Cotton Pellet-induced Granuloma Formation Research Articles

Anti-inflammatory effects of Pikad Tri-phol-sa-mut-than remedy, consisting of dried fruits of Aegle marmelos (L.) Corrêa, Coriandrum sativum L., and Morinda citrifolia L.

Ethnopharmacological relevanceInflammation has been known to possess some essential roles in many diseases, especially those with chronic or severe conditions. Pikad Tri-phol-sa-mut-than, a Thai traditional herbal remedy, has long been used to treat gastrointestinal sicknesses, fever, and severe illness caused by the deformities of Tridosha. In particular, this recipe has also been applied for inflammation-related conditions including gout and rheumatoid arthritis. The Pikad Tri-phol-sa-mut-than recipe consists of dried fruits of three herbs including Aegle marmelos (L.) Corrêa, Morinda citrifolia L., and Coriandrum sativum L. Each of these plant components of Pikad Tri-phol-sa-mut-than exhibited anti-inflammatory activities. However, anti-inflammatory effect of Pikad Tri-phol-sa-mut-than remedy has not been reported. Aim of the studyThe objective of this study was to elucidate the anti-inflammatory activities of Pikad Tri-phol-sa-mut-than extract (TS) against acute and chronic inflammation in rats. Materials and methodsTo study the effects of TS on acute inflammation, ethyl phenylpropiolate (EPP)-induced ear edema, carrageenan- and arachidonic acid (AA)-induced hind paw edema models were carried out. In addition, cotton pellet-induced granuloma formation was performed to specify the inhibitory effects of TS on chronic inflammation. ResultsThe topical application of TS significantly inhibited EPP-induced ear edema in rats. In the carrageenan- and AA-induced paw edema models, the oral administration of TS significantly reduced paw volumes, compared to those of the control groups. In addition, the 7-day oral treatment of TS demonstrated a significant suppressive effect on cotton pellet-induced granuloma formation. ConclusionsThe current study revealed that TS possesses anti-inflammatory activities against acute and chronic inflammation. Our studies support the use of TS in traditional medicine, and the development of TS as a novel natural product for treating diseases associated with inflammation.

Stauntonia hexaphylla leaf extract (YRA-1909) suppresses inflammation by modulating Akt/NF-κB signaling in lipopolysaccharide-activated peritoneal macrophages and rodent models of inflammation.

BackgroundInflammation is emerging as a key contributor to many vascular diseases and furthermore plays a major role in autoimmune diseases, arthritis, allergic reactions, and cancer. Lipopolysaccharide (LPS), which is a component constituting the outer membrane of Gram-negative bacteria, is commonly used for an inflammatory stimuli to mimic inflammatory diseases. Nuclear factor-kappa B (NF-κB) is a transcription factor and regulates gene expression particularly related to the inflammatory process. Stauntonia hexaphylla (Lardizabalaceae) is widely used as a traditional herbal medicine for rheumatism and osteoporosis and as an analgesic, sedative, and diuretic in Korea, Japan, and China.ObjectiveThe purpose of this study was to investigate the anti-inflammatory activity of YRA-1909, the leaf aqueous extract of Stauntonia hexaphylla using LPS-activated rat peritoneal macrophages and rodent inflammation models.ResultsYRA-1909 inhibited the LPS-induced nitric oxide (NO) and proinflammatory cytokine production in rat peritoneal macrophages without causing cytotoxicity and reduced inducible NO synthase and prostaglandin E2 levels without affecting the cyclooxygenase-2 expression. YRA-1909 also prevented the LPS-stimulated Akt and NF-κB phosphorylation and reduced the carrageenan-induced hind paw edema, xylene-induced ear edema, acetic acid-induced vascular permeation, and cotton pellet-induced granuloma formation in a dose-dependent manner in mice and rats.ConclusionsS. hexaphylla leaf extract YRA-1909 had anti-inflammatory activity in vitro and in vivo that involves modulation of Akt/NF-κB signaling. Thus, YRA-1909 is safe and effective for the treatment of inflammation.

