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Article ; Online: Nimbolide Targets Multiple Signalling Pathways to Reduce Neuroinflammation in BV-2 Microglia.

Katola, Folashade O / Olajide, Olumayokun A

2023 Volume 60, Issue 9, Page(s) 5450–5467

Abstract: Nimbolide, a limonoid compound found in the neem plant, was investigated for effects on neuroinflammation in BV-2 microglia activated with lipopolysaccharide (LPS). Cultured BV-2 cells were treated with nimbolide (125, 250 and 500 nM) followed by ... ...

Abstract	Nimbolide, a limonoid compound found in the neem plant, was investigated for effects on neuroinflammation in BV-2 microglia activated with lipopolysaccharide (LPS). Cultured BV-2 cells were treated with nimbolide (125, 250 and 500 nM) followed by stimulation with LPS (100 ng/ml). Results showed that nimbolide caused a significant reduction in the levels of TNFα, IL-6, IFNγ, NO/iNOS and PGE
MeSH term(s)	Humans ; NF-kappa B/metabolism ; Limonins/pharmacology ; Neuroinflammatory Diseases ; NF-E2-Related Factor 2/metabolism ; Microglia/metabolism ; Lipopolysaccharides/pharmacology ; Antioxidants/metabolism ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/metabolism ; Nitric Oxide Synthase Type II/metabolism
Chemical Substances	NF-kappa B ; nimbolide (25990-37-8) ; Limonins ; NF-E2-Related Factor 2 ; Lipopolysaccharides ; Antioxidants ; Anti-Inflammatory Agents ; Nitric Oxide Synthase Type II (EC 1.14.13.39)
Language	English
Publishing date	2023-06-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-023-03410-y
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Zs.A 2411: Show issues

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Article ; Online: Neuroprotection by Skimmianine in Lipopolysaccharide-Activated BV-2 Microglia.

Ogunrinade, Folashade A / Iwuanyanwu, Victoria U / Sarker, Satyajit D / Olajide, Olumayokun A

Molecules (Basel, Switzerland)

2023 Volume 28, Issue 3

Abstract: Skimmianine is a furoquinoline alkaloid which is found in ... ...

Abstract	Skimmianine is a furoquinoline alkaloid which is found in the
MeSH term(s)	Cell Line ; Culture Media, Conditioned/pharmacology ; Cyclooxygenase 2/metabolism ; Interleukin-6/metabolism ; Lipopolysaccharides/pharmacology ; Microglia ; Neuroprotection ; NF-kappa B/metabolism ; NF-KappaB Inhibitor alpha/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Animals ; Mice ; Quinolines/pharmacology
Chemical Substances	Culture Media, Conditioned ; Cyclooxygenase 2 (EC 1.14.99.1) ; Interleukin-6 ; Lipopolysaccharides ; NF-kappa B ; NF-KappaB Inhibitor alpha (139874-52-5) ; skimmianine (4E1KLC380B) ; Tumor Necrosis Factor-alpha ; Quinolines
Language	English
Publishing date	2023-01-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules28031317
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Article ; Online: Neuroprotection by Alstonia boonei De Wild., Anacardium occidentale L., Azadirachta indica A.Juss. and Mangifera indica L.

Iwuanyanwu, Victoria U / Banjo, Owolabi W / Babalola, Kabirat T / Olajide, Olumayokun A

Journal of ethnopharmacology

2023 Volume 310, Page(s) 116390

Abstract: Ethnopharmacology relevance: Alstonia boonei De Wild. (stem bark), Anacardium occidentale L. (stem bark), Azadirachta indica A.Juss (leaves), Enantia chlorantha Oliv. (stem bark), Khaya senegalensis A.Juss (stem bark) Mangifera indica L. (stem bark), ... ...

