Search results for: inflammatory myopathies

Authors: Tamphasana Wairokpam

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Inflammatory myopathies (IMs) have long been recognised as a heterogenous family of myopathies with acute, subacute, and sometimes chronic presentation and are potentially treatable. Necrotizing autoimmune myopathies (NAM) are a relatively new subset of myopathies. Patients generally present with subacute onset of proximal myopathy and significantly elevated creatinine kinase (CK) levels. It is being increasingly recognised that there are limitations to the independent diagnostic utility of muscle biopsy. Immunohistochemistry tests may reveal important information in these cases. The traditional classification of IMs failed to recognise NAM as a separate entity and did not adequately emphasize the diversity of IMs. This review and case report on NAM aims to highlight the heterogeneity of this entity and focus on the distinct clinical presentation, biopsy findings, specific auto-antibodies implicated, and available treatment options with prognosis. This article is a meta-analysis of literatures on NAM and a case report illustrating the clinical course, investigation and biopsy findings, antibodies implicated, and management of a patient with NAM. The main databases used for the search were Pubmed, Google Scholar, and Cochrane Library. Altogether, 67 publications have been taken as references. Two biomarkers, anti-signal recognition protein (SRP) and anti- hydroxyl methylglutaryl-coenzyme A reductase (HMGCR) Abs, have been found to have an association with NAM in about 2/3rd of cases. Interestingly, anti-SRP associated NAM appears to be more aggressive in its clinical course when compared to its anti-HMGCR associated counterpart. Biopsy shows muscle fibre necrosis without inflammation. There are reports of statin-induced NAM where progression of myopathy has been seen even after discontinuation of statins, pointing towards an underlying immune mechanism. Diagnosisng NAM is essential as it requires more aggressive immunotherapy than other types of IMs. Most cases are refractory to corticosteroid monotherapy. Immunosuppressive therapy with other immunotherapeutic agents such as IVIg, rituximab, mycophenolate mofetil, azathioprine has been explored and found to have a role in the treatment of NAM. In conclusion,given the heterogeneity of NAM, it appears that NAM is not just a single entity but consists of many different forms, despite the similarities in presentation and its classification remains an evolving field. A thorough understanding of underlying mechanism and the clinical correlation with antibodies associated with NAM is essential for efficacious management and disease prognostication.

Keywords: inflammatory myopathies, necrotising autoimmune myopathies, anti-SRP antibody, anti-HMGCR antibody, statin induced myopathy

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Authors: Benoit Jauniaux, Azzam Ismail

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Objectives: The aims were to identify all incident adult cases of idiopathic inflammatory myopathies (IIMs) in the City of Leeds, UK, and to estimate the risk of cancer in IIMs as compared with the general population. Methods: Cases of IIMs were ascertained by review of all muscle biopsy reports from the Neuropathology Laboratory. A review of medical records was undertaken for each case to review the clinical diagnosis and collect epidemiological data such as age, ethnicity, sex, and comorbidities, including cancer. Leeds denominator population numbers were publicly obtainable. Results: Two hundred and six biopsy reports were identified, and after review, 50 incident cases were included in the study between June 2010 and January 2021. Out of the 50 cases, 27 were male, and 23 were female. The mean incidence rate of IIMs in Leeds throughout the study period was 7.42/1 000 000 person years. The proportion of IIMs cases with a confirmed malignancy was 22%. Compared to the general population, the relative risk of cancer was significantly greater in the IIMs population(31.56, P < 0.01). Conclusions: The incidence rate of IIMs in Leeds was consistent with data from previous literature, however, disagreement exists between different methods of IIMs case inclusion due to varying clinical criteria and definitions. IIMs are associated with increased risk of cancer however, the pathogenesis of this relationship still requires investigating. This study supports the practice of malignancy screening and long-term surveillance in patients with IIMs.

Keywords: idiopathic inflammatory myopathies, myositis, polymyositis, dermatomyositis, malignancy, epidemiology, incidence rate, relative risk

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Authors: Rachna Agarwal, R. Naveen, Darpan Thakre, Rohit Shahi, Maryam Abbasi, Upendra Rathore, Latika Gupta

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Aim: Retinal changes are the window to systemic vasculature. Therefore, we explored retinal changes in patients with idiopathic inflammatory myopathies (IIM) as a surrogate for vascular health. Methods: Adult and juvenile IIM patients visiting a tertiary care centre in 2021 satisfying the International Myositis Classification Criteria were enrolled for detailed ophthalmic examination in comparison with healthy controls (HC). Patients with conditions that precluded thorough posterior chamber examination were excluded. Scale variables are expressed as median (IQR). Multivariate analysis (binary logistic regression-BLR) was conducted, adjusting for age, gender, and comorbidities besides factors significant in univariate analysis. Results: 43 patients with IIM [31 females; age 36 (23-45) years; disease duration 5.5 (2-12) months] were enrolled for participation. DM (44%) was the most common diagnosis. IIM patients exhibited frequent attenuation of retinal vessels (32.6% vs. 4.3%, p <0.001), AV nicking (14% vs. 2.2%, p=0.053), and vascular tortuosity (18.6% vs. 2.2%, p=0.012), besides decreased visual acuity (53.5% vs. 10.9%, p<0.001) and immature cataracts (34.9% vs. 2.2%, p<0.001). Attenuation of vessels [OR 10.9 (1.7-71), p=0.004] emerged as significantly different from HC after adjusting for covariates in BLR. Notably, adults with IIM were more predisposed to retinal abnormalities [21 (57%) vs. 1 (16%), p=0.068], especially attenuation of vessels [14(38%) vs. 0(0), p=0.067] than jIIM. However, no difference was found in retinal features amongst the subtypes of adult IIM, nor did they correlate with MDAAT, MDI, or HAQ-DI. Conclusion: Retinal microvasculopathy and diminution of vision occur in nearly one-third to half of the patients with IIM. Microvasculopathy occurs across subtypes of IIM, and more so in adults, calling for further investigation as a surrogate for damage assessment and potentially even systemic vascular health.

