Zingerone (4-(four-hydroxy-3-methylphenyl) butane-two-1) modulates adjuvant-induced rheumatoid arthritis by regulating inflammatory cytokines and antioxidants.

OBJECTIVE: Ginger (Zingiber officinale Roscoe) is considered to be one of the most commonly consumed dietary condiments of the world. The present study was designed to explicate the protective role of zingerone; an active ingredient of ginger in complete Freund's adjuvant (FCA)-immunized arthritic rats. METHODS: 24 Wistar rats were divided into 4 groups with 6 rats each. Group I as control followed by group II, III and IV were treated with single intradermal injection of FCA (0.1 ml = 100 µg) to induce rheumatoid arthritis. Group III and IV were also administered with zingerone orally at 25 mg/kg b.w for 3 weeks at two different time points. RESULTS: Adjuvant-treated rats exhibited a significant increase in lipid peroxidation and a reduction in the enzymatic antioxidants such as SOD, catalase and GPx, in the liver and joint tissues. Moreover, FCA inoculation resulted in the increase in levels of NF-κB, TGF-ß, TNF-α, IL-1ß, IL-6 and Hs-CRP and a decrease in IL-10 levels. Zingerone significantly reduced the levels of NF-κB, TGF-ß, TNF-α, IL-1ß, IL-6 and Hs-CRP and markedly increased IL-10 levels. Levels of antioxidant enzymes were also restored by zingerone treatment. DISCUSSION: Oral administration of zingerone ameliorated inflammatory outburst and decreased oxidative stress, suggesting its role in the prevention of rheumatoid arthritis. Further mechanistic insights are necessary to study the exact mechanism involved.

Folic acid-modified celastrol nanoparticles: synthesis, characterization, anticancer activity in 2D and 3D breast cancer models.

Celastrol is used in traditional Chinese medicine for treating cancers. However, its low water solubility and poor tumour selection represent major pitfalls for clinical application. In the present study, gold nanoparticle (AuNP) firstly was conjugated with PVP-co-2-dimethylaminoethyl methacrylate (Polymer) and celastrol then modified by folic acid. The as-prepared folate receptor-targeted celastrol AuNP (FCA) was characterized using attenuated total reflection Fourier transform infrared spectroscopy, UV-Vis spectrometry, transmission electron microscope, and inductively coupled plasma mass spectrometry. The physical properties of FCA were also determined in solubility, drug encapsulation and in vitro drug release. Its anticancer activities were assessed in the 2D and 3D breast cancer models. The results showed that FCA was synthesized successfully with good solubility, high encapsulation efficiency and loading content. FCA showed the optimal cumulative release at pH 5.0 and high cellular uptake and exhibited significant inhibition on breast cancer cells. FCA also induced more significant apoptosis either in 2D and 3D breast cancer model than the celastrol AuNP and celastrol alone. These findings demonstrate that FCA improves water solubility of celastrol and enhances its anticancer activities against breast cancer. FCA might be a potential candidate of anticancer drug for breast cancer in the future if further development.

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

BACKGROUND: 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. AIMS: 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. DESIGN: Rheumatoid arthritis (RA) was induced in male albino rats by Freund's complete adjuvant (FCA) at a dose of (0.25 mg 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 ± 10 g) were divided into 6 groups: Sham control; Arthritis control; Standard treatment indomethacin (0.25 mg 100 g(-1) p.o. × 5 alternative days), Gua MT (1 ml kg(-1) p.o. × 5 days) treated; Gua (30c 1 ml kg(-1) p.o. × 5 days) treated; Gua (200c; 1 ml kg(-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. RESULTS: 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-1ß/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. CONCLUSION: 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.

Therapeutic effects of dichloromethane fraction of Securidaca inappendiculata on adjuvant-induced arthritis in rat.

ETHNOPHARMACOLOGICAL RELEVANCE: Securidaca inappendiculata (SI) is a traditional antirheumatic medicine used in China. The present study was designed to investigate the therapeutic efficacy of dichloromethane fraction of SI (SID) at three different doses on adjuvant induced arthritis (AA) rats. METHODS: Arthritis severity was evaluated by arthritic score, body weight loss, paw circumference, histological changes and hyperplasia of lymphatic tissues. Serum samples were collected for estimation of superoxide dismutase (SOD), glutathione (GSH), hydroxy radical (OH·), nitric oxide (NO), malondialdehyde (MDA), N-acetyl glucosaminidase (NAG), sialic acid (SA), alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT). The levels of GSH, MDA, NAG and SA in liver were also assessed. The levels of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1) and vascular endothelial growth factor (VEGF) were determined using ELISA method. Another portion of blood was used for total and differential leucocyte counts. RESULTS: Administration with SID (at high dose with 100 mg/kg) significantly ameliorated the AA severity, suggested by the modulatory effects on body weight loss, paw swelling, hyperplasia of lymphatic tissues and synovial membrane, neutrocytosis and lymphocytosis. It also decreased levels of NO, MDA and OH·, restored SOD and GSH levels in serum. The abnormal increased levels of AST, ALT, ALP, NAG and SA significantly were reverted (compared with AA rats, P<0.01). A similar result was observed in livers. Levels of IL-1, TNF-α, MCP-1 and VEGF were reduced dramatically by SID too. CONCLUSION: The results suggest SID possesses substantial anti-arthritic activity. The therapeutic efficacy may be due to immumodepressive effects, cytokines regulation, increasing membrane stability and antioxidantive activity.

Curcumin potentiates the anti-arthritic effect of prednisolone in Freund's complete adjuvant-induced arthritic rats.

