diospyros and Inflammation

Rheumatoid arthritis is a chronic inflammatory disorder of polyarticular tissues, characterised by progressive synovitis. Its prolonged treatment imparts a huge burden on the healthcare system and results in toxicity, which necessitates the search for safe, efficacious and cost-effective therapies. Diospyros malabarica (Desr.) Kostel is traditionally used for anti-inflammatory purposes; however, to the best of our knowledge, there is no detailed study reporting the in vivo anti-inflammatory potential of this plant. Therefore, in the current study, the methanol extract of D. malabarica (Desr.) Kostel fruit (mDMF) was evaluated for its antioxidant, anti-inflammatory and anti-arthritic potentials, along with its underlying mechanisms. The antioxidant activity was evaluated by DPPH assay. Total phenolic and flavonoid contents were estimated via colorimetric and high-performance liquid chromatography (HPLC) methods. Different doses (250, 500 and 750 mg/kg) of mDMF were used to evaluate the anti-inflammatory and anti-arthritis actions in acute inflammatory (carrageenan and histamine-induced paw oedema) and Freund's complete adjuvant (FCA)-induced arthritis rat models. Levels of various pro- and anti-inflammatory biomarkers were estimated using ELISA and RT-PCR techniques. Paw samples were used for different histopathological and radiographic studies. Qualitative phytochemical and HPLC analyses indicated the presence of various polyphenolic compounds in mDMF, which exhibited marked antioxidant activity in the DPPH assay. mDMF showed time-dependent anti-inflammatory and anti-arthritic effects in in vivo models. ELISA assay data showed significant (p < 0.05) reduction in the serum levels of C-reactive protein and rheumatoid factor in the mDMF treatment groups. RT-PCR data showed significant (p < 0.05) down-regulation of various pro-inflammatory markers (TNF-α, NF-κB, COX-2, IL-1β and IL-6) and up-regulation of anti-inflammatory markers (IκB, IL-4 and IL-10) in serum samples of rats treated with mDMF. The histopathology of the ankle joints showed reduced pannus formation, joint swelling and synovial hyperplasia in mDMF-treated animals when compared with the untreated disease control group. Overall, it may be concluded that the antioxidant, anti-inflammatory and anti-arthritis properties of mDMF are due to its flavonoid and phenolic constituents. Further studies using a stable oral dosage form of D. malabarica (Desr.) Kostel fruits extract are warranted to explore i

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Arthritis, Experimental; Biomarkers; Cytokines; Diospyros; Edema; Flavonoids; Fruit; Inflammation; Plant Extracts; Rats; Rats, Sprague-Dawley

Nontuberculous mycobacteria (NTM), including Mycobacterium avium complex (MAC), cause opportunistic chronic pulmonary infections. Notably, MAC susceptibility is regulated by various factors, including the host immune system. Persimmon (Ebenaceae Diospyros kaki Thunb.) tannin is a condensed tannin composed of a polymer of catechin groups. It is well known that condensed tannins have high antioxidant activity and bacteriostatic properties. However, it is hypothesized that condensed tannins might need to be digested and/or fermented into smaller molecules in vivo prior to being absorbed into the body to perform beneficial functions. In this study, we evaluated the effects of soluble persimmon-derived tannins on opportunistic MAC disease. Soluble tannins were hydrolyzed and evaluated by the oxygen radical absorbance capacity (ORAC) method. The ORAC value of soluble tannin hydrolysate was approximately five times greater than that of soluble tannin powder. In addition, soluble tannin hydrolysate exhibited high bacteriostatic activity against MAC in vitro. Furthermore, in an in vivo study, MAC infected mice fed a soluble tannin-containing diet showed significantly higher anti-bacterial activity against MAC and less pulmonary granuloma formation compared with those fed a control diet. Tumor necrosis factor α and inducible nitric oxide synthase levels were significantly lower in lungs of the soluble tannin diet group compared with the control diet group. Moreover, proinflammatory cytokines induced by MAC stimulation of bone marrow-derived macrophages were significantly decreased by addition of soluble tannin hydrolysate. These data suggest that soluble tannin from persimmons might attenuate the pathogenesis of pulmonary NTM infection.

