Anti-inflammatory and anti-proliferative activities of the wild edible cruciferous: Diplotaxis simplex

Context The present study deals with new biological properties of the wild edible Diplotaxis simplex (Viv.) Spreng (Brassicaceae).

Objectives The current study evaluates the antioxidant, the anti-inflammatory and the anti-cancer properties of ethyl acetate and ethanol extracts from D. simplex flowers.

Materials and methods The anti-proliferative activity of the extracts (10–70?μg/mL) was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) against human colon cancer cell line Caco-2. The anti-inflammatory potential was evaluated by the inhibitory effect of the extracts (1.5–7.5?mg/mL) on phospholipase A2 activity as well as on carrageenan-induced paw oedema in mice. Extracts (200?mg/kg) or indomethacin (50?mg/kg) as positive control were injected intraperitoneally for albino mice prior to the induction of the oedema by carrageenan. Antioxidant activities were investigated using various complementary methods.

Results Flower extracts contained a high level of polyphenolics (17.10–52.70?mg GAE/g) and flavonoids (74.20–100.60?mg QE/g), which correlate with its appreciable antioxidant potential in β-carotene peroxidation (IC₅₀ value: 12.50–27.10?μg/mL), DPPH^? radical-scavenging (IC₅₀ value: 0.20–0.40?mg/mL), Fe^3+?reducing (EC₅₀ value: 0.10–0.14?mg/mL) and Fe^2+?chelating (IC₅₀ value: 0.20–0.60?mg/mL) assays. These extracts were effective in inhibiting cancer cell growth (IC₅₀ value: 62.0–63.25?μg/mL). Besides, the ethyl acetate extract inhibited phospholipase A2 activity (IC₅₀ value: 2.97?mg/mL) and reduced the paw oedema in mice (from 0.38?±?0.01 to 0.24?±?0.01?cm), 4?h post-carrageenan challenge.

Conclusion These data suggest that D. simplex may be useful as a candidate in the treatment of inflammation and the colon cancer.     

Antioxidant and anti-inflammatory activities of Aerva pseudotomentosa leaves

Context: Aerva pseudotomentosa Blatt. &; Hallb. (Amaranthaceae), commonly called ‘Bui’, is a medicinal plant of the arid region. It is used for the treatment of inflammatory disorders, such as rheumatic pain, and healing of wounds, which are associated with oxidative stress.

Objective: The present study evaluated the antioxidant potential of Aerva pseudotomentosa leaves by in vitro models and its anti-inflammatory effect in rats.

Material and methods: The aqueous extract (APAE) was analyzed by HPTLC and HPLC. The antioxidant effect of APAE was evaluated by various in vitro methods [DPPH (1, 1-diphenyl-2-picryl-hydrazil) and hydrogen peroxide free radical scavenging, reducing power, and anti-lipid peroxidation assays]. Anti-inflammatory effect was studied in carrageenan and formalin-induced paw oedema models in rats. APAE (200 and 400?mg/kg) and standard drug, indomethacin (10?mg/kg), were administered orally 1?h before carrageenan/formalin administration and inflammation was noted up to 5?h.

Results: HPLC analysis of APAE revealed the presence of rutin. APAE showed significant scavenging effect on DPPH (IC₅₀ 49.37?μg/mL) and peroxide (IC₅₀ 288.2?μg/mL) radicals. The extract exhibited reducing potential and inhibition of lipid peroxidation. APAE treatment significantly attenuated mean increase in paw volume and exhibited inhibition of paw oedema in both in vivo models with inhibition of 45.11% and 49.42%, respectively at 5?h.

Discussion and conclusion: APAE exhibited in vitro antioxidant and anti-inflammatory activities. Anti-inflammatory effect of APAE may be attributed to its antioxidant potential, due to the presence of rutin and other phenolics. This study substantiates folk use of leaves in inflammatory disorders.     

Anti-inflammatory,free radical scavenging and alpha-glucosidase inhibitory activities of Hamelia patens and its chemical constituents

Context Hamelia patens Jacq. (Rubiaceae) is traditionally used to treat wounds, inflammation and diabetes. However, there is still a lack of scientific evidence to support these applications.

Objective The objective of this study is to evaluate the anti-inflammatory, antioxidant and antidiabetic activities of Hamelia patens, and identify its bioactive compounds.

