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Use of prednisolone to aid propagation of Toxoplasma gondii in mice

Puvanesuaran VR, Nowroji K, Sreenivasan S, Noordin R, Balakrishnan V

Eur Rev Med Pharmacol Sci, 2012 Aug;16(8):1028-32.
PMID: 22913152

AIM: To determine the usefulness of prednisolone in increasing the number of Toxoplasma (T.) gondii tachyzoites and bradyzoites in mice.
MATERIALS AND METHODS: The mice were water-fasted prior to being immunosuppressed with oral inoculation of prednisolone. Tachyzoites of 7T gondii RH strain were inoculated into mice and the number of the parasites in the intraperitoneal fluids was then determined at 96 hs post-infection. In addition, tachyzoites of T. gondii ME49 strains were orally introduced into mice and the number of brain cysts formed was observed by microscopic observation at 45 days post-infection.
RESULTS: T. gondii propagation was found to be significantly improved by introduction of the prednisolone (p = 0.0004); and the number of parasite showed positive correlation with the increment in dosage of prednisolone (r = 0.9051).
CONCLUSIONS: The use of prednisolone greatly improved the number of parasite formed in mice: both tachyzoite and cyst forms.

Matched MeSH terms: Immunosuppressive Agents/pharmacology*
Immunosuppressive effects of the standardized extract of Zingiber zerumbet on innate immune responses in Wistar rats

Ghazalee NS, Jantan I, Arshad L, Haque MA

Phytother Res, 2019 Apr;33(4):929-938.
PMID: 30618097 DOI: 10.1002/ptr.6285

Zingiber zerumbet rhizome has been used in traditional medicine mainly for the treatment of various immune-inflammatory related ailments and has been shown to exhibit a wide spectrum of biological effects especially antioxidant and anti-inflammatory activities. The present study was aimed to investigate the immunosuppressive effects of the standardized 80% ethanol extract of Z. zerumbet at 100, 200, and 400 mg/kg on the innate immune responses in male Wistar rats. The immune parameters determined were chemotaxis of neutrophils, Mac-1 expression, engulfment of Escherichia coli by neutrophils, reactive oxygen species production, and plasma lysozyme and ceruloplasmin levels. Zerumbone was qualitatively and quantitatively determined in the extract by using a validated reversed-phase HPLC, whereas liquid chromatography tandem-mass spectrometry (LC -MS/MS) was used to profile the secondary metabolites. Z. zerumbet significantly inhibited the migration of neutrophils, expressions of CD11b/CD18 integrin, phagocytic activity, and production of reactive oxygen species in a dose-dependent manner. The extract also dose-dependently inhibited the expressions of lysozyme and ceruloplasmin in the rat plasma. Z. zerumbet extract possessed strong inhibitory effects on the innate immune responses and has potential to be developed into an effective immunosuppressive agent.

Matched MeSH terms: Immunosuppressive Agents/pharmacology*
Fulltext Standardized ethanol extract, essential oil and zerumbone of Zingiber zerumbet rhizome suppress phagocytic activity of human neutrophils

Akhtar NMY, Jantan I, Arshad L, Haque MA

BMC Complement Altern Med, 2019 Nov 21;19(1):331.
PMID: 31752812 DOI: 10.1186/s12906-019-2748-5

BACKGROUND: Zingiber zerumbet rhizome and its bioactive metabolites have previously been reported to exhibit innumerable pharmacological properties particularly anti-inflammatory activities. In the present study, the 80% ethanol extract, essential oil and zerumbone of Z. zerumbet rhizomes were explored for their in vitro immunosuppressive properties on chemotaxis, CD11b/CD18 expression, phagocytosis and chemiluminescence of isolated human polymorphonuclear neutrophils (PMNs).
METHODS: The extract was analyzed quantitatively by performing a validated reversed phase high performance liquid chromatography (RP-HPLC). Zerumbone was isolated by chromatographic technique while the essential oil was acquired through hydro-distillation of the rhizomes and further analyzed by gas chromatography (GC) and GC-MS. Chemotaxis assay was assessed by using a 24-well cell migration assay kit, while CD18 integrin expression and phagocytic engulfment were measured using flow cytometry. The reactive oxygen species (ROS) production was evaluated by applying lucigenin- and luminol-enhanced chemiluminescence assays.
RESULTS: Zerumbone was found to be the most abundant compound in the extract (242.73 mg/g) and the oil (58.44%). Among the samples tested, the oil revealed the highest inhibition on cell migration with an IC50 value of 3.24 μg/mL. The extract, oil and zerumbone showed moderate inhibition of CD18 integrin expression in a dose-dependent trend. Z. zerumbet extract showed the highest inhibitory effect on phagocytic engulfment with percentage of phagocytizing cells of 55.43% for PMN. Zerumbone exhibited strong inhibitory activity on oxidative burst of zymosan- and PMA-stimulated neutrophils. Zerumbone remarkably inhibited extracellular ROS production in PMNs with an IC50 value of 17.36 μM which was comparable to that of aspirin.
CONCLUSION: The strong inhibition on the phagocytosis of neutrophils by Z. zerumbet extract and its essential oil might be due the presence of its chemical components particularly zerumbone which was capable of impeding phagocytosis at different stages.

