The Aqueous Stem Bark Extract of Alstonia boonei Exhibits Anticataract Activity in Sprague Dawley Rat.

In Africa, Alstonia boonei is used folklorically for the management of the multitude of conditions including cataract, which accounts for 50% of cases of blindness in the region. The current study set out to probe the traditional use of the aqueous extract of Alstonia boonei stem bark (ABE) as an anticataract remedy using Sprague Dawley rat models. We investigated the probable phytochemical constituents in the extract, in vitro antioxidant potential, and its in vitro aldose reductase inhibition. For the anticataract investigations, diabetic cataract was induced using galactose in 3-week-old Sprague Dawley rats, and age-related cataract was induced by the administration of sodium selenite to 10-day-old rat pups. Cataract scores in both models were determined after treatment with 30, 100, and 300 mgkg-1 doses of ABE and 10 mlkg-1 of distilled water. Lens glutathione, total lens protein, soluble lens proteins (alpha-A) crystallin, and aquaporin 0 levels in the enucleated lens homogenates were determined. Changes in lens to body weight were also determined with histopathological analysis done on the lenses in the selenite-induced cataract model. The presence of alkaloids, tannins, flavonoids, glycosides, and triterpenoids was identified in the extract. The extract inhibited aldose reductase activity with IC50 of 92.30 µgml-1. The 30, 100, and 300 mgkg-1ABE-treated rats recorded significantly (p < 0.05) reduced cataract scores indicating a delay in cataractogenesis in galactose-induced cataract and in selenite-induced cataractogenesis as well. Markers of lens transparency such as AQP0, alpha-A crystallin, and total lens proteins and lens glutathione levels were significantly (p < 0.05) preserved. In conclusion, this study establishes the anticataract potential of the aqueous stem bark extract of Alstonia boonei in Sprague Dawley rat models.

Anticataract Effect of the Aqueous Extract of the Flowers of Aspilia africana in Murine Model of Diabetic and Age-Related Cataracts.

Background: The use of Aspilia africana in traditional medicine for the management of ocular diseases has been reported in India and some indigenous communities of Africa. The aim of this study was to investigate the aqueous extract of the flowers of A. africana (AAE) as an anticataract remedy using murine models of diabetic and senile cataracts. Methods: Preliminary phytochemical screening of the extract, in vitro antioxidant assays, and in vitro aldose reductase inhibitory activity were performed. For anticataract investigations of the extracts, diabetic cataract was induced by galactose administration in 3-week-old Sprague Dawley rats. The evaluation of experimentally induced age-related cataract was performed by administering sodium selenite to 10-day-old rat pups. Results: The phytochemical analysis revealed the presence of alkaloids, tannins, flavonoids, glycosides, and saponins. In vitro aldose reductase inhibitory property of the extract on rat lenses revealed that the AAE inhibited the enzyme activity with IC50 of 12.12 µg/ml. For the anticataract investigations, 30, 100, and 300 mg·kg-1AAE-treated rats recorded significantly low (p ≤ 0.0001) cataract scores compared to the negative control rats, indicating a delay in cataractogenesis from the second week of treatment in the galactose-induced cataractogenesis. Similarly, the treatment with AAE caused a significant reduction (p ≤ 0.0001) in cataract scores compared to the negative control rats in the selenite-induced cataractogenesis. Markers of lens transparency, such as aquaporin 0, alpha-A crystallin, and total lens proteins and lens glutathione levels, were significantly preserved (p ≤ 0.05-0.0001) in each cataract model after AAE treatment. Conclusion: The study established the anticataract potential of the aqueous extract of flowers of A. africana in murine models, hence giving scientific credence to its folkloric use in the management of cataract.

Acetic acid-induced colitis modulating potential of total crude alkaloidal extract of Picralima nitida seeds in rats.

