Exploration of the anti-inflammatory, analgesic, and wound healing activities of Bletilla Striata polysaccharide.

Bletilla Striata (BS) Polysaccharide (BSP) is one of the main components of the traditional Chinese medicinal plant Bletilla striata Rchb. F. BSP has been widely used in antimicrobial and hemostasis treatments in clinics. Despite its use in skin disease treatment and cosmetology, the effects of BSP on wound healing remain unclear. Here we investigated the anti-inflammatory, antioxidant, and analgesic effects of BSP and explored its impact on morphological changes and inflammatory mediators during wound healing. A carrageenan-induced mouse paw edema model was established to evaluate the anti-inflammatory effect of BSP. Antioxidant indicators, including NO, SOD, and MDA, were measured in the blood and liver. The increased pain threshold induced by BSP was also determined using the hot plate test. A mouse excisional wound model was applied to evaluate the wound healing rate, and HE staining and Masson staining were used to detect tissue structure changes. In addition, ELISA was employed to detect the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß in serum. BSP significantly decreased the concentration of NO and MDA in serum and liver while increasing SOD activity. It exhibited a notable improvement in mouse paw edema induced by carrageenan. BSP dose-dependently delayed the appearance of licking behavior in mice, indicating its analgesic effect. Compared to the control group, the wound healing rate was significantly improved in the BSP treatment group. HE and Masson staining results showed that the BSP and 'Jingwanhong' ointment groups had slightly milder inflammatory responses and significantly promoted more new granulation tissue formation. The levels of serum inflammatory mediators TNF-α, IL-1ß, and IL-6 were reduced to varying degrees. The results demonstrated that BSP possesses anti-inflammatory, antioxidant, analgesic, and wound healing properties, and it may promote wound healing through inhibition of inflammatory cytokine synthesis and release.

Therapeutic Potential of Clove Essential Oil in Diabetes: Modulation of Pro-Inflammatory Mediators, Oxidative Stress and Metabolic Enzyme Activities.

Type 1 diabetes is characterized by insulin deficiency due to the destruction of pancreatic ß cells, leading to hyperglycemia, which in turn induces vascular complications. In the current study, we investigated the effect of intraperitoneal administration of clove essential oil (CEO: 20 mg/kg body weight) on certain oxidative stress and glucose metabolism enzymes, as well as the expression of proinflammatory mediators. Administration of CEO to diabetic rats showed a significant decline in blood glucose levels, total cholesterol, and xanthine oxidase, compared to the streptozotocin group. Furthermore, these treated rats elicited a notable attenuation in the levels of lipid peroxides, and thiols groups in both liver and brain tissues. The activities of antioxidant and metabolic enzymes were reverted to normality in diabetic upon CEO administration. In addition to its protective effects on red blood cell hemolysis, CEO is a potent α-amylase inhibitor with an IC50 =298.0±2.75 µg/mL. Also, treatment of diabetic rats with CEO significantly reduced the iNOS expression in the spleen. Our data showed that CEO has potential beneficial effects on diabetes, which can possibly prevent the pathogenesis of diabetic micro- and macrovascular complications.

Increased nitrate intake from beetroot juice does not alter soluble cellular adhesion molecules and circulating inflammatory cytokines in individuals with treated hypertension: a randomised, controlled trial.

Dietary nitrate, found predominantly in green leafy vegetables and other vegetables such as radish, celery, and beetroot, has been shown to beneficially modulate inflammatory processes and immune cell function in animals and healthy individuals. The impact of increased nitrate intake on soluble inflammatory mediators in individuals with hypertension is unclear. We assessed whether the daily consumption of dietary nitrate via beetroot juice for 1-week lowered levels of circulating inflammatory markers in men and women with treated hypertension. Twenty-seven male and female participants were recruited to a randomized, placebo-controlled, double-blind crossover trial. The effects of 1-week intake of nitrate-rich beetroot juice versus 1-week intake of nitrate-depleted beetroot juice (placebo) were investigated. Plasma concentrations of circulating soluble adhesion molecules (ICAM-1, VCAM-1, CD62E, CD62P), inflammatory cytokines (IL-1ß, IL-6, IL-10, IL-12p70, TNF-α) and chemokines (IL-8, MCP-1) were measured by multiplex flow cytometric bead array in samples collected on day 7 of each intervention period. Other outcomes included alterations in nitrate metabolism assessed by measuring nitrate and nitrite concentrations in plasma, saliva, and urine. One week of beetroot juice did not alter levels of the soluble adhesion markers or cytokines assessed. A 7-fold increase in salivary nitrite, an 8-fold increase in salivary nitrate, a 3-fold increase in plasma nitrate and nitrite, and a 4-fold increase in urinary nitrate and nitrite compared to the placebo was observed (p < 0.001 for all comparisons). Increasing dietary nitrate consumption over 7 days is not effective in reducing soluble inflammatory mediators in individuals with treated hypertension. This trial was registered at anzctr.org.au as ACTRN 12613000116729.