Matched MeSH terms: Immunosuppressive Agents/pharmacology*
Fulltext Caprine pancreatic islet xenotransplantation into diabetic immunosuppressed BALB/c mice

Hani H, Allaudin ZN, Mohd-Lila MA, Ibrahim TA, Othman AM

Xenotransplantation, 2014 Mar-Apr;21(2):174-82.
PMID: 24645790 DOI: 10.1111/xen.12087

BACKGROUND: Type 1 diabetes mellitus is a devastating disease for which there is currently no cure, but only lifetime management. Islet xenotransplantation is a promising technique for the restoration of blood glucose control in patients with diabetes mellitus. The purpose of this study was to explore the potential use of caprine (goat) islet cells as xenogeneic grafts in the treatment for diabetes in a mouse model.
METHODS: Caprine pancreases were harvested and transported to the laboratory under conditions optimized to prevent ischemia. Islets were isolated, purified, and tested for functionality. Caprine islets (2000 islet equivalent) were transplanted beneath the kidney capsules of diabetic BALB/c mice under thalidomide-induced immunosuppression. Blood glucose and insulin levels of grafted mice were evaluated by glucometer and enzyme-linked immunosorbent assay kit, respectively. The functionality and quality of caprine pancreatic islet grafts were assessed by intraperitoneal glucose tolerance tests.
RESULTS: The viability of purified islet cells exceeded 90%. Recipient mice exhibited normoglycemia (<11 mM glucose) for 30 days. In addition, weight gain negatively correlated with blood glucose level. The findings verified diabetes reversal in caprine islet recipient mice. A significant drop in non-fasting blood glucose level (from 23.3 ± 5.4 to 8.04 ± 0.44 mM) and simultaneous increase in serum insulin level (from 0.01 ± 0.001 to 0.56 ± 0.17 μg/l) and body weights (from 23.64 ± 0.31 to 25.85 ± 0.34 g) were observed (P < 0.05). Immunohistochemical analysis verified insulin production in the transplanted islets.
CONCLUSIONS: Purified caprine islets were demonstrated to successfully sustain viability and functionality for controlling blood glucose levels in an immunosuppressed mouse model of diabetes. These results suggest the use of caprine islets as an addition to the supply of xenogeneic islets for diabetes research.
KEYWORDS: caprine islets; streptozotocin‐injected mice; type 1 diabetes; xenotransplantation

Matched MeSH terms: Immunosuppressive Agents/pharmacology*
Synthesis and evaluation of chalcone derivatives as inhibitors of neutrophils' chemotaxis, phagocytosis and production of reactive oxygen species

Bukhari SN, Tajuddin Y, Benedict VJ, Lam KW, Jantan I, Jalil J, et al.

Chem Biol Drug Des, 2014 Feb;83(2):198-206.
PMID: 24433224 DOI: 10.1111/cbdd.12226

Inhibitory effects on neutrophils' chemotaxis, phagocytosis and production of reactive oxygen species (ROS) are among the important targets in developing anti-inflammatory agents and immunosuppressants. Eight series of chalcone derivatives including five newly synthesized series were assessed for their inhibitory effects on chemotaxis, phagocytosis and ROS production in human polymorphonuclear neutrophils (PMNs). Inhibition of PMNs' chemotaxis and phagocytosis abilities were investigated using the Boyden chamber technique and the Phagotest kit, respectively, while ROS production was evaluated using luminol- and lucigenin-based chemiluminescence assay. The new derivatives (4d and 8d), which contain 4-methylaminoethanol functional group were active in all the assays performed. It was also observed that some of the compounds were active in inhibiting chemotaxis while others suppressed phagocytosis and ROS production. The information obtained gave new insight into chalcone derivatives with the potential to be developed as immunomodulators.

