Anti-inflammatory activity of patchouli alcohol isolated from Pogostemonis Herba in animal models

Pogostemonis Herba has long been used in traditional Chinese medicine for the treatment of inflammatory disorders. Patchouli alcohol (PA), a tricyclic sesquiterpene isolated from Pogostemonis Herba, is known to possess a variety of pharmacological activities. The present study aimed to investigate the in vivo anti-inflammatory effect of PA using two common inflammatory animal models i.e., xylene-induced ear edema in mice and carrageenan-induced paw edema in rats. The degree of edema in both inflammatory animals, as well as the protein and mRNA expression of some inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), prostaglandin E₂ (PGE₂) and nitric oxide (NO) in the hind paw of carrageenan-treated rats were measured. Results showed that PA (10–40 mg/kg) significantly inhibited the ear edema induced by xylene in mice and the paw edema induced by carrageenan in rats. In addition, treatment with PA (10–40 mg/kg) also dose-dependently decreased the production of TNF-α, IL-1β, PGE₂ and NO in the hind paw of carrageenan-treated rats. Furthermore, PA treatment also suppressed the mRNA expression of TNF-α, IL-1β, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the hind paw of carrageenan-treated rats. These results suggest that PA possesses potent anti-inflammatory activity, which may be mediated, at least in part, by down-regulating the mRNA expression of a panel of inflammatory mediators including TNF-α, IL-1β, iNOS and COX-2.     

Effects of Morus alba leaf extract on the production of nitric oxide, prostaglandin E2 and cytokines in RAW264.7 macrophages

Morus alba leaf methanolic extract and its fractions (chloroform, butanol, and aqueous fractions) were found to inhibit NO production in LPS-activated RAW264.7 macrophages without an appreciable cytotoxic effect at concentration from 4 to 100 microg/ml. LPS-induced PGE2 production was significantly reduced only by butanol fraction. In addition, M. alba leaf extract and its fractions significantly decreased the production of TNF-alpha. These findings suggest that M. alba leaf extract seems to be able in suppressing inflammatory mediators. Moreover, the inhibitory activities on COX-2 and iNOS of its butanol fraction are warranted for further elucidation of active principles for development of new antiinflammatory agents.     

Berberine hydrochloride attenuates cyclooxygenase-2 expression in rat small intestinal mucosa during acute endotoxemia

The effect of berberine hydrochloride (BBR) on inducible cyclooxygenase-2 (COX-2) in small intestinal mucosa and related mechanisms was investigated in a rat model of acute endotoxemia. The results showed that lipopolysaccharide (LPS) increased COX-2 expression, whereas SB202190 and BBR curtailed it. LPS increased phosphorylation of mucosal p38 MAPK and ATF2 as well as production of ATF2, whereas BBR attenuated these effects. LPS upregulated mucosal peroxisome proliferator-activated receptor gamma (PPARγ), but BBR reduced this receptor. GW9662 aggravated LPS-induced and reversed BBR-attenuated COX-2 expression. The findings showed that BBR ameliorated COX-2 overexpression partially via modulation of p38 and PPARγ pathways during acute endotoxemia.     

Anti-inflammatory activity of sulfate-containing phenolic compounds isolated from the leaves of Myrica rubra

Three sulfated phenolic compounds, juglanin B (11R)-O-sulfate (1), myricetin 3´-O-sulfate (2), and ampelopsin 3´-O-sulfate (3), were isolated from the leaves of Myrica rubra. Compound 1 was a new sulfated lignan, 2 was a new sulfated flavone, and 3 was a known sulfated flavone. The structures of the new compounds (1 and 2) were determined by acid hydrolysis and spectroscopic methods, including IR, FAB-MS, 1D and 2D NMR. The inhibitory activities of compounds 1–3 and their hydrolysates (1a–3a) against LPS-induced cytokine (TNF-α, IL-1β, and IL-6) production in macrophage RAW 264.7 cells were evaluated. The 2 new compounds (1 and 2) and their aglycones (1a and 2a) significantly reduced LPS-induced expression of iNOS and COX-2 proteins.     

