lignans and Arthritis--Rheumatoid

Matrix metalloproteinases, zinc dependent proteolytic enzymes, have significant implications in extracellular matrix degradation associated with tissue damage in inflammation and Rheumatoid arthritis. Numerous orchestrated pathways affects instigation and blockade of metalloproteinases as well as various factors that increase the expression of MMPs including inflammatory cytokines, hormones and growth factors. Direct inhibition of these proteolytic enzymes or modulation of these pathways can provide protection against tissue destruction in inflammation and rheumatoid arthritis. Inclination towards use of plant derived phytochemicals to prevent tissue damage has been increasing day by day. Diversity of phytochemicals have been known to directly inhibit metalloproteinases. Hence, thorough knowledge of phytochemicals is very important in novel drug discovery.. Present communication evaluates various classes of phytochemicals, in effort to unveil the lead molecules as potential therapeutic agents, for prevention of MMPs mediated tissue damage in inflammation and rheumatoid arthritis. Data have been analyzed through different search engines.. Numerous phytochemicals have been studied for their role as MMPs inhibitors which can be processed further to develop into useful drugs for the treatment of inflammation and rheumatoid arthritis.. In search of new drugs, phytochemicals like flavonoids, glycosides, alkaloids, lignans & terpenes offer a wide canvas to develop into valuable forthcoming medicaments.

Topics: Alkaloids; Arthritis, Rheumatoid; Flavonoids; Glycosides; Humans; Inflammation; Lignans; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Phytochemicals; Signal Transduction; Terpenes

To review the progress in the research of the active ingredients of Zushima and their pharmacological activities.. Base on the articles of the chemical constituents and pharmacological activities of Zushima.. Traditional Chinese drug, Zushima contains coumarins, diteropenoids, lignans, flavonoids, anthraquinones and sterols. Pharmacological investigation concludes that it has actions of painkilling, antiinflammation, inhibiting bacteria, antithrombus, antitumer and antifertility.. Zushima has extensive actions in pharmacology. And plant resources are very rich. It is a meaning job to study the chemical ingredients and pharmacological activities of Zushima further.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Phytogenic; Arthritis, Rheumatoid; Coumarins; Daphne; Humans; Lignans; Phytotherapy; Plant Bark; Plant Roots; Plants, Medicinal

Inflammation is one of the main characteristics of rheumatoid arthritis. Based on the antiinflammatory properties of sesame, this study was conducted to evaluate the sesamin supplement effects on serum levels of some proteolytic enzymes, inflammatory biomarkers, and clinical indices in women with rheumatoid arthritis. In this randomized, triple-blind, placebo-controlled clinical trial, 44 patients were randomly divided in intervention and control groups. Patients received 200-mg/day sesamin supplement or placebo in the intervention and control group for 6 weeks. Serum levels of proteolytic enzymes (hyaluronidase, aggrecanase, and matrix metalloproteinases-3) and inflammatory biomarkers (hs-CRP, IL-1β, IL-6, TNF-α, and cyclooxygenase-2) were measured with enzyme-linked immunosorbent assay method at the beginning and end of the study. After intervention, serum levels of hyaluronidase and matrix metalloproteinases-3 decreased significantly in sesamin group. Also, serum levels of hs-CRP, TNF-α, and cyclooxygenase-2 in intervention group were significantly decreased in intervention group compared with placebo group. Sesamin supplementation also caused a significant reduction in the number of tender joints and severity of pain in these patients. According to the results, it seems that the sesamin by reducing inflammatory mediators can relieve clinical symptoms and pathological changes that caused by inflammatory impairment in patients with rheumatoid arthritis.

