Isoliquiritigenin and liquiritin from Glycyrrhiza uralensis inhibit α-synuclein amyloid formation

Liao, Mingyan; Zhao, Yongdan; Huang, Lizi; Huang, Kun

doi:10.1039/c6ra17770k

Cited by 15 publications

(10 citation statements)

References 48 publications

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“…G. uralensis is one of the main herbs in approximately 40% of traditional medical prescriptions described in pharmacopeias for the treatment of PD. ILG showed inhibitory effects against membrane toxicity in in vitro aggregated α-syn and disaggregated preformed mature fibrils in a transgenic Caenorhabditis elegans PD model ( Liao et al, 2016 ).…”

Section: Pharmacological Activities Against Nddsmentioning

confidence: 99%

Phytochemical and Pharmacological Role of Liquiritigenin and Isoliquiritigenin From Radix Glycyrrhizae in Human Health and Disease Models

Mahesh

Kim

Lee

et al. 2018

Front. Aging Neurosci.

127

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The increasing lifespan in developed countries results in age-associated chronic diseases. Biological aging is a complex process associated with accumulated cellular damage by environmental or genetic factors with increasing age. Aging results in marked changes in brain structure and function. Age-related neurodegenerative diseases and disorders (NDDs) represent an ever-growing socioeconomic challenge and lead to an overall reduction in quality of life around the world. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are most common degenerative neurological disorders of the central nervous system (CNS) in aging process. The low levels of acetylcholine and dopamine are major neuropathological feature of NDDs in addition to oxidative stress, intracellular calcium ion imbalance, mitochondrial dysfunction, ubiquitin-proteasome system impairment and endoplasmic reticulum stress. Current treatments minimally influence these diseases and are ineffective in curing the multifunctional pathological mechanisms. Synthetic neuroprotective agents sometimes have negative reactions as an adverse effect in humans. Recently, numerous ethnobotanical studies have reported that herbal medicines for the treatment or prevention of NDDs are significantly better than synthetic drug treatment. Medicinal herbs have traditionally been used around the world for centuries. Radix Glycyrrhizae (RG) is the dried roots and rhizomes of Glycyrrhiza uralensis or G. glabra or G. inflata from the Leguminosae/Fabaceae family. It has been used for centuries in traditional medicine as a life enhancer, for the treatment of coughs and influenza, and for detoxification. Diverse chemical constituents from RG have reported including flavanones, chalcones, triterpenoid saponins, coumarines, and other glycosides. Among them, flavanone liquiritigenin (LG) and its precursor and isomer chalcone isoliquiritigenin (ILG) are the main bioactive constituents of RG. In the present review, we summarize evidence in the literature on the structure and phytochemical properties and pharmacological applications of LG and ILG in age-related diseases to establish new therapeutics to improve human health and lifespan.

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Section: Pharmacological Activities Against Nddsmentioning

confidence: 99%

Phytochemical and Pharmacological Role of Liquiritigenin and Isoliquiritigenin From Radix Glycyrrhizae in Human Health and Disease Models

Mahesh

Kim

Lee

et al. 2018

Front. Aging Neurosci.

127

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“…Additionally, previously established methods by Shan et al applied liquid–liquid extraction which requires acidification with HCl for the extraction of glycyrrhizin and glycyrrhetinic acid and a larger plasma sample volume (100 μL) and the LLOQs for glycyrrhizin and three flavones were 1 and 0.34–0.5 ng/mL, respectively [19]. Herein, we used a protein-precipitation method with methanol containing IS rather than a previously described liquid–liquid extraction method or sample preparation via evaporation and reconstitution method [8,17,19], and then directly injected an aliquot of the supernatant after centrifugation of protein-precipitated plasma samples.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, glycyrrhizin is commonly used owing to its therapeutic effects against arthritis, hepatotoxicity, leukemia, allergies, stomach ulcers, and inflammation. Moreover, the major active flavonoids of Glycyrrhizae Radix, such as isoliquiritigenin, liquiritin, and liquiritigenin [8], are often used as anti-depressants or as anticancer, cardio-protective, anti-microbial, and neuroprotective agents [9,10,11,12,13,14]. Based on the literature search, glycyrrhizin, isoliquiritigenin, liquiritin, and liquiritigenin were selected as predominant or pharmacological components of GRE.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Determination and Pharmacokinetic Characterization of Glycyrrhizin, Isoliquiritigenin, Liquiritigenin, and Liquiritin in Rat Plasma Following Oral Administration of Glycyrrhizae Radix Extract

