Natural Anti-inflammatory Agent Research Articles

Mechanistic perspective of the oxido‐immunopathologic resolution property of kolaviron in mice influenza pneumonitis

Implicated in influenza-associated pathology are innate defence overzealousness and unabated secretion of oxidative tissue-sensitive antimicrobial agents. At different time points, mice were pre-treated with kolaviron (400 mg/kg), a natural antioxidant and anti-inflammatory agent, and subsequently challenged with 2 LD50 influenza A/H3N2/Perth/16/09 virus. After euthanasia at day 6, blood, lungs, liver and spleen were collected and processed for biochemical, immunohistochemical and flow cytometric assessment of redo-inflammatory imbalance, cytokine storm indices and T helper 1 host response. Previously kolaviron was reported to delay mortality onset, improve morbidity and attenuate myeloperoxidase activity and nitric oxide production with minimal impact on viral clearance. This study additionally confirmed nitric oxide, but not hydrogen peroxide, as the major culprit implicated in influenza virus-induced oxido-pathology. Systemic effect of the sustained inflammation and nitrosative stress was more prominent in the spleen and lung than in the liver of mice infected with A/H3N2/Perth/16/09. Influential to immunopathology was heightened pulmonary expression of IL-1β, RANTES, IL-10, MCP-1, NF-κB, iNOS and COX-2. However, kolaviron combated the influenza-established nitrative stress, reversed the elicited cytokine storm and restored the oxidized environment to a reductive milieu. Our data also suggest that kolaviron administration early in infection may foster CD4+ response. These data indicate that kolaviron may confer disease-dwindling properties during acute influenza infection via a system-wide protective approach involving multiple targets especially at the early stage of the infection.

5,7-Dihydroxyflavone Analogues May Regulate Lipopolysaccharide-Induced Inflammatory Responses by Suppressing IκBα-Linked Akt and ERK5 Phosphorylation in RAW 264.7 Macrophages.

We studied the anti-inflammatory activity of twelve 5,7-dihydroxyflavone analogues in lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. We found that chrysin (1) and 4′-methoxytricetin (9) showed relatively significant anti-inflammatory activity and low cytotoxicity. Moreover, 1 and 9 recovered the expression levels of iNOS and COX2, as well as those of the intracellular inflammatory mediators IL-1β and IL-6, which were upregulated by LPS stimulation. In addition, 1 and 9 actively regulated the phosphorylation of IκBα, leading to the activation of NFκB. Phosphorylation of Akt and ERK5 (upstream of NFκB) by LPS stimulation was significantly regulated by 1 and 9, as well as by BIX 02189 and LY 294002, which are phosphorylation inhibitors of ERK5 and Akt, respectively. The results suggest that compounds 1 and 9 may suppress the levels of iNOS and COX2 by regulating phosphorylation of Akt, ERK5, and IκBα and thus NFκB-related signaling pathways, resulting in anti-inflammatory effects in the cells. Because 1 and 9 showed low cytotoxicity and regulated both PGE2 and NO production caused by inflammatory responses, they may hold promise as natural anti-inflammatory agents.

Anti-inflammatory activity of 3β-hydroxycholest-5-en-7-one isolated from Hippocampus trimaculatus leach via inhibiting iNOS, TNF-α, and 1L-1β of LPS induced RAW 264.7 macrophage cells.

Hippocampus trimaculatus leach has been widely used in beverage and herbal medicine fabrication. However, the study of the molecular mechanism of its bioactivity especially the anti-inflammatory activity is still scanty. In the present study, the pure HEO isolated from the dried Hippocampus trimaculatus leach was firstly found to have anti-inflammatory activity in vitro. The molecular mechanism of the anti-inflammatory activity was detailed using the lipopolysaccharide (LPS) stimulated RAW 264.7 macrophage cells, suggesting that the HEO can significantly suppress the inflammatory factors of nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and interleukin (1L)-1β (1L-1β). Cellular signaling analyses demonstrated that the HEO downregulated the NF-κB and extracellular signal-regulated kinase (ERK) of mitogen-activated protein kinase (MAPK) signaling pathways. All the results suggested that the HEO is a potential natural anti-inflammatory agent.