PURPOSE: The total crude alkaloidal extract of Picralima nitida seeds (PNE) is known to possess anti-inflammatory activity among other therapeutic benefits although its benefits in colitis has not been investigated. The current study therefore seeks to investigate the anti-colitis potential of PNE using acetic acid-induced colitis model in rats. METHODS: Sprague Dawley rats were treated with oral 500 mg/kg sulphasalazine or 30, 100, and 300 mg/kg of PNE daily for 8 days with induction of colitis on the fourth day with acetic acid. Rats were killed 24 h after the last treatment and whole blood was obtained from the jugular vein for hematological analysis and biochemical assays. Colons were extirpated for assessment of macroscopic and histological damage to the colon. RESULTS: Treatment with PNE protected against colonic injury induced with acetic acid by decreasing mucosal ulceration, epithelial erosion, inflammatory cell infiltration, and colonic edema. Thus, PNE preserved mucosal architecture and suppressed goblet cells depletion. Moreover, treatment with PNE was associated with improved hematological parameters and reductions in the expression of serum tumor necrosis factor-alpha, interleukin-1ß, and p38 mitogen-activated protein kinase. Also, PNE treatment exerted antioxidant effects by reducing nitric oxide production and increasing glutathione levels. In addition, PNE inhibited colonic lipid peroxidation by decreasing myeloperoxidase activity and malondialdehyde production. CONCLUSION: It can be concluded that PNE attenuates intestinal oxidative and inflammatory damages following intrarectal acetic acid challenge. Thus, demonstrates potential for use in chronic intestinal inflammatory diseases such as ulcerative colitis.

Hydroethanolic Leaf Extract of Cordia vignei Hutch and Dalziel Inhibits Carrageenan-Induced Foot Oedema in Chicks, Prostaglandin E2-Induced Paw Oedema in Mice, and Bradykinin-Induced Paw Oedema in Mice.

Background: Cordia vignei Hutch and Dalziel (Fam. Boraginaceae) is a woody plant found in west tropical Africa. The aim of this research is to find out if the leaf extract of this plant prevents oedema in animal models. Methods: (a) Inflammation was induced in the animals by injecting 100 µl of 2% lambda carrageenan into the subplantar tissue of the right footpads of 7-day-old chicks 1 h before or after oral administration of 30-300 mgkg-1 CVE. Oedema was measured for 5 h using the water displacement method. (b) Oedema was induced in ICR mice by subplantar injection of prostaglandin E2 (PGE2) (50 µl of 1 nM) 30 minutes before or after CVE administration. Oedema was measured for 3 h. (c) Oedema was induced in ICR mice by subplantar injection of bradykinin (BK) (10 nmol/paw) 30 min before or after administration of extract. Results: We found that CVE significantly (P < 0.05) prevented inflammation that was induced by injecting carrageenan into the footpads of the chicks. Also, we observed that CVE prevented inflammation produced by injecting PGE2 into the subplantar tissue of mice. Finally, we also report that CVE prevented inflammation produced by injecting BK into the subplantar tissues of mice. All these effects were observed in both preventive and curative protocols. Conclusion: We conclude that Cordia vignei leaf extract has potential anti-inflammatory activity.

Coadministration of Stigmasterol and Dexamethasone (STIG+DEX) Modulates Steroid-Resistant Asthma.