Keywords: idiopathic inflammatory myopathies, vascular health, retinal microvasculopathy, arterial attenuation

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Authors: M. A. Ferhat, M. N. Boukhatem, F. Chemat

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Since the available anti-inflammatory drugs exert an extensive variety of side effects, the search for new anti-inflammatory agents has been a priority of pharmaceutical industries. The aim of the present study was to assess the anti-inflammatory activities of the essential oil of rose geranium (RGEO). The chemical composition of the RGEO was investigated by gas chromatography. The major components were citronellol (29.13%), geraniol (12.62%), and citronellyl formate (8.06%). In the carrageenan induced paw edema, five different groups were established and RGEO was administered orally in three different doses. RGEO (100 mg/kg) was able to significantly reduce the paw edema with a comparable effect to that observed with diclofenac, the positive control. In addition, RGEO showed a potent anti-inflammatory activity by topical treatment in the method of croton oil-induced ear edema. When the dose was 5 or 10 ml of RGEO per ear, the inflammation was reduced by 73 and 88%, respectively. This is the first report to demonstrate a significant anti-inflammatory activity of Algerian RGEO. In addition, histological analysis confirmed that RGEO inhibited the inflammatory responses in the skin. Our results indicate that RGEO may have significant potential for the development of novel anti-inflammatory drugs with improved safety profile.

Keywords: anti-inflammatory effect, carrageenan, citronellol, histopathology, Rose geranium

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Authors: Demosthenes Panagiotakos

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The aim of the present work was to evaluate dietary habits’ inflammatory potential with various components of arterial blood pressure (hypertension, mean arterial pressure (MAP) and pulse pressure (PP)) in a sample of older Mediterranean people without known cardiovascular disease. During 2005-2011, 2,813 older (aged 65-100 years) individuals from 21 Mediterranean islands and the rural Mani region (Peloponnesus) were voluntarily enrolled. Standard procedures were used to determine arterial blood pressure, as well as PP and MAP, and for the evaluation of dietary habits, lifestyle, anthropometric and clinical characteristics of the participants. A dietary inflammatory index (DII) was assessed based on the participants specific dietary habits, and its calculation was based on a standard procedure. It was reported that the higher the DII level of a diet (adherence to a more pro-inflammatory diet) the greater was the likelihood of having an older adult hypertension [OR=3.82 (95% CI): 1.24 to 11.71]. Moreover, the higher the level of DII (more pro-inflammatory dietary habits) the greater were the levels of MAP [b-coefficient (95% CI): 7.23 (+1.86 to +12.59)] and PP, [b-coefficient (95% CI): 10.86 (+2.70 to +19.01)]. Diet’s inflammatory potential is related with various components of arterial pressure. Adherence to a more pro-inflammatory diet seems to be associated with increased arterial peripheral resistance and arterial stiffness.

Keywords: dietary inflammatory index, hypertension, mean arterial pressure, elderly

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Authors: S. K. Hemalata, M. N. Shiva Kameshwari

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The present work focusses on anti-inflammatory action of Urginea wightii in-vitro. Urginea wightii is a member of Hyacinthaceae and considered to be wonder plant because of its varied important medicinal properties. The plant is endemic to India, Africa, and Mediterranian regions. Presence of alkaloids, flavonoid-glycosides especially flavonone derivatives are responsible for the strong anti-inflammatory activity of Urginea wightii. In present research work, anti-inflammatory activity of methanol extract of the bulb powder was tested on Male Wistar Rats. In these test animals, inflammation was induced by injecting carrageenan as the irritant to induce paw edema in Wistar rats. Inflammation of Paw edema was treated with both plant extract and Pyrox gel a known synthetic anti-inflammatory drug through external application. The result indicated that anti-inflammatory activity of Urginea wightii extract was almost similar to the synthetic Pyrox gel. This disproves the modern world's scepticism towards the herbal medicines and encourages to rely on natural plant extracts.

Keywords: anti-inflammatory activity, flavonoid-glycosides, Pyrox gel, Urginia wightii

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Authors: Liu Yuhong, Hussen Mansai, Mei Chunli

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Inflammatory discitis is a sterile inflammatary disease that typically presents with abnormalities in two adjacent vertebral bodies and the intervening disk. Diagnosis this disorder is usually difficult and ideal management remains controversial. In this report，we examine a case of inflammatory discitis in a 56 year old female in which treatment with adalimumab ameliorated symptoms. The 56-year-old female patient developed repeatedly inflammatory discitis in the past three years, presenting with severe back pain, an elevated C-reactive protein and erythrocyte sedimentation rate, radiological erosive changes in vertebral and intervertebral disk of the spine. Surgical treatment, antibiotics and non steroidal anti-inflammatory drugs(NSAIDs) were used, but the patient still suffered from recurrent onset of unbearable backache. Three years later from the patient’s first admission，adalimumab was prescribed due to the third occurrence of Anderson lesions, which she had been suffering from for years. Soon after the same day of adalimumab therapy, her symptoms had a dramatic improvement. On the following day she could stand and walk slowly, her CRP and ESR were decreased to nearly normal levels in 4 weeks. Human leukocyte antigen (HLA)-typing analysis revealed a positive result for HLA-B27, the patient’s inflammatory discitis was considered to be associated with spondyloarthropathy.