Topics: Antioxidants; Arthritis, Rheumatoid; Biomarkers; Dietary Supplements; Dioxoles; Double-Blind Method; Female; Humans; Inflammation; Lignans; Middle Aged; Peptide Hydrolases

To study x-ray development and clinical effects, tolerability and safety after 2 years treatment of RA patients with Reumacon (CPH82) or methotrexate (MTX).. This study is a 74 week open continuation of a 24 week double blind comparison of 100 patients with early RA (disease duration less than 2 years) treated either with Reumacon or MTX.. The mean Larsen scores and the mean number of erosions increased significantly from baseline to 24 weeks and from 24 weeks to endpoint in both groups with no significant difference between them. Both groups had improved significantly in all clinical variables after 24 weeks and this improvement was sustained after two years.. Radiological progression in patients treated with CPH82 was similar to that in patients treated with MTX. The clinical effect of the two drugs was sustained over the two year trial in both treatment groups.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Arthrography; Disease Progression; Double-Blind Method; Female; Glycosides; Humans; Joints; Lignans; Male; Methotrexate; Middle Aged; Severity of Illness Index; Treatment Outcome

CPH 82 [Reumacon] is a purified semi-synthetic lignan glycoside derivative of the medicinal herb Podophyllum emodi which inhibits microtubules. It has been jointly developed by the Swedish company Conpharm and the Swiss company Analytecon SA. It has potential for the treatment of rheumatoid arthritis. The Swedish company Meda is licencing the drug and has taken over responsibility from Conpharm for development and documentation. Meda has obtained exclusive marketing rights for Reumacon worldwide, except in China and some other Asian countries. Meda plans to form partnerships with other companies in the marketing of Reumacon.

Topics: Administration, Oral; Arthritis, Rheumatoid; Clinical Trials as Topic; Glycosides; Humans; Lignans; Paclitaxel; Podophyllotoxin

CPH 82 is a non-steroid antirheumatic drug containing two benzylidenated podophyllotoxin glucosides with no affinity for the glucocorticoid receptor. Treatment with CPH 82 as single drug therapy significantly decreased serum and urinary cortisol and cortisol metabolites, serum adrenal androgens and urinary androgen metabolites, plasma ACTH and serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), and increased serum levels of sex hormone-binding globulin (SHBG). Significant positive correlations were found between serum TNF-alpha and plasma ACTH and between serum IL-6 and TNF-alpha on the one hand and serum and urinary cortisol and cortisol metabolites on the other. The initial action of CPH 82 on adrenal steroidogenesis may be a reduction in cytokine levels due to the drugs' antiinflammatory effect. This causes decreased ACTH stimulation, resulting in a reduced adrenocortical steroid secretion. Accumulation of the drug in the adrenal cortex may also affect adrenal steroidogenesis. The elevated SHBG levels may be caused by a weak estrogenic activity of the drug.

Topics: Adrenocorticotropic Hormone; Adult; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Endocrine Glands; Female; Glycosides; Homeostasis; Humans; Lignans; Male; Middle Aged; Podophyllotoxin; Steroids; Tumor Necrosis Factor-alpha

The objectives of this study were to evaluate the therapeutic efficacy of CPH 82 in comparison with methotrexate (MTX) in adult patients with early, active rheumatoid arthritis (RA) and to compare the tolerance and safety profiles of the two drugs.. The study was a 24-week, double-blind, randomized study in 10 centres of 100 patients with active RA, with a disease duration of less than 2 yr at the start of treatment, which consisted of either CPH 82 300 mg/day or MTX 10 mg/week. The six primary effect variables were: number of swollen joints, Ritchie's articular index, patient's pain score, patient's global score, Health Assessment Questionnaire (HAQ) and C-reactive protein (CRP). Erythrocyte sedimentation rate (ESR), physician's global score and the efficacy according to the European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) response criteria were also analysed.. There was a significant improvement for both drugs in all variables. Significant differences between the drugs in favour of MTX were found only in patient's pain score, CRP and ESR. By the EULAR criteria, 76% and 86% were judged to be responders in the CPH 82 and MTX groups, respectively. By the ACR criteria, the corresponding figures were 58% and 64%. The most common side-effects were gastrointestinal, which were similar in both groups. The numbers of treatment failures due to adverse events were two with CPH 82 and 14 with MTX.. The clinical effect of CPH 82 in this study was comparable to that of MTX at a dose of 10 mg/week. Both drugs reduced acute-phase reactants, MTX more effectively than CPH 82. The safety profile of CPH 82 was more favourable than that of MTX without folic acid supplementation.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Blood Sedimentation; Double-Blind Method; Female; Glycosides; Humans; Joints; Lignans; Male; Methotrexate; Middle Aged; Pain; Severity of Illness Index; Treatment Outcome

