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Article ; Online: Neuroprotective Effects of Curcumin in Cerebral Ischemia: Cellular and Molecular Mechanisms.

Subedi, Lalita / Gaire, Bhakta Prasad

ACS chemical neuroscience

2021 Volume 12, Issue 14, Page(s) 2562–2572

Abstract: Despite being a major global health concern, cerebral ischemia/stroke has limited therapeutic options. Tissue plasminogen activator (tPA) is the only available medication to manage acute ischemic stroke, but this medication is associated with adverse ... ...

Abstract	Despite being a major global health concern, cerebral ischemia/stroke has limited therapeutic options. Tissue plasminogen activator (tPA) is the only available medication to manage acute ischemic stroke, but this medication is associated with adverse effects and has a narrow therapeutic time window. Curcumin, a polyphenol that is abundantly present in the rhizome of the turmeric plant (
MeSH term(s)	Animals ; Brain Ischemia/drug therapy ; Curcumin/pharmacology ; Neuroprotective Agents/pharmacology ; Stroke/drug therapy ; Tissue Plasminogen Activator
Chemical Substances	Neuroprotective Agents ; Tissue Plasminogen Activator (EC 3.4.21.68) ; Curcumin (IT942ZTH98)
Language	English
Publishing date	2021-07-12
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/acschemneuro.1c00153
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Article ; Online: Terpenoids from

Subedi, Lalita / Yumnam, Silvia

International journal of molecular sciences

2021 Volume 22, Issue 2

Abstract: We have previously reported that phytochemicals ... ...

Abstract	We have previously reported that phytochemicals from
MeSH term(s)	Abies/chemistry ; Animals ; Anti-Inflammatory Agents/isolation & purification ; Anti-Inflammatory Agents/pharmacology ; Cells, Cultured ; Down-Regulation/drug effects ; Inflammation/chemically induced ; Inflammation/metabolism ; Inflammation/prevention & control ; Inflammation Mediators/metabolism ; JNK Mitogen-Activated Protein Kinases/metabolism ; Lipopolysaccharides ; MAP Kinase Signaling System/drug effects ; Mice ; Microglia/drug effects ; Microglia/physiology ; Neuritis/chemically induced ; Neuritis/metabolism ; Neuritis/prevention & control ; Neuroimmunomodulation/drug effects ; Neuroprotective Agents/isolation & purification ; Neuroprotective Agents/pharmacology ; Plant Extracts/pharmacology ; Terpenes/isolation & purification ; Terpenes/pharmacology ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Anti-Inflammatory Agents ; Inflammation Mediators ; Lipopolysaccharides ; Neuroprotective Agents ; Plant Extracts ; Terpenes ; Tumor Necrosis Factor-alpha ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2021-01-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22020965
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Article ; Online: Phytochemicals as regulators of microglia/macrophages activation in cerebral ischemia.

Subedi, Lalita / Gaire, Bhakta Prasad

Pharmacological research

2021 Volume 165, Page(s) 105419

Abstract: The search for novel therapeutic agents for the management of cerebral ischemia/stroke has become an appealing research interest in the recent past. Neuroprotective phytochemicals as novel stroke drug candidates have recently drawn significant interests ... ...

