Natural Anti-inflammatory Compounds Research Articles

Determination of betaine, a natural potential anti-inflammatory compound, using sildenafil as an internal standard in human plasma by high performance liquid chromatography–mass spectrometry

Betaine is a naturally occurring cationic functional group which shows a wide range of therapeutic activities. The present research work involves rapid; robust and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method developed and validated for s analysis of betaine in human plasma. This method involved a solid phase extraction and a subsequent analysis performed on an LC-MS system which contained the turbo spray ionization interface. Chromatographic separation was performed using a Gemini C18 column. Good linearity was observed over the concentration range of 10.00 ng/mL to 1203.26 ng/mL with a correlation coefficient (r² ≥ 0.9984). Sildenafil was used as the internal standard in the present method. The method involves simple isocratic chromatography conditions and mass spectrometric detection in the positive ionization mode. The intra-day and inter-day precision and accuracy of the quality control samples were within the acceptance criteria of ±15%. The total elution time was about 5 min which allows higher throughput. This validated method can be applied for analysis of real samples from a bioequivalence study involving administration of formulations containing betaine as their active therapeutic components.

Smart Dressings Based on Nanostructured Fibers Containing Natural Origin Antimicrobial, Anti-Inflammatory, and Regenerative Compounds.

A fast and effective wound healing process would substantially decrease medical costs, wound care supplies, and hospitalization significantly improving the patients’ quality of life. The search for effective therapeutic approaches seems to be imperative in order to avoid the aggravation of chronic wounds. In spite of all the efforts that have been made during the recent years towards the development of artificial wound dressings, none of the currently available options combine all the requirements necessary for quick and optimal cutaneous regeneration. Therefore, technological advances in the area of temporary and permanent smart dressings for wound care are required. The development of nanoscience and nanotechnology can improve the materials and designs used in topical wound care in order to efficiently release antimicrobial, anti-inflammatory and regenerative compounds speeding up the endogenous healing process. Nanostructured dressings can overcome the limitations of the current coverings and, separately, natural origin components can also overcome the drawbacks of current antibiotics and antiseptics (mainly cytotoxicity, antibiotic resistance, and allergies). The combination of natural origin components with demonstrated antibiotic, regenerative, or anti-inflammatory properties together with nanostructured materials is a promising approach to fulfil all the requirements needed for the next generation of bioactive wound dressings. Microbially compromised wounds have been treated with different essential oils, honey, cationic peptides, aloe vera, plant extracts, and other natural origin occurring antimicrobial, anti-inflammatory, and regenerative components but the available evidence is limited and insufficient to be able to draw reliable conclusions and to extrapolate those findings to the clinical practice. The evidence and some promising preliminary results indicate that future comparative studies are justified but instead of talking about the beneficial or inert effects of those natural origin occurring materials, the scientific community leads towards the identification of the main active components involved and their mechanism of action during the corresponding healing, antimicrobial, or regenerative processes and in carrying out systematic and comparative controlled tests. Once those natural origin components have been identified and their efficacy validated through solid clinical trials, their combination within nanostructured dressings can open up new avenues in the fabrication of bioactive dressings with outstanding characteristics for wound care. The motivation of this work is to analyze the state of the art in the use of different essential oils, honey, cationic peptides, aloe vera, plant extracts, and other natural origin occurring materials as antimicrobial, anti-inflammatory and regenerative components with the aim of clarifying their potential clinical use in bioactive dressings. We conclude that, for those natural occurring materials, more clinical trials are needed to reach a sufficient level of evidence as therapeutic agents for wound healing management.

Sulfated and Glucuronated trans-Resveratrol Metabolites Regulate Chemokines and Sirtuin-1 Expression in U-937 Macrophages.