Keywords: adalimumab, inflammatory discitis, spondyloarthropathy, patient

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Authors: Aroonsri Priprem, Sucharat Limsitthichaikoon, Suttasinee Thappasarapong

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Anthocyanins are natural pigments with effective UV protection but their topical use could be limited due to their physicochemical characteristics. An attempt to overcome such limitations by complexation of 2 major anthocyanin-rich sources, C. ternatea, and Z. mays, for investigation on potential use as topical anti-inflammatory. Cell studies indicate no cytotoxicity of the anthocyanin complex (AC) up to 1 mg/ml tested in HaCaT and human forehead fibroblasts by MTT. Croton oil-induced ear edema in Wistar rats suggests an effective dose of 5 mg/cm2 of AC as a topical anti-inflammatory in comparison to 0.5 mg/cm2 of fluocinolone acetonide. Niosomal encapsulation of the AC significantly prolonged the anti-inflammatory activity particularly at 8 h after topical application (p = 0.0001). The AC was not cytotoxic and its anti-inflammatory and activity was dose-dependent and prolonged by niosomal encapsulation. It has also shown to promote collagen type 1 production in cell culture. Thus, AC could be a potential candidate for topical anti-inflammatory agent from natural resources.

Keywords: anthocyanin complex, ear edema, inflammation, niosomes, skin

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Authors: Soumeya Krimat, Tahar Dob, Aicha Kesouri, Ahmed Nouasri, Hafidha Metidji

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Lavandula antineae Maire is an endemic medicinal plant of Algeria which is traditionally used for the treatment of chills, bruises, oedema and rheumatism. The objective of this study is to evaluate the anti-inflammatory of hydromethanolic aerial parts extract of Lavandula antineae for the first time using carrageenan-paw edema and croton oil-ear odema models. The plant extract, at the dose of 200 mg/kg, showed a significant anti-inflammatory activity (P˂0.05) in the carrageenan induced edema test in mice, showing 80.74% reduction in the paw thikness comparable to that produced by the standard drug aspirin 83.44% at 4h. When it was applied topically at a dosage of 1 and 2 mg per ear, the percent edema reduction in treated mice was 29.45% and 74.76%, respectively. These results demonstrate that Lavandula antineae Maire extract possess remarkable anti-inflammatory activity, supporting the folkloric usage of the plant to treat various inflammatory and pain diseases.

Keywords: lavandula antineae maire, medicinal plant, anti-inflammatory activity, carrageenan-paw edema, croton oil-ear edema

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Authors: A. N. Ukwuani, M. G. Abubakar, S. W. Hassan

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Grewia crenata is used locally in the treatment of fractured bones, wound healing and inflammatory conditions. The anti-inflammatory activity of hydromethanolic extract of G. crenata leaves was investigated using egg albumin induced-hind paw oedema model in albino rat. The extract produced a time-dependent inhibition of egg albumin induced-hind paw oedema at 30th minutes up to 150th minutes in all the groups compared to the control. Significant reduction (p<0.05) of hind paw oedema was observed 150 minutes after egg albumin injection. The percentage inhibition produced by the extract at 200 mg/kg (22.1%) was comparable to that produced by 10 mg/kg indomethacin (24.9%) at the 150th minutes of post-egg albumin injection. Preliminary qualitative phytochemical analysis revealed the presence of saponins, steroids, flavonoids, anthraquinones and glycosides. The results obtained in this study suggest that Grewia crenata can be a potential source of anti-inflammatory agent and validates its use in the treatment of inflammatory conditions.

Keywords: Grewia crenata, anti-inflammatory, hind paw, oedema

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Authors: Somaiya Mateen, Shagufta Moin, Mohammad Owais, Abdul Khan, Atif Zafar

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In rheumatoid arthritis (RA), impaired oxidative metabolism and imbalance between pro-and anti-inflammatory cytokines are responsible for causing inflammation and the degradation of cartilage and bone. The present study was done to evaluate the level and hence the role of reactive oxygen species (ROS) and inflammatory cytokines in the pathogenesis of RA. The present study was performed in the blood of 80 RA patients and 55 age and sex-matched healthy controls. The level of ROS (in 5% hematocrit) and the plasma level of pro-inflammatory cytokines [TNF-α, interleukin-6 (IL-6), IL-22] and anti-inflammatory cytokines (IL-4 and IL-5) were monitored in healthy subjects and RA patients. For evaluating the role of rheumatoid factor (RF) in the pathogenesis of RA, patients were sub-divided on the basis of presence or absence of RF. Reactive species and inflammatory cytokines were correlated with disease activity measure-Disease Activity Score for 28 joints (DAS28). The level of ROS, TNF-α, IL-6 and IL-22 were found to be significantly higher in RA patients as compared to the healthy controls, with the increase being more significant in patients positive for rheumatoid factor and those having high disease severity. On the other hand, a significant decrease in the level of IL-4 and IL-10 were observed in RA patients compared with healthy controls, with the decrease being more prominent in severe cases of RA. Higher ROS (indicative of impaired anti-oxidant defence system) and pro-inflammatory cytokines level in RA patients may lead to the damage of biomolecules which in turn contributes to tissue damage and hence to the development of more severe RA. The imbalance between pro-and anti-inflammatory cytokines may lead to the development of multi-system immune complications. ROS and inflammatory cytokines may also serve as a potential biomarker for assessing the disease severity.

Keywords: rheumatoid arthritis, reactive oxygen species, pro-inflammatory cytokines, anti-inflammatory cytokines

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Authors: Khadse Saurabh, Talele Gokul, Surana Sanjay

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In an endeavor to find a new class of anti-inflammatory agents, a series of novel benzamides (ab1-ab16) were synthesized by utilizing some arylideneoxazolones (az1-az4) having 2-acetyloxyphenyl substitution on their second position. Structures of these synthesized compounds were confirmed by IR, 1H-NMR, 13C NMR, and HRMS. Among the tested benzamide compounds 3ab1, 3ab2, 3ab11, and 3ab16 showed promising anti-inflammatory activity with lessened propensity to cause gastro-intestinal hypermotility and ulceration when compared with standard Indomethacin. Virtual screening was performed by docking the designed compounds into the ATP binding site of COX-2 receptor to predict if these compounds have analogous binding mode to the COX-2 inhibitor.