In this retrospective analysis of the DMARD CPH 82 in 44 Icelandic patients with severe refractory arthritis, clinical tolerance was good and serious side effects absent, although the majority were using the drug in combination with other DMARDS. Side effects leading to discontinuation were seen in 16% and the three year drug-survival was 51%.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Drug Therapy, Combination; Female; Glycosides; Humans; Lignans; Male; Middle Aged; Retrospective Studies; Time Factors; Treatment Failure; Treatment Outcome

Plants are rich natural sources of antioxidants in addition to other nutrients. Interventions and cross sectional studies on subjects consuming uncooked vegan diet called living food (LF) have been carried out. We have clarified the efficacy of LF in rheumatoid diseases as an example of a health problem where inflammation is one of the main concerns. LF is an uncooked vegan diet and consists of berries, fruits, vegetables and roots, nuts, germinated seeds and sprouts, i.e. rich sources of carotenoids, vitamins C and E. The subjects eating LF showed highly increased levels of beta and alfa carotenes, lycopen and lutein in their sera. Also the increases of vitamin C and vitamin E (adjusted to cholesterol) were statistically significant. As the berry intake was 3-fold compared to controls the intake of polyphenolic compounds like quercetin, myricetin and kaempherol was much higher than in the omnivorous controls. The LF diet is rich in fibre, substrate of lignan production, and the urinary excretion of polyphenols like enterodiol and enterolactone as well as secoisolaricirecinol were much increased in subjects eating LF. The shift of fibromyalgic subjects to LF resulted in a decrease of their joint stiffness and pain as well as an improvement of their self-experienced health. The rheumatoid arthritis patients eating the LF diet also reported similar positive responses and the objective measures supported this finding. The improvement of rheumatoid arthritis was significantly correlated with the day-to-day fluctuation of subjective symptoms. In conclusion the rheumatoid patients subjectively benefited from the vegan diet rich in antioxidants, lactobacilli and fibre, and this was also seen in objective measures.

Topics: Antioxidants; Arthritis, Rheumatoid; Carotenoids; Chromatography, High Pressure Liquid; Diet, Vegetarian; Dietary Fiber; Eating; Female; Fibromyalgia; Flavonoids; Flavonols; Fruit; Humans; Lactobacillus; Lignans; Middle Aged; Severity of Illness Index; Treatment Outcome; Vegetables

The onset of action rate of CPH-82 (Reumacon), was compared with that of auranofin (AUR; Ridaura) in a 36-week randomised, double-blind, multicentre study of 60 patients with rheumatoid arthritis (RA). As compared with respective baseline values, the CPH-82 group manifested significant improvement in grip strength, Ritchie's articular index (RAI), pain ratings, and HAQ (health assessment questionnaire) scores after 8, 12, 24, and 36 weeks of treatment, with the exception of the 24-week HAQ score. The AUR group manifested corresponding improvement in RAI after 8, 12, 24, and 36 weeks. Significant differences in changes from baseline values in favour of the CPH-82 group were found for grip strength at 12 and 24 weeks, RAI score at 8 weeks, VAS score at 8 and 12 weeks, and HAQ score at 8 weeks. The findings suggest CPH-82 to manifest a more rapid onset of action than AUR. The two drugs were similar in tolerance and safety.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Auranofin; Double-Blind Method; Female; Glycosides; Hand Strength; Health Status; Humans; Lignans; Male; Middle Aged; Safety; Surveys and Questionnaires; Treatment Outcome

The efficacy, tolerance, and safety of CPH 82 (semisynthetic lignan glycosides) (Conpharm AB) for patients with rheumatoid arthritis (RA) were assessed in a 12-week double-blind placebo-controlled study. Thirteen patients out of 15 in the CPH 82 group and 10 out of 15 in the placebo group completed the study. No improvement was seen in placebo treated patients. Patients treated with CPH 82 showed a statistically significant improvement in most clinical and immunological variables. Some patients treated with CPH 82 reported gastrointestinal discomfort (diarrhoea and abdominal pain).

