Microbial transformation and inhibitory effect assessment of uvaol derivates against LPS and HMGB1 induced NO production in RAW264.7 macrophages

Author(s):  
Xuewa Jiang ◽  
Pingping Shen ◽  
Jing Zhou ◽  
Haixia Ge ◽  
Richa Raj ◽  
...  
2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Chureeporn Imphat ◽  
Pakakrong Thongdeeying ◽  
Arunporn Itharat ◽  
Sumalee Panthong ◽  
Sunita Makchuchit ◽  
...  

Zanthoxylum rhetsa has been consumed in the diet in northern Thailand and also used as a medicament in ancient scripture for arthropathies. Thus, this study aimed to evaluate the activity of various extracts from differential parts of Z. rhetsa via inhibition of inflammatory mediators (NO, TNF-α, and PGE2) in RAW264.7 macrophages. The chemical composition in active extracts was also analyzed by GC/MS. The parts of this plant studied were whole fruits (F), pericarp (P), and seed (O). The methods of extraction included maceration in hexane, 95% ethanol and 50% ethanol, boiling in water, and water distillation. The results demonstrated that the hexane and 95% ethanolic extract from pericarp (PH and P95) and seed essential oil (SO) were the most active extracts. PH and P95 gave the highest inhibition of NO production with IC50 as 11.99 ± 1.66 μg/ml and 15.33 ± 1.05 μg/ml, respectively, and they also showed the highest anti-inflammatory effect on TNF-α with IC50 as 36.08 ± 0.55 μg/ml and 34.90 ± 2.58 μg/ml, respectively. PH and P95 also showed the highest inhibitory effect on PGE2 but less than SO with IC50 as 13.72 ± 0.81 μg/ml, 12.26 ± 0.71 μg/ml, and 8.61 ± 2.23 μg/ml, respectively. 2,3-Pinanediol was the major anti-inflammatory compound analyzed in PH (11.28%) and P95 (19.82%) while terpinen-4-ol constituted a major anti-inflammatory compound in SO at 35.13%. These findings are the first supportive data for ethnomedical use for analgesic and anti-inflammatory activity in acute (SO) and chronic (PH and P95) inflammation.


2016 ◽  
Vol 54 (2) ◽  
pp. 214 ◽  
Author(s):  
Nguyen Manh Cuong ◽  
Pham Ngoc Khanh ◽  
Ho Viet Duc ◽  
Tran Thu Huong ◽  
Youn-Chui Kim ◽  
...  

Phytochemical investigation of the leaves and stems of Callistemon citrinus (Curtis) Skeels led to the isolation of 12 flavonoid and triterpenoid compounds,  including one new flavonoid, callistine A (1) and six known flavonoids 6,7- dimethyl-5,7-dihydroxy-4’-methoxy flavone (2), astragalin (3), quercetin (4), catechin (5), eucalyptin (6), and 8-demethyleucalyptin (7), along with 5 triterpenoids, 3-β-acetylmorolic acid (8), 3β-hydroxy-urs-11-en-13(28)-olide (9), betulinic acid (10), diospyrolide (11) and ursolic acid (12). Their chemical structures were determined from the spectroscopic evidences counting 1D- and 2D-NMR and HR-MS data. All the isolated compounds were examined for their anti-inflammatory activity against LPS-activated NO production in macrophage RAW264.7 cells. Among them, quercetin (4) and 3β-hydroxy-urs-11-en-13(28)-olide (9) showed potential inhibition activity in nitric oxide (NO)  production in RAW264.7 cells exposed to LPS.


2016 ◽  
Vol 11 (7) ◽  
pp. 1934578X1601100 ◽  
Author(s):  
Do Thi Trang ◽  
Le Thi Huyen ◽  
Nguyen Xuan Nhiem ◽  
Tran Hong Quang ◽  
Dan Thi Thuy Hang ◽  
...  