Keywords: benzamides, anti-inflammatory, gastro-intestinal hypermotility, ulcerogenic activity, docking

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Authors: M. Samsami, A. Hekmatdoost, N. Ebrahimi Daryani, P. Rezanejad Asl

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Ulcerative colitis (UC) is an inflammatory bowel disease in which immune and inflammatory factors are thought to be effective in this disease. Resveratrol is an antioxidant and anti-inflammatory compound. This study determined the effects of resveratrol compound on inflammatory factors in patients with ulcerative colitis. This study was a double-blind randomized clinical trial conducted on 50 patients with UC. Subjects received one capsule daily for 6 wk of either resveratrol (500 mg) or a placebo. Inflammatory factors, anthropometric measures, and IBDQ-9 (Inflammatory Bowel Disease Questionnaire-9) scores were assessed at baseline and at the end of the study. STATA12 software was used for data analysis. No significant differences were found in the background variables between the two groups at baseline. The results indicated that resveratrol supplementation for 6 week significantly decreased plasma levels of TNF-a and hs-CRP and the activity of NF-κB over the placebo group (p<0.001). Significant differences remained after adjustment for vitamin C (p<0.0001). The IBDQ-9 scores increased significantly in the resveratrol group over the placebo group (p<0.001). The findings of this study showed that resveratrol supplementation can be useful in patients with ulcerative colitis.

Keywords: IBD, inflammation, resveratrol, ulcerative colitis

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Authors: Saimir Heta, Ilma Robo, Nevila Alliu, Tea Meta

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Background: Plasma levels of inflammatory markers are the expression of the infectious wastes of existing periodontitis, as well as of existing inflammation everywhere in the body. Materials and Methods: The study consists of the clinical part of the measurement of inflammatory markers of 23 patients diagnosed with chronic periodontitis and the recording of parental periodontal parameters of patient periodontal status: hemorrhage index and probe values, before and 7-10 days after non-surgical periodontal treatment. Results: The level of fibrinogen drops according to the categorization of disease progression, active and passive, with the biggest % (18%-30%) at the fluctuation 10-20 mg/d. Fluctuations in fibrinogen level according to the age of patients in the range 0-10 mg/dL under 40 years and over 40 years was 13%-26%, in the range 10-20 mg/dL was 26%-22%, in the 20-40 mg/dL was 9%-4%. Conclusions: Non-surgical periodontal treatment significantly reduces the level of non-inflammatory markers in the blood. Oral health significantly reduces the potential source for periodontal bacteria, with the potential of promoting thromboembolism, through interaction between thrombocytes.

Keywords: chronic periodontitis, atherosclerosis, risk factor, inflammatory markers

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Authors: Jun Yang, Ching-Liang Hsieh, Yi-Wen Lin

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Chronic inflammatory pain results from peripheral tissue injury or local inflammation to increase the release of protons, histamines, adenosine triphosphate, and several proinflammatory cytokines. Transient receptor potential vanilloid 1 (TRPV1) is involved in fibromyalgia, neuropathic, and inflammatory pain; however, its exact mechanisms in chronic inflammatory pain are still unclear. We investigate the analgesic effect of EA by injecting complete Freund’s adjuvant (CFA) in the hind paw of mice to induce chronic inflammatory pain ( > 14 d). Our results showed that EA significantly reduced chronic mechanical and thermal hyperalgesia in the chronic inflammatory pain model. Chronic mechanical and thermal hyperalgesia was also abolished in TRPV1−/− mice. TRPV1 increased in the dorsal root ganglion (DRG) and spinal cord (SC) at 2 weeks after CFA injection. The expression levels of downstream molecules such as pPKA, pPI3K, and pPKC increased, as did those of pERK, pp38, and pJNK. Transcription factors (pCREB and pNFκB) and nociceptive ion channels (Nav1.7 and Nav1.8) were involved in this process. Inflammatory mediators such as GFAP (Glial fibrillary acidic protein), S100B, and RAGE (Receptor for advanced glycation endproducts) were also involved. The expression levels of these molecules were reduced in EA (electroacupuncture) and TRPV1−/−mice but not in the sham EA group. The present study demonstrated that EA or TRPV1 gene deletion reduced chronic inflammatory pain through TRPV1 and related molecules. In addition, our data provided evidence to support the clinical use of EA for treating chronic inflammatory pain.

Keywords: auricular electric-stimulation, epileptic seizures, anti-inflammation, electroacupuncture

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Authors: Hainan Chen, Jina Qing, Xiao Zhu, Ling Gao, Ampadu O. Jackson, Min Zhang, Kai Yin

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Objective: Editing macrophage activation to dampen inflammatory diseases by promoting the repolarization of inflammatory (M1) macrophages to anti-inflammatory (M2) macrophages is highly associated with mitochondrial respiration. Recent studies have suggested that mitochondrial apolipoprotein A-1 binding protein (APOA1BP) was essential for the cellular metabolite NADHX repair to NADH, which is necessary for the mitochondrial function. The exact role of APOA1BP in the repolarization of M1 to M2, however, is uncertain. Material and method: THP-1-derived macrophages were incubated with LPS (10 ng/ml) or/and IL-4 (100 U/ml) for 24 hours. Biochemical parameters of oxidative phosphorylation and M1/M2 markers were analyzed after overexpression of APOA1BP in cells. Results: Compared with control and IL-4-exposed M2 cells, APOA1BP was downregulated in M1 macrophages. APOA1BP restored the decline in mitochondrial function to improve metabolic and phenotypic reprogramming of M1 to M2 macrophages. Blocking oxidative phosphorylation by oligomycin blunts the effects of APOA1BP on M1 to M2 repolarization. Mechanistically, LPS triggered the hydration of NADH and increased its hydrate NADHX which inhibit cellular NADH dehydrogenases, a key component of electron transport chain for oxidative phosphorylation. APOA1BP decreased the level of NADHX via converting R-NADHX to biologically useful S-NADHX. The mutant of APOA1BP aspartate188, the binding site of NADHX, fail to repair oxidative phosphorylation, thereby preventing repolarization. Conclusions: Restoring mitochondrial function by increasing mitochondrial APOA1BP might be useful to improve the reprogramming of inflammatory macrophages into anti-inflammatory cells to control inflammatory diseases.

