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Interactions with the macrophages: An emerging targeted approach using novel drug delivery systems in respiratory diseases

Mehta M, Deeksha, Sharma N, Vyas M, Khurana N, Maurya PK, et al.

Chem Biol Interact, 2019 May 01;304:10-19.
PMID: 30849336 DOI: 10.1016/j.cbi.2019.02.021

Macrophages are considered as the most flexible cells of the hematopoietic system that are distributed in the tissues to act against pathogens and foreign particles. Macrophages are essential in maintaining homeostatic tissue processes, repair and immunity. Also, play important role in cytokine secretion and signal transduction of the infection so as to develop acquired immunity. Accounting to their involvement in pathogenesis, macrophages present a therapeutic target for the treatment of inflammatory respiratory diseases. This review focuses on novel drug delivery systems (NDDS) including nanoparticles, liposomes, dendrimers, microspheres etc that can target alveolar macrophage associated with inflammation, intracellular infection and lung cancer. The physiochemical properties and functional moieties of the NDDS attributes to enhanced macrophage targeting and uptake. The NDDS are promising for sustained drug delivery, reduced therapeutic dose, improved patient compliance and reduce drug toxicity. Further, the review also discuss about modified NDDS for specificity to the target and molecular targeting via anti-microbial peptides, kinases, NRF-2 and phosphodiesterase.

Matched MeSH terms: Macrophages/drug effects*
Physicochemical and biological characterization of the lipid particles with bovine serum albumin corona

Chen C, Alfredo YY, Lee YY, Tan CP, Wang Y, Qiu C

Int J Biol Macromol, 2024 Nov;281(Pt 1):136223.
PMID: 39366617 DOI: 10.1016/j.ijbiomac.2024.136223

Diacylglycerol-based nanoparticles are promising bioactive delivery systems. However, limited understanding of their interaction with biological entities restricts their clinical use. This study investigated the protein corona formed on medium and long chain diacylglycerol (MLCD)-based solid lipid nanoparticles (NPs) modified by Polyoxethylene stearate (PEG) and compared to glyceryl tristearate (TG) and cetyl palmitate (CP) nanoparticles. Bovine serum albumin (BSA) formed corona with MLCD NPs through hydrophobic interactions and hydrogen bonding, contributing to a decrease in α-helix, an increase in β-sheet and a change in the microenvironment of Tyr residues. Owing to higher lipid hydrophilicity, MLCD NPs showed a much lower affinity for BSA than TG and CP NPs, and the binding constant with BSA was increased for larger NPs. PEG modification and the protein corona reduced the uptake of NPs by macrophages but exerted little influence on B16 cell. Among the NPs with different lipid core, the MLCD NPs showed a lower macrophages cell uptake but higher B16 cell uptake, suggesting a longer circulation time in blood but higher cancer cell internalization. This work shed light on the interactions between MLCD NPs and proteins, which is significant for application as nanocarriers with improved biological efficacy.

Matched MeSH terms: Macrophages/drug effects
Inhibition of macromolecular synthesis in cultured macrophages by Pseudomonas pseudomallei exotoxin

Mohamed R, Nathan S, Embi N, Razak N, Ismail G

Microbiol. Immunol., 1989;33(10):811-20.
PMID: 2615673

Pseudomonas pseudomallei exotoxin was found to be a potent inhibitor of protein and DNA synthesis in cultured macrophages. Inhibition of DNA synthesis occurred at toxin concentrations as low as 1-2 micrograms/ml and inhibition of 3H-thymidine uptake was almost complete at concentrations of 8 micrograms/ml or more. A close correlation between cell damage and inhibition by DNA synthesis was observed. For protein synthesis, inhibition was obtained at much lower doses (0.06-2.0 micrograms/ml) of the toxin. At similar toxin concentrations, DNA synthesis was marginally affected. Further, it was shown that protein synthesis inhibition occurred almost immediately after incubation, reaching its maximal inhibitory effect of 70% after 6 hr. DNA synthesis, however, was minimally affected by a similar toxin concentration even after 10 hr of incubation. The inhibition of macromolecular synthesis in macrophages by P. pseudomallei exotoxin may be relevant to its modulatory effect on the host defense mechanism.

Matched MeSH terms: Macrophages/drug effects
The Immunomodulating Properties of Tiger Milk Medicinal Mushroom, Lignosus rhinocerus TM02® Cultivar (Agaricomycetes) and Its Associated Carbohydrate Composition

Sum AYC, Li X, Yeng YYH, Razif MFM, Jamil AHA, Ting NS, et al.

