Novel 18β-glycyrrhetinic acid derivatives as a Two-in-One agent with potent antimicrobial and anti-inflammatory activity

Tu, Borong; Liang, Jianying; Ou, Yi; Zahang, Xinyue; Zheng, Wende; Wu, Rihui; Gan, Li‐She; Li, Dongli; Lu, Yu‐Jing; Wu, Jia‐Qiang; Hong, W. David; Zhang, Kun; Wu, Panpan; Jin, Jingwei; Wong, Wing‐Leung

doi:10.1016/j.bioorg.2022.105714

Cited by 12 publications

(6 citation statements)

References 51 publications

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“…Previous data proved that Rifampicin could achieve protective effects by reducing AB apoptosis, oxidative stress, and pro-inflammatory cytokine release [ 33 ]. As to bacteria-induced inflammation, GA could exert its anti-inflammatory activity by down-regulating NO, pro-inflammatory cytokines, chemokines, and anti-inflammatory cytokines, and the anti-inflammatory mechanism may involve inhibition of NF-κB, mitogen-activated protein kinase (MAPKs) and phosphatidylinositol-3-kinases (PI3K) /protein kinase B (PKB) related inflammatory signaling pathways and Nrf2 / heme oxygenase 1 (HO-1) signaling pathway activation [ 21 ]. In this study, we found that MDR-AB could activate the NF-κB signaling pathway by binding to TLRs receptors, and increased the expression of inflammatory cytokines IL-1β, IL-6 and TNF.…”

Section: Discussionmentioning

confidence: 99%

“…Glycyrrhetinic acid (GA) was the main effective component of Licorice [ 20 ]. GA has various pharmacological activities, including antibacterial, anti-inflammatory, antiviral, and other effects, and treating inflammatory diseases caused by microbial infection [ 21 – 23 ]. For instance, GA had anti-inflammatory effects on radiation-induced skin damage by inhibiting the activation of p38 mitogen activated protein kinase (p38MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways, as well as the DNA-binding activity of P65 and activating protein-1 (AP-1), thereby inhibiting the production of pro-inflammatory cytokines [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

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Glycyrrhetinic acid protects against Multidrug-resistant Acinetobacter baumannii-induced lung epithelial cells injury by regulating inflammation and oxidative stress

Guo

Jin

Zhou

et al. 2023

BMC Pharmacol Toxicol

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Glycyrrhetinic acid (GA) is a bio-effective component of Licorice. The GA is a monomer and the ingredient is an Oleanane-type pentacyclic triterpenes that has been used as a remedy for years. Due to the abuse of antibiotics, people pay attention to the emergence of Multidrug-resistant Acinetobacter baumannii (MDR-AB). As a conditional pathogen, MDR-AB causes severe infection, endangering human lives. Our previous studies found GA played an important role in Yinhua Pinggan, a Chinese medicine. However, whether GA could protect lung epithelium from MDR-AB-induced cell injury was elusive. Herein, we investigated the effects of GA on MDR-AB-infected A549 cells. The results showed GA had slightly antibacterial activity to MDR-AB in the GA (high concentration) but no impact on drug resistance genes. Notwithstanding, GA could reverse MDR-AB-induced cell apoptosis, hampered adhesion and invasion of MDR-AB to cells, and inhibit pro-inflammatory cytokines expression of IL-1β, IL-6, and TNF. Besides, MDR-AB-induced reactive oxygen species, pro-oxidative protein malonaldehyde, and myeloperoxidase of cells were decreased by GA, while antioxidative proteins were recovered, showing antioxidative capacity of GA might play a critical role. The expressions of toll-like receptor (TLRs) - 1, 2, 4, 5, 6, and 9 were increased by MDR-AB infection, while GA reversed the tendency. Interestingly, GA inhibited MDR-AB induced myeloiddifferentiationfactor88 expression (MYD88), one downstream con-factors of TLRs, but no affection on Interferon regulatory Factor 3 (IRF3), the other one, indicating GA inhibited MDR-AB induced cell injury by impact TLR/MYD88 pathway to attenuate inflammation. Altogether, our results demonstrated that GA protects against MDR-AB-induced cell injury through its antioxidative and anti-inflammatory properties, which deserve further study in the future.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Glycyrrhetinic acid protects against Multidrug-resistant Acinetobacter baumannii-induced lung epithelial cells injury by regulating inflammation and oxidative stress

Guo

Jin

Zhou

et al. 2023

BMC Pharmacol Toxicol

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“…18 β -Glycyrrhetinic acid (GA, Figure ), an oleanane-type triterpenoid, is a major active metabolite of glycyrrhizic acid in vivo after the hydrolysis of glycyrrhizic acid by the intestinal microorganism to remove two glucuronic acids. , Recently, investigations on GA mainly focus on its biological potentials, such as anti-tumor, anti-inflammatory, immunoregulatory, antioxidative, and hepatoprotective effects. − In 1958, GA’s anti-inflammatory effect is first reported, , and subsequent studies have demonstrated that its effect depended on nuclear factor erythroid 2-related factor 2. , Furthermore, GA regulates the phosphoinositide 3-kinase (PI3K)/Akt-mediated mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways as well, exerting an anti-inflammatory effect. − However, a mass of GA accumulates in the gut after its oral administration, reducing the bioavailability and influencing the bioactivity under the action of the intestinal microbe. Therefore, we used the human intestinal fungus, Aspergillus niger RG13B1 isolated from human feces, to mimic the metabolism of GA and search for its structural diversity and biodiversity.…”