Matched MeSH terms: Immunosuppressive Agents/pharmacology
Hybrid ABSORB bioresorbable vascular scaffold and drug eluting stent or hybrid BVS-DES percutaneous coronary intervention: Method and rationale for hybrid overlapping PCI

Yew KL

Int J Cardiol, 2015;186:74-6.
PMID: 25814348 DOI: 10.1016/j.ijcard.2015.02.092
Matched MeSH terms: Immunosuppressive Agents/pharmacology
Hepatoprotective and Immunosuppressive Effect of Synedrella nodiflora L. on Carbon Tetrachloride (CCl4)-Intoxicated Rats

Gnanaraj C, Shah MD, Haque AT, Makki JS, Iqbal M

J Environ Pathol Toxicol Oncol, 2016;35(1):29-42.
PMID: 27279582 DOI: 10.1615/JEnvironPatholToxicolOncol.2016013802

Synedrella nodiflora is a medicinal plant that is used by the natives of Sabah, Malaysia to treat rheumatism and several other ailments. This study aims to evaluate the ability of the crude aqueous extract of S. nodiflora leaves to protect against carbon tetrachloride (CCl4)-mediated hepatic injury in rats. S. nodiflora aqueous extract was orally administered to adult Sprague Dawley rats once daily for 14 days (150 and 300 mg/kg body weight [b.w.]) before CCl4 oral treatment (1.0 mL/kg b.w.) on the 13th and 14th days. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), hepatic antioxidant enzymes, and malondialdehyde (MDA) levels were estimated. Immunohistochemistry was performed for oxidative stress markers (4-hydroxynonenal [HNE], 8-hydroxy-deoxyguanosine [8-OHdG]) and proinflammatory markers (tumor necrosis factor-α, interleukin-6, prostaglandin E2). Biochemical, immunohistochemical, histological, and ultrastructural findings were in agreement to support the hepatoprotective effect of S. nodiflora against CCl4-mediated oxidative hepatic damage. Hepatoprotective effects of S. nodiflora might be attributable to the presence of phenolic antioxidants and their free radical scavenging property.

Matched MeSH terms: Immunosuppressive Agents/pharmacology
Fulltext Targeted Therapy for Acute Autoimmune Myocarditis with Nano-Sized Liposomal FK506 in Rats

Okuda K, Fu HY, Matsuzaki T, Araki R, Tsuchida S, Thanikachalam PV, et al.

PLoS One, 2016;11(8):e0160944.
PMID: 27501378 DOI: 10.1371/journal.pone.0160944

Immunosuppressive agents are used for the treatment of immune-mediated myocarditis; however, the need to develop a more effective therapeutic approach remains. Nano-sized liposomes may accumulate in and selectively deliver drugs to an inflammatory lesion with enhanced vascular permeability. The aims of this study were to investigate the distribution of liposomal FK506, an immunosuppressive drug encapsulated within liposomes, and the drug's effects on cardiac function in a rat experimental autoimmune myocarditis (EAM) model. We prepared polyethylene glycol-modified liposomal FK506 (mean diameter: 109.5 ± 4.4 nm). We induced EAM by immunization with porcine myosin and assessed the tissue distribution of the nano-sized beads and liposomal FK506 in this model. After liposomal or free FK506 was administered on days 14 and 17 after immunization, the cytokine expression in the rat hearts along with the histological findings and hemodynamic parameters were determined on day 21. Ex vivo fluorescent imaging revealed that intravenously administered fluorescent-labeled nano-sized beads had accumulated in myocarditic but not normal hearts on day 14 after immunization and thereafter. Compared to the administration of free FK506, FK506 levels were increased in both the plasma and hearts of EAM rats when liposomal FK506 was administered. The administration of liposomal FK506 markedly suppressed the expression of cytokines, such as interferon-γ and tumor necrosis factor-α, and reduced inflammation and fibrosis in the myocardium on day 21 compared to free FK506. The administration of liposomal FK506 also markedly ameliorated cardiac dysfunction on day 21 compared to free FK506. Nano-sized liposomes may be a promising drug delivery system for targeting myocarditic hearts with cardioprotective agents.

