C-7), 130.3 (C-8), 61.6 (C-9), 102.7 (C-1 ), 77.3 (C-2 ), 76.5 (C-3 ), 69.9 (C-4 ), 74.2 (C-5 ), 60.9 (C-6 ), 56.5 (2, 5-OCH3). 10-Hydroxyligstroside (3). C25H32O13, yellow powder. UV spectrum (MeOH, max, nm): 275, 225. 1H NMR (600 MHz, DMSO-d6, , ppm, J/Hz): 2.45 (1H, dd, J = 9.6, 15, H-6a), 2.61 (1H, dd, J = 10.2, 15, H-6b), 2.75 (2H, t, J = 7.8, H-7 ), 3.08 (1H, m, Glc-5), 3.10 (1H, m, Glc-4), 3.20 (1H, m, Glc-3), 3.22 (1H, m, Glc-2), 3.45 (1H, dd, J = 6, 12, Glc-6b), 3.64 (3H, s, OCH3), 3.68 (1H, d, J = 10.8, Glc-6a), 3.80 (1H, dd, J = 4.2, 9, H-5), 3.99 (1H, dd, J = 5.4, 12.6, H-10a), 4.12 (2H, m, H-8 ), 4.13 (1H, m, H-10b), 4.67 (1H, d, J = 7.8, Glc-1), 5.89 (1H, s, H-1), 5.99 (1H, t, J = 6.0, H-8), 6.69 (2H, d, J = 8.4, H-2 , 6 ). 7.03 (2H, d, J = 8.4, H-3 , 5 ), 7.53 (1H, s, H-3). 13C NMR (150 MHz, DMSO-d6, , ppm): 92.8 (C-1), 153.6 (C-3), 107.7 (C-4), 30.8 (C-5), 39.9 (C-6), 170.9 (C-7), 128.4 (C-8), 129.2 (C-9), 57.3 (C-10), 166.3 (C-11), 128.0 (C-1 ), 115.2 (C-2 , 6 ), 129.9 (C-3 , 5 ), 155.8 (C-4 ), 33.6 (C-7 ), 65.3 (C-8 ), 99.2 (Glc-1), 73.3 (Glc-2), 76.5 (Glc-3), 70.0 (Glc-4), 77.4 (Glc-5), 61.1 (Glc-6), 51.5 (OMe). (+)-1-Hydroxypinoresinol 4 -O-D-Glucopyranoside (4). C26H32O12, brown oil. UV spectrum (MeOH, max, nm): 276, 227. 1H NMR (600 MHz, DMSO-d6, , ppm, J/Hz): 2.89 (1H, m, H-5), 3.15 (1H, m, Glc-2), 3.24 (1H, m, Glc-5), 3.25 (1H, m, Glc-4), 3.26 (1H, m, Glc-3), 3.44 (1H, dd, J = 5.4, 12.0, Glc-6b), 3.64 (1H, m, H-4b), 3.70 (1H, br.d, J = 12.0, Glc-6a), 3.73 (1H, d, J = 9, H-8b), 3.75 (6H, s, OMe-3 , 3 ), 3.94 (1H, d, J = 9.0, H-8a), 4.35 (1H, dd, J = 8.4, 9.0, H-4a), 4.57 (1H, s, H-2), 4.74 (1H, d, J = 5.4, H-6), 4.86 (1H, d, J = 7.2, Glc-1), 6.75 (1H, d, J = 7.8, H-5 ), 6.79 (1H, dd, J = 1.8, 7.8, H-6 ), 6.86 (1H, dd, J = 1.8, 7.8, H-6 ), 6.96 (1H, br.s, H-2 ), 6.99 (1H, br.s, H-2 ), 7.01 (1H, d, J = 8.4, H-5 ), 8.45 (1H, s,

The incredible benefits of Nagarmotha (Cyperus rotundus)

