alloin and Disease-Models--Animal

Previous studies reported that Aloe vera ameliorated DSS-induced colitis and promoted mucus secretion. However, the effect of Aloin A (AA), a major compound of Aloe vera, on colitis and its exact mechanism remains uncovered.. C57BL/6 mice were successively subjected to 3% DSS solution for 5 days and distilled water for 2 days. Concurrently, AA (25, 50 mg/kg) and 5-aminosalicylic (500 mg/kg) were administrated intragastrically from day 1 to day 7. Colitis was evaluated by disease active index (DAI), colon length, inflammation response, and intestinal barrier function. In vitro LS174T cells challenged with 50 ng/ml of lipopolysaccharides (LPS) were used to validate the modulatory action of AA on the Notch signaling pathway.. Our results showed that oral administration with AA prominently prevented DSS-induced colitis symptoms in terms of decreased DAI, prevention of colon shortening, and reduced pathological damage. AA mitigated the inflammatory response evidenced by the decreased proinflammatory cytokines (TNF-α, IL-1β, IL-6) and increased anti-inflammatory cytokine (IL-10). Besides, AA inhibited apoptosis and facilitated proliferation in colons. Moreover, AA treatment up-regulated the expression of tight junction (TJ) proteins (ZO-1, Occludin) and promoted the secretion of MUC2 to decrease colon permeability. Mechanistically, AA inhibited the Notch pathway to promote the secretion of MUC2, which was consistent with LPS-challenged LS174 cells.. These results suggested that AA could prevent colitis by enhancing the intestinal barrier function via suppressing the Notch signaling pathway. Thus, AA might be a prospective remedy for ulcerative colitis.

Topics: Animals; Anti-Inflammatory Agents; Colitis; Colitis, Ulcerative; Colon; Cytokines; Dextran Sulfate; Disease Models, Animal; Emodin; Interleukin-10; Interleukin-6; Intestinal Mucosa; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Occludin; Prospective Studies; Signal Transduction; Tight Junction Proteins; Tumor Necrosis Factor-alpha; Water

As a class of difurancoumarin compounds with similar structures, aflatoxins (AF) are commonly found in the environment, soil, and food crops. AF pose a serious threat to the health of humans, poultry, and livestock. This study aimed to investigate the neuroprotective effect and detailed mechanism of aloin on hepatic injury induced by subchronic AFB1 in rats. The result showed that aloin could significantly inhibit the decrease in food intake, body weight growth, immune organ index, and serum albumin content caused by long-term AFB1 exposure. Meanwhile, aloin reduced the level of serum liver function and improved renal swelling and pathological changes of liver tissue. Aloin could also inhibit liver lipid peroxidation and improve liver antioxidant capacity. Further investigation revealed that aloin inhibited the activity and expression of hepatic CYP1A2 and CYP3A4 and down-regulated

Topics: Aflatoxin B1; Animals; Antioxidants; Chemical and Drug Induced Liver Injury; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP3A; Disease Models, Animal; Down-Regulation; Emodin; Interleukin-1beta; Lipid Peroxidation; Liver; Male; Rats

Aloin is a small-molecule drug well known for its protective actions in various models of damage. Traumatic brain injury (TBI)-induced cerebral edema from secondary damage caused by disruption of the blood-brain barrier (BBB) often leads to an adverse prognosis. Since the role of aloin in maintaining the integrity of the BBB after TBI remains unclear, we explored the protective effects of aloin on the BBB using in vivo and in vitro TBI models. Adult male C57BL/6 mice underwent controlled cortical impact injury, and mouse brain capillary endothelial bEnd.3 cells underwent biaxial stretch injury, then both received aloin treatment. In the animal experiments, we found 20 mg/kg aloin to be the optimum concentration to decrease cerebral edema, decrease disruption of the BBB, and improve neurobehavioral performance after cortical impact injury. In the cellular studies, the optimum concentration of 40 μg/mL aloin reduced apoptosis and reversed the loss of tight junctions by reducing the reactive oxygen species levels and changes in mitochondrial membrane potential after stretch injury. The mechanisms may be that aloin downregulates the phosphorylation of p38 mitogen-activated protein kinase, the activation of p65 nuclear factor-kappa B, and the ratios of B cell lymphoma (Bcl)-2-associated X protein/Bcl-2 and cleaved caspase-3/caspase-3. We conclude that aloin exhibits these protective effects on the BBB after TBI through its anti-oxidative stress and anti-apoptotic properties in mouse brain capillary endothelial cells. Aloin may thus be a promising therapeutic drug for TBI.

