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Ophthalmology / Saflogin
  1. Clin Ophthalmol. 2013;7:1403-10. doi: 10.2147/OPTH.S47657. Epub 2013 Jul 9.

Assessment of the tolerability profile of an ophthalmic solution of 5% glycyrrhizin and copolymer PEG/PPG on healthy volunteers and evaluation of its efficacy in the treatment of moderate to severe blepharitis.

Mencucci R1Favuzza EMenchini U.

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Abstract

PURPOSE:

To evaluate the tolerability on healthy volunteers and the efficacy on subjects affected by chronic moderate/severe blepharitis of a 5% glycyrrhizin and copolymer poly(ethylene glycol)/poly(propylene glycol)(PEG/PPG) ophthalmic solution.

METHODS:

The study was a randomized, controlled, open label, intra-patient monocentric study. It consisted of two different phases, the assessment of tolerability phase on 20 healthy volunteers, and the evaluation of the efficacy on 21 subjects affected by chronic moderate/severe blepharitis; the treatment period was 2 weeks, followed by 1-week of follow-up. In the efficacy phase, in both eyes, eyelid hygiene was also performed. At day 0, 3, 7, 14, and 21 a complete ophthalmological examination was performed. In the tolerability phase, signs of clinical toxicity were recorded and subject-reported symptoms were collected using a questionnaire. In the efficacy phase, global signs and symptoms of blepharitis scores were collected using standardized photographic scales and questionnaire. The statistical analysis was performed using the Wilcoxon signed-rank test.

RESULTS:

No ocular signs of drug toxicity were reported. During the treatment period for tolerability phase, there were statistically significant higher scores of tearing and ocular discomfort in the tolerability study group versus the tolerability control group. In the efficacy phase, differences between global scores of the two groups were statistically significant at day 0 (score of the efficacy study group was higher than the efficacy control group; P = 0.005) and at day 21 (score of the efficacy study group was lower than the efficacy control group (P ≤ 0.001).The difference of global scores at day 3, 7, 14, and 21 versus day 0 was statistically significant in both groups. No serious adverse events occurred.

CONCLUSION:

The 5% glycyrrhizin ophthalmic solution was well tolerated in healthy volunteers and in patients with chronic moderate/severe blepharitis, and in association with eyelid hygiene showed good clinical anti-inflammatory activity that lasted after instillation suspension.

KEYWORDS:

HMGB1; blepharitis; glycyrrhizin

https://www.ncbi.nlm.nih.gov/pubmed/23874081

 

  1. Ophthalmic Res. 1987;19(4):213-20.

Quantitative evaluation of ocular anti-inflammatory drugs based on measurements of corneal temperature in rabbits: dexamethasone and glycyrrhizin.

Tanaka H1Hasegawa TMatsushita MMiichi HHayashi S.

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Abstract

A method for the quantitative evaluation of topically applied anti-inflammatory agents is described. Conjunctival inflammation was induced in rabbits by topical instillation of n-butanol. The intensity of inflammation was determined by measuring changes of corneal surface temperature with an infrared thermometer. The closest correlation was obtained between corneal temperature change and the Draize score which is widely used as a subjective scoring method. Dexamethasone showed a good logarithmic dose-response inhibitory effect between 0.0001 and 0.1%, and glycyrrhizin the same at 0.25-5%. Glycyrrhizin in a 5% solution showed a comparable anti-inflammatory effect to that of dexamethasone (0.1%). The inflammation model induced by n-butanol was mediated, in part, by the degranulation of mast cells because of some inhibitory effect of disodium cromoglycate (2%), an inhibitor of mast cell degranulation, and diphenhydramine hydrochloride (0.5%), an antihistaminic agent.

https://www.ncbi.nlm.nih.gov/pubmed/3501091

 

 

  1. Chem Biol. 2007 Apr;14(4):431-41.

Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities.

Mollica L1De Marchis FSpitaleri ADallacosta CPennacchini DZamai MAgresti ATrisciuoglio LMusco GBianchi ME.