Abstract	The search for novel therapeutic agents for the management of cerebral ischemia/stroke has become an appealing research interest in the recent past. Neuroprotective phytochemicals as novel stroke drug candidates have recently drawn significant interests from stroke scientists due to their strong brain protective effects in animal stroke models. The underlying mechanism of action is likely owing to their anti-inflammatory properties, even though other mechanisms such as anti-oxidation and vasculoprotection have also been proposed. It is generally held that the early proinflammatory responses after stroke can lead to a secondary brain injury, mainly due to the damaging effect exerted by over-activation of brain resident microglial cells and infiltration of circulating monocytes and macrophages. This review focuses on the anti-inflammatory properties of bioactive phytochemicals, including activation and polarization of microglia/macrophages in the post-ischemic brain. The latest studies in animal stroke models demonstrate that this group of bioactive phytochemicals exerts their anti-inflammatory effects via attenuation of brain proinflammatory microglia and macrophages M1 polarization while promoting anti-inflammatory microglial and macrophages M2 polarization. As a result, stroked animals treated with brain protective phytochemicals have significantly fewer brain active M1 microglia and macrophages, smaller brain infarct volume, better functional recovery, and better survival rate. Therefore, this review provides insights into a new category of drug candidates for stroke drug development by employing neuroprotective phytochemicals.
MeSH term(s)	Animals ; Brain Ischemia/drug therapy ; Humans ; Macrophage Activation/drug effects ; Macrophages/drug effects ; Microglia/drug effects ; Neuroinflammatory Diseases/drug therapy ; Neuroprotective Agents/therapeutic use ; Phytochemicals/therapeutic use
Chemical Substances	Neuroprotective Agents ; Phytochemicals
Language	English
Publishing date	2021-01-12
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2021.105419
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Article ; Online: Tanshinone IIA: A phytochemical as a promising drug candidate for neurodegenerative diseases.

Subedi, Lalita / Gaire, Bhakta Prasad

Pharmacological research

2021 Volume 169, Page(s) 105661

Abstract: Tanshinones, lipophilic diterpenes isolated from the rhizome of Salvia miltiorrhiza, have diverse pharmacological activities against human ailments including neurological diseases. In fact, tanshinones have been used to treat heart diseases, stroke, and ... ...

Abstract	Tanshinones, lipophilic diterpenes isolated from the rhizome of Salvia miltiorrhiza, have diverse pharmacological activities against human ailments including neurological diseases. In fact, tanshinones have been used to treat heart diseases, stroke, and vascular diseases in traditional Chinese medicine. During the last decade, tanshinones have been the most widely studied phytochemicals for their neuroprotective effects against experimental models of cerebral ischemia and Alzheimer's diseases. Importantly, tanshinone IIA, mostly studied tanshinone for biological activities, is recently reported to attenuate blood-brain barrier permeability among stroke patients, suggesting tanshinone IIA as an appealing therapeutic candidate for neurological diseases. Tanshinone I and IIA are also effective in experimental models of Parkinson's disease, Multiple sclerosis, and other neuroinflammatory diseases. In addition, several experimental studies suggested the pleiotropic neuroprotective effects of tanshinones such as anti-inflammatory, antioxidant, anti-apoptotic, and BBB protectant further value aiding to tanshinone as an appealing therapeutic strategy in neurological diseases. Therefore, in this review, we aimed to compile the recent updates and cellular and molecular mechanisms of neuroprotection of tanshinone IIA in diverse neurological diseases.
MeSH term(s)	Abietanes/therapeutic use ; Alzheimer Disease/drug therapy ; Animals ; Brain Ischemia/drug therapy ; Humans ; Multiple Sclerosis/drug therapy ; Neurodegenerative Diseases/drug therapy ; Neuroprotective Agents/therapeutic use ; Parkinson Disease/drug therapy
Chemical Substances	Abietanes ; Neuroprotective Agents ; tanshinone (03UUH3J385)
Language	English
Publishing date	2021-05-07
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2021.105661
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Article ; Online: Glyoxalase System in the Progression of Skin Aging and Skin Malignancies.

Yumnam, Silvia / Subedi, Lalita / Kim, Sun Yeou

International journal of molecular sciences

2020 Volume 22, Issue 1

Abstract: Dicarbonyl compounds, including methylglyoxal (MGO) and glyoxal (GO), are mainly formed as byproducts of glucose metabolism. The main glyoxalase system consists of glyoxalase I and II (Glo1 and Glo2) and is the main enzyme involved in the detoxification ... ...