Keywords: inflammatory diseases, macrophage repolarization, mitochondrial respiration, apolipoprotein A-1 binding protein, NADHX, NADH

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Authors: Sharareh Sharifi

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In this study, the crude extracts of Virgularia gustavina were examined as antibacterial, antifungal and anti-inflammatory agent. To assess inflammation, Xylene was applied to the ear of mice. The mice of the experimental group were fed with doses of 10 mg/kg, 20 mg/kg, and 40 mg/kg of lipid extract of chloroform and hexane as a separate group and then statistical analysis was performed on the results. Chloroform and hexane extracts of sea pen have strong anti-inflammatory effects even at low doses which is probably due to 54% arachidonic acid. Antibacterial and antifungal effects of hexane and chloroform extracts were measured with MIC and MBC methods and it is shown that chloroform extract has best activity against Staphylococcus aureus on 125 µg/ml doze in MIC method.

Keywords: sea pen (virgularia gustaviana), lipid extract, anti-inflammatory and anti-bacterial activities, fatty acid

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Authors: Yi-Feng Kao, Huey-Jine Chai, Chin-I Chang, Yi-Chen Chen, June-Ru Chen

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Microglia is a macrophage that resides in brain, and overactive microglia may result in brain neuron damage or inflammation. In this study, the phospholipids was extracted from squid skin and manufactured into a liposome (SQ liposome) to mimic apoptotic body. We then evaluated anti-inflammatory effects of SQ liposome on mouse microglial cell line (BV-2) by lipopolysaccharide (LPS) induction. First, the major phospholipid constituents in the squid skin extract were including 46.2% of phosphatidylcholine, 18.4% of phosphatidylethanolamine, 7.7% of phosphatidylserine, 3.5% of phosphatidylinositol, 4.9% of Lysophosphatidylcholine and 19.3% of other phospholipids by HPLC-UV analysis. The contents of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the squid skin extract were 11.8 and 28.7%, respectively. The microscopic images showed that microglia cells can engulf apoptotic cells or SQ-liposome. In cell based studies, there was no cytotoxicity to BV-2 as the concentration of SQ-liposome was less than 2.5 mg/mL. The LPS induced pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were significant suppressed (P < 0.05) by pretreated 0.03~2.5mg/ml SQ liposome. Oppositely, the anti-inflammatory cytokines transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10) secretion were enhanced (P < 0.05). The results suggested that SQ-liposome possess anti-inflammatory properties on BV-2 and may be a good strategy for against neuro-inflammatory disease.

Keywords: apoptotic mimicry, neuroinflammation, microglia, squid processing by-products

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Authors: Somaiya Mateen, Shagufta Moin, Abdul Qayyum, Atif Zafar

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Cytokines and reactive species play an important role in the pathophysiology of rheumatoid arthritis (RA). This study was done to determine the levels of reactive oxygen and nitrogen species (ROS and RNS), inflammatory cytokines and the markers of protein, DNA and lipid oxidation in the blood of RA patients, with the aim to study the antioxidant and anti-inflammatory role of moderate intensity exercises in the management of RA. RA patients were subdivided into two groups- first group (n=30) received treatment with conventional RA drugs while the second group (n=30) received moderate exercise therapy along with the conventional drugs for a period of 12 weeks. The levels of ROS, RNS, inflammatory cytokines and markers of biomolecule oxidation were monitored before and after 12 weeks of treatment. RA patients showed a marked increase in the levels of ROS, RNS, inflammatory cytokines, lipid, protein and DNA oxidation as compared to the healthy controls. These parameters were ameliorated after treatment with drugs alone and exercise combined with drugs, with the amelioration being more significant in patients given drugs along with the moderate intensity exercise treatment. In conclusion, the role of ROS, RNS and inflammatory cytokines in the pathogenesis of RA has been confirmed by this study. These may also serve as potential biomarker for assessing the disease severity. Finally, the addition of moderate intensity exercises in the management of RA may be of great value.

Keywords: rheumatoid arthritis, reactive oxygen species, inflammatory cytokines, moderate intensity exercises

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Authors: Asif Husain, Shah Alam Khan

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Coumarins and flavones are oxygen containing heterocyclic compounds which are present in various biologically active compounds. Both the heterocyclic rings are associated with diverse biological actions, therefore considered as an important scaffold for the design of molecules of pharmaceutical interest. Aim: To synthesize and evaluate the in vivo anti-inflammatory activity of few coumrain and flavone derivatives containing 1,4 dioxane ring system. Materials and methods: Coumarin derivatives (3a-d) were synthesized by reacting 7,8 dihydroxy coumarin (2a) and its 4-methyl derivative (2b) with epichlorohydrin/ethylene dibromide. The flavone derivatives (10a-d) were prepared by using quercetin and 3,4 dihydroxy flavones. Compounds of both the series were also evaluated for their anti-inflammatory, analgesic activity and ulcerogenicity in animal models by reported methods. Results and Discussion: The structures of all newly synthesized compounds were confirmed with the help of IR, 1H NMR, 13C NMR and Mass spectral studies. Elemental analyses data for each element analyzed (C, H, N) was found to be within acceptable range of ±0.4 %. Flavone derivatives, but in particular quercetin containing 1,4 dioxane ring system (10d) showed better anti-inflammatory and analgesic activity along with reduced gastrointestinal toxicity as compared to other synthesized compounds. The results of anti-inflammatory and analgesic activities of both the series are comparable with the positive control, diclofenac. Conclusion: Compound 10d, a quercetin derivative, emerged as a lead molecule which exhibited potent anti-inflammatory and analgesic activity with significant reduced gastric toxicity.