Int J Med Mushrooms, 2020;22(8):803-814.
PMID: 33389874 DOI: 10.1615/IntJMedMushrooms.2020035658

Natural compounds found in Lignosus rhinocerus like polysaccharides and polysaccharide-protein complexes have the capabilities to modulate the immune system. It possesses antitumor and anti-inflammatory properties and is commonly used in Southeast Asia and Southern China to alleviate illness. To investigate its immunomodulating properties, composition of polysaccharides and the expression of cytokines/chemokines from L. rhinocerus (TM02®) cultivar treated RAW 264.7 were explored. It was revealed, CWE contains linear polysaccharides with 1,4-linkages and rhinoprolycan fraction (HMW & MMW) possesses 1,4-Glcp and 1,6-Glcp backbone and branched chain (1,3,6-Glcp, 1,4,6-Glcp, 1,3,6-Glcp, 1,2,4,6-Glcp). Cytokines profile showed upregulation from CWE (IL-5: 12.078 ± 1.225), HMW (IL-6: 7.297 ± 0.338; TIMP-1: 3.358 ± 0.200), MMW (IL-5: 15.412 ± 5.823; TIMP-1: 1.747 ± 0.053), and LMW (MIP-2: 3.495 ± 0.416; TIMP-1: 7.573 ± 0.088) and possible involvement of NF-κB and MAPK signaling pathway. Further in vivo studies are needed to fully understand the immunomodulatory effects of TM02®.

Matched MeSH terms: Macrophages/drug effects
Comparative efficacy of vanilloids in inhibiting toll-like receptor-4 (TLR-4)/myeloid differentiation factor (MD-2) homodimerisation

Mai CW, Kang YB, Hamzah AS, Pichika MR

Food Funct, 2018 Jun 20;9(6):3344-3350.
PMID: 29808897 DOI: 10.1039/c8fo00136g

Vanilloid (4-hydroxy-3-methoxyphenyl benzenoid) containing foods are reported to possess many biological activities including anti-inflammatory properties. Homodimerisation of the Toll-like receptor-4 (TLR-4)/Myeloid differentiation factor 2 (MD-2) complex results in life-threatening complications in inflammatory disorders. In this study, we report activity of vanilloids in inhibition of TLR-4/MD-2 homodimersization and their molecular interactions with the receptor. The inhibitory activities of vanilloids were assessed in vitro by determining their antagonistic actions of lipopolysaccharide from Escherichia coli (LPSEc) in activation of TLR-4/MD-2 homodimerisation in TLR-4/MD-2/CD-14 transfected HEK-293 cells. The in vitro anti-inflammatory activity of vanilloids was also determined using RAW 264.7 cells. All the vanilloids were found to be active in the inhibition of TLR-4/MD-2 homodimersiation and nitric oxide production in RAW 264.7 cells. Rigid and flexible molecular docking studies were performed to gain insight into interactions between vanilloids and the binding site of the TLR-4/MD-2 complex.

Matched MeSH terms: Macrophages/drug effects
The effect of L-arginine on Porphyromonas gingivalis-induced phagocytosis of a murine macrophage-like RAW264.7 cell line

Sosroseno W

Immunopharmacol Immunotoxicol, 2004 May;26(2):309-13.
PMID: 15209366

The aim of this study was to determine the effect of L-arginine on Porphyromonas gingivalis-induced phagocytosis by RAW264.7 cells. The cells were pretreated with L-arginine or D-arginine prior to incubation with either unopsonized or opsonized P. gingivalis. In other experiments, the cells were pretreated with L-arginine and various concentrations of NMLA (N(G)-monomethyl-L-arginine) prior to incubation with the bacteria. The phagocytosis was microscopically assessed and determined by the phagocytic index. The results showed that L-arginine, but not D-arginine enhances the ability of RAW264.7 cells to engulf the bacteria. The upregulatory effect of L-arginine on P. gingivalis-induced phagocytosis was abolished by NMLA. The results of the present study suggest that L-arginine may upregulate the P. gingivalis-induced phagocytic activity of RAW264.7 cells, perhaps, via modulation of nitric oxide synthase.

Matched MeSH terms: Macrophages/drug effects*
In vitro methods used for discovering plant derived products as wound healing agents - An update on the cell types and rationale

Low JS, Mak KK, Zhang S, Pichika MR, Marappan P, Mohandas K, et al.