Airway inflammation in asthma is managed with anti-inflammatory steroids such as dexamethasone (DEX). However, about 20% of asthmatics do not respond to this therapy and are classified as steroid-resistant. Currently, no effective therapy is available for steroid-resistant asthma. This work therefore evaluated the effect of a plant sterol, stigmasterol (STIG), and stigmasterol-dexamethasone combination (STIG+DEX) in LPS-ovalbumin-induced steroid-resistant asthma in Guinea pigs. To do this, the effect of drugs on inflammatory features such as airway hyperreactivity and histopathology of lung tissue was evaluated. Additionally, the possible pathway of drug action was assessed by measuring events such neutrophil levels, oxidative and nitrative stress, and histone deacetylase 2 (HDAC2) and interleukin 17 (IL-17) levels. STIG alone did not affect inflammatory features, although it caused some changes in the molecular events associated with steroid-resistant asthma. However, STIG+DEX caused significant modulation of inflammatory features by protecting against destruction of lung tissue. The modulation of inflammatory features was associated with significant inhibition of neutrophilia and oxidative and nitrative stress, decrease in HDAC2, and increase in IL-17 levels that are usually associated with steroid-resistant asthma. Our findings show that although STIG and DEX individually do not protect against steroid-resistant asthma, their coadministration results in significant modulation of inflammatory features and the associated molecular events that lead to steroid-resistant asthma.

Anti-Arthritic Effect of the Hydroethanolic Root Extract of Psydrax subcordata in Rats.

Background: In Ghana, decoctions of various parts of Psydrax subcordata, Bridson (Rubiaceae) are employed in the management of inflammatory conditions. However, not much scientific data is available to back such folkloric use of the plant. This study, therefore, seeks to investigate the chronic anti-inflammatory activity of hydroethanolic root extract of Psydrax subcordata (PSRE) using the adjuvant-induced arthritis model in rats. Methods: Freund's adjuvant-induced arthritis model was used to assess the ameliorative effects of PSRE in chronic inflammation. The effect of PSRE on tissue and joint integrity in arthritis was also evaluated by histopathology and microscopy. The effect of PSRE on oxidative markers and serum transforming growth factor (TGF) beta 1 was also determined via chemical assays. Results: Oral PSRE (30-300 mg/kg) inhibited both ipsilateral and contralateral paw arthritis when given prophylactically and therapeutically in rats. It reduced paw defect on X-ray with histologically-reduced inflammatory cells and synovial hyperplasia. Finally, PSRE significantly reduced TGF-beta 1 levels and raised antioxidants such as reduced glutathione, catalase, and superoxide dismutase levels in arthritic rats. Conclusion: The findings show that hydroethanolic root extract of Psydrax subcordata possesses anti-inflammatory properties in rodents.

Inflammation Modulating Activity of the Hydroethanol Stem Bark Extract of Bombax costatum in Murine Models.

Bombax costatum (Bombacaceae) is traditionally used as a decoction of the leaves, stem, and root to treat headaches, fever, and oedema that may be associated with inflammatory conditions. Thus, the aim of this study was to evaluate the effect of 70%v/v ethanolic extract of the stem bark of Bombax costatum on acute and chronic inflammation. The effect of Bombax costatum extract (10, 50, 100 mg kg-1, p.o) was studied in prostaglandin E2-induced paw oedema in Sprague-Dawley rats (n = 5). Subsequently, the effect of the extract on clonidine and haloperidol-induced catalepsy was also investigated in ICR mice (n = 5). Finally, the ability of the extract to inhibit chronic inflammation was studied using a rat adjuvant-induced arthritis model. Pre-emptive and therapeutic administration of the extract at all doses significantly suppressed the formation of oedema following prostaglandin E 2 administration. As a measure of indirect antihistaminic effect, treatment with the extract suppressed clonidine-induced catalepsy but not haloperidol-induced catalepsy. Moreover, Bombax costatum extract significantly inhibited joint inflammation and damage following injection of complete Freund's adjuvant. Treatment with the extract also inhibited the onset of polyarthritis; thus, suppressing the systemic spread of joint inflammation from ipsilateral limbs to contralateral limbs. In conclusion, the hydroethanol extract of the stem bark of Bombax costatum inhibits both acute and chronic inflammation.

Xylopic Acid Suppresses Adjuvant-induced Arthritis in Sprague Dawley Rats via Reduction in Serum Levels of IL-6 and TNF-alpha.