Keywords: analgesic, anti-inflammatory, 1, 4 dioxane, coumarin, flavone

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Authors: Shirajul Islam Khan, Muhammad Ashraful Alam Bhuiyan, Syeda Tania Begum

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Introduction: Acne vulgaris is one of the most common dermatologic conditions and affects the vast majority of people at some point during their lifetime, so effective treatment is of major importance. The failure of usual treatment modalities, teratogenic effects with some severe side effects, and resistance to P.Acne by Retinoides have been focusing on new therapeutic options for the treatment of acne. More recently, pulsed dye laser therapy has been reported to reduce acne lesion counts. The negligible morbidity of these treatment modalities and some other benefits of subsequent acne scar management lead this therapy more attractive. Objective: The objective of this study is to assess the efficacy and safety of pulsed dye laser therapy in the treatment of inflammatory acne vulgaris. Materials and Methods: A prospective clinical trial was done in the Department of Dermatology and Venereology, Combined Military Hospital (CMH), Dhaka, to find out the role of pulse dye laser in the treatment of inflammatory acne vulgaris. The study was carried out with 60 patients with mild to moderate acne vulgaris, and those were treated with pulsed dye laser therapy at baseline and after 4, 8, and 12 weeks. Results: Among 60 patients with inflammatory acne, 42(70%) were in the age group of less than 20 years, and 36(60%) were female. Regarding the number of inflammatory lesions, the baseline mean number (± SD) was 12.77 ± 4.01; after 4 weeks of treatment of inflammatory acne by pulsed dye laser was 7.80 ± 4.11; after 8 weeks of treatment, 6.10 ± 4.03 and after 12 weeks of treatment was 4.17 ± 4.02. After 4 weeks of treatment by pulse dye laser, the level of improvement was excellent at 3.3%, good at 10%, fair at 60%, and poor at 26.7%; after 8 weeks of treatment, excellent was 13.3%, good was 46.7%, the fair was 30% and poor 10% and after 12 weeks of treatment, excellent was 56.7%, good 13.3%, fair 23.3% and poor 6.7%. Regarding safety level, out of 60 patients of inflammatory acne vulgaris treated by pulsed dye laser, about 52(86.7%) patients did not observe any side effects. Conclusions: On the basis of the study results, it can be concluded that pulsed-dye laser is highly effective and well tolerated by patients in the treatment of inflammatory acne.

Keywords: pulsed-dye laser, inflammatory acne, acne vulgaris, retinoids

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Authors: Akhmadjon Sultanov, Eun-Ho Lee, Hye-Jin Park, Young-Je Cho

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This study tested the anti-inflammatory effect of wild indigo (Baptisia tinctoria) root in Raw 264.7 cells. We prepared two extracts of B. tinctoria; one in water and the other in 50% ethanol. Then we evaluated the toxicities of the B. tinctoria root extracts at 10 to 100 mg mL-1 concentrations in raw 264.7 cells and observed 80% cell viability. The anti-inflammatory effect of B. tinctoria root extract in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells were observed with concentrations at 10, 30, and 50 μg mL-1. The results showed that 77.27-66.82% of nitric oxide (NO) production was inhibited by 50 μg mL-1 B. tinctoria root extract. The protein expression of Inducible NO synthase (iNOS) expression dramatically decreased by 93.14% and 52.65% in raw 264.7 cells treated with water and ethanol extracts of B. tinctoria root, respectively. Moreover, cyclooxygenase-2 (COX-2) protein expression decreased by 42.85% and 69.70% in raw 264.7 cells treated with water and ethanol extracts of B. tinctoria root, respectively. Furthermore, the mRNA expression of pro-inflammatory markers, such as tumor necrosis factor-alpha, interleukin-1β, interleukin-6, monocyte chemoattractant protein-1, and prostaglandin E synthase 2, was significantly suppressed in a concentration-dependent manner. Additionally, the B. tinctoria root extracts effectively inhibited enzymes involved in physiological activities. The B. tinctoria root extracts showed excellent anti-inflammatory effects and can be used as a functional material for biological activities.

Keywords: cytokine, macrophage, pro-inflammatory, protein expression, real-time PCR

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Authors: Parinaz Tavakoli Zaniani, Dimitrios Balomenos

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Mitochondrial reactive oxygen species (mROS) play a crucial role in macrophage pro-inflammatory activation, although a detailed understanding of the mechanism and kinetics by which mROS drive signaling molecules is still lacking. In general, it is thought that NF-κB activation drives mROS and general ROS production. Here, We performed a detailed kinetic analysis of mROS production during macrophage activation. We found early mROS generation after LPS (lipopolysaccharide) stimulation. Remarkably as early as 5 minutes, mROS signaling promoted initial NF-κB, MAPK activation and pro-inflammatory cytokine production, as established through inhibition or quenching of mROS. On the contrary, NF-κB inhibition had no effect on mROS production. Our findings point to a mechanism by which mROS increase TRAF-6 ubiquitination and, thus NF-κB activity. mROS inhibition reduced LPS-induced lethality in an in vivo septic shock model by controlling pro-inflammatory cytokine production. Overall, our research provides novel insights into the role of mROS as a primary messenger in the pathway of macrophage and as a regulator of inflammatory responses. We found that early mROS production promotes initial NF-κB, and MAPK activation by regulating TRAF-6 ubiquitination and that mROS inhibition can reduce LPS-induced inflammatory cytokines and lethality in a septic shock model. These findings might lead to novel immunotherapeutic strategies targeting early mROS production and control of extreme inflammation in the context of sepsis and other inflammatory diseases.