Topics: Arthritis, Rheumatoid; Gastrointestinal Diseases; Glycosides; Humans; Lignans; Placebos; Plant Extracts; Plants, Medicinal; Plants, Toxic; Podophyllum

Rheumatoid arthritis (RA) is a severe inflammatory auto-immune disorder affecting millions of people across the globe. The current therapeutic options are not adequate to address the complications of RA. Therefore, the present study was conducted to elucidate the protective effect of lariciresinol, a lignan, against Complete Freund's adjuvant (CFA)-induced arthritis in rats. The results of the study showed that lariciresinol improves paw swelling and arthritic scores in rats as compared to CFA rats. Lariciresinol also showed a significant reduction in rheumatoid factor, C-reactive protein, tumor necrosis factor-α, interleukin (IL)-17, and tissue inhibitor of metalloproteinases-3 level with a simultaneous increase in IL-4 level. The burden of oxidative stress was also reduced in CFA rats, as shown by reduced MDA levels and increased SOD and GPx after the administration of lariciresinol. In a Western blot analysis, lariciresinol showed a significant reduction of transforming growth factor-β and nuclear factor-κB (NF-κB) protein levels in CFA rats. To understand the binding characteristic of lariciresinol with NF-κB, molecular docking analysis was conducted, which showed Larciresinol interacted with the active site of NF-κB. Our study demonstrated the significant protective effect of lariciresinol against RA via multi-target action.

Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Freund's Adjuvant; Lignans; Molecular Docking Simulation; NF-kappa B; Rats; Transforming Growth Factor beta; Transforming Growth Factors

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes cartilage damage. Anti-inflammatories are widely used in the management of RA, but they can have side effects such as gastrointestinal and/or cardiovascular disorders. Studies published by our group showed that the synthesis of hybrid triazole analogs neolignan-celecoxib containing the substituent groups sulfonamide (L15) or carboxylic acid (L18) exhibited anti-inflammatory activity in an acute model of inflammation, inhibited expression of P-selectin related to platelet activation and did not induce gastric ulcer, minimizing the related side effects. In continuation, the present study evaluated the anti-inflammatory effects of these analogs in an experimental model of arthritis and on the functions of one of the important cells in this process, macrophages. Mechanical hyperalgesia, joint edema, leukocyte recruitment to the joint and damage to cartilage in experimental arthritis and cytotoxicity, spread of disease, phagocytic activity and nitric oxide (NO) and hydrogen peroxide production by macrophages were evaluated. Pre-treatment with L15 and L18 reduced mechanical hyperalgesia, joint edema and the influx of leukocytes into the joint cavity after different periods of the stimulus. The histological evaluation of the joint showed that L15 and L18 reduced cartilage damage and there was no formation of rheumatoid pannus. Furthermore, L15 and L18 were non-cytotoxic. The analogs inhibited the spreading, the production of NO and hydrogen peroxide. L15 decreased the phagocytosis. Therefore, L15 and L18 may be potential therapeutic prototypes to treat chronic inflammatory diseases such as RA.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Celecoxib; Edema; Hydrogen Peroxide; Hyperalgesia; Lignans; Zymosan

Lipid mediators (LM) encompass pro-inflammatory prostaglandins (PG) and leukotrienes (LT) but also specialized pro-resolving mediators (SPM) which display pivotal bioactivities in health and disease. Pharmacological intervention with inflammatory disorders such as osteoarthritis and rheumatoid arthritis commonly employs anti-inflammatory drugs that can suppress PG and LT formation, which however, possess limited effectiveness and side effects. Here, we report on the discovery and characterization of the two novel benzoxanthene lignans 1 and 2 that modulate select LM biosynthetic enzymes enabling the switch from pro-inflammatory LT to SPM biosynthesis as potential pharmacological strategy to intervene with inflammation. In cell-free assays, compound 1 and 2 inhibit microsomal prostaglandin E

Topics: Adult; Animals; Anti-Inflammatory Agents; Arachidonate 5-Lipoxygenase; Arthritis, Rheumatoid; HEK293 Cells; Humans; Leukocytes; Leukotrienes; Lignans; Macrophages; Mice; Prostaglandin-E Synthases

Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic synovitis, cartilage degradation and bone deformities. Synovitis is the term for inflammation of the synovial membrane, an early stage of RA. The pathogenesis of the disease occurs through cytokine induction. The major cytokine that increases the severity of RA is TNF-α. Thus, inhibition of the TNF-α cascade is an effective way to diminish the progression of the disease. We are interested in investigating the difference between primary human synovial fibroblast (hSF) cells and SW982 as synovitis models induced by TNF-α and in monitoring their responses to sesamin as an anti-inflammatory phytochemical.. The designed experiments were performed in hSF cells or the SW982 cell line treated with 10 ng/ml TNF-α with or without 0.25, 0.5 or 1 μM sesamin. Subsequently, pro-inflammatory cytokine genes and proteins were measured in parallel with a study of associated signalling transduction involved in inflammatory processes, including NF-κB and MAPK pathways.. The results demonstrated that although hSF and SW982 cells responded to TNF-α induction in the same fashion, they reacted at different levels. TNF-α could induce IL-6, IL-8 and IL-1β in both cell types, but the levels in SW982 cells were much higher than in hSF cells. This characteristic was due to the different induction of MAPKs in each cell type. Both cell types reacted to sesamin in almost the same fashion. However, hSF cells were more sensitive to sesamin than SW982 cells in terms of the anti-RA effect.. The responses of TNF-α-induced hSF and SW982 were different at the signal transduction level. However, the two cell types showed almost the same reaction to sesamin treatment in terms of the end point of the response.

Topics: Arthritis, Rheumatoid; Cell Line; Cytokines; Dioxoles; Fibroblasts; Humans; Lignans; Models, Biological; Signal Transduction; Synovial Membrane; Synovitis; Tumor Necrosis Factor-alpha

Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammatory arthritis. TNF-α and OSM are pro-inflammatory cytokines that play a key role in RA progression. Thus, reducing the effects of both cytokines is practical in order to relieve the progression of the disease. This current study is interested in sesamin, an active compound in sesame seeds. Sesamin has been shown to be a chondroprotective agent in osteoarthritis models. Here, we have evaluated a porcine cartilage explant as a cartilage degradation model related to RA induced by TNF-α and/or OSM in order to investigate the effects of sesamin on TNF-α and OSM in the cartilage degradation model.. A porcine cartilage explant was induced with a combination of TNF-α and OSM (test group) or IL-1β and OSM (control group) followed by a co-treatment of sesamin over a long-term period (35 days). After which, the tested explants were analyzed for indications of both the remaining and the degradation aspects using glycosaminoglycan and collagen as an indicator.. The combination of TNF-α and OSM promoted cartilage degradation more than either TNF-α or OSM alone and was comparable with the combination of IL-1β and OSM. Sesamin could be offering protection against cartilage degradation by reducing GAGs and collagen turnover in the generated model.. Sesamin might be a promising agent as an alternative treatment for RA patients. Furthermore, the generated model revealed itself to be an impressive test model for the analysis of phytochemical substances against the cartilage degradation model for RA. The model could be used to test for the prevention of cartilage degradation in other biological agents induced with TNF-α and OSM as well.

Topics: Animals; Arthritis, Rheumatoid; Cartilage; Dioxoles; Immunohistochemistry; Lignans; Models, Biological; Oncostatin M; Protective Agents; Swine; Tumor Necrosis Factor-alpha

Rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) play an important role in the initiation and progression of RA, which are resistant to apoptosis and proliferate in an anchorage-independent manner.. The effects of arctigenin on the proliferation and apoptosis of RAFLSs were explored.. Arctigenin (0-160 µM) was used to treat RAFLSs for 48 h. Cell viability and apoptosis were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay and annexin V/propidium iodide staining. Western blot analysis was performed to detect the changes in apoptosis-related genes.. Arctigenin decreased cell viability by 23, 30, and 38% at the dose of 10, 20, and 30 µM, respectively. The half maximal inhibitory concentration (IC50) of arctignein on RAFLSs was about 38 µM. Moreover, 9, 15, and 21% of RAFLSs are induced apoptosis by 10, 20, and 30 µM of arctigenin. The apoptotic response was due to the loss of mitochondrial membrane potential, coupled with the release of cytochrome C into cytoplasm, the up-regulation of pro-apoptotic protein, Bax, and down-regulation of antiapoptotic protein, B cell lymphoma 2 (Bcl-2). The activation of mitochondrial pathway in arctigenin-treated RAFLSs induced the cleavage of caspase-9, caspase-3, and poly (ADP-ribose) polymerase (PARP). Additionally, arctigenin inhibited the nuclear translocation of p65, decreased the degradation of inhibitor of kappa B alpha (IκBα), and attenuated the phosphorylation of Akt.. Our results reveal that arctigenin inhibits cell proliferation and induces mitochondrial apoptosis of RAFLSs, which is associated with the modulation of NF-κB and Akt signaling pathways.