The natural anti-inflammatory compound resveratrol (RES) is metabolized upon ingestion. After dietary-scale doses, plasma concentrations of sulfated and glucuronated metabolites in humans exceed those of RES. The aim of this in vitro study was to assess the effect of physiological concentrations (1 μM) of the most abundant RES metabolites (RES-3-O-sulfate, R3S; RES-disulfates, RdS; RES-3-O-glucuronide, R3G; RES-4'-O-glucuronide, R4G) on genes and proteins involved in immune cell chemotaxis and inflammation (IL-8, MIP-1b, MCP-1, CCR1, CCR2, CXCR2, SIRT1) in a cell model of lipopolysaccharide (LPS)-activated U-937 macrophages. Levels of MCP-1 mRNA were comparably decreased after 3 h of treatment with R3S and RdS by -24.7 ± 5.51 and -28.7 ± 19.2%, respectively. LPS-induced MCP-1 protein release was reduced after 3 h of treatment by R3S (-20.8 ± 13.9%) and RdS (-25.7 ± 8.29%). After a 9 h treatment, RdS also inhibited IL-8 and MIP-1b protein release by -22.9 ± 3.57 and -20.1 ± 7.00%, respectively. Glucuronides showed differential effects after 6 h of treatment, with R4G up-regulating mRNA of MIP-1b (24.5 ± 14.8%) and R3G and R4G down-regulating CXCR2 surface protein compared to cells treated with LPS alone, by -5.33 ± 4.18 and -15.2 ± 5.99%, respectively. On the contrary, R3G and R4G up-regulated SIRT1 mRNA by 22.7 ± 17.9 and 22.8 ± 16.9%, respectively, in LPS-stimulated U-937 macrophages, showing anti-inflammatory properties. In conclusion, sulfated RES metabolites show an interesting beneficial potential for attenuating inflammatory immune processes.

4β-Hydroxywithanolide E isolated from Physalis pruinosa calyx decreases inflammatory responses by inhibiting the NF-κB signaling in diabetic mouse adipose tissue

Chronic inflammation in adipose tissue together with obesity induces insulin resistance. Inhibitors of chronic inflammation in adipose tissue can be a potent candidate for the treatment of diabetes; however, only a few compounds have been discovered so far. The objective of this study was to find a novel inhibitor that can suppress the inflammatory response in adipose tissue and to elucidate the intracellular signaling mechanisms of the compound. To find the active compounds, we established an assay system to evaluate the inhibition of induced MCP-1 production in adipocyte/macrophage coculture in a plant extract library. The active compound was isolated by performing high-performance liquid chromatography (HPLC) and was determined as 4β-hydroxywithanolide E (4βHWE) by nuclear magnetic resonance (NMR) and mass spectroscopy (MS) spectral analyses. The effect of 4βHWE on inflammation in adipose tissue was assessed with adipocyte culture and db/db mice. During the screening process, Physalis pruinosa calyx extract was found to inhibit production of MCP-1 in coculture strongly. 4βHWE belongs to the withanolide family of compounds, and it has the strongest MCP-1 production inhibitory effect and lowest toxicity than any other withanolides in coculture. Its anti-inflammatory effect was partially dependent on the attenuation of NF-κB signaling in adipocyte. Moreover, in vivo experiments showed that the oral administration of 4βHWE to db/db mice resulted in the inhibition of macrophage invasion and cytokine expression in adipose tissue after 2 weeks of treatment; improved the plasma adiponectin, non-esterified fatty acids and MCP-1 concentrations; and increased glucose tolerance after 3 to 4 weeks of treatment. These results suggest that 4βHWE has anti-inflammatory effect via inhibition of NF-κB activation in adipocyte. Moreover, the attenuation of inflammation in adipocyte has an effect on the inhibition of macrophage accumulation in obese adipose tissue. Consequently, 4βHWE improves impaired glucose tolerance. Thus, 4βHWE is a useful natural anti-inflammatory compound to attenuate progression of diabetes and obesity.

The modulatory effect of ellagic acid and rosmarinic acid on ultraviolet-B-induced cytokine/chemokine gene expression in skin keratinocyte (HaCaT) cells.

Ultraviolet radiation (UV) induces an increase in multiple cutaneous inflammatory mediators. Ellagic acid (EA) and rosmarinic acid (RA) are natural anti-inflammatory and immunomodulatory compounds found in many plants, fruits, and nuts. We assessed the ability of EA and RA to modulate IL-1β, IL-6, IL-8, IL-10, MCP-1, and TNF-α gene expression in HaCaT cells after UVB irradiation. Cells were treated with UVB (100 mJ/cm2) and simultaneously with EA (5 μM in 0.1% DMSO) or RA (2.7 μM in 0.5% DMSO). Moreover, these substances were added to the UVB-irradiated cells 1 h or 6 h before harvesting, depending on the established UVB-induced cytokine expression peak. Cytokine gene expression was examined using quantitative real time polymerase chain reaction. RA produced a significant reduction in UVB-induced expression of IL-6, IL-8, MCP-1, and TNF-α when applied at the same time as irradiation. EA showed milder effects compared with RA, except for TNF-α. Both substances decreased IL-6 expression, also when applied 5 h after irradiation, and always produced a significant increase in UVB-induced IL-10 expression. Our findings suggest that EA and RA are able to prevent and/or limit the UVB-induced inflammatory cascade, through a reduction in proinflammatory mediators and the enhancement of IL-10, with its protective function.