CHEMICAL ANALYSIS, ANTIOXIDANT, ANTI-INFLAMMATORY AND ANTINOCICEPTIVE EFFECTS OF ACETONE EXTRACT OF ALGERIAN SOLENOSTEMMA ARGEL (DELILE) HAYNE LEAVES

Objective: To investigate the qualitative composition of the acetonic extract from leaves of S. argel (AESA) and their anti-inflammatory and analgesic properties in vivo.
 Methods: AESA profile was established by UHPLC/DAD/ESI-MS2. AESA was subjected to the acute oral toxicity study according to the OECD-420 method. Antioxydant activity of AESA was performed by DPPH radical scavenging assay. Anti-inflammatory effects of AESA were determined in two animal models: carrageenan-induced paw edema in rats and cotton pellet-induced granuloma formation in rats. Further, anti-nociceptives activities of AESA were assessed by hot plate test, acetic acid-induced abdominal writhing test and formalin test.
 Results: The in vivo AESA toxicity was low. AESA expresses a maximum radical scavenging activity with a IC50 value of 36,05 μg/ml. The AESA at 250 and 400 mg/kg significantly reduced carrageen an induced paw edema by 70.09% and 85.53% 6h after carrageenan injection, respectively. AESA produced significant dose-dependent anti-inflammatory effect against cotton pellets-induced granuloma formation in rats. In addition, AESA at 250 and 400 mg/kg significantly reduced acetic acid-induced writhing by 56.83 and 80.41%, respectively. Oral administration of 250 and 400 mg/kg of AESA caused a significant dose dependent anti-nociceptive effect in both neurogenic and inflammatory phases of formalin-induced licking. AESA also impacted the pain latency in the hot plat test.
 Conclusion: These data suggest that AESA possesses antioxidant, anti-inflammatory and anti-nociceptive effects. These results support the traditional use of S. argel to cure pain and inflammatory diseases in the Algerian Sahara.

In vivo evaluation of pharmacological properties of Argentine stingless bee geopropolis

BackgroundPropolis is a natural product that has been widely utilized as medicine and dietary supplement because of its broad biological activities. However, although meliponide hive products have many advantages, meliponiculture has not yet become popular in Argentina, and few scientific studies on its chemical composition and/or its bioactive properties were reported, so the use of stingless bee propolis Argentine in popular medicine continues to be based on empirical knowledge.Our work aims to evaluate in vivo anti-inflammatory, antitussive and expectorant activities, and acute toxicity of the Argentine geopropolis ethanol extracts of two stingless bee’s species, Scaptotrigona jujuyensis Schrottky and Tetragonisca fiebrigi Schwarz. Wistar male rats were used for all in vivo studies. Anti-inflammatory activities were evaluated through carrageenan-induced edema and cotton pellet-induced granuloma formation. Antitussive activity was assessed against ammonia-induced cough. Expectorant activity was measured by volume of phenol red in the rats’ tracheas. The extract doses tested were 125, 250, 500, and 1000 mg/kg (p.o.). The safety was evaluated with test of acute toxicity (48 h).ResultsThe results showed that S. jujuyensis and T. fiebrigi propolis (1000 mg/kg) significantly reduced the carrageenan-induced edema and cotton pellet-induced granuloma formation 3 h post-dosing. In the ammonia liquor-induced cough, both propolis significantly enhanced the latent period and reduced cough frequency as compared with those of the negative control. However, they did not increase the expulsion of red phenol in the treated rats.ConclusionsThis study shows that ethanol extracts of S. jujuyensis and T. fiebrigi propolis have anti-inflammatory and antitussive effects. These findings would justify the use of geopropolis in medicine as a potential phytotherapeutic product.Graphical abstract

Spirulina consumption effectively reduces anti-inflammatory and pain related infectious diseases

BackgroundInflammation and pain triggers several pathological illnesses. Synthetic drugs used for the controlling of inflammatory conditions convey significant toxic effects. Global scientific community continually attempt to improve effective, economic and harmless naturally derived remedies against inflammation and pain. The present study aimed to quantify the phytochemical constituents of the freshly cultivated Spirulina and targeted to examining the anti-inflammatory and analgesic activity of Spirulina extract (SE) derived from Arthrospira platensis. MethodsThe anti-inflammatory effect of SE was evaluated in animal models including carrageenan-induced rat hind paw oedema, and cotton pellet-induced granuloma formation. Analgesic effects of SE were evaluated by acetic acid induced writhing response and hot plate test. ResultsPhytochemical quantification guided to identify seven carbohydrates, thirteen amino acids, eleven fatty acids and polyphenolic compounds respectively. The results indicated that SE significantly attenuated carrageenan-induced hind paw oedema, and cotton pellet-induced granuloma. Preliminary molecular mechanistic studies established that SE decreased the productions of TNF-α, IL-1β, IL-6, PGE2 and NO, and suppressed the activities of COX-2 and iNOS. ConclusionThese results provide a strong scientific foundation for the anti-inflammatory and analgesic activities of SE against different studies in animal models.