BACKGROUND: Xylopic acid (XA) is the principal constituent obtained from the biofractionation of the dried fruits of Xylopia aethiopica. Our initial reports have established the acute anti-inflammatory activity of this kaurene diterpene. OBJECTIVE: Currently, we investigate the chronic anti-inflammatory activity of xylopic acid. METHODS: The adjuvant-induced arthritis model in rats was employed in carrying out the study. RESULTS: It was observed from the study that XA significantly (P < 0.05) suppressed the oedema associated with adjuvant arthritis while preventing associated joint deformation as identified from the radiographs. Histopathological analysis of joints of treated animals revealed signs of bone reformation and re-calcification following XA administration. From the haematological analysis, xylopic acid significantly decreased eosinophil sedimentation rate (ESR) while also decreasing white blood cells (WBC), which were increased after arthritis induction. Serum analysis showed the inhibitory effect of XA on serum expression of IL-6 and TNF-alpha in arthritic rats. CONCLUSION: Our study demonstrates the anti-arthritic activity of orally administered XA while pointing to a possible mechanism of its anti-inflammatory action.

Regulation of Nrf2 and NF-κB activities may contribute to the anti-inflammatory mechanism of xylopic acid.

Xylopic acid (XA) is a kaurene diterpene which naturally exists in African plants such as Xylopia aethiopica. It has been established to exhibit acute and chronic anti-inflammatory activities from our earlier studies. This current work sets out to shed light on the potential molecular target(s) of xylopic acid. Selection of investigated targets (NF-κB, Nrf2 and PTP1B) was based on an unbiased approach, using the SPiDER in silico prediction tool, and a candidate approach, examining well-known anti-inflammatory targets. Reporter gene assays were used to test for altered NF-κB and Nrf2 activities in transfected HEK or CHO cells, respectively, and immunoblot and flow cytometric analyses examined protein expression of the Nrf2/NF-kB target genes HO-1 and VCAM-1 in HUVEC. An effect of XA on PTP1B activity assay was studied using an in vitro enzyme assay with recombinant human enzyme and pNPP as substrate as well as by looking at insulin receptor phosphorylation in HepG2 cells. XA at 30 µM significantly (p < 0.001) inhibited the NF-κB-dependent reporter gene expression and enhanced activation of Nrf2 in a concentration-dependent manner when compared to the control. XA also marginally increased HO-1 protein expression levels while expression of VCAM-1 was reduced to 70% in XA-treated endothelial cells. However, XA did not show any sign of inhibition of PTP1B or a related phosphatase. Our findings suggest that the anti-inflammatory mechanism of XA entails the inhibitory effect on NF-κB and an increased activity of Nrf2, accompanied by increased expression of HO-1 and reduced expression of VCAM-1.

Hydro-ethanol extract of Holarrhena floribunda stem bark exhibits anti-anaphylactic and anti-oedematogenic effects in murine models of acute inflammation.

BACKGROUND: Holarrhena floribunda (G.Don) T.Durand & Schinz stem bark has anecdotal use in Ghanaian folk medicine for the management of inflammatory conditions. This study was conducted to investigate the in vivo anti-inflammatory activity of the bark extract using models of acute inflammation in male Sprague Dawley rats, C57BL/6 mice and ICR mice. METHODS: A 70% hydro-ethanol extract of the stem bark (HFE) was evaluated at doses of 5-500 mg/kg bw. Local anaphylaxis was modelled by the pinnal cutaneous anaphylactic test. Systemic anaphylaxis or sepsis were modeled by compound 48/80 or lipopolysaccharide, respectively. Clonidine-induced catalepsy was used to investigate the effect on histamine signaling. Anti-oedematogenic effect was assessed by induction with carrageenan. Effects on mediators of biphasic acute inflammation were studied using histamine and serotonin (early phase) or prostaglandin E2 (late phase). RESULTS: HFE demonstrated anti-inflammatory and/or anti-oedematogenic activity comparable to standard doses of aspirin and diclofenac (inhibitors of cyclooxygenases-1 and -2), chlorpheniramine (histamine H1-receptor antagonist), dexamethasone (glucocorticoid receptor agonist), granisetron (serotonin receptor antagonist) and sodium cromoglycate (inhibitor of mast cell degranulation). All observed HFE bioactivities increased with dose. CONCLUSIONS: The data provide evidence that the extract of H. floribunda stem bark has anti-anaphylactic and anti-oedematogenic effects; by interfering with signalling or metabolism of histamine, serotonin and prostaglandin E2 which mediate the progression of inflammation. The anti-inflammatory and antihistaminic activities of HFE may be relevant in the context of the management of COVID-19.