Nagarmotha (Cyperus rotundus), a cosmopolitan weed, is found in all tropical, subtropical and temperate regions of the world. In India, it is commonly known as Nagarmotha and it belongs to the family Cyperacea. The major chemical components of this herb are essential oils, flavonoids, terpenoids, sesquiterpenes, cyprotene, cyperene, aselinene, rotundene, valencene, cyperol, gurjunene, trans-calamenene, cadalene, cyperotundone, mustakone, isocyperol, acyperone, etc., Research studies have shown that it possesses various pharmacological activities such as diuretic, carminative, emmenagogue, anthelminthic, analgesic, anti-inflammatory, anti-dysenteric, antirheumatic activities. An extensive review of the ancient traditional literature and modern research revealed that the drug has numerous therapeutic actions, several of which have been established scientifically, which may help the researchers to set their minds for approaching the utility, efficacy and potency of nagarmotha.

Network Pharmacology in Traditional Chinese Medicine

Network Pharmacology in Traditional Chinese Medicine

PEGylated HM-3 presents anti-rheumatic bioactivity by inhibiting angiogenesis and inflammation.

PEGylation improves the pharmacokinetic and pharmacodynamic properties of polypeptide drugs. After PEGylation, the modified HM-3 (PEG-HM-3) exhibited a prolonged half-life in blood. In this paper, we evaluated the anti-rheumatic effect of PEG-HM-3, and investigated the target for angiogenesis and inflammation. The anti-rheumatic activity of PEG-HM-3 was documented in an adjuvant-induced arthritis (AIA) model. PEG-HM-3 significantly decreased the paw increase percentage and clinical scores, inhibited characteristic signs such as synovial hyperplasia, pannus formation, inflammatory infiltration and bone erosion in histological analysis, and reduced bone erosion with the X-ray analysis of the hint paws of rats. The target for angiogenesis and inflammation was assessed with in vivo and in vitro techniques. The in vivo experiments confirmed that PEG-HM-3 decreased the number of blood vessels in rheumatic synovium, reduced the level of serum anti-CII autoantibodies, and decreased the levels of synovial TNF-alpha and VEGF in a collagen-induced arthritis (CIA) model. The in vitro results confirmed that the anti-angiogenic effect of PEG-HM-3 was mainly achieved through the inhibition of HUVEC migration. PEG-HM-3 inhibited the mitotic effects in the T-cell population. PEG-HM-3 could significantly inhibit the TNF-alpha and VEGF levels in the LPS-stimulated macrophage and the latter effect was stronger than that seen with HM-3. Furthermore, the simulated molecule docking result showed that the RGD motif of PEG-HM-3 inserted into the pocket site of integrin αvβ3, and PEG-HM-3 had a higher predicted affinity with integrin αvβ3 compared to the predicted affinity of HM-3 and integrin αvβ3. This study has uncovered that PEGylate HM-3 could present an anti-rheumatic bioactivity with a less frequent schedule, and PEG-HM-3 exhibited its anti-rheumatic effects by inhibiting angiogenesis and inflammation. Furthermore, the main targeting site has been confirmed, which explained the changes in the bioactivity of PEG-HM-3.

The Histone Deacetylase Inhibitors MS-275 and SAHA Suppress the p38 Mitogen-Activated Protein Kinase Signaling Pathway and Chemotaxis in Rheumatoid Arthritic Synovial Fibroblastic E11 Cells

MS-275 (entinostat) and SAHA (vorinostat), two histone deacetylase (HDAC) inhibitors currently in oncological trials, have displayed potent anti-rheumatic activities in rodent models of rheumatoid arthritis (RA). To further elucidate their anti-inflammatory mechanisms, the impact of MS-275 and SAHA on the p38 mitogen-activated protein kinase (MAPK) signaling pathway and chemotaxis was assessed in human rheumatoid arthritic synovial fibroblastic E11 cells. MS-275 and SAHA significantly suppressed the expression of p38α MAPK, but induced the expression of MAPK phosphatase-1 (MKP-1), an endogenous suppressor of p38α in E11 cells. At the same time, the association between p38α and MKP-1 was up-regulated and consequently, the activation (phosphorylation) of p38α was inhibited. Moreover, MS-275 and SAHA suppressed granulocyte chemotactic protein-2 (GCP-2), monocyte chemotactic protein-2 (MCP-2) and macrophage migration inhibitory factor (MIF) in E11 cells in a concentration-dependent manner. Subsequently, E11-driven migration of THP-1 and U937 monocytes was inhibited. In summary, suppression of the p38 MAPK signaling pathway and chemotaxis appear to be important anti-rheumatic mechanisms of action of these HDAC inhibitors.