Immunomodulatory effects of the methanolic extract of Epimedium alpinum in vitro

The effect of the methanolic extract of root and rhizome of Epimedium alpinum (MEEA) on phenotype and functions of rat lymphocytes in vitro was studied. It has been found that MEEA at lower concentrations (0.1 microg/ml and 1 microg/ml) significantly enhanced proliferation of splenocytes and thymocytes triggered by concanavalin A (Con A), whereas higher concentrations of the extract (50 microg/ml-500 microg/ml) were inhibitory. The stimulatory effect of MEEA on Con A-induced proliferation of splenocytes correlated with the up-regulation of interleukin-2 receptor alpha (IL-2Ralpha) expression. In addition, increased production of IL-2 was observed when a blocking IL-2Ralpha monoclonal antibody (mAb) was added to cell cultures. MEEA-suppressed proliferation of splenocytes was due to the inhibition of IL-2 production, the down-regulation of IL-2Ralpha expression and the induction of apoptosis. Cellular proliferation in the presence of inhibitory concentrations of MEEA higher than 50 microg/ml could not be restored by the addition of exogenous IL-2.     

Anti-inflammatory, cyclooxygenase inhibitory and antioxidant activities of standardized extracts of Tridax procumbens L.

The standardized EtOAc, MeOH and 70% EtOH extracts of Tridax procumbens aerial parts showed significant inhibition of rat paw edema at a medium dose of 200 mg/kg and the EtOAC extract was the most active. These extracts were standardized by HPLC with the help of chemical markers. Further, the extracts were evaluated for COX-1 and COX-2 inhibitory activity and EtOAc extract exhibited the highest inhibition of COX-1 and COX-2 at 50 μg/mL. Cent aurein, centaureidin and bergenin were isolated as COX-1 and COX-2 inhibitory principles from the EtOAc extract. The extracts also exhibited antioxidant activity against DPPH and ABTS free radicals. The anti-inflammatory activity of T. procumbens aerial parts could be at least in part due to COX-1, COX-2 enzyme inhibition and free radical-scavenging activities which may be attributed to the presence of flavonoids and other polyphenols in the extracts.     

Toll-like receptor-mediated anti-inflammatory action of glaucine and oxoglaucine

Two isochinoline alkaloids, glaucine and oxoglaucine were investigated for their suggested anti-inflammatory influence concerning nitric oxide and cytokine production. Mouse peritoneal macrophages were stimulated with different Toll-like receptor (TLR) ligands such as LPS for TLR4, zymosan for TLR2 and CpG for TLR9. The alkaloids inhibited TNF-α and IL-6 production induced by these ligands. In regard to IL-12 suppressive effect was registered in the case of CpG stimulation. Glaucine succeeded to enhance LPS and zymosan-induced IL-10 production. The reduction of pro-inflammatory cytokines and increase of anti-inflammatory IL-10 are indicative for their use in different acute and chronic inflammatory diseases.     

Biologically active components of a Papua New Guinea analgesic and anti-inflammatory lichen preparation

A traditional preparation of Parmotrema saccatilobum (Taylor) Hale (Family: Parmeliaceae) is being considered for inclusion into the PNG national drug formulary by the Ministry of Health Taskforce on Traditional Medicines. The lichen preparation is traditionally used in the Milne Bay province of Papua New Guinea for analgesic and anti-inflammatory activities. A hexane extract of P. saccatilobum yielded the principle components atranorin and chloroatranorin. Atranorin and chloroatranorin were tested in a COX-1 and -2 enzyme inhibition assay, which showed that atranorin inhibited COX-1 in a dose dependent manner and suggests partial inhibition by atranorin and chloroatranorin of COX-2 and COX-1, respectively.     

Cyclooxygenase-2 inhibitors in ginger (Zingiber officinale)

Ginger roots have been used to treat inflammation and have been reported to inhibit cyclooxygenase (COX). Ultrafiltration liquid chromatography mass spectrometry was used to screen a chloroform partition of a methanol extract of ginger roots for COX-2 ligands, and 10-gingerol, 12-gingerol, 8-shogaol, 10-shogaol, 6-gingerdione, 8-gingerdione, 10-gingerdione, 6-dehydro-10-gingerol, 6-paradol, and 8-paradol bound to the enzyme active site. Purified 10-gingerol, 8-shogaol and 10-shogaol inhibited COX-2 with IC₅₀ values of 32 μM, 17.5 μM and 7.5 μM, respectively. No inhibition of COX-1 was detected. Therefore, 10-gingerol, 8-shogaol and 10-shogaol inhibit COX-2 but not COX-1, which can explain, in part, the anti-inflammatory properties of ginger.     