Topics: Animals; Blood-Brain Barrier; Brain Injuries, Traumatic; Disease Models, Animal; Emodin; Endothelial Cells; Male; Mice; Mice, Inbred C57BL; Stress, Mechanical

Osteoarthritis (OA) is a progressive and degenerative joint disease. Aloin is a bitter and yellow-brown-coloured compound from the Aloe plant and is allowed for use in foods as a "natural flavour". In our study, we examined the protective effects of Aloin on the inhibition of OA development as well as its underlying mechanism in both in vitro and vivo experiments. In in-vitro experiments, the protective effect of aloin on the anabolism and catabolism of the extracellular matrix (ECM) induced by IL-1 β in chondrocytes by inhibiting the expression of pro-inflammatory factors, including TNF-α (p = 0.016), IL-6 (p = 0.006), iNOS (p = 0.001) and COX-2 (p = 0.006). Mechanistically, Aloin suppressed the IL-1β-induced activation of the PI3K/Akt/NF-κB signalling pathway cascades. Moreover, molecular docking studies demonstrated that Aloin bound strongly to PI3K. In vivo, Aloin ameliorated the OA process in the destabilization of the medial meniscus (DMM) model. In summary, our findings demonstrate that Aloin ameliorates the progression of OA via the PI3K/Akt/NF-κB signalling pathways, which supports Aloin as a promising therapeutic agent for the treatment of OA.

Topics: Animals; Anti-Inflammatory Agents; Cells, Cultured; Chondrocytes; Disease Models, Animal; Emodin; Extracellular Matrix; Interleukin-1beta; Joints; Male; Mice, Inbred C57BL; Molecular Docking Simulation; NF-kappa B; Osteoarthritis; Phosphatidylinositol 3-Kinase; Phosphorylation; Proto-Oncogene Proteins c-akt; Signal Transduction

BACKGROUND Barbaloin is one of the main medicinal ingredients of aloe vera, which displays various anti-inflammatory and anti-apoptosis properties in several inflammatory and fibrotic diseases. Our study evaluated its efficacy against dextran sulfate sodium (DSS)-induced colitis in rats. MATERIAL AND METHODS Ulcerative colitis (UC) rat models were established in vivo, and after barbaloin treatment, body weight and inflammation index were measured. Additionally, the signaling mechanism by which barbaloin protects against UC was investigated using LPS-infected Caco-2 cells. RESULTS Barbaloin could significantly reverse UC-induced weight loss and colon injury. Further, it could effectively increase the mRNA expression of IL-4 and IL-10 in colon tissues, while decreasing the expression of IFN-γ, IL-6, IL-1ß, and TNF-alpha. Furthermore, it significantly enhanced UC-inhibited atresia band 1 (ZO-1), occludin, and E-cadherin, and was also found to activate the AMPK signaling pathway. Additionally, si-RAN-induced knockdown, and overexpression assay showed that barbaloin could inhibit the UC-enhanced MLCK signaling pathway by activating the AMPK signaling pathway. CONCLUSIONS Barbaloin can effectively inhibit inflammation and reverse epithelial barrier function to protect against UC, possibly via activation of the AMPK signaling pathway.