Materials and methods Four extracts were obtained by maceration and liquid–liquid extraction: HEX, DCM–EtOAc, MeOH–EtOAc and MeOH–Aq. The anti-inflammatory effect was evaluated orally on rat paw carrageenan-induced oedema over 6?h (50, 200 and 500?mg/kg), and topically in mouse ear oedema induced by 12-tetradecanoylphorbol-13-acetate (TPA) after 4?h (0.5 and 1?mg/ear). We also evaluated myeloperoxidase levels in ear tissue, 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging ability, and in vitro α-glucosidase inhibition. The chemical compounds were separated by column chromatography and identified by spectroscopic analysis.

Results We found that the oral administration of the HEX extract at 500 and 200?mg/kg significantly decreased the carrageenan-induced inflammation after 1 and 3?h, respectively. The MeOH–EtOAc extract significantly inhibited myeloperoxidase activity (83.5%), followed by the DCM–EtOAc extract (76%), β-sitosterol/stigmasterol (72.7%) and the HEX extract (55%), which significantly decreased oedema induced by TPA at both doses, giving a similar effect to indomethacin. We also found that the MeOH–EtOAc, MeOH–Aq and DCM–EtOAc extracts showed good DPPH scavenging activity (IC₅₀ values of 18.6, 93.9 and 158.2?μg/mL, respectively). The HEX extract showed the lowest α-glucosidase inhibition (an IC₅₀ value of 26.07?μg/mL), followed by the MeOH–EtOAc extract (an IC₅₀ value of 30.18?μg/mL), β-sitosterol/stigmasterol (IC₅₀ 34.6?μg/mL) and compound A ((6E,10E,14E,18E)-2,6,10,14,18,23-hexamethyl-2,6,10,14,18,22-tetracosahexaene, an IC₅₀ value of 114.6?μg/mL), which were isolated for the first time from Hamelia patens.

Discussion and conclusion Hamelia patens possesses anti-inflammatory, antioxidant and α-glucosidase inhibitory activities, which support its traditional use. These effects can be attributed to the identified compounds.     

Anticholinesterase,antioxidant, analgesic and anti-inflammatory activity assessment of Xeranthemum annuum L. and isolation of two cyanogenic compounds

Context: Xeranthemum annuum L. (Asteraceae) (XA) is an ornamental and medicinal species with limited bioactivity and phytochemical data.

Objective: Identification of anticholinesterase, antioxidant, anti-inflammatory and analgesic effects of the flower and root–stem (R-S) extracts of XA.

Materials and methods: Anticholinesterase (at 100?μg mL^?1) and antioxidant (at 1000?μg mL^?1) effects of various extracts were evaluated via microtiter assays, while anti-inflammatory and analgesic effects of the R-S extracts were tested using carrageenan-induced hind paw oedema (100 and 200?mg kg^?1) and p-benzoquinone (PBQ) writhing models (200?mg kg^?1) in male Swiss albino mice. The R-S ethanol extract of XA was subjected to isolation studies using conventional chromatographic methods.

Results: Most of the extracts showed inhibition over 85% against butyrylcholinesterase and no inhibition towards acetylcholinesterase. The flower chloroform and the R-S ethyl acetate extracts were most effective (97.85?±?0.94% and 96.89?±?1.09%, respectively). The R-S ethanol extract displayed a remarkable scavenging activity against DPPH (77.33?±?1.99%) and in FRAP assay, while the hexane extract of the R-S parts possessed the highest metal-chelating capacity (72.79?±?0.33%). The chloroform extract of the R-S caused a significant analgesic effect (24.4%) in PBQ writhing model. No anti-inflammatory effect was observed. Isolation of zierin and zierin xyloside, which were inactive in anticholinesterase assays, was achieved from the R-S ethanol extract.

Discussion and conclusion: This is the first report of anticholinesterase, antioxidant, analgesic and anti-inflammatory activities and isolation of zierin and zierin xyloside from XA. Therefore, XA seems to contain antioxidant and BChE-inhibiting compounds.     

Anti-inflammatory and antinociceptive effect of Pachygone ovata leaves

Context: Pachygone ovata (Poir.) Miers ex Hook. F. et Thoms (Menispermaceae) is a rich source of bioactive bisbenzylisoquinoline and aporphine alkaloids.

Objective: This study investigates the in vitro and in vivo anti-inflammatory and antinociceptive potential of Pachygone ovata leaves.

Materials and methods: Lipoxygenase (LOX) assay for anti-inflammatory activity was conducted using MeOH, EA, H and Aq extracts; followed by alkaloid isolation. The anti-inflammatory potential was determined using carrageenan-induced paw oedema and formalin tests for evaluation of Pachygone ovata analgesic effect. Different doses (100, 300 and 400?μg/kg) were administered orally to Wistar rats for a period of one week, once daily.