Anti-inflammatory,cyclooxygenase (COX)-2, COX-1 inhibitory and antioxidant effects of Dysophylla stellata Benth.

The n-hexane and ethyl acetate extracts of whole plants of Dysophylla stellata significantly inhibited edema when applied topically at doses of 0.5 and 1 mg/ear in TPA-induced ear edema assay in mice. Further, both the extracts were evaluated for COX-1 and COX-2 inhibitory activities and showed 85.42 and 57.38%; and 71.79 and 89.27% inhibition at 50 µg/ml, respectively. Chromones (1 and 2) present in these extracts could be responsible for their COX-1 and COX-2 inhibitory and anti-inflammatory activities. The ethyl acetate extract showed antioxidant activity in DPPH and ABTS radical scavenging assay where as n-hexane extract found to be inactive.     

Semisynthesis and pharmacological investigation of lipo-alkaloids prepared from aconitine

Processed aconite drugs are widely used in Eastern medicine as painkillers and antirheumatic agents. It is known that the traditional processing of aconite drugs increases the amount of lipo-alkaloids. In order to obtain information about the pharmacological potential of these compounds, semisynthesis of 9 aconitine-derived lipo-alkaloids was carried out and their COX-1, COX-2 and LTB₄ formation inhibitory activities were investigated. It was found that compounds esterified with unsaturated fatty acids demonstrated significant COX-2 inhibitory effects, while in the COX-1 assay only 14-benzoylaconine-8-O-eicosapentaenoate exerted remarkable activity. The inhibition of LTB₄ formation was pronounced in cases of long chain fatty acid derivatives.     

Effect of Mahonia aquifolium stem bark crude extract and one of its polysaccharide components on production of IL-8.

The crude hydroalcoholic extract of Mahonia aquifolium stem bark and a polysaccharide isolated from the extract were tested for their activity on interleukin-8 (IL-8) production by human monocytic cell line THP-1. The crude extract partly inhibited the IL-8 spontaneous production after 48-h treatment of the cells, while the polysaccharide was found to be a potent inducer of IL-8 production.     

Ocotea quixos Lam. essential oil: In vitro and in vivo investigation on its anti-inflammatory properties

Here we investigated the anti-inflammatory properties of Ocotea quixos essential oil and of its main components, trans-cinnamaldehyde and methyl cinnamate, in in vitro and in vivo models. Ocotea essential oil and trans-cinnamaldehyde but not methyl cinnamate significantly reduced LPS-induced NO release from J774 macrophages at non-toxic concentrations, inhibited LPS-induced COX-2 expression and increased forskolin-induced cAMP production. The essential oil (30–100 mg/kg os) and trans-cinnamaldehyde (10 mg/kg os) in carrageenan-induced rat paw edema showed anti-inflammatory effect without damaging gastric mucosa. In conclusion we provide the first evidence of a significant anti-inflammatory gastro-sparing activity of O.quixos essential oil.     

Leonurine ameliorates LPS-induced acute kidney injury via suppressing ROS-mediated NF-κB signaling pathway

Acute kidney injury (AKI) is an abrupt loss of kidney function. Severe AKI requires renal replacement therapy and has high mortality. Leonurine (LEO), an alkaloid isolated from Leonurus cardiaca, has shown biological effects such as antioxidant, anticoagulant, and anti-apoptosis. We have examined the effect of LEO on lipopolysaccharide (LPS)-induced AKI in mice and further studied the mechanism involved. Blood urea nitrogen (BUN), creatinine and cytokine were estimated in the serum or tissue. Kidney tissue specimens were used for biochemical estimations of lipid peroxides (LPO), reduced glutathione (GSH), and reactive oxygen species (ROS). The effects of LEO on LPS-induced renal tissue damage were detected by hematoxylin and eosin (HE) stain and electron microscopy. The production of cytokines in the tissue and blood was measured by ELISA. Protein phosphorylation and protein subcellular localization were tested by Western blot. LEO is protected against LPS-induced AKI, improved animal survival and maintained the redox balance. The beneficial effects of LEO were accompanied by the down-regulation of TNF-α, IL-1, IL-6, IL-8, KIM-1 expression and by the inhibition of the phosphorylation of IκBα and p65 translocalization. These results suggest that LEO may suppress NF-κB activation and inhibit pro-inflammatory cytokine production via decreasing cellular ROS production. Accumulating studies have demonstrated that LEO reduces kidney injury and protects renal functions from LPS-induced kidney injury.     