Topics: Adult; Apoptosis; Arthritis, Rheumatoid; Cell Proliferation; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Female; Fibroblasts; Furans; Humans; Lignans; Male; Middle Aged; Synovial Fluid; Synovial Membrane

To observe the anti-inflammatory effects of honokiol in primary cultures of peripheral blood mononuclear cells of rheumatoid arthritis patients, the pro-inflammatory cytokines and potential targets were investigated.. The levels of GM-CSF, IL-1β, TNF-α and IL-8 were determined by ELISA assay. The genes and proteins expression were analyzed by real-time PCR and Western blotting respectively.. The serum IL-1β, TNF-α and GM-CSF levels were 1.76-, 2.16- and 3.57-fold increased in patients with RA as compared to those of control group. Honokiol inhibited the expression levels of IL-1β, TNF-α, GM-CSF and IL-8 in PBMCs with a dose-dependent manner. Measurements obtained from supernatants were positively correlated between TNF-α and IL-1β, moreover, similar results found TNF-α levels positively correlated with GM-CSF and IL-8 activity in the supernatants of PBMCs isolated from RA patients. Furthermore, the mRNA and protein expression of IL-1β, GM-CSF and IL-8 were up-regulated when the PBMCs exposure to TNF-α, however, honokiol treatment significantly reversed the expression of IL-1β, TNF-α and GM-CSF in response to TNF-α with a dose-dependent manner.. This study demonstrates that honokiol could possess potential anti-inflammatory effects and inhibits TNF-α-induced IL-1β, GM-CSF and IL-8 production in PBMCs from rheumatoid arthritis patients.

Topics: Adult; Aged; Anti-Inflammatory Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Biphenyl Compounds; Case-Control Studies; Cells, Cultured; Dose-Response Relationship, Drug; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Inflammation Mediators; Interleukin-1beta; Interleukin-8; Leukocytes, Mononuclear; Lignans; Male; Middle Aged; Primary Cell Culture; Signal Transduction; Tumor Necrosis Factor-alpha

Chemical investigation of Vitex negundo seeds afforded four new lignans, including a phenylindene-type lignan, vitexdoin F (1), and three phenylnaphthalene-type lignans, vitexdoins G, H and I (2-4). Their structures were elucidated by detailed spectroscopic analyses on the basis of NMR, IR, and MS data. All compounds were evaluated for their anti-inflammatory and anti-osteoporotic activities, employing RAW264.7 macrophages, osteoblast-like UMR106 and osteoclastic cells, respectively. Compound 1 showed significant inhibition on the nitric oxide (NO) production (IC50 4.17 μg/mL) due to its down-regulation of the inducible nitric oxide synthase (iNOS) protein expression in LPS-stimulated RAW264.7 cells, which also exhibited potent stimulatory effects on the proliferation and ALP (alkaline phosphatase) activity of UMR106 cells, and significantly up-regulated the OPG/RANKL protein ratio.

Topics: Animals; Animals, Newborn; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Bone Density Conservation Agents; Cell Line; Drug Evaluation, Preclinical; Lignans; Phytotherapy; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; Seeds; Vitex