Results: MeOH and EA extract efficiently inhibited LOX (IC₅₀ 1.43 and 2.15?μg/mL, respectively). MeOH extract had better inhibiting capacity (57%) than indomethacin (51%) in carrageenan induced rats. MeOH extract (300?μg/kg) significantly reduced the increased levels of nitric oxide (8?±?0.57 M), total leukocyte count (4.5?±?0.05 cells 10³/cells) and C-reactive protein (55?±?0.45?mg/mL). There was a decrease in various serum biochemical markers (ALT, AST). Histopathological studies revealed reduction in oedema and decreased cellular infiltration on supplementation with MeOH extract. Furthermore, MeOH extract (300?μg/kg) and alkaloid fraction (400?μg/kg) effected both phases (neurogenic and inflammatory) of formalin injected models.

Discussion and conclusion: Inflammatory mediators play a key role in inflammation; therefore, keeping it in control is of utmost importance. The usefulness of Pachygone ovata leaves on pain and inflammation has been described, probably due to its effect on inflammatory mediators and high alkaloid content.     

Patent Evaluation: Nonapeptide Phospholipase A2 Inhibitors

Summary

Novelty: A nonapeptide sequence of human lipocortin V (residues 204-212) is claimed to have anti-inflammatory properties and be useful for dermatological and collagen inflammatory conditions.

Biology: Data are presented which indicate that the peptide can inhibit PGE₂ release from rat leukocytes and human fibroblasts (94% inhibition at 100 μg/ml), inhibit PLA₂-induced contractions in rat stomach strip (60% at 20 μg/ml), inhibit PLA₂-induced oedema in rat paw in vivo and of carrageenin-induced oedema in rat paw (37% inhibition at 4 hours with 2 mg/kg).

Chemistry: The peptide is synthesized by solid phase methodology and has the structure given below.

Structure:      

Anti-inflammatory and antinociceptive activities of Homalium letestui

Abstract

Context. Homalium letestui Pellegr (Flacourtiaceae) is used in various decoctions traditionally by the Ibibios of the Niger Delta of Nigeria to treat stomach ulcer, malaria and other inflammatory diseases, as well as an aphrodisiac.

Objective: To investigate the anti-inflammatory and antinociceptive activities of the stem extract of the plant.

Materials and methods: The ethanol stem extract (500, 750, 1000?mg/kg, i.p.) of H. letestui was investigated for anti-inflammatory activity using carrageenan, egg albumin-induced and xylene-induced ear edema models and analgesic activity using acetic acid-induced writhing, formalin-induced paw licking and thermal-induced pain models. The ethanol extract was administered to the animals orally, 30?min to 1?h depending on the model, before induction of inflammation/pain. The LD₅₀ was also determined. GC–MS analysis of dichloromethane fraction was carried out.

Results: The extract caused a significant (p?<?0.05–0.001) reduction of inflammation induced by carrageenan (8.3–70.0%), egg albumin (10.0–71.42%) and xylene (39.39–84.84%). The extract also reduced significantly (p?<?0.05–0.001) pain induced by acetic acid (44.22–73.65%), formalin (55.89–79.21%) and hot plate (93.0–214.5%). The LD₅₀ was determined to be 4.38?±?35.72?g/kg.

Discussion and conclusion: The results of this study suggest that the ethanol stem extract of H. letestui possesses anti-inflammatory and analgesic properties which may in part be mediated through the chemical constituents of the plant as revealed by the GC–MS.     

Phytochemical screening and anti-inflammatory properties of Algerian Hertia cheirifolia methanol extract

Context: Hertia cheirifolia L. (Asteraceae) is traditionally used in Northern Africa to treat various inflammatory infections. However, few studies on this plant have been reported.

Objective: The anti-inflammatory activity of methanol extract of H. cheirifolia leaves was investigated using different experimental models.

Materials and methods: Phytochemical analysis was performed to determine phenolic compounds. Acute toxicity of the extract (2000?mg/kg) was examined in Swiss albino mice for 14 days, before croton oil-induced ear oedema in mice, carrageenan-induced paw oedema in Swiss albino rats, cotton pellet-induced granuloma in rats and carrageenan-induced air pouch in mice were conducted. The IL-1β and TNF-α release from concanavalin A-stimulated monocytes was measured by ELISA.