Anti-inflammatory, antinociceptive and antidiarrhoeal activities of methanol and ethyl acetate extract of Hemigraphis alternata leaves in mice

BackgroundThe study was designed to investigate the qualitative phytochemical constituents and evaluate the anti-inflammatory, anti-nociceptive and anti-diarrhoeal activities of methanol (MHAL) and ethyl acetate (EAHAL) extract of Hemigraphis alternata leaves in Swiss albino mice.MethodsQualitative phytochemical constituents of MHAL and EAHAL were determined by different tests such as Molisch’s test, Fehling test, Mayer’s test, Frothing test, FeCl3 test, Alkali test, Salkowski’s test, Keller-killiani test and CuSO4 test. In addition, Xylene induced-ear edema test and Cotton pellet-induced granuloma formation test had been performed to evaluate the anti-inflammatory activity. Moreover, Formalin-induced paw licking test, Acetic acid-induced writhing tests and Castor oil induced antidiarrheal test had been performed to evaluate the anti-nociceptive and anti-diarrhoeal activities respectively.ResultsThese crude extracts were figured the presence of carbohydrates, flavonoids, tannins, glycosides, triterpenoids, fat and fixed oils. No mortality, behavioral changes or sign of any toxicity were observed up to the dose as high as 4000 mg/kg in mice. During anti-inflammatory test, MHAL 400 mg/kg and EAHAL 200 mg/kg & 400 mg/kg were significantly reduced ear weight differences and granuloma formation in mice. Highest percentage inhibition was offered by EAHAL 400 mg/kg dose (35.15 ± 11.78% and 34.76 ± 11.30%) in both anti-inflammatory tests respectively. In anti-nociceptive experiments, all extracts were significantly reduced paw licking and abdominal writhing of mice. Highest percentage inhibition was offered by EAHAL 400 mg/kg dose (88.21 ± 2.23% and 54.00 ± 2.38%) in both anti-nociceptive tests respectively. In addition, both extracts were showed significant inhibition of percentage of diarrhea in anti-diarrhoeal models except EAHAL 200 mg/kg dose and the apex percentage inhibition is offered by MHAL 400 mg/kg dose (67.73 ± 5.77%).ConclusionThese results confirm that the leaves extract of Hemigraphis alternata are nontoxic and may provide a source of plant compounds with anti-inflammatory, anti-nociceptive and anti-diarrhoeal activities.

Anti-Inflammatory Effect of Ethanolic Extract of Carica Papaya Leaves and Indomethacin in Cotton Pellet Induced Granuloma in Animal Model

Background: Anti-inflammatory effect can be exerted by Carica papaya.
 Objective: The purpose of the present study was to see the anti-inflammatory effect of ethanolic extract of Carica papaya leaves and indomethacin in carrageenan induced rat paw edema animal model.
 Methodology: This was an animal study carried out in the Department of Pharmacology at Dhaka Medical College, Dhaka, Bangladesh during the period from July 2014 to June 2015 for a period of one (01) year. The leaves of Carica Papaya collected from Botanical garden, Mirpur, Dhaka, Bangladesh. The animals were divided into four groups. The animals were divided into four groups. In all the animals granuloma were induced by implantation of autoclaved cotton pellet on the 1st day and they treated as follows: Group I were served as control that was received normal saline. Group II were received ethanolic extract of Carica Papaya leaves. Group III were received ethanolic extract of Carica Papaya leaves. Group IV were received indomethacin. On the 15th day animals were anesthetized, implanted pellets were dissected out, dried at hit air oven and the final weights were measured.
 Result: The experiment was carried out on 48 Long Evan Norwegian rats. Rats were divided in 4 groups of six animals each. The mean increase of weight of cotton pellet was 48.06±1.02, 24.48±0.36, 22.42±0.56 and 18.02±0.43 in group I, II, III and IV respectively. The inhibition of granuloma formation was 49.06%, 53.35% and 62.51% in group II, III and IV respectively.
 Conclusion: In conclusion the ethanolic extract of Carica Papaya leaves has effects on cotton pellet induced granuloma formation in experimental rat.
 Journal of Current and Advance Medical Research 2019;6(1):2-5

Evaluation of Anti-Inflammatory Activities of a Triterpene β-Elemonic Acid in Frankincense In Vivo and In Vitro.