Quantitative analysis of catalpol in chinese patent medicine Lixin pill by near-infrared diffuse reflectance spectroscopy

Lixin pill is a typical Chinese patent medicine with anti-rheumatic heart disease activity that has been widely used in clinical practice. Therefore it is very important to detect the concentration of catalpol, as the main component of the active ingredient. Near-infrared reflectance(NIR) spectroscopy was used to study the content of catalpol in the unprocessed Chinese patent medicine of Lixin pills. NIR is applied to quantitatively analyze 77 samples, which were randomly divided into a calibration set containing 61 samples and a prediction set containing 16 samples. To get a satisfying result, partial least squares(PLS) regression was utilized to establish quantitative models. In PLS regression, the values of coefficient of determination(R2) and root mean square error of cross-validation (RMSECV) of PLS regression are 0.9419 and 0.0216, respectively. The process of establishing model, parameters of model, and prediction results were also discussed in detail(root mean square error of prediction is 0.0164). The overall results show that NIR spectroscopy can be efficiently utilized for the rapid and accurate analysis of routine chemical compositions in the Chinese patent medicine of Lixin pills. The prediction set suggests that this quantitative analysis model has excellent generalization ability and prediction precision. Accordingly, the result can provide technical support for the further analysis of catalpol in unprocessed Lixin pill. Moreover, this study supplied technical support for the further analysis of other Chinese patent medicine samples.

Chloroquine enjoys a renaissance as an antineoplastic therapy

Chloroquine (CQ) and hydroxychloroquine (HCQ), oral lysosomotropic agents with well-studied toxicity profiles, and antimalarial and antirheumatic activity, have been repurposed as antineoplastic agents based on preclinical data showing efficacy in preinvasive cancer, cancer stem cells and metastatic cancer. Phase I/II clinical trials are providing safety and efficacy data regarding CQ or HCQ monotherapy or combination therapy with molecularly targeted inhibitors in patients diagnosed with glioblastoma multiforme, breast ductal carcinoma in situ, non-small-cell lung cancer, hepatocellular, pancreatic, or renal cancer, multiple myeloma, or chronic lymphocytic leukemia. Disruption of autophagy-mediated cell survival is a major therapeutic rationale for using CQ and HCQ. CQ and HCQ are the first agents that rationally target cytoprotective autophagy in cancer. Short-term treatment of preinvasive breast cancer with CQ introduces the concept of preventing invasive cancer by killing preinvasive lesions.

Bioinformatics Analysis for the Antirheumatic Effects of Huang-Lian-Jie-Du-Tang from a Network Perspective

Huang-Lian-Jie-Du-Tang (HLJDT) is a classic TCM formula to clear “heat” and “poison” that exhibits antirheumatic activity. Here we investigated the therapeutic mechanisms of HLJDT at protein network level using bioinformatics approach. It was found that HLJDT shares 5 target proteins with 3 types of anti-RA drugs, and several pathways in immune system and bone formation are significantly regulated by HLJDT's components, suggesting the therapeutic effect of HLJDT on RA. By defining an antirheumatic effect score to quantitatively measure the therapeutic effect, we found that the score of each HLJDT's component is very low, while the whole HLJDT achieves a much higher effect score, suggesting a synergistic effect of HLJDT achieved by its multiple components acting on multiple targets. At last, topological analysis on the RA-associated PPI network was conducted to illustrate key roles of HLJDT's target proteins on this network. Integrating our findings with TCM theory suggests that HLJDT targets on hub nodes and main pathway in the Hot ZENG network, and thus it could be applied as adjuvant treatment for Hot-ZENG-related RA. This study may facilitate our understanding of antirheumatic effect of HLJDT and it may suggest new approach for the study of TCM pharmacology.

