Atherogenic diet induced lipid accumulation induced NFκB level in heart, liver and brain of Wistar rat and diosgenin as an anti-inflammatory agent

Binesh, Ambika; Devaraj, S. Niranjali; Devaraj, Halagowder

doi:10.1016/j.lfs.2018.01.012

Cited by 49 publications

(24 citation statements)

References 50 publications

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“…Binesh et al have investigated the efficacy of DG in the amelioration of atherosclerotic progression in the heart and inhibition of inflammatory mediators in the liver and brain of Wistar rats treated with an atherogenic diet. DG can inhibit the inflammatory mediators triggered by atherogenic diet in the heart, liver, and brain of rats via the downregulation of COX-2, TNF-α, and NF-κBp65, thereby preventing atherosclerotic disease progression [81]. Yang et al have reported that Compound 3 can rescue endotoxemiainduced neuroinflammation and has a neuroprotective effect on hippocampal neurogenesis impaired by neuroinflammation, which is consistent with the results obtained in the behavior test showing that Compound 3 reversed cognitive impairment.…”

Section: Pharmacological Activity and Mechanism Of Diosgenin And Itssupporting

confidence: 63%

Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances

Cai

Zhang

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Diosgenin (DG), a well-known steroidal sapogenin, is present abundantly in medicinal herbs such as Dioscorea rhizome, Dioscorea villosa, Trigonella foenum-graecum, Smilax China, and Rhizoma polgonati. DG is utilized as a major starting material for the production of steroidal drugs in the pharmaceutical industry. Due to its wide range of pharmacological activities and medicinal properties, it has been used in the treatment of cancers, hyperlipidemia, inflammation, and infections. Numerous studies have reported that DG is useful in the prevention and treatment of neurological diseases. Its therapeutic mechanisms are based on the mediation of different signaling pathways, and targeting these pathways might lead to the development of effective therapeutic agents for neurological diseases. The present review mainly summarizes recent progress using DG and its derivatives as therapeutic agents for multiple neurological disorders along with their various mechanisms in the central nervous system. In particular, those related to therapeutic efficacy for Parkinson’s disease, Alzheimer’s disease, brain injury, neuroinflammation, and ischemia are discussed. This review article also critically evaluates existing limitations associated with the solubility and bioavailability of DG and discusses imperatives for translational clinical research. It briefly recapitulates recent advances in structural modification and novel formulations to increase the therapeutic efficacy and brain levels of DG. In the present review, databases of PubMed, Web of Science, and Scopus were used for studies of DG and its derivatives in the treatment of central nervous system diseases published in English until December 10, 2019. Three independent researchers examined articles for eligibility. A total of 150 articles were screened from the above scientific literature databases. Finally, a total of 46 articles were extracted and included in this review. Keywords related to glioma, ischemia, memory, aging, cognitive impairment, Alzheimer, Parkinson, and neurodegenerative disorders were searched in the databases based on DG and its derivatives.

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Section: Pharmacological Activity and Mechanism Of Diosgenin And Itssupporting

confidence: 63%

Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances

Cai

Zhang

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Cell morphological changes were observed in the ciprofloxacin‐treated cells starting at 48 hours. The morphology of these cells was continuously observed up to 14 days, which showed gradual morphological changes from monocyte to plaque‐like cells on day 12 and foam cells, which are an intermediate stage in atherosclerosis, observed at day 8, which was confirmed with Oil Red O staining …”

Section: Discussionmentioning

confidence: 58%

“…The concentration used in this study was less than the clinically relevant dose. Lipoproteins have been classified by their electrophoretic mobility . In this study, the electrophoretic mobility of oxidized lipoproteins (LDL) showed greater electrophoretic mobility than the native lipoproteins …”

Section: Discussionmentioning

confidence: 97%

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Monocytes treated with ciprofloxacin and oxyLDL express myristate, priming atherosclerosis