Matched MeSH terms: Immunosuppressive Agents/pharmacology*
Appraisal of immunomodulatory potential of Spirulina fusiformis: an in vivo and in vitro study

Rasool M, Sabina EP

J Nat Med, 2009 Apr;63(2):169-75.
PMID: 19093070 DOI: 10.1007/s11418-008-0308-2

In recent years, Spirulina has gained more and more attention from medical scientists as a nutraceutical and a source of potential pharmaceuticals. The present study was conducted to elucidate the immunomodulatory effect of Spirulina fusiformis (a cyanobacterium of the family Oscillatoriaceae) in vivo and in vitro. The in vivo effect of S. fusiformis (400 or 800 mg/kg body wt.) on humoral immune response, cell-mediated immune response and tumour necrosis factor alpha was investigated in mice. We also evaluated the effect of S. fusiformis (50 or 100 microg/ml) in vitro on mitogen (phytohaemagglutinin)-induced T lymphocyte proliferation in heparinized human peripheral blood. For comparison, dexamethasone was used as a standard. In mice, S. fusiformis (400 or 800 mg/kg body wt.) administration significantly inhibited the humoral immune response, cell-mediated immune response (delayed-type hypersensitivity reaction (DTH)) and tumour necrosis factor alpha in a dose-dependent manner. In vitro, S. fusiformis (50 or 100 microg/ml) decreased the mitogen (phytohaemagglutinin)-induced T lymphocyte proliferation in a concentration-dependent manner when compared with control cells. These observations clearly suggest that S. fusiformis has a remarkable immunosuppressive effect, which provides a scientific validation for the popular use of this drug, and helped us in further work on investigating its complete mechanism of action.

Matched MeSH terms: Immunosuppressive Agents/pharmacology*
The influence of CYP3A gene polymorphisms on cyclosporine dose requirement in renal allograft recipients

Eng HS, Mohamed Z, Calne R, Lang CC, Mohd MA, Seet WT, et al.

Kidney Int, 2006 May;69(10):1858-64.
PMID: 16612333

Cyclosporine is a substrate of cytochrome P-450 3A (CYP3A) subfamily of enzymes and characterized by a narrow therapeutic range with wide interindividual variation in pharmacokinetics. A few single-nucleotide polymorphisms detected in CYP3A genes have been shown to correlate significantly with the CYP3A protein expression and activity. We therefore postulated that these polymorphisms could be responsible for some of the interindividual variation in cyclosporine pharmacokinetics. The objective of our study is to determine correlation if any between single-nucleotide polymorphisms of CYP3A5 and CYP3AP1 on cyclosporine dose requirement and concentration-to-dose ratio in renal allograft recipients. Cyclosporine-dependent renal allograft recipients were genotyped for CYP3A5 A6986G and CYP3AP1 G-44A. The cyclosporine dosages prescribed and the corresponding cyclosporine trough levels for each patient were recorded so that cyclosporine dose per weight (mg/kg/day) and concentration-to-dose ratio (C(0)/D, whereby C(0) is trough level and D is daily dose per weight) could be calculated. A total of 67 patients were recruited for our study. The dose requirement for 1, 3, and 6 months post-transplantation ranged 2.3-11.4, 1.0-9.0, and 1.4-7.2 mg/kg/day, respectively. Patients with *1*1*1*1 (n=5) CYP3A5- and CYP3AP1-linked genotypes needed higher dose of cyclosporine compared to patients with *1*3*1*3 (n = 27) and *3*3*3*3 (n = 33) linked genotypes in months 3 and 6 post-transplantation (P < 0.016). The identification of patients with *1*1*1*1 by CYP3A5 and CYP3AP1 genotyping may have a clinically significant and positive impact on patient outcome with reduced rejection rate by providing pretransplant pharmacogenetic information for optimization of cyclosporine A dosing.