Inhibitory Effect of Natural Anti-Inflammatory Compounds on Cytokines Released by Chronic Venous Disease Patient-Derived Endothelial Cells

Large vein endothelium plays important roles in clinical diseases such as chronic venous disease (CVD) and thrombosis; thus to characterize CVD vein endothelial cells (VEC) has a strategic role in identifying specific therapeutic targets. On these bases we evaluated the effect of the natural anti-inflammatory compounds α-Lipoic acid and Ginkgoselect phytosome on cytokines/chemokines released by CVD patient-derived VEC. For this purpose, we characterized the levels of a panel of cytokines/chemokines (n = 31) in CVD patients' plasma compared to healthy controls and their release by VEC purified from the same patients, in unstimulated and TNF-α stimulated conditions. Among the cytokines/chemokines released by VEC, which recapitulated the systemic profile (IL-8, TNF-α, GM-CSF, INF-α2, G-CSF, MIP-1β, VEGF, EGF, Eotaxin, MCP-1, CXCL10, PDGF, and RANTES), we identified those targeted by ex vivo treatment with α-Lipoic acid and/or Ginkgoselect phytosome (GM-CSF, G-CSF, CXCL10, PDGF, and RANTES). Finally, by investigating the intracellular pathways involved in promoting the VEC release of cytokines/chemokines, which are targeted by natural anti-inflammatory compounds, we documented that α-Lipoic acid significantly counteracted TNF-α-induced NF-κB and p38/MAPK activation while the effects of Ginkgo biloba appeared to be predominantly mediated by Akt. Our data provide new insights into the molecular mechanisms of CVD pathogenesis, highlighting new potential therapeutic targets.

Inhibition of Prostaglandin D2 Production by Trihydroxy Fatty Acids Isolated from Ulmus davidiana var. japonica

The stem and root barks of Ulmus davidiana var. japonica (Ulmaceae) have been used to treat inflammatory diseases including mastitis, rhinitis, sinusitis, and enteritis. In an ongoing study focused on the discovery of natural anti-inflammatory compounds from natural products, a methanol extract of the stem and root barks of U. davidiana var. japonica showed anti-inflammatory activities. Activity-guided fractionation of the methanol extract yielded a new trihydroxy fatty acid, 9,12,13-trihydroxyoctadeca-10(Z),15(Z)-dienoic acid (1), and a known compound, pinellic acid (2). These two trihydroxy fatty acids 1 and 2 inhibited prostaglandin D₂ production with IC₅₀ values of 25.8 and 40.8 μM, respectively. These results suggest that 9,12,13-trihydroxyoctadeca-10(Z),15(Z)-dienoic acid (1) and pinellic acid (2) are among the anti-inflammatory principles in this medicinal plant.

Antioxidant and anti-inflammatory activities of Pittocaulon species from México

Context: Stems and leaves of Pittocaulon spp. (Asteraceae) are used in Mexican traditional medicine as an anti-inflammatory substance and for the treatment of skin injuries.Objective: This study evaluated the antioxidant activity of methanol (MeOH) and dichloromethane (DC) extracts of five Pittocaulon species.Materials and methods: DC and MeOH extracts from flowers, roots, and stems of Pittocaulon praecox (Cav.) H. Rob. & Brettell, P. bombycophole (Bullock) H. Rob. & Brettell, P. filare (Mc Vaugh) H. Rob. & Brettell, P. velatum (Greenm.) Rob. & Brettell and P. hintonii H. Rob. & Brettell.Result and Discussion: In the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, the flower extracts obtained with MeOH were the most active with IC50 values ranging from 51.83 ± 4.08 to 154.19 ± 8.39 ppm. In the thiobarbituric acid reactive substances (TBARS) model, the best activity was shown by DC extracts of roots with IC50 values ranging from 55.54 ± 1.28 to 160.82 ± 5.37 ppm. The MeOH extract of flowers of P. bombycophole had the highest IC50 value in both DPPH (51.83 ± 4.08 ppm) and TBARS (39.78 ± 1.97 ppm). The samples with the best values in the antioxidant activity assays were evaluated in the anti-inflammatory tests. The DC root extract of P. velatum at a dose of 1 mg/ear produced the greatest reduction (84.96%) of the 2-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema. This extract also reduced the activity of the enzyme myeloperoxidase (MPO) (73.65%) at the same dose. In contrast, DC root extract of this species did not show significant inhibition of the increase in paw edema induced by carrageenan at the doses tested (100 mg/kg).Conclusion: These results support the traditional use of these plants as anti-inflammatory. DC extracts of P. velatum and MeOH extracts of P. bombycophole may be a potential resource of natural anti-inflammatory and antioxidant compounds, respectively. Additional studies must be done to identify the compounds responsible of the activity on these plants and to establish the mechanism of action.