Endocannabinoid system and its modulation of brain, gut, joint and skin inflammation.

The discovery of endogenous cannabinoid receptors CB1 and CB2 and their endogenous ligands has generated interest in the endocannabinoid system and has contributed to the understanding of the role of the endocannabinoid system. Its role in the normal physiology of the body and its implication in pathological states such as cardiovascular diseases, neoplasm, depression and pain have been subjects of scientific interest. In this review the authors focus on the endogenous cannabinoids, and the critical role of cannabinoid receptor signaling in neurodegeneration and other inflammatory responses such as gut, joint and skin inflammation. This review also discusses the potential of endocannabinoid pathways as drug targets in the amelioration of some inflammatory conditions. Though the exact role of the endocannabinoid system is not fully understood, the evidence found much clearly points to a great potential in exploiting both its central and peripheral pathways in disease management. Cannabinoid therapy has proven promising in several preclinical and clinical trials.

Solid-lipid nanoparticle formulation improves antiseizure action of cryptolepine.

Following the high treatment gap and massive impact of epilepsy on global health particularly in low- and middle-income countries, our study aims to investigate cryptolepine, the major alkaloid of Cryptolepis sanguinolenta as well as its solid-lipid nanoparticle formulation for potential antiseizure activity. Cryptolepine was isolated and a solid-lipid formulation was prepared. Antiseizure activity of Solid-Lipid Nanoparticle formulation of cryptolepine (SLN-CRYP) was investigated using Pentylenetetrazole (PTZ)-induced model of seizure-like behaviors in Zebrafish with 2.5 and 5 mg/kg each of cryptolepine and SLN-CRYP. Drug receptor binding and permeability of the compound across the Blood Brain Barrier (BBB) were also assessed. SLN formulation of cryptolepine increased its permeability to the BBB from 0.32 × 10-6 cm/s to 10.81 × 10-6 cm/s. 2.5 and 5 mg/kg of SLN-CRYP significantly reduced mean seizure score (P = 0.0018; F(6, 63) = 23.52) and significantly increased (P < 0.0001; F(6, 63) = 65.41) latency to onset of seizures. The total distance swam by fish administered with 2.5 and 5 mg/kg of SLN-CRYP was significantly (P < 0.000; F(6, 63) = 161.9) decreased. 5 mg/kg of cryptolepine also significantly decreased swimming distance. Cryptolepine exhibited inhibitory modulation of human voltage-gated calcium channels (Cav1.2), H1-receptor, Peripheral Benzodiazepine Receptor and Sigma 2 receptor with a high Ki values of 6133.38 nM and 2945.0 nM, indicating less potent antagonism on Cav1.2 and Sigma 2 receptors compared to Nifedipine and Haloperidol respectively. This study reveals that the solid-lipid nanoparticle formulation of cryptolepine improves its BBB permeability and hence antiseizure activity.

Acetic Acid-Induced Ulcerative Colitis in Sprague Dawley Rats Is Suppressed by Hydroethanolic Extract of Cordia vignei Leaves through Reduced Serum Levels of TNF-α and IL-6.