Matched MeSH terms: Immunosuppressive Agents/pharmacology
Early experience of transradial multivessel percutaneous coronary intervention with new generation STENTYS sirolimus eluting self-apposing stents for ectatic coronary arteries

Yew KL

Int J Cardiol, 2015 Apr 15;185:155-6.
PMID: 25795209 DOI: 10.1016/j.ijcard.2015.03.003
Matched MeSH terms: Immunosuppressive Agents/pharmacology
Potential immunosuppressive and antiinflammatory activities of Malaysian medicinal plants characterized by reduced cell surface expression of cell adhesion molecules

Tanaka S, Yoichi S, Ao L, Matumoto M, Morimoto K, Akimoto N, et al.

Phytother Res, 2001 Dec;15(8):681-6.
PMID: 11746860

In the search for agents effective against immune-mediated disorders and inflammation, we have screened Malaysian medicinal plants for the ability to inhibit the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the surface of murine endothelial cells (F-2), and mouse myeloid leukaemia cells (M1), respectively. Of 41 kinds (29 species, 24 genera, 16 families) of Malaysian plants tested, 10 and 19 plant samples significantly downregulated the expression of ICAM-1 and VCAM-1, respectively. Bioassay-directed fractionation of an extract prepared from the bark of Goniothalamus andersonii showed that its ingredients, goniothalamin (1) and goniodiol (2) inhibited the cell surface expression of both ICAM-1 and VCAM-1. The present results suggest that Malaysian medicinal plants may be abundant natural resources for immunosuppressive and antiinflammatory substances.

Matched MeSH terms: Immunosuppressive Agents/pharmacology*
Zerumbone from Zingiber zerumbet inhibits innate and adaptive immune responses in Balb/C mice

Jantan I, Haque MA, Ilangkovan M, Arshad L

Int Immunopharmacol, 2019 Aug;73:552-559.
PMID: 31177081 DOI: 10.1016/j.intimp.2019.05.035

Zerumbone exhibited various biological properties including in vitro immunosuppressive effects. However, its modulatory activity on the immune responses in experimental animal model is largely unknown. This investigation was conducted to explore the effects of daily treatment of zerumbone (25, 50, and 100 mg/kg) isolated from Zingiber zerumbet rhizomes for 14 days on various cellular and humoral immune responses in Balb/C mice. For measurement of adaptive immunity, sheep red blood cells (sRBC) were used to immunize the mice on day 0 and orally fed with similar doses of zerumbone for 14 days. The effects of zerumbone on phagocytosis, nitric oxide (NO) release, myeloperoxidase (MPO) activity, proliferation of T and B cells, lymphocyte phenotyping, cytokines release in serum by activated T cells, delayed type hypersensitivity (DTH) and immunoglobulins production (IgG and IgM) were investigated. Zerumbone downregulated the engulfment of E. coli by peritoneal macrophages and the release of NO and MPO in a concentration-dependent manner. Zerumbone showed significant and concentration-dependent suppression of T and B lymphocytes proliferation and inhibition of the Th1 and Th2 cytokines release. At higher concentrations of zerumbone, the % expression of CD4+ and CD8+ in splenocytes was significantly inhibited. Zerumbone also concentration-dependently demonstrated strong suppression on sRBC-triggered swelling of mice paw in DTH. Substantial suppression of anti-sRBC immunoglobulins antibody titer was noted in immunized and zerumbone-treated mice in a concentration-dependent manner. The potent suppressive effects of zerumbone on the immune responses suggest that zerumbone can be a potential candidate for development of immunosuppressive agent.

Matched MeSH terms: Immunosuppressive Agents/pharmacology*
Eosinophilic granulomatosis with polyangiitis and mononeuritis multiplex responded to induction cyclophosphamide

Mohammad N, Wan Ghazali WS

BMJ Case Rep, 2017 May 27;2017.
PMID: 28551593 DOI: 10.1136/bcr-2016-218252

We report a case of 28-year-old Malay woman who initially presented with multiple joints pain with underlying poorly controlled asthma since her childhood. She was treated as seronegative arthritis. However, the involvement of joints, asthma and high-eosinophil counts raised suspicion of Churg-Strauss syndrome. This disease is undoubtedly rare in Malaysians or even in Asian populations. After appropriate therapy was delivered for the correct diagnosis her clinical condition improved. She is currently receiving maintenance treatment.

