Unveiling the anti-inflammatory activity of Sutherlandia frutescens using murine macrophages

W, Lei; Browning, Jimmy D.; Eichen, P. A.; Brownstein, Korey J.; Folk, William R.; Sun, Grace Y.; Lubahn, Dennis B.; Rottinghaus, George E.; Fritsche, Kevin L.

doi:10.1016/j.intimp.2015.11.012

Cited by 16 publications

(17 citation statements)

References 39 publications

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“…Our previous studies with microglial cells showed that ethanol extracts of Sutherlandia suppressed LPS- and IFNγ-induced ROS and NO production by inhibition of the JAK/STAT and ERK1/2 signaling pathways (Jiang et al, 2014). Similar anti-inflammatory activity was reported in murine macrophages, but did not appear to be mediated by sutherlandiosides or sutherlandins, which are glycosylated derivatives (Lei et al, 2015a). Moreover, our recent in vivo studies demonstrated that dietary Sutherlandia mitigates cerebral ischemia-induced neuronal damage, in part by attenuating p47phox and phospho-ERK1/2 expression in microglial cells(Chuang et al, 2014).…”

Section: Discussionsupporting

confidence: 68%

Phytochemicals and botanical extracts regulate NF-κB and Nrf2/ARE reporter activities in DI TNC1 astrocytes

Ajit

Simonyi

Zhao

et al. 2016

Neurochemistry International

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The increase in oxidative stress and inflammatory responses associated with neurodegenerative diseases has drawn considerable attention towards understanding the transcriptional signaling pathways involving NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and Nrf2 (Nuclear Factor Erythroid 2-like 2). Our recent studies with immortalized murine microglial cells (BV-2) demonstrated effects of botanical polyphenols to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) and enhance Nrf2-mediated antioxidant responses (Sun et al., 2015). In this study, an immortalized rat astrocyte (DI TNC1) cell line expressing a luciferase reporter driven by the NF-κB or the Nrf2/Antioxidant Response Element (ARE) promoter was used to assess regulation of these two pathways by phytochemiscals such as quercetin, rutin, cyanidin, cyanidin-3-O-glucoside, as well as botanical extracts from Withania somnifera (Ashwagandha), Sutherlandia frutescens (Sutherlandia) and Euterpe oleracea (Açaí). Quercetin effectively inhibited LPS-induced NF-κB reporter activity and stimulated Nrf2/ARE reporter activity in DI TNC1 astrocytes. Cyanidin and the glycosides showed similar effects but only at much higher concentrations. All three botanical extracts effectively inhibited LPS-induced NF-κB reporter activity. These extracts were capable of enhancing ARE activity by themselves and further enhanced ARE activity in the presence of LPS. Quercetin and botanical extracts induced Nrf2 and HO-1 protein expression. Interestingly, Ashwagandha extract was more active in inducing Nrf2 and HO-1 expression in DI TNC1 astrocytes as compared to Sutherlandia and Açaí extracts. In summary, this study demonstrated NF-kB and Nrf2/ARE promotor activities in DI TNC1 astrocytes, and further showed differences in ability for specific botanical polyphenols and extracts to down-regulate LPS-induced NF-kB and up-regulate the NRF2/ARE activities in these cells.

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Section: Discussionsupporting

confidence: 68%

Phytochemicals and botanical extracts regulate NF-κB and Nrf2/ARE reporter activities in DI TNC1 astrocytes

Ajit

Simonyi

Zhao

et al. 2016

Neurochemistry International

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“…Importantly, we observed that treatment with SFE significantly diminished the expression of genes involved in signaling pathways associated with immune responses, such as: NF-κB, MAPK, and JAK-STAT. These findings are in agreement with our previous studies7,8 In this study, our use of RNA-seq provided insights into some of the possible molecular mechanisms through which Sutherlandia modulates macrophage function. For example, the treatment of SFE increased the expression of Nfkbia and Ikbke, which are two inhibitors of the NF-κB pathway.…”

supporting

confidence: 92%

“…The mechanisms for these putative medicinal properties of S. frutescens have not been investigated extensively. We and others have reported that ethanolic and aqueous extracts of this plant possess anti-inflammatory and immuno-stimulatory activities, respectively 6,7 .…”

Section: Introductionmentioning

confidence: 90%

“…was purchased from Big Tree Nutraceutical (Fish Hoek, South Africa) and verified as described previously 10 . The ethanol extract of S. frutescens (SFE) was prepared, and the dry matter concentration was determined as described previously 7 . SFE was dried at 55°C under a vacuum (CentriVap Concentrater, Labconco, Kansas City, MO, USA), and then the dried SFE was re-suspended in DMSO with the final concentration of 84 mg/mL.…”

Section: Preparation Of Ethanol Extract Of S Frutescensmentioning

confidence: 99%

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RNA Sequence Analysis Reveals Expected and Novel Immuno-Modulatory Activities by <em>Sutherlandia frutescens</em>