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Abstract

High-mobility group box 1 protein (HMGB1) is a nuclear component, but extracellularly it serves as a signaling molecule involved in acute and chronic inflammation, for example in sepsis and arthritis. The identification of HMGB1 inhibitors is therefore of significant experimental and clinical interest. We show that glycyrrhizin, a natural anti-inflammatory and antiviral triterpene in clinical use, inhibits HMGB1 chemoattractant and mitogenic activities, and has a weak inhibitory effect on its intranuclear DNA-binding function. NMR and fluorescence studies indicate that glycyrrhizin binds directly to HMGB1 (K(d) approximately 150 microM), interacting with two shallow concave surfaces formed by the two arms of both HMG boxes. Our results explain in part the anti-inflammatory properties of glycyrrhizin, and might direct the design of new derivatives with improved HMGB1-binding properties.

https://www.ncbi.nlm.nih.gov/pubmed/17462578

  1. Invest Ophthalmol Vis Sci. 2016 Oct 1;57(13):5799-5809. doi: 10.1167/iovs.16-20103.

Glycyrrhizin Reduces HMGB1 and Bacterial Load in Pseudomonas aeruginosa Keratitis.

Ekanayaka SA1McClellan SA1Barrett RP1Kharotia S1Hazlett LD1.

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Abstract

PURPOSE:

High mobility group box 1 (HMGB1) contributes to poor disease outcome in Pseudomonas aeruginosa keratitis. This study tests the prophylactic effect of treatment with HMGB1 inhibitors, glycyrrhizin (GLY) and its derivative, carbenoxolone (CBX), for Pseudomonas keratitis.

METHODS:

We treated C57BL/6 (B6) mice subconjunctivally with GLY or CBX, infected with a noncytotoxic clinical isolate (KEI 1025) or a cytotoxic strain (ATCC 19660) of P. aeruginosa, and injected intraperitoneally with either agent. Clinical score, photography with a slit lamp, real-time RT-PCR, ELISA, myeloperoxidase (MPO) assay, bacterial plate count, histopathology, and absorbance assays were used to assess treatment efficacy and bacteriostatic activity.

RESULTS:

After KEI 1025 infection, GLY treatment reduced HMGB1 (mRNA and protein levels) and improved disease outcome with significant reduction in mRNA levels of IL-1β, TLR4, CXCL2, and IL-12; protein expression (IL-1β, CXCL2); neutrophil infiltrate; and bacterial load. Treatment with GLY enhanced antimicrobial proteins, including CRAMP and mBD2, but not mBD3. Glycyrrhizin also reduced clinical scores and improved disease outcome in corneas infected with strain 19660. However, neither HMGB1 mRNA or protein levels were reduced, but rather, CXCL2 expression (mRNA and protein), neutrophil infiltrate, and bacterial load were reduced statistically. Treatment with GLY initiated 6 hours after infection reduced plate count; GLY also was bacteriostatic for KEI 1025 and ATCC 19660.

CONCLUSIONS:

Glycyrrhizin reduces HMGB1 and is protective against P. aeruginosa-induced keratitis with a clinical isolate that is noncytotoxic. It was similar, but less effective when used after infection with a cytotoxic strain, which did not reduce HMGB1.

https://www.ncbi.nlm.nih.gov/pubmed/27792814

 

 

  1. Drugs Today (Barc). 2007 Dec;43(12):887-96. doi: 10.1358/dot.2007.43.12.1162080.

Clinical evaluation of the efficacy of PEG/PG lubricant eye drops with gelling agent (HP-Guar) for the relief of the signs and symptoms of dry eye disease: a review.

Foulks GN1.

