Anti-arthritic potential of crude sulfated polysaccharide from marine macroalgae Sargassum ilicifolium (Turner) C. Agardh: Regulation of cytokine cascade.

Aim:The aim of this objective is to evaluate the antinociceptive and anti-inflammatory potential of sulfated polysaccharide purified fractions isolated from brown seaweed Sargassum wightii and seagrass Halophila ovalis in male Wistar rats.Subjects and Methods:Crude sulfated polysaccharide from S. wightii and H. ovalis was subjected to anion exchange chromatography, and the chemical composition was investigated. The antinociceptive activity of purified fractions was investigated using formalin and hot plate test. Carrageenan-induced paw edema, peritonitis model, and Freund's Complete Adjuvant-induced arthritis model were employed to determine the anti-inflammatory activity.Results:In the formalin test, there was a significant reduction in licking time in both phases of the test at a dose of 10 mg/kg. In the hot plate test, the antinociceptive effect was observed only in animals treated with 5, 10 mg/kg suggesting that the analgesic effect occurs through a central action mechanism. Sw FrIV and Ho FrIV significantly inhibited paw edema induced by carrageenan, especially at 3 h after treatment and potentially decreased neutrophil migration at 10 mg/kg, respectively. In Freund's adjuvant-induced arthritic rats, a significant reduction in paw volume was observed in Sw FrIV and Ho FrIV-treated groups (10 mg/kg).Conclusion:Purified components from S. wightii and H. ovalis have strong antinociceptive and anti-inflammatory effect on animal model. However, to determine the molecular mechanism, it is necessary to investigate the effect of purified fractions on inhibition of nitric oxide synthase expression mediated by inhibiting the phosphorylation of various signal proteins in lipopolysaccharide-stimulated RAW264.7 cells.

Anti-inflammatory effects of Solanum procumbens on a low dose complete Freund's adjuvant-induced arthritis rat model

Seaweeds are widely consumed as vegetables and medicinal products. The green seaweed Caulerpa cupressoides var. lycopodium sulfated polysaccharides (SPs) demonstrated anticoagulant (in vitro) and anti- and prothrombotic (in vivo) effects. However, their toxicity in vivo has not been fully determined. This study evaluated their toxicity in vivo in male Swiss mice. Animals (20-26 g, six group-1) received crude SP (9 mg kg-1, i.p.) or 0.9% saline (0.1 mL 10 g-1, i.p.) for 14 consecutive days, and then analyzed the wet weight of animal’s body organs-1 and biochemical/hematological parameters. Histopathological evaluation was also performed related to crude SP treatment. The results showed that crude SP did not cause toxicity and mortality. Regarding the biochemical analyses, crude SP did not lead to hepatic or renal dysfunctions, but affected (p < 0.05) the platelet count (1530.75 ± 1.05 × 103 µL-1) compared with the control (969.75 ± 0.51 × 103 µL-1) according to the hematological evaluation. Although histological changes in the liver and kidney have occurred, results suggested reversibility. The increased spleen size (p < 0.05) also had no toxicological significance based on histopathological analysis. Therefore, crude SP from C. cupressoides could represent safe pharmacological tool in future studies on immunomodulation and thrombosis in vivo.

Objective: The primary purpose of this study is to characterize Codium edule crude sulfated polysaccharide (CSP) and its fractions and to determineits potential antiproliferative and apoptotic properties.Methods: The CSP was obtained through hot water extraction followed by precipitation with absolute ethanol. CSP was further purified using ionexchangechromatography, Sepharose DEAE Fast Flow column and yielded three fractions (F1, F2, and F3). The CSP and fractions were characterizedfor their sulfate, protein, carbohydrate, and uronic acid content. Fourier-transformed infrared spectroscopy (FT-IR) was used to determine thefunctional groups present in CSP and SP fractions. Antiproliferative activity against human breast adenocarcinoma (MCF-7) was analyzed using MTTassay with doxorubicin as positive control. Apoptotic activity of C. edule was analyzed using caspase 3/7 and annexin V-FITC assay.Results: CSP afforded 6.3% sulfate, 4.1% protein, and 68.7% carbohydrate. F1 has the highest content of sulfate, protein, carbohydrate, and uronicacid among the fractions. FT-IR shows a broadband around 3400 cm−1 indicates the presence of hydroxyl stretching vibration of polysaccharide (-OH)and a band at 2922 cm−1 suggests a C-H stretch (alkane). 1658 cm−1 may be attributed to the C=O stretches of amide C=N group. Peak around 1259 cm−1is a characteristic band for S=O sulfate ester. The antiproliferative activity of C. edule against MCF-7 showed significant difference in the mean percentinhibition between CSP and F3 (p=0.001), F1 and F3 (p≤0.001), F2 and doxorubicin (p=0.025), and F3 and doxorubicin (p≤0.000). F1 of C. edule hasthe lowest IC50 of 5.54 μg/ml and displayed apoptotic phase and caspase 3/7 activity.Conclusion: The investigation revealed that SP from green seaweed, C. edule, could be used as potential anticancer treatment against breast canceradenocarcinoma.

