linoleic-acid and Edema

Munziq Balgam (MBm) is a classic preparation of a traditional Uyghur medicine used for many years to treat abnormal body fluid diseases. The formula, as an in-hospital preparation, has already been used in the Hospital of Xinjiang Traditional Uyghur Medicine to treat rheumatoid arthritis (RA) with significant clinical effects.. This study intends to reveal the intervention effect of MBm on collagen-induced arthritis (CIA) rats, discover the potential biomarkers with efficacy, and explore the mechanisms of metabolic regulation by using metabolomics method.. Sprague Dawley (SD) rats were randomly divided into five groups: blank group, CIA model group, Munziq Balgam nomal-dosage, Munziq Balgam high-dosage group and control group. Body weight, paw swelling, arthritis index, immune indices and histopathological experiments were carried out. Plasma from rats were detected by UPLC-MS/MS. Metabolomics of plasma was performed to analyze metabolic profiles, potential biomarkers, and metabolic pathways of MBm for CIA rats. The main metabolic result of Uyghur medicine MBm was compared with that of Zhuang medicine Longzuantongbi granules (LZTBG) to explore the characteristics of two ethnic medicines from different regions for RA.. MBm could significantly alleviate symptoms of CIA rats by relieving arthritis symptoms on paw redness and swelling, inflammatory cell infiltration, synovial hyperplasia, pannus, cartilage and bone tissue destruction, as well as inhibiting the expression of IL-1β, IL-6, TNF-α, UA and ALP. Linoleic acid, alpha-linolenic acid, pantothenate and CoA biosynthesis, achidonic acid, gycerophospholipid, sphingolipid metabolism, primary bile acid biosynthesis, porphyrin and chlorophyll metabolism and fatty acid degradation served as the main nine pathways of the interventional effect of MBm on CIA rats. Twenty-three different metabolites were screened out and strongly associated with the indicator makes of RA. Eight potential efficacy-related biomarkers were finally discovered in metabolic pathway network (phosphatidylcholine, bilirubin, sphinganine 1-phosphate, phytosphingosine, SM (d18:1/16:0), pantothenic acid, l-palmitoylcarnitine, chenodeoxycholate). Three metabolites (chenodeoxycholate, hyodeoxycholic acid and O-palmitoleoylcarnitine) were changed in both the metabolic study of MBm and LZTBG intervention effects on CIA rats. Additionally, MBm and LZTBG shared the same 6 metabolic pathways including linoleic acid, alpha-linolenic acid, pantothenate and CoA biosynthesis, achidonic acid, gycerophospholipid, and primary bile acid biosynthesis.. The study suggested that MBm may effectively alleviate RA by regulating inflammation, immunity-related pathways and multiple targets. Metabolomics analysis showed that MBm (Xinjiang, the north of China) and LZTBG (Guangxi, the south of China), two ethnic medicines from different regions in China, share common metabolites and pathways but also have distinct differences in their interventions for RA.

Topics: alpha-Linolenic Acid; Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Bile Acids and Salts; Biomarkers; China; Chromatography, High Pressure Liquid; Chromatography, Liquid; Edema; Linoleic Acid; Metabolomics; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry

Inflammation is a primary defense and immune response. However, under pathological conditions, the inflammation processes always become uncontrolled and lead to chronic diseases. Bufotenine, as a natural component from toad venom, showed great potential for development as a novel anti-inflammation and analgesia agent. This study aimed to investigate the therapeutic effects of bufotenine against inflammation and pain on animal models with a focus on lipid metabolism. In pharmacological studies, bufotenine significantly inhibited the swelling rates on formalin-induced paw edema model, and increased paw withdrawal mechanical thresholds (PWMTs) in von Frey test and thermal pain thresholds (TPTs) in hot-plate test. High-sensitivity lipidomics analysis revealed the effects might be related to the down-regulation of inflammatory mediators from cyclooxygenase (COX), lipoxygenase (LOX), cytochrome P450 (CYP450), linoleic acid (LA), docosahexaenoic acid (DHA) and other pathways. The activities might result from the binding of bufotenine and its receptors, including sigma-1 receptor and 5-Hydroxytryptamine receptor 3A, thus regulating lipid metabolism pathway. The research provided a systemic evidence for the actions and mechanism of bufotenine. It suggested that the natural compound might be a potential candidate for reducing inflammatory pain disorders.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Bufotenin; Cyclooxygenase 2; Cytochrome P-450 Enzyme System; Docosahexaenoic Acids; Edema; Female; Linoleic Acid; Lipid Metabolism; Lipoxygenase; Male; Mice, Inbred ICR; Molecular Docking Simulation; Pain; Receptors, Serotonin; Receptors, sigma; Sigma-1 Receptor; Signal Transduction