OBJECTIVES: The present study was aimed at investigating the effect of curcumin in combination with prednisolone for the effective treatment of arthritis with reduced side effects when glucocorticoids therapy is indicated. METHODS: Arthritis was induced in wistar rats by subplantar injection of Freund's complete adjuvant, and animals were observed for the symptoms of arthritis during the period of 21 days. Combined treatment of curcumin with various doses of prednisolone (1.25, 2.5 and 5 mg/kg) was evaluated in order to ascertain the efficacy and toxicity induced by steroid. KEY FINDINGS: Arthritic animals showed significant increase in tumour necrosis factor-α and IL-1ß levels in paw tissue and IL-1ß in serum. Combined therapy of curcumin with low doses of prednisolone showed pronounced beneficial effect on joint swelling, leucocyte count and biochemical parameters compared with prednisolone groups. Among the different doses used in the study, prednisolone at 1.25 mg/kg in combination with curcumin showed beneficial anti-arthritic activity and also reduced the steroid toxicity. This is evidenced by increase in body weight, low toxicity to immune organs, reduction in leucocyte count, increase in spleen anti-oxidant enzymes and potent inhibition of cytokines in combination group. CONCLUSION: Therefore, combined treatment of curcumin with low doses of prednisolone may find therapeutic use in arthritis.

Effect of Nitric Oxide on the Change of Spinal Neuropeptide in the Inflammation Model by Freund's Complete Adjuvant / 대한해부학회지

Injection of Freund's complete adjuvant (FCA) into the plantar surface of the rat induces inflammatory responses with accompanying pain behaviors. Signs of pain behaviors observed in FCA-injected animals are reported to be similar to symptoms seen in patients with inflammatory pain. In the previous study, injection of FCA produced a significant mechanical allodynia over time. The role of substance-P and calcitonin gene-related peptide(CGRP) on allodynia induced by inflammation is still controversial. We investigated the change of spinal neuropeptides and nitric oxide (NO) in rats with inflammation induced by subcutaneous injection of FCA into hind paw. The results are: 1. The number of NADPH-diaphorase and substance P positive neurons increased at ipsilateral spinal ventral horn after FCA injection. No significant changes were found with L-NAME posttreatment. 2. Staining intensity of substance P-immunoreactive area increased at ipsilateral spinal dorsal horn after FCA injection. No significant changes were found with L-NAME posttreatment. 3. CGRP immunoreactivity changed in the same pattern with substance P in all group. The results suggest that spinal neuropeptide substance P and CGRP are involved in the mechanism of the development and maintenance of allodynia in a state of FCA-induced inflammaion. NO may be also involved in the regulation of the quantity of substance P and CGRP in spinal cord.

Effect of Nitric Oxide on Neuropeptide Y Immunoreactivity in Rat Spinal Cord on the Allodynia of Inflammation Induced by Freund's Complete Adjuvant / 대한해부학회지

Injection of Freund's complete adjuvant (FCA) into peripheral tissue induces inflammatory responses with accompanying pain behaviors. Injection of FCA produced a significant mechanical allodynia over time and nitric oxide(NO) is involved in this mechanism. The role of neuropeptide Y (NPY) on allodynia induced by inflammation is still controversal. We invastigated the change of spinal NPY and nitric oxide in rats with inflammation induced by subcutaneous injection of FCA and L-NG-nitro arginine methyl ester (L-NAME) into hind paw. The results are: The number of NADPH-diaphorase positive neurons and staining intensity of area increased at ipsilateral spinal ventral/dorsal horn of inflammation model. No significant changes were found with L-NAME posttreatment. Staining intensity of NPY immunoreactive (ir) area increased at ipsilateral spinal dorsal horn after FCA injection. No significant changes were found with L-NAME posttreatment. NPY-ir and NADPH-d reactive neurons were found in Rexed III-IV lamina at spinal dorsal horn. No significant change were found on all groups. The results suggest that spinal NPY is involved in the mechanism of the development and maintenance of allodynia in a state of FCA-induced inflammaion. NO may be also involved in the regulation of the quantity of NPY in spinal cord level.

A change of nitric oxide in rat DRG following Freund's Complete Adjuvant induced inflammtory pain / 대한해부학회지

It has been reported that injection of Freund's complete adjuvant (FCA) into the hindpaw of a rat induces inflammatory responses with accompanying pain behaviors. Signs of pain behaviors observed in FCA-injected animals were reported to be similar to symptoms seen in patients with inflammatory pain. The nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) is a selective histochemical marker for the nitric oxide synthesizing enzyme, nitric oxide synthase (NOS). N (G)-nitro-L-arginine methyl ester (L-NAME) is a NOS inhibitor. In the present study, we examined if inflammaory pain causes increases in NADPH-diaphorase reactivities in neurons of the dorsal root ganglia (DRG). The results were as follows; 1. FCA-induced inflammation on a limb increased staining density (SD) of NADPH-d positive neurons in the ipsilateral side DRG. 2. Pretreatment of L-NAME did not changed SD of NADPH-d positive neurons on the inflammation of contralateral side DRG 3. Posttreatment of L-NAME decreased the inflammation induced SD of NADPH-d positive neurons. 4. n-NOS immunoreactivity did not match NADPH-d histochemical study, implying the constant level of enzyme itself. Inflammation pain on a hindlimb increased staining density of NADPH-diaphorase positive neuron in the DRG, which was decreased by L-NAME. L-NAME also decreased pain perception. This suggests a role of NO in the pain perception and/or modulation at the level of DRG.