Sulfated polysaccharides (SPs) from algae have been shown to be effective in a number of biological applications. Therefore, the chemical composition and different biological functions of various SPs were determined for three brown seaweed species from the Egyptian Red Sea: <i>Dictyopteris polypodioides, Polycladia myrica</i>, and <i>Turbinaria decurrens</i>. It has been found that the yield of crude SPs was higher than that of alginate and fucoidan with a range of 43.64% to 61.90%. Fucoidan, which has the maximum carbohydrate content of 56.89%, was found in <i>D. polypodioides.</i> The crude SPs of <i>P. myrica </i>had the greatest sulfate content of 22.44%. All functional groups of the examined samples were confirmed by the Fourier Transform Infrared spectrum (FTIR). Experimentally, three applicable assays were used to quantify the antioxidant activity of the extracted SPs depending on the method used, the type of polysaccharides, and algal species. The anti-diabetic activity of <i>T. decurrens</i>-crude SPs was highly active scoring 85.85% in the α-glucosidase assay. The anti-obesity activity showed the highest value (95.25%) for <i>T. decurrens</i>-fucoidan. Besides, <i>T. decurrens</i>-crude SPs showed the highest anti-arthritic activity (89.89%). In addition, a few positive records of antibacterial activity were detected. Furthermore, the most potent <i>T. decurrens</i>-crude SPs extract was tested for cytotoxicity against human liver cells and found to be safe. The activity of the isolated SPs and their chemical composition were shown to be correlated. Conclusively, the bioactivities recorded herein by the tested SPs pose promising medicinal applications towards developing a new therapeutic intervention.

Clematis orientalis Linn has long been used as ethnopharmacy for the treatment of arthritis. This study is intended to evaluate the curative efficacy of Clematis orientalis in treating polyarthritis in rats. Aqueous ethanolic extract and fractions (hexane, butanol and aqueous) were administered orally at 200mg/kg for 28days after CFA immunization. Paw swelling, paw diameter, arthritic score, body weight, hematological parameters, radiographic and histological analysis of ankle joints were evaluated. Moreover, levels of various inflammatory markers through RT-PCR and ELISA were measured. DPPH and reducing power assays were used to appraise antioxidant capacity. Qualitative phytochemical analysis, determination of total phenolic and flavonoid contents were also carried out. Aqueous ethanolic extract and fractions significantly (p < 0.001) reduced paw volume, paw thickness and arthritic score and considerably prevented decrease in body weight along with anomalous alterations in hematological parameters in comparison with arthritic control. X-ray and histological examination revealed no significant structuralchanges in ankle joints of treated rats. Expression levels of IL-1β, TNF-α, IL-6, COX-2 and NF-Kβ were significantly (p < 0.05-0.001) suppressed as well as noteworthy increasein the levels of IL-4 and IL-10 among treated animalshas been detected. Overproduction of TNF-α and PGE2 was substantially prevented in animals given different treatments. Aqueous ethanol extract and its fractions demonstrated significant and concentration-dependent antioxidant potential. In general, among fractions aqueous fraction exhibited a greater anti-arthritic effect. Phytochemical analysis of aqueous fraction confirmed the presence of flavonoids and glycosides, 215.29mgGAE/ml phenolic content and 633.03μgQE/ml flavonoid content. Thus, we suggest Clematis orientalis as a potent strategy for the treatment of rheumatoid arthritis.