Topics: AMP-Activated Protein Kinases; Animals; Anthracenes; Caco-2 Cells; Cadherins; Colitis; Dextran Sulfate; Dextrans; Disease Models, Animal; Fluorescein-5-isothiocyanate; Humans; Inflammation; Inflammation Mediators; Intestinal Mucosa; Lipopolysaccharides; Male; Myosin-Light-Chain Kinase; Occludin; Organ Size; Rats, Wistar; Signal Transduction; Zonula Occludens-1 Protein

Barbaloin (Bar) has a myocardial protective effect, but its mechanism of action is uncertain. The endoplasmic reticulum stress (ERS)‑mediated apoptosis pathway serves an important role in the pathogenesis of myocardial ischemia‑reperfusion injury (MIRI). Inhibiting ERS may significantly improve the progression of MIRI and serve a role in its prevention. Therefore, based on current knowledge of ERS‑mediated cardiomyocyte apoptosis and the cardioprotective effect of Bar, the purpose of the present study was to further evaluate the myocardial protective effect and potential mechanisms of Bar pretreatment in MIRI. The present study established a MIR rat model and randomly divided these rats into four groups. Prior to myocardial ischemia, Bar (20 mg/kg) was administered to rats once daily for 1 week. Myocardial blood serum lactate dehydrogenase and creatine kinase were subsequently measured. A terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay was used to evaluate the myocardial protective effect of Bar pretreatment on MIRI. To assess whether the ERS signaling pathway was involved in the myocardial protection mechanism of Bar pretreatment, the expression levels of ERS‑associated proteins, protein canopy homolog 2 (CNPY2), glucose regulatory protein 78, transcriptional activator 4, C/EBP‑homologous protein (CHOP), PKR endoplasmic reticulum kinase (PERK), caspase‑12 and caspase‑3 were detected by western blot analysis, immunohistochemistry or reverse transcription‑quantitative polymerase chain reaction. The results confirmed that Bar pretreatment significantly reduced the damage and the level of apoptosis caused by MIR. Bar pretreatment significantly inhibited the expression of ERS‑associated proteins in cardiomyocytes. In addition, the immunohistochemistry results demonstrated that Bar pretreatment significantly inhibited the CNPY2‑positive cell apoptosis ratio of cardiomyocytes. Therefore, the results of the current study suggested that CNPY2 is present in cardiomyocytes and participates in the development of MIRI by initiating the PERK‑CHOP signaling pathway. Bar pretreatment may attenuate MIRI by inhibiting the CNPY2‑PERK apoptotic pathway.

Topics: Animals; Anthracenes; Apoptosis; Cardiotonic Agents; Creatine Kinase; Disease Models, Animal; eIF-2 Kinase; Endoplasmic Reticulum Stress; L-Lactate Dehydrogenase; Male; Membrane Proteins; Myocardial Reperfusion Injury; Myocytes, Cardiac; Rats, Sprague-Dawley; RNA, Messenger

Numerous herbal-derived natural products are excellent anti-inflammatory agents. Several studies have reported that aloin, the major anthraquinone glycoside obtained from the

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Cell Survival; Cyclooxygenase 2; Cytokines; Disease Models, Animal; Emodin; Inflammation; Inflammation Mediators; Lipopolysaccharides; Macrophages; Mice; Models, Biological; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Phosphorylation; Protein Transport; Signal Transduction; Transcription Factor RelA

Topics: Ammonia; Animals; Aquaporin 4; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Emodin; Ependymoglial Cells; Hepatic Encephalopathy; Liver; Male; Potassium Channels, Inwardly Rectifying; Rats, Sprague-Dawley; Retina; Retinal Degeneration; Thioacetamide