Results: Methanol extract of H. cheirifolia is rich in polyphenols and flavonoids. Cinnamic acid and rutin represent the major constituents. Methanol extract up to 2000?mg/kg did not produce any toxic effects. Topical application of 2?mg/ear of the extract produced 78.7% of inhibition on ear swilling. Oral pre-treatment of rats with 200 and 400?mg/kg of the extract inhibited paw oedema by 70% and 89%, respectively. At 200?mg/kg, granuloma dry and wet weights were reduced by 41.85% and 61.72%, respectively. Moreover, the treatment with methanol extract at 1?mg/kg exerted 62.7% of inhibition on leucocytes migrated into the ear pouch. TNF-α and IL-1β release was reduced by 69% and 78%, respectively, with 1?μg/mL of the extract.

Conclusion: Methanol extract of H. cheirifolia possesses a strong anti-inflammatory activity and may be considered an interesting source of effective anti-inflammatory compounds.     

Nanoparticle formulation of 11-keto-β-boswellic acid (KBA): anti-inflammatory activity and in vivo pharmacokinetics

Context: The oleo-gum-resin of Boswellia serrata Roxb. (Burseraceae) is widely used for the treatment of inflammatory diseases such as osteoarthritis, rheumatoid arthritis and cancer. Anti-inflammatory activity of 11-keto-β-boswellic acid (KBA) is impeded by poor oral bioavailability due to its high lipid solubility, rapid phase-1 metabolism and poor intestinal permeability.

Objective: This study developed a poly-dl-lactide-co-glycolide-based nanoparticle formulation of KBA to improve its oral bioavailability and in vivo anti-inflammatory activity.

Materials and methods: KBA was isolated from the oleo-gum resin of B. serrata, and its nanoparticle formulation (KBA-NPs) was prepared by the emulsion–diffusion–evaporation method. Oral bioavailability of KBA and KBA-NPs was studied at 50?mg/kg p.o. dose in Sprague–Dawley rats, and further evaluated for in vivo anti-inflammatory activity in carrageenan-induced rat paw oedema assay at the same dose level.

Results: The prepared KBA-NPs had a particle size of 152.6?nm with polydispersity index of 0.194, 79.7% entrapment efficiency and a cumulative 61.5% release of KBA from KBA-NPs, at 72?h. KBA-NPs showed 60.8% inhibition of rat paw oedema at 5?h as compared to 34.9% as that of KBA. The results of oral bioavailability study and in vivo anti-inflammatory activity showed 7- and 1.7-fold increase in bioavailability and anti-inflammatory activity, respectively, of KBA in KBA-NPs as compared to KBA alone.

Conclusion: The results of improved oral bioavailability and in vivo anti-inflammatory activity of KBA-NPs suggested successful development of KBA nanoparticle formulation.     

Tephrosia sinapou ethyl acetate extract inhibits inflammatory pain in mice: Opioid receptor dependent inhibition of TNFα and IL-1β production

Abstract

Context. Tephrosia toxicaria is currently known as Tephrosia sinapou (Buc'hoz) A. Chev. (Fabaceae) and is a source of compounds such as flavonoids that inhibit inflammatory pain.

Objective: To investigate the analgesic effect and mechanisms of the ethyl acetate extract of T. sinapou in inflammatory pain in mice.

Materials and methods: Behavioral responses were evaluated using mechanical (1–24?h) and thermal hyperalgesia (0.5–5?h), writhing response (20?min) and rota-rod (1–5?h) tests. Neutrophil recruitment (myeloperoxidase activity), cytokines (tumor necrosis factor [TNF]α and interleukin [IL]-1β), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels were determined by colorimetric assays. Pharmacological treatments were opioid receptor antagonist (naloxone, 0.1–1?mg/kg) and control opioid (morphine, 5?mg/kg). Inflammatory stimuli were carrageenin (100?µg/paw), complete Freund’s adjuvant (CFA, 10?µl/paw), prostaglandin E₂ (PGE₂, 100?ng/paw) and acetic acid (0.8%).

Results: The intraperitoneal pre-treatment with extract inhibited in a dose-dependent (30–300?mg/kg) dependent manner the mechanical hyperalgesia induced by carrageenin (up to 93% inhibition). The post-treatment (100?mg/kg) inhibited CFA-induced hyperalgesia (up to 63% inhibition). Naloxone (1?mg/kg) prevented the inhibitory effect of the extract over carrageenin-induced mechanical (100%) and thermal (100%) hyperalgesia, neutrophil recruitment (52%) and TNFα (63%) and IL-1β (98%) production, thermal threshold in naïve mice (99%), PGE₂-induced mechanical hyperalgesia (88%) and acetic acid-induced writhing response (49%). There was no significant alteration in the rota-rod test, and AST and ALT serum levels by extract treatment.