Venlafaxine is a serotonin-norepinephrine reuptake inhibitor used to treat depression. Previous studies demonstrated its anti-nociceptive and anti-inflammatory activities through the suppression of pro-inflammatory cytokines. Present research aimed to explore its anti-arthritic potential. Different in-vitro assays including egg albumin, bovine serum albumin denaturation and human red blood cell (RBC) membrane stabilization assays along with in-vivo models of formaldehyde and complete Freund's adjuvant-induced arthritis were used to study its anti-arthritic effect. Venlafaxine inhibited egg albumin and bovine serum albumin denaturation and preserve the integrity of red blood cells membrane in concentration-dependent manner. In formaldehyde-induced arthritis venlafaxine significantly (p < 0.001) reduced the paw edema on treatment for 10 days. Chronic administration of venlafaxine for 28days in Freund's adjuvant-induced arthritis model decreased the paw volume (p < 0.001), arthritic index (p < 0.01), flexion pain score (p < 0.05), mobility score (p < 0.05), and improved the stance score (p < 0.05). Venlafaxine also significantly declined the rheumatoid factor (p < 0.01) and C-reactive protein (p < 0.05) levels and increased the RBC count (p < 0.01) and Hb value (p < 0.001). Upon PCR analysis venlafaxine remarkably turndown the mRNA expression of TNF-α, IL-6, IL-1β, and COX-2. Taken together it is inferred from current findings that venlafaxine possesses the significant anti-arthritic activity and could be a potential therapeutic option for the treatment of rheumatoid arthritis.

Backgroundβ-Caryophyllene oxide (BCPO) has wooden odor so widely used as cosmetic and food additives. It is naturally found in various spice and food plant such as basil, black pepper, clove, salvia, and indian bay leaf. It is traditionally used to treat arthritis. The present study anticipated to appraise the anti-inflammatory and anti-arthritic potential of BCPO alone and in combination with methotrexate.ResultsData from in vitro assays showed that BCPO exerted the highest percentage inhibition at 1600 μg/ml. Complete Freund’s Adjuvant-induced arthritis in Wistar rats treated with BCPO and its combination with methotrexate (MTX) revealed a notable restoration of body weight and reduced pain, arthritic score, oxidative stress, and hematological alterations in contrast to disease control. The histopathological examination showed that BCPO therapy decreased joint inflammation, pannus formation, and bone erosion. Biochemical studies revealed that BCPO alone and in combination not only downregulated the mRNA expression of TNF-α, IL-1β, NF-kB, and COX-2 but also increased the expression of IL-4, and IL-10.ConclusionIt can be inferred from the finding that BCPO in combination with MTX can be effectively used to manage polyarthritis due to notable anti-inflammatory, antioxidant, and anti-nociceptive activities than monotherapy.Graphical abstract

BackgroundCurrently, natural products have built a well-recognized role in the management of many degenerative diseases, mainly rheumatoid arthritis. Recent studies suggest that Spirulina, a unicellular blue-green alga, may have a variety of health benefits and curative properties and is also competent of acting as an anti-inflammatory, antioxidant and recently anti-angiogenic agent. In the present study, the antioxidant and the immunomodulatory effect of Spirulina platensis as well as its anti-angiogenic effect against complete Freund's adjuvant-induced arthritis (AIA) in rat model were tested.ResultsWe found that the development of arthritis was concealed; moreover it successfully inhibited the development of macroscopic as well as microscopic and histopathological lesions in AIA rats when compared to control. Spirulina treated group showed a higher survival rate and moreover, it reduced the clinical score of RA in a dose dependent manner. Furthermore, Spirulina decreased serum levels of COX-2, TNF-α, IL-6, TBARS, VEGF and increased serum levels of GSH compared to the RA non-treated group.ConclusionsThe present study concluded that Spirulina is able to restrain the changes produced through adjuvant-induced arthritis. The suppressing effect of Spirulina could be attributed, at least in part, to anti-inflammatory, antioxidant and anti-angiogenic properties.