Modeling Natural Anti-Inflammatory Compounds by Molecular Topology

One of the main pharmacological problems today in the treatment of chronic inflammation diseases consists of the fact that anti-inflammatory drugs usually exhibit side effects. The natural products offer a great hope in the identification of bioactive lead compounds and their development into drugs for treating inflammatory diseases. Computer-aided drug design has proved to be a very useful tool for discovering new drugs and, specifically, Molecular Topology has become a good technique for such a goal. A topological-mathematical model, obtained by linear discriminant analysis, has been developed for the search of new anti-inflammatory natural compounds. An external validation obtained with the remaining compounds (those not used in building up the model), has been carried out. Finally, a virtual screening on natural products was performed and 74 compounds showed actual anti-inflammatory activity. From them, 54 had been previously described as anti-inflammatory in the literature. This can be seen as a plus in the model validation and as a reinforcement of the role of Molecular Topology as an efficient tool for the discovery of new anti-inflammatory natural compounds.

경북약용작물(홍화자, 향부자, 형개, 위유, 작약)의 항산화 및 Nitric Oxide 저해활성

본 연구는 5가지 경북약용작물(홍화자, 향부자, 형개, 위유, 작약)의 항산화와 항염증 효과에 대해서 검증하였다. 추출은 70% 에탄올에서 추출하였다. 항산화 활성을 측정하기 위해 총플라보노이드, 폴리페놀 함량을 측정하였고, 추출물의 소거활성은 a-a-Diphenyl-<TEX>${\beta}$</TEX>-picrylhydrazyl (<TEX>$DPPH{\cdot}$</TEX>), 2,2-azino-bis 3-ethylbenzthiazoline-6-sulfonic acid (<TEX>$ABTS{\cdot}$</TEX>), ferric reducing antioxidant power (FRAP), superoxide anion 저해활성으로 측정하였다. 홍화자 추출물에서 높은 총 폴리페놀과 플라보노이드 함량과 뛰어난 <TEX>$DPPH{\cdot}$</TEX>, <TEX>$ABTS{\cdot}$</TEX>, FRAP, superoxide anion 소거활성을 나타내었다. 또한, 홍화자 추출물에서 가장 높은 NO 생성 저해 활성을 나타냈다. 그 결과 홍화자 추출물은 항산화와 항염증 활성에 효과를 가진 기능성 소재로 사용될 수 있을 것이다. This study was carried out to search for natural anti-oxidants and anti-inflammatory compounds from 5 medicinal plants (Carthamus tinctorius seed, Cyperus rotundus, Schizonepeta tenuifolia, Polygonatum odoratum var. pluriflorum, and Paeonia lactiflora). These plants were extracted with 70% ethanol. In order to measure total antioxidant activity of flavonoids, polyphenol content was measured. Radical scavenging activities of extracts were examined using a-a-Diphenyl-<TEX>${\beta}$</TEX>-picrylhydrazyl (<TEX>$DPPH{\cdot}$</TEX>), 2,2-azino-bis 3-ethylbenzthiazoline-6-sulfonic acid (<TEX>$ABTS{\cdot}$</TEX>), ferric reducing antioxidant power (FRAP) and superoxide anion radical assays. C. tinctorius seed extracts showed the highest polyphenol and flavonoid contents as well as strong <TEX>$DPPH{\cdot}$</TEX>, <TEX>$ABTS{\cdot}$</TEX>, FRAP, and superoxide anion radical scavenging activity. Also, C. tinctorius seed extracts showed the highest nitric oxide (NO) production inhibitory effect. Theses results indicate that the C. tinctorius seed extracts can be used as a functional material due to their effective anti-oxidative and antiinflammatory activities.