Response of COX2/PGE2 Inflammatory Pathway to Brown Seaweed Extract in Rats Exposed to Gamma Radiation

Background: Systemic inflammation due to radiation exposure has been identified in a biological system by certain metabolic and behavioral disorders. These anarchies mostly mediated under a regulation of cyclooxygenase 2 (COX2) induced production of an inflammatory mediator prostaglandin E2 (PGE2). Aim: This study was undertaken to investigate the anti-inflammatory impact of brown sea weed extract (BSWE) against induction of COX2/PGE2 inflammatory pathway in gamma-irradiated rats. Rats were orally administrated with BSWE (27 mg/kg body weight/day) for 7 consecutive days before exposure to 8 Gy fractionated gamma radiation (2 Gy × 4; every 3 days). Treatment with BSWE was extended along with and in-between irradiation doses for another 14 successive days. Our data demonstrated that the administration of BSWE to rats exposed to gamma radiation, following the regimen suggested, significantly neutralize the changes induced in the inflammatory molecules COX2, PGE2, tumor necrosis alpha (TNF-α), and nitric oxide (NO). In addition, it adjusted significantly the cellular redox tone via regulation of changes induced in malondialdehyde (MDA) reduced glutathione (GSH), superoxide dismutase (SOD) catalase (CAT) and xanthine oxidoreductase system (XOR). Credibly, from the results emerged in this study, it could be suggested that BSWE has substantial anti-inflammatory activities and gamma radiation protection capabilities. It is recommended to include BSWE in the treatment strategy of various inflammatory diseases especially cancer as a safe natural anti-inflammatory agent.

Bioactivity-guided isolation of anti-inflammatory triterpenoids from the sclerotia of Poria cocos using LPS-stimulated Raw264.7 cells

Poria cocos Wolf (Polyporaceae) has been used as a medicinal fungus to treat various diseases since ancient times. This study aimed to investigate the anti-inflammatory chemical constituents of the sclerotia of P. cocos. Based on bioassay-guided fractionation using lipopolysaccharide (LPS)-stimulated Raw264.7 cells, chemical investigation of the EtOH extract of the sclerotia of P. cocos resulted in the isolation and identification of eight compounds including six triterpenoids, namely poricoic acid A (1), 3-O-acetyl-16α-hydroxydehydrotrametenolic acid (2), polyporenic acid C (3), 3β-hydroxylanosta-7,9(11),24-trien-21-oic acid (4), trametenolic acid (5), and dehydroeburicoic acid (6), as well as (−)-pinoresinol (7) and protocatechualdehyde (8). The structures of the isolated compounds were determined by spectroscopic analysis, including 1H and 13C NMR spectra, and LC/MS analysis. The anti-inflammatory activities of the isolates were evaluated by estimating their effect on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated Raw264.7 as well as on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Compounds 1–5 inhibited NO production and iNOS expression in LPS-stimulated Raw264.7 cells. Among them, compound 1 exerted the highest anti-inhibitory activity and reduced PGE2 levels via downregulation of COX-2 protein expression. The findings of this study provide experimental evidence that the sclerotia of P. cocos are a potential source of natural anti-inflammatory agents for use in pharmaceuticals and functional foods. Furthermore, the most active compound 1, seco-lanostane triterpenoid, could be a promising lead compound for the development of novel anti-inflammatory agents.

Bergapten exerts inhibitory effects on diabetes-related osteoporosis via the regulation of the PI3K/AKT, JNK/MAPK and NF-κB signaling pathways in osteoprotegerin knockout mice.

