scholarly journals Oleuropein-Rich Leaf Extract as a Broad Inhibitor of Tumour and Macrophage iNOS in an Apc Mutant Rat Model

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1577
Author(s):  
Jessica Ruzzolini ◽  
Sofia Chioccioli ◽  
Noemi Monaco ◽  
Silvia Peppicelli ◽  
Elena Andreucci ◽  
...  

Oleuropein, the major compound found in olive leaves, has been reported to exert numerous pharmacological properties, including anti-inflammatory, anti-diabetic and anti-cancer effects. The purpose of this study was to evaluate, for the first time, the effect of oleuropein-rich leaf extracts (ORLE) in already-developed colon tumours arising in Apc (adenomatous polyposis coli) mutated PIRC rats (F344/NTac-Apcam1137). Here, we were able to investigate in parallel the anti-cancer effect of ORLE, both in vivo and in vitro, and its anti-inflammatory effect on macrophages, representing a critical and abundant population in most solid tumour microenvironment. We found that in vivo ORLE treatment promoted apoptosis and attenuated iNOS activity both in colon tumours as in peritoneal macrophages of PIRC rats. We this confirmed in vitro using primary RAW264.7 cells: ORLE reduced iNOS activity in parallel with COX-2 and pro-inflammatory cytokines, such as IL-1β, IL-6 and TGF-β. These findings suggest that ORLE possess a strong anti-inflammatory activity, which could be crucial for dampening the pro-tumourigenic activity elicited by a chronic inflammatory state generated by either tumour cells or tumour-associated macrophages.

Author(s):  
Jessica Ruzzolini ◽  
Sofia Chiccoli ◽  
Noemi Monaco ◽  
Silvia Peppicelli ◽  
Elena Andreucci ◽  
...  

Abstract: Oleuropein, the major compound of olive leaves, has been reported to exert numerous pharmacological properties, including anti-inflammatory, antidiabetic and anticancer. The purpose of this study is to evaluate, for the first time, the effect of oleuropein-rich leaf extracts (ORLE) in already-developed colon tumours colon tumours arising in an Apc (adenomatous polyposis coli) mutated PIRC rats (F344/NTac-Apcam1137). Here, we were able to investigate in parallel the anti-cancer effect of ORLE, both in vivo and in vitro, and its anti-inflammatory effect on macrophages, which represents a critical and abundant population in most solid tumours microenvironment. We found that in vivo ORLE treatment promoted apoptosis and attenuated iNOS activity both in colon tumours as in peritoneal macrophages of PIRC rats. We confirmed in vitro using primary RAW264.7 cells: ORLE reduced iNOS activity in parallel with COX-2 and pro-inflammatory cytokines, such as IL-1, IL-6 and TGF-. These findings suggest that ORLE possess a strong anti-inflammatory activity, which could be crucial for dampening the pro-tumourigenic activity elicited by a chronic inflammatory state generated by either tumour cells or tumour-associated macrophages.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 991
Author(s):  
Melanie S. Matos ◽  
José D. Anastácio ◽  
Cláudia Nunes dos Santos

Inflammation is a crucial and complex process that reestablishes the physiological state after a noxious stimulus. In pathological conditions the inflammatory state may persist, leading to chronic inflammation and causing tissue damage. Sesquiterpene lactones (SLs) are composed of a large and diverse group of highly bioactive plant secondary metabolites, characterized by a 15-carbon backbone structure. In recent years, the interest in SLs has risen due to their vast array of biological activities beneficial for human health. The anti-inflammatory potential of these compounds results from their ability to target and inhibit various key pro-inflammatory molecules enrolled in diverse inflammatory pathways, and prevent or reduce the inflammatory damage on tissues. Research on the anti-inflammatory mechanisms of SLs has thrived over the last years, and numerous compounds from diverse plants have been studied, using in silico, in vitro, and in vivo assays. Besides their anti-inflammatory potential, their cytotoxicity, structure–activity relationships, and pharmacokinetics have been investigated. This review aims to gather the most relevant results and insights concerning the anti-inflammatory potential of SL-rich extracts and pure SLs, focusing on their effects in different inflammatory pathways and on different molecular players.


2016 ◽  
Vol 4 (6) ◽  
pp. 319-323
Author(s):  
Narendra K ◽  
DSD Suman Joshi ◽  
M Satya Prasad ◽  
KVN Rathnakar Reddi ◽  
Swathi J ◽  
...  