Keywords: mitochondria, reactive oxygen species, nuclear factor κB, lipopolysaccharide, macrophages

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Authors: Gina Cecilia Pistol, Loredana Calin, Mariana Stancu, Veronica Chedea, Ionelia Taranu

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Inflammatory-associated diseases have an increased trend in the past decades. The pharmacological strategies aimed to treat these inflammatory diseases are very expensive and with non-beneficial results. The current trend is to find alternative strategies to counteract or to control inflammatory component of diseases. The grape by-products either seeds or pomace are rich in bioactive compounds (e.g. polyphenols) which may be beneficial in prevention of inflammation associated with cancer progression and other pathologies with inflammatory component. The in vivo models are very useful for studying the immune and inflammatory status. The domestic pig (Sus scrofa domesticus) is related to human from anatomic and physiologic point of view, representing a feasible model for studying the human inflammatory pathologies. Starting from these data, we evaluated the effect of a diet containing 5% grape seed cakes (GS) on piglets blood biochemical parameters and immune pro- and anti-inflammatory biomarkers (IL-1 beta, IL-8, TNF-alpha, IL-6, IFN-gamma, IL-10, IL-4) in spleen and lymph nodes. 12 weaned piglets were fed for 30 days with a control diet or an experimental diet containing 5% GS. At the end of trial, plasma and tissue samples (spleen and lymph nodes) were collected and the biochemical and inflammatory markers were analysed by using biochemistry analyser and ELISA techniques. Our results showed that diet included 5% GS did not influence the health status determined by plasma biochemical parameters. Only a tendency for a slight increase of the biochemical parameters associated with energetic profile (glucose, cholesterol, triglycerides) was observed. Also, GS diet had no effect on pro- and anti-inflammatory cytokines content in spleen and lymph nodes tissue. Further experiments are needed in order to investigate other rate of dietary inclusion which could provide more evidence about the effect of grape bioactive compounds on pigs used as animal model.

Keywords: animal model, inflammation, grape seed by-product, immune organs

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Authors: T. E. Tshikalange, B. C. Mophuting

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Traditional medicine often consists of complex ingredients prepared from a mixture of plant species. These herbal mixtures are used in the treatment of various ailments such as sexually transmitted diseases including HIV. The present study was carried out to determine the biological activities of the herbal mixture used traditionally in the treatment of sexually transmitted diseases. This herbal mixture consists of four plant species from families Asteraceae, Bignoniaceae, Fabaceae, and Myrtaceae. Five crude extracts (hexane, dichloromethane, methanol, water and boiled) of the herbal mixture were investigated for anti-gonococcal, anti-inflammatory, and reverse transcriptase activities. The anti-inflammatory activity of the plant extracts was determined by measuring the extract inhibitory effect on the pro-inflammatory enzyme lipoxygenase. The extracts were also tested for anti-HIV activity against recombinant HIV-1 enzyme using non-radioactive HIV-RT colorimetric assay. The boiled extract exhibited good anti-inflammatory activity with an IC₅₀ of 87 µg/ml compared to that of the positive control quercetin (IC₅₀= 92 µg/ml). All the other extracts showed little or no activity. Hexane extract was the only extract that showed reverse transcriptase extract inhibitory effect with an IC₅₀ of 74 µg/ml. Anti-gonococcal and cytotoxicity investigations are underway. The preliminary results support the use of herbal mixture by traditional healers.

Keywords: sexually transmitted diseases, lipoxygenase, anti-inflammatory, herbal mixture

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Authors: Khairy M. A. Zoheir

Abstract:

One of the most severe complications of Rheumatoid arthritis is delayed recovery. lipoic acid possesses antioxidant, hypoglycemic, and anti-inflammatory activity. In the present study, the effects of lipoic acid was investigated on the key mediators of Rheumatoid arthritis, namely, CD4+CD25+ T cell subsets, GITR expressing cells, CD4+CD25+Foxp3+ regulatory T (Treg) cells, T-helper-17 (Th17) cells, and pro-inflammatory cytokines Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumor Necrosis Factor- α (TNF-α)] through flow-cytometry and qPCR analyses. Lipoic acid treated mice showed a significant decrease in the Rheumatoid arthritis, the frequency of GITR-expressing cells, and Th1 cytokines (IL-17A, TNF-αand Interferon- γ (IFN-γ) compared with positive and negative controlled mice. Lipoic acid treatment also down regulated the mRNA expression of the inflammatory mediators compared with the Rheumatoid arthritis mouse model and untreated mice. The number of Tregs also found to be significantly upregulated in lipoic acid treated mice. Our results were confirmed by the histopathological examination. This study showed the beneficial role of lipoic acid in promoting a well-balanced tool for therapy Rheumatoid arthritis.

Keywords: lipoic acid, chemokines, inflammatory, rheumatoid arthritis

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Authors: Zohreh Afsharmand, Sokhanguei Yahya

Abstract:

A growing body of literature suggests that that low-grade systemic inflammation associated to obesity plays a key role in the pathogenic mechanism of several disorders. In this study, the effect of 6 weeks aerobic training on IL-6 and IL-1B as inflammatory cytokine were investigated in adult obese women. For this purpose, 26 sedentary adult obese women were divided into exercise and control groups (n=12). Pre and post training of mentioned cytokines were measured in two groups. Student’s t-tests for paired samples were performed to determine whether there were significant within-group changes in the outcomes. A p value less than 0.05 was considered statistically significant. There were no statistically significant differences between the exercise and control groups with regard to anthropometrical markers or inflammatory cytokines. Despite the significant decrease in all anthropometrical markers, no significant differences were found in serum IL-6 and IL-1B by aerobic training with compared to baseline. Our findings indicate that aerobic training intervention for a short time is not associated with the anti-inflammatory property in obese women.