Topics: Animals; Anti-Bacterial Agents; Diospyros; Disease Models, Animal; Female; Inflammation; Mice; Mice, Inbred BALB C; Mycobacterium avium-intracellulare Infection; Tannins

Diospyros lotus is traditionally used for the treatment of diabetes, diarrhea, tumor, and hypertension. The purpose of this study was to investigate the anti-inflammatory effect and underlying molecular mechanisms of myricetin in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Myricetin dose-dependently suppressed the production of pro-inflammatory mediators (NO, iNOS, PGE2, and COX-2) in LPS-stimulated RAW264.7 macrophages. Myricetin administration decreased the production of NO, iNOS, TNF-α, IL-6, and IL-12 in mice. Myricetin decreased NF-κB activation by suppressing the degradation of IκBα, nuclear translocation of p65 subunit of NF-κB, and NF-κB DNA binding activity in LPS-stimulated RAW264.7 macrophages. Moreover, myricetin attenuated the phosphorylation of STAT1 and the production of IFN-β in LPS-stimulated RAW264.7 macrophages. Furthermore, myricetin induced the expression of HO-1 through Nrf2 translocation. In conclusion, these results suggest that myricetin inhibits the production of pro-inflammatory mediators through the suppression of NF-κB and STAT1 activation and induction of Nrf2-mediated HO-1 expression in LPS-stimulated RAW264.7 macrophages.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Diospyros; Flavonoids; Gene Expression Regulation; Heme Oxygenase-1; Inflammation; Interferon-beta; Lipopolysaccharides; Macrophage Activation; Macrophages; Male; Membrane Proteins; Mice; Mice, Inbred BALB C; NF-E2-Related Factor 2; NF-kappa B; NF-KappaB Inhibitor alpha; Nitric Oxide; Nitric Oxide Synthase Type II; Phosphorylation; Signal Transduction; STAT1 Transcription Factor; Tumor Necrosis Factor-alpha

Diospyros kaki (DK) contains an abundance of flavonoids and has been used in folk medicine in Korea for centuries. Here, we report for the first time the anti-inflammatory activities of Quercetin (QCT) and Quercetin 3-O-β-("2"-galloyl)-glucopyranoside (Q32G) isolated from DK. We have determine the no cytotoxicity of Q32G and QCT against RAW 264.7 cells up to concentration of 50 μM. QCT and Q32G demonstrated potent anti-inflammatory activities by reducing expression of nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and mitogen-activated protein kinase (MAPKs) in mouse RAW 264.7 macrophages activated with lipopolysaccharide (LPS). Both QCT or Q32G could decrease cellular protein levels of COX-2 and iNOS as well as secreted protein levels of NO, PGE

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Cyclooxygenase 2; Cytokines; Diospyros; Glucosides; Glycosides; Inflammation; Inflammation Mediators; Lipopolysaccharides; Macrophages; Mice; Mitogen-Activated Protein Kinases; Nitric Oxide; Phytotherapy; Plant Extracts; Quercetin; RAW 264.7 Cells; Republic of Korea

Diospyros kaki (D. kaki) has been cultivated throughout Eastern Asia for hundreds of years. D. kaki contains various biological active compounds, such as amino acids, carotenoids, flavonoids, tannins, catechins and vitamin A. Previous studies have shown that D. kaki has beneficial effects on homeostasis, constipation, hypertension, atherosclerosis and allergic dermatitis and is a good source of antioxidants, polyphenols and dietary fiber. However, the anti-allergic and anti-inflammatory effects of D. kaki have not yet been elucidated. This study aimed to investigate the protective effects of the aqueous extract of Diospyros kaki (AEDK) on mast cell-mediated allergic inflammation and to determine its possible mechanisms of action by using in vitro and in vivo mast cell-based models. The cAMP and intracellular calcium levels were measured to clarify the mechanisms by which AEDK inhibits the release of histamine from mast cells. AEDK inhibited the release of histamine and β-hexosaminidase from mast cells by modulating cAMP and intracellular calcium levels. We also measured the expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β. AEDK decreased gene expression and the secretion of the pro-inflammatory cytokines, TNF-α and IL-1β by inhibiting nuclear factor-κB. In addition, AEDK inhibited systemic and cutaneous allergic reaction. The inhibitory effects of AEDK on allergic reaction and the release of histamine were found to be similar to those of disodium cromoglycate, a known anti-allergic drug. To isolate the active component of AEDK, activity-guided fractionation was performed, based on the inhibitory effects on systemic anaphylaxis. Catechin was identified as an active compound. The present findings provide evidence that AEDK inhibits allergic inflammation and suggest the therapeutic application of AEDK in allergic inflammatory disorders.