BACKGROUND: Ulcerative colitis (UC) is a recurrent inflammatory bowel disease (IBD) that causes long-lasting inflammation on the innermost lining of the colon and rectum. Leaf decoctions of Cordia vignei have been used in traditional medicine either alone or in combination with other plant preparations to treat the disease. AIM: In this study, we investigated the effect of hydroethanolic extract of Cordia vignei have been used in traditional medicine either alone or in combination with other plant preparations to treat the disease. METHOD: Male Sprague Dawley rats received oral treatment of either saline (10 ml/kg), sulfasalazine (500 mg/kg), or CVE (30-300 mg/kg) daily for 7 days. On day 4, colitis was induced by a single intrarectal administration of 500 µl of acetic acid (4% v/v/. RESULTS: CVE significantly (P < 0.05) prevented colonic ulceration and reduced the inflammatory score. Serum levels of TNF-α and IL-6 were significantly reduced. Depletion of superoxide dismutase (SOD) and catalase (CAT) activities by acetic acid was significantly inhibited while lipid peroxidation indexed as malondialdehyde (MDA) level in the colon was reduced. However, loss of body weight was not significantly affected by treatment with CVE. CONCLUSION: This data suggest that CVE has a potential antiulcerative effect.

Potential effects of xylopic acid on acetic acid-induced ulcerative colitis in rats.

BACKGROUND/AIMS: Xylopic acid (XA) has been reported to exhibit analgesic activity, alleviate neuropathic pain in rodents, and demonstrate anti-inflammatory effects. Intrarectal challenge of rats with acetic acid induces colitis that bears resemblance in terms of its pathogenesis, histopathology, and inflammatory profile to that in humans. Reactive oxygen species are implicated as the main driving force in this inflammatory bowel disease. This study aimed to investigate the anti-colitic potential of XA. MATERIALS AND METHODS: We investigated the effect of XA on body weight, disease activity, inflammatory cell infiltration, and generation of reactive oxygen species. Rats were treated with XA or sulphasalazine, challenged intrarectally with acetic acid with macroscopic and microscopic findings made after eight days. RESULTS: Administration of XA to rats with colitis resulted in an increase in body weight with significant (p<0.05) improvement of the disease profile macroscopically. We observed decreased gross mucosal injury, reduced inflammation, and cellular proliferation with XA administration. Treatment with XA also resulted in decreased colonic epithelial expression of argyrophylic nucleolar organizer regions (AgNORs) with significant decrease (p<0.0001) in the quantitative expression of AgNORs/nucleus ratio to levels comparable with non-colitic control. We also observed reduced proliferation of mucosal mast cell in the colonic segment of the rats treated with XA. Treatment with XA also significantly (p<0.0001) increased the activity of SOD, CAT, and APx while it decreased the activity of MPO and MDA levels. CONCLUSION: Xylopic acid possesses anti-colitic activity in rats induced with acetic acid colitis.

Allergic Airway-Induced Hypersensitivity Is Attenuated by Bergapten in Murine Models of Inflammation.

Bergapten (5-methoxypsoralen, 5-MOP) is a plant-derived furocoumarin with demonstrated anti-inflammatory action. The present study investigated its effects on allergic inflammation in two related pathways of mast cell degranulation. Compound 48/80 and lipopolysaccharide (LPS) were used to activate the IgE-independent pathway while bovine serum albumin (BSA) was used as allergen for the IgE-dependent pathway. The modulatory effect of bergapten on mast cell degranulation, neutrophil extravasation, protein concentration, lung histopathology, and oxidative stress was assessed. Bergapten at 10, 30, and 100 µg/ml for 15 min stabilized mast cells in rat mesenteric tissue from disruption in vitro and when administered in vivo at 3, 10, and 30 mg kg-1 for 1 h protected mice from fatal anaphylaxis induced by compound 48/80. Similarly, treatment of LPS-challenged mice with bergapten (3, 10, and 30 mg kg-1) for 24 h significantly decreased neutrophil infiltration into bronchoalveolar lavage fluid, mean protein concentration, and inflammatory cell infiltration of pulmonary tissues when compared to the saline-treated LPS-challenged control. In addition, lung histology of the bergapten-treated LPS-challenged mice showed significantly less oedema, congestion, and alveolar septa thickening when compared to the saline-treated LPS-challenged disease control. LPS-induced oxidative stress was significantly reduced through increased tissue activities of catalase and superoxide dismutase and reduced malondialdehyde levels on treatment with bergapten. In the triple antigen-induced active anaphylaxis, daily administration of bergapten at 3, 10, and 30 mg kg-1 for 10 days, respectively, protected previously sensitized and challenged mice against anaphylactic shock. Overall, our study demonstrates the ability of bergapten to attenuate allergic airway-induced hypersensitivity in murine models of inflammation, suggesting its possible therapeutic benefit in this condition.

