Inhibition Of Granuloma Formation Research Articles

Therapeutic Doses of Efzofitimod Demonstrate Efficacy in Pulmonary Sarcoidosis

BackgroundIn a phase 1b/2a clinical trial of efzofitimod in patients with corticosteroid-requiring pulmonary sarcoidosis, treatment resulted in dose-dependent improvement in key endpoints. We undertook a post hoc analysis pooling dose arms that achieved therapeutic concentrations of efzofitimod (Therapeutic group)versusthose that did not (Subtherapeutic group).MethodsPeripheral blood mononuclear cells incubated with tuberculin-coated beads were exposed to varying concentrations of efzofitimod in anin vitroassay to determine concentrations that inhibited granuloma formation. In the post hoc analysis, we compared time-to-first-relapse and changes in pulmonary function after a protocolised corticosteroid taper in the Therapeutic and Subtherapeutic groups.ResultsEfzofitimod at ≥300 nM (19 µg·mL−1) inhibited granuloma formationin vitro. Based on average efzofitimod serum concentrations achieved in the phase 1b/2a study, the 3 and 5 mg·kg−1dose arms were pooled as the Therapeutic group, while the 1 mg·kg−1arm was pooled with the placebo arm as the Subtherapeutic group. Relapse rates were 54.4% and 7.7% in the Subtherapeutic group and Therapeutic group, respectively. Median time-to-first-relapse in the Subtherapeutic group was 126 days, whereas in the Therapeutic group, only one of 17 patients relapsed by the end of the 24-week study (p=0.017). Slopes analysis showed that forced vital capacity increased in the Therapeutic group, but decreased in the Subtherapeutic group, over the course of the trial (p=0.035).ConclusionTreatment with efzofitimod at therapeutic doses, as compared with a subtherapeutic dose or placebo, was associated with a lower rate of relapse as corticosteroids were tapered.

Leveraging in vitro and pharmacokinetic models to support bench to bedside investigation of XTMAB-16 as a novel pulmonary sarcoidosis treatment.

Background: Sarcoidosis is a chronic, multisystem inflammatory disorder characterized by non-caseating epithelioid granulomas; infiltration of mononuclear cells; and destruction of microarchitecture in the skin, eye, heart, and central nervous system, and the lung in >90% of cases. XTMAB-16 is a chimeric anti-tumor necrosis factor alpha (TNFα) antibody, distinct from other anti-TNF antibodies based on its molecular structure. The efficacy of XTMAB-16 has not been clinically demonstrated, and it is still undergoing clinical development as a potential treatment for sarcoidosis. The current study demonstrates the activity of XTMAB-16 in a well-established in vitro sarcoidosis granuloma model, although XTMAB-16 is not yet approved by the United States Food and Drug Administration (FDA) for treatment of sarcoidosis, or any other disease. Objective: To provide data to guide safe and efficacious dose selection for the ongoing clinical development of XTMAB-16 as a potential treatment for sarcoidosis. Methods: First, XTMAB-16 activity was evaluated in an established in vitro model of granuloma formation using peripheral blood mononuclear cells from patients with active pulmonary sarcoidosis to determine a potentially efficacious dose range. Second, data obtained from the first-in-human study of XTMAB-16 (NCT04971395) were used to develop a population pharmacokinetic (PPK) model to characterize the pharmacokinetics (PK) of XTMAB-16. Model simulations were performed to evaluate the sources of PK variability and to predict interstitial lung exposure based on concentrations in the in vitro granuloma model. Results: XTMAB-16 dose levels of 2 and 4mg/kg, once every 2weeks (Q2W) or once every 4 weeks (Q4W) for up to 12weeks, were supported by data from the non-clinical, in vitro secondary pharmacology; the Phase 1 clinical study; and the PPK model developed to guide dose level and frequency assumptions. XTMAB-16 inhibited granuloma formation and suppressed interleukin-1β (IL-1β) secretion in the in vitro granuloma model with a half maximal inhibitory concentration (IC50) of 5.2 and 3.5μg/mL, respectively. Interstitial lung concentrations on average, following 2 or 4mg/kg administered Q2W or Q4W, are anticipated to exceed the in vitro IC50 concentrations. Conclusion: The data presented in this report provide a rationale for dose selection and support the continued clinical development of XTMAB-16 for patients with pulmonary sarcoidosis.