Fitoterapia, 2021 Oct;154:105026.
PMID: 34480992 DOI: 10.1016/j.fitote.2021.105026

Wounds still pose a huge burden on human health and healthcare systems in many parts of the world. Phytomedicines are being used to heal the wounds since ancient times. Now-a-days also many researchers are exploring the wound healing activity of phytomedicines. Wound healing is a complex process thus, it is always a question mark regarding the best test model (in vivo, ex vivo and in vitro) model to assess the wound healing activity of phytomedicines. In general, the researchers would opt for in vivo model - probably because of closer physiological relevance to human wounds. However, in vivo experimental models are not suitable for high throughput screening and not ethical in terms of initial screening of the phytomedicines. The in vivo models are associated with difficulties in obtaining the ethical approvals, requires huge budget, and resources. We argue that judicious selection of cell types would serve the purpose of developing a physiologically relevant in vitro experimental model. A lot of progress has been made in molecular biology techniques to bridge the gap between in vitro models and their physiological relevance. The in vitro models are the best suited for high throughput screening and to elucidate the molecular mechanisms. The main aim of this review is to provide insights on selection of the cell types for developing physiologically relevant in vitro wound healing assays, which can be used to improve the value of phytomedicines further.

Matched MeSH terms: Macrophages/drug effects
Cytotoxicity and inhibition of nitric oxide in lipopolysaccharide induced mammalian cell lines by aqueous extracts of brown seaweed

Jaswir I, Monsur HA, Simsek S, Amid A, Alam Z, bin Salleh MN, et al.

J Oleo Sci, 2014;63(8):787-94.
PMID: 25007746

Aqueous extracts obtained from five Malaysian brown seaweeds, Sargassum duplicatum, Sargassum binderi, Sargassum fulvellum, Padina australis, and Turbinaria turbinata, were investigated for their abilities to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-induced macrophage RAW 264.7 cell lines as well as to determine their chemical composition. The percentage yield of extracts varied among species, with P. australis having the lowest yield and T. turbinata having the highest yield. The chemical compositions of the extracts showed that the percentage of sulfate ions as well as uronic acid and total sugar content varied significantly. All extracts contained high fucose and inhibited NO secretion in a dose-dependent manner. Extracts of P. australis and T. turbinata dosed at 200 μg/mL were able to inhibit NO secretion by > 75%. Furthermore, cytotoxicity assays revealed that some extracts were moderately toxic, while others were not. Based on these results, brown seaweed of Malaysian origin should be investigated for the production of additional anti-inflammatory compounds.

Matched MeSH terms: Macrophages/drug effects*
Zinc Carnosine Inhibits Lipopolysaccharide-Induced Inflammatory Mediators by Suppressing NF-κb Activation in Raw 264.7 Macrophages, Independent of the MAPKs Signaling Pathway

Ooi TC, Chan KM, Sharif R

Biol Trace Elem Res, 2016 Aug;172(2):458-464.
PMID: 26749414 DOI: 10.1007/s12011-015-0615-x

This study aimed to investigate the role of the mitogen-activated protein kinases (MAPKs) signaling pathway in the anti-inflammatory effects of zinc carnosine (ZnC) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Cells were pretreated with ZnC (0-100 μM) for 2 h prior to the addition of LPS (1 μg/ml). Following 24 h of treatment, ZnC was found not to be cytotoxic to RAW 264.7 cells up to the concentration of 100 μM. Our current findings showed that ZnC did not protect RAW 264.7 cells from LPS-induced "respiratory burst". Significant increment in intracellular glutathione (GSH) level and reduction in thiobarbituric acid reactive substances (TBARS) concentration can only be observed in cell pretreated with high doses of ZnC only (50 and 100 μM for GSH and 100 μM only for TBARS). On the other hand, pretreatment of cells with ZnC was able to inhibit LPS-induced inducible nitric oxide synthase and cyclooxygenase-2 expression significantly. Furthermore, results from immunoblotting showed that ZnC was able to suppress nuclear factor-kappaB (NF-κB) activation, and highest suppression can be observed at 100 μM of ZnC pretreatment. However, pretreatment of ZnC did not inhibit the early activation of MAPKs. In conclusion, pretreatment with ZnC was able to inhibit the expression of inflammatory mediators in LPS-induced RAW 264.7 cells, mainly via suppression of NF-κB activation, and is independent of the MAPKs signaling pathway.

