18α-Glycyrrhetinic acid (GA) ameliorates fructose-induced nephropathy in mice by suppressing oxidative stress, dyslipidemia and inflammation

Cheng, Xiaoli; Qiu, Linwei; Wang, Fen

doi:10.1016/j.biopha.2019.109702

Cited by 17 publications

(14 citation statements)

References 61 publications

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“…Along with the antitumor potential, GA displayed significant anti-inflammatory activity in vitro in lipopolysaccharide (LPS)-and trychophytin-activated RAW264.7 macrophages [ [48][49][50][51] and fructose-stimulated HK2 kidney cells [52], as well as in a panel of murine models [52][53][54][55][56]. Some GA derivatives also showed good anti-inflammatory effects in LPS-challenged macrophages in vitro [57] and experimental inflammation induced by histamine, carrageenan, influenza A, or CCl 4 in mice [58][59][60][61].…”

Section: Discussionmentioning

confidence: 99%

“…Given that GA and its derivatives display significant anti-inflammatory potential, along with their antitumor activity [ [48][49][50][51][52][53][54][55][56][57][58][59][60][61], we questioned in the second block of the study whether the novel GA derivatives-3'-substituted-1',2',4'-oxadiazoles and their O-acylated amidoximes-have anti-inflammatory properties. Firstly, in order to decline the number of processed compounds and only select hypothetically more bioactive molecules, an in silico approach was used.…”

Section: Anti-inflammatory Potential Of Novel Ga Derivativesmentioning

confidence: 99%

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Novel 3′-Substituted-1′,2′,4′-Oxadiazole Derivatives of 18βH-Glycyrrhetinic Acid and Their O-Acylated Amidoximes: Synthesis and Evaluation of Antitumor and Anti-Inflammatory Potential In Vitro and In Vivo

Markov

Sen’kova

Popadyuk

et al. 2020

IJMS

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A series of novel 18βH-glycyrrhetinic acid (GA) derivatives containing 3′-(alkyl/phenyl/pyridin(-2″, -3″, and -4″)-yl)-1′,2′,4′-oxadiazole moieties at the C-30 position were synthesized by condensation of triterpenoid’s carboxyl group with corresponding amidoximes and further cyclization. Screening of the cytotoxicity of novel GA derivatives on a panel of tumor cell lines showed that the 3-acetoxy triterpenoid intermediates—O-acylated amidoxime 3a-h—display better solubility under bioassay conditions and more pronounced cytotoxicity compared to their 1′,2′,4′-oxadiazole analogs 4f-h (median IC50 = 7.0 and 49.7 µM, respectively). Subsequent replacement of the 3-acetoxy group by the hydroxyl group of pyridin(-2″, 3″, and -4″)-yl-1′,2′,4′-oxadiazole-bearing GA derivatives produced compounds 5f-h, showing the most pronounced selective toxicity toward tumor cells (median selectivity index (SI) > 12.1). Further detailed analysis of the antitumor activity of hit derivative 5f revealed its marked proapoptotic activity and inhibitory effects on clonogenicity and motility of HeLa cervical carcinoma cells in vitro, and the metastatic growth of B16 melanoma in vivo. Additionally, the comprehensive in silico study revealed intermediate 3d, bearing the tert-butyl moiety in O-acylated amidoxime, as a potent anti-inflammatory candidate, which was able to effectively inhibit inflammatory response induced by IFNγ in macrophages in vitro and carrageenan in murine models in vivo, probably by primary interactions with active sites of MMP9, neutrophil elastase, and thrombin. Taken together, our findings provide a basis for a better understanding of the structure–activity relationship of 1′,2′,4′-oxadiazole-containing triterpenoids and reveal two hit molecules with pronounced antitumor (5f) and anti-inflammatory (3d) activities.

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Section: Discussionmentioning

confidence: 99%

Section: Anti-inflammatory Potential Of Novel Ga Derivativesmentioning

confidence: 99%

Novel 3′-Substituted-1′,2′,4′-Oxadiazole Derivatives of 18βH-Glycyrrhetinic Acid and Their O-Acylated Amidoximes: Synthesis and Evaluation of Antitumor and Anti-Inflammatory Potential In Vitro and In Vivo

Markov

Sen’kova

Popadyuk

et al. 2020

IJMS

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“…While scientific researches in animals report that fructose affects the inflammatory processes and may be related to many diseases [17,18], the researches in human bodies have not revealed the safe dose of fructose for human intake yet.…”