IMMUNE RESPONSE UPON THE ADMINISTRATION OF RECOMBINANT PROTEIN ANTIBODIES Ag-38 KDa Mycobacterium tuberculosis AND RIFAMPICIN EX-VIVO.

Background:Development a granuloma model resembling latent tuberculosis in vitro is needed with a fast and efficient time to be used as an effective therapy. This study aimed to form efficient granulomas, increase cellular immunity and humoral immunity, and evaluate growth on media using recombinant protein antibody Ag38kDa, Rifampicin, and a combination of both. Peripheral Blood Mononuclear Cell (PBMC) in vitro is derived from a healthy individual separated from monocytes and lymphocytes.Materials and methods:Monocytes are matured into macrophages and then combined macrophages and lymphocytes to the Roswell Park Memorial Institute (RPMI) medium. Flow cytometry analysis was used to count the number of cells, and cytokine levels were measured using ELISA. The result from the treatment was planted on the Lowenstein-Jensen medium.Results:Granulomas-like aggregates was formed after one-day post-infection with Mycobacterium tuberculosis (M.tb). A significant increase in immune response occurred in the number of macrophages, Th1, and Tregs in the combination group compared to the Mtb infection group. The number of Th2 and Th17 cells in the combination group was compared with the control but not significantly. TNF-α cytokine levels increased in the combination group compared to Mtb infection, while in IL-4, we found between all groups, there was no significant difference. Bacterial colonies on culture in the Lowenstein-Jensen medium were only seen in positive controls.Conclusion:Our study concluded that administration of a combination between Ag38kDa recombinant antibody and rifampicin could inhibit granuloma formation and enhance immune response.

Ficus vogelii methanol leaf extract ameliorates inflammation and arthritis by modulating osmotic fragility in C57BL/6J mice

The study evaluated the membrane-stabilizing potentials in red blood cells and anti-inflammatory properties in C57BL/6J mice of the methanol leaf extract of Ficus vogelii. Animals were treated orally with different doses of the extract (50, 100, 200 mg/kg) for 30 days and their blood was measured for membrane stability at different saline concentrations. Diclofenac (12.5 mg/kg) or Indomethacin (10 mg/kg) was used as standard in the anti-inflammatory studies. The mean corpuscular fragility (MCF) values and their corresponding percentage stabilization increased significantly (p≤0.05) in the treatment groups compared to the negative control. Treatment of mice with 50, 100 and 200 mg/kg of the extract significantly (p≤0.05) inhibited carrageenan-induced paw oedema in mice. The highest dose (200 mg/kg) showed lower anti-inflammatory activity compared to Diclofenac (12.5 mg/kg). Daily administration of the extract significantly (p≤0.05) suppressed adjuvant-induced paw arthritis by day 15 and 30 post arthritis induction. Ficus vogelii extract inhibited granuloma formation significantly. The anti-inflammatory effects of methanol leaf extract of Ficus vogelii on granuloma formation were comparable to that of Indomethacin (10 mg/kg). In summary, this study showed that the methanol leaf extract of Ficus vogelii possessed membrane-stabilizing potentials and anti-inflammatory properties, therefore, providing further proof that the leaves contain an active compound with potent anti-inflammatory activity

Ficus vogelii methanol leaf extract ameliorates inflammation and arthritis by modulating osmotic fragility in C57BL/6J mice.