Matched MeSH terms: Macrophages/drug effects*
Fulltext Capgermacrenes A and B, Bioactive Secondary Metabolites from a Bornean Soft Coral, Capnella sp

Phan CS, Ng SY, Kim EA, Jeon YJ, Palaniveloo K, Vairappan CS

Mar Drugs, 2015 May;13(5):3103-15.
PMID: 25996100 DOI: 10.3390/md13053103

Two new bicyclogermacrenes, capgermacrenes A (1) and B (2), were isolated with two known compounds, palustrol (3) and litseagermacrane (4), from a population of Bornean soft coral Capnella sp. The structures of these metabolites were elucidated based on spectroscopic data. Compound 1 was found to inhibit the accumulation of the LPS-induced pro-inflammatory IL-1b and NO production by down-regulating the expression of iNOS protein in RAW 264.7 macrophages.

Matched MeSH terms: Macrophages/drug effects
Evaluation of antioxidant and nitric oxide inhibitory activities of selected Malaysian medicinal plants

Saha K, Lajis NH, Israf DA, Hamzah AS, Khozirah S, Khamis S, et al.

J Ethnopharmacol, 2004 Jun;92(2-3):263-7.
PMID: 15138010

Methanol extracts of seven Malaysian medicinal plants were screened for antioxidant and nitric oxide inhibitory activities. Antioxidant activity was measured by using FTC, TBA and DPPH free radical scavenging methods and Griess assay was used for the measurement of nitric oxide inhibition in lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma)-treated RAW 264.7 cells. All the extracts showed strong antioxidant activity comparable to or higher than that of alpha-tocopherol, BHT and quercetin in FTC and TBA methods. The extracts from Leea indica and Spermacoce articularis showed strong DPPH free radical scavenging activity comparable with quercetin, BHT and Vit C. Spermacoce exilis showed only moderate activity but other species were weak as compared to the standards. In the Griess assay Lasianthus oblongus, Chasalia chartacea, Hedyotis verticillata, Spermacoce articularis and Leea indica showed strong inhibitory activity on nitric oxide production in LPS and IFN-gamma-induced RAW 264.7 cells. Extracts from Psychotria rostrata and Spermacoce exilis also inhibited NO production but this was due to their cytotoxic effects upon cells during culture.

Matched MeSH terms: Macrophages/drug effects
Anti-inflammatory evaluation of Scurrula ferruginea (jack) danser parasitizing on Tecoma stans (L.) H.B.K. in LPS/IFN-γ-induced RAW 264.7 macrophages

Hong X, Ajat M, Fakurazi S, Noor AM, Ismail IS

J Ethnopharmacol, 2021 Mar 25;268:113647.
PMID: 33271242 DOI: 10.1016/j.jep.2020.113647

ETHNOPHARMACOLOGICAL RELEVANCE: Scurrula ferruginea (Jack) Danser (locally known as 'Dedalu' or 'dian nan ji sheng' in Malaysia and China) is a hemi-parasitic shrub that is widely used as herbal medicine to treat inflammation, rheumatism, and stroke. However, the scientific basis of its anti-inflammatory function and mechanism remain to be proven.
AIM OF THE STUDY: To evaluate the anti-inflammatory activity as well as the preliminary mechanism of S. ferruginea parasitizing on Tecoma stans.
MATERIALS AND METHODS: The anti-inflammatory capability of freeze-dried stem aqueous extract was assessed via inhibition of inflammatory cytokines interleukin- (IL-) 1β, IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α) production in lipopolysaccharide (LPS) and interferon-γ (IFN-γ) stimulated RAW 264.7 macrophages. The underlying anti-inflammatory mechanism was deciphered through reverse transcriptase and real time quantitative polymerase chain reactions (RT-PCR and qPCR) for inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), IL-1β, and TNF-α mRNA expression.
RESULTS: The results exhibited that aqueous extract of freeze-dried S. ferruginea stem sample concentration-dependently inhibited IL-1β protein production along with the down regulation of iNOS and IL-1β mRNA expression. Moreover, it significantly suppressed the protein release of IL-6 and IL-10 in a concentration-dependent manner. However, it slightly reduced TNF-α at higher sample concentration (250 μg/mL) without affecting the mRNA expression levels of COX-2 and TNF-α.
CONCLUSIONS: This study suggests that S. ferruginea parasitizing on Tecoma stans exerted anti-inflammatory capability attributed to inhibition of iNOS and IL-1β mRNA expression, NO creation, IL-1β, IL-6, IL-10, and TNF-α protein production, indicating this plant might be a useful plant-derived candidate against inflammation.