Abstract	Ethnopharmacology relevance: Alstonia boonei De Wild. (stem bark), Anacardium occidentale L. (stem bark), Azadirachta indica A.Juss (leaves), Enantia chlorantha Oliv. (stem bark), Khaya senegalensis A.Juss (stem bark) Mangifera indica L. (stem bark), and Nauclea latifolia Sm. (stem bark) are used for treating malaria in southwest Nigeria. Surveys revealed that these plants are also employed for treating symptoms of malaria and cerebral malaria in the region. Aim of the study: In this study, the effects of freeze-dried extracts of these plants were investigated on synthetic hemozoin (HZ)-induced neuroinflammation, neuronal damage, and increased permeability of brain microvascular endothelial cells. Materials and methods: Effects of freeze-dried plant extracts were investigated on neuroinflammation by measuring levels of pro-inflammatory mediators in culture supernatants, while in-cell western assays were used to measure protein levels of iNOS and NLRP3. Effects on HZ-induced neurotoxicity and ROS generation was measured using MTT and DCFDA assays, respectively. HZ-induced permeability of hCMEC/D3 endothelial cells was determined using the in vitro vascular permeability assay kit. Results: The extracts produced significant (p < 0.05) reduction in TNFα, IL-6, IL-1β, MCP-1, RANTES and iNOS/NO production in HZ-stimulated BV-2 microglia. Pre-treatment with 50 μg/mL of A. boonei, A. indica, A. occidentale, E. chlorantha and M. indica also resulted in the inhibition of NF-κB activation. Pre-treatment with A. indica produced, A. occidentale, M. indica and A. boonei reduced HZ-induced increased NLRP3 protein expression. HZ-induced increased caspase-1 activity was also reduced by A. boonei, A. occidentale, A. indica, E. chlorantha, and M. indica. Freeze-dried extracts of A. boonei, A. occidentale, A. indica and M. indica produced neuroprotective effect in HT-22 neuronal cells incubated with HZ by preventing HZ-induced neurotoxicity, ROS generation, DNA fragmentation and caspase 3/7 activity. Inhibition of HZ-induced increase in permeability of human hCMEC/D3 brain endothelial cells was also observed with A. boonei, A. occidentale, A. indica and M. indica, while reducing the release of TNFα and MMP-9. Conclusions: These results suggest that A. boonei, A. occidentale, A. indica and M. indica are neuroprotective through inhibition of neuroinflammation, neuronal damage and increased permeability of blood brain barrier. The outcome of the study provides pharmacological evidence for the potential benefits of plants as herbal treatments for cerebral malaria symptoms.
MeSH term(s)	Humans ; Azadirachta ; Tumor Necrosis Factor-alpha ; Anacardium ; Alstonia ; Mangifera ; Malaria, Cerebral/drug therapy ; Neuroinflammatory Diseases ; Neuroprotection ; Endothelial Cells ; Reactive Oxygen Species ; Plant Extracts/pharmacology ; Plant Extracts/therapeutic use
Chemical Substances	Tumor Necrosis Factor-alpha ; Reactive Oxygen Species ; Plant Extracts
Language	English
Publishing date	2023-03-24
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2023.116390
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Zs.A 1494: Show issues

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Article ; Online: Alzheimer's disease: natural products as inhibitors of neuroinflammation.

Olajide, Olumayokun A / Sarker, Satyajit D

Inflammopharmacology

2020 Volume 28, Issue 6, Page(s) 1439–1455

Abstract: Alzheimer's disease (AD) is the most common form of dementia and affects 44 million people worldwide. New emerging evidence from pre-clinical and clinical investigations shows that neuroinflammation is a major pathological component of AD suggesting that ...

Abstract	Alzheimer's disease (AD) is the most common form of dementia and affects 44 million people worldwide. New emerging evidence from pre-clinical and clinical investigations shows that neuroinflammation is a major pathological component of AD suggesting that anti-inflammatory strategies are important in delaying the onset or slowing the progression of the disease. However, efforts to employ current anti-inflammatory agents in AD clinical trials have produced limited success. Consequently, there is a need to explore anti-inflammatory natural products, which target neuroinflammatory pathways relevant to AD pathogenesis. This review summarises important druggable molecular targets of neuroinflammation and presents classes of anti-neuroinflammatory natural products with potentials for preventing and reducing symptoms of AD.
MeSH term(s)	Alzheimer Disease/drug therapy ; Animals ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Biological Products/pharmacology ; Biological Products/therapeutic use ; Disease Progression ; Humans ; Inflammation/drug therapy ; Neurons/drug effects ; Signal Transduction/drug effects
Chemical Substances	Anti-Inflammatory Agents ; Biological Products
Language	English
Publishing date	2020-09-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1080058-x
ISSN	1568-5608 ; 0925-4692
ISSN (online)	1568-5608
ISSN	0925-4692
DOI	10.1007/s10787-020-00751-1
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Article ; Online: Neuroprotection by Skimmianine in Lipopolysaccharide-Activated BV-2 Microglia

Folashade A. Ogunrinade / Victoria U. Iwuanyanwu / Satyajit D. Sarker / Olumayokun A. Olajide

Molecules, Vol 28, Iss 1317, p

2023 Volume 1317

Abstract: Skimmianine is a furoquinoline alkaloid which is found in the Zanthoxylum genus and also in other plants of the Rutaceae family. This study evaluated the effects of skimmianine on the production of pro-inflammatory mediators in LPS-activated BV-2 ... ...