The study evaluated the membrane-stabilizing potentials in red blood cells and anti-inflammatory properties in C57BL/6J mice of the methanol leaf extract of Ficus vogelii. Animals were treated orally with different doses of the extract (50, 100, 200 mg/kg) for 30 days and their blood was measured for membrane stability at different saline concentrations. Diclofenac (12.5 mg/kg) or Indomethacin (10 mg/kg) was used as standard in the anti-inflammatory studies. The mean corpuscular fragility (MCF) values and their corresponding percentage stabilization increased significantly (p≤0.05) in the treatment groups compared to the negative control. Treatment of mice with 50, 100 and 200 mg/kg of the extract significantly (p≤0.05) inhibited carrageenan-induced paw oedema in mice. The highest dose (200 mg/kg) showed lower anti-inflammatory activity compared to Diclofenac (12.5 mg/kg). Daily administration of the extract significantly (p≤0.05) suppressed adjuvant-induced paw arthritis by day 15 and 30 post arthritis induction. Ficus vogelii extract inhibited granuloma formation significantly. The anti-inflammatory effects of methanol leaf extract of Ficus vogelii on granuloma formation were comparable to that of Indomethacin (10 mg/kg). In summary, this study showed that the methanol leaf extract of Ficus vogelii possessed membrane-stabilizing potentials and anti-inflammatory properties, therefore, providing further proof that the leaves contain an active compound with potent anti-inflammatory activity.

Methanolic extract of Ephedra ciliata promotes wound healing and arrests inflammatory cascade in vivo through downregulation of TNF-α.

Chronic wounds may lead to the development of various pathological conditions such as diabetic foot ulcers and pressure sores. The current study evaluated wound healing and anti-inflammatory potentials of methanolic extract of Ephedra ciliata using series of in vivo models. Methanolic extract of Ephedra ciliata was prepared by maceration (Ec.Me). Qualitative and quantitative (HPLC) phytochemical and metal analyses were conducted to explore the chemical and metal profiles of Ec.Me. Safety profile (behavioural)and, antimicrobial, antioxidant, wound healing, anti-inflammatory and anti-angiogenic potentials of Ec.Me were evaluated using well-established in vitro and in vivo models. ELISA assay was performed to estimate the effects of Ec.Me treatment on serum levels of TNF-α. HPLC analysis identified quercetin as one of the major compounds in Ec.Me. Safety study data showed that Ec.Me was safe up to the dose of 2000mg/kg. Antimicrobial assay data showed that Ec.Me was active against bacterial (Staphylococcus aureus) as well as fungal (Candida albicans and Aspergillus niger) strains. Ec.Me showed modertate antioxidant potential in in vitro and in vivo models. Data of excision and burn woundhealing models showed that Ec.Me, promoted wound closure in a dose and time-dependent manner. Treatment with 20% Ec.Me cream and heparin showed almost the same effects with no statistical differences (p > 0.05). Ec.Me also showed time-dependent anti-inflammatory activities in both acute and chronic models. In carrageenan model, treatment with 200mg/kg of Ec.Me showed comparable anti-inflammatory effects (p > 0.05) with quercetin and indomethacin throughout the study. In cotton pellet granuloma model treatment with 200mg/kg of Ec.Me and indomethacin inhibited granuloma formation significantly better (p < 0.05) as compared with the rest of the treatment groups. Histopathological examination of skin samples showed marked improvement in architecture with minimal infiltration of inflammatory cells. Data of in vivo angiogenesis assay showed marked improvement in vessels length, density, branching points, total segments and total nets after treatment with Ec.Me, indicating no toxic effects towards vasculature development. Significant (p < 0.05) downregulation of TNF-α was observed in serum samples of animals treated with Ec.Me. Based on data of the current study, it is concluded that quercetin-rich extract of Ephedra ciliata has wound healing and anti-inflammatory potentials via downregulation of TNF-α. Moreover, it is suggested that the antimicrobial activity of Ec.Me prevented microbial invasion, thus promoted natural woundhealing mechanismsas well.