Ajwa dates (Phoenix dactylifera L.) attenuate cisplatin-induced nephrotoxicity in rats via augmenting Nrf2, modulating NADPH oxidase-4 and mitigating inflammatory/apoptotic mediators.

In the therapy of cisplatin (CP), nephrotoxicity is a main limiting issue that associated with oxidative stress and apoptosis. According to many studies, the antioxidant and anti-inflammatory properties of Ajwa dates are very strong, due to the unique phytochemical profile. Here, we investigated the possible mitigative effects of Ajwa dates fruits extract (ADFE) vs CP-induced nephrotoxicity in rats, in addition to phytochemical profiling of its components via LC-MS/MS. Six groups were formed from forty-two male rats. G1: control, G2: ADFE 0.25 g/kg, G3: ADFE 0.5 g/kg (for 21 days), G4: CP -intoxicated group (single i.p. dose of 7.0 mg/kg b.w) on day 16th, G5: ADFE 0.25 + CP, G6: ADFE 0.5 + CP. LC-MS/MS analysis revealed the tentative identification of 17 compounds of different chemical nature, including organic/phenolic acids, and flavonoids and their sulphated/glycosides derivatives. ADFE has considerable antioxidant potential (DPPH with IC50 326.65 µg/ml and FRAP= 20.91 mM FeSO4/g extract) and total phenolic content (TPC = 35.44 mg/GAE/g extract). It (especially at dose 0.5 g/kg b.w) significantly modulated the toxicity of CP via enhancing food intake and hematobiochemical indices (renal functions, anemia, and leucopenia), increasing the renal antioxidant status (GSH, SOD, and CAT), decreasing the production of oxidative stress and inflammatory markers (MDA, NO, H2O2, MPO, MCP-1, TNF-α and IL-6), augmenting mRNA expression of Nrf2, and modulating NOX4 mRNA expression. The existence of bioactive compounds in ADFE may be responsible for their prophylactic properties, demonstrating natural usefulness in the treatment of oxidative stress, hypochromic anemia, immunodeficiency, and inflammatory complications, all of which are chemotherapy side effects.

Non-target toxic effects of avermectin on carp spleen involve oxidative stress, inflammation, and apoptosis.

Avermectin is one of the most widely used pesticides, but its toxicity to non-target organisms, especially aquatic organisms, has been ignored. Therefore, an acute spleen injury model of avermectin in carp was established to assess the non-target toxicity of avermectin to carp. In this study, 3.005 µg/L and 12.02 µg/L were set as the low and high dose groups of avermectin, respectively, and a four days acute exposure experiment was conducted. Pathological structure observation showed that avermectin damaged spleen tissue structure and produced inflammatory cell infiltration. Biochemical analysis showed that avermectin significantly reduced the activities of antioxidant enzymes CAT, SOD, and GSH-px, but increased the content of MDA, a marker of oxidative damage. Avermectin exposure also significantly increased the transcription levels of inflammatory cytokines such as IL-1ß, IL-6, TNF-α, and INOS, and also significantly enhanced the activity of the inflammatory mediator iNOS, but suppressed the transcription levels of anti-inflammatory factors TGF-ß1 and IL-10. In addition, TUNEL detected that the apoptosis rate increased significantly with the increase of avermectin dosage, and the transcription levels of apoptosis-related genes BAX, P53, and Caspase 3/9 also increased in a dose-dependent manner. This study is preliminary evidence that avermectin induces spleen injury in carp through oxidative stress, inflammation, and apoptosis, which has important implications for subsequent studies on the effects of avermectin on non-target organisms.

Evaluation of antiobesity and hepatorenal protective activities of Salvia officinalis extracts pre-treatment in high-fat diet-induced obese rats.