One new tirucallane- type triterpene glycoside, antidesoside (1), along with two biflavones, podocarpusflavone A (2) and amentoflavone (3) and two megastigmane glycosides, byzantionoside B (4), and (6 S,9 R)-roseoside (5) were isolated from the methanol extract of Antidesma bunius leaves. Their structures were determined by spectroscopic methods and in comparison with the published data. Compounds 1 - 3 were found to show strong inhibitory effect of NO production in BV2 cells and RAW264.7 macrophages LPS-stimulated, with IC50 values ranging from 8.5 to 26.9 μM.


2014 ◽  
Vol 2014 ◽  
pp. 1-11
Author(s):  
Lisu Wang ◽  
Shu-Yuan Chiou ◽  
Yi-Ting Shen ◽  
Fu-Tsun Yen ◽  
Hsiou-Yu Ding ◽  
...  

The green fruit ofSolanum integrifoliumPoir. has been used traditionally as an anti-inflammatory and analgesic remedy in Taiwanese aboriginal medicine. The goal of this study is to evaluate the anti-inflammatory activity and mechanism of the green fruit extract ofS. integrifolium. A bioactivity-guided fractionation procedure was developed to identify the active partition fraction. The methanol fraction (ME), with the highest phenolic content, exhibited the strongest inhibitory effect against LPS-mediated nitric oxide (NO) release and cytotoxicity in RAW264.7 macrophages. ME also significantly downregulated the expression of LPS-induced proinflammatory genes, such as iNOS, COX-2, IL-1β, IL-6, CCL2/MCP-1, and CCL3/MIP1α. Moreover, ME significantly upregulated HO-1 expression and stimulated the activation of extracellular-signal-regulated kinase 1/2 (ERK1/2). Pretreatment of cells with the HO-1 inhibitor zinc protoporphyrin and MEK/ERK inhibitor U0126 attenuated ME’s inhibitory activity against LPS-induced NO production. Taken together, this is the first study to demonstrate the anti-inflammatory activity of green fruit extract ofS. integrifoliumand its activity may be mediated by the upregulation of HO-1 expression and activation of ERK1/2 pathway.


Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
SR Lee ◽  
S Lee ◽  
HJ Eom ◽  
HR Kang ◽  
JS Yu ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3480
Author(s):  
Adriana Maite Fernández-Fernández ◽  
Eduardo Dellacassa ◽  
Tiziana Nardin ◽  
Roberto Larcher ◽  
Adriana Gámbaro ◽  
...  

The present investigation aimed to provide novel information on the chemical composition and in vitro bioaccessibility of bioactive compounds from raw citrus pomaces (mandarin varieties Clemenule and Ortanique and orange varieties Navel and Valencia). The effects of the baking process on their bioaccessibility was also assessed. Samples of pomaces and biscuits containing them as an ingredient were digested, mimicking the human enzymatic oral gastrointestinal digestion process, and the composition of the digests were analyzed. UHPLC-MS/MS results of the citrus pomaces flavonoid composition showed nobiletin, hesperidin/neohesperidin, tangeretin, heptamethoxyflavone, tetramethylscutellarein, and naringin/narirutin. The analysis of the digests indicated the bioaccessibility of compounds possessing antioxidant [6.6–11.0 mg GAE/g digest, 65.5–97.1 µmol Trolox Equivalents (TE)/g digest, and 135.5–214.8 µmol TE/g digest for total phenol content (TPC), ABTS, and ORAC-FL methods, respectively; significant reduction (p < 0.05) in Reactive Oxygen Species (ROS) formation under tert-butyl hydroperoxide (1 mM)-induced conditions in IEC-6 and CCD-18Co cells when pre-treated with concentrations 5–25 µg/mL of the digests], anti-inflammatory [significant reduction (p < 0.05) in nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 macrophages], and antidiabetic (IC50 3.97–11.42 mg/mL and 58.04–105.68 mg/mL for α-glucosidase and α-amylase inhibition capacities) properties in the citrus pomaces under study. In addition, orange pomace biscuits with the nutrition claims “no-added sugars” and “source of fiber”, as well as those with good sensory quality (6.9–6.7, scale 1–9) and potential health promoting properties, were obtained. In conclusion, the results supported the feasibility of citrus pomace as a natural sustainable source of health-promoting compounds such as flavonoids. Unfractionated orange pomace may be employed as a functional food ingredient for reducing the risk of pathophysiological processes linked to oxidative stress, inflammation, and carbohydrate metabolism, such as diabetes, among others.