The seeds of Vitex negundo L. (Verbenaceae) have been commonly used as a folk remedy for the treatment of rheumatism and joint inflammation in Traditional Chinese Medicine. This study aimed to evaluate the anti-arthritic activity of the extract of V. negundo seeds (EVNS) using Freund's complete adjuvant (CFA) induced arthritis (AA) in rat model. As a result, EVNS, with abundant phenylnaphthalene-type lignans, significantly inhibited the paw edema, decreased the arthritis score and spleen index, and reversed the weight loss of CFA-injected rats. Histopathological studies showed a marked decrease of synovial inflammatory infiltration and synovial lining hyperplasia in the joints of EVNS-treated animals. The remarkable decrement of serum inflammatory factors (TNF-α, IL-1β and IL-6) were observed in EVNS-treated rats, whereas, IL-10, an anti-inflammatory cytokine, was found to be significantly increased by EVNS. The expressions of COX-2 and 5-LOX in PBMC were also inhibited by administration of EVNS. Our results demonstrated that V. negundo seeds possessed potential therapeutic effect on adjuvant induced arthritis in rats by decreasing the levels of TNF-α, IL-1β and IL-6 and increasing that of IL-10 in serum as well as down-regulating the levels of COX-2 and 5-LOX, and therefore may be an effective cure for the treatment of human rheumatoid arthritis.

Topics: Animals; Anti-Inflammatory Agents; Antirheumatic Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Cyclooxygenase 2; Down-Regulation; Edema; Freund's Adjuvant; Inflammation; Inflammation Mediators; Interleukins; Joints; Leukocytes, Mononuclear; Lignans; Lipoxygenases; Male; Naphthalenes; Phytotherapy; Plant Extracts; Rats, Wistar; Seeds; Synovial Membrane; Tumor Necrosis Factor-alpha; Vitex; Weight Loss

Investigation of the bark of Zanthoxylum simulans afforded six new dimeric lignans zanthpodocarpins C-H (1-6) bearing an unusual α,β-unsaturated ketone group. The new structures of 1-6 were determined by using detailed spectroscopic analysis. All of the isolated compounds were examined for their inhibitory effects against rat joint synovial cell and splenocyte proliferation. Compounds 1-6 showed potent anti-inflammatory activities with IC50 values ranging from 18.6 to 36.1μM, and 13.8 to 74.3μM.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cell Proliferation; Dimerization; Disease Models, Animal; Dose-Response Relationship, Drug; Ketones; Lignans; Rats; Spleen; Structure-Activity Relationship; Synovial Fluid; Zanthoxylum

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Dehydroepiandrosterone; Glucocorticoids; Glycosides; Humans; Hypothalamo-Hypophyseal System; Immunosuppressive Agents; Lignans; Pituitary-Adrenal System; Premenopause

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Drug Therapy, Combination; Glycosides; Humans; Lignans; Podophyllotoxin

Chromosomal changes were assessed in 19 patients with rheumatoid arthritis (RA) treated with CPH82, a benzylidated podophyllotoxin glycoside, for up to one year. The frequency of chromosomal aberrations (CA) and sister chromatid exchanges (SCE) in peripheral lymphocytes increased significantly after 12 weeks of treatment and remained elevated after 48 weeks treatment in peripheral lymphocytes. The number of CA and SCE were significantly increased in CPH82 treated patients compared with the RA patients treated with other disease modifying anti-rheumatic drug (sulphasalazine, gold, D-penicillamine, azathioprine, methotrexate, cyclophosphamide). Only two patients treated with cyclophosphamide and azathioprine had changes of comparable levels. The results of this study suggest a mutagenic potential of CPH82 similar to that described for other immunosuppressive drugs and the newer podophyllotoxin derivatives, etoposide and teniposide.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Chromosome Aberrations; Cytotoxins; Female; Glycosides; Humans; Lignans; Male; Middle Aged; Sister Chromatid Exchange; Time Factors

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Female; Glycosides; Humans; Lignans; Male; Middle Aged

Treatment with CPH 82, a mixture of two benzylidated podophyllotoxin glycosides, has been shown to improve inflammatory activity in patients with RA. The drug has few side effects but some patients have developed clinical features of Cushing's syndrome. We studied the hypothalamic-pituitary-adrenocortical axis in two female patients before and during treatment with CPH82. The results clearly demonstrate that CPH82 was associated with suppression of the endogeneous production of ACTH and cortisol with a concomitant paradoxical picture of clinical hypercortisolism. These observations suggest that CPH82 has glucocorticoid receptor agonistic effects.

Topics: Adrenocorticotropic Hormone; Adult; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Female; Glycosides; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Lignans; Microtubules; Pituitary-Adrenal System; Plant Extracts