carnosol and Disease-Models--Animal

Mitochondrial dysfunction is a major factor in nonalcoholic fatty liver disease (NAFLD), preceding insulin resistance and hepatic steatosis. Carnosol (CAR) is a kind of diterpenoid with antioxidant, anti-inflammatory and antitumor activities. Peroxiredoxin 3 (PRDX3), a mitochondrial H

Topics: Abietanes; Animals; Antioxidants; Apoptosis; Cell Line; Diet, High-Fat; Disease Models, Animal; Enzyme Activation; Enzyme Activators; Hepatocytes; Liver; Male; Mice, Inbred C57BL; Mitochondria, Liver; Mitochondrial Dynamics; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Palmitic Acid; Peroxiredoxin III

Topics: Abietanes; Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Biomarkers; Cytokines; Disease Management; Disease Models, Animal; Disease Susceptibility; Drug Synergism; Inflammation Mediators; Male; Mice; Molecular Structure; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Plant Extracts; Signal Transduction; Toll-Like Receptor 4

Osteolysis is characterized by the imbalance of bone remodeling triggered by excessive activation of osteoclasts, which ultimately leads to pathological bone destruction. Diseases caused by overactive osteoclasts, such as osteolysis around the prosthesis, periodontitis and osteoporosis, are clinically common but lack effective treatment. Therefore, exploring regimens that could specifically impair the formation and function of osteoclasts has become a breakthrough in the treatment of these diseases. Carnosol is a natural phenolic diterpene with anti-inflammatory, antibacterial, anti-tumor and antioxidant properties. In this study, we found that carnosol can impede RANKL-induced osteoclastogenesis via modulating the activation of NF-κb and JNK signaling pathways in vitro. Additionally, we confirmed that carnosol could alleviate bone loss in amurine model of LPS-induced inflammatory bone erosion in vivo. Thence, these findings demonstrate that carnosol may be a potentially effective regent for the treatment of osteoclast-related disorders.

Topics: Abietanes; Animals; Anti-Inflammatory Agents; Bone Remodeling; Disease Models, Animal; JNK Mitogen-Activated Protein Kinases; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Osteoclasts; Osteogenesis; Osteolysis; Phosphorylation; RANK Ligand; RAW 264.7 Cells; Signal Transduction

Acute kidney injury, which is caused by renal ischemia-reperfusion injury (IRI), occurs in several clinical situations and causes severe renal damage. There is no effective therapeutic agent available for renal IRI at present. In this study, we performed an experiment based on an in vivo murine model of renal IRI to examine the effect of carnosol. Thirty Sprague-Dawley rats were randomized into three groups (10 rats in each group): the sham, IRI, and carnosol groups. Rats in the carnosol group were injected intravenously with 3 mg/kg of carnosol, and those in the sham and IRI groups were injected intravenously with 10% dimethyl sulfoxide 1 h before ischemia. Rats were sacrificed after 24 h of reperfusion. The blood and kidneys were harvested, renal function was assessed, and histologic evaluation was performed to analyze renal injury. A renal myeloperoxidase activity assay, in-situ apoptosis examination, enzyme-linked immunosorbent assay, immunohistochemical assay, and western blot were also performed. Carnosol pretreatment significantly reduced renal dysfunction and histologic damage induced by renal IRI. Carnosol pretreatment suppressed renal inflammatory cell infiltration and pro-inflammatory cytokine expression. In addition, carnosol markedly inhibited apoptotic tubular cell death, caspase-3 activation, and activation of the p38 pathway. Carnosol pretreatment protects rats against renal IRI by inhibiting inflammation and apoptosis. Although future investigation is needed, carnosol may be a potential therapeutic agent for preventing renal IRI.

Topics: Abietanes; Acute Kidney Injury; Animals; Apoptosis; Caspase 3; Cytokines; Disease Models, Animal; Inflammation Mediators; Injections, Intravenous; Kidney Tubules; Male; MAP Kinase Signaling System; Rats, Sprague-Dawley; Reperfusion Injury; Severity of Illness Index