Discussion and conclusion. Tephrosia sinapou ethyl acetate extract reduces inflammatory pain by activating an opioid receptor-dependent mechanism.     

Mechanistic assessment of the analgesic,anti-inflammatory and antipyretic actions of Dalbergia saxatilis in animal models

Context: Aqueous root extract of Dalbergia saxatilis, Hook, f., (Leguminosae) (DS) is reported useful for toothache, pains, and fever, but not scientifically proven.

Objective: This study determined its effectiveness in pain, inflammation, and fever, applying scientific models.

Materials and methods: Swiss mice or Sprague–Dawley rats (n?=?5) were pretreated with distilled water, DS (100 or 200?mg/kg), or standard drug for 30?min. The analgesic activity was measured by acetic acid writhing, tail flick, tail immersion, tail clip, hot plate, and formalin pain tests; anti-inflammatory effects were determined via carrageenan and dextran rat paw oedema tests; antipyretic activity was measured by Escherichia coli lipopolysaccharide (ECL) and turpentine in rabbits, and d-amphetamine sulphate (d-AS) pyrexia test in rats.

Results: Writhing frequency inhibition was produced by 200?mg/kg DS (33.10%), aspirin (38.19%) and morphine (93.68%). Unlike morphine, DS did not produce significant prolongation of the reaction times in the hot-plate, tail immersion, tail flick, and tail clip tests. In the first and second phases of formalin test, respectively, % inhibition was: 200?mg/kg DS (25.70% and 0%), aspirin (4.76% and 67.33%), morphine (81.42% and 66.11%); for carrageenan and dextran tests, significant difference was recorded between 200?mg/kg DS and control up to 6?h. Significant reduction in ECL, turpentine and d-AS pyrexia was recorded at 100 and 200?mg/kg DS.

Conclusion: DS produces mild non-steroidal analgesic and anti-inflammatory, as well as significant antipyretic actions involving cyclooxygenase, α₂ adrenoceptor and interleukin-1 β1 due to any of glycosides, saponins or phenolic tannins.     

Evaluation of anti-inflammatory activity and standardisation of hydro-methanol extract of underground tuber of Dioscorea alata

Context The underground edible tuber of Dioscorea alata L. (Dioscoreaceae) is a functional food with high nutritive value and therapeutic potential. The tuber is known to possess anti-inflammatory properties in traditional medicine.

Objective The present study explores the anti-inflammatory activity and standardisation of D. alata tuber hydromethanol extract.

Materials and methods Hydromethanol extract (70%) of D. alata tuber was chemically characterised using HPLC and GC-MS techniques. Murine lymphocytes were cultured for 48?h with six different concentrations (0–80?μg/mL) of the extract. The expression of nitric oxide (NO), TNF-α, COX-1, COX-2, and PGE₂ were evaluated using colorimetric and ELISA methods.

Results Dioscorea alata extract inhibited the expression of NO and TNF-α with an IC₅₀ value of 134.51?±?6.75 and 113.30?±?7.44?μg/mL, respectively. The IC₅₀ values for inhibition of total COX, COX-1, COX-2 activities and PGE₂ level were 41.96?±?3.07, 141.41?±?8.99, 32.50?±?1.69, and 186.34?±?15.36?μg/mL, respectively. Inhibition of PGE₂ level and COX-2 activity was positively correlated (R²?=?0.9393). Gallic acid (GA), 4-hydroxy benzoic acid (4HBA), syringic acid (SYA), p-coumaric acid (PCA), and myricetin (MY) were identified and quantified using HPLC. GC-MS analysis revealed the presence of 13 different phytocompounds such as hexadecanoic acid, methyl stearate, cinnamyl cinnamate, and squalene.

Conclusion The D. alata extract significantly down-regulated the pro-inflammatory signals in a gradual manner compared with control (0?μg/mL). Different bioactive phytocompounds individually possessing anti-inflammatory activities contributed to the overall bioactivity of the D. alata tuber extract.     

Biochemical characterization,anti-inflammatory properties and ulcerogenic traits of some cold-pressed oils in experimental animals

Context: Cold-pressed oils (CPO) are commercially available in the market and characterized by their health-promoting properties.

Objective: Clove oil (CLO), coriander seed oil (COO) and black cumin oil (BCO) were evaluated for their bioactive lipids. Pharmacological screening was performed to evaluate acute toxicity, anti-inflammatory and ulcerogenic effects as well as histopathological changes in tissues of albino rats fed with CPO.