Diabetes, as a serious metobolic disorder, poses global threat to human health. It is estimated that over 50 million individuals are already affected by diabetes. Currently, diabetes-related osteoporosis has been a research hotspot due to its high incidence rate in older individuals. Osteoprotegerin, as an important protein for the prevention of osteoporosis, has been proven to be key to the suppression of osteoporosis. Hence, the loss of function of osteoprotegerin may promote the development of osteoporosis. Bergapten, as a natural anti-inflammatory and anti-tumor agent isolated from bergamot essential oil, other citrus essential oils, and grapefruit juice, has been proven to have the ability to attenuate a number of metabolic disorders. In view of these findings, in this study, we used a high-fat diet to construct a mouse model of diabetes-related osteoporosis and a mouse model of diabetes-related osteoporosis using osteoprotegerin knockout mice. Enzyme-linked immunosorbent assay (ELISA), qPCR, western blot analysis, immunohistochemical assay, H&E staining, Oil Red O staining, Masson's staining and other biochemical analyses were used to evaluate the related signaling pathways involved in the development of diabetes-related osteoporosis. We also examined the role of osteoprotegerin in the activation of these pathways and in the development of osteoporosis, as well as the protective effects of bergapten against diabetes-related osteoporosis and on the activation of related signaling pathways. Our results revealed that in diabetes-related osteoporosis, the phosphoinositide 3-kinase (PI3K)/AKT, c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways were activated and the expression levels of related indicators were increased. At the same time, osteoprotegerin knockout further promoted the activation of these pathways. By contrast, bergapten exerted effects similar to those of osteoprotegerin. Bergapten exhibited the ability to significantly inhibit RANKL-RANK signaling transduction, and to suppress the activation of the PI3K/AKT, JNK/MAPK and NF-κB signaling pathways, thus protecting trabecular structure and decreasing osteoclastogenic differentiation.

NITRIC OXIDE INHIBITORY ACTIVITY OF STRYCHNOS SPINOSA (LOGANIACEAE) LEAF EXTRACTS AND FRACTIONS.

Background:The study was aimed at determining the anti-inflammatory activity of fractions and extracts obtained from Strychnos spinosa leaves on a mediator of inflammation nitric oxide (NO).Materials and Methods:Leaves were extracted with acetone and separated into fractions with different polarities by solvent-solvent fractionation. The Griess assay was used to determine the nitric oxide (NO) inhibitory activity. Cellular toxicity was determined by “using the MTT reduction assay”.Results:With the exception of the ethyl acetate fraction which had an IC50 >750 μg/mL, all extracts and fractions had significant nitric oxide-inhibitory activity. The most active being the water fraction, chloroform fraction and the dichloromethane/methanol extracts with IC50 values of 88.43 μg/mL, 96.72 μg/mL and 115.62 μg/mL, respectively. The extracts and fractions had low cytotoxicity on macrophage U937 cell lines.Conclusion:Extracts and fractions of Strychnos spinosa leaves may be promising sources of natural anti-inflammatory agents. Findings obtained from this study showed that Strychnos spinosa leaves possess promising anti-inflammatory action and could be used in the treatment of inflammation-related conditions.

Anti-inflammatory, antioxidant and anti-Mycobacterium tuberculosis activity of viridiflorol: The major constituent of Allophylus edulis (A. St.-Hil., A. Juss. & Cambess.) Radlk.