The purpose of this research was to extract and separate the compounds from frankincense, and then evaluate their anti-inflammatory effects. The isolated compound was a representative tetracyclic triterpenes of glycine structure according to 1H-NMR and 13C-NMR spectra, which is β-elemonic acid (β-EA). We determined the content of six different localities of frankincense; the average content of β-EA was 41.96 mg/g. The toxic effects of β-EA administration (400, 200, 100 mg/kg) for four weeks in Kunming (KM) mice were observed. Compared with the control group, the body weight of mice, the visceral coefficients and serum indicators in the β-EA groups showed no systematic variations. The anti-inflammatory effects of β-EA were evaluated in LPS-induced RAW264.7 cells, xylene-induced induced ear inflammation in mice, carrageenin-induced paw edema in mice, and cotton pellet induced granuloma formation in rats. β-EA inhibited overproduction of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1), soluble TNF receptor 1 (sTNF R1), Eotaxin-2, Interleukin 10 (IL-10) and granulocyte colony-stimulating factor (GCSF) in the RAW264.7 cells. Intragastric administration with β-EA (300, 200, and 100 mg/kg in mice, and 210, 140, and 70 mg/kg in rats) all produced distinct anti-inflammatory effects in vivo in a dose-dependent manner. Following treatment with β-EA (300 mg/kg, i.g.), the NO level in mice ears and PGE2 in mice paws both decreased (p < 0.01). In conclusion, our study indicates that β-EA could be a potential anti-inflammatory agent for the treatment of inflammatory diseases.

In Vitro and In Vivo Anti-Inflammatory Effects of Polyphyllin VII through Downregulating MAPK and NF-κB Pathways.

Background: Polyphyllin VII (PP7), a steroidal saponin from Paris polyphylla, has been found to exert strong anticancer activity. Little is known about the anti-inflammatory property of PP7. In this study, the anti-inflammatory activity and its underlying mechanisms of PP7 were evaluated in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and in multiple animal models. Methods: The content of nitric oxide (NO) was determined by spectrophotometry. The levels of prostaglandin E2 (PGE2) and cytokines were measured by enzyme-linked immunosorbent assay (ELISA) assay. The mRNA expression of pro-inflammatory genes was determined by qPCR. The total and phosphorylated protein levels were examined by Western blotting. The in vivo anti-inflammatory activities were evaluated by using mouse and zebrafish models. Results: PP7 reduced the production of NO and PGE2 and the protein and mRNA expressions of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and enzymes (inducible NO synthase [iNOS], cyclooxygenase-2 [COX-2], and Matrix metalloproteinase-9 [MMP-9]) in LPS-induced RAW264.7 cells by suppressing the NF-κB and MAPKs pathways. Notably, PP7 markedly inhibited xylene-induced ear edema and cotton pellet-induced granuloma formation in mice and suppressed LPS and CuSO4-induced inflammation and toxicity in zebrafish embryos. Conclusion: This study demonstrates that PP7 exerts strong anti-inflammatory activities in multiple in vitro and in vivo models and suggests that PP7 is a potential novel therapeutic agent for inflammatory diseases.

COSTUS SPECIOSUS AND ITS ANTIPSORIATIC ARTHRITIS ACTIVITY: A REVIEW

Objective: Psoriatic arthritis is an autoimmune disease. The marketed drugs cannot totally cure the disease state as well as they have severe side effects and for that reason researcher and scientists are going for traditional medicines. Costus speciosus is the plant of choice for its several positive activities against psoriatic arthritis.Methods: Wistar albino healthy rat was taken for 0.1 ml of Freund adjuvant-induced anti-arthritic and anti-inflammatory test, and diclofenac sodium (15 mg/kg) was taken as standard drug. The paw volume was measured at different time 1st, 7th, 14th, and 21st days of experiment. In another study, the protocol is same, but indomethacin (10 mg/kg) was taken as standard drug. Another study was performed to know that the plant drug has any lipopolysaccharide (LPS)-stimulated COX-protein inhibitor activity or not. An acute anti-inflammatory property was studied in carrageenan-induced paw edema and result is measured by plethysmometer. The chronic anti-inflammatory property was studied by cotton pellet-induced granuloma formation. 400 mg/kg and 800 mg/kg dose of ethanolic extract is administered to the animal of both acute and chronic studies.Results: In anti-arthritic and anti-inflammatory study, after the 21st day, it has found that standard drug (diclofenac sodium) decreases paw volume 40 % where the plant drug reduces it 68.33% &amp; 75.50% at higher and lower dose respectively. In the other study the Standard drug (Indomethacin) show arthritic score of 0.83 and the extract shows 1.67 at its higher concentration. In LPS-stimulated cyclooxygenase-2 (COX-2) inhibition study, extract helps to decrease the LPS-stimulated COX-2 protein nearly similar as methotrexate without any side effect. In the cotton pallet-induced anti-inflammatory study, 400 mg/kg and 800 mg/kg dose of ethanolic extract shows similar result against standard drug.Conclusion: Although its activity is less compared to the marketed drug, in the other sides, it has very mild adverse effect compared to the marketed Drug. It can be used as a supportive drug in the treatment of Psoriatic arthritis and by chemical modification the activity may be increased without any side effect.