W¹,

Lu²,

Hou³

et al. 2018

Preprint

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Sutherlandia frutescens (S. frutescens) has been traditionally used as an herbal medicine to ameliorate symptoms associated with cancer, infectious diseases, as well as inflammation. The objective of this investigation was to explore the impact of S. frutescens on the expression of genes in a murine macrophage cell line (i.e., RAW 264.7). We found that treatment with an ethanolic-extract of S. frutescens (SFE) 1 h prior to the stimulation with LPS and IFNγ for 24 h significantly affected the expression of 715 genes in RAW 264.7 cells. When the post-stimulation period was shortened to 8 h, the number of genes that were significantly impacted by SFE diminished to 50. Pathway analysis revealed that inflammatory signaling pathways, such as NF-κB, MAPK, and TNF, as well as signaling pathways associated with immune-related responses, were inhibited by SFE treatment. These findings are consistent with previously reported anti-inflammatory activity of SFE and enable better understanding of the immune-modulating properties of this botanical. To our knowledge, this represents the first report on the impact of S. frutescens on global gene expression in an immune cell population.

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“…Meanwhile, the decrease of the articular diameter caused by the administration of the extracts of A. tequilana can be associated to the presence of active secondary metabolites like β-sitosterol glycoside, 3,7,11,15-tetramethyl-2-hexadecen-1-ol (phytol), octadecadienoic acid 2,3-dihydroxy-propyl ester, stigmasta-3,5-dien-7-one, cycloartenone, cycloartenol and fructans. β-Sitosterol glycoside, phytol, cycloartenone and cycloartenol isolated from Agave tequilana have been reported to present anti-inflammatory and immunomodulatory capacity in different inflammatory studies [ 19 , 20 , 21 , 22 ] and the articular anti-inflammatory effect of the fructans from A. tequilana could be due to the fact fructans participate in the activation of toll-like receptors type 2 and 4 (TLR 2and TLR4) that have also been related to have immunomodulatory and anti-inflammatory capacity which is independent to the prebiotic effect of said molecules [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Effect of Agave tequilana Evaluated on an Autoimmunity Like-SLE Model Induced in Balb/c Mice with Pristane

et al. 2017

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In this work, the immunomodulatory activity of the acetone extract and the fructans obtained from Agave tequilana were evaluated, on the systemic autoimmunity type-SLE model generated by the administration of 2,6,10,14-tetramethylpentadecane (TMPD, also known as pristane) on Balb/c female mice. The systemic autoimmunity type-SLE was observed seven months after the application of TMPD, in which the animals from the negative control group (animals with damage and without any other treatment) developed articular inflammation, proteinuria, an increment of the antinuclear antibody titters and tissue pro-inflammatory cytokines levels (IL-1β, IL-6, TNF-α e IFN-γ) as well as the anti-inflammatory cytokine IL-10. The administration of the different treatments and the extracts of A. tequilana, provoked the decrease of: articular inflammation, the development of proteinuria, ssDNA/dsDNA antinuclear antibody titters and cytokines IL-1β, IL-6, TNF-α, IFN-γ and IL-10. The phytochemical analysis of the acetone extract identified the presence of the following compounds: β-sitosterol glycoside; 3,7,11,15-tetramethyl-2-hexadecen-1-ol (phytol); octadecadienoic acid-2,3-dihydroxypropyl ester; stigmasta-3,5-dien-7-one; cycloartenone and cycloartenol. Therefore, A. tequilana contains active compounds with the capacity to modify the evolution of the systemic autoimmunity type-SLE on a murine model.

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Unveiling the anti-inflammatory activity of Sutherlandia frutescens using murine macrophages

Cited by 16 publications

References 39 publications

Phytochemicals and botanical extracts regulate NF-κB and Nrf2/ARE reporter activities in DI TNC1 astrocytes

Phytochemicals and botanical extracts regulate NF-κB and Nrf2/ARE reporter activities in DI TNC1 astrocytes

RNA Sequence Analysis Reveals Expected and Novel Immuno-Modulatory Activities by <em>Sutherlandia frutescens</em>

Immunomodulatory Effect of Agave tequilana Evaluated on an Autoimmunity Like-SLE Model Induced in Balb/c Mice with Pristane

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Unveiling the anti-inflammatory activity of Sutherlandia frutescens using murine macrophages

Cited by 16 publications

References 39 publications

Phytochemicals and botanical extracts regulate NF-κB and Nrf2/ARE reporter activities in DI TNC1 astrocytes

Phytochemicals and botanical extracts regulate NF-κB and Nrf2/ARE reporter activities in DI TNC1 astrocytes

RNA Sequence Analysis Reveals Expected and Novel Immuno-Modulatory Activities by <em>Sutherlandia&nbsp;frutescens</em>

Immunomodulatory Effect of Agave tequilana Evaluated on an Autoimmunity Like-SLE Model Induced in Balb/c Mice with Pristane

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RNA Sequence Analysis Reveals Expected and Novel Immuno-Modulatory Activities by <em>Sutherlandia frutescens</em>