Abstract	Skimmianine is a furoquinoline alkaloid which is found in the Zanthoxylum genus and also in other plants of the Rutaceae family. This study evaluated the effects of skimmianine on the production of pro-inflammatory mediators in LPS-activated BV-2 microglia. Cultured BV-2 cells were treated with skimmianine (10, 20 and 30 μM), followed by stimulation with LPS (100 ng/mL). Levels of TNFα and IL-6 in cell supernatants were measured using ELISA, while NO and PGE 2 levels were evaluated with Griess assay and EIA, respectively. Western blotting was used to determine the protein expression of iNOS, COX-2, phospho-p65 and phospho-IκBα. Results showed that Skimmianine reduced LPS-induced elevated the secretion of TNFα, IL-6, NO, and PGE 2 , as well as the increased protein expression of iNOS and COX-2. Experiments to elucidate the mechanisms of the anti-neuroinflammatory activity of skimmianine revealed the significant inhibition of LPS-induced increased NF-κB-mediated luciferase activity. Pre-treatment with skimmianine also reduced LPS-induced the increased phosphorylation of NF-κB/p65 and IκBα proteins. Furthermore, skimmianine interfered with the binding capacity of NF-κB to consensus sites. Skimmianine pre-treatment protected HT-22 cells from toxicity induced by microglia-conditioned media, as well as increasing MAP-2 expression. The results of this study suggest that skimmianine inhibits neuroinflammation in LPS-activated microglia by targeting the NF-κB activation pathway. Skimmianine also produced neuroprotection against neurotoxicity induced by microglia-conditioned media.
Keywords	natural products ; skimmianine ; neuroinflammation ; neuroprotection ; microglia ; neurons ; Organic chemistry ; QD241-441
Subject code	630
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Chemical characterisation of sulfated polysaccharides from the red seaweed Centroceras clavulatum and their in vitro immunostimulatory and antioxidant properties

Aluta, Uzeme P. / Aderolu, Ademola Z. / Ishola, Ismail O. / Alyassin, Mohammad / Morris, Gordon A. / Olajide, Olumayokun A.

Food Hydrocolloids for Health. 2023 Dec., v. 3 p.100135-

2023

Abstract: Phycocolloids have aroused research interest due to their remarkable functional properties, including immunostimulatory and antioxidant activities. In this study, the yield of Centroceras clavulatum sulfated polysaccharides (CCSP) was 4.36% and had a ... ...

Abstract	Phycocolloids have aroused research interest due to their remarkable functional properties, including immunostimulatory and antioxidant activities. In this study, the yield of Centroceras clavulatum sulfated polysaccharides (CCSP) was 4.36% and had a sulfate content of 9.42%. The main monosaccharide units of CCSP were galactose (25.23 ± 0.81 mg/l) and glucose (4.32 ± 0.31 mg/l). Specifically, FT-IR spectrum of CCSP revealed a peak at 843 cm⁻¹ which indicates the occurrence of sulfate groups on C-4 of galactose. CCSP stimulated Carp Leukocyte Culture (CLC) cell line to generate reactive oxygen species (ROS) and nitric oxide (NO) in a dose-dependent manner. Remarkably, exposure of CLC cells to CCSP at a dose of 12.5 µg/ml significantly increased superoxide dismutase activity and reduced malondialdehyde level. These results suggest that CCSP could stimulate CLC cells without compromising the intracellular antioxidant system, hence, may have potential applications as nutraceuticals.
Keywords	Centroceras ; cell lines ; dietary supplements ; dose response ; galactose ; glucose ; hydrocolloids ; immunostimulants ; leukocytes ; malondialdehyde ; nitric oxide ; polysaccharides ; reactive oxygen species ; sulfates ; superoxide dismutase ; Centroceras clavulatum ; Sulfated polysaccharides ; Carp leukocyte culture ; Reactive intermediates ; Antioxidant activity
Language	English
Dates of publication	2023-12
Publishing place	Elsevier B.V.
Document type	Article ; Online
Note	Use and reproduction
ISSN	2667-0259
DOI	10.1016/j.fhfh.2023.100135
Database	NAL-Catalogue (AGRICOLA)

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Article: New cytotoxic compounds from the leaves of

Famojuro, Tayo I / Elufioye, Taiwo O / Olajide, Olumayokun A / Dybek, Michael / Adejare, Adeboye

Avicenna journal of phytomedicine

2021 Volume 11, Issue 1, Page(s) 54–67

Abstract: Objective: The incidence of multi-drug resistant cancer and the adverse effects associated with available chemotherapy have necessitated the search for new drug candidates. This study investigates the cytotoxic activity of : Materials and methods: ... ...