Matched MeSH terms: Immunosuppressive Agents/pharmacology
Safety and efficacy of the COMBO bio-engineered stent in an all-comer PCI cohort: 1-Year final clinical outcomes from the MASCOT post-marketing registry

Colombo A, Chandrasekhar J, Aquino M, Ong TK, Sartori S, Baber U, et al.

Int J Cardiol, 2019 05 15;283:67-72.
PMID: 30826192 DOI: 10.1016/j.ijcard.2019.01.053

BACKGROUND: The COMBO stent (OrbusNeich Medical, Ft. Lauderdale, Florida) is a new-generation bio-engineered drug eluting stent, combining an abluminal coating of a bioabsorbable polymer matrix for sustained release of sirolimus and luminal anti-CD34 coating for endothelial progenitor cell capture and rapid endothelialization.
METHODS: The Multinational Abluminal Sirolimus Coated BiO-Engineered StenT (MASCOT) registry was a prospective post-marketing study conducted from June 2014-May 2017 across 60 centers globally. Patients were eligible if COMBO stent implantation was attempted, and they received dual antiplatelet therapy (DAPT) per local guidelines. Follow-up was conducted by trained research staff at 1, 6 and 12 months by phone or clinic visit to capture clinical events and DAPT cessation events. The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, non-fatal myocardial infarction not clearly attributable to a non-target vessel, or ischemia-driven target lesion revascularization.
RESULTS: A total of 2614 patients were enrolled over the study period with 96.7% completion of 1-year follow-up. The mean age of enrolled patients was 62.9 ± 11.2 years and 23.0% were female. Diabetes mellitus was present at baseline in 33.5%. A total of 56.1% patients underwent PCI for acute coronary syndrome (ACS). The 1-year primary endpoint of TLF occurred in 3.4% patients (n = 88). Definite stent thrombosis occurred in 0.5% patients (n = 12).
CONCLUSION: The MASCOT post marketing registry provides comprehensive safety and efficacy outcomes following contemporary PCI using the novel COMBO stent in an all-comer population. This platform is associated with low rates of 1-year TLF and ST. CLINICALTRIALS.
GOV IDENTIFIER: NCT02183454.

Matched MeSH terms: Immunosuppressive Agents/pharmacology
Fulltext Thalidomide as a Potential HIV Latency Reversal Agent: Is It the Right Time to Forget the Ancestral Sins?

Vignesh R, Shankar EM

EBioMedicine, 2017 Oct;24:20-21.
PMID: 28865747 DOI: 10.1016/j.ebiom.2017.08.025
Matched MeSH terms: Immunosuppressive Agents/pharmacology*
Fulltext Enhanced immunosuppressive effects of 3,5-bis[4(diethoxymethyl)benzylidene]-1-methyl-piperidin-4-one, an α, β-unsaturated carbonyl-based compound as PLGA-b-PEG nanoparticles

Arshad L, Jantan I, Bukhari SNA

Drug Des Devel Ther, 2019;13:1421-1436.
PMID: 31118577 DOI: 10.2147/DDDT.S185191

Background: 3,5-Bis[4-(diethoxymethyl)benzylidene]-1-methyl-piperidin-4-one (BBP), a novel synthetic curcumin analogue has been revealed to possess strong in vitro and in vivo immunosuppressive effects. Purpose: The aim of present study was to prepare and characterize BBP-encapsulated polylactic-co-glycolic acid-block-polyethylene glycol (PLGA-b-PEG) nanoparticles and to evaluate its in vivo efficacy against innate and adaptive immune responses. Methods: Male BALB/c mice were orally administered with BBP alone and BBP- encapsulated nanoparticles equivalent to 5, 10 and 20 mg/kg of BBP in distilled water for a period of 14 days. The immunomodulatory potential was appraised by determining its effects on non-specific and specific immune parameters. Results: The results showed that BBP was successfully encapsulated in PLGA-b-PEG polymer with 154.3 nm size and high encapsulation efficiency (79%) while providing a sustained release for 48 hours. BBP nanoparticles showed significant enhanced dose-dependent reduction on the migration of neutrophils, Mac-1 expression, phagocytic activity, reactive oxygen species (ROS) production, serum levels of ceruloplasmin and lysozyme, immunoglobulins and myloperoxidase (MPO) plasma levels when compared to unencapsulated BBP. Enhanced dose-dependent inhibition was also observed on lymphocyte proliferation along with the downregulation of effector cells expression and release of cytokines, and reduction in rat paw oedema in BBP nanoparticles treated mice. At higher doses the suppressive effects of the BBP nanoparticles on various cellular and humoral parameters of immune responses were comparable to that of cyclosporine-A at 20 mg/kg. Conclusion: These findings suggest that the immunosuppressive effects of BBP were enhanced as PLGA-b-PEG nanoparticles.