Binesh

Sivasitambaram

Devaraj

2020

J Biochem & Molecular Tox

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Antibiotics are essential in many life‐threatening diseases. On the other hand, improper use of antibiotics can be disastrous. Cell morphological changes were observed in the ciprofloxacin‐treated cells starting at 48 hours. Changes in cell morphology were continuously observed up to 14 days, which showed gradual morphological changes from monocyte to plaque‐like cells at day 12, and foam cell, which is an intermediate stage in atherosclerosis was observed at day 8, which was confirmed with Oil Red O staining. Flow cytometry data revealed that oxidized LDL (oxyLDL)‐induced cells showed 60.16% of CD64 (proinflammatory macrophage markers) and no expression of CD23 (anti‐inflammatory macrophage markers), whereas ciprofloxacin‐treated cells expressed 67.97% of CD64 and 13.78% of CD23. Chemokine antibody array analysis revealed that ciprofloxacin exposed cells showed a proinflammatory role (ENA78, Eotaxin1, Eotaxin2, IP‐10, MIG, MIP‐3β, SDF‐1β, TECK, CXCL16, and Fractalkine). Liquid chromatography with tandem mass spectrometry (LC‐MS/MS) revealed that myristic acid was incorporated into a protein with 68 kDa molecular mass in exposing oxyLDL‐induced monocytes with ciprofloxacin, which could be a reason for the observed foam cells and in vitro plaque formation. As myristic acid primes atherosclerosis, it is better to limit the intake of antibiotics like ciprofloxacin for common illness, specifically the high‐risk patients, which may contribute to atherosclerosis.

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“…Group III: Diosgenin‐treated rats. Group IV: Diosgenin control rats . Details of all the experimental groups are provided in the Supporting Information Material.…”

Section: Methodsmentioning

confidence: 99%

Expression of chemokines in macrophage polarization and downregulation of NFκB in aorta allow macrophage polarization by diosgenin in atherosclerosis

Binesh

Devaraj

2019

J Biochem & Molecular Tox

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M1 macrophages serve one edge as proinflammatory and M2 macrophages serve the other edge as an anti-inflammatory macrophage. It appears that a related "switch" in macrophage morphology may also happen in the course of atherosclerosis, which has not yet been elucidated. An atherogenic diet (AD) was given to rats, and induction of macrophage differentiation and the nuclear localization of nuclear factor-kappa B (NFκB) were investigated by Western blot and immunofluorescence. Chemokines were analyzed using an antibody array with 32 target proteins. M2 macrophage transformation was confirmed in diosgenin-treated aorta by immunofluorescence and was validated in vitro using THP-1 cells. MAC387 (macrophage marker) and NFκBp65 (inflammatory hub) were upregulated in oxidatively-modified low-density lipoprotein (OxyLDL) and AD-induced condition. Macrophage differentiation, which induced the formation of inflammatory mediators, was not significantly suppressed by the inhibition of NFκB using dexamethasone. M1 macrophage polarization was identified in OxyLDL-induced monocytes, which are proinflammatory in nature, whereas M2 macrophage polarization was noticed in diosgenin-treated monocytes, which exhibit anti-inflammatory properties. M1-and M2-specific chemokines were analyzed using chemokine antibody array. Furthermore, the expression of proinflammatory macrophage (M1) was noticed in AD-induced aorta and anti-inflammatory macrophage (M2) was observed in diosgenin-treated aorta. This is the first report where, unifying the mechanism of diosgenin as aan nti-atherosclerotic and the expression of M1 and M2 specific chemokines is shown by downregulating NFκB and not by preventing the differentiation of monocyte into a macrophage, but by allowing macrophage to differentiate into M2, which aids in preventing the atherosclerotic progression.

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Atherogenic diet induced lipid accumulation induced NFκB level in heart, liver and brain of Wistar rat and diosgenin as an anti-inflammatory agent

Cited by 49 publications

References 50 publications

Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances

Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances

Monocytes treated with ciprofloxacin and oxyLDL express myristate, priming atherosclerosis

Expression of chemokines in macrophage polarization and downregulation of NFκB in aorta allow macrophage polarization by diosgenin in atherosclerosis

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