The present study evaluated the effects of Hail Salvia officinalis total extract (SOTE) and its high flavonoid fraction (SOHFF) on the high-fat diet (HFD)-induced obesity and hepatorenal damage in rats. Salvia officinalis plants were collected from Hail region, Saudi Arabia. Rats were fed HFD and supplemented orally with SOTE (250 mg kg-1) or SOHFF (100 mg kg-1) or simvastatin (SVS; 10 mg kg-1) every day for 8 weeks. Compared to the controls, HFD-induced obesity led to significant increases in body weight, body weight gained, blood insulin, leptin, cardiac enzymes (LDH and CPK) activity, and atherogenic index (AI). HFD rats also showed higher levels of hepatic and renal function biomarkers (ALT, urea, and creatinine), as well as lower levels of PPARγ and Nrf2-gene expression and a disrupted lipid profile. Moreover, HFD rats had lower levels of hepatic and renal antioxidant biomarkers (CAT, GPx, SOD, GR, and GSH), accompanied by higher levels of hepatic and renal lipid peroxidation (LPO), nitric oxide (NO), and inflammatory mediators (interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α)). In addition, histological examination of hepatic and renal tissues revealed histopathological changes that validated the biochemical findings. Compared to HFD group, SOTE and SOHFF treatment led to marked amelioration of all the aforementioned parameters. Collectively, supplementation with SOTE and SOHFF effectively reversed HFD-induced alterations through its antioxidant, hypolipidemic, and anti-inflammatory properties. Hence, SOTE and SOHFF have therapeutic potential in controlling obesity and related pathologies.

Artemisia anomala Herba Alleviates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions in Mice and the Production of Pro-Inflammatory Mediators in Tumor Necrosis Factor Alpha-/Interferon Gamma-Induced HaCaT Cells.

Artemisia anomala S. Moore is a perennial herbaceous plant classified as Asteraceae of the genus Artemisia. Many species of Artemisia have been used as medicinal materials. Artemisia anomala S. Moore has been widely used in China to treat inflammatory diseases. However, the mechanism of its action on the keratinocyte inflammatory response is poorly understood. Here, we investigated the anti-inflammatory reaction of Artemisia anomala S. Moore ethanol extract (EAA) using human keratinocyte (HaCaT) cells, which involved investigating the nuclear factor kappa B (NF-κB), signal transducer, and activator of transcription-1 (STAT-1), as well as mitogen-activated protein kinase (MAPK) signaling pathways and atopic dermatitis-like skin lesions in mice. We elucidated the anti-inflammatory effects of EAA on tumor necrosis factor-α/interferon-γ (TNF-α/IFN-γ)-treated human keratinocyte cells and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like mice. The levels of chemokines and cytokines (IL-8, IL-6, TARC, and RANTES) were determined by an enzyme-linked immunosorbent assay. The NF-κB, STAT-1, and MAPK signaling pathways in HaCaT cells were analyzed by western blotting. Thickening of the mice dorsal and ear skin was measured and inflammatory cell infiltration was observed by hematoxylin and eosin staining. Results showed that EAA suppressed IL-8, IL-6, TARC, and RANTES production. EAA inhibited nuclear translocation of NFκB and STAT-1, as well as reduced the levels of phosphorylated ERK MAPKs. EAA improved AD-like skin lesions in DNCB-treated mice. These findings suggest that EAA possesses stronger anti-inflammatory properties and can be useful as a functional food or candidate agent for AD.

Targeted treatment for osteoarthritis: drugs and delivery system.

The management of osteoarthritis (OA) is a clinical challenge due to the particular avascular, dense, and occluded tissue structure. Despite numerous clinical reports and animal studies, the pathogenesis and progression of OA are still not fully understood. On the basis of traditional drugs, a large number of new drugs have been continuously developed. Intra-articular (IA) administration for OA hastens the development of targeted drug delivery systems (DDS). OA drugs modification and the synthesis of bioadaptive carriers contribute to a qualitative leap in the efficacy of IA treatment. Nanoparticles (NPs) are demonstrated credible improvement of drug penetration and retention in OA. Targeted nanomaterial delivery systems show the prominent biocompatibility and drug loading-release ability. This article reviews different drugs and nanomaterial delivery systems for IA treatment of OA, in an attempt to resolve the inconsonance between in vitro and in vivo release, and explore more interactions between drugs and nanocarriers, so as to open up new horizons for the treatment of OA.

Resolution-Based Therapies: The Potential of Lipoxins to Treat Human Diseases.