Topics: Animals; Anti-Asthmatic Agents; Calcium; Cell Line; Cromolyn Sodium; Diospyros; Disease Models, Animal; Histamine Release; Humans; Hypersensitivity; Inflammation; Interleukin-1beta; Interleukin-6; Male; Mast Cells; Mice; Mice, Inbred ICR; NF-kappa B; Plant Extracts; Tumor Necrosis Factor-alpha

Persimmon proanthocyanidin was fractionated on Toyopearl TSK-HW-50-F to yield a fraction with strong inhibition on the catalytic activity and edema-inducing activity and lethality of Chinese cobra PLA(2). Thiolysis suggested that the terminal units included C, EGCG and myricetin, and epicatechin, epigallocatechin, (epi)gallocatechin-3-O-gallate, and (epi)catechin-3-O-gallate occurred as extender units. The mean degree of polymerization was 23.7. MALDI TOF/MS, thioly-HPLC, FTIR and circular dichroism (CD) analyses showed that the fraction had high prodelphinidin content (55%) and a very high degree of 3-O-galloylation (92%). A type linkage is dominant in it and it had 4β linkage of the flavanyl substituent and 4R absolute configuration.

Topics: Animals; Anti-Inflammatory Agents; Diospyros; Elapidae; Female; Fruit; Inflammation; Male; Mice; Molecular Structure; Phospholipase A2 Inhibitors; Plant Exudates; Polymers; Proanthocyanidins; Rats; Reptilian Proteins; Snake Venoms

Recent evidence strongly suggests that oxidative stress due to redox imbalance is causally associated with inflammatory processes and various diseases including diabetes. We examined the effects of proanthocyanidin from persimmon peel, using both oligomers and polymers, against oxidative stress with elucidation of the underlying mechanisms in streptozotocin-induced diabetic rats. The elevation of lipid peroxidation in the kidney and serum under the diabetic condition was decreased by the administration of proanthocyanidin. The suppression of reactive oxygen species generation and elevation of the reduced glutathione/oxidized glutathione ratio were observed in the groups administered proanthocyanidin. These results support the protective role of proanthocyanidin from oxidative stress induced by diabetes. Moreover, proanthocyanidin, especially its oligomeric form, affected the inflammatory process with regulation of related protein expression, inducible nitric oxide synthase, cyclooxygenase-2, and upstream regulators, nuclear factor kappaB, and inhibitor-binding protein kappaB-alpha. Proanthocyanidin ameliorated the diabetic condition by decreases of serum glucose, glycosylated protein, serum urea nitrogen, urinary protein, and renal advanced glycation endproducts. In particular, oligomeric proanthocyanidin exerted a stronger protective activity than the polymeric form. This suggests that the polymerization of proanthocyanidin has an effect on its protective effect against diabetes. The present study supports the beneficial effect of proanthocyanidin against diabetes and oxidative stress-related inflammatory processes.

Topics: Animals; Diabetes Mellitus, Experimental; Diospyros; Fruit; Glutathione; Inflammation; Kidney; Lipid Peroxidation; Male; Oxidative Stress; Proanthocyanidins; Rats; Rats, Wistar

Pharmacological studies were conducted with the hexane extract of the dry stem of Diospyros variegata Kruz. (Ebenaceae) on experimental animals for evaluating the analgesic, antipyretic and anti-inflammatory activities. In the analgesic test, the hexane extract elicited inhibitory intensity on acetic acid-induced writhing response and on the late phase of formalin test but possessed only a weak effect on the tail-flick response and on the early phase of formalin test. The hexane extract also elicited antipyretic action when tested in yeast-induced hyperthermia in rats. In addition, the hexane extract showed an anti-inflammatory effect when tested in ethyl phenylpropiolate (EPP)- and arachidonic acid (AA)-induced rat ear edema.

Topics: Acetic Acid; Analgesics, Non-Narcotic; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Diospyros; Fever; Formaldehyde; Hexanes; Inflammation; Male; Methanol; Mice; Morphine; Pain; Pain Measurement; Phenylbutazone; Plant Extracts; Rats; Rats, Sprague-Dawley; Reaction Time; Solvents