Anin VitroAnalysis System Using a Fluorescence Protein Reporter for Evaluating Anti-Inflammatory Effects in Macrophages

Monitoring of inflammation in adipose tissues, which causes insulin resistance, is valuable in evaluating insulin resistance. We developed an in vitro analysis system using a fluorescence protein (FP) as a reporter gene driven by pro-inflammatory cytokine promoters such as monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNFα). In the reporter-transfected RAW264 cells, the protein expression levels of green fluorescence protein (GFP) were increased by inflammatory stimulations such as lipopolysaccharide (LPS), conditioned medium prepared using hypertrophied 3T3-L1 adipocytes, and a co-culture system. The changes in fluorescence intensity were equivalent to those of the mRNA and protein expression levels for each cytokine. Moreover, the effects of 15-deoxy-12,14Δ-prostaglandine J(2), a natural anti-inflammatory compound, were detectable in this system. These data indicate that the FP system developed here is an analysis system of low cost with simple procedures for evaluating inflammation, suggesting usability in the large-scale screening of anti-inflammatory compounds.

18β-Glycyrrhetinic acid inhibits periodontitis via glucocorticoid-independent nuclear factor-κB inactivation in interleukin-10-deficient mice

18β-Glycyrrhetinic acid (GA) is a natural anti-inflammatory compound derived from licorice root extract (Glycyrrhiza glabra). The effect of GA on experimental periodontitis and its mechanism of action were determined in the present study. Periodontitis was induced by oral infection with Porphyromonas gingivalis W83 in interleukin-10-deficient mice. The effect of GA, which was delivered by subcutaneous injections in either prophylactic or therapeutic regimens, on alveolar bone loss and gingival gene expressions was determined on day 42 after initial infection. The effect of GA on lipopolysaccharide (LPS)-stimulated macrophages, T cell proliferation and osteoclastogenesis was also examined in vitro. 18β-Glycyrrhetinic acid administered either prophylactically or therapeutically resulted in a dramatic reduction of infection-induced bone loss in interleukin-10-deficient mice, which are highly disease susceptible. Although GA has been reported to exert its anti-inflammatory activity via downregulation of 11β-hydroxysteroid dehydrogenase-2 (HSD2), which converts active glucocorticoids to their inactive forms, GA did not reduce HSD2 gene expression in gingival tissue. Rather, in glucocorticoid-free conditions, GA potently inhibited LPS-stimulated proinflammatory cytokine production and RANKL-stimulated osteoclastogenesis, both of which are dependent on nuclear factor-κB. Furthermore, GA suppressed LPS- and RANKL-stimulated phosphorylation of nuclear factor-κB p105 in vitro. These findings indicate that GA inhibits periodontitis by inactivation of nuclear factor-κB in an interleukin-10- and glucocorticoid-independent fashion.

Oleocanthal, a Natural anti-Inflammatory Compound in Extra Virgin Olive Oil

Recent research on the olive oil phenolic, oleo canthal has led to speculation that it may confer some of the health benefits associated with a traditional Mediterranean diet. Oleocanthal produces a peppery, stinging sensation at the back of the throat similar to that of the non-steroidal anti-inflammatory drug (NSAID), ibuprofen. This led to the hypothesis that the perceptual similarity between oleocanthal and ibuprofen may indicate similar pharmacological properties. Subsequent studies have proved the hypothesis and oleocanthal was shown not only to inhibit inflammation in the same way as ibuprofen does, but it was found to be substantially more potent than this NSAID. It is important to note that inflammation has been demonstrated to playa significant role in the development of a number of chronic diseases, such as cardiovascular disease (CVD) and certain types of cancers. Therefore, as a result of dietary feeding with olive oil as a part of the traditional Mediterranean diet, a reduction in inflammation produced by oleocanthal is speculated to be the potential mechanism that is partially responsible for the health benefits associated with this dietary pattern. This review summarizes the current knowledge on oleocanthal, in tenns of its physiological and sensory properties, as well as a discussion on the factors that have the ability to affect oleocanthal concentrations in extra virgin olive oils (EVOOs).