Ethnopharmacological relevanceThe leaves of Allophylus edulis (A. St.-Hil., A. Juss. & Cambess.) Radlk. (Sapindaceae) are traditionally used as a natural anti-inflammatory agent; however, there are no scientific studies demonstrating its activity essential oil. The content of essential oil in A. edulis may be the chemical basis to explain its ethnobotanical uses, since infusions of this plant are used to treat inflammation in the traditional medicine in Brazil. Aim of the studyThis study evaluated the anti-inflammatory, antioxidant and anti-mycobacterial activities of the essential oil (EOAE) and viridiflorol, its main compound. Material and methodsEssential oil from fresh leaves of A. edulis (EOAE) was obtained by hydrodistillation in a Clevenger-type apparatus. Forty-one compounds, accounting for 99.10% of the oil, were identified by gas chromatography-mass spectrometry (GC–MS). The major constituent of the oil was viridiflorol (30.88%). Additionally, the essential oil and viridiflorol were evaluated using an in vitro test against Mycobacterium tuberculosis and in 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays. Both EOAE (30 and 100mg/kg) and viridiflorol (3 and 30mg/kg) by oral administration were assayed in carrageenan-induced mice paw oedema and pleurisy using subcutaneous injection of dexamethasone (0.5mg/kg) as the positive control. ResultsEOAE and viridiflorol displayed moderate in vitro activity in the M. tuberculosis assay. In all tests, EOAE and viridiflorol showed moderate antioxidant activity compared with reference standards. Both EOAE and viridiflorol showed significant inhibition in the carrageenan-induced mice paw oedema via oral administration of the oil (30 and 100mg/kg), compound (3 and 30mg/kg), and subcutaneous injection of dexamethasone (0.5mg/kg, reference drug). Also EOAE and viridiflorol significantly inhibited carrageenan (Cg) induced pleurisy, reducing the migration of total leucocytes in mice by 62±5% (30mg/kg of oil), 35±8% (100mg/kg of oil), 71±5% (3mg/kg of viridiflorol) and 57±3% (30mg/kg of viridiflorol). ConclusionFor the first time, the results from this work corroborate the literature, showing that A. edulis can be used as a natural anti-inflammatory agent. Moreover, both EOAE and viridiflorol exhibited biological activities, such as anti-mycobacterial, anti-inflammatory and antioxidant activity.

The protective effects of resveratrol on social stress-induced cytokine release and depressive-like behavior

Social stress is a risk factor for psychiatric disorders, however only a subset of the population is susceptible while others remain resilient. Inflammation has been linked to the pathogenesis of psychosocial disorders in humans and may underlie these individual differences. Using a resident-intruder paradigm capable of revealing individual differences in coping behavior and inflammatory responses, the present study determined if resveratrol (RSV; 0, 10, 30mg/kg/day) protected against persistent stress-induced inflammation in socially defeated rats. Furthermore, the antidepressant efficacy of RSV was evaluated using the sucrose preference test. Active coping rats were characterized by more time spent in upright postures and increased defeat latencies versus passive coping rats. Five days after defeat, flow cytometry revealed enhanced stimulation of proinflammatory proteins (IL-β, TNF-α) in spleen cells of passive rats as compared to active coping and controls, an effect that was blocked by both doses of RSV. Furthermore, only passive coping rats exhibited increased proinflammatory proteins (IL-1β, TNF-α, GM-CSF) in the locus coeruleus (LC), a noradrenergic brain region implicated in depression. Notably, only 30mg/kg RSV blocked LC neuroinflammation and importantly, was the only dose that blocked anhedonia. Alternatively, while stress had minimal impact on resting cytokines in the dorsal raphe (DR), RSV dose-dependently reduced DR cytokine expression. However, this did not result in changes in indoleamine 2,3-dioxygenase activity or serotonin levels. Taken together, these data suggest that social stress-induced depressive-like behavior evident in passive coping rats may be driven by stress-induced neuroinflammation and highlight natural anti-inflammatory agents to protect against social stress-related consequences.

10-DHGD ameliorates cisplatin-induced nephrotoxicity in rats.

10-DHGD exhibited a marked anti-inflammatory potential, alleviated to a great extent of nephrotoxicity and renal fibrosis induced by cisplatin.

Vasoactive intestinal peptide dampens formyl-peptide-induced ROS production and inflammation by targeting a MAPK-p47phox phosphorylation pathway in monocytes.