2017 ◽  
Vol 45 (04) ◽  
pp. 847-861 ◽  
Author(s):  
Chia-Yang Li ◽  
Katsuhiko Suzuki ◽  
Yung-Li Hung ◽  
Meng-Syuan Yang ◽  
Chung-Ping Yu ◽  
...  

Aloe, a polyphenolic anthranoid-containing Aloe vera leaves, is a Chinese medicine and a popular dietary supplement worldwide. In in vivo situations, polyphenolic anthranoids are extensively broken down into glucuronides and sulfate metabolites by the gut and the liver. The anti-inflammatory potential of aloe metabolites has not been examined. The aim of this study was to investigate the anti-inflammatory effects of aloe metabolites from in vitro (lipopolysaccharides (LPS)-activated RAW264.7 macrophages) and ex vivo (LPS-activated peritoneal macrophages) to in vivo (LPS-induced septic mice). The production of proinflammatory cytokines (TNF-[Formula: see text] and IL-12) and NO was determined by ELISA and Griess reagents, respectively. The expression levels of iNOS and MAPKs were analyzed by Western blot. Our results showed that aloe metabolites inhibited the expression of iNOS, decreased the production of TNF-[Formula: see text], IL-12, and NO, and suppressed the phosphorylation of MAPKs by LPS-activated RAW264.7 macrophages. In addition, aloe metabolites reduced the production of NO, TNF-[Formula: see text] and IL-12 by murine peritoneal macrophages. Furthermore, aloe administration significantly reduced the NO level and exhibited protective effects against sepsis-related death in LPS-induced septic mice. These results suggest that aloe metabolites exerted anti-inflammatory effects in vivo, and that these effects were associated with the inhibition of inflammatory mediators. Therefore, aloe could be considered an effective therapeutic agent for the treatment of sepsis.


2008 ◽  
Vol 36 (05) ◽  
pp. 899-912 ◽  
Author(s):  
Ting-Yu Wang ◽  
Jun Li ◽  
Jin-Fang Ge ◽  
Chang-Yu Li ◽  
Yong Jin ◽  
...  

Litsea coreana Levl., a traditional Chinese medicine, has long been used for its diverse benefits such as detoxification and detumescence. Total flavonoids from Litsea coreana Levl. (TFLC) are the effective fraction of L. coreana. This study was designed to investigate the anti-inflammatory effects and mechanisms of TFLC against Feund's complete adjuvant (FCA)-induced arthritis in rats. Arthritis was evaluated by secondary paw swelling, polyarthritis index, body weight and histopathologic analysis. Con A- or LPS-stimulated splenocyte proliferation and cytokine (IL-1 and IL-2) production were assessed by MTT assay and activated mouse cell proliferation assay, respectively. The results indicate that therapeutic administration of TFLC (50, 100, 200 mg/kg, ig × 12 days ) could significantly suppress secondary arthritis in rats with adjuvant-induced arthritis (AA). In vivo, TFLC (50, 100, 200 mg/kg, ig × 12 days ) augmented splenocyte proliferation and increased IL-2 production in splenocytes, while reduced IL-1 activity in peritoneal macrophages (PMΦ) of AA rats. In vitro, TFLC at concentrations from 0.005 to 50 μg/ml exerted the same immunoregulatory effects on AA rats as those in vivo. In addition, an attractive feature of TFLC lies in its apparent lack of toxicity. These results suggest that TFLC without toxicity has a significant anti-arthritic effect on AA rats which could be associated with its anti-inflammatory and immunomodulatory properties.


2018 ◽  
Vol 10 (2) ◽  
pp. 195-210
Author(s):  
M. Shahriar ◽  
M. A. Bhuiyan ◽  
M. S. Rana

