Antiphlogistic Activity Research Articles

Angiotensinergic effect of β-Caryophyllene on Lipopolysaccharide- induced systemic inflammation

Renin-Angiotensin System (RAS) is a peptidergic system, canonically known for its role in blood pressure regulation. Furthermore, a non-canonical RAS regulates pathophysiological phenomena, such as inflammation since it consists of two main axes: the pro-inflammatory renin/(pro)renin receptor ((P)RR) axis, and the anti-inflammatory angiotensin-converting enzyme 2 (ACE2)/Angiotensin-(1–7) (Ang-(1–7))/Mas Receptor (MasR) axis. Few phytochemicals have shown to exert angiotensinergic and anti-inflammatory effects through some of these axes; nevertheless, anti-inflammatory drugs, such as phytocannabinoids have not been studied regarding this subject. Among phytocannabinoids, β-Caryophyllene stands out as a dietary phytocannabinoid with antiphlogistic activity that possess a unique sesquiterpenoid structure. Although its cannabinergic effect has been studied, its angiotensinergic effect reminds underexplored. This study aims to explore the angiotensinergic effect of β-Caryophyllene on inflammation and stress at a systemic level. After intranasal Lipopolysaccharide (LPS) installation and oral treatment with β-Caryophyllene, the concentration and activity of key RAS elements in the serum, such as Renin, ACE2 and Ang-(1–7), along with the stress hormone corticosterone and pro/anti-inflammatory cytokines, were measured in mice serum. The results show that β-Caryophyllene treatment modified RAS levels by increasing Renin and Ang-(1–7), alongside the reduction of pro-inflammatory cytokines and corticosterone levels. These results indicate that β-Caryophyllene exhibits angiotensinergic activity in favor of anti-inflammation.

Synthesis and Evaluation of Antiphlogistic Activity of Some New 4-Fluorophenyltriazolothiadiazines

The reaction between 4-fluorobenzoic acid hydrazide (1) and carbon disulfide in the existence of alcoholic potassium hydroxide yielded N?-(4-fluoro-benzoyl)-hydrazinecarbodithioic acid (2). Subsequently, product 2 on reaction with an aqueous solution of hydrazine hydrate led to the formation of compound 3. The condensation of compound 3 with various substituted ?-bromoacetophenones in ethanol furnished the targeted triazolothiadiazines, bearing a 4-fluorophenyl moiety (4a-l). Subsequently, a comprehensive evaluation of the antiphlogistic potential of the synthesized molecules 4a-l was conducted. This assessment was completed using albino Wistar rats that had their paws swollen with carrageenan. Compounds 4l and 4b demonstrated significant (P < 0.01) antiphlogistic activity. Furthermore, compounds 4d, 4f, and 4k exhibited noteworthy antiphlogistic effects (P < 0.05), comparable to the standard drug indomethacin. This study sheds light on the antiphlogistic properties of these compounds and holds promise for further research in this area. . KEYWORDS :Antiphlogistic, Anti-inflammatory, 4-Fluorophenyl, Triazole, Thiadiazine.

Genotoxic Potential, Total Flavonoid and Phenolic Contents of Solanum anomalum Thonn. Ex Schumach Leaf

Solanum anomalum, a medicinal plant, used in ethnomedicine for their antimalarial, antidiabetic, and antiphlogistic activities was investigated for cytotoxic and genotoxic effects on the root meristem cells of Allium cepa. The extract and fractions was also screened for total flavonoid and phenol content using standard methods. Onion bulbs were exposed to 2.5 mg/mL, 5mg/mL, and 10 mg/mL concentrations of the leaf extract for macroscopic and microscopic analysis. Tap water was used as a negative control and Methotrexate (0.1 mg/mL) as a positive control. There was statistically significant (P < 0.05) inhibition of root growth depending on concentration by the extract when compared with the negative control group. All the tested concentrations of the extract were observed to have cytotoxic effects on cell division in A. cepa. The extract- induced chromosomal aberrations and micronuclei (MNC) formations in A. cepa root tip cells were significant (p<0.05) when compared with control group. The extract treatment further induced cell death, ghost cells, cells membrane damage, and binucleated cells. The dichloromethane fraction was found to contain the highest level of total flavonoid and phenol followed by the crude extract. These results suggest that Solanum anomalum leaf extract possess cytotoxic and genotoxic effects on A. cepa which is as a results of its phytochemical constituents.