The diterpenoids carnosol (CS) and carnosic acid (CA) from Salvia spp. exert prominent anti-inflammatory activities but their molecular mechanisms remained unclear. Here we investigated the effectiveness of CS and CA in inflammatory pain and the cellular interference with their putative molecular targets.. The effects of CS and CA in different models of inflammatory pain were investigated. The inhibition of key enzymes in eicosanoid biosynthesis, namely microsomal prostaglandin E. CS and CA displayed significant and dose-dependent anti-inflammatory and anti-nociceptive effects in carrageenan-induced mouse hyperalgesia 4 h post injection of the stimuli, and also inhibited the analgesic response in the late phase of the formalin test. Moreover, both compounds potently inhibited cell-free mPGES-1 and 5-LO activity and preferentially suppressed the formation of mPGES-1 and 5-LO-derived products in cellular studies. Our in silico analysis for mPGES-1 and 5-LO supports that CS and CA are dual 5-LO/mPGES-1 inhibitors.. In summary, we propose that the combined inhibition of mPGES-1 and 5-LO by CS and CA essentially contributes to the bioactivity of these diterpenoids. Our findings pave the way for a rational use of Salvia spp., traditionally used as anti-inflammatory remedy, in the continuous expanding context of nutraceuticals.. This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.

Topics: Abietanes; Analgesics; Animals; Anti-Inflammatory Agents; Computer Simulation; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Inflammation; Lipoxygenase Inhibitors; Male; Mice; Molecular Docking Simulation; Monocytes; Neutrophils; Pain; Prostaglandin-E Synthases; Salvia

Rosmarinus officinalis, also named rosemary, is a native plant from the Mediterranean region that is useful for the treatment of inflammatory diseases. Studies using experimental models and/or in vitro tests have shown the important biological effects of rosemary. In this context, the mechanism of the anti-inflammatory activity of rosemary must be investigated to support the discovery of new substances with anti-inflammatory effects. The aim of the present study was to investigate the anti-inflammatory effects of crude extract oil free obtained from the leaves of rosemary in an animal model of inflammation, thus evaluating its medicinal use for the treatment of inflammatory conditions. Also its ethanol, hexane, and ethyl acetate fractions, as well as its isolated compounds carnosol and rosmarinic acid were analyzed. Swiss mice were used for the in vivo experiments. The effect of this herb on the inhibition of the leukocytes, exudation, myeloperoxidase, and adenosine-deaminase activities, nitrite/nitrate, interleukin 17A, and interleukin 10 levels and mRNA expression was determined. The crude extract and its derived fractions, in addition to its isolated compounds, inhibited leukocytes and decreased exudation and myeloperoxidase and adenosine-deaminase activities, as well as nitrite/nitrate and interleukin 17A levels and mRNA expression, besides increasing interleukin 10 levels and mRNA expression. Rosemary showed important anti-inflammatory activity by inhibiting leukocytes and decreasing exudation. These effects were associated with a decrease in the proinflammatory parameters (myeloperoxidase, adenosine-deaminase, nitrite/nitrate, and interleukin 17A) and an increase in the anti-inflammatory cytokine (interleukin 10). This study confirms the anti-inflammatory properties of rosemary and validates its use in folk medicine to treat inflammatory diseases such as rheumatism and asthma.

Topics: Abietanes; Adenosine Deaminase; Animals; Anti-Inflammatory Agents; Carrageenan; Cinnamates; Cytokines; Depsides; Disease Models, Animal; Inflammation; Inflammation Mediators; Leukocytes; Mice; Mice, Inbred Strains; Nitrates; Nitrites; Peroxidase; Phytotherapy; Plant Extracts; Plant Leaves; Pleurisy; RNA, Messenger; Rosmarinic Acid; Rosmarinus

The anti-inflammatory and anti-nociceptive properties of Rosmarinus officinalis L. (ROL) extract and its major constituent, carnosol in male NMRI mice (W:25-30 g) have been evaluated in the present study. Formalin (2%, 20 microL) was injected into the plantar portion of the hind paw and resulting pain and inflammation was studied for 60 min. The plant extract, carnosol and other drugs were administered intraperitoneally or subcutaneously 30 min before formalin injection. In a separate experiment, the effects of the extract and carnosol on plasma corticosterone levels and activity of the enzymes cyclooxygenase type 1 and 2 (COX1 and COX2) were investigated. Injection of different doses of ROL and carnosol reduced pain in the phase 2 of the formalin test, which was not inhibited by naloxone and/or memantine. In addition, pretreatment of the animals with ROL and/or carnosol reduces the formalin-induced inflammation. Furthermore, the extract and carnosol did not affect plasma corticosterone levels compared with the control group. Interestingly, both the extract and carnosol inhibited COX1 and COX2 activity. It could be concluded that ROL extract and carnosol suppressed pain and inflammation induced by formalin injection, which may be due to inhibition of COX1 and COX2 enzymes activity.