Matched MeSH terms: Macrophages/drug effects
Cell Proliferation and DNA Repair Ability of Ganoderma neo-japonicum (Agaricomycetes): An Indigenous Medicinal Mushroom from Malaysia

Tan WC, Kuppusamy UR, Phan CW, Sabaratnam V

Int J Med Mushrooms, 2018;20(2):155-163.
PMID: 29773007 DOI: 10.1615/IntJMedMushrooms.2018025445

Ganoderma neo-japonicum is an annual polypore that grows on decaying bamboo in the forests of Malaysia. The indigenous Temuan tribe uses this species as a medicinal mushroom to cure fever and epilepsy and to improve body strength. The potential use of G. neo-japonicum in genoprotection and DNA repair was established using a single-cell gel electrophoresis (comet) assay. The effects of the ethanol and hot aqueous extracts from wild and cultivated basidiocarps, solid substrate-fermented (SSF) wheat grains, and mycelia via submerged culture on H2O2-damaged murine RAW264.7 macrophages were investigated. An ethanol extract from wild basidiocarps showed the most significant protective effect on murine RAW264.7 macrophages, followed by ethanol and hot water extracts of cultivated basidiocarps, and this effect was dose dependent. However, only the ethanol extracts from SSF and submerged culture showed significant protective effects compared with the control. As for DNA repair ability, only the ethanol extract from wild and cultivated basidiocarps showed significant results when compared with the negative control. The findings suggest the potential therapeutic use of G. neo-japonicum in genome protection and as a DNA repair stimulator.

Matched MeSH terms: Macrophages/drug effects
Acetyl- and O-alkyl- derivatives of β-mangostin from Garcinia mangostana and their anti-inflammatory activities

Karunakaran T, Ee GCL, Ismail IS, Mohd Nor SM, Zamakshshari NH

Nat Prod Res, 2018 Jun;32(12):1390-1394.
PMID: 28715912 DOI: 10.1080/14786419.2017.1350666

Pure β-mangostin (1) was isolated from the stem bark of Garcinia mangostana L. One monoacetate (2) and five O-alkylated β-mangostin derivatives (3-7) were synthesised from β-mangostin. The structures of these compounds were elucidated and determined using spectroscopic techniques such as 1D NMR and MS. The cytotoxicities and anti-inflammatory activities of these five compounds against RAW cell 264.7 were tested. The structural-activity relationship studies indicated that β-mangostin showed a significant activity against the LPS-induced RAW cell 264.7, while the acetyl- as well as the O-alkyl- β-mangostin derivatives did not give good activity. Naturally occurring β-mangostin demonstrated comparatively better anti-inflammatory activity than its synthetic counterparts.

Matched MeSH terms: Macrophages/drug effects
Critical physicochemical and biological attributes of nanoemulsions for pulmonary delivery of rifampicin by nebulization technique in tuberculosis treatment

Shah K, Chan LW, Wong TW

Drug Deliv, 2017 Nov;24(1):1631-1647.
PMID: 29063794 DOI: 10.1080/10717544.2017.1384298

The study investigated aerosolization, pulmonary inhalation, intracellular trafficking potential in macrophages and pharmacokinetics profiles of rifampicin-oleic acid first-generation nanoemulsion and its respective chitosan- and chitosan-folate conjugate-decorated second and third-generation nanoemulsions, delivered via nebulization technique. The nanoemulsions were prepared by conjugate synthesis and spontaneous emulsification techniques. They were subjected to physicochemical, drug release, aerosolization, inhalation, cell culture and pharmacokinetics analysis. The nanoemulsions had average droplet sizes of 40-60 nm, with narrow polydispersity indices. They exhibited desirable pH, surface tension, viscosity, refractive index, density and viscosity attributes for pulmonary rifampicin administration. All nanoemulsions demonstrated more than 95% aerosol output and inhalation efficiency greater than 75%. The aerosol output, aerosolized and inhaled fine particle fractions were primarily governed by the size and surface tension of nanoemulsions in an inverse relationship. The nanoemulsions were found to be safe with third-generation nanoemulsion exhibiting higher cell internalization potential, reduced plasma drug concentration, and higher lung drug content.

