Immunomodulatory effects of glutathione, garlic derivatives, and hydrogen sulfide.

PMID: 

Nutrients. 2019 Jan 30 ;11(2). Epub 2019 Jan 30. PMID: 30704060

Abstract Title: 

Immunomodulatory Effects of Glutathione, Garlic Derivatives, and Hydrogen Sulfide.

Abstract: 

Glutathione and aged garlic extract are sulfur-containing products that play important protective and regulatory roles within the immune system and in oxidative processes. Hydrogen sulfide (H₂S), an endogenous, gaseous, signaling transmitter, has also been shown to be involved in the regulation of inflammation. Recent studies have shown that sulfur-containing compounds from garlic have beneficial effects in attenuating outcomes associated with cardiovascular disease and inflammation by a mechanism that may be related to the H₂S signaling pathway. In this review, we summarize the main functions of glutathione (GSH), garlic derivatives and H₂S and their role in the immune response and impact on health and disease.

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Alliin alters gut microbiota and gene expression of colonic epithelial tissues.

PMID: 

J Food Biochem. 2019 Apr ;43(4):e12795. Epub 2019 Feb 21. PMID: 31353605

Abstract Title: 

Alliin alters gut microbiota and gene expression of colonic epithelial tissues.

Abstract: 

Alliin is a natural organosulfur-containing phytochemical in garlic. It is possible that alliin can regulate the gut microbiota for its strong antimicrobial activity against many pathogens. Here, we assessed whether alliin impacts the distal small intestinal bacteria, hence the cecal microbiota, thus altering the gene expression of colonic epithelial tissues (CETs). Eighty mg/kg alliin was orally administered to rats for 14 days, and the 16S rDNA from small intestinal and cecal microbiota as well as mRNA from CETs were sequenced and analyzed. The results showed that alliin consumption affected microbiota composition in both the small intestine and cecum, although there was only one specific genus, Allobaculum that was significantly altered in the rat cecum. The altered composition of microbiota indirectly impacted 174 genes in the CETs. Specifically, five genes, including RT1-Ba, RT1-Bb, Cd80, Madcam1, and Aicda, indicated this consumption related to the intestinal immune network for IgA production. PRACTICAL APPLICATIONS: We firstly reported alliin consumption in vivo potentially affected the intestinal immunity of healthy rats by slightly alteration of microbiota composition in small intestine and cecum. The alteration subsequently amplified, resulting in the change of the colonic epithelial expressionof several genes related to the intestinal immune network for IgA production. Hence, we suggested the alliin consumption may potentially affect the immune system of healthy individuals by alteration of gut microbiota and epithelial gene expression.

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Carnosol inhibits inflammasome activation by directly targeting HSP90 to treat inflammasome-mediated diseases

PMID: 

Cell Death Dis. 2020 Apr 20 ;11(4):252. Epub 2020 Apr 20. PMID: 32312957

Abstract Title: 

Carnosol inhibits inflammasome activation by directly targeting HSP90 to treat inflammasome-mediated diseases.

Abstract: 

Aberrant activation of inflammasomes, a group of protein complexes, is pathogenic in a variety of metabolic and inflammation-related diseases. Here, we report that carnosol inhibits NLRP3 inflammasome activation by directly targeting heat-shock protein 90 (HSP90), which is essential for NLRP3 inflammasome activity, thereby treating inflammasome-mediated diseases. Our data demonstrate that carnosol inhibits NLRP3 inflammasome activation in primary mouse bone marrow-derived macrophages (BMDMs), THP-1 cells and human peripheral blood mononuclear cells (hPBMCs). Mechanistically, carnosol inhibits inflammasome activation by binding to HSP90 and then inhibiting its ATPase activity. In vivo, our results show that carnosol has remarkable therapeutic effects in mouse models of NLRP3 inflammasome-mediated diseases, including endotoxemia and nonalcoholic steatohepatitis (NASH). Our data also suggest that intraperitoneal administration of carnosol (120 mg/kg) once daily for two weeks is well tolerated in mice. Thus, our study reveals the inhibitory effect of carnosol on inflammasome activation and demonstrates that carnosol is a safe and effective candidate for the treatment of inflammasome-mediated diseases.

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Attenuation of allergen-mediated mast cell activation by rosemary extract (Rosmarinus officinalis L.).

PMID: 

J Leukoc Biol. 2020 Mar 23. Epub 2020 Mar 23. PMID: 32202360

Abstract Title: 

Attenuation of allergen-mediated mast cell activation by rosemary extract (Rosmarinus officinalis L.).