Section: Discussionmentioning

confidence: 99%

High fructose intake may be related to carotid artery stenosis

Kuyumcu

2021

Turkish Journal of Clinics and Laboratory

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Aim: It is known that high fructose intake is related to cardiovascular diseases but there is a limited number of researches in this era. The objective of this research is to evaluate the relation between Carotid Artery Stenosis (CAS) and high fructose intake. Material And Methods:The patients are categorized into three groups: Patients with CAS≥60% (60 patients), patients with CAS<60% (60 patients) and patients with no carotid atherosclerosis (60 patients). Nutrient intake level of patients is observed and recorded by 24-Hour Dietary Recall Forms and the intake frequency of high-fructose dietary is enquired.Physical activity levels are also evaluated. All the collected data is compared among the groups.Results: Fructose intake among ordinary people is found to be lower than the patients with CAS<60% (p<0.001). Besides, fructose intake of patients with CAS<60% is lower than fructose intake of patients with CAS≥60%. Multivariate regression analysis showed that high fructose intake is an independent risk factor for carotid stenosis over 60% (p<0.001). Fructose intake levels were higher in the calcific plaque group than in the non-calcific plaque group (p<0.001). Conclusions:We determined a high fructose intake in patients with CAS. In light of our research data, we consider high fructose intake to have a potential role in the pathophysiology of CAS.

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“…Glycyrrhetinic acid can bind to glucocorticoid receptors and has a weak glucocorticoid-like effect [ 15 ]. In addition, glycyrrhizic acid can block the production of inflammatory mediators by inhibiting the activity of phospholipase A2 and the classical activation pathway of complement C2, thus exerting anti-inflammatory effects [ 16 , 17 ]. Glycyrrhizic acid has the structural characteristics of saponin amphiphilic substances and can interact with cholesterol or phospholipids on cell membrane to induce porosity and enhance membrane permeability.…”

Section: Introductionmentioning

confidence: 99%

A novel biomimetic nanomedicine system with anti-inflammatory and anti-osteoporosis effects improves the therapy efficacy of steroid-resistant nephrotic syndrome

Zhao

Xiang

et al. 2021

J Nanobiotechnol

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Clinically, steroid-resistant nephrotic syndrome (SRNS) is always prolonged and difficult to treat and easily develops into end-stage renal disease, resulting in a low survival rate. Strategies to reverse steroid resistance and reduce the long-term use of high doses of steroid medicines are urgently needed. In this study, a novel nanoparticle drug system (Pm-GCH) with a core–shell structure was designed. Metal–organic frameworks, synthesized by glycyrrhizic acid (G) and calcium ions (Ca2+) loaded with hydrocortisone (H) were the core of the nanoparticles. Platelet membrane vesicles were the shells. The natural platelet membrane endows Pm-GCH with good biocompatibility and the ability to promote immune escape. In addition, under the chemotaxis of inflammatory factors, platelet membranes assist Pm-GCH in nonspecific targeting of the inflammatory sites of the kidney. Under an inflammatory acid environment, GCH slowly degrades and releases glycyrrhizic acid and hydrocortisone. Glycyrrhizic acid inhibits the inactivation of hydrocortisone, jointly inhibits the activity of phospholipase A2 (PLA2) and the classic activation pathway of complement C2, blocks the production of inflammatory factors, plays an anti-inflammatory role, and enhances the efficacy of hydrocortisone in the treatment of SRNS. Moreover, glycyrrhizic acid alleviates osteoporosis induced by long-term use of glucocorticoids. These results indicate that Pm-GCH is a promising treatment strategy for SRNS. Graphical Abstract

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18α-Glycyrrhetinic acid (GA) ameliorates fructose-induced nephropathy in mice by suppressing oxidative stress, dyslipidemia and inflammation

Cited by 17 publications

References 61 publications

Novel 3′-Substituted-1′,2′,4′-Oxadiazole Derivatives of 18βH-Glycyrrhetinic Acid and Their O-Acylated Amidoximes: Synthesis and Evaluation of Antitumor and Anti-Inflammatory Potential In Vitro and In Vivo

Novel 3′-Substituted-1′,2′,4′-Oxadiazole Derivatives of 18βH-Glycyrrhetinic Acid and Their O-Acylated Amidoximes: Synthesis and Evaluation of Antitumor and Anti-Inflammatory Potential In Vitro and In Vivo

High fructose intake may be related to carotid artery stenosis

A novel biomimetic nanomedicine system with anti-inflammatory and anti-osteoporosis effects improves the therapy efficacy of steroid-resistant nephrotic syndrome

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