Natural anti-inflammatory compounds for the management and adjuvant therapy of inflammatory bowel disease and its drug delivery system

This project aims to investigate the anti-inflammatory properties of mastic [(Pistacia lentiscus var. Chia (Anacardiaceae)] extracted from the Chios mastic plant to help reduce intestinal inflammation in inflammatory bowel disease patients. Mastic and mastic resin were obtained from the Chios Mastiha Growers Association (www.mastihashop.com). The resin was ground into a fine powder using a pestle and mortar and formulated in factorial design manner. Evaluation of the efficacy of specific anti-inflammatory/antioxidant compounds in mitigating the clinical colitis parameters in a mouse model of colitis were performed with mastic itself and combination of tocopherol compounds. Colonic drug delivery system was developed consisting of two compartment model and its release profile was also investigated.

Influence of Heat on Biological Activity and Concentration of Oleocanthala Natural Anti-inflammatory Agent in Virgin Olive Oil

The olive oil phenolic oleocanthal is a natural nonsteroidal anti-inflammatory compound that irritates the oral pharynx in a dose-dependent manner. It has been proposed that the biological activity of oleocanthal is partially responsible for the beneficial health effects of the Mediterranean diet. Virgin olive oil containing oleocanthal is often added as an ingredient in a number of cooked dishes, and therefore it is of great importance to understand how best to preserve the putative health-promoting benefits of this compound, as olive oil phenolics are subject to degradation upon heating in general. One extra virgin olive oil containing 53.9 mg/kg oleocanthal was heated at various temperatures (100, 170, and 240 degrees C) for set time periods (0, 1, 5, 20, 60, and 90 min). Oleocanthal concentrations were quantified using HPLC, and its biological activity was determined with a taste bioassay measuring the intensity of throat irritation. Results demonstrated that oleocanthal was heat stable compared with other olive oil phenolics, with a maximum loss of 16% as determined by HPLC analysis. However, there was a significant decrease of up to 31% (p < 0.05) in the biological activity of oleocanthal as determined by the taste bioassay. Although there was minimal degradation of oleocanthal concentration, there was a significant decrease in the biological activity of oleocanthal upon extended heating time, indicating a possible loss of the putative health -benefiting properties of oleocanthal. Alternatively, the difference in the concentration and biological activity of oleocanthal after heat treatment could be a result of an oleocanthal antagonist forming, decreasing or masking the biological activity of oleocanthal.

Anti-inflammatory Action of Components from Melastoma malabathricum.

Ethnic folklore or empirical therapeutic uses of plant parts have often provided the early indication of the possibility of discovering some pharmacologically active substance from a plant. Melastoma malabathricum. L. (Melastomaceae), locally known as sendudok putih, is a small shrub. Traditional medicinal uses include diarrhea, dysentery, ulcers, wound care, and piles. In the search for natural compounds useful against anti-inflammatory activity, α.-amyrin, betulinic acid, and isolated flavonoids, including quercetin and quercitrin, were assessed in vitro. by determining their inhibitory effects on platelet activating factor (PAF) binding to rabbit platelets using 3H-PAF as a ligand. The results indicated that quercetin, quercitrin, α.-amyrin, and betulinic acid showed inhibition of PAF receptor binding with IC50 values of 33.0, 45.4, 20.0, and 22.2 µM, respectively. The IC50 values of these compounds were comparable to Cedrol (13.1 µM), which is a known PAF receptor antagonist. These results suggest that natural flavonoid and pentacyclic triterpenes from M. malabathricum. possess selective antagonistic activity toward PAF and could be an attractive candidate as a natural anti-inflammatory compound.

Ibuprofen-like activity in extra-virgin olive oil

Newly pressed extra-virgin olive oil contains oleocanthal--a compound whose pungency induces a strong stinging sensation in the throat, not unlike that caused by solutions of the non-steroidal anti-inflammatory drug ibuprofen. We show here that this similar perception seems to be an indicator of a shared pharmacological activity, with oleocanthal acting as a natural anti-inflammatory compound that has a potency and profile strikingly similar to that of ibuprofen. Although structurally dissimilar, both these molecules inhibit the same cyclooxygenase enzymes in the prostaglandin-biosynthesis pathway.