Inflammation is an a physiological response instead an essential response of the organism to injury and its adequate resolution is essential to restore homeostasis. However, defective resolution can be the precursor of severe forms of chronic inflammation and fibrosis. Nowadays, it is known that an excessive inflammatory response underlies the most prevalent human pathologies worldwide. Therefore, great biomedical research efforts have been driven toward discovering new strategies to promote the resolution of inflammation with fewer side-effects and more specificity than the available anti-inflammatory treatments. In this line, the use of endogenous specialized pro-resolving mediators (SPMs) has gained a prominent interest. Among the different SPMs described, lipoxins stand out as one of the most studied and their deficiency has been widely associated with a wide range of pathologies. In this review, we examined the current knowledge on the therapeutic potential of lipoxins to treat diseases characterized by a severe inflammatory background affecting main physiological systems, paying special attention to the signaling pathways involved. Altogether, we provide an updated overview of the evidence suggesting that increasing endogenously generated lipoxins may emerge as a new therapeutic approach to prevent and treat many of the most prevalent diseases underpinned by an increased inflammatory response.

The effects of rice bran oil on left ventricular systolic function, cardiometabolic risk factors and inflammatory mediators in men with coronary artery disease: a randomized clinical trial.

BACKGROUND/OBJECTIVE: In the current study, we aimed to explore the effects of rice bran oil (RBO) in adjunct to conventional medical therapy on left ventricular ejection fraction (LVEF), cardiometabolic risk factors, and inflammatory mediators in male patients with coronary artery disease (CAD). SUBJECTS/METHODS: The present randomized controlled trial included 40 men diagnosed with CAD (mean age = 55.76 years) who were randomly allocated into two groups to receive either 30 grams per day of RBO (intervention group) or sunflower oil (control group) plus a standard diet for eight weeks. At the initial visit, demographic and anthropometric data and blood samples were collected. LVEF levels and serum concentrations of lipid profile, glucose, uric acid, hs-CRP, and TNF-α were investigated. RESULTS: A total of 37 participants completed the study (n = 18 in the intervention group, n = 19 in the control group). Analysis of covariance (ANCOVA) adjusted for baseline values, age and body mass index revealed that RBO significantly improved LVEF (51.34%) and reduced triglyceride (125.01 mg dl-1), blood sugar (110.4 mg dl-1), total cholesterol (123.01 mg dl-1) and low density lipoprotein (56.88 mg dl-1) levels compared to sunflower oil ((45.56%), (155.93 mg dl-1), (128.94 mg dl-1), (163.93 mg dl-1) and (83.79 mg dl-1), respectively) following a 8-week trial (P-values < 0.05). Additionally, the test demonstrated that RBO consuming patients had significantly lower levels of serum uric acid (4.60 mg dl-1), TNF-α (6.99 ng L-1) and hs-CRP (2.11 mg L-1) compared to the control group ((5.92 mg dl-1), (15.23 ng L-1), (4.47 mg L-1), respectively) (P-value < 0.05). However, no significant changes were found regarding weight, blood pressure or serum HDL levels throughout the trial. CONCLUSION: Consumption of 30 grams per day RBO within a standard diet could be considered an effective non-pharmacological approach in improving LVEF, cardiometabolic risk factors, and inflammatory state in CAD. However, future trials are recommended for more clarification.

Synthesis of two new lipid mediators from docosahexaenoic acid by combinatorial catalysis involving enzymatic and chemical reaction.

Omega-3 polyunsaturated fatty acids (PUFAs) have been known to have beneficial effects in the prevention of various diseases. Recently, it was identified that the bioactivities of omega-3 are related to lipid mediators, called pro-resolving lipid mediators (SPMs), converted from PUFAs, so they have attracted much attention as potential pharmaceutical targets. Here, we aimed to build an efficient production system composed of enzymatic and chemical catalysis that converts docosahexaenoic acid (DHA) into lipid mediators. The cyanobacterial lipoxygenase, named Osc-LOX, was identified and characterized, and the binding poses of enzyme and substrates were predicted by ligand docking simulation. DHA was converted into three lipid mediators, a 17S-hydroxy-DHA, a 7S,17S-dihydroxy-DHA (RvD5), and a 7S,15R-dihydroxy-16S,17S-epoxy-DPA (new type), by an enzymatic reaction and deoxygenation. Also, two lipid mediators, 7S,15R,16S,17S-tetrahydroxy-DPA (new type) and 7S,16R,17S-trihydroxy-DHA (RvD2), were generated from 7S,15R-dihydroxy-16S,17S-epoxy-DPA by a chemical reaction. Our study suggests that discovering new enzymes that have not been functionally characterized would be a powerful strategy for producing various lipid mediators. Also, this combination catalysis approach including biological and chemical reactions could be an effective production system for the manufacturing lipid mediators.