Abstract	Objective: The incidence of multi-drug resistant cancer and the adverse effects associated with available chemotherapy have necessitated the search for new drug candidates. This study investigates the cytotoxic activity of Materials and methods: Column chromatography (CC) and preparative thin layer chromatography (PTLC) were used to isolate compounds. Structural elucidation was done by spectroscopic analysis. MTT assay was used to evaluate cytotoxicity of the compounds against three human adenocarcinoma cells, using methotrexate and dimethyl sulfoxide (DMSO) as positive and negative controls, respectively. CyQuant direct cell proliferation and caspase-3/7 green detection assays were used to investigate the dichloromethane fraction. IC Results: Four new cytotoxic compounds, benthamianoate (2), benthamiacone (3), benthamianin (5) and benthamianol (6), and two known compounds, methyl gallate (1) and 2-methoxyacrylic acid (4) were identified. All the compounds were active with the new monoterpenoid characterized as benthamiacone exhibiting the highest activity (IC Conclusion: This study revealed potential cytotoxic compounds which are here reported for the first time from
Language	English
Publishing date	2021-02-08
Publishing country	Iran
Document type	Journal Article
ZDB-ID	2658672-1
ISSN	2228-7949 ; 2228-7930
ISSN (online)	2228-7949
ISSN	2228-7930
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Article ; Online: Iminosugar Amino Acid idoBR1 Reduces Inflammatory Responses in Microglia.

Olajide, Olumayokun A / Iwuanyanwu, Victoria U / Banjo, Owolabi W / Kato, Atsushi / Penkova, Yana B / Fleet, George W J / Nash, Robert J

Molecules (Basel, Switzerland)

2022 Volume 27, Issue 10

Abstract: 1) Background. Inflammation is reported to be a key factor in neurodegeneration. The microglia are immune cells present in the central nervous system; their activation results in the release of inflammatory cytokines and is thought to be related to ... ...

Abstract	(1) Background. Inflammation is reported to be a key factor in neurodegeneration. The microglia are immune cells present in the central nervous system; their activation results in the release of inflammatory cytokines and is thought to be related to aging and neurodegenerative disorders, such as Alzheimer's disease. (2) Methods. A mouse BV-2 microglia cell line was activated using LPS and the anti-inflammatory cucumber-derived iminosugar amino acid idoBR1, (2
MeSH term(s)	Amino Acids/metabolism ; Animals ; Anti-Inflammatory Agents/metabolism ; Anti-Inflammatory Agents/pharmacology ; Lipopolysaccharides ; Mice ; Microglia ; Nitric Oxide Synthase Type II/metabolism
Chemical Substances	Amino Acids ; Anti-Inflammatory Agents ; Lipopolysaccharides ; Nitric Oxide Synthase Type II (EC 1.14.13.39)
Language	English
Publishing date	2022-05-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules27103342
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Zs.MO 81: Show issues

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Article ; Online: Synthesis of novel isoflavone/benzo-δ-sultam hybrids as potential anti-inflammatory drugs.

Mengheres, Gabriel / Rice, Craig R / Olajide, Olumayokun A / Hemming, Karl

Bioorganic & medicinal chemistry letters

2020 Volume 34, Page(s) 127761

Abstract: A small series of novel isoflavone/benzo-δ-sultam hybrids was synthesised and evaluated as potential anti-inflammatory and neuroprotective drugs in LPS-activated BV2 microglia. The benzo-δ-sultam core was constructed in a two-step reaction by coupling 2- ... ...

Abstract	A small series of novel isoflavone/benzo-δ-sultam hybrids was synthesised and evaluated as potential anti-inflammatory and neuroprotective drugs in LPS-activated BV2 microglia. The benzo-δ-sultam core was constructed in a two-step reaction by coupling 2-halobenzenesulfonamide derivatives with terminal alkynes, followed by a 6-endo-dig cyclisation. The synthesised compounds, including precursors and hybrids, were tested for their ability to inhibit NO and TNF-α production in LPS-stimulated BV2 microglial cells, and the results are promising. The most potent hybrid reduces the NO production to 41%, and the TNF-α to 34% at 20 µM final concentration in the well.
MeSH term(s)	Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis ; Anti-Inflammatory Agents, Non-Steroidal/chemistry ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Cell Line ; Dose-Response Relationship, Drug ; Isoflavones/chemistry ; Isoflavones/pharmacology ; Lipopolysaccharides/antagonists & inhibitors ; Lipopolysaccharides/pharmacology ; Mice ; Microglia/drug effects ; Microglia/metabolism ; Molecular Structure ; Nitric Oxide/antagonists & inhibitors ; Nitric Oxide/biosynthesis ; Structure-Activity Relationship ; Sulfonamides/chemistry ; Sulfonamides/pharmacology ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Tumor Necrosis Factor-alpha/biosynthesis
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Isoflavones ; Lipopolysaccharides ; Sulfonamides ; Tumor Necrosis Factor-alpha ; beta-sultam ; Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2020-12-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1063195-1
ISSN	1464-3405 ; 0960-894X
ISSN (online)	1464-3405
ISSN	0960-894X
DOI	10.1016/j.bmcl.2020.127761
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Zs.A 3203: Show issues