COSTUS SPECIOSUS AND ITS ANTIPSORIATIC ARTHRITIS ACTIVITY: A REVIEW

Objective: Psoriatic arthritis is an autoimmune disease. The marketed drugs cannot totally cure the disease state as well as they have severe side effects and for that reason researcher and scientists are going for traditional medicines. Costus speciosus is the plant of choice for its several positive activities against psoriatic arthritis.Methods: Wistar albino healthy rat was taken for 0.1 ml of Freund adjuvant-induced anti-arthritic and anti-inflammatory test, and diclofenac sodium (15 mg/kg) was taken as standard drug. The paw volume was measured at different time 1st, 7th, 14th, and 21st days of experiment. In another study, the protocol is same, but indomethacin (10 mg/kg) was taken as standard drug. Another study was performed to know that the plant drug has any lipopolysaccharide (LPS)-stimulated COX-protein inhibitor activity or not. An acute anti-inflammatory property was studied in carrageenan-induced paw edema and result is measured by plethysmometer. The chronic anti-inflammatory property was studied by cotton pellet-induced granuloma formation. 400 mg/kg and 800 mg/kg dose of ethanolic extract is administered to the animal of both acute and chronic studies.Results: In anti-arthritic and anti-inflammatory study, after the 21st day, it has found that standard drug (diclofenac sodium) decreases paw volume 40 % where the plant drug reduces it 68.33% &amp; 75.50% at higher and lower dose respectively. In the other study the Standard drug (Indomethacin) show arthritic score of 0.83 and the extract shows 1.67 at its higher concentration. In LPS-stimulated cyclooxygenase-2 (COX-2) inhibition study, extract helps to decrease the LPS-stimulated COX-2 protein nearly similar as methotrexate without any side effect. In the cotton pallet-induced anti-inflammatory study, 400 mg/kg and 800 mg/kg dose of ethanolic extract shows similar result against standard drug.Conclusion: Although its activity is less compared to the marketed drug, in the other sides, it has very mild adverse effect compared to the marketed Drug. It can be used as a supportive drug in the treatment of Psoriatic arthritis and by chemical modification the activity may be increased without any side effect.

Investigation of bioactivities of methanolic and ethyl acetate extracts of Dioscorea pentaphylla leaf along with its phenolic composition

The present study was performed to investigate the in-vitro antioxidant properties, brine shrimp lethality bioassay, and antimicrobial activity and in-vivo analgesic, anti-inflammatory, and antidiarrheal potentiality of methanolic and ethyl acetate extracts of Dioscorea pentaphylla (D. pentaphylla) leaf along with determining the bioactive phenolic compounds by HPLC analysis. Standard methods were used to investigate the aforementioned bioactivities. Methanol extract showed higher total phenolic activity, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical and Nitric oxide (NO) radical scavenging activities, whereas ethyl acetate extract showed better activities in total flavonoid and total antioxidant capacity assays. Dose-dependent moderate reducing capacity was observed for both extracts in cupric reducing and reducing power capacity assays. The methanol extract was found to be more potent than ethyl acetate extract according to brine shrimp lethality bioactivity test. Both extracts exhibited broad-spectrum antimicrobial activity in the disk diffusion method. In tail immersion test, at 1000 mg/kg dose, both extracts of D. pentaphylla showed a significant (p < 0.05) reduction in pain sensation. Ethyl acetate extract has significantly (p < 0.05) decreased writhing of the tested mice which were induced by acetic acid. The number of licks in formalin-induced paw licking test was markedly (p < 0.05) lessened in both extracts administration. Ethyl acetate extract revealed better anti-inflammatory activities than methanol extract in two well-known anti-inflammatory models (Xylene-induced ear edema, Cotton pellet-induced granuloma formation). Methanol extract displayed potent anti-diarrheal activity. HPLC analysis confirmed the existence of phenolic compounds (gallic acid, rutin, and quercetin) in the leaf extract of D. pentaphylla. These phytochemical constituents might have the role in the observed activities.

Antinociceptive and anti-inflammatory properties of Tetracera alnifolia Willd. (Dilleniaceae) hydroethanolic leaf extract.