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Abstract

The objective of this review is to evaluate the efficacy of polyethylene glycol (PEG) 400/propylen glycol (PG) in-situ gellable lubricant eyedrops with HP-Guar (as the gelling agent) in reducing dry eye signs and symptom. A systematic literature search utilizing MEDLINE was conducted to identify peer-reviewed articles related to dry eye disease and in-situ PEG/PG gellable lubricant eye drops. The search covered the period prior to July 2007. Articles were selected based on their direct applicability to the subject matter. A manual search was also conducted based on citations in the published literature. Additional original reports were referenced at the author's discretion if deemed applicable to the subject matter of the review. Forty-three (43) articles were identified and are reviewed here. The published literature indicated that dry eye disease is a prevalent condition in the United States, especially among women and the elderly. The biphasic mechanism of action of in-situ PEG/PG gellable lubricant eye drops, afforded by their unique structure, renders them more effective at reducing the signs and symptoms of dry eye than many commercially available over-the-counter products

https://www.ncbi.nlm.nih.gov/pubmed/18174974

 

 

  1. Sci Rep. 2017 Aug 3;7(1):7222. doi: 10.1038/s41598-017-07833-1.

Anti-allergic activity of glycyrrhizic acid on IgE-mediated allergic reaction by regulation of allergy-related immune cells.

Han S1Sun L2He F2Che H3.

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Abstract

Glycyrrhizic acid (GA), the major bioactive triterpene glycoside of glycyrrhiza, has been shown to possess a wide range of pharmacological properties, including anti-inflammatory and anti-viral properties. However, few studies have examined the anti-allergic activity and exact mechanism of action of GA. In the present work, the anti-allergic activity and possible mechanisms of action of GA on an immunoglobulin (Ig) E-mediated allergic reaction has been studied using three models of allergic reaction in vivo and in vitro. Active systemic allergic reaction in Balb/c mice showed that GA can suppress the increased level of IL-4 to restore the immune balance of TH1/TH2 cells in a dose-dependent manner. Additionally, GA attenuated significantly the B cells producing allergen-specific IgE and IgG1 partly because of the low levels of TH2 cytokines. Both passive cutaneous anaphylaxis in vivo and an RBL-2H3 cell-based immunological assay in vitro indicated that GA acted as a "mast cell stabilizer", as it inhibited mast cell degranulation and decreased vascular permeability by inhibiting the expression of Orai1, STIM1 and TRPC1, which blocked extracellular Ca2+ influxes. The current study suggests that GA may serve as an effective anti-allergic agent derived from food for the prevention and treatment of IgE-mediated allergic reaction.

https://www.ncbi.nlm.nih.gov/pubmed/28775294

 

  1. Ocul Immunol Inflamm. 2011 Jun;19(3):180-5. doi: 10.3109/09273948.2010.538121. Epub 2011 Mar 22.

18β-glycyrrhetic acid inhibits immune activation triggered by HMGB1, a pro-inflammatory protein found in the tear fluid during conjunctivitis and blepharitis.

Cavone L1Muzzi MMencucci RSparatore BPedrazzi MMoroni FChiarugi A.

Author information

Abstract

PURPOSE:

High-mobility group proteins are chromatin-binding factors with key roles in nuclear homeostasis. Evidence indicates that extracellularly released high-mobility group box 1 protein (HMGB1) behaves as a cytokine, promoting inflammation and disease pathogenesis. HMGB1 release occurs during endophtalmitis or uveoretinitis.

METHODS:

The authors investigated the presence of HMGB1 in tear fluid of patients with different inflammatory disorders of the external eye.

RESULTS:

Data demonstrate that HMGB1 content is close to detection limit in tears of control subjects but highly increased (about 15-fold) in patients with conjunctivitis or blepharitis. The authors also report that 18β-glycyrrhetic acid impairs antibody recognition of HMGB1, suggesting direct binding to the protein. Accordingly, 18β-glycyrrhetic acid prevented HMGB1-dependent COX2 expression and cluster formation in primary cultures of human macrophages.

CONCLUSION:

Together, these findings suggest that HMGB1 contributes to inflammatory disorders of the external eye, and 18β-glycyrrhetic acid may scavenge the protein and inhibit its detrimental effects.

https://www.ncbi.nlm.nih.gov/pubmed/21426233

 

 

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