Matched MeSH terms: Macrophages/drug effects
Fulltext Suppression of Proinflammatory Cytokines and Mediators in LPS-Induced RAW 264.7 Macrophages by Stem Extract of Alternanthera sessilis via the Inhibition of the NF-κB Pathway

Muniandy K, Gothai S, Badran KMH, Suresh Kumar S, Esa NM, Arulselvan P

J Immunol Res, 2018;2018:3430684.
PMID: 30155492 DOI: 10.1155/2018/3430684

Alternanthera sessilis, an edible succulent herb, has been widely used as herbal drug in many regions around the globe. Inflammation is a natural process of the innate immune system, accompanied with the increase in the level of proinflammatory mediators, for example, nitric oxide (NO) and prostaglandin (PGE2); cytokines such as interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor alpha (TNFα); and enzymes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) via the activation and nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunit p65 due to the phosphorylation of inhibitory protein, IκBα. Inflammation over a short period of time is essential for its therapeutic effect. However, prolonged inflammation can be detrimental as it is related to many chronic diseases such as delayed wound healing, cardiovascular disease, arthritis, and autoimmune disorders. Therefore, ways to curb chronic inflammation have been extensively investigated. In line with that, in this present study, we attempted to study the suppression activity of the proinflammatory cytokines and mediators as a characteristic of anti-inflammatory action, by using stem extract of A. sessilis in the lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophage cell line. The results showed that the extract has significantly inhibited the production of the proinflammatory mediators including NO and PGE2; cytokines comprising IL-6, IL-1β, and TNFα; and enzymes covering the iNOS and COX-2 by preventing the IκBα from being degraded, to inhibit the nuclear translocation of NF-κB subunit p65 in order to hinder the inflammatory pathway activation. These results indicated that the stem extract of A. sessilis could be an effective candidate for ameliorating inflammatory-associated complications.

Matched MeSH terms: Macrophages/drug effects
Fulltext Stimulatory effects of polysaccharide fraction from Solanum nigrum on RAW 264.7 murine macrophage cells

Razali FN, Ismail A, Abidin NZ, Shuib AS

PLoS One, 2014;9(10):e108988.
PMID: 25299340 DOI: 10.1371/journal.pone.0108988

The polysaccharide fraction from Solanum nigrum Linne has been shown to have antitumor activity by enhancing the CD4+/CD8+ ratio of the T-lymphocyte subpopulation. In this study, we analyzed a polysaccharide extract of S. nigrum to determine its modulating effects on RAW 264.7 murine macrophage cells since macrophages play a key role in inducing both innate and adaptive immune responses. Crude polysaccharide was extracted from the stem of S. nigrum and subjected to ion-exchange chromatography to partially purify the extract. Five polysaccharide fractions were then subjected to a cytotoxicity assay and a nitric oxide production assay. To further analyze the ability of the fractionated polysaccharide extract to activate macrophages, the phagocytosis activity and cytokine production were also measured. The polysaccharide fractions were not cytotoxic, but all of the fractions induced nitric oxide in RAW 264.7 cells. Of the five fractions tested, SN-ppF3 was the least toxic and also induced the greatest amount of nitric oxide, which was comparable to the inducible nitric oxide synthase expression detected in the cell lysate. This fraction also significantly induced phagocytosis activity and stimulated the production of tumor necrosis factor-α and interleukin-6. Our study showed that fraction SN-ppF3 could classically activate macrophages. Macrophage induction may be the manner in which polysaccharides from S. nigrum are able to prevent tumor growth.

Matched MeSH terms: Macrophages/drug effects*
Fulltext Enhanced anti-inflammatory potential of cinnamate-zinc layered hydroxide in lipopolysaccharide-stimulated RAW 264.7 macrophages