Jasmonates from Chinese acorns (Quercus serrata var. brevipetiolata) exert pronounced anti-neuroinflammatory activities.

Chinese oak (Quercus serrata var. brevipetiolata) belongs to the genus Quercus in Fagaceae family. Its seed, called as Chinese acorn, has been served as a traditional medicine and foodstuff in China. In this study, ten jasmonates were isolated and purified from Chinese acorn, including five new (1-5) and five known jasmonates (6-10). The new jasmonates were identified as butyl (1R,2R)-2-[(2'Z)-5'-hydroxy-penten-2'-enyl]-3-oxo-cyclopentane acetate (1), methyl {2-[4'-(ß-d-glucopyranosyloxy)-pentyl}-3-oxo-cyclopentane acetate (2), methyl {(1R,2R)-2-[(2'Z,4'R)-4'-(ß-d-glucopyransyloxy)-pent-2'-enyl]}-3-oxo-cyclopentane acetate (3), methyl {(1R,2R)-2-[(2'E,4'S)-4'-(ß-d-glucopyransyloxy)-pent-2'-enyl]}-3-oxo-cyclopentane acetate (4), and methyl {(1R,2R)-2-[(2'S,3'E)-2'-(ß-D-glucopyransyloxy)-pent-3'-enyl]}-3-oxo-cyclopentane acetate (5), respectively. The isolated jasmonates were evaluated for anti-neuroinflammatory activity, and some showed pronounced inhibitory effects on the production of nitric oxide (NO) induced by lipopolysaccharide (LPS) in BV-2 microglia cells. Some jasmonates could dose-dependently reduce the expression of LPS-induced pro-inflammatory factors (iNOS and COX-2) and could block NF-κB nuclear translocation. This study suggested that Chinese acorns could be served as a healthy product for neuroinflammatory related diseases, such as Alzheimer's disease.

Inhibition of Proinflammatory Enzymes and Attenuation of IL-6 in LPS-Challenged RAW 264.7 Macrophages Substantiates the Ethnomedicinal Use of the Herbal Drug Homalium bhamoense Cubitt & W.W.Sm.

Commonly used to treat skin injuries in Asia, several Homalium spp. have been found to promote skin regeneration and wound healing. While ethnobotanical surveys report the use of H. bhamoense trunk bark as a wound salve, there are no studies covering bioactive properties. As impaired cutaneous healing is characterized by excessive inflammation, a series of inflammatory mediators involved in wound healing were targeted with a methanol extract obtained from H. bhamoense trunk bark. Results showed concentration-dependent inhibition of hyaluronidase and 5-lipoxygenase upon exposure to the extract, with IC50 values of 396.9 ± 25.7 and 29.0 ± 2.3 µg mL-1, respectively. H. bhamoense trunk bark extract also exerted anti-inflammatory activity by significantly suppressing the overproduction of interleukin 6 (IL-6) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages at concentrations ranging from 125 to 1000 µg mL-1, while leading to a biphasic effect on nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) levels. The phenolic profile was elucidated by HPLC-DAD, being characterized by the occurrence of ellagic acid as the main constituent, in addition to a series of methylated derivatives, which might underlie the observed anti-inflammatory effects. Our findings provide in vitro data on anti-inflammatory ability of H. bhamoense trunk bark, disclosing also potential cutaneous toxicity as assessed in HaCaT keratinocytes.

Bioactive Compounds in Moringa oleifera Lam. Leaves Inhibit the Pro-Inflammatory Mediators in Lipopolysaccharide-Induced Human Monocyte-Derived Macrophages.