Materials and methods: Fatty acids, tocols and total phenolics were analyzed. The acute toxicity test for each CPO was estimated during 14 d. Carrageenan-induced rat paw oedema was used for assessment of anti-inflammatory activity of CPO. Animals were fasted overnight, and via oral gavage given indomethacin (10?mg/kg) or CPO (400?mg/kg) to investigate ulcerogenecity. Histopathological changes in liver, kidney, heart, spleen and stomach were screened.

Results: Amounts of α-, β-, γ- and δ-tocopherols in CLO were 1495, 58, 4177 and 177?mg/kg oil, respectively. In COO, α, β, γ and δ-tocopherols were 10.0, 18.2, 5.1 and 34.8%, respectively. In BCO, β-tocotrienol was the main constituent. CLO, COO and BCO contained 4.6, 4.2 and 3.6?mg GAE/g, respectively. Acute toxicity test determined that 400?mg/kg of CPO to be used. In the carrageenan model of inflammation, pretreatment of rats with indomethacin (10?mg/kg) or CLO (400?mg/kg) induced a significant (p?Conclusions: CPO, particularly CLO, could minimize acute inflammation.     

In vivo anti-inflammatory properties of aerial parts of Nasturtium officinale

Context: Nasturtium officinale R. Br. (watercress) has long been used in Iranian folk medicine to treat hypertension, hyperglycemia, and renal colic. Moreover, anticancer, antioxidant, and hepatoprotective properties of N. officinale have been reported.

Objective: In this study, anti-inflammatory activity of the hydro-alcoholic extract from aerial parts of N. officinale was investigated.

Materials and methods: Oral administration of the hydro-alcoholic extract of N. officinale (250, 500 and 750?mg?kg^?1) was investigated on two well-characterized animal models of inflammation, including carrageenan- or formalin-induced paw edema in rats. Then, the topical anti-inflammatory effect of N. officinale (2 and 5?mg/ear) was studied on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema. Finally, biopsy of the paw or ear was performed for pathological evaluation.

Results: Acute toxicity tests of N. officinale in rats established an oral LD₅₀ of >5?g?kg^?1. The extract of watercress (250, 500 and 750?mg?kg^?1) significantly inhibited carrageenan-induced paw edema 1, 2, 3 and 4?h after carrageenan challenge (p??1) also showed considerable activity against formalin-evoked paw edema over a period of 24?h (p?N. officinale (5?mg/ear) reduced TPA-induced ear edema (p?Discussion and conclusion: Our findings indicate potent anti-inflammatory activity of N. officinale in systemic and topical application and propose its potential as an anti-inflammatory agent for treatment of inflammatory conditions.     

Citrus hallabong [(Citrus unshiu × C. sinensis) × C. reticulata)] exerts potent anti-inflammatory properties in murine splenocytes and TPA-induced murine ear oedema model

Context: Hallabong [(Citrus unshiu?×?C. sinensis) X C. reticulata)] (Rutaceae) is a hybrid citrus cultivated in temperate regions of South Korea. Its fruit is well-known for pharmacological properties.

Objective: This study examined the anti-inflammatory effect of 80% ethanol extract of Hallabong (HE) on concanavalin A (Con A)-stimulated splenocytes and mouse oedema model induced by 12-O-tetradecanoylphorbal acetate (TPA).

Materials and methods: Murine splenocytes treated with HE were stimulated with Con A (10?μg/mL, for 24?h) were evaluated for T-cell population and production of inflammatory cytokines IL-2, IL-4 and IFN-γ. Anti-inflammatory effect of topically applied HE (100?μg/20?μL) on TPA (4?μg/20?μL/ear)-induced ear oedema was investigated in mouse model.

Results: HE-treated Con A-stimulated murine splenocytes showed a marked decrease in CD44/CD62L⁺ memory T-cell population, an important marker for anti-inflammatory activity, and a significant inhibition in the production of IL-2 and IFN-γ. HE treatment had reduced the mouse skin oedema (47%) and myeloperoxidase (MPO) activity significantly (40%) in TPA-challenged tissues. More importantly, immunohistochemical localization revealed the suppressed (p?<?0.05) expression of inducible nitric oxide (iNOS), cyclooxygenase-2 (COX2). HE decreased the infiltration of CD3⁺ T cells and F4/80⁺ macrophages to the site of inflammation and a topical application of HE significantly suppressed the expression of TNF-α (20.2%).

Discussion and conclusion: A topical application of HE can exert a potential anti-inflammatory effect and HE can be explored further as a putative alternative therapeutic agent for inflammatory oedema.     