Reactive oxygen species (ROS) produced by the phagocyte NADPH oxidase (NOX2) are required for microbial clearance; however, when produced in excess they exacerbate inflammatory response and injure surrounding tissues. NOX2 is a multicomponent enzyme composed of membrane-associated cytochrome b588 and cytosolic components p47phox, p67phox, p40phox, and rac1/2. We investigated whether vasoactive intestinal peptide (VIP), an endogenous immune-modulatory peptide, could affect ROS production by NOX2 in primary human phagocytes. VIP did not modulate basal ROS production by phagocytes, but it inhibited monocyte and not neutrophil ROS production in response to the bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (fMLF). The action of VIP was essentially mediated by high-affinity G-protein coupled receptors VPAC1 as its specific agonist, [ALA11,22,28]VIP, mimicked VIP-inhibitory effect, whereas the specific VPAC1 antagonist, PG97-269, blunted VIP action. Further, we showed that VIP inhibited fMLF-induced phosphorylation of ERK1/2 (extracellular signal-regulated kinase 1/2), p38MAPK (p38 mitogen-activated protein kinase) pathways, and phosphorylation of p47phox on Ser345 residue. Also, VIP exerted an anti-inflammatory effect in a model of carrageenan-induced inflammation in rats. We thus found that VIP exerts anti-inflammatory effects by inhibiting the "MAPK-p47phox phosphorylation-NOX2 activation" axis. These data suggest that VIP acts as a natural anti-inflammatory agent of the mucosal system and its analogs could be novel anti-inflammatory molecules.

In vitro immunomodulatory activity and in vivo anti-inflammatory and analgesic potential with gastroprotective effect of the Mediterranean red alga Laurencia obtusa

Context: Red algae have been recognized as a rich natural source of compounds possessing interesting biological and pharmacological activities.Objective: This work investigates anti-inflammatory, analgesic and gastroprotective activities of MeOH/CH2Cl2 crude extract and its fractions F1 (50% MeOH) and F2 (80% MeOH) from the whole alga plant Laurencia obtusa Hudson (Rhodomelaceae).Materials and methods: Anti-inflammatory activity was evaluated in vitro using cytometric bead array (CBA) technology to follow up the secretion of tumour necrosis factor alpha (TNF-α) in lipopolysaccharide activated THP-1 monocytic cells at doses of 10–250 μg/mL and in vivo using carrageenan-induced paw oedema in Wistar rats at doses of 25, 50, 100 and 200 mg/kg. Crude extract and fractions were tested at the doses of 25, 50, 100 and 200 mg/kg for peripheral and central analgesic activity by acetic acid-induced writhing test and hot-plate method, respectively, in Swiss albino mice. Gastroprotective activity was evaluated using HCl/ethanol-induced gastric ulcer test in rats at doses of 25, 50, 100 and 200 mg/kg.Results: Crude extract, F1 and F2 showed an interesting inhibition of TNF-α secretion with IC50 values of 25, 52 and 24 μg/mL, respectively, and a significant anti-inflammatory activity in vivo (p < 0.01), 3 h after carrageenan injection, the oedema inhibition was 55.37%, 52.18% and 62.86%, respectively, at the dose of 100 mg/kg. Furthermore, they showed a significant peripheral analgesic activity with 53.79%, 55.92% and 57.37% (p < 0.01) of writhing inhibition, respectively. However, no significant activity was found in the hot-plate test. An interesting gastroprotective effect was observed with crude extract and its fractions F1 and F2 with a gastric ulcer inhibition of 65.48%, 77.42% and 81.29%, respectively, at the dose of 50 mg/kg.Discussion and conclusion: These results suggest that L. obtusa might be used as a potential source of natural anti-inflammatory and analgesic agents with gastroprotective effect.

Anti-Lipoxygenase Activity of Leaf Gall Extracts of Terminalia chebula (Gaertn.) Retz. (Combretaceae).