Background Tetracera alnifolia Willd. (Dilleniaceae) is used in traditional African Medicine for the treatment of headache, abdominal pain, and rheumatism. Hence, this study sought to investigate the antinociceptive and anti-inflammatory effects of the hydroethanolic leaf extract of T. alnifolia (HeTA) in rodents. Methods Antinociceptive activity was evaluated using the acetic acid-induced writhing, formalin-/capsaicin-induced paw licking and hot plate tests in mice. The contribution of opioidergic, l-arginine-nitric oxide, and ATP-sensitive potassium channel pathways in HeTA-induced antinociception was also evaluated. The anti-inflammatory effect was assessed using the carrageenan-induced paw edema, xylene ear edema, cotton pellet granuloma, and complete Freund's adjuvant (CFA)-induced arthritis in rats. Results HeTA (100, 200, and 400 mg/kg, p.o.) produced significant (p<0.05) decrease in mean number of acetic acid-induced writhing, time spent licking paw in formalin, and capsaicin tests as well as time course increase in nociceptive reaction latency in hot plate test. HeTA-induced antinociception was prevented by pretreatment of mice with naloxone (non-selective opioid receptor antagonist), l-arginine (nitric oxide precursor), or glibenclamide (ATP-sensitive potassium channel blocker). HeTA (100 mg/kg, p.o.) produced a significant anti-inflammatory effect against carrageenan-induced rat paw edema (1-5 h), xylene-induced ear edema, cotton pellet-induced granuloma formation, and CFA-induced arthritis in rats. The effects of HeTA in various models were similar to the effect of the standard reference drugs. Conclusions Findings from this study showed that HeTA possesses antinociceptive effect possibly mediated through peripheral opioid receptors with activation of l-arginine-nitric oxide and ATP-sensitive potassium channel pathway as well as anti-inflammatory activity.

Phytochemical composition and pharmacological evaluation of different extracts of Oenothera rosea L´Hér. ex Ait (Onagraceae) aerial part

Oenothera genus consists of 145 herbs species which has been used for the treatment of skin diseases, diabetes mellitus, renal and liver problems, and as anti-diarrheic and anti-inflammatory drugs, among others. A great variety of chemical compounds have been reported from Oenothera genus among them tannins, flavonoids, steroids, carbohydrates and lipids. This study was focused on investigating the effect of different extracts of Oenothera rosea L´ Hér. ex Ait aerial part (from water ethanol, methanol, ethyl acetate, chloroform and hexane) on total flavonoid and phenolic compounds content; as well as the evaluation of their antioxidant, analgesic and anti-inflammatory activities. Antioxidant activity was performed considering the ability of the extracts to scavenge DPPH• free radicals, while analgesic and anti-inflammatory activities of most potent extracts were evaluated by acetic acid writhing reflex, hot plate and cotton pellet-induced granuloma formation models, respectively. Methanol, ethanol and ethyl acetate extracts showed a high phenolic compounds content, being ethanol the best solvent for extraction of flavonoids (28.84 ± 0.46 mg flavonoids/g extract). The highest antioxidant activity was observed with methanol, hexane and ethyl acetate extracts (89.51 ± 0.38, 89.42 ± 0.42 and 89.05 ± 0.34%, respectively). Ethanol and ethyl acetate extracts showed analgesic activity with inhibition percentages of the evaluated parameters of more than 50%. Ethyl acetate extract down-regulated chronic inflammation without inducing gastrointestinal damage. These findings provide scientific evidence of O. rosea folkloric use and highlight their importance as a possible natural treatment for several diseases.

Anti-inflammatory and Analgesic Effects of Polygonum orientale L. Extracts.

Background and Purpose: Polygonum orientale L. (family: Polygonaceae), named Hongcao in China, is a Traditional Chinese Medicinal and has long been used for rheumatic arthralgia and rheumatoid arthritis. However, no pharmacological and mechanism study to confirm these clinic effects have been published. In this investigation, the anti-inflammatory, analgesic effects and representative active ingredient compounds of P. orientale have been studied.Methods: Dried small pieces of the stems and leaves of P. orientale were decocted with water and partitioned successively to obtain ethyl acetate and ethyl ether extract of P. orientale (POEa and POEe). Chemical compositions of them were analyzed by UPLC-Q-Exactive HRMS. Anti-inflammatory and analgesic effects of POEa and POEe were evaluated using xylene induced ear edema, carrageenan induced paw edema, Freunds’ complete adjuvant induced arthritis, and formaldehyde induced pain in rat. Their mechanisms of anti-inflammatory and analgesic effects were also studied via assays of TNF-α, IL-1β, IL-6, and PGE2 in serum.Results: UPLC-Q-Exactive HRMS analysis showed that POEa and POEe mainly contained flavonoids including orientin, isoorientin, vitexin, luteolin, and quercetin. Furthermore, anti-inflammatory effects of POEa and POEe were evident in xylene induced ear edema. The paw edema in Freund’s complete adjuvant and carrageenan were significantly (P < 0.05, 0.01) inhibited by POEa (5, 7.5 g/kg). POEe (7.5 g/kg) was significantly (P < 0.05, 0.01) inhibited Freunds’ complete adjuvant induced paw edema and cotton pellet induced granuloma formation. Similarly, POEe significantly (P < 0.05, 0.01) inhibited the pain sensation in acetic acid induced writhing test. POEa (5, 7.5 g/kg) significantly (P < 0.05, 0.01) inhibited formaldehyde induced pain in both phases. POEa (7.5 g/kg) markedly (P < 0.05) prolonged the latency period of hot plate test after 30 and 60 min. The concentrations of TNF-α, IL-1β, IL-6, and PGE2 were significantly (P < 0.01) decreased by POEa (3.75, 5 g/kg).Conclusion: POEa and POEe have anti-inflammatory and analgesic effects, which was mainly relevant to the presence of flavonoids, including orientin, isoorientin, vitexin, luteolin, and quercetin. The mechanism of anti-inflammatory and analgesic effects of POEa may be to decrease the concentrations of TNF-α, IL-1β, IL-6, and PGE2 in serum.