In vitro immunomodulatory activity and in vivo anti-inflammatory and analgesic potential with gastroprotective effect of the Mediterranean red alga Laurencia obtusa

Context: Red algae have been recognized as a rich natural source of compounds possessing interesting biological and pharmacological activities.

Objective: This work investigates anti-inflammatory, analgesic and gastroprotective activities of MeOH/CH₂Cl₂ crude extract and its fractions F1 (50% MeOH) and F2 (80% MeOH) from the whole alga plant Laurencia obtusa Hudson (Rhodomelaceae).

Materials and methods: Anti-inflammatory activity was evaluated in vitro using cytometric bead array (CBA) technology to follow up the secretion of tumour necrosis factor alpha (TNF-α) in lipopolysaccharide activated THP-1 monocytic cells at doses of 10–250?μg/mL and in vivo using carrageenan-induced paw oedema in Wistar rats at doses of 25, 50, 100 and 200?mg/kg. Crude extract and fractions were tested at the doses of 25, 50, 100 and 200?mg/kg for peripheral and central analgesic activity by acetic acid-induced writhing test and hot-plate method, respectively, in Swiss albino mice. Gastroprotective activity was evaluated using HCl/ethanol-induced gastric ulcer test in rats at doses of 25, 50, 100 and 200?mg/kg.

Results: Crude extract, F1 and F2 showed an interesting inhibition of TNF-α secretion with IC₅₀ values of 25, 52 and 24?μg/mL, respectively, and a significant anti-inflammatory activity in vivo (p?< 0.01), 3?h after carrageenan injection, the oedema inhibition was 55.37%, 52.18% and 62.86%, respectively, at the dose of 100?mg/kg. Furthermore, they showed a significant peripheral analgesic activity with 53.79%, 55.92% and 57.37% (p?< 0.01) of writhing inhibition, respectively. However, no significant activity was found in the hot-plate test. An interesting gastroprotective effect was observed with crude extract and its fractions F1 and F2 with a gastric ulcer inhibition of 65.48%, 77.42% and 81.29%, respectively, at the dose of 50?mg/kg.

Discussion and conclusion: These results suggest that L. obtusa might be used as a potential source of natural anti-inflammatory and analgesic agents with gastroprotective effect.     

An evaluation of the anti-inflammatory,antipyretic and analgesic effects of hydroethanol leaf extract of Albizia zygia in animal models

Context: The leaves of Albizia zygia (DC.) J.F. Macbr. (Leguminosae-Mimosoideae) are used in Ghanaian traditional medicine for the treatment of pain, inflammatory disorders and fever (including malaria).

Objectives: The present study evaluated the anti-inflammatory, antipyretic and analgesic effects of the hydroethanol leaf extract of Albizia zygia (AZE) in animal models.

Materials and methods: The anti-inflammatory and antipyretic effects of AZE were examined in the carrageenan-induced foot oedema model and the baker’s yeast-induced pyrexia test respectively. The analgesic effect and possible mechanisms of action were also assessed in the formalin test.

Results: AZE (30–300?mg/kg, p.o.), either preemptively or curatively, significantly inhibited carrageenan-induced foot edema in 7-day-old chicks (ED₅₀ values; preemptive: 232.9?±?53.33?mg/kg; curative: 539.2?±?138.28?mg/kg). Similarly, the NSAID diclofenac (10–100?mg/kg, i.p.) significantly reduced the oedema in both preemptive (ED₅₀: 21.16?±?4.07?mg/kg) and curative (ED₅₀: 44.28?±?5.75?mg/kg) treatments. The extract (30–300?mg/kg, p.o.) as well as paracetamol (150?mg/kg, p.o.) also showed significant antipyretic activity in the baker’s yeast-induced pyrexia test (ED₅₀ of AZE: 282.5?±?96.55?mg/kg). AZE and morphine (1–10?mg/kg, i.p.; positive control), exhibited significant analgesic activity in the formalin test. The analgesic effect was partly or wholly reversed by the systemic administration of naloxone, theophylline and atropine.

Conclusion: The results suggest that AZE possesses anti-inflammatory, antipyretic and analgesic properties, which justifies its traditional use. Also, the results show the involvement of the opioidergic, adenosinergic and the muscarinic cholinergic pathways in the analgesic effects of AZE.     

In vivo and in vitro pharmacological activity of Aristolochia tagala (syn: Aristolochia acuminata) root extracts

Context: Aristolochia tagala Cham. (syn: Aristolochia acuminata Lam.) (Aristolochiaceae), known as Nallayishwari in Telugu, has been of interest to researchers because of its traditional uses for treating rheumatic pains and fever.