Liu Shen Wan inhibits influenza virus-induced secondary Staphylococcus aureus infection in vivo and in vitro

Ethnopharmacological relevanceLiu Shen Wan (LSW) is a traditional Chinese medicine (TCM) with detoxification and antiphlogistic activity; it is composed of bezoar, toad venom, musk, pearl powder, borneol and realgar. In recent years, LSW has been widely used in traditional medicine for the treatment of influenza, tonsillitis, pharyngitis, mumps, cancer and leukaemia. Aim of studyThe anti-influenza virus properties of LSW and its inhibition of the inflammatory response was demonstrated in our previous research; however, the effect and potential mechanism of LSW against influenza induced secondary bacteria have remained obscure. Therefore, in the present study, a model of influenza virus PR8 with secondary infection by Staphylococcus aureus (S. aureus) in vitro and in mice was established to examine the effect and potential mechanism by which LSW inhibits bacterial adhesion and subsequent severe pneumonia after viral infection. Materials and methodsWe investigated the effect of LSW on the PR8-induced adhesion of live S. aureus in A549 cells. RT-qPCR was used to detect the expression of adhesion molecules. Western blotting was used to determine the expression of CEACAM1, RIG-1, MDA5, p–NF–κB, and NF-κB in A549 cells. Inflammatory cytokines were detected using a Bio-Plex Pro Human Cytokine Screening Panel (R&D) in A549 cells and Mouse Magnetic Luminex Assays (R&D) in mice infected with PR8 virus and secondarily with S. aureus, respectively. Moreover, the survival rate, lung index, viral titre, bacterial loads and pathological changes in the lung tissue of mice infected with PR8 and S. aureus were investigated to estimate the effect of LSW in inhibiting severe pneumonia. ResultsLSW significantly decreased S. aureus adhesion following influenza virus infection in A549 cells, which may have occurred by suppressing expression of the adhesion molecule CEACAM1. In addition, treatment with LSW dramatically suppressed the induction of proinflammatory cytokines (CCL2/MCP-1 and CXCL-9/MIG) and chemokines (IL-6 and TNF-α) by PR8 infection following secondary LPS stimulation in A549 cells. Upregulation of related signalling proteins (RIG-I, MDA5 and NF-κB) induced by viruses and bacteria was suppressed by LSW in A549 cells. LSW significantly decreased the viral titres and bacterial load, prolonged survival time, and ameliorated lung inflammation and injury in mice with S. aureus infection secondary to PR8 infection. ConclusionsWe demonstrated that LSW prevents S. aureus adherence to influenza virus-infected A549 cells, perhaps by inhibiting the expression of the adhesion molecule CEACAM1. The upregulation of proinflammatory cytokines and related signalling proteins induced by viruses and bacteria was suppressed by LSW in A549 cells. LSW significantly ameliorated lung injury caused by viral and secondary bacterial infection. These findings provide a further evaluation of LSW and suggest a beneficial effect of LSW for the prevention of secondary bacterial infection and related complications.

Anti-inflammatory activity of Xanthium indicum on carrageenan-induced paw edema in rats

The present study was aimed to evaluate the antiphlogistic activity of Xanthium indicum methanolic extract in carrageenan-induced paw edema in rats as an acute inflammatory model. Plant extract was analyzed for phytochemical screening of different phytoconstituents. 36 rats were randomly divided into 6 groups. Paw edema was induced with 1.5% carrageenan to all the groups except normal. Ibuprofen was used as a standard drug and Xanthium indicum 100, 300, 500 mg/kg dose with carrageenan was administered in the paw. Paw thickness was measured at 0, 1, 2, and 4 h. Inflammatory cytokines and oxidative stress were measured in paw tissue homogenate. Paw thickness was increased from 1 to 4 h and the Xanthium indicum treated group shows a decrease in paw thickness. SOD and GSH content were decreased and the MDA level increased in the carrageenan injected group, however, treatment groups show reverse effects also we found that increase in cytokine levels in the carrageenan group and decrease in the treatment group. From this study, we conclude that Xanthium indicum has anti-inflammatory activity by reducing paw inflammation as well as oxidative stress and cytokine in paw tissue homogenate.

The Influence of Toothpaste Containing Australian Melaleuca alternifolia Oil and Ethanolic Extract of Polish Propolis on Oral Hygiene and Microbiome in Patients Requiring Conservative Procedures.