Abstract: 

Mast cells are immune sentinels and a driving force in both normal and pathological contexts of inflammation, with a prominent role in allergic hypersensitivities. Crosslinking of FcεRI by allergen-bound IgE Abs leads to mast cell degranulation, resulting in an early-phase response and release of newly synthesized pro-inflammatory mediators in the late-phase. The MAPK and NF-κB pathways are established as critical intracellular mechanisms directing mast cell-induced inflammation. Rosemary extract (RE) has been shown to modulate the MAPK and NF-κB pathways in other cellular contexts in vitro and in vivo. However, the effect of RE on mast cell activation has not been explored, and thus we aim to evaluate the potential of RE in modulating mast cell activation and FcεRI/c-kit signaling, potentially via these key pathways. Primary murine mast cells were sensitized with anti-TNP IgE and stimulated with cognate allergen (TNP-BSA) under stem cell factor (SCF) potentiation while treated with 0-25 µg/ml RE. RE treatment inhibited phosphorylation of p38 and JNK MAPKs while also impairing NF-кB transcription factor activity. Gene expression and mediator secretion analysis showed that RE treatment decreased IL-6, TNF, IL-13, CCL1, and CCL3, but major component polyphenols do not contribute to these effects. Importantly, RE treatment significantly inhibited early phase mast cell degranulation (down to 15% of control), with carnosic acid and carnosol contributing. These findings indicate that RE is capable of modulating mast cell functional outcomes and that further investigation of the underlying mechanisms and its potential therapeutic properties in allergic inflammatory conditions is warranted.

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Protective effects of carnosic acid on retinal ganglion cells in acute ocular hypertension rats.

PMID: 

Int Ophthalmol. 2020 Apr 10. Epub 2020 Apr 10. PMID: 32277323

Abstract Title: 

Protective effects of carnosic acid on retinal ganglion cells in acute ocular hypertension rats.

Abstract: 

OBJECTIVE: To observe the protective effects of carnosic acid on rat retinal ganglion cells (RGCs) among acute ocular hypertension rats.METHODS: Sixty male SPF (specific-pathogen-free) SD rats (10 weeks) were randomly assigned to untreated group, carnosic-acid-treated group and hypertensive group with 20 rats for each. The acute ocular hypertension animal model was induced by the perfusion of normal saline solution into anterior chamber of eyes to elevate the intraocular pressure (IOP) to 110 mmHg for 60 min in the rats of the carnosic-acid-treated group and hypertensive group. Then, the carnosic acid dissolving in dimethyl sulfoxide (DMSO) was intraperitoneally injected for consecutive 7 days in the carnosic-acid-treated group, and only DMSO was used in the same way in the hypertensive group. The rats were killed 2 weeks after experiment, and retinal sections were prepared for histopathological and apoptotic retinal ganglion cells (RGCs) examination by hemotoxylin and eosin staining and TUNEL staining. Use immunofluorescence employed to examine the survival of RGCs. This study protocol was approved by the Ethic Committee for Experimental Animal of Three Gorges University.RESULTS: The retinal morphology and structure were clear in the untreated group. The edema of retinal tissue, loosely arranged RGCs and swollen nucleus were seen in the hypertensive group. In the carnosic-acid-treated group, the retinal morphology and structure were regular. The retinal nerve fiber layer (RNFL) thickness was (32.96 ± 1.63), (58.96 ± 1.57) and (50.11 ± 2.37) μm, and the apoptotic cell number was (6.92 ± 2.96), (29.85 ± 6.40) and (14.69 ± 2.98)/field, and the survived cell number was (2363.17 ± 148.45), (1308.67 ± 106.02) and (1614.17 ± 96.39)/0.235 mmin the untreated group, hypertensive group and carnosic-acid-treated group, respectively, showing significant differences among groups (F = 339.284, 81.583, 122.68, all at P 

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Rosmarinus officinalis L. and Salvia officinalis L. were found to have an antitumoral activity.

PMID: 

J Complement Integr Med. 2020 Mar 31. Epub 2020 Mar 31. PMID: 32229691

Abstract Title: 

The cytotoxic activity of Salvia officinalis L. and Rosmarinus officinalis L. Leaves extracts on human glioblastoma cell line and their antioxidant effect.

Abstract: 

Background Rosmarinus officinalis L. (Rosemary) and Salvia officinalis L. (Sage) are two Mediterranean species growing spontaneously in some area in Morocco. They are used in traditional and complementary medicine to treat numerous disorders. The aim of this work was to assess the in vitro antitumoral effect of the methanolic total extract prepared from rosemary and sage on human glioblastoma cell line (42 GMBA), conjointly with their antioxidant activity. Methods The accelerated solvent extractor was used to obtain the total extract of the studied plants. The antitumor activity was performed using the microculture tetrazolium cytotoxique assay while the antioxidant effect was evaluated using the ferric reducing antioxidant power (FRAP), and the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay. Results Our results show that the total extract of R.O and S.O have a cytotoxic effect on glioblastoma but not on cortical neurons. On the other hand, the results obtained in the FRAP and DPPH tests show a dose-dependent antioxidant activity correlated with an important level of phenols and flavonoids. Conclusion Rosmarinus officinalis L. and Salvia officinalis L. were found to have an antitumoral activity which may be linked, probably, to an antioxidant process.