Objective: The anti-inflammatory activity of the petroleum ether, ethyl acetate, and ethanol extracts of A. tagala roots were investigated for the first time.

Materials and Methods: In vivo and in vitro anti-inflammatory effects were investigated employing the carrageenan-induced hind paw edema in rats and the macrophage cell line RAW264.7 stimulated with proinflammatory stimuli (lipopolysaccharide interferon γ or the calcium ionophore A23187) to determine PGE₂ or LTB₄ release, respectively.

Results: All the extracts exhibited anti-inflammatory effects which were found to be significant (p?<?0.001) at 200 and 400?mg/kg, p.o, in rats tested and the ethyl acetate extract inhibited the induction of PGE₂ with IC₅₀?=?39.1?mg mL^?1 and LTB₄ with IC₅₀?=?29.5?mg mL^?1.

Discussion and conclusion: These findings demonstrate that the A. tagala roots have excellent anti-inflammatory activity and validate the traditional indications of this plant in its origin country.     

In-vivo effects of nociceptin and its structural analogue [Orn9] nociceptin on the antioxidant status of rat blood and liver after carrageenan-induced paw inflammation

The production of reactive oxygen species (ROS) in cells is well balanced with their elimination by the antioxidant defence system. This balance is essential for maintenance of physiological conditions, and its disturbance (oxidative stress) has been suggested as a potential pathogenic mechanism in a variety of diseases, accompanied by inflammation. In this study, the in-vivo effects of nociceptin (N/OFQ(1–13)NH₂) and its structure analogue [Orn⁹]N/OFQ(1–13)NH₂ were studied on markers of oxidative stress in erythrocytes and liver of rats 4 hours after subplantar administration of carrageenan (CG) (1%, 100 µl) in the right hind paw. A considerable inflammatory oedema of the paw was observed. CG did not change blood haemoglobin content, hematocrit value, glutathione level and antioxidant enzyme activities in the erythrocytes, but there was an increase in lipid peroxidation. In liver, CG-induced imbalance was manifested by an increase in lipid peroxidation and a decrease in glutathione level. Both peptides (20 µg, i.p.), when administered alone, had no effect on all parameters tested. When either [Orn⁹]N/OFQ(1–13)NH₂ or N/OFQ(1–13)NH₂ was injected simultaneously with CG or 15 minutes before it, they did not affect the CG-induced changes in the antioxidant status of the erythrocytes and liver. Our results suggest that the peptides tested did not play a role in the free radical processes that accompany CG-induced paw inflammation.     

Studies on phytochemical,antioxidant, anti-inflammatory,hypoglycaemic and antiproliferative activities of Echinacea purpurea and Echinacea angustifolia extracts

Context: Echinacea (Asteraceae) is used because of its pharmacological properties. However, there are few studies that integrate phytochemical analyses with pharmacological effects.

Objective: Evaluate the chemical profile and biological activity of hydroalcoholic Echinacea extracts.

Materials and methods: Density, dry matter, phenols (Folin–Ciocalteu method), flavonoids (AlCl₃ method), alkylamides (GC-MS analysis), antioxidant capacity (DPPH and ABTS methods), antiproliferative effect (SRB assay), anti-inflammatory effect (paw oedema assay, 11 days/Wistar rats; 0.4?mL/kg) and hypoglycaemic effect (33 days/Wistar rats; 0.4?mL/kg) were determined in three Echinacea extracts which were labelled as A, B and C (A, roots of Echinacea purpurea L. Moench; B, roots, leaves, flowers and seeds of Echinacea purpurea; C, aerial parts and roots of Echinacea purpurea and roots of Echinacea angustifolia DC).

Results: Extract C showed higher density (0.97?g/mL), dry matter (0.23?g/mL), phenols (137.5?±?2.3 mEAG/mL), flavonoids (0.62?±?0.02 mEQ/mL), and caffeic acid (0.048?mg/L) compared to A and B. A, B presented 11 alkylamides, whereas C presented those 11 and three more. B decreased the oedema (40%) on day 2 similar to indomethacin. A and C showed hypoglycaemic activity similar to glibenclamide. Antiproliferative effect was only detected for C (IC₅₀ 270?μg/mL; 8171?μg/mL; 9338?μg/mL in HeLa, MCF-7, HCT-15, respectively).

Discussion and conclusion: The difference in the chemical and pharmacological properties among extracts highlights the need to consider strategies and policies for standardization of commercial herbal extracts in order to guarantee the safety and identity of this type of products.