Protective Effect of Crocodile Hemoglobin and Whole Blood Against Hydrogen Peroxide-Induced Oxidative Damage in Human Lung Fibroblasts (MRC-5) and Inflammation in Mice.

A putative protective effect of cHb and cWb against H2O2-induced oxidative damage was evaluated in detail using MRC-5 cells. In addition, the carrageenan (Carr)-induced mouse paw edema model and the cotton pellet-induced granuloma model were employed to examine the in vivo anti-inflammatory activity of cHb and cWb in mice. It was demonstrated that both cHb and cWb treatments significantly increased cell viability and inhibited morphology alterations in MRC-5 cells exposed to H2O2. Orally administered cHb and cWb significantly reduced Carr-induced paw edema volume and cotton pellet-induced granuloma formation. Moreover, cHb and cWb decreased the expression levels of important pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), while only cWb was found to increase the expression of the anti-inflammatory cytokine IL-10 significantly. Finally, the activity of antioxidant enzymes (SOD, CAT, and GPx) in the liver improved after cHb and cWb treatment under acute and chronic inflammation. Taken collectively, the results of this study suggest that both cHb and cWb protect against hydrogen peroxide-induced damage in fibroblast cells. Moreover, cHb and cWb were found to exhibit anti-inflammatory activity in both the acute and chronic stages of inflammation and appear to enhance antioxidant enzyme activity and decrease lipid peroxidation in the livers of mice. Therefore, this study indicates that cHb and cWb have great potential to be used in the development of dietary supplements for the prevention of oxidative stress related to inflammatory disorders.

The total alkaloid fraction of bulbs of Fritillaria cirrhosa displays anti-inflammatory activity and attenuates acute lung injury

Ethnopharmacological relevanceBulb of Fritillaria cirrhosa D.Don (BFC) has been wildly used in China for a long time for folk medicine since its significant therapeutic effects on respiratory diseases, such as cough, expectoration, pneumonia and bronchial inflammation, which are related to respiratory inflammatory response. However, there is a lack of investigation on the in vivo anti-inflammatory properties of BFC. Aim of the studyThe aim of this study was to evaluate the in vivo anti-inflammatory activity of the purified total alkaloid fraction of BFC (TAF) by using different animal models of inflammation to provide scientific evidence for its traditional use. Materials and methodsThe total alkaloid fraction from BFC was prepared by using H-103 resin column. Anti-inflammatory effect of TAF was evaluated by models of acetic acid-induced capillary permeability accentuation, carrageenan-induced rat paw edema, cotton pellet-induced granuloma formation and LPS-induced acute lung injury (ALI). The level of cytokines (TNF, IL-6, IL-4 and IL-10) was measured by ELISA. Histopathological analyses were performed by using hematoxylin and eosin staining. ResultsTAF can inhibit acetic acid-induced capillary permeability accentuation, carrageenan-induced paw edema, cotton pellet-induced granuloma formation, suppress inflammatory cells recruitment and cytokine production in the bronchoalveolar lavage fluid from LPS-induced ALI mice, and attenuate pathological changes in the lung tissues of ALI mice. ConclusionThis study provides scientific evidence for bulb of F. cirrhosa to treat respiratory inflammation.

Anti-inflammatory Effect of Picrorhiza kurroa in Experimental Models of Inflammation.