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

Background: Anti-inflammatory effect can be exerted by Carica papaya.&#x0D; Objective: The purpose of the present study was to see the anti-inflammatory effect of ethanolic extract of Carica papaya leaves and indomethacin in carrageenan induced rat paw edema animal model.&#x0D; Methodology: This was an animal study carried out in the Department of Pharmacology at Dhaka Medical College, Dhaka, Bangladesh during the period from July 2014 to June 2015 for a period of one (01) year. The leaves of Carica Papaya collected from Botanical garden, Mirpur, Dhaka, Bangladesh. The animals were divided into four groups. The animals were divided into four groups. In all the animals granuloma were induced by implantation of autoclaved cotton pellet on the 1st day and they treated as follows: Group I were served as control that was received normal saline. Group II were received ethanolic extract of Carica Papaya leaves. Group III were received ethanolic extract of Carica Papaya leaves. Group IV were received indomethacin. On the 15th day animals were anesthetized, implanted pellets were dissected out, dried at hit air oven and the final weights were measured.&#x0D; Result: The experiment was carried out on 48 Long Evan Norwegian rats. Rats were divided in 4 groups of six animals each. The mean increase of weight of cotton pellet was 48.06±1.02, 24.48±0.36, 22.42±0.56 and 18.02±0.43 in group I, II, III and IV respectively. The inhibition of granuloma formation was 49.06%, 53.35% and 62.51% in group II, III and IV respectively.&#x0D; Conclusion: In conclusion the ethanolic extract of Carica Papaya leaves has effects on cotton pellet induced granuloma formation in experimental rat.&#x0D; Journal of Current and Advance Medical Research 2019;6(1):2-5

Oral activity of the antimalarial endoperoxide 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) against Leishmania donovani complex.

Visceral leishmaniasis (VL) is a major problem worldwide and causes significant morbidity and mortality. Existing drugs against VL have limitations, including their invasive means of administration long duration of treatment regimens. There are also concerns regarding increasing treatment relapses as well as the identification of resistant clinical strains with the use of miltefosine, the sole oral drug for VL. There is, therefore, an urgent need for new alternative oral drugs for VL. In the present study, we show the leishmanicidal effect of a novel, oral antimalarial endoperoxide N-251. In our In vitro studies, N-251 selectively and specifically killed Leishmania donovani D10 amastigotes with no accompanying toxicity toward the host cells. In addition, N-251 exhibited comparable activities against promastigotes of L. donovani D10, as well as other L. donovani complex parasites, suggesting a wide spectrum of activity. Furthermore, even after a progressive infection was established in mice, N-251 significantly eliminated amastigotes when administered orally. Finally, N-251 suppressed granuloma formation in mice liver through parasite death. These findings indicate the therapeutic effect of N-251 as an oral drug, hence suggest N-251 to be a promising lead compound for the development of a new oral chemotherapy against VL.

An Expandable Mechanopharmaceutical Device (2): Drug Induced Granulomas Maximize the Cargo Sequestering Capacity of Macrophages in the Liver.

Drug-induced liver injuries (DILI) comprise a significant proportion of adverse drug reactions leading to hospitalizations and death. One frequent DILI is granulomatous inflammation from exposure to harmful metabolites that activate inflammatory pathways of immune cells of the liver, which may act as a barrier to isolate the irritating stimulus and limit tissue damage. Paralleling the accumulation of CFZ precipitates in the liver, granulomatous inflammation was studied to gain insight into its effect on liver structure and function. A structural analog that does not precipitate within macrophages was also studied using micro-analytical approaches. Depleting macrophages was used to inhibit granuloma formation and assess its effect on drug bioaccumulation and toxicity. Granuloma-associated macrophages showed a distinct phenotype, differentiating them from non-granuloma macrophages. Granulomas were induced by insoluble CFZ cargo, but not by the more soluble analog, pointing to precipitation being a factor driving granulomatous inflammation. Granuloma-associated macrophages showed increased activation of lysosomal master-regulator transcription factor EB (TFEB). Inhibiting granuloma formation increased hepatic necrosis and systemic toxicity in CFZ-treated animals. Granuloma-associated macrophages are a specialized cell population equipped to actively sequester and stabilize cytotoxic chemotherapeutic agents. Thus, drug-induced granulomas may function as drug sequestering "organoids" -an induced, specialized sub-compartment- to limit tissue damage.