The study was based on the use of a toothpaste with antiphlogistic activity, containing Australian Melaleuca alternifolia oil (tea tree oil—TTO) and ethanolic extract of Polish propolis (EEP). Fifty-one patients with varying conditions of the gingiva were divided into two groups. The study group received the toothpaste with TTO and EEP, while the control group received the same toothpaste but without TTO and EEP. Approximal plaque index (API), simplified oral hygiene index (OHI-s) and modified sulcus bleeding index (mSBI) were assessed in three subsequent stages. During each examination, swabs were employed for microbiological inoculation. During the period of use of toothpastes with TTO and EEP, a significant reduction of the API was observed, as assessed upon the control visit after 7 days and after 28 days, compared to baseline. A statistically significant reduction of mSBI was observed after 7 and 28 days of using the toothpaste with TTO and EEP, as compared to the value upon the initial visit. Statistically significant differences in the OHI-s value were observed in the study group, which was using the active toothpaste. The use of a toothpaste containing TTO and EEP helps to maintain microbiome balance. The observed stabilisation of bacterial microflora confirms the beneficial activity of toothpaste containing EEP and TTO compared to the control group, where the lack of these substances contributed to the emergence of qualitative and quantitative changes in oral microbiome.

Evaluation of an Aqueous Extract from Horseradish Root (Armoracia rusticana Radix) against Lipopolysaccharide‐Induced Cellular Inflammation Reaction

Horseradish (Armoracia rusticana) is a perennial crop and its root is used in condiments. Traditionally, horseradish root is used to treat bacterial infections of the respiratory tract and urinary bladder. The antiphlogistic activity, determined in activated primary human peripheral blood mononuclear cells (PBMC), was evaluated for an aqueous extract and its subfractions, separated by HPLC. Compound analysis was done by UHPLC-QToF/MS and GC-MS. The aqueous extract concentration-dependently inhibited the anti-inflammatory response to lipopolysaccharide (LPS) in terms of TNF-α release at ≥37 μg/mL. Further, the cyclooxygenase as well as lipoxygenase pathway was blocked by the extract as demonstrated by inhibition of COX-2 protein expression and PGE2 synthesis at ≥4 μg/mL and leukotriene LTB4 release. Mechanistic studies revealed that inhibition of ERK1/2 and c-Jun activation preceded COX-2 suppression upon plant extract treatment in the presence of LPS. Chemical analysis identified target compounds with a medium polarity as relevant for the observed bioactivity. Importantly, allyl isothiocyanate, which is quite well known for its anti-inflammatory capacity and as the principal pungent constituent in horseradish roots, was not relevant for the observations. The results suggest that horseradish root exerts an antiphlogistic activity in human immune cells by regulation of the COX and LOX pathway via MAPK signalling.

Phytochemical profile of Paulownia tomentosa (Thunb). Steud.

Paulownia tomentosa, a member of the plant family Paulowniaceae and a rich source of biologically active secondary metabolites, is traditionally used in Chinese herbal medicine. Flavonoids, lignans, phenolic glycosides, quinones, terpenoids, glycerides, phenolic acids, and miscellaneous other compounds have been isolated from different parts of P. tomentosa plant. Recent interest in this species has focused on isolating and identifying of prenylated flavonoids, that exhibit potent antioxidant, antibacterial, and antiphlogistic activities and inhibit severe acute respiratory syndrome coronavirus papain-like protease. They show cytotoxic activity against various human cancer cell lines and inhibit the effects of human cholinesterase, butyrylcholinesterase, and bacterial neuraminidases. Most of the compounds considered here have never been isolated from any other species of plant. This review summarizes the information about the isolated compounds that are active, their bioactivities, and the structure–activity relationships that have been worked out for them.

Evaluation of anti-inflammatory activity of prenylated substances isolated from Morus alba and Morus nigra.

Chromatographic separation of root extracts of Morus alba and M. nigra led to the identification of the 2-arylbenzofurans moracin C (1), mulberrofuran Y (2), and mulberrofuran H (3), and the prenylated flavonoids kuwanon E (4), kuwanon C (5), sanggenon H (6), cudraflavone B (7), and morusinol (8), and the Diels-Alder adducts soroceal (9), and sanggenon E (10). The cytotoxicity and their antiphlogistic activity, determined as the attenuation of the secretion of TNF-α and IL-1β and the inhibition of NF-κB nuclear translocation in LPS-stimulated macrophages, were evaluated for compounds 1-10.