Lipoxygenase (LOX) inhibitors are the promising therapeutic target for treating a wide spectrum of inflammatory-related diseases such as cancer, asthma, lymphoma, leukemia, and autoimmune disorders. In the present study, the photochemical constituents and the anti-LOX potential of leaf galls of Terminalia chebula are evaluated to exemplify its further potential development as medicine. Extracts of T. chebula galls were tested for anti-LOX activity using linoleic acid as substrate and lipoxidase as an enzyme and also the total content of polyphenols with phytochemical analysis of the extract were determined. The presence of highest total phenolic and flavonoid content of 141 ± 2.2 mg of gallic acid equivalent/g d.w and 125 ± 1.4 mg of quercetin equivalent/g d.w and maximal LOX inhibitory activity (52.67%) at 800 μg/mL concentrations were identified in the ethanolic extracts of leaf galls of T.chebula. The higher LOX inhibitory activity was positively correlated to the high content of total polyphenols/flavonoids. The results of this study confirm the folklore use of T. chebula leaves gall extracts as a natural anti-inflammatory agent and justify its ethnobotanical use. Therefore, the results encourage the use of T. chebula leave gall extracts for medicinal health, functional food, and nutraceuticals applications.SUMMARYThe present investigation demonstrated promising anti-LOX proper-ties of T. chebula leaves gall extracts. Presumably, these activities could be attributed in part to the polyphenolic features of the extract, as there was a strong correlation of higher LOX inhibiting activities with that of high total phenolic and flavonoid content in the methanolic leaf gall extracts of T. chebula. The results of this study confirm the folklore use of T. chebula leaves gall extracts as a natural anti-inflammatory agent and justify the ethnobotanical approach in the search for novel bioactive com-pounds.

Olive Leaf Extract Reduces Myeloid-Derived Suppressor Cells, and Modulates the Function of Residual Cells in Experimental Model of Melanoma

Background: Immunosuppression in melanoma is mediated by increased accumulation of Myeloid Derived Suppressor Cells (MDSCs). Olive Leaf Extract (OLE) has been developed as a natural anti-inflammatory, anti-oxidant, anti-proliferative and antiapoptotic agent on cancer immunotherapy. Objective: To investigate whether OLE could inhibit MDSCs, enhance anti-tumor activities and consequently increase the survival rate of the murine melanoma model. Methods: The C57BL/6 mice were inoculated subcutaneously with B16/F10 melanoma tumor cell lines. Induced mice were orally treated with 500 mgkg-1 of olive extract per kg of body weight for 8 consecutive days. The frequency and function of MDSCs and induction of inflammatory mediators as well as tumor growth and survival rate were assessed in treated and untreated mice. Results: The results of current study revealed that the optimal dose of OLE (500 mgkg-1) reduced the tumor growth (40%), and prolonged mice survival (25%) by significant decreasing (P<0.05) the number (over 50%), and suppressive function of MDSCs (over 60%) (P<0.05). OLE was also significantly (P<0.05) down regulated the induction of inflammatory agents in melanoma-bearing mice (over 50%) at the applied dose (500 mgkg-1). Conclusion: Therefore, these results altogether provided some evidence that regulation of immunosuppression were the possible therapeutic effects of OLE in tumor cells.

Protective Effect of Diospyros kaki against Glucose-Oxygen-Serum Deprivation-Induced PC12 Cells Injury.

Ischemic cerebrovascular disease is one of the most common causes of death in the world. Recent interests have been focused on natural antioxidants and anti-inflammatory agents as potentially useful neuroprotective agents. Diospyros kaki (persimmon) has been shown to exert anti-inflammatory, antioxidant, and antineoplastic effects. However, its effects on ischemic damage have not been evaluated. Here, we used an in vitro model of cerebral ischemia and studied the effects of hydroalcoholic extract of peel (PeHE) and fruit pulp (PuHE) of persimmon on cell viability and markers of oxidative damage mainly intracellular reactive oxygen species (ROS) induced by glucose-oxygen-serum deprivation (GOSD) in PC12 cells. GOSD for 6 h produced significant cell death which was accompanied by increased levels of ROS. Pretreatment with different concentrations of PeHE and PuHE (0–500 μg/mL) for 2 and 24 h markedly restored these changes only at high concentrations. However, no significant differences were seen in the protection against ischemic insult between different extracts and the time of exposure. The experimental results suggest that persimmon protects the PC12 cells from GOSD-induced injury via antioxidant mechanisms. Our findings might raise the possibility of potential therapeutic application of persimmon for managing cerebral ischemic and other neurodegenerative disorders.