Topics: Abietanes; Alcohols; Analgesics; Animals; Anti-Inflammatory Agents; Corticosterone; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Disease Models, Animal; Dose-Response Relationship, Drug; Formaldehyde; Inflammation; Injections, Intraperitoneal; Injections, Subcutaneous; Male; Membrane Proteins; Mice; Pain; Phytotherapy; Plant Extracts; Plants, Medicinal; Rosmarinus; Solvents

Salvia officinalis L. has been used as a traditional herbal medicine for gastric disturbances and inflammatory processes. This study investigated the toxicological, antinociceptive and anti-inflammatory effects of the hydroalcoholic extract (HE) from leaves of Salvia officinalis and its isolated compounds in mice.. Mice were treated with HE before the induction of nociceptive response by chemical agents (acetic-acid, formalin, glutamate, capsaicin and cinnamaldehyde). Total leukocytes and plasma extravasation induced by acetic acid and paw oedema induced by glutamate, capsaicin and cinnamaldehyde were also measured. The antinociceptive effect of carnosol and ursolic acid/oleanolic acid were evaluated on formalin and cinnamaldehyde models.. In the acute toxicity test the value of estimated LD50 for HE was 44.7579 g/kg. Oral administration of HE (10, 30 and 100 mg/kg) inhibited the number of writhings, total leukocytes and plasma extravasation induced by acetic acid. In the formalin test, HE reduced both neurogenic and inflammatory phases, effect that was affected by naloxone. The glutamate-, capsaicin- and cinnamaldehyde-induced nociception and paw oedema were reduced by HE at doses that did not affect the locomotor activity of mice in the open field test. Carnosol (10mg/kg) and ursolic acid/oleanolic acid (30 mg/kg) inhibited the inflammatory phase of formalin and the nociception and mechanical allodynia induced by cinnamaldehyde.. These results demonstrate that HE presents significant anti-inflammatory and also antinociceptive effects on chemical behavioral models of nociception that involves an opioid mechanism. In addition, carnosol and ursolic acid/oleanolic acid contained in this plant appears to contribute for the antinociceptive property of the extract, possibly through a modulatory influence on TRPA1-receptors. However, further studies regarding the precise site and the mechanism of action of HE and carnosol and ursolic acid/oleanolic acid merited exploring further.

Topics: Abietanes; Administration, Oral; Analgesics; Animals; Anti-Inflammatory Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Inflammation; Lethal Dose 50; Mice; Motor Activity; Narcotic Antagonists; Oleanolic Acid; Pain; Pain Measurement; Plant Extracts; Plant Leaves; Plants, Medicinal; Salvia officinalis; Time Factors; Triterpenes; Ursolic Acid

We recently reported that (Lamiaceae) may alleviate CCl(4)-induced acute hepatotoxicity in rats, possibly blocking the formation of free radicals generated during CCl(4) metabolism. Carnosol, one of the main constituents of Rosmarinus, has been shown to have antioxidant and scavenging activities. Therefore, it is plausible to expect that carnosol may mediate some of the effects of Rosmarinus on oxidative stress consequences induced by CCl(4) in the liver.. We evaluated the effectiveness of carnosol to normalize biochemical and histological parameters of CCl(4)-induced acute liver injury.. Male Sprague Dawley rats (n = 5) injured by CCl(4) (oral dose 4 g/kg of body weight) were treated with a single intraperitoneal dose (5 mg/kg) of carnosol. Twenty-four hours later, the rats were anaesthetized deeply to obtain the liver and blood, and biochemical and histological parameters of liver injury were evaluated.. Carnosol normalized bilirubin plasma levels, reduced malondialdehyde (MDA) content in the liver by 69%, reduced alanine aminotransferase (ALT) activity in plasma by 50%, and partially prevented the fall of liver glycogen content and distortion of the liver parenchyma.. Carnosol prevents acute liver damage, possibly by improving the structural integrity of the hepatocytes. To achieve this, carnosol could scavenge free radicals induced by CCl(4), consequently avoiding the propagation of lipid peroxides. It is suggested that at least some of the beneficial properties of Rosmarinus officinalis are due to carnosol.

Topics: Abietanes; Acute Disease; Animals; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Hepatocytes; Liver; Liver Diseases; Male; Phenanthrenes; Rats; Rats, Sprague-Dawley