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Article ; Online: Induction of Neuroinflammation and Neurotoxicity by Synthetic Hemozoin.

Velagapudi, Ravikanth / Kosoko, Ayokulehin M / Olajide, Olumayokun A

Cellular and molecular neurobiology

2019 Volume 39, Issue 8, Page(s) 1187–1200

Abstract: Hemozoin produced by Plasmodium falciparum during malaria infection has been linked to the neurological dysfunction in cerebral malaria. In this study, we determined whether a synthetic form of hemozoin (sHZ) produces neuroinflammation and neurotoxicity ... ...

Abstract	Hemozoin produced by Plasmodium falciparum during malaria infection has been linked to the neurological dysfunction in cerebral malaria. In this study, we determined whether a synthetic form of hemozoin (sHZ) produces neuroinflammation and neurotoxicity in cellular models. Incubation of BV-2 microglia with sHZ (200 and 400 µg/ml) induced significant elevation in the levels of TNFα, IL-6, IL-1β, NO/iNOS, phospho-p65, accompanied by an increase in DNA binding of NF-κB. Treatment of BV-2 microglia with sHZ increased protein levels of NLRP3 with accompanying increase in caspase-1 activity. In the presence of NF-κB inhibitor BAY11-7082 (10 µM), there was attenuation of sHZ-induced release of pro-inflammatory cytokines, NO/iNOS. In addition, increase in caspase-1/NLRP3 inflammasome activation was blocked by BAY11-7082. Pre-treatment with BAY11-7082 also reduced both phosphorylation and DNA binding of the p65 sub-unit. The NLRP3 inhibitor CRID3 (100 µM) did not prevent sHZ-induced release of TNFα and IL-6. However, production of IL-1β, NO/iNOS as well as caspase-1/NLRP3 activity was significantly reduced in the presence of CRID3. Incubation of differentiated neural progenitor (ReNcell VM) cells with sHZ resulted in a reduction in cell viability, accompanied by significant generation of cellular ROS and increased activity of caspase-6, while sHZ-induced neurotoxicity was prevented by N-acetylcysteine and Z-VEID-FMK. Taken together, this study shows that the synthetic form of hemozoin induces neuroinflammation through the activation of NF-κB and NLRP3 inflammasome. It is also proposed that sHZ induces ROS- and caspase-6-mediated neurotoxicity. These results have thrown more light on the actions of malarial hemozoin in the neurobiology of cerebral malaria.
MeSH term(s)	Animals ; Caspase 1/metabolism ; Caspase 6/metabolism ; Cell Differentiation ; Cell Line ; Cell Survival/drug effects ; Cytokines/biosynthesis ; DNA/metabolism ; Hemeproteins/toxicity ; Humans ; Inflammation/pathology ; Inflammation Mediators/metabolism ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Neurons/drug effects ; Neurons/metabolism ; Neurotoxicity Syndromes/pathology ; Nitric Oxide Synthase Type II/metabolism ; Nitriles/pharmacology ; Nitrites/metabolism ; Protein Binding/drug effects ; Reactive Oxygen Species/metabolism ; Sulfones/pharmacology ; Transcription Factor RelA/metabolism
Chemical Substances	3-(4-methylphenylsulfonyl)-2-propenenitrile ; Cytokines ; Hemeproteins ; Inflammation Mediators ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nitriles ; Nitrites ; Reactive Oxygen Species ; Sulfones ; Transcription Factor RelA ; hemozoin (39404-00-7) ; DNA (9007-49-2) ; Nitric Oxide Synthase Type II (EC 1.14.13.39) ; Caspase 6 (EC 3.4.22.-) ; Caspase 1 (EC 3.4.22.36)
Language	English
Publishing date	2019-07-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	283404-2
ISSN	1573-6830 ; 0272-4340
ISSN (online)	1573-6830
ISSN	0272-4340
DOI	10.1007/s10571-019-00713-4
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