Analysis of Volatile Components of Adenosma indianum (Lour.) Merr. by Steam Distillation and Headspace Solid‐Phase Microextraction

The essential oil of Adenosma indianum (Lour.) Merr. plays an important role in its antibacterial and antiphlogistic activities. In this work, the volatile components were extracted by steam distillation (SD) and headspace solid‐phase microextraction (HS‐SPME) and analysed by gas chromatography‐mass spectrometry (GC‐MS). A total of 49 volatile components were identified by GC‐MS, and the major volatile components were α‐limonene (20.59–35.07%), fenchone (15.79–31.81%), α‐caryophyllene (6.98–10.32%), β‐caryophyllene (6.98–10.19%), and piperitenone oxide (1.96–11.63%). The comparison of the volatile components from A. indianum (Lour.) Merr. grown in two regions of China was reported. Also, the comparison of the volatile components by SD and HS‐SPME was discussed. The results showed that the major volatile components of A. indianum (Lour.) Merr. from two regions of China were similar but varied with different extraction methods. These results were indicative of the suitability of HS‐SPME method for simple, rapid, and solvent‐free analysis of the volatile components of the medicinal plants.

Synthesis and preliminary biological evaluation of novel N-substituted 1-amino-3-[1-methyl(phenyl)-1H-indazol-4-yloxy]-propan-2-ols interesting as potential antiarrhythmic, local anaesthetic and analgesic agents.

A series of indazoloxypropanolamines 7 and 8, pindolol isosteres, were synthesized to extend the structure activity relationship (SAR) which was observed in an earlier series of related derivatives. Compounds 7, characterized by methyl substitution on the N-1 indazole nucleus, generally exhibited significant antiarrhythmic, local anaesthetic and analgesic activities. The preliminary radioligand binding assay highlighted, in compounds 7, an interesting beta 1-affinity which can be well correlated to their antiarrhyhtmic activity. Analogues 8 characterized by a phenyl group on the N-1 indazole nucleus, were generally less active as antiarrhyhtmic agents but generally interesting as local anaesthetics. Due to the importance of the indazole moiety as a carrier of antiphlogistic activity, the two classes of derivatives 7 and 8 were evaluated for their NSAID behaviour. Once again, compounds 7 resulted having more interesting analgesic and antipyretic effects than analogues 8.

STRUCTURAL REQUIREMENTS FOR THE ANTIPHLOGISTIC ACTIVITY IN SOME NOVEL DERIVATIVES OF CHLORTHENOXAZIN.

STRUCTURAL REQUIREMENTS FOR THE ANTIPHLOGISTIC ACTIVITY IN SOME NOVEL DERIVATIVES OF CHLORTHENOXAZIN.

Evaluation of cytotoxicity and genotoxicity of Inula viscosa leaf extracts with Allium test.

I. viscosa has been used for years in folk medicine for its anti-inflammatory, antipyretic, antiseptic, and paper antiphlogistic activities. In this study, cytotoxic and genotoxic effects of I. viscosa leaf extracts on the root meristem cells of Allium cepa have been examined. Onion bulbs were exposed to 2.5 mg/ml, 5 mg/ml, and 10 mg/ml concentrations of the extracts for macroscopic and microscopic analysis. Tap water has been used as a negative control and Ethyl methanesulfonate (EMS) (2 · 10−2 M) has been used as a positive control. The test concentrations have been determined according to doses which are recommended for use in alternative medicine. There has been statistically significant (P < .05) inhibition of root growth depending on concentration by the extracts when compared with the control groups. All the tested extracts have been observed to have cytotoxic effects on cell division in A. cepa. I. viscosa leaf extract induces the total number of chromosomal aberrations and micronuclei (MNC) formations in A. cepa root tip cells significantly when compared with control groups. Also, this paper shows for the first time the induction of cell death, ghost cells, cells with membrane damage, and binucleated cells by extract treatment. These results suggest the cytotoxic and genotoxic effects of the I. viscosa leaf extracts on A. cepa.

Synthesis and anti-inflammatory activity of acyl derivatives of taraxasterol

Acylation of taraxasterol with acid chloranhydrides in the presence of N-dimethylaminopyridine yielded the new compounds 3β-acetoxy-20-methylidenetaraxastane, 3β-trifluoroacetoxy-20-methylidenetaraxastane, and 3β-benzoyl-20-methylidenetaraxastane. The antiphlogistic activities of taraxasterol and its acyl derivatives were studied. All study compounds had anti-inflammatory activity comparable to that of reference agent prednisolone.

Achillea millefolium L. s.l. – Is the anti-inflammatory activity mediated by protease inhibition?