Moringa oleifera (MO) is an important plant for traditional medicine. The present study aimed to identify the MO active phytochemical compounds for their ability against inflamed macrophages. An ethyl acetate extract fraction of MO was fractionation by flash column chromatography. Human macrophages were stimulated by Lipopolysaccharide and then treated with fractions of MO to examine their anti-inflammatory activity and cellular mechanism. The active fractions were analyzed by liquid chromatography with electrospray ionization quadrupole time-of-flight mass spectrometer (LC-ESI-QTOF-MS). MO treated cells showed a decreased production of pro-inflammatory mediator in response to lipopolysaccharide. This was evident at both mRNA and protein levels. The study revealed that MO suppressed mRNA expression of IL-1, IL-6, TNF-α, PTGS2, NF-κB (P50), and RelA. Furthermore, the extract effectively inhibited the expression of inflammatory mediators, including IL-6, TNF-α, and cyclooxygenase-2. Interestingly, the effect of MO inhibited phosphorylation of IκB-α and the ability to reduce expression of the nuclear factor (NF)-κB p65, suppressing its nuclear translocation. Moreover, LC-ESI-QTOF-MS analysis of the MO active fraction revealed seven compounds, namely 3,4-Methyleneazelaic acid, (2S)-2-phenylmethoxybutane-1,4-diol, (2R)-2-phenylmethoxybutane-1, 4-diol, γ-Diosphenol, 2,2,4,4-Tetramethyl-6-(1-oxobutyl)-1,3,5-cyclohexanetrione, 3-Hydroxy-ß-ionone, and Tuberonic acid. Our findings highlight the ability of MO compounds to inhibit inflammation through regulation of the NF-κB pathway.

The effect of green tea on inflammatory mediators: A systematic review and meta-analysis of randomized clinical trials.

Catechin in green tea might be able to reduce inflammatory mediators; therefore, in this study, we aimed to indicate green tea effects on inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and interleukin-6 (IL-6). The advanced search methods of electronic databases were used to find randomized clinical trials that assessed green tea effect on inflammatory mediators among adult population. Google Scholar, PubMed/Medline, EMBASE, SCOPUS, and ISI Web of Science were searched until January 2019. Delphi checklist was used for assessing the quality of included articles. Mean changes in serum inflammatory biomarkers were calculated by subtracting endpoint values from the baseline in each study arm. Then the effect size for each selected study was estimated as the difference between mean changes in the intervention and control groups. We included 16 articles in our meta-analysis and 17 articles in systematic review. Our results indicated that green tea could not significantly decrease serum CRP levels and significantly increased IL-6 and significantly decreased TNF-α levels. In conclusion, green tea might not be able to change inflammatory mediators especially in diseases with low inflammation, but scientists who want to assess green tea effect on inflammatory mediators should perform their study on patients with high inflammation. Studies exclusive on male or female and considering nutrients intake as a confounding factor are a necessity.

MYMD-1, a Novel Immunometabolic Regulator, Ameliorates Autoimmune Thyroiditis via Suppression of Th1 Responses and TNF-α Release.

MYMD-1 is a synthetic derivative of tobacco alkaloids, compounds that possess immunoregulatory properties and have been linked to the epidemiological observation that smoking reduces the odds of developing thyroid Abs and hypothyroidism. To assess the effect and mechanism(s) of the action of MYMD-1, we chose the NOD.H-2h4 mouse model of spontaneous thyroiditis. We began in vitro using T cells isolated from NOD.H-2h4 spleens and found that MYMD-1 suppressed TNF-α production by CD4+ T cells in a dose-dependent manner. We then treated 58 NOD.H-2h4 mice for 12 wk with either unsupplemented water that contained (10 mice) or did not contain (16 mice) MYMD-1 (185 mg/l) or water supplemented with sodium iodide (500 mg/l) that contained (16 mice) or did not contain (16 mice) MYMD-1. Mice were bled at baseline and then every 2 wk until sacrifice. MYMD-1 decreased the incidence and severity (p < 0.001) of thyroiditis, as assessed by histopathology. Similarly, the number of CD3+ T cells and CD19+ B cells infiltrating the thyroid was dampened by MYMD-1, as assessed by flow cytometry. Interestingly, the subset of thyroidal CD3+CD4+Tbet+RORγT- effector Th1 cells and the systemic levels of TNF-α were decreased by MYMD-1. Serum thyroglobulin Abs decreased in the MYMD-1 group. Thyroid hormones did not differ among the four groups, whereas thyroid-stimulating hormone increased upon iodine supplementation but remained normal in MYMD-1-treated mice. Overall, the study suggests that MYMD-1 ameliorates thyroiditis acting on specific lymphoid subsets. Further studies, including other models of autoimmunity, will confirm the potential clinical use of MYMD-1 as a novel immunometabolic regulator.

