Olumayokun A. Olajide

Effects of the aqueous extract of Bridelia ferruginea stem bark on carrageenan-induced oedema and granuloma tissue formation in rats and mice.

The anti-inflammatory activity of the aqueous extract of the stem bark of Bridelia ferruginea was evaluated using carrageenan-induced paw oedema in rats and mice, and the cotton pellet granuloma method. The extract at doses ranging from 10 to 80 mg/kg p.o. significantly inhibited the carrageenan-induced rat paw oedema, with an ID50 value of 36 mg/kg. However, a low activity was produced in the mouse paw oedema. The extract also suppressed the granulomatous tissue formation of chronic inflammation. B. ferruginea therefore proved to be effective in both the acute and chronic phases of the inflammatory process.

Pharmacological studies on the leaf of Psidium guajava

The methanol extract of the leaves of Psidium guajava was found to inhibit paw oedema induced by carrageenan in rats and pain induced by acetic acid in mice, and exhibited an antipyretic effect. Oral administration of the extract reduced intestinal transit time and prevented castor oil-induced diarrhoea in mice. A CNS depressant activity was exhibited by the extract by potentiating the phenobarbitone sleeping time in mice.

Biological effects of Myristica fragrans (nutmeg) extract

The chloroform extract of nutmeg has been evaluated for antiinflammatory, analgesic and antithrombotic activities in rodents. The extract inhibited the carrageenan‐induced rat paw oedema, produced a reduction in writhings induced by acetic acid in mice and offered protection against thrombosis induced by ADP/adrenaline mixture in mice. Copyright

Antiplasmodial and antipyretic screening of Mangifera indica extract

The stem bark extract of Mangifera indica was evaluated for antiplasmodial activity against Plasmodium yoelii nigeriensis. The extract was also screened for antipyretic activity in mice. The extract exhibited a schizontocidal effect during early infection, and also demonstrated repository activity. A reduction in yeast‐induced hyperpyrexia was also produced by the extract.

Tiliroside, a dietary glycosidic flavonoid, inhibits TRAF-6/NF-κB/p38-mediated neuroinflammation in activated BV2 microglia

BACKGROUND Tiliroside is a dietary glycosidic flavonoid which has shown in vivo anti-inflammatory activity. This study is aimed at evaluating the effect of tiliroside on neuroinflammation in BV2 microglia, and to identify its molecular targets of anti-neuroinflammatory action. METHODS BV2 cells were stimulated with LPS+IFNγ in the presence or absence of tiliroside. TNFα, IL-6, nitrite and PGE2 production was determined with ELISA, Griess assay and enzyme immunoassay, respectively. iNOS, COX-2, phospho-p65, phospho-IκBα, phospho-IKKα, phospho-p38, phospho-MK2, phosopho-MKK3/6 and TRAF-6 were determined by western blot analysis. NF-κB activity was also investigated using a reporter gene assay in HEK293 cells. LPS-induced microglia ROS production was tested using the DCFDA method, while HO-1 and Nrf2 activation was determined with western blot. RESULTS Tiliroside significantly suppressed TNFα, IL-6, nitrite and PGE2 production, as well as iNOS and COX-2 protein expression from LPS+IFNγ-activated BV2 microglia. Further mechanistic studies showed that tiliroside inhibited neuroinflammation by targeting important steps in the NF-κB and p38 signalling in LPS+IFNγ-activated BV2 cells. This compound also inhibited LPS-induced TRAF-6 protein expression in BV2 cells. Antioxidant activity of tiliroside in BV2 cells was demonstrated through attenuation of LPS+IFNγ-induced ROS production and activation of HO-1/Nrf2 antioxidant system. CONCLUSIONS Tiliroside inhibits neuroinflammation in BV2 microglia through a mechanism involving TRAF-6-mediated activation of NF-κB and p38 MAPK signalling pathways. These activities are possibly due, in part, to the antioxidant property of this compound. GENERAL SIGNIFICANCE Tiliroside is a potential novel natural compound for inhibiting neuroinflammation in neurodegenerative disorders.

Anti-inflammatory properties of cryptolepine.

Cryptolepine is the major alkaloid of the West African shrub, Cryptolepis sanguinolenta. Cryptolepine has been shown to inhibit nitric oxide production, and DNA binding of Nuclear Factor‐kappa B following inflammatory stimuli in vitro. In order to validate the anti‐inflammatory property of this compound in vivo, we investigated its effects on a number of animal models of inflammation. Cryptolepine (10–40 mg/kg i.p.) produced significant dose‐dependent inhibition of the carrageenan‐induced rat paw oedema, and carrageenan‐induced pleurisy in rats. These effects were compared with those of the non‐steroidal anti‐inflammatory drug indomethacin (10 mg/kg). At doses of 10–40 mg/kg i.p., cryptolepine inhibited lipopolysaccharide (LPS)‐induced microvascular permeability in mice in a dose‐related fashion. Oral administration of up to 40 mg/kg of the compound for four consecutive days did not induce gastric lesion formation in rats. Analgesic activity was also exhibited by cryptolepine through a dose‐related (10–40 mg/kg i.p.) inhibition of writhing induced by i.p. administration of acetic acid in mice. The results of this study reveal that cryptolepine possesses in vivo anti‐inflammatory activity. Copyright

Anti-inflammatory studies on Adenanthera pavonina seed extract.