Increased expression of matrix metalloproteinase 13 (MMP13) in chondrocytes contributes to the development of osteoarthritis. The hypothesis of this study was that diet with a low ratio of n-6/n-3 polyunsaturated fatty acids (PUFAs) is associated with reduced MMP13 expression in inflammatory chondrocytes in vitro and in vivo. Human chondrocytes were cultured with different ratios of linoleic acid (LA, n-6 PUFA) to α-linolenic acid (n-3 PUFA) from 1:1 to 10:1. Proliferation of chondrocytes, MMP13 protein and mRNA levels were detected, respectively. Sprague-Dawley rats (n=30) were fed diets containing different ratios of n-6/n-3 PUFA. Freund's complete adjuvant was injected to make the model of arthritis. Paw swelling rate was measured and all rats were euthanized after 6 weeks of treatment. Serum MMP13 and IL-1 were measured by enzyme-linked immunosorbent assay. Joint histological sections were stained with safranin-O Fast Green to evaluate cartilage damage. Low ratio of LA/α-linolenic acid decreased the mRNA and protein levels of MMP13 but did not affect chondrocytes proliferation. Ratios of PUFA such as 1:1 and 2:1 significantly reduced paw swelling rate, and serum MMP13 and IL-1 levels in a rat model. Histological staining showed that ratios of 1:1 and 2:1 PUFA significantly alleviated cartilage damage in adjuvant-induced arthritis. A ratio of n-6/n-3 PUFA of 1:1 showed the strongest inhibitory effect on MMP13. Our results indicate that a low ratio of n-6/n-3 PUFA at 1:1 significantly suppressed MMP13 expression both in vitro and in vivo and reduced adjuvant-induced arthritis in rats could be a means to control and reduce the symptoms of osteoarthritis.

Topics: alpha-Linolenic Acid; Animals; Arthritis, Experimental; Cartilage; Cartilage Diseases; Chondrocytes; Edema; Humans; Interleukin-1; Joints; Linoleic Acid; Male; Matrix Metalloproteinase 13; Osteoarthritis; Rats, Sprague-Dawley; RNA, Messenger

α-Lipoic acid (ALA) has been termed the 'ideal' antioxidant, a readily absorbed and bioavailable compound capable of scavenging a number of free radicals, and it has been used for treating diseases in which oxidative stress plays a major role. The present study was designed to gain a better understanding for the positive effects of ALA on the models of acute and chronic inflammation in rats, and also determine its anti-oxidative potency. In an acute model, three doses of ALA (50, 100 and 200 mg/kg) and one dose of indomethacin (25 mg/kg) or diclofenac (25 mg/kg) were administered to rats by oral administration. The paw volumes of the animals were calculated plethysmometrically, and 0·1 ml of 1 % carrageenan (CAR) was injected into the hind paw of each animal 1 h after oral drug administration. The change in paw volume was detected as five replicates every 60 min by plethysmometry. In particular, we investigated the activities of catalase, superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), inducible NO synthase (iNOS) and myeloperoxidase (MPx), and the amounts of lipid peroxidation (LPO) or total GSH in the paw tissues of CAR-injected rats. We showed that ALA exhibited anti-inflammatory effects on both acute and chronic inflammations, and a strongly anti-oxidative potency on linoleic acid oxidation. Moreover, the administration of CAR induced oedema in the paws. ALA significantly inhibited the ability of CAR to induce: (1) the degree of acute inflammation, (2) the rise in MPx activity, (3) the increases of GST and iNOS activities and the amount of LPO and (4) the decreases of GPx, GR and SOD activities and the amount of GSH. In conclusion, these results suggest that the anti-inflammatory properties of ALA, which has a strong anti-oxidative potency, could be related to its positive effects on the antioxidant system in a variety of tissues in rats.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Carrageenan; Cotton Fiber; Disease Models, Animal; Edema; Enzymes; Hindlimb; Inflammation; Linoleic Acid; Lipid Peroxidation; Male; Rats; Rats, Wistar; Thioctic Acid