Anti-inflammatory activity of the essential oil obtained from Ocimum basilicum complexed with β-cyclodextrin (β-CD) in mice

Cyclodextrins (CDs) are cyclic oligosaccharides can enhance the bioavailability of drugs. Ocimum basilicum is an aromatic plant found in Brazil used in culinary. The essential oil of this plant presents anti-edematogenic and anti-inflammatory activities in acute and chronic inflammation. The aim of this study was to investigate the anti-inflammatory effects of the essential oil obtained from O. basilicum complexed with β – cyclodextrin (OBEO/β-CD) in mice. The complexation with β-cyclodextrin (β-CD) was performed by different methods and analyzed by differential scanning calorimetry (DSC), thermogravimetry (TG) and scanning electron microscopy (SEM). The anti-inflammatory activity was evaluated using mice models of paw edema induced by carrageenan, dextran, histamine and arachidonic acid (AA); vascular permeability and peritonitis induced by carrageenan and granuloma induced by cotton block introduction. The DSC, TG and SEM analysis indicated that the OBEO was successfully complexed with β-CD. The oral administration of OEOB/β-CD prevented paw edema formation by decreasing vascular permeability in vivo, inhibited leukocyte recruitment to the peritoneal cavity, and inhibited granuloma formation in mice. Our results indicate that conjugation with β-CD improves the anti-inflammatory effects of OBEO in mice models of acute and chronic inflammation, indicating that this complex can be used in anti-inflammatory drug development.

Approach to Management of Coccidioidomycosis in Patients Receiving Inhibitors of Tumor Necrosis Factor-α

Abstract Inhibitors of tumor necrosis factor-α (TNFIs) have revolutionized the treatment for patients with a variety of inflammatory illnesses, including rheumatoid arthritis, psoriasis and psoriatic arthritis, ankylosing spondylitis, and other inflammatory diseases, and have improved the outcomes and quality of life for such patients. Endemic fungal infections, such as coccidioidomycosis, are observed to occur in persons who are treated with these agents and who live in the Coccidioides-endemic area with similar frequency as persons in the general, healthy public but with an increased likelihood of symptomatic infection and extrapulmonary dissemination. Because the control of coccidioidal infections requires the formation and maintenance of granuloma, it is not unexpected that TNFIs, which inhibit granuloma formation, seem to increase the risk of clinical disease. No guidelines exist to address the prevention and management of disease in patients whose treatment course with TNFIs is complicated by subclinical or clinical coccidioidal infection. Therefore, we reviewed the available medical literature and offer suggestions to the approach and treatment of patients with various forms of coccidioidomycosis before and during therapy with TNFIs.

Ceratonia siliqua pod extract ameliorates Schistosoma mansoni-induced liver fibrosis and oxidative stress.

BackgroundSchistosomiasis is a prevalent parasitic disease found predominantly in tropical and sub-tropical areas of the developing world, with the second highest socioeconomic and public health burden despite strenuous control efforts. In the present study, we aimed to investigate the ameliorative effects of Ceratonia siliqua pod extract (CPE) on liver fibrosis and oxidative stress in mice infected with Schistosoma mansoni.MethodsThe schistosomal hepatopathologic mouse model was established by tail immersion with schistosomal cercaria. The extract was given daily for 10 days beginning 42 days post-infection. Liver samples were obtained from mice sacrificed 9 weeks after infection. Liver histopathological changes were observed with hematoxylin-eosin and Masson trichrome staining.ResultsTypical schistosomal hepatopathologic changes were induced in the untreated mice. However, the oral administration of CPE was effective in reducing worm number and the egg load in the liver. This treatment also decreased granuloma size and collagen deposition by inhibiting tissue inhibitor of metalloproteinases-2 (TIMP-2) expression. Schistosomal infection induced oxidative stress by increasing lipid peroxidation (LPO) and nitrite/nitrate (nitric oxide; NO) production along with concomitant decreases in glutathione (GSH) and various antioxidant enzymes, including superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. However, treatment of mice with CPE at 300 or 600 mg/kg inhibited LPO and NO production, increased GSH content, and restored the activities of the antioxidant enzymes compared with untreated infected mice. Furthermore, treatment with CPE inhibited apoptosis, as indicated by the reduced Bax expression in hepatic tissue.ConclusionThese data indicated that extracts from Ceratonia siliqua pods may play an important role in combating schistosomal hepatopathology and may inhibit granuloma formation and liver fibrosis through down-regulation of TIMP-2 expression.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1389-1) contains supplementary material, which is available to authorized users.