Polyunsaturated fatty acids levels and initial presentation of somatic symptoms induced by interferon-alpha therapy in patients with chronic hepatitis C viral infection

Objectives: Somatic symptoms are common in depressive disorder and are similar to sickness behaviors due to inflammatory activation after cytokine administration. Omega-3 polyunsaturated fatty acids (PUFAs) are natural anti-inflammatory agents and may reduce inflammation-induced behavioral changes. The aim of this study was to investigate the role of PUFAs on the development of somatic symptoms and depression in patients of hepatitis C virus infection (HCV) receiving interferon-alpha therapy (IFN-α) in a prospective manner.Methods: In this 24-week, prospective cohort study, 43 patients with chronic HCV ongoing IFN-α therapy were assessed with the mini-international neuropsychiatric interview for major depressive episodes and neurotoxicity rating scale (NRS) for somatic symptoms.Results: One-third later developed IFN-α-induced depression (depression (DEP) group). As compared to subjects without depression, DEP group had higher NRS scores (P < 0.001), lower eicosapentaenoic acid (EPA) levels (P = 0.038) at week 2. Somatic symptoms, regardless of painful/non-painful characteristics, had positive association with arachidonic acid (P < 0.05), and negative association with EPA (P < 0.05).Conclusion: This study implies that early intervention with omega-3 PUFAs might be a promising strategy to prevent depression and somatic symptoms in patients receiving cytokine therapy.

Phytochemical Screening, Antioxidant Effect and Down Regulation of TGF-β Induced by Ophiocoma erinaceus Brittle Star Crude Extract

Background: Recent investigations get focused on characterization and isolation of natural compounds with pharmaceutical applications from terrestrial and aquatic ecosystem. Marine invertebrate natural products have been proposed due to various structural diversity. Ophiocoma eraniceus (O. erinaceus) is a brittle star species belonging to Echinodermata that distributed in Qeshm island in the Persian Gulf. Recent scientist researches have concentrated on discovery of natural resources with pharmacological and biomedical potential. Objectives: This experiment aimed to discover phytochemical analysis and in vitro antioxidant and anti-inflammatory properties of O. erinaceus methanolic extract. Materials and Methods: In this experimental study, the phytochemical analysis were conducted to determine saponin, phenolic and flavonoid content of brittle star and the free radical scavenging activity with two in vitro assays. In addition, the effect of methanolic brittle star extract on TGF-β expression were analysed by RT-PCR. Results: The phytochemical studies established the presence of saponins, phenol, and flavonoids compounds in the brittle star extract and the antioxidant results from DPPH (1, 1-diphenyl-2-picrylhydrazyl), ABTS (azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) revealed that O. erinaceus displayed antioxidant activity as dose dependent manner. On the other hand, O. erinaceus extract inhibited TGF-β expression which indicate anti-inflammatory properties of O. erinaceus. Conclusions: In conclusion, these results clearly exhibited that the O. erinaceus methanolic extract possess valuable constituents that may correspond as a natural antioxidant and anti-inflammatory agent useful in biomedicine.