Keywords: aerobic training, cytokine, inflammation, obesity

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Authors: Khairy Mohamed Abdalla Zoheir

Abstract:

One of the most severe complications of Rheumatoid arthritis is delayed recovery. lipoic acid possesses antioxidant, hypoglycemic, and anti-inflammatory activity. In the present study, the effects of lipoic acid were investigated on the key mediators of Rheumatoid arthritis, namely, CD4+CD25+ T cell subsets, GITR expressing cells, CD4+CD25+Foxp3+ regulatory T (Treg) cells, T-helper-17 (Th17) cells and pro-inflammatory cytokines Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumor Necrosis Factor- α (TNF-α)] through flow-cytometry and qPCR analyses. Lipoic acid-treated mice showed a significant decrease in Rheumatoid arthritis, the frequency of GITR-expressing cells, and Th1 cytokines (IL-17A, TNF-αand Interferon- γ (IFN-γ) compared with positive and negative controlled mice. Lipoic acid treatment also downregulated the mRNA expression of the inflammatory mediators compared with the Rheumatoid arthritis mouse model and untreated mice. The number of Tregs was also found to be significantly upregulated in lipoic acid-treated mice. Our results were confirmed by the histopathological examination. This study showed the beneficial role of lipoic acid in promoting a well-balanced tool for the therapy of Rheumatoid arthritis.

Keywords: lipoic acid, inflammatory markers, rheumatoid arthritis, qPCR

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Authors: Anna Pick Kiong Ling, Jia May Chin, Rhun Yian Koh, Ying Pei Wong

Abstract:

Background: Uncontrolled inflammation may cause serious inflammatory diseases if left untreated. Non-steroidal anti-inflammatory drug (NSAIDs) is commonly used to inhibit pro-inflammatory enzymes, thus, reduce inflammation. However, long term administration of NSAIDs leads to various complications. Medicinal plants are getting more attention as it is believed to be more compatible with human body. One of them is a flavonoid-containing medicinal plants, Strobilanthes crispus which has been traditionally claimed to possess anti-inflammatory and antioxidant activities. Nevertheless, its anti-inflammatory activities are yet to be scientifically documented. Objectives: This study aimed to examine the anti-inflammatory activity of S. crispus by investigating its effects on intracellular oxidative stress and prostaglandin E₂ (PGE₂) levels. Materials and Methods: In this study, the Maximum Non-toxic Dose (MNTD) of methanol extract of both leaves and stems of S. crispus was first determined using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenytetrazolium Bromide (MTT) assay. The effects of S. crispus extracts at MNTD and half MNTD (½MNTD) on intracellular ROS as well as PGE₂ levels in 1.0 µg/mL LPS-stimulated RAW 264.7 macrophages were then be measured using DCFH-DA and a competitive enzyme immunoassay kit, respectively. Results: The MNTD of leaf extract was determined as 700µg/mL while for stem was as low as 1.4µg/mL. When LPS-stimulated RAW 264.7 macrophages were subjected to the MNTD of S. crispus leaf extract, both intracellular ROS and PGE₂ levels were significantly reduced. In contrast, stem extract at both MNTD and ½MNTD did not significantly reduce the PGE₂ level, but significantly increased the intracellular ROS level. Conclusion: The methanol leaf extract of S. crispus may possess anti-inflammatory properties as it is able to significantly reduce the intracellular ROS and PGE₂ levels of LPS-stimulated cells. Nevertheless, further studies such as investigating the interleukin, nitric oxide and cytokine tumor necrosis factor-α (TNFα) levels has to be conducted to further confirm the anti-inflammatory properties of S. crispus.

Keywords: anti-inflammatory, natural products, prostaglandin E2, reactive oxygen species

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Authors: Yonghwa Lee, Yoon Suk Kim, Yongsub Yi

Abstract:

This study was to confirm the effects of anti-melanogenesis and anti-inflammatory effects from Opuntia humifusa fruit and stem extracts. A potent anti-oxidant activity was shown from the leaf extract at IC50 value of 38.33±1.07 μg/mL and fruit extract at IC50 value of 40.23±2.21 μg/mL by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Also, phenolic contents were confirmed total phenolic assay by high performance liquid chromatography (HPLC). Fraction of taxifolin from leaf extract was identified using HPLC and gas chromatography/mass spectrometry. The extracts of Opuntia humifusa fruit and stem were confirmed about toxicity effect in B16 F1 by cell viability. Melanin contents were decreased. Opuntia humifusa fruit and stem extracts had a positive effect of melanin synthesis inhibition for skin whitening. In investigating the anti-inflammatory activities of Opuntia humifusa, the results of cell viability indicated that taxifolin did not show cytotoxicity on RAW264.7 cells at 500 μM of concentration. The results show that taxifolin inhibited lipopolysaccharide (LPS)-induced production of Nitrite oxide (NO). In addition, taxifolin indicated the inhibition of lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) -α and interleukin (IL) -6 productions by cytokine assay and cyclooxygenase (COX)-2 expression by western blot analysis, meaning that taxifolin had a significant anti-inflammatory effect. Our results suggested that taxifolin from Opuntia humifusa has anti-melanogenesis and anti-inflammatory activities.

Keywords: anti-melanogenesis, anti-inflammatory, Opuntia humifusa, taxifolin

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