Why it is necessary to translate curcumin into clinical practice for the prevention and treatment of metabolic syndrome?

Curcumin (diferuloylmethane) is the yellow-orange pigment of dried Curcuma longa L. rhizomes (turmeric). During the past two decades, there has been a large volume of published studies describing the biological and pharmacological properties of this phytochemical including anticancer, anti-inflammatory, antioxidant, antithrombotic, antiatherosclerotic, cardioprotective, neuroprotective, memory enhancing, antiparkinsonism, antirheumatic, anti-infectious, antiaging, antipsoriatic, and anticonvulsant activities. In addition, curcumin has been shown to be extremely safe and interact with multiple molecular targets that are involved in the pathogenesis of metabolic syndrome. Curcumin could favorably affect all leading components of metabolic syndrome including insulin resistance, obesity, hypertriglyceridemia, decreased HDL-C and hypertension, and prevent the deleterious complications of MetS including diabetes and cardiovascular disease. Owing to its antioxidant and anti-inflammatory properties, curcumin can also exert several pleiotropic effects and improve endothelial dysfunction, adipokine imbalances, and hyperuricemia which usually accompany MetS. Despite the potential tremendous benefit of this multifaceted phytopharmaceutical, no trial result has yet been publicized on this issue. This review seeks to briefly summarize the ample scientific evidence that supports the therapeutic efficacy of curcumin, at least as an adjunctive treatment, in patients with MetS.

Mukia maderaspatana (Linn.) M. Roemer: A potentially antidiabetic and vasoprotective functional leafy-vegetable

Mukia maderaspatana (Linn.) M. Roemer, (Family: Cucurbitaceae) [syn.: Melothria maderaspatana (L.) Cogn.], is distributed throughout the tropics and subtropics of the Old World. Different organs of the drug-plant are utilised in Ayurveda, Siddha, Naturopathy and Folkloric traditional medicines of India as well as the indigenous medical systems of the Sub-Saharan African, Asian and Australian communities for health-care needs. The leafy vegetable is reported to exhibit potent antioxidant capacity in vitro and in vivo and to possess anti hypertensive, vasodialatory, antihyperglycemic, antihyperlipidemic, hepatoprotective, immunomodulatory, antiinflammatory, antirheumatic, antiulcer, anxiolytic, antimicrobial, and antiplatelet aggregation activities. The present review is an attempt to highlight, for the first time, the current clinical and experimental evidences available in literature on the extent of its potentials to protect against vascular events and diabetes.

Adenosine A2A Receptor and TNF-α Regulate the Circadian Machinery of the Human Monocytic THP-1 Cells

Morning stiffness and increased symptoms of inflammatory arthritis are among the most common manifestations of rheumatoid arthritis (RA). Tumor necrosis alpha (TNF-α), an important mediator of inflammation in RA, regulates the circadian expression of clock proteins, and adenosine A(2A) receptors (A(2A)R) mediate many of the anti-inflammatory and antirheumatic actions of methotrexate, the cornerstone drug in the treatment of RA. We found that A(2A)R activation and TNF-α activated the clock core loop of the human monocytic THP-1 cell line. We further observed that interleukin (IL)-10, but not IL-12, mRNA expression fluctuates in a circadian fashion and that TNF-α and A(2A)R stimulation combined increased IL-10 expression. Interestingly, TNF-α, but not CGS21680, dramatically inhibited IL-12 mRNA expression. The demonstration that A(2A)R and TNF-α regulate the intrinsic circadian clock in immune cells provides an explanation for both the pathologic changes in circadian rhythms in RA and for the adverse circadian effects of methotrexate, such as fatigue.