Adewoyin M, Mohsin SM, Arulselvan P, Hussein MZ, Fakurazi S

Drug Des Devel Ther, 2015;9:2475-84.
PMID: 25995619 DOI: 10.2147/DDDT.S72716

BACKGROUND: Cinnamic acid (CA) is a phytochemical originally derived from Cinnamomum cassia, a plant with numerous pharmacological properties. The intercalation of CA with a nanocarrier, zinc layered hydroxide, produces cinnamate-zinc layered hydroxide (ZCA), which has been previously characterized. Intercalation is expected to improve the solubility and cell specificity of CA. The nanocarrier will also protect CA from degradation and sustain its release. The aim of this study was to assess the effect of intercalation on the anti-inflammatory capacity of CA.
METHODS: In this study, the anti-inflammatory activity of ZCA was investigated and compared with that of nonintercalated CA. Evaluations were based on the capacity of ZCA and CA to modulate the release of nitric oxide, prostaglandin E2, interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), IL-1β, and IL-10 in lipopolysaccharide-induced RAW 264.7 cells. Additionally, the expression of proinflammatory enzymes, ie, cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor kappa B (NF-κB), were examined.
RESULTS: Although both ZCA and CA downregulated nitric oxide, prostaglandin E2, tumor necrosis factor alpha, IL-1β, and IL-6, ZCA clearly displayed better activity. Similarly, expression of cyclooxygenase-2 and inducible nitric oxide synthase were inhibited in samples treated with ZCA and CA. The two compounds effectively inactivated the transcription factor NF-κB, but the anti-inflammatory cytokine, IL-10, was significantly upregulated by ZCA only.
CONCLUSION: The present findings suggest that ZCA possesses better anti-inflammatory potential than CA, while zinc layered hydroxide had little or no effect, and these results were comparable with the positive control.

Matched MeSH terms: Macrophages/drug effects*
Fractionation and Biological Activities of Water-Soluble Polysaccharides from Sclerotium of Tiger Milk Medicinal Mushroom, Lignosus rhinocerotis (Agaricomycetes)

Keong CY, B V, Daker M, Hamzah MY, Mohamad SA, Lan J, et al.

Int J Med Mushrooms, 2016;18(2):141-54.
PMID: 27279536 DOI: 10.1615/IntJMedMushrooms.v18.i2.50

This study investigated antioxidant and anti-inflammatory properties, and the direct cytotoxic effect of Lignosus rhinocerotis fractions, especially the polysaccharide fraction, on nasopharyngeal carcinoma cells. L. rhinocerotis crude extract was obtained through hot water extraction. The precipitate saturated with 30% ammonium sulfate was purified with ion-exchanged chromatography. Gel permeation chromatography multiangle laser light scattering analysis equipped with light scattering and UV signals revealed two district groups of polymers. A total of four peaks were observed in the total carbohydrate test. Fraction C, which was the second region of the second peak eluted with 0.3 M NaOH, showed the highest integrated molecular weight, whereas fraction E had the lowest integrated molecular weight of 19,790 Da. Fraction A contained the highest β-D-glucan content. Enzymatic analysis showed that most of the polysaccharide fractions contained β-1-3 and β-1-6 skeletal backbones. The peak eluted with 0.6 M NaOH was separated in fraction D (flask 89-92) and fraction E (93-96). The results showed that fraction E expressed higher antioxidant activities than fraction D whereas fraction D expressed higher chelating activity than fraction E. The extract saturated with 30% ammonium sulfate exhibited higher reducing power than the extract saturated with 100% ammonium sulfate. Fractions D and E significantly inhibited the secretion of tumor necrosis factor-α in lipopolysaccharide-stimulated RAW 264.7 macrophages in a dose-dependent manner. There was no apparent difference in the viability of cells exposed or unexposed to L. rhinocerotis fractions.

Matched MeSH terms: Macrophages/drug effects
Fulltext Immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum on LPS- or LPS+IFN-γ-stimulated J774A.1 cells

Mohamad D, Suppian R, Mohd Nor N

Hum Vaccin Immunother, 2014;10(7):1880-6.
PMID: 25424796 DOI: 10.4161/hv.28695

Macrophage phagocytosis is the first line of defense of the innate immune system against malaria parasite infection. This study evaluated the immunomodulatory effects of BCG and recombinant BCG (rBCG) strains expressing the C-terminus of the merozoite surface protein-1 (MSP-1C) of Plasmodium falciparum on mouse macrophage cell line J774A.1 in the presence or absence of lipopolysaccharide (LPS) or LPS + IFN-γ. The rBCG strain significantly enhanced phagocytic activity, production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, nitric oxide (NO), and inducible nitric oxide synthase (iNOS) as compared with parental BCG strain, and these activities increased in the presence of LPS and LPS+IFN-γ. Furthermore, the rBCG strain also significantly reduced the macrophage viability as well as the rBCG growth suggesting the involvement of macrophage apoptosis. Taken together, these data indicate that the rBCG strain has an immunomodulatory effect on macrophages, thus strengthen the rational use of rBCG to control malaria infection.

Matched MeSH terms: Macrophages/drug effects*

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