The present study was designed to investigate the protective effect of aloin against alcoholic liver disease in a chronic alcohol feeding mouse model. Mice were given alcohol twice a day by intragastric administration for 11 weeks (4.0, 4.7, 5.5 g/kg bw/day for the first 3 weeks respectively, 6.3 g/kg bw/day for the following 8 weeks). Aloin (10, 30 mg/kg bw) or vehicle was given by gavage to mice after each alcohol administration. Alcohol elevated the serum transaminases alanine aminotransferase, aspartate aminotransferase, total cholesterol and triglyceride levels which were significantly attenuated by the co-administration of aloin (p < 0.05). Histopathological observations were consistent with these indices. Co-administration of aloin significantly suppressed the alcohol-dependent induction of sterol regulatory element-binding protein-1c expression (p < 0.01) and remarkably up-regulated the mRNA levels of AMP-activated protein kinase-α2 (p < 0.001). Furthermore, aloin supplementation significantly inhibited the alcohol-dependent elevation of malondialdehyde and cytochrome P4502E1 expression (p < 0.05), and significantly elevated superoxide dismutase activity (p < 0.01). The up-regulation of serum lipopolysaccharide (LPS), hepatic nitric oxide, tumor necrosis factor α, toll-like receptor-4, and myeloid differentiation primary response gene 88 were also markedly suppressed by the co-administration of aloin (p < 0.05) in alcohol-treated mice. These results suggest that aloin may represent a novel, protective strategy against chronic alcoholic liver injury by attenuating lipid accumulation, oxidative stress and LPS-induced inflammatory response.

Topics: Animals; Antioxidants; Biomarkers; Cytokines; Disease Models, Animal; Emodin; Hepatitis, Alcoholic; Lipid Metabolism; Lipid Peroxidation; Liver Function Tests; Male; Mice, Inbred Strains; Oxidative Stress

Ultraviolet B (UVB) irradiation mainly affects biological tissues by inducing an increase in reactive oxygen species (ROS) production which leads to deleterious outcomes for the skin, including pain and inflammation. As a protective strategy, many studies have focused on the use of natural products. The aim of this study was to investigate the effects of Aloe saponaria on nociceptive, inflammatory, and oxidative parameters in a model of UVB-induced sunburn in adult male Wistar rats. Sunburned animals were topically treated with vehicle (base cream), 1% silver sulfadiazine (positive control) or A. saponaria (10%) once a day for 6days. UVB-induced nociception (allodynia and hyperalgesia), inflammation (edema and leukocyte infiltration) and oxidative stress (increases in H2O2, protein carbonyl levels and lipid peroxidation and a decrease in non protein thiol content) were reduced by both A. saponaria and sulfadiazine topical treatment. Furthermore, A. saponaria or its constituents aloin and rutin reduced the oxidative stress induced by H2O2 in skin homogenates in vitro. Our results demonstrate that topical A. saponaria treatment displayed anti-nociceptive and anti-inflammatory effects in a UVB-induced sunburn model, and these effects seem to be related to its antioxidant components.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Chromatography, High Pressure Liquid; Disease Models, Animal; Emodin; Inflammation; Male; Oxidative Stress; Plant Extracts; Plant Leaves; Rats; Rats, Wistar; Saponaria; Silver Sulfadiazine; Skin; Sunburn; Time Factors; Ultraviolet Rays

Nanobiotechnology is an emerging biological branch of nanotechnology. Application of nanoparticles with specific size and shape in biology has already shown unforeseen and interesting results. A study was conducted to evaluate the therapeutic potential of phytogenically derived aloin mediated nanosilver particles (AAgNPs), prepared by reduction of silver nitrate with aloin, in Staphylococcus aureus induced murine mastitis. A total of 40 female mice were divided into five groups of eight animals each. Group I served as lactating control, groups II-V were inoculated with 20 μl of 24 h broth culture of S. aureus containing 4.0 × 105 cfu/quarter under ketamine anaesthesia. After 6 h post inoculation, groups III and IV received 20 μl of aloin nanosilver (AAgNPs) through intramammary and intraperitoneal routes, respectively. Group V received antibiotic cefepime at 1 mg/kg body weight through the intra-peritoneal route. After 18 h post-treatment, serum C reactive protein, weights of mammary glands, mammary gland bacterial load, thiobarbituric acid reactive substances content, reduced glutathione content, superoxide dismutase activity and catalase activity and histopathology were determined. The compound showed a minimum inhibitory concentration of 21.8 ng/ml against S. aureus. Significant reduction (98%) in poly-morpho nuclear cell infiltration was observed with AAgNPs than antibiotic (50%).