Innate immunity in sarcoidosis pathobiology.

The immunopathogenesis of sarcoidosis is considered to involve contributions from both adaptive and innate immune responses. Although the identification of adaptive responses to candidate pathogenic antigens will elucidate mechanisms that regulate inflammation in sarcoidosis, innate mechanisms likely represent the 'missing link' to the initiation, maintenance, and resolution of noncaseating granulomatous inflammation, the hallmark feature of sarcoidosis. Furthermore, environments that expose patients to candidate pathogenic antigens for sarcoidosis also provide opportunities for engagement with innate ligands. Several studies have identified enhanced responsiveness via pattern recognition receptor pathways, potentiating the local induction of cytokines relevant to granulomatous inflammation, such as through stimulation of nucleotide-binding oligomerization domain-like receptor and Toll-like receptor pathways. These pathways contribute to the inherent properties of granulomas including, in some cases, persistent localization of pathogens and antigen. Serum amyloid A has been identified to be abundant in sarcoidosis tissues, and this promiscuous host protein can serve as an innate ligand to regulate experimental granulomatous inflammation. Nascent evidence supports a potential role for alternatively activated macrophages to direct histopathological outcomes in sarcoidosis. Innate pathways deserve further investigation as potential therapeutic targets for inhibiting granuloma formation in sarcoidosis.

Garlic attenuates histological and histochemical alterations in livers of Schistosoma mansoni infected mice

Interest in screening for new anti-schistosomal agents is growing because of increased concerns about resistance to and safety of praziquantel. We investigated the anti-schistosomal action of prophylactic and therapeutic doses of garlic on the histological and histochemical alterations caused by Schistosoma mansoni infection. Livers of infected mice were characterized by granulomas, periportal inflammation and fibrosis, hepatocyte vacuolation, fatty degeneration and necrosis, and hypertrophy and pigmentation of Kupffer cells. Significant depletion of carbohydrates and increased lipid vacuoles also were observed. All garlic regimens caused suppression of granuloma formation and amelioration of histological and histochemical changes; the continuous treatment protocol produced the best results. Garlic appears to be a safe and economical anti-schistosomal adjuvant for attenuating the pathogenicity of schistosomiasis.

In in vivo evaluation of the anti-inflammatory and analgesic activities of compound Muniziqi granule in experimental animal models.

BackgroundCompound Muniziqi granule (MNZQ), a traditional Uighur medicinal preparation, comprises 13 species of medicinal plants. MNZQ is traditionally used for regulating body immunity, modulating inflammation and pain, detoxification, and inhibiting tumor growth. This study aims to scientifically evaluate the anti-inflammatory and analgesic activities of MNZQ, support its clinical use and further research with scientific evidence.MethodsThe analgesic activity of MNZQ was evaluated using hot plate test and acetic acid-induced abdominal writhing test. Acute inflammation was evaluated using xylene-induced ear edema and carrageenan-induced paw edema models, while chronic inflammation was evaluated using cotton pellet-induced granuloma model.ResultsMNZQ exerted analgesic activities with a significant dose-dependent increase in latency in the hot plate test. The percentage inhibition suggested that MNZQ exhibited analgesic activities in the central nervous system. Meanwhile, MNZQ at 0.8, 2.4, and 7.2 g/kg strongly inhibited the acetic acid-induced writhing response by 25.22 % (p < 0.01), 44.60 % (p < 0.001), and 49.41 % (p < 0.001), respectively. MNZQ also exerted analgesic activities in the peripheral nervous system. Moreover, MNZQ was demonstrated a significant anti-inflammatory effect against xylene-induced edema in a dose-dependent manner. The percentage inhibition was 22.24 % (p < 0.01) at the highest dosage of 7.2 g/kg. MNZQ at 1.62 and 4.86 g/kg significantly reduced carrageenan-induced rat hind paw edema by 82.43 % and 84.32 % (p < 0.001), respectively, 1 h after injecting carrageenan, and the inhibitory effect lasted for 5 h. MNZQ also exerted a significant anti-inflammatory effect against cotton pellet-induced granuloma formation. MNZQ at 1.62 and 4.86 g/kg could inhibit granuloma formation by 17.07 % and 17.60 %, respectively, whereas the percentage inhibition of diclofenac was 33.12 %.ConclusionsThe results obtained suggest that MNZQ possesses potential anti-inflammatory and analgesic activities. This study provides a scientific basis for the use of MNZQ in alleviating pain and treating inflammatory disorders.