A methanol extract of the seeds of Adenanthera pavonina was evaluated for pharmacological effects in animal models. The extract (50–200 mg/kg) produced statistically significant (P < 0.05) inhibition of the carrageenan-induced paw oedema in the rat, as well as the acetic-acid-induced vascular permeability in mice. At doses of 100 and 200 mg/kg, pleurisy induced with carrageenan was also inhibited. The extract (50–200 mg/kg) exhibited a dose-dependent and significant (P < 0.05) analgesic activity in the acetic-induced writhing in mice. In addition, both early and late phases of the formalin-induced paw licking in mice was inhibited by the extract. Acute toxicity studies revealed that the extract produced reduced motor activity. The LD50 value of the extract was found to be 1.36 g/kg. This study demonstrated the anti-inflammatory and analgesic effects of A. pavonina extract.

Inhibition of neuroinflammation in LPS-activated microglia by cryptolepine

Cryptolepine, an indoloquinoline alkaloid in Cryptolepis sanguinolenta, has anti-inflammatory property. In this study, we aimed to evaluate the effects of cryptolepine on lipopolysaccharide (LPS)- induced neuroinflammation in rat microglia and its potential mechanisms. Microglial activation was induced by stimulation with LPS, and the effects of cryptolepine pretreatment on microglial activation and production of proinflammatory mediators, PGE2/COX-2, microsomal prostaglandin E2 synthase and nitric oxide/iNOS were investigated. We further elucidated the role of Nuclear Factor-kappa B (NF-κB) and the mitogen-activated protein kinases in the antiinflammatory actions of cryptolepine in LPS-stimulated microglia. Our results showed that cryptolepine significantly inhibited LPS-induced production of tumour necrosis factor-alpha (TNFα), interleukin-6 (IL-6), interleukin-1beta (IL-1β), nitric oxide, and PGE2. Protein and mRNA levels of COX-2 and iNOS were also attenuated by cryptolepine. Further experiments on intracellular signalling mechanisms show that IκB-independent inhibition of NF-κB nuclear translocation contributes to the anti-neuroinflammatory actions of cryptolepine. Results also show that cryptolepine inhibited LPS-induced p38 and MAPKAPK2 phosphorylation in the microglia. Cell viability experiments revealed that cryptolepine (2.5 and 5 μM) did not produce cytotoxicity in microglia. Taken together, our results suggest that cryptolepine inhibits LPS-induced microglial inflammation by partial targeting of NF-κB signalling and attenuation of p38/MAPKAPK2.

Punicalagin inhibits neuroinflammation in LPS-activated rat primary microglia.

SCOPE In this study, the effects of punicalagin on neuroinflammation in LPS-activated microglia were investigated. METHODS AND RESULTS The ability of punicalagin to reduce the production of TNF-α, IL-6 and prostaglandin E2 was measured in culture medium using enzyme immunoassay. TNF-α and IL-6 gene expression in mouse hippocampal slices was measured with PCR. cyclooxygenase-2 and microsomal prostaglandin E synthase 1 protein and mRNA were evaluated with Western blotting and PCR, respectively. Further experiments to investigate effects of punicalagin on protein expressions of inflammatory targets were also determined with Western blotting. Pretreatment of rat primary microglia with punicalagin (5-40 μM) prior to LPS (10 ng/mL) stimulation produced a significant (p < 0.05) inhibition of TNF-α, IL-6 and prostaglandin E2 production. Punicalagin completely abolished TNF-α and IL-6 gene expression in LPS-stimulated hippocampal slices. Protein and mRNA expressions of cyclooxygenase-2 and microsomal prostaglandin E synthase 1 were also reduced by punicalagin pretreatment. Results show that punicalagin interferes with NF-κB signalling through attenuation of NF-κB-driven luciferase expression, as well as inhibition of IκB phosphorylation and nuclear translocation of p65 subunit in the microglia. CONCLUSION These results suggest that punicalagin inhibits neuroinflammation in LPS-activated microglia through interference with NF-κB signalling, suggesting its potential as a nutritional preventive strategy in neurodegenerative disorders.

Anti-inflammatory properties of Amaranthus Spinosus Leaf Extract

The methanol extract of Amaranthus spinosus L. leaves was evaluated for anti-inflammatory activities in different animal models. The effect of the plant extract was also studied on castor oil–induced diarrhea and gastric mucosal integrity. The extract (25–100 mg/kg) inhibited the carrageenan-induced rat paw edema and produced significant (p < 0.05) inhibition of acetic acid–induced increased vascular permeability. Inhibition of the cotton pellet granuloma was also inhibited by 100 mg/kg of the plant extract. Analgesic activity was exhibited with the significant and dose-related reduction in the number of writhings induced with acetic acid, as well reduction in paw licking induced by injection of formalin in mice. The extract (50 and 100 mg/kg) produced gastric erosion in rats, following repeated administration for 4 days, and with 25–100 mg/kg of the extract, there was a statistically significant (p < 0.05) reduction in castor oil–induced diarrhea in rats. These results demonstrate the anti-inflammatory properties of the leaf extract of A. spinosus. It is also suggested that the plant extract probably acts by the inhibition of prostaglandin biosynthesis.