In vivo, Extract from Withania somnifera Root Ameliorates Arthritis via Regulation of Key Immune Mediators of Inflammation in Experimental Model of Arthritis.

BACKGROUND: Rheumatoid Arthritis (RA) is a devastating disease characterized by continual addition of leukocytes and T cells within the articular cavity causing inflammation and cartilage destruction. Withania somnifera is one of the most precious medicinal herbs, reported to have antioxidant, anti-inflammatory, and immunomodulatory properties. OBJECTIVE: The purpose of this study was to evaluate anti-inflammatory activity of aqueous extract of Withania somnifera roots (WSAq) in Collagen Induced Arthritic (CIA) rats. METHODS: To achieve this, we assessed the level of inflammatory cytokines such as Tumor Necrosis Factor (TNF)-α, IL-1ß, IL-6 and IL-10 in CIA rats. Further, transcription factor, oxidative stress parameters and CD+8 expressions were also analyzed in CIA rats. RESULTS: Arthritic rats showed a greater increase in the levels of pro inflammatory cytokines such as TNF-α, IL-1ß, IL-6, transcription factor NF-κB and a decrease in IL-10 concentration than controls rats. Oral administration of WSAq at a dose of 300mg/kg.wt. (WSAq300) appreciably attenuated the production of these pro inflammatory cytokines. This anti-inflammatory activity of WSAq300 might be partly mediated through an increase in the secretion of IL-10 and inhibition of NF-κB activity. Further, arthritic rats also show increased oxidative stress as compared to control rats. This increased oxidative stress in the arthritic rats appears to be the outcome of both an activated pro-oxidant and a poor antioxidant defense system. Treatment with WSAq300 strongly ameliorates all these ROS parameters significantly to near normal. Additional, metalloproteinase MMP-8 levels were also measured and found to be increased in CIA rats, which after treatment with WSAq300 came down to near normal. CONCLUSION: From the above results, it can be concluded that the use of WSAq300 may be a valuable supplement which can improve human arthritis.

Peucedani Japonici Radix ameliorates lipopolysaccharide-induced neuroinflammation by regulating microglial responses.

Neuroinflammation is an inflammatory process within the central nervous system that is mediated by microglial activation, which releases pro-inflammatory mediators leading to neurodegeneration. In this study, we investigated the effects of Peucedani Japonici Radix (PJR), a medicinal herb traditionally used in East Asia to treat neuroinflammation both in vitro and in vivo. First, we examined the effects of PJR on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. The results showed that PJR suppressed the LPS-induced increase of several inflammatory factors, such as nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, prostaglandin E2, interleukin-1ß, and tumor necrosis factor-α. We also revealed that PJR inhibited the nuclear factor kappa B (NF-κB) pathway, which is the upstream modulator of inflammatory processes. Furthermore, to confirm the regulatory effects of PJR on microglia in vivo, we measured the number of ionized calcium-binding adapter molecule 1-positive cells in mouse brains and found that PJR treatment reduced microglial activation. Taken together, these results suggest that PJR inhibits microglia-mediated neuroinflammation through the modulation of NF-κB signaling and has the therapeutic potential to prevent inflammation-related neurodegenerative diseases.

Can Specialized Pro-resolving Mediators Deliver Benefit Originally Expected from Fish Oil?

PURPOSE OF THE REVIEW: Fish oil (FO) supplementation has historically been used by individuals suffering from cardiovascular disease and other inflammatory processes. However, a meta-analysis of several large randomized control trials (RCTs) suggested FO conferred no benefit in reducing cardiovascular risk. Skeptics surmised that the lack of benefit was related to FO dose or drug interactions; therefore, the widely accepted practice of FO consumption was brought into question. RECENT FINDINGS: Thereafter, Serhan et al. identified specialized pro-resolving mediators (SPMs) to be one of the bioactive components and mechanisms of action of FO. SPMs are thought to enhance resolution of inflammation, as opposed to classic anti-inflammatory agents which inhibit inflammatory pathways. Numerous diseases, including persistent Inflammation, immunosuppression, and catabolic syndrome (PICS), are rooted in a burden of chronic inflammation. SPMs are gaining traction as potential therapeutic agents used to resolve inflammation in cardiovascular disorders, inflammatory bowel disease, sepsis, pancreatitis, and acute respiratory distress syndrome (ARDS). This narrative reviews the history of FO and the various studies that made the health benefits of FO inconclusive, as well as an overview of SPMs and their use in specific disease states.