Matched MeSH terms: Immunosuppressive Agents/pharmacology*
Fulltext Immunosuppressive effects of the standardized extract of Phyllanthus amarus on cellular immune responses in Wistar-Kyoto rats

Ilangkovan M, Jantan I, Mesaik MA, Bukhari SN

Drug Des Devel Ther, 2015;9:4917-30.
PMID: 26347462 DOI: 10.2147/DDDT.S88189

Phyllanthus amarus (family: Euphorbiaceae) is of immense interest due to its wide spectrum of biological activities. In the present study, the standardized 80% ethanol extract of P. amarus was investigated for its modulatory activity on various cellular immune parameters, including chemotaxis of neutrophils, engulfment of Escherichia coli by neutrophils, and Mac-1 expression, in leukocytes isolated from treated/nontreated Wistar-Kyoto rats. The detailed cell-mediated activity of P. amarus was also investigated, including analysis of the effects on T- and B-cell proliferation and CD4(+) and CD8(+) T-cell subsets in splenic mononuclear cells, and estimation of serum cytokine production by activated T-cells. The main components of the extract, phyllanthin, hypophyllanthin, corilagin, geraniin, ellagic acid, and gallic acid were identified and quantitatively analyzed in the extracts, using validated reversed-phase high-performance liquid chromatography (HPLC) methods. N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced neutrophils isolated from rats administered with the extract of P. amarus, at doses ranging from 100 to 400 mg/kg for 14 days, revealed a significant dose-dependent reduction in neutrophil migration (P<0.05). Similar patterns of inhibition were also observed in phagocytic activity and in fMLP-induced changes in expression of β2 integrin polymorphonuclear neutrophils. The results in P. amarus-treated rats also demonstrated a dose-dependent inhibition of both lipopolysaccharide-stimulated B-cell proliferation and concanavalin A-stimulated T-cell proliferation as compared with sensitized control. At a dose of 400 mg/kg (P<0.01), there was a significant decrease in the (%) expression of CD4(+) and CD8(+) in splenocytes and in serum cytokines of T helper (Th1) (IL-2 and IFN-γ) and Th2 (IL-4). In conclusion, P. amarus showed effective immunosuppressive activities in cellular immune response, by various immune regulatory mechanisms, and may be useful for improvement of immune-related disorders.

Matched MeSH terms: Immunosuppressive Agents/pharmacology*
Fingolimod affects gene expression profile associated with LPS-induced memory impairment

Omidbakhsh R, Rajabli B, Nasoohi S, Khallaghi B, Mohamed Z, Naidu M, et al.

Exp Brain Res, 2014 Nov;232(11):3687-96.
PMID: 25098558 DOI: 10.1007/s00221-014-4052-4

Lipopolysaccharide is an endotoxin to induce sickness behavior in several animal models to explore the link between immune activation and cognition. Neuroinflammation playing a pivotal role in disease progress is evidently influenced by sphingosine-1-phosphate. As one of the sphingosine analogs in clinical use for multiple sclerosis, fingolimod (FTY720) was shown to substantially affect gene expression profile in the context of AD in our previous experiments. The present study was designed to evaluate the drug efficacy in the context of the mere inflammatory context leading to memory impairment. FTY720 was repeatedly administered for a few days before or after intracerebral lipopolysaccharide (LPS) injection in rats. Animal's brains were then assigned to histological as well as multiplex mRNA assay following memory performance test. Both FTY720 pre-treatment and post-treatment were similarly capable of ameliorating LPS-induced memory impairment as assessed by passive avoidance test. Such amending effects may be partly accountable by the concomitant alterations in transcriptional levels of mitogen-activated protein kinases as well as inflammatory genes determined by QuantiGene Plex analysis. These findings confirming FTY720 application benefits suggest its efficacy may not differ significantly while considered either as a preventive or as a therapeutic approach against neuroinflammation.

Matched MeSH terms: Immunosuppressive Agents/pharmacology

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