Antipleuritic and Vascular Permeability Inhibition of the Ethyl Acetate-Petroleum Ether Stem Bark Extract of Maerua angolensis DC (Capparaceae) in Murine.

Maerua angolensis has been used traditionally in the management of pain, arthritis, and rheumatism in Ghana and Nigeria but no scientific evidence is currently available to give credence to its folkloric use. The aim of this study was therefore to evaluate the anti-inflammatory effects of a stem bark extract of Maerua angolensis DC (MAE) in acute inflammatory models. The effects of MAE (30-300 mg kg-1) on neutrophil infiltration, exudate volume, and endogenous antioxidant enzymes in lung tissues and lung morphology were evaluated with the carrageenan induced pleurisy model in Sprague Dawley rats. The effects of MAE (30-300 mg kg-1) on vascular permeability were also evaluated in the acetic acid induced vascular permeability in ICR mice. MAE significantly reduced neutrophil infiltration, exudate volume, and lung tissue damage in carrageenan induced pleurisy. MAE increased the activities of antioxidant enzymes glutathione, superoxide dismutase, and catalase in lung tissues. The extract was also able to reduce myeloperoxidase activity and lipid peroxidation in lung tissues in carrageenan induced rat pleurisy. Vascular permeability was also attenuated by the extract with marked reduction of Evans blue dye leakage in acetic acid induced permeability assay. The results indicated that Maerua angolensis is effective in ameliorating inflammation induced by carrageenan and acetic acid. It also has the potential of increasing the activity of endogenous antioxidant enzymes.

Stigmasterol Alleviates Cutaneous Allergic Responses in Rodents.

The therapeutic potential of stigmasterol, a natural steroid alcohol with established immune-modulatory properties, was assessed on allergic cutaneous responses. We examined its suppressive effect on immunoglobulin E (IgE)-mediated active cutaneous anaphylaxis (ACA), compound 48/80 (C48/80)-induced pruritus, and irritant dermatitis induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Stigmasterol at 10-100 mg/kg significantly inhibited ACA with reduction in reaction area and concentration of the extravasated Evans blue dye. Given at 50 and 100 mg/kg, stigmasterol significantly inhibited C48/80-induced scratching behaviour when compared to saline-treated C48/80-injected control. Skin histopathology of injected sites confirmed that stigmasterol reduced mast cell trafficking and degranulation associated with C48/80-induced pruritus. Stigmasterol controlled inflammatory features such as ear skin oedema and neutrophilia and also reduced serum levels of TNFα induced by topical application of TPA. Epidermal layer thickening and inflammatory cell infiltration of ear skin tissue were significantly reduced by stigmasterol. Taken together, stigmasterol demonstrates significant potential as a molecule of interest in allergic skin disease therapy.

The acute anti-inflammatory action of xylopic acid isolated from Xylopia aethiopica.