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Specific inhibition of S. aureus virulence using topical formulations of rosemary extract may offer a practical approach to preventing and treating flares of atopic dermatitis.

PMID: 

Antibiotics (Basel). 2020 Mar 31 ;9(4). Epub 2020 Mar 31. PMID: 32244277

Abstract Title: 

(Rosemary) Extracts Containing Carnosic Acid and Carnosol are Potent Quorum Sensing Inhibitors ofVirulence.

Abstract: 

is an opportunistic pathogen and a common cause of skin infection.also plays a role in the pathogenesis of the chronic inflammatory skin disease, atopic dermatitis.virulence involves activation of the quorum sensingoperon. In this paper, we show that the diterpene carnosic acid, present in. (rosemary) leaves, is a specific inhibitor ofexpression as low as 5μM. Carnosol and rosmarinic acid are two other phytochemicals present in rosemary leaves. Carnosol, but not rosmarinic acid, is also a potentexpression inhibitor. Natural rosemary extracts containing carnosic acid and carnosol inhibitexpression, both in luciferase reporter strains and in wild type strains isolated from patients with atopic dermatitis. Specific inhibition ofvirulence using topical formulations of rosemary extract may offer a practical approach to preventing and treating flares of atopic dermatitis.

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α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice.

PMID: 

Int J Nanomedicine. 2017 ;12:4479-4491. Epub 2017 Jun 19. PMID: 28684908

Abstract Title: 

α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice.

Abstract: 

Acute respiratory distress syndrome (ARDS) is a severe clinical condition of respiratory failure due to an intense inflammatory response with different etiologies. Despite all efforts, therapy remains limited, and ARDS is still associated with high mortality and morbidity. Plants can provide a vast source of active natural products for the discovery of new drugs.α-bisabolol (α-bis), a constituent of the essential oil from chamomile, has elicited pharmacological interest. However, the molecule has some limitations to its biological application. This study was conducted to develop a drug delivery system using lipid-core nanocapsules (LNCs) to improve the anti-inflammatory effects of orally administered α-bis. α-bis-loaded LNCs (α-bis-LNCs) were prepared by interfacial deposition of poly(ε-caprolactone) and orally administered in a mouse model of ARDS triggered by an intranasal administration of lipopolysaccharide (LPS). We found that α-bis-LNCs (30, 50, and 100 mg kg) significantly reduced airway hyperreactivity (AHR), neutrophil infiltration, myeloperoxidase activity, chemokine levels (KC and MIP-2), and tissue lung injury 18 hours after the LPS challenge. By contrast, freeα-bis failed to modify AHR and neutrophil accumulation in the bronchoalveolar lavage effluent and lung parenchyma and inhibited elevation in the myeloperoxidase and MIP-2 levels only at the highest dose. Furthermore, only α-bis-LNCs reduced LPS-induced changes in mitogen-activated protein kinase signaling, as observed by a significant reduction in phosphorylation levels of ERK1/2, JNK, and p38 proteins. Taken together, our results clearly show that by using LNCs, α-bis was able to decrease LPS-induced inflammation. These findings may be explained by the robust increase of α-bis concentration in the lung tissue that was achieved by the LNCs. Altogether, these results indicate that α-bis-LNCs should further be investigated as a potential alternative for the treatment of ARDS.

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Alpha-bisobolol possesses corneal antinociceptive activity.

PMID: 

Pharm Biol. 2017 Dec ;55(1):1089-1092. PMID: 28193100

Abstract Title: 

Corneal antinociceptive effect of (-)-α-bisabolol.

Abstract: 

CONTEXT: (-)-α-Bisabolol (BISA) is a sesquiterpene alcohol widely used as scent in cosmetic preparations, perfumes, shampoos, toilet soaps and other toiletries with potential for use in the pharmaceutical area.OBJECTIVE: To evaluate the corneal antinociceptive efficacy of BISA and to analyze the best solubilizing agent.MATERIALS AND METHODS: Acute corneal nociception was induced by the local application of hypertonic saline (5 M NaCl; 20 μL) to the corneal surface of Swiss mice (n = 8/group) 60 min after topical treatment with solutions or ointment containing BISA (50-200 mg/mL). The number of eye wipes performed with the ipsilateral forepaw was counted for a period of 30 s. Control groups (vehicles) were included.RESULTS: BISA (50, 100 or 200 mg/mL) solubilized with Tween 80 did not reduce the number of eye wipes. Animals treated with the ointment (BISA 50, 100 or 200 mg/mL; p 

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