Sesuvium sesuvioides (Fenzl) Verdc (Aizoaceae) has been traditionally used in the treatment of inflammation, arthritis, and gout. However, its antiarthritic potential has not been evaluated scientifically. The current study was designed to assess the antiarthritic properties of the n-butanol fraction of S. sesuvioides (SsBu) by phytochemical analysis, in vitro and in vivo pharmacological activities, and in silico studies. Phytochemical analysis showed total phenolic contents (90.7 ± 3.02mg GAE/g) and total flavonoid contents (23.7 ± 0.69mg RE/g), and further analysis by GC-MS identified possible bioactive phytocompounds belonging to phenols, flavonoids, steroids, and fatty acids. The in vitro antioxidant potential of SsBu was assessed by DPPH (175.5 ± 7.35mgTE/g), ABTS (391.6 ± 17.1mgTE/g), FRAP (418.2 ± 10.8mgTE/g), CUPRAC (884.8 ± 7.97mgTE/g), phosphomolybdenum (5.7 ± 0.33mmolTE/g), and metal chelating activity (9.04 ± 0.58mg EDTAE/g). Moreover, in the in vitro studies, inhibition (%) of egg albumin and bovine serum albumin denaturation assays showed that the anti-inflammatory effect of SsBu at the dose of 800μg/ml was comparable to that of diclofenac sodium used as a standard drug. The in vivo antiarthritic activity was assessed to determine the curative impact of SsBu against formalin-induced (dose-dependent significant (p < 0.05) effect 72.2% inhibition at 750mg/kg compared to standard; 69.1% inhibition) and complete Freund's adjuvant-induced arthritis (40.8%; inhibition compared to standard, 42.3%). SsBu significantly controlled PGE-2 level compared to the control group (p < 0.001) and restored the hematological parameters in rheumatoid arthritis. Treatment with SsBu significantly reduced oxidative stress by reinstating superoxide dismutase, GSH, and malondialdehyde along with pro-inflammatory markers (IL-6 and TNF-α) in arthritic rats. Molecular docking revealed the antiarthritic role of major identified compounds. Kaempferol-3-rutinoside was found to be more potent for COX-1 (-9.2kcal/mol) and COX-2 inhibition (-9.9kcal/mol) than diclofenac sodium (COX-1, -8.0 and COX-2, -6.5kcal/mol). Out of the 12 docked compounds, two for COX-1 and seven for COX-2 inhibition showed more potent binding than the standard drug. The results from the in vitro, in vivo, and in silico approaches finally concluded that the n-butanol fraction of S. sesuvioides had antioxidant and antiarthritic potential, which may be due to the presence of potential bioactive compounds.

Current treatments for rheumatoid arthritis produce untoward effects; thus, considerable effort has been made to recognize effective herbal medicines against the condition. In the present study, the therapeutic effect of Diospyros kaki fruit hydroalcoholic extract (DFHE) on complete Freund's adjuvant (CFA)-induced arthritis in rats was investigated. The extract was characterized using liquid chromatography-electrospray mass spectrometry (LC-ESIMS). Male Wistar rats were grouped as follows (eight rats in each): control, CFA, CFA + indomethacin (5 mg/kg), CFA + DFHE (50 mg/kg), and CFA + DFHE (100 mg/kg). Paw volume, mechanical allodynia, thermal hyperalgesia, and arthritis score were evaluated. Serum levels of malondialdehyde (MDA), thiol groups, tumor necrosis factor-alpha (TNF-α), as well as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were evaluated. Carotenoids were found to be the major components of DFHE. Administration of DFHE (100 mg/kg) significantly decreased arthritis score, paw volume, and thermal hyperalgesia, and improved mechanical allodynia. MDA and TNF-α levels were decreased while thiol levels and SOD and GPx activities were increased in DFHE-treated groups compared to the CFA group. These results suggest that D. kaki extract caused an improvement in clinical signs of rheumatoid arthritis symptoms possibly through suppression of oxidative stress and inflammation.

In our article entitled "Moringa rivae leaf extracts attenuate Complete Freund's adjuvant-induced arthritis in Wistar rats via modulation of inflammatory and oxidative stress biomarkers", we described the anti-arthritic effects of the plant leaves from Pakistan that we referred to as Moringa rivae (Saleem et al. 2019). Unfortunately, the identity of the plant material was incorrect. In fact, the plant leaves under study were later identified as belonging to wild type Moringa oleifera Lam. rather than Moringa rivae Chiov.

Effects of an antagonist of the bombesin/gastrin-releasing peptide receptor on complete Freund's adjuvant-induced arthritis in rats

Activation of the Nrf2/HO-1 signaling pathway by dimethyl fumarate ameliorates complete Freund's adjuvant-induced arthritis in rats

Anti-inflammatory, anti-nociceptive, and anti-psychiatric effects by the rhizomes of Alpinia officinarum on complete Freund's adjuvant-induced arthritis in rats