Herbals, Cancer Prevention and Health

The use of herbs for medical benefit has played an important role in nearly every culture on earth. Herbal medicine was practiced by ancient cultures in Asia, Africa, Europe and the Americas. The recent popularity in use of herbals can be tied to the belief that herbs can provide some benefit over and above allopathic medicine and allow users to feel that they have some control in their choice of medications. The widespread use of herbs, either directly or as dietary supplements, has raised many scientific questions. Are herbal preparations safe? Do herbs interact with pharmaceutical medications to enhance or reduce their efficacy? The first interaction can be shown by the effects of St. John's Wort, a mild herbal antidepressant, and many commonly used medicines. St. John's Wort can induce the CYP3A family of activation enzymes through which approximately 50% of drugs are metabolized. This poses some risk of inadvertently reducing the half-life of such drugs as indinavir, cyclosporin and cyclophosphamide. On the other hand, herbal products may act in a pathway similar to pharmaceuticals yet without side effects. Natural anti-inflammatory compounds abound in the herbal world and are found in green tea, the spices turmeric and rosemary, feverfew and others. Because the use of nonsteroidal anti-inflammatory drugs (NSAID) is associated with a reduced risk for several cancers, it is at least plausible that natural NSAID should be explored for possible use as cancer preventives.

Inhibition of 5-lipoxygenase activity by the natural anti-inflammatory compound aethiopinone.

We have investigated the mechanisms of action of aethiopinone, an anti-inflammatory compound from Salvia aethiopis L. roots. Human neutrophils from healthy volunteers and murine peritoneal macrophages. Swiss mice were randomly divided into groups of six animals. Test compounds were applied topically in the mouse ear oedema test. In the air pouch, mice received aethiopinone (0.001-0.5 pmol/pouch or 12.5-50 mg/kg p.o.). LTB4 production was assayed in human neutrophils and COX-2 and iNOS activities in murine macrophages. Air pouches were induced subcutaneously in mice and injected with zymosan on the day six. Mouse ear oedema was induced by arachidonic acid. Dunnett's t-test was employed for statistical analysis. We have observed potent inhibitory effects on human neutrophil LTB4 production without effects on COX or NOS activities. Aethiopinone is an in vitro inhibitor of 5-LO from human neutrophils (IC50 = 0.11 microM). In addition, aethiopinone reduced leukocyte accumulation and showed in vivo inhibitory activity on this enzyme. Our results indicate that inhibition of 5-LO could participate in the anti-inflammatory properties of this natural product.

Therapeutic efficacy of l-ornithine- l-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: Results of a placebo-controlled, double-blind study : Kircheis, G., Nilius, R., Held, C., Berndt, H., Buchner, M., Gortelmeyer, R., Hendricks, R., Kruger, B., Kuklinski, B., Meister, H., Otto, H.-J., Rink, C., Rosch, W., Stauch, S. Merz Clinical Research Department, Eckenheimer Landstrasse 100-104, 60318 Frankfurt/Main, Germany Hepatol 1997;

Excessive inflammation contributes greatly to the pathogenesis and development of rheumatoid arthritis (RA). Oroxylin A (OA) is a natural anti-inflammatory flavonoid compound. In this study, we investigated the effects of OA on collagen-induced arthritis (CIA) and human RA fibroblast-like synoviocytes (FLS). CIA was induced in DBA/1 mice and mice were intraperitoneally treated with OA (10 mg/kg) for 10 days. Arthritis severity was evaluated every day and the histopathologic examination of joints was done. Serum levels of anti-collagen II antibodies (anti-CII Abs) and cytokines were determined by ELISA. Frequency of regulatory T cells (Tregs) and Th17 cells in draining inguinal lymph nodes (ILN) was quantified by flow cytometry. FLS from patients with active RA were treated with varying doses of oroxylin A, followed by stimulation with tumor necrosis factor (TNF)-α (10 ng/mL). The production of cytokines was measured by ELISA. Signal transduction proteins were examined by western blot. OA significantly diminished the arthritis and histological damage. Serum anti-CII Abs, IL-1β, IL-6, TNFα, and IL-17 were significantly diminished by OA treatment. Analysis of CD4 + T cell populations in OA-treated mice showed an increase in Tregs and reduction in Th17 cells in the ILN. In vitro, OA decreased the secretion of IL-1β and IL-6 from TNFα-stimulated RA FLS in a dose-dependent manner. TNFα-induced p38 MAPK, ERK1/2 and NF-κB signaling pathways were suppressed by OA. Our results indicate that OA exerts an anti-inflammatory activity and may have therapeutic potential for human RA.