Effects of methanolic extract and fractions from Litsea cubeba bark on the production of inflammatory mediators in RAW264.7 cells

Both the methanolic extract and its fractions (0.01 mg/ml) from Litsea cubeba bark were found to inhibit NO and PGE2 production in LPS-activated RAW264.7 macrophages without significant cytotoxicity at less than 0.01 mg/ml concentration. Moreover, L. cubeba bark extract and its fractions significantly decreased the activity of myeloperoxidase catalyzing oxidation of chloride to HOCl and O2- production was reduced by methanol extract (0.05 mg/ml), chloroform fraction (0.025-0.05 mg/ml) and butanol fraction (0.005 mg/ml). These findings suggest that L. cubeba is beneficial for inflammatory conditions and may contain compound(s) with anti-inflammatory properties.     

Protective effect of Codium fragile against UVB-induced pro-inflammatory and oxidative damages in HaCaT cells and BALB/c mice

Acute exposure to ultraviolet (UV) radiation causes pro-inflammatory responses via diverse mechanisms including oxidative stress. Codium fragile is a green alga of Codiales family and has been reported to exhibit anti-edema, anti-allergic, anti-protozoal and anti-mycobacterial activities. In this study, we have investigated a novel anti-inflammatory potential of C. fragile using in vitro cell culture as well as in vivo animal models. In HaCaT cells, buthanol and ethylacetate fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60 mJ/cm²)-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF- α). Moreover, CFB, CFE and CLS effectively suppressed UVB-induced production of pro-inflammatory mediators such as prostaglandin E₂ (PGE₂) and nitric oxide (NO). In another experiment, topical application of CFB, CFE or CLS prior to UVB irradiation (200 mJ/cm²) on BALB/c mice, inhibited the UVB-elevated protein levels of COX-2, iNOS, and TNF-α. Furthermore, CFB, CFE and CLS suppressed oxidative damages caused by UVB irradiation for example lipid peroxidation and/or protein carbonylation, which seemed to be mediated by up-regulation of antioxidant defense enzymes. These results suggest that C. fragile could be an effective therapeutic agent providing protection against UVB-induced inflammatory and oxidative skin damages.     

The inhibitory effect of piperine from Fructus piperis extract on the degranulation of RBL-2H3 cells

Allergy is an abnormal immune response to an allergen. Type I hypersensitivity is an immunoglobulin (Ig) E-mediated allergic disorder. Fructus piperis is derived from the ripe fruit of the pepper, which is widely used as a spice in human diets and is also administered as a medicine in many countries. Piperine has been shown to have anti-oxidant, anti-depressant, anti-tumor, and anti-inflammatory activities. However, the effect of piperine on IgE-mediated allergic responses has not been reported. Here, the rat basophilic leukemia cells by membrane chromatography (RBL-2H3/CMC) coupled to high performance liquid chromatography/mass spectrometry (HPLC/MS) to discover and identify piperine can bind to RBL-2H3 cell membranes. Piperine inhibited the expression of cytokines, and the release of both β-hexosaminidase and histamine, which could be stimulated by antigen in RBL-2H3 mast cells. We found that the levels of intracellular Ca^2 + also decreased. Furthermore, RT-PCR showed that the mRNA expression levels of IL-4, IL-13, and TNF-α were significantly suppressed by piperine. The inhibitory effect of piperine on IgE-mediated degranulation and cytokine production by RBL-2H3 cells may be caused by the inhibition of IgE-mediated signaling pathways, including the phosphorylation of Lyn, p38, Erk, and Ras. In summary, piperine can inhibit antigen-induced allergic reactions that control degranulation.     

Antidiarrhoeal activity of Strychnos potatorum seed extract in rats

The antidiarrhoeal activity of the methanol extract of the dried seeds of Strychnos potatorum (MESP) has been evaluated out in rats using different models (castor oil-induced diarrhoea, effects on gastrointestinal motility and on PGE(2)-induced gastric enteropooling. MESP (100, 200 and 400 mg/kg, p.o.) significantly (P<0.001) inhibited the frequency of defaecation and reduced the wetness of faecal droppings in castor oil-induced diarrhoea, decreased the propulsion of charcoal meal through the gastrointestinal tract, and also reduced the PGE(2)-induced enteropooling.