Evaluation of the anti-inflammatory activity of the aqueous and ethanolic extracts of the leaves of Albizzia lebbeck in rats

Albizzia lebbeck Benth. (Mimosaceae) is a medicinal tree used to treat several inflammatory ailments in the Indian traditional Ayurvedic system of medicine. The aim of the present study was to evaluate the possible anti-inflammatory activity of the aqueous (AE) and ethanolic (EE) extracts of the leaves of A. lebbeck to support the ethnopharmacological claims. The study was carried out using Wistar rats (100–150 g). The AE and EE were prepared using the Soxhlet extraction process. The anti-inflammatory activity of the AE and EE of the leaves of A. lebbeck were studied using carrageenan-induced paw edema and cotton pellet-induced granuloma models. The AE and EE of the leaves of A. lebbeck at doses of 50, 100, and 200 mg/kg p.o. (oral administration) showed a dose-dependent and significant (p < 0.05) inhibition of carrageenan-induced hind paw edema with maximum percentage inhibition (PI) values of 22.34, 30.85, 39.36 and 22.53, 32.98, 42.55, respectively. The AE and EE at doses of 50, 100, 200 mg/kg p.o. significantly (p < 0.05) inhibited granuloma formation with PI values of 19.07, 27.57, 38.55 and 23.93, 32.23, 42.33, respectively. The AE and EE of the leaves of A. lebbeck showed significant (p < 0.05) anti-inflammatory activity.

MyD88 signaling inhibits protective immunity to the gastrointestinal helminth parasite Heligmosomoides polygyrus.

Helminth parasites remain one of the most common causes of infections worldwide, yet little is still known about the immune signaling pathways that control their expulsion. C57BL/6 mice are chronically susceptible to infection with the gastrointestinal helminth parasite Heligmosomoides polygyrus. In this article, we report that C57BL/6 mice lacking the adapter protein MyD88, which mediates signaling by TLRs and IL-1 family members, showed enhanced immunity to H. polygyrus infection. Alongside increased parasite expulsion, MyD88-deficient mice showed heightened IL-4 and IL-17A production from mesenteric lymph node CD4+ cells. In addition, MyD88−/− mice developed substantial numbers of intestinal granulomas around the site of infection, which were not seen in MyD88-sufficient C57BL/6 mice, nor when signaling through the adapter protein TRIF (TIR domain–containing adapter–inducing IFN-β adapter protein) was also ablated. Mice deficient solely in TLR2, TLR4, TLR5, or TLR9 did not show enhanced parasite expulsion, suggesting that these TLRs signal redundantly to maintain H. polygyrus susceptibility in wild-type mice. To further investigate signaling pathways that are MyD88 dependent, we infected IL-1R1−/− mice with H. polygyrus. This genotype displayed heightened granuloma numbers compared with wild-type mice, but without increased parasite expulsion. Thus, the IL-1R–MyD88 pathway is implicated in inhibiting granuloma formation; however, protective immunity in MyD88-deficient mice appears to be granuloma independent. Like IL-1R1−/− and MyD88−/− mice, animals lacking signaling through the type 1 IFN receptor (i.e., IFNAR1−/−) also developed intestinal granulomas. Hence, IL-1R1, MyD88, and type 1 IFN receptor signaling may provide pathways to impede granuloma formation in vivo, but additional MyD88-mediated signals are associated with inhibition of protective immunity in susceptible C57BL/6 mice.