Background Our earlier studies had given evidence of the traditional application of Xylopia aethiopica in the management of inflammation. The principal constituent obtained from its bio-fractionation is xylopic acid. It is a crystalline diterpene that belongs to the class of kauranes. This work sets out to investigate the anti-inflammatory potential of the xylopic acid isolated from the dried fruit of X. aethiopica. Methods A preliminary anti-inflammatory study, using the protein denaturation model, and in vivo anti-inflammatory assay were employed in the investigation of acute inflammation. The modulation of the effect of the pro-inflammatory markers histamine, serotonin, bradykinin, and prostaglandin E2 by xylopic acid was investigated by in vivo mice paw oedema models. Results Xylopic acid showed a concentration-dependent inhibition of albumen denaturation with an IC50 of 15.55 µg mL-1. Xylopic acid (10, 30, 100 mg kg-1) inhibited the maximal oedema and the average paw thickness (oedema) over the period of each study considerably for all phlogistic agents employed (i.e. carrageenan, histamine, serotonin, bradykinin, and prostaglandin E2) in the inflammation induction for both prophylactic and therapeutic protocols. Conclusion This study establishes that xylopic acid has anti-inflammatory action in acute inflammation.

Stigmasterol inhibits lipopolysaccharide-induced innate immune responses in murine models.

Stigmasterol is a naturally occurring steroid alcohol which occurs in vegetables, soya and a large variety of medicinal plants. Stigmasterol and other phytosterols have been documented as immunomodulators with huge therapeutic potential. We assessed the mitigating effect of stigmasterol on non-fatal and fatal innate immune responses in murine models after intraperitoneal challenge with an endotoxin, lipopolysaccharide, LPS. The effect of stigmasterol on LPS-induced febrile response, inflammatory cell proliferation, multiple organ damage and mortality were respectively investigated. Pretreatment with stigmasterol 10, 50 and 100mg/kg reduced total LPS-induced fever response by 39.93±10.52%, 53.05±5.84% and 77.27±6.25% respectively. Neutrophil proliferation both in blood and recovered peritoneal fluid was significantly reversed by stigmasterol at 50 and 100mg/kg. Lung and liver histopathology showed stigmasterol effectively controlled organ damage. The lung inflammation score of 9.20±0.73 for the polyethylene glycol, PEG-treated disease control mice was reduced respectively to 6.50±0.54, 4.60±0.40 and 4.10±0.42 with 10, 50 and 100mg/kg of stigmasterol. Serum levels of liver enzyme markers, alanine transaminase, ALT and aspartate transaminase, AST were consistent with the observed histological changes. Stigmasterol at 50 and 100mg/kg significantly protected mice from LPS-induced mortality with 40% survival. Overall, stigmasterol inhibits LPS-induced innate immune responses in murine models.

The Ethanolic Stem-Bark Extract of Antrocaryon micraster Inhibits Carrageenan-Induced Pleurisy and Pedal Oedema in Murine Models of Inflammation.

We investigated the antioxidant and anti-inflammatory effects of a 70% v/v ethanol extract of the stem bark of Antrocaryon micraster on murine models of carrageenan-induced pleurisy and paw oedema. Rat pleural fluid was analysed for volume, protein content, and leucocytes, while lung histology was assessed for damage. Lung tissue homogenates were assayed for glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and myeloperoxidase (MPO). Phytochemical analysis was carried out on the stem bark. Acute toxicity studies were conducted in rats. In the pleurisy model the extract (30-300 mg/kg) significantly reduced the volume and amount of proteins and leucocytes in the exudate and also protected against lung injury. Tissue level of GSH and SOD and CAT expression were increased while MDA level and MPO activity were reduced. The peak and total oedema responses were significantly suppressed when given both preemptively and curatively in the mice paw oedema test. Saponins, alkaloids, triterpenoids, and tannins were present in the stem bark. A. micraster extract exhibited no apparent acute toxicity. We conclude that the ethanolic stem-bark extract of A. micraster has antioxidant action and exhibits significant anti-inflammatory activity through suppression of pleurisy and paw oedema induced with carrageenan.