Picrorhiza kurroa is an important medicinal plant in the Ayurvedic system of medicine. The root and rhizome of this plant are used for the treatment of various liver and inflammatory conditions. In the present study, we sought to investigate the anti-inflammatory activity of P. kurroa rhizome extract against carrageenan-induced paw edema and cotton pellet implantation-induced granuloma formation in rats. In addition, its immunomodulatory activity was evaluated in Complete Freund's Adjuvant-induced stimulation of a peritoneal macrophage model and lipopolysaccharide-stimulated RAW 264.7 murine macrophages. Pretreatment with P. kurroa rhizome extract inhibited carrageenan-induced paw edema and cotton pellet-induced granuloma formation in a dose-dependent manner. This was associated with reduced levels of inflammatory cytokines (TNF-α, IL-1β, IL-6) accompanied with increased anti-inflammatory cytokine (IL-10) in the serum and peritoneal macrophages. Additionally, P. kurroa rhizome extract inhibited inflammatory TNF-receptor 1 and cyclooxygenase-2 in Complete Freund's Adjuvant-induced activated peritoneal macrophages. Furthermore, P. kurroa rhizome extract treatment significantly inhibited iNOS and suppressed the activation of NF-κB through inhibition of its phosphorylation and by blocking the activation of IκB kinase alpha in lipopolysaccharide-stimulated RAW264.7 macrophages. Taken together, these results suggest that P. kurroa has anti-inflammatory activity that is mediated through the suppression of macrophage-derived cytokine and mediators via suppression of NF-κB signaling.

ANTINOCICEPTIVE, ANTI-INFLAMMATORY EFFECTS AND SAFETY OF ZIZIPHUS MISTOL FRUITS

Ziziphus mistol Griseb. (Rhamnaceae), popularly known as “mistol,” is widely distributed throughout Perú, Bolivia, Paraguay and Argentina. Its fruit is consumed in different forms in several argentinean communities and used against biliary colic, dysentery, cold stomach and diseases of the respiratory system characterized by pain and inflammation. The present study was carried out to investigate the medicinal properties and safety of Ziziphus mistol (mistol) fruits ethanol and aqueous extracts and arrope. Antinociceptive activity was assessed using the formalin, acetic acid-induced writhing and tail-flick tests in rats. Anti-inflammatory effects were determined through carrageenan induced edema test and cotton pellet-induced granuloma formation, in rats. The safety was evaluated with test of acute toxicity (48 hours) and sub-chronic toxicity (91 days). All extracts (1,000 mg/kg b.w.) showed significant inhibition (P &lt;0.05) in the three model of pain experimentally induced in comparison to control. In a combination test using naloxone, diminished analgesic activity of aqueous extract and arrope were observed, indicating that their antinociceptive activity is connected with the opioid receptors. At dose 1000 mg/kg bw, the aqueous extract and arrope showed higher anti-inflammatory activity than the ethanol extract, in carrageenan and cotton pellet granuloma model used. In the acute toxicity study, a single dose of 4000 and 8000 mg/kg b.w., produced no mortality and no clinical signs of disease were observed after 48 hours. In the sub-chronic toxicity study the extracts no caused significant visible signs of toxicity, nor mortality for 91 consecutive days of treatment. Extracts and arrope of Z. mistol fruits could be good source of antinociceptive and anti-inflammatory agents because of its good activity and safety.

An Herbal Formula (GPC) Suppresses the Releases of Pro-Inflammatory Effectors in Lipopolysaccharide/Peptidoglycan-Activated RAW264.7 Macrophages and Reduces the Extent of Chemical-Induced Acute/Chronic Inflammation in Rodents

Pharyngitis (an inflammation in the pharynx) is a commonly occurring symptom of upper respiratory tract infection in patients suffering from common cold. The high prevalence of upper respiratory tract infection necessitates a safe and effective antiinflammatory agent for pharyngitis. Chinese herbal medicine, which has been clinically prescribed for thousands of years, may offer a basis for the treatment of common cold as well as the amelioration of pharyngitis. In the present study, we investigated the in vitro and in vivo anti-inflammatory activities of a Chinese herbal formula, namely GPC, which is comprised of Glycyrrhiza Radix, Platycodonis Radix, Citri Reticulatae Pericarpium, Phyllanthi Fructus and Taraxaci Herba. Incubation with GPC (30, 100 and 300 μg/mL) suppressed the releases of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and nitric oxide in lipopolysaccharide/peptidoglycanactivated RAW264.7 macrophages. In addition to the cell-based study, long-term treatment with GPC (0.35, 1.05 and 2.10 mL/kg/day × 30 doses) was found to reduce the extent of inflammation in animal models of carrageenan-induced paw edema (acute inflammation) as well as cotton pellet-induced granuloma formation (chronic inflammation) in mice. The ability of GPC to enhance the tracheobronchial expectorant action suggested its immunomodulatory activity in the respiratory tract. This postulation was supported by the observation that GPC reduced the degree of pharyngitis and reversed the changes in plasma TNF-α and IL-6 levels in capsaicininduced pharyngitis in rats. The ensemble of results suggests that GPC may offer a promising prospect for alleviating the extent of pharyngitis by virtue of antiinflammatory activities.