Design, synthesis and biological evaluation of some novel benzylidene-2-(4-phenylthiazol-2-yl) hydrazines as potential anti-inflammatory agents

A series of substituted benzylidene-2-(4-phenylthiazol-2-yl) hydrazines (2a–q) have been synthesized, characterized and evaluated for their anti-inflammatory activity by carrageenin-induced hind paw edema (acute inflammation) and cotton pellet granuloma (chronic inflammation) methods in rats. In carrageenin-induced hind paw edema method, compounds 2a, 2b, 2c, 2d, 2h, 2k and 2p at a dose of 20 mg kg−1 body weight, p.o. showed excellent inhibitions (51.80–86.74 %) in between 1 and 4 h. Similarly, in cotton pellet granuloma method, compounds 2a, 2b, 2c, 2d, 2h, 2k and 2p at a dose of 20 mg kg−1 body weight, p.o. inhibited the granuloma formation (71.71–90.19 % inhibition) which was comparable to that of standard drug, ibuprofen (90.36 % inhibition of paw volume at 3 h and 94.02 % inhibition of granuloma formation). Structure activity relationship studies showed excellent activity of the compounds containing electron withdrawing group (fluoro, chloro, bromo or nitro) in phenyl ring at C2 and/or C4 position of thiazole ring.

Anti-inflammatory and analgesic effects of Yaotuitong Capsules in experimental rats with chemically induced radicular neuritis

ObjectiveThe aims of this study were to determine the anti-inflammatory and analgesic effects of Yaotuitong (translation: low back and leg pain) capsules, a Chinese herbal preparation, and the histological changes it induces in experimental rats with chemically induced radicular neuritis. MethodsWistar rats were randomly divided into normal, model, Western medicine, and traditional Chinese medicine groups (n=24 per group). We surgically duplicated a chemical radicular neuritis model to simulate lumbar intervertebral disc protrusion. Granuloma formation was measured on postoperative days (PODs) 3, 7, 14, and 21. Prostaglandin E2 and 5-hydroxytryptamine (inflammation mediators) levels in the surrounding tissue and the histology of the nerve root were determined on PODs 7 and 14. ResultsYaotuitong capsules significantly reduced prostaglandin E2 (P<0.01) and 5-hydroxytryptamine (P<0.01) levels in tissue surrounding the nerve root. It also inhibited granuloma formation (P<0.05). ConclusionYaotuitong capsules have anti-inflammatory and analgesic effects that can alleviate the discomfort of lumbar intervertebral disc protrusion.

Evaluation of anti-inflammatory activity of Typha angustifolia pollen grains extracts in experimental animals

Objective:This study was designed to evaluate the anti-inflammatory activity of aqueous and 70% methanolic extracts of pollen grains of Typha angustifolia.Materials and Methods:Female Sprague Dawley rats were used for the study. The acute anti-inflammatory activity of pollen grains of T. angustifolia was studied using the carrageenan as phlogistic agent, whereas its chronic anti-inflammatory effect was investigated by the percentage inhibition of cotton pellet-induced granuloma.Results:Both aqueous and 70% methanolic extracts of pollen grains of T. angustifolia showed significant dose-dependent inhibition of carrageenan-induced paw edema as compared to the control (P<0.001). It was observed that both the extracts at dose of 125 mg/kg inhibited the granuloma formation by 44.30% which is higher than at dose of 500, 250 mg/kg, thus causing a significant (P<0.001) non-dose-related inhibition of granuloma formation.Conclusion:The results of this study indicate that extracts of pollen grains of T. angustifolia are effective in the treatment of both acute and chronic inflammatory conditions and thus support its traditional utilization.