Abstract	Dicarbonyl compounds, including methylglyoxal (MGO) and glyoxal (GO), are mainly formed as byproducts of glucose metabolism. The main glyoxalase system consists of glyoxalase I and II (Glo1 and Glo2) and is the main enzyme involved in the detoxification of dicarbonyl stress, which occurs as an accumulation of MGO or GO due to decreased activity or expression of Glo1. Dicarbonyl stress is a major cause of cellular and tissue dysfunction that causes various health issues, including diabetes, aging, and cancer. The skin is the largest organ in the body. In this review, we discuss the role of the glyoxalase system in the progression of skin aging, and more importantly, skin malignancies. We also discuss the future prospects of the glyoxalase system in other skin abnormalities such as psoriasis and vitiligo, including hyperpigmentation. Finally, in the present review, we suggest the role of glyoxalase in the progression of skin aging and glyoxalase system as a potential target for anticancer drug development for skin cancer.
MeSH term(s)	Animals ; Disease Susceptibility ; Gene Expression Regulation ; Genetic Predisposition to Disease ; Glyoxal/metabolism ; Humans ; Lactoylglutathione Lyase/genetics ; Lactoylglutathione Lyase/metabolism ; Pyruvaldehyde/metabolism ; Skin Aging/genetics ; Skin Neoplasms/etiology ; Skin Neoplasms/metabolism ; Skin Neoplasms/pathology ; Thiolester Hydrolases/genetics ; Thiolester Hydrolases/metabolism ; Wound Healing/genetics
Chemical Substances	Glyoxal (50NP6JJ975) ; Pyruvaldehyde (722KLD7415) ; Thiolester Hydrolases (EC 3.1.2.-) ; hydroxyacylglutathione hydrolase (EC 3.1.2.6) ; Lactoylglutathione Lyase (EC 4.4.1.5)
Language	English
Publishing date	2020-12-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22010310
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Article ; Online: Effect of Cysteine on Methylglyoxal-Induced Renal Damage in Mesangial Cells.

Lee, Jae Hyuk / Subedi, Lalita / Kim, Sun Yeou

Cells

2020 Volume 9, Issue 1

Abstract: Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is a key precursor of the formation of advanced glycation end products (AGEs). MGO and MGO-AGEs were reportedly increased in patients with diabetic dysfunction, including diabetic nephropathy. ... ...

Abstract	Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is a key precursor of the formation of advanced glycation end products (AGEs). MGO and MGO-AGEs were reportedly increased in patients with diabetic dysfunction, including diabetic nephropathy. The activation of glyoxalase-I (GLO-I) increases MGO and MGO-AGE detoxification. MGO-mediated glucotoxicity can also be ameliorated by MGO scavengers such as
MeSH term(s)	Acetylcysteine/chemistry ; Acetylcysteine/metabolism ; Acetylcysteine/pharmacology ; Animals ; Apoptosis/drug effects ; Apoptosis/genetics ; Cell Line ; Cell Survival/drug effects ; Cysteine/chemistry ; Cysteine/metabolism ; Cysteine/pharmacology ; Guanidines/pharmacology ; Humans ; L-Lactate Dehydrogenase/metabolism ; Lactic Acid/metabolism ; Lactoylglutathione Lyase/metabolism ; MAP Kinase Signaling System/drug effects ; MAP Kinase Signaling System/genetics ; Mesangial Cells/cytology ; Mesangial Cells/drug effects ; Mice ; Pyruvaldehyde/metabolism ; Pyruvaldehyde/toxicity ; Reactive Oxygen Species/metabolism ; Sirtuin 1/metabolism
Chemical Substances	Guanidines ; Reactive Oxygen Species ; Lactic Acid (33X04XA5AT) ; Pyruvaldehyde (722KLD7415) ; L-Lactate Dehydrogenase (EC 1.1.1.27) ; SIRT1 protein, human (EC 3.5.1.-) ; Sirtuin 1 (EC 3.5.1.-) ; GLO1 protein, human (EC 4.4.1.5) ; Lactoylglutathione Lyase (EC 4.4.1.5) ; Cysteine (K848JZ4886) ; pimagedine (SCQ4EZQ113) ; Acetylcysteine (WYQ7N0BPYC)
Language	English
Publishing date	2020-01-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells9010234
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Article ; Online: Nitric Oxide as a Target for Phytochemicals in Anti-Neuroinflammatory Prevention Therapy.