The methanol, ethanol and chlorofom leaf extracts of Satkara, Citrus assamensis (family: Rutaceae), were subjected to in vitro anti-bacterial, thrombolytic, membrane stabilizing and in vivo anti-inflammatory and antitumor activity tests. The chloroform extract of C. assamensis showed the most important spectrum of activity against Bacillus subtilis, Bacillus cereus, Sarcina lutea among 6 gram positive and against 11 gram negative bacteria at the concentration of 1000 μg/disc, while the range of zones of inhibition were within 7-16 mm. Among the tested three extracts CHCl3 extract showed potent thrombolytic activity and hypotonic solution induced haemolytic activity where the percentages of inhibition were found to be 35% and 55% respectively. All the extracts established significant (p<0.05) anti-inflammatory effect by regulating biphasic inflammatory process induced by carrageenan. The leaf extract dose-dependently and significantly decreases the number of EAC cell count and inhibition of cell growth in comparison to the EAC control and standard. The results obtained in the present study indicate that, C. assamensis leaf can be a potential source of anti-bacterial, thrombolytic, membrane stabilizing, anti-inflammatory and antitumor agents.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Rodolfo Abarca-Vargas ◽  
Vera L. Petricevich

Background. Different pharmacological properties, such as antioxidant, antiproliferative, and anti-inflammatory properties, have been described among natural products. We previously described that the Bougainvillea xbuttiana (Variety Orange) ethanolic extract (BxbO) has an anti-inflammatory effect; however, this action is not fully understood. In this study, the action of the BxbO extract on the secretion of inflammatory mediators in two experimental models, in vitro and in vivo, after LPS challenge was evaluated. Methods. Peritoneal macrophages were obtained from female BALB/c mice and LPS-challenged with or without the BxbO extract. For the evaluation of mediators, the supernatants at 0, 12, 24, 36, and 48 hours were collected. For in vivo estimation, groups of female BALB/c mice were first intraperitoneously injected with different amounts of LPS and later administered the oral BxbO extract (v.o.) for 144 hours. To understand the mechanism of action, sera obtained from mice were collected at 0, 2, 4, 8, 12, and 24 hours after LPS challenge (with or without BxbO) for the detection of mediators. Results. The results showed that, in both peritoneal macrophages and sera of mice treated with the BxbO extract 1 hour before or together with LPS challenge, proinflammatory cytokines and nitric oxide release were unquestionably repressed. In contrast, in both systems studied here, the IL-10 levels were elevated to 5 to 9 times. At lethal doses of LPS, the BxbO extract treatment was found to protect animals from death. Conclusions. The results revealed that the inhibitory, protective, and benign effects of the BxbO extract were due to its capacity to balance the secretion of mediators.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Deyse C. M. Carvalho ◽  
Luiz Henrique Agra Cavalcante-Silva ◽  
Éssia de A. Lima ◽  
José G. F. M. Galvão ◽  
Anne K. de A. Alves ◽  
...  

Cardiotonic steroids, such as ouabain and digoxin, are known to bind to Na+/K+-ATPase and to promote several biological activities, including anti-inflammatory activity. However, there are still no reports in the literature about inflammation and marinobufagenin, a cardiotonic steroid from the bufadienolide family endogenously found in mammals. Therefore, the aim of this work was to analyze, in vivo and in vitro, the role of marinobufagenin in acute inflammation. Swiss mice were treated with 0.56 mg/kg of marinobufagenin intraperitoneally (i.p.) and zymosan (2 mg/mL, i.p.) was used to induce peritoneal inflammation. Peritoneal fluid was collected and used for counting cells by optical microscopy and proinflammatory cytokine quantification (IL-1β, IL-6, and TNF-α) by immunoenzymatic assay (ELISA). Zymosan stimulation, as expected, induced increased cell migration and proinflammatory cytokine levels in the peritoneum. Marinobufagenin treatment reduced polymorphonuclear cell migration and IL-1β and IL-6 levels in the peritoneal cavity, without interfering in TNF-α levels. In addition, the effect of marinobufagenin was evaluated using peritoneal macrophages stimulated by zymosan (0.2 mg/mL) in vitro. Marinobufagenin treatment at different concentrations (10, 100, 1000, and 10000 nM) showed no cytotoxic effect on peritoneal macrophages. Interestingly, the lowest concentration, which did not inhibit Na+/K+-ATPase activity, attenuated proinflammatory cytokines IL-1β, IL-6, and TNF-α levels. To investigate the putative mechanism of action of marinobufagenin, the expression of surface molecules (TLR2 and CD69) and P-p38 MAPK were also evaluated, but no significant effect was observed. Thus, our results suggest that marinobufagenin has an anti-inflammatory role in vivo and in vitro and reveals a novel possible endogenous function of this steroid in mammals.


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