Section: Introductionmentioning

confidence: 99%

Biotransformation of 18β-Glycyrrhetinic Acid by Human Intestinal Fungus Aspergillus niger RG13B1 and the Potential Anti-Inflammatory Mechanism of Its Metabolites

Zhang

Wang

et al. 2022

J. Agric. Food Chem.

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18β-Glycyrrhetinic acid (GA) is a triterpenoid possessing an anti-inflammatory activity in vivo, while the low bioavailability limits its application due to its intestinal accumulation. In order to investigate the metabolism of GA in intestinal microbes, it was incubated with human intestinal fungus Aspergillus niger RG13B1, finally leading to the isolation and identification of three new metabolites (1−3) and three known metabolites (4−6) based on 1D and 2D NMR and high-resolution electrospray ionization mass spectroscopy spectra. Metabolite 6 could target myeloid differentiation protein 2 (MD2) to suppress the activation of nuclear factor-kappa B (NF-κB) signaling pathway via inhibiting the nuclear translocation of p65 to downregulate its target proteins and genes in lipopolysaccharide (LPS)-mediated RAW264.7 cells. Molecular dynamics suggested that metabolite 6 interacted with MD2 through the hydrogen bond of amino acid residue Arg90. These findings demonstrated that metabolite 6 could serve as a potential candidate to develop the new inhibitors of MD2.

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“…[20] 18β-GA is one of the key bioactive compounds of licorice, one of the most commonly used herbs in traditional Chinese medicine. [21] In the literature data, 18β-GA has been shown a variety of pharmacological actions, including anticancer, antiviral, anti-inflammatory, antioxidant, and hepatoprotective effects. [21][22][23] In addition, it has been stated that GA has antiapoptotic, neuroprotective, and cardioprotective effects.…”

mentioning

confidence: 99%

“…[21] In the literature data, 18β-GA has been shown a variety of pharmacological actions, including anticancer, antiviral, anti-inflammatory, antioxidant, and hepatoprotective effects. [21][22][23] In addition, it has been stated that GA has antiapoptotic, neuroprotective, and cardioprotective effects. [20,24] Recently, GA has been reported to enhance the protective effects against doxorubicin-induced cardiotoxicity by activating the Nrf2/ HO-1 signaling pathway.…”

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confidence: 99%

18β‐Glycyrrhetinic acid exerts cardioprotective effects against BPA‐induced cardiotoxicity through antiapoptotic and antioxidant mechanisms

Bayav,

Darendelioğlu,

Caglayan

2024

J Biochem & Molecular Tox

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Bisphenol A (BPA) is a synthetic environmental pollutant widely used in industry, as well as is an endocrine disrupting chemicals and has a toxic effects on heart tissue. The aim of this study is to reveal the cardioprotective effects of 18β‐glycyrretinic acid (GA) against BPA‐induced cardiotoxicity in rats. In this study, 40 male rats were used and five different groups (each group includes eight rats) were formed. The rats were applied BPA (250 mg/kg b.w.) alone or with GA (50 and 100 mg/kg b.w.) for 14 days. Rats were killed on Day 15 and heart tissues were taken for analysis. GA treatment decreased serum lactate dehydrogenase and creatine kinase MB levels, reducing BPA‐induced heart damage. GA treatment showed ameliorative effects against lipid peroxidation and oxidative stress caused by BPA by increasing the antioxidant enzyme activities (glutathione peroxidase, superoxide dismutase, and catalase) and GSH level of the heart tissue and decreasing the MDA level. In addition, GA showed antiapoptotic effect by increasing Bcl‐2, procaspase‐3, and ‐9 protein expression levels and decreasing Bax, cytochrome c, and P53 protein levels in heart tissue. As a result, it was found that GA has cardioprotective effects on heart tissue by exhibiting antioxidant and antiapoptotic effects against heart damage caused by BPA, an environmental pollutant. Thus, it was supported that GA could be a potential cardioprotective agent.

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Novel 18β-glycyrrhetinic acid derivatives as a Two-in-One agent with potent antimicrobial and anti-inflammatory activity

Cited by 12 publications

References 51 publications

Glycyrrhetinic acid protects against Multidrug-resistant Acinetobacter baumannii-induced lung epithelial cells injury by regulating inflammation and oxidative stress

Glycyrrhetinic acid protects against Multidrug-resistant Acinetobacter baumannii-induced lung epithelial cells injury by regulating inflammation and oxidative stress

Biotransformation of 18β-Glycyrrhetinic Acid by Human Intestinal Fungus Aspergillus niger RG13B1 and the Potential Anti-Inflammatory Mechanism of Its Metabolites

18β‐Glycyrrhetinic acid exerts cardioprotective effects against BPA‐induced cardiotoxicity through antiapoptotic and antioxidant mechanisms

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