Lythrum salicaria (purple loosestrife) known as "Tibbi hevhulma" in Turkish is used for its several beneficial health effects against as diarrhea, chronic intestinal catarrh, hemorrhoid and eczema in the form of a decoction or a fluid extract and to treat varicose veins, bleeding of the gums, hemorrhoid and eczema, externally. Dried herbal parts of Lythrum salicaria L. (Lythraceae) were sequentially extracted with different solvents such as petroleum ether, ethyl acetate, methanol and 50% aqueous methanol. Water extract of Lythrum salicaria was also prepared under reflux. Antioxidant, anti-inflammatory and anti-nociceptive activities of all the extracts were investigated using in vitro and in vivo methods, respectively. Free radical scavenging activity (1,1-diphenyl-2-picrylhydrazyl, DPPH* assay), iron(III) reductive activity, capacity of the inhibition of linoleic acid peroxidation and MDA formation, anti-nociceptive activity (p-benzoquinone-induced abdominal constriction test) and anti-inflammatory activity (carrageenan-induced hind paw edema model) were used for all the extracts. In addition, the content of total phenolics, flavonoids and flavonols in all the extracts were determined with spectrophotometric methods. Results were compared with reference antioxidants via ascorbic acid, butylated hydroxytoluene, and gallic acid. Qualitative and quantitative compositions of all the extracts were analysed using a HPLC-PDA system. Polar fractions were found to be rich in flavonoids such as isovitexin and isoorientin.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Edema; Flavonoids; Free Radical Scavengers; Iron; Linoleic Acid; Lipid Peroxidation; Lythrum; Male; Malondialdehyde; Medicine, Traditional; Mice; Pain; Pain Measurement; Phenols; Phytotherapy; Plant Extracts; Turkey

Decreased synthesis of arachidonic acid by inhibition of the Delta6 or Delta5 desaturase was evaluated as a means to mitigate inflammation. Using quantitative in vitro and in vivo radioassays, novel compounds representing five classes of Delta5 desaturase inhibitors and one class of Delta6 desaturase inhibitor were identified. The Delta6 desaturase inhibitor, SC-26196, had pharmacokinetic and pharmacodynamic profiles in mice that allowed for the evaluation of the pharmacological effects of chronic inhibition of desaturase activity. SC-26196 decreased edema to the same extent as indomethacin or essential fatty acid deficiency in the carrageenan paw edema model in the mouse. The antiinflammatory properties of SC-26196 were consistent with its mechanism of action as a Delta6 desaturase inhibitor: 1) A correlation existed between inhibition of liver Delta6 desaturase activity and decreases in edema. 2) The onset of the decrease in edema was time dependent. 3) Selective reduction of arachidonic acid occurred dose dependently in liver, plasma and peritoneal cells. 4) In the presence of SC-26196, controlled refeeding of arachidonic acid, but not oleic acid, reversed the changes resulting from desaturase inhibition. The Delta6 desaturase may be a target for development of antiinflammatory drugs whose mechanism of action is unique.

Topics: Animals; Anti-Inflammatory Agents; Arachidonic Acid; Edema; Enzyme Inhibitors; Fatty Acid Desaturases; Fatty Acids, Essential; Female; Linoleic Acid; Male; Mice; Mice, Inbred BALB C; Peroxidase; Rats; Rats, Sprague-Dawley