Effect of Propolis on Induced Alveolar Bone Loss in Diabetic Rats

inflammatory diseases. As DM accelerates bone resorption; when periodontal disease affects a diabetic individual, extensive alveolar boneloss occurs. Propolis is a natural antibiotic & anti-inflammatory agent that honey bees (Apis mellifera) collect from tree buds or otherbotanical sources; and use in the construction as well as the protection of their hives. Due to its broad pharmacological potential, propolis hasbeen employed extensively in medicine, since ancient times.Objective: Was to evaluate the effect of systemic administration of propolis on the alveolar bone loss, induced by periodontitis, in diabeticrats.Materials and methods: Twenty-four Albino rats were divided into three equal groups: group (1) normal control (NC), group (2) Diabetes+ Periodontitis (DP) and group (3) Diabetes + Periodontitis + Propolis (DP-Pro). DM type 1was induced in rats of groups (2) and (3), bysingle intraperitoneal injection of Streptozotocin. Then, periodontitis was induced by ligature placement sub marginally around the rightmandibular 1st molar. In group (3), propolis was administrated systemically by gastric feeding 400mg/Kg/day for 8weeks. At the end of thisperiod, animals were sacrificed and dissected. The alveolar bone surface integrity interproximally was evaluated by scanning electronmicroscopy (SEM), and results were compared between groups.Results: After 2 months, group (2) showed more alveolar bone loss compared to the 2 other groups. Groups (1) & (3) showed an intact,smooth & regular bone surface, while group (2) specimens showed an irregular & porous bone surface with extensive resorption.Conclusion: This study showed that the systemic administration of propolis effectively prevented the extensive alveolar bone lossassociated with experimental periodontitis in diabetic rat models. Thus, propolis might be used as an adjunctive treatment for periodontitisassociated with Diabetes.

Kolaviron Improves Morbidity and Suppresses Mortality by Mitigating Oxido-Inflammation in BALB/c Mice Infected with Influenza Virus.

Influenza A viruses (IAV) induce cytokine storm and host's intracellular redox imbalance to ensure continuous replication and survival, leading to severe immunopathology and death. The unpredictability of broad-spectrum vaccines, the emergence of drug-resistant and/or more virulent strains, the prevalence of the amantadane-resistant IAV, and the prohibitive cost of available drugs especially in resource-poor countries necessitate exploring drugs with novel action mechanisms as anti-influenza agents. This study presents the protective role of kolaviron (KV), a natural antioxidant and anti-inflammatory agent from Garcinia kola seeds, on BALB/c mice challenged with influenza A/Perth/H3N2/16/09 (Pr/H3N2) virus. KV at 400 mg/kg was administered orally to groups of BALB/c mice for 3 days, 3 h, and 1 h prior to infection with 1LD50 or 3LD50 (14-day study) and 5LD50 (6-day study) Pr/H3N2. Pr/H3N2 in the lungs was detected by hemagglutination assay, while oxidative stress and inflammatory biomarkers were assayed in both lungs and liver. Infected mice treated with KV progressively increased in weight with minimal mortality. Single-dose administration of KV at 1 h or 3 h before viral challenge and 3 days pretreatment improved lung aeration and reduced lung consolidation as well as inflammatory cells infiltration in a way that had minimal impact on viral clearance, but attenuated myeloperoxidase activity and nitric oxide production via priming of reduced glutathione levels, thus enhancing the preservation of function in the lungs and liver. This study suggests that KV may be effective for delaying the development of clinical symptoms of influenza virus, and this may be through a mechanism unrelated to those deployed by the existing anti-influenza drugs but closely associated to its antioxidant and immunomodulatory properties.

Anti-inflammatory activity and phenolic composition of Dendropanax morbifera leaf extracts

Although a number of steroidal or non-steroidal anti-inflammatory drugs have been used to treat inflammatory diseases, the discovery of plant-based drugs continues to contribute to new anti-inflammatory agents. In this study, we introduced Dendropanax morbifera Leveille as a potential source for natural anti-inflammatory agents. To investigate the anti-inflammatory activity of D. morbifera leaf extracts and to explore the possible related mechanism, LPS-stimulated RAW 264.7 macrophages were used as a model system. Methanolic extracts from two different stages of D. morbifera leaves (green and senescent leaves) exhibited a strong suppressive effect on the production of LPS-induced pro-inflammatory mediators and cytokines via the suppression of iNOS and COX-2 protein expression and the inhibition of the ERK1/2 signaling pathway. In addition, the quantitative HPLC analysis of phenolic compounds suggested that D. morbifera leaf extracts contained the active phenolic compounds including rutin, chlorogenic acid, (+)−catechin, ferulic acid, myricetin, quercetin, and resveratrol, which have anti-inflammatory effects.