Subedi, Lalita / Gaire, Bhakta Prasad / Parveen, Amna / Kim, Sun-Yeou

International journal of molecular sciences

2021 Volume 22, Issue 9

Abstract: Nitric oxide (NO) is a neurotransmitter that mediates the activation and inhibition of inflammatory cascades. Even though physiological NO is required for defense against various pathogens, excessive NO can trigger inflammatory signaling and cell death ... ...

Abstract	Nitric oxide (NO) is a neurotransmitter that mediates the activation and inhibition of inflammatory cascades. Even though physiological NO is required for defense against various pathogens, excessive NO can trigger inflammatory signaling and cell death through reactive nitrogen species-induced oxidative stress. Excessive NO production by activated microglial cells is specifically associated with neuroinflammatory and neurodegenerative conditions, such as Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, ischemia, hypoxia, multiple sclerosis, and other afflictions of the central nervous system (CNS). Therefore, controlling excessive NO production is a desirable therapeutic strategy for managing various neuroinflammatory disorders. Recently, phytochemicals have attracted considerable attention because of their potential to counteract excessive NO production in CNS disorders. Moreover, phytochemicals and nutraceuticals are typically safe and effective. In this review, we discuss the mechanisms of NO production and its involvement in various neurological disorders, and we revisit a number of recently identified phytochemicals which may act as NO inhibitors. This review may help identify novel potent anti-inflammatory agents that can downregulate NO, specifically during neuroinflammation and neurodegeneration.
MeSH term(s)	Animals ; Anti-Inflammatory Agents/chemistry ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Drug Discovery ; Humans ; Inflammation/drug therapy ; Inflammation/metabolism ; Molecular Targeted Therapy ; Neurodegenerative Diseases/drug therapy ; Neurodegenerative Diseases/metabolism ; Neuroprotective Agents/chemistry ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Nitric Oxide/antagonists & inhibitors ; Nitric Oxide/metabolism ; Oxidative Stress/drug effects ; Phytochemicals/chemistry ; Phytochemicals/pharmacology ; Phytochemicals/therapeutic use ; Reactive Nitrogen Species/metabolism
Chemical Substances	Anti-Inflammatory Agents ; Neuroprotective Agents ; Phytochemicals ; Reactive Nitrogen Species ; Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2021-04-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22094771
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Article ; Online: Moringa oleifera

Ghimire, Saurav / Subedi, Lalita / Acharya, Namrata / Gaire, Bhakta Prasad

Journal of agricultural and food chemistry

2021 Volume 69, Issue 48, Page(s) 14358–14371

Abstract: ... Moringa ... ...

Abstract	Moringa oleifera
MeSH term(s)	Humans ; Moringa oleifera ; Neurodegenerative Diseases/drug therapy ; Plant Extracts ; Plant Leaves ; Plants, Medicinal
Chemical Substances	Plant Extracts
Language	English
Publishing date	2021-11-29
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	241619-0
ISSN	1520-5118 ; 0021-8561
ISSN (online)	1520-5118
ISSN	0021-8561
DOI	10.1021/acs.jafc.1c04581
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Zs.A 1172: Show issues

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Article: Moringa oleifera: A Tree of Life as a Promising Medicinal Plant for Neurodegenerative Diseases

Ghimire, Saurav / Subedi, Lalita / Acharya, Namrata / Gaire, Bhakta Prasad

Journal of agricultural and food chemistry. 2021 Nov. 29, v. 69, no. 48

2021

Abstract: Moringa oleifera, popularly known as a miracle tree or tree of life, has been extensively used as a functional food and nutritional asset worldwide. Ethnomedicinal and traditional uses of M. oleifera indicate that this plant might have a pleiotropic ... ...