2021 ◽  
Vol 22 (15) ◽  
pp. 7856
Author(s):  
Sang Min Lee ◽  
Kyung-No Son ◽  
Dhara Shah ◽  
Marwan Ali ◽  
Arun Balasubramaniam ◽  
...  

Macrophages play a critical role in the inflammatory response to environmental triggers, such as lipopolysaccharide (LPS). Inflammatory signaling through macrophages and the innate immune system are increasingly recognized as important contributors to multiple acute and chronic disease processes. Nitric oxide (NO) is a free radical that plays an important role in immune and inflammatory responses as an important intercellular messenger. In addition, NO has an important role in inflammatory responses in mucosal environments such as the ocular surface. Histatin peptides are well-established antimicrobial and wound healing agents. These peptides are important in multiple biological systems, playing roles in responses to the environment and immunomodulation. Given the importance of macrophages in responses to environmental triggers and pathogens, we investigated the effect of histatin-1 (Hst1) on LPS-induced inflammatory responses and the underlying molecular mechanisms in RAW264.7 (RAW) macrophages. LPS-induced inflammatory signaling, NO production and cytokine production in macrophages were tested in response to treatment with Hst1. Hst1 application significantly reduced LPS-induced NO production, inflammatory cytokine production, and inflammatory signaling through the JNK and NF-kB pathways in RAW cells. These results demonstrate that Hst1 can inhibit LPS-induced inflammatory mediator production and MAPK signaling pathways in macrophages.


2021 ◽  
Vol 22 (11) ◽  
pp. 5920
Author(s):  
Hyun Hwangbo ◽  
Seon Yeong Ji ◽  
Min Yeong Kim ◽  
So Young Kim ◽  
Hyesook Lee ◽  
...  

Chronic inflammation, which is promoted by the production and secretion of inflammatory mediators and cytokines in activated macrophages, is responsible for the development of many diseases. Auranofin is a Food and Drug Administration-approved gold-based compound for the treatment of rheumatoid arthritis, and evidence suggests that auranofin could be a potential therapeutic agent for inflammation. In this study, to demonstrate the inhibitory effect of auranofin on chronic inflammation, a saturated fatty acid, palmitic acid (PA), and a low concentration of lipopolysaccharide (LPS) were used to activate RAW264.7 macrophages. The results show that PA amplified LPS signals to produce nitric oxide (NO) and various cytokines. However, auranofin significantly inhibited the levels of NO, monocyte chemoattractant protein-1, and pro-inflammatory cytokines, such as interleukin (IL)-1β, tumor necrosis factor-α, and IL-6, which had been increased by co-treatment with PA and LPS. Moreover, the expression of inducible NO synthase, IL-1β, and IL-6 mRNA and protein levels increased by PA and LPS were reduced by auranofin. In particular, the upregulation of NADPH oxidase (NOX) 4 and the translocation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) induced by PA and LPS were suppressed by auranofin. The binding between the toll-like receptor (TLR) 4 and auranofin was also predicted, and the release of NO and cytokines was reduced more by simultaneous treatment with auranofin and TLR4 inhibitor than by auranofin alone. In conclusion, all these findings suggested that auranofin had anti-inflammatory effects in PA and LPS-induced macrophages by interacting with TLR4 and downregulating the NOX4-mediated NF-κB signaling pathway.


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