Topics: Animals; Antioxidants; Body Weight; Disease Models, Animal; Drug Design; Emodin; Female; Mastitis; Metal Nanoparticles; Mice; Phylogeny; Silver; Staphylococcal Infections

Aloe has been a very popular folk remedy for inflammation-related pathological conditions despite the lack of studies reporting its efficacy in vivo. The present study evaluated the anti-inflammatory effects of aloe components (aloin, aloesin and aloe-gel) known to be biologically active in the rat model of colitis.. Male Sprague Dawley rats were fed experimental diets for 2 weeks before and during the induction of colitis. Drinking water containing 3% dextran sulfate sodium (DSS) was provided for 1 week to induce colitis. At the end of the experimental period, clinical and biochemical markers were compared.. Plasma leukotriene B(4) (LTB(4)) and tumor necrosis factor-α (TNF-α) concentrations were significantly decreased in all groups supplemented with aloe components compared to the colitis control group (p<0.05). Animals fed both a 0.1% and 0.5% aloesin supplemented diet showed colonic myeloperoxidase (MPO) activities which were decreased by 32.2% and 40.1%, respectively (p<0.05). Colonic mucosa TNF-α and interleukin-1ß (IL-1β) mRNA expressions were significantly reduced in all animals fed aloin, aloesin, or aloe-gel (p<0.05).. Dietary supplementation of aloe components ameliorates intestinal inflammatory responses in a DSS-induced ulcerative colitis rat model. In particular, aloesin was the most potent inhibitor. Further studies are required for a more complete understanding of the specific mechanism of the action of these supplements.

Topics: Aloe; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chromones; Colitis; Colon; Diet; Dietary Supplements; Disease Models, Animal; Emodin; Gels; Glucosides; Interleukin-1beta; Leukotriene B4; Male; Peroxidase; Plant Preparations; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

A 2-y carcinogenicity study of Aloe, Aloe arborescens Miller var. natalensis Berger, a food additive, was conducted for assessment of toxicity and carcinogenic potential in the diet at doses of 4% or 0.8% in groups of male and female Wistar Hannover rats. Both sexes receiving 4% showed diarrhea, with loss of body weight gain. The survival rate in the 4% female group was significantly increased compared with control females after 2 y. Hematological and biochemical examination showed increase of RBC, Hb, and Alb in the 4% males. The cause of these increases could conceivably have been dehydration through diarrhea. AST and Na were significantly decreased in the males receiving 4%, and Cl was significantly decreased in both 4% and 0.8% males. A/G was significantly increased in the 4% females, and Cl was significantly decreased (0.8%) in the female group. Histopathologically, both sexes receiving 4% showed severe sinus dilatation of ileocecal lymph nodes, and yellowish pigmentation of ileocecal lymph nodes and renal tubules. Adenomas or adenocarcinomas in the cecum, colon, and rectum were observed in 4% males but not in the 0.8% and control male groups. Similarly, in females, adenomas in the colon were also observed in the 4% but not 0.8% and control groups. In conclusion, Aloe, used as a food additive, exerted equivocal carcinogenic potential at 4% high-dose level on colon in the 2-y carcinogenicity study in rats. Aloe is not carcinogenic at nontoxic-dose levels and that carcinogenic potential in at 4% high-dose level on colon is probably due to irritation of the intestinal tract by diarrhea.

Topics: Aloe; Animals; Colonic Neoplasms; Diarrhea; Disease Models, Animal; Emodin; Female; Glucosides; Male; Plant Extracts; Plant Leaves; Rats; Rats, Wistar; Survival Rate