Abstract	Moringa oleifera, popularly known as a miracle tree or tree of life, has been extensively used as a functional food and nutritional asset worldwide. Ethnomedicinal and traditional uses of M. oleifera indicate that this plant might have a pleiotropic therapeutic efficacy against most human ailments. In fact, M. oleifera is reported to have several pharmacological activities, including antioxidant, antibacterial, antifungal, antidiabetic, antipyretic, antiulcer, antispasmodic, antihypertensive, antitumor, hepatoprotective, and cardiac stimulant properties. Recently, a few experimental studies reported the neuroprotective effects of M. oleifera against Alzheimer’s disease, dementia, Parkinson’s disease, stroke, and neurotoxicity-related symptoms. In addition, several neuroprotective phytochemicals have been isolated from M. oleifera, which signifies that it can have promising neuroprotective effects. Therefore, this review aimed to explore the current updates and future prospective of neuroprotective efficacies of M. oleifera.
Keywords	Moringa oleifera ; antioxidants ; cardioprotective agents ; food chemistry ; functional foods ; humans ; medicinal plants ; parasympatholytics ; phytochemicals ; stroke ; therapeutics ; trees
Language	English
Dates of publication	2021-1129
Size	p. 14358-14371.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	241619-0
ISSN	1520-5118 ; 0021-8561
ISSN (online)	1520-5118
ISSN	0021-8561
DOI	10.1021/acs.jafc.1c04581
Database	NAL-Catalogue (AGRICOLA)

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Z 1185: Show issues

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Article: Sulforaphane Inhibits MGO-AGE-Mediated Neuroinflammation by Suppressing NF-κB, MAPK, and AGE-RAGE Signaling Pathways in Microglial Cells.

Subedi, Lalita / Lee, Jae Hyuk / Gaire, Bhakta Prasad / Kim, Sun Yeou

Antioxidants (Basel, Switzerland)

2020 Volume 9, Issue 9

Abstract: Advanced glycation end products (AGEs) are produced through the binding of glycated protein or lipid with sugar, and they are known to be involved in the pathogenesis of both age-dependent and independent neurological complications. Among dicarbonyl ... ...

Abstract	Advanced glycation end products (AGEs) are produced through the binding of glycated protein or lipid with sugar, and they are known to be involved in the pathogenesis of both age-dependent and independent neurological complications. Among dicarbonyl compounds, methylglyoxal (MGO), which is produced from glucose breakdown, is a key precursor of AGE formation and neurotoxicity. Several studies have shown the toxic effects of bovine serum albumin (BSA)-AGE (prepared with glucose, sucrose or fructose) both in in vitro and in vivo. In fact, MGO-derived AGEs (MGO-AGEs) are highly toxic to neurons and other cells of the central nervous system. Therefore, we aimed to investigate the role of MGO-AGEs in microglial activation, a key inflammatory event, or secondary brain damage in neuroinflammatory diseases. Interestingly, we found that sulforaphane (SFN) as a potential candidate to downregulate neuroinflammation induced by MGO-AGEs in BV2 microglial cells. SFN not only inhibited the formation of MGO-AGEs, but it did not show breaking activity on the MGO-mediated AGEs cross-links with protein, indicating that SFN could potentially trap MGO or inhibit toxic AGE damage. In addition, SFN significantly attenuated the production of neuroinflammatory mediators induced by MGO-AGEs in BV2 microglial cells. SFN also lowered the expression levels of AGE receptor (RAGE) in microglial cells, suggesting that SFN could downregulate MGO-AGE-mediated neurotoxicity at the receptor activation level. Altogether, our current study revealed that SFN might show neuropharmacological potential for downregulating MGO-AGEs-mediated neuronal complications thorough attenuating AGE formation and neuroinflammatory responses induced by MGO-AGEs in vitro.
Language	English
Publishing date	2020-08-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox9090792
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