Achillea millefolium L. s.l. is traditionally used not only in the treatment of gastro-intestinal and hepato-biliary disorders, but also as an antiphlogistic drug. As various proteases, for instance human neutrophil elastase (HNE) and matrix metalloproteinases (MMP-2 and -9), are associated with the inflammatory process, the aim of this study was to test a crude plant extract in in vitro-protease inhibition assays for understanding the mechanisms of anti-inflammatory action. Furthermore, two fractions enriched in flavonoids and dicaffeoylquinic acids (DCQAs), respectively, were also tested in order to evaluate their contribution to the antiphlogistic activity of the plant. The extract and the flavonoid fraction inhibited HNE showing IC 50 values of approximately 20 μg/ml, whereas the DCQA fraction was less active (IC 50 = 72 μg/ml). The inhibitory activity on MMP-2 and -9 was observed at IC 50 values from 600 to 800 μg/ml, whereas the DCQA fraction showed stronger effects than the flavonoid fraction and the extract. In conclusion, the in vitro-antiphlogistic activity of Achillea is at least partly mediated by inhibition of HNE and MMP-2 and -9. After the recently described spasmolytic and choleretic effects the obtained results give further insights into the pharmacological activity of Achillea and confirm the traditional application as antiphlogistic drug.

Synthesis and biological activity of 5-aryl-4-acyl-3-hydroxy-1-morpholinoalkyl-3-pyrrolin-2-ones

A series of 5-aryl-4-acyl-3-hydroxy-1-morpholinoalkyl-3-pyrroline-2-ones was synthesized via the reactions of methyl esters of acylpyruvic acids with a mixture of aromatic aldehyde and 2-(4-morpholino)-1-ethylamine or 3-(4-morpholino)-1-propylamine. All compounds possess weak antibacterial properties. The antiamnesic, analgesic, and antiphlogistic activity and acute toxicity of several compounds were studied. It was established that one compound produced a significant antiamnesic effect and two compounds exhibited pronounced analgesic activity.

Distribution of Phenolic Compounds in Middleeuropean Taxa of the Achillea millefolium L. Aggregate

Achillea millefolium L. s.l. is a cytogenetically, morphologically, and chemically polymorphic aggregate. Besides the sesquiterpenes that possess chemotaxonomic relevance and mediate the antiphlogistic activity, the plant contains phenolic compounds such as dicaffeoylquinic acids and flavonoids causing choleretic and spasmolytic effects. To evaluate their contribution to the chemotaxonomy of European taxa of the A. millefolium group, we developed a SPE-HPLC/UV method that allows quantification of the phenolic constituents in the different taxa. The investigated species displayed differences in the quantitative and qualitative composition of phenolic acids and flavonoids. Hence, they seem to be of chemotaxonomic significance, especially for the distinction of the diploid taxa. Combining the obtained results with the data of the sesquiterpene analyses gives a comprehensive insight into the distribution of those pharmacologically relevant plant constituents in the A. millefolium group.

Achillea millefolium L. s.l. – is the antiphlogistic activity mediated by protease inhibition?

Achillea millefolium L. s.l. – is the antiphlogistic activity mediated by protease inhibition?

Anti-Inflammatory Activity of Two Diterpenes of Hyptis suaveolens from El Salvador

Separation and isolation of the two main compounds suaveolol and methyl suaveolate from leaves of chichinguaste (Hyptis suaveolens Poit., Lamiaceae) could be achieved by means of repeated column chromatography and repeated preparative thin layer chromatography. Their chemical structures were approved by MS, 1H NMR, 13C NMR and 2D-NMR experiments. The anti-inflammatory activity of the two compounds was tested for the first time as inhibition of croton oil-induced dermatitis of the mouse ear. Suaveolol and methyl suaveolate showed nearly the same dose-dependent topical anti-inflammatory activity, only two to three times lower than that of the reference drug indomethacin. The anti-inflammatory properties of these compounds could contribute to the antiphlogistic activity of extracts of Hyptis species and confirm the rational use of Hyptis suaveolens extracts in dermatological diseases.

Topical anti-inflammatory activity of Bauhinia tarapotensis leaves.

The topical anti-inflammatory properties of Bauhinia tarapotensis Benth. (Leguminosae) leaves have been studied by the inhibition of the croton oil-induced ear edema in mice. A bioassay-guided fractionation showed an interesting anti-inflammatory activity of the chloroform extract, that justifies the activity of the whole herbal drug. The main anti-inflammatory principles of B. tarapotensis leaves are triterpenic acids of ursane and oleanane series. The antiphlogistic activity of mixtures constituted of two ursane and oleanane isomers with different hydroxylation pattern, in the ratio 2:1, is comparable to that of indomethacin (ID50 ranging from 95 to 147 microg/cm2 and 93 microg/cm2, respectively).