et al. 2019

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Glycyrrhizae Radix is widely used as herbal medicine and is effective against inflammation, various cancers, and digestive disorders. We aimed to develop a sensitive and simultaneous analytical method for detecting glycyrrhizin, isoliquiritigenin, liquiritigenin, and liquiritin, the four marker components of Glycyrrhizae Radix extract (GRE), in rat plasma using liquid chromatography-tandem mass spectrometry and to apply this analytical method to pharmacokinetic studies. Retention times for glycyrrhizin, isoliquiritigenin, liquiritigenin, and liquiritin were 7.8 min, 4.1 min, 3.1 min, and 2.0 min, respectively, suggesting that the four analytes were well separated without any interfering peaks around the peak elution time. The lower limit of quantitation was 2 ng/mL for glycyrrhizin and 0.2 ng/mL for isoliquiritigenin, liquiritigenin, and liquiritin; the inter- and intra-day accuracy, precision, and stability were less than 15%. Plasma concentrations of glycyrrhizin, isoliquiritigenin, liquiritigenin, and liquiritin were quantified for 24 h after a single oral administration of 1 g/kg GRE to four rats. Among the four components, plasma concentration of glycyrrhizin was the highest and exhibited a long half-life (23.1 ± 15.5 h). Interestingly, plasma concentrations of isoliquiritigenin and liquiritigenin were restored to the initial concentration at 4–10 h after the GRE administration, as evidenced by liquiritin biotransformation into isoliquiritigenin and liquiritigenin, catalyzed by fecal lysate and gut wall enzymes. In conclusion, our analytical method developed for detecting glycyrrhizin, isoliquiritigenin, liquiritigenin, and liquiritin could be successfully applied to investigate their pharmacokinetic properties in rats and would be useful for conducting further studies on the efficacy, toxicity, and biopharmaceutics of GREs and their marker components.

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“… EC 50 /IC 50 Other targets Status Ref. Antibiotics Glucosides 21 EC 50 = 6.96 μM Aβ, tau a [ 103 , 105 ] 51−53 N/A N/A a, a, b [ 137 – 139 ] 22 EC 50 = 6.06 μM Aβ a [ 105 ] Quinones Dopamine and its analogs 54 IC 50 = 30 μM N/A a [ 140 ] 23 IC 50 = 7.1 μM Aβ, tau a [ 105 , 106 , 109 ] 55 IC 50 = 29 μM N/A a [ 140 ] 24−28 N/A N/A a [ 108 ] 56 IC 50 = 18 μM N/A a [ 140 ] Dyes and pigments 57 IC 5 0 = 15 μM N/A a [ 140 ] 29 IC 50 = 14.7 μM Aβ, tau a [ 109 ] 58−59 …”

Section: Small Molecule Inhibitors Against α-Synuclein Aggregationmentioning

confidence: 99%

“…In vitro studies have demonstrated that compound 53 can inhibit both oligomerization and fibrillation of α-syn. In a transgenic C. elegans expressing human α-syn, compound 53 significantly inhibited α-syn aggregation and extended the life span of the treated worms [ 139 ].…”

Section: Small Molecule Inhibitors Against α-Synuclein Aggregationmentioning

confidence: 99%

Advances in the development of imaging probes and aggregation inhibitors for alpha-synuclein

Ryan

Rudrawar

et al. 2019

Acta Pharmacol Sin

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Abnormal protein aggregation has been linked to many neurodegenerative diseases, including Parkinson’s disease (PD). The main pathological hallmark of PD is the formation of Lewy bodies (LBs) and Lewy neurites, both of which contain the presynaptic protein alpha-synuclein (α-syn). Under normal conditions, native α-syn exists in a soluble unfolded state but undergoes misfolding and aggregation into toxic aggregates under pathological conditions. Toxic α-syn species, especially oligomers, can cause oxidative stress, membrane penetration, synaptic and mitochondrial dysfunction, as well as other damage, leading to neuronal death and eventually neurodegeneration. Early diagnosis and treatments targeting PD pathogenesis are urgently needed. Given its critical role in PD, α-syn is an attractive target for the development of both diagnostic tools and effective therapeutics. This review summarizes the progress toward discovering imaging probes and aggregation inhibitors for α-syn. Relevant strategies and techniques in the discovery of α-syn-targeted drugs are also discussed.

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Isoliquiritigenin and liquiritin from Glycyrrhiza uralensis inhibit α-synuclein amyloid formation

Abstract: Bioactive isoliquiritigenin and liquiritin inhibit α-synuclein aggregation and extend the life span of the C. elegans model of Parkinson's disease.

Cited by 15 publications

References 48 publications

Phytochemical and Pharmacological Role of Liquiritigenin and Isoliquiritigenin From Radix Glycyrrhizae in Human Health and Disease Models

Phytochemical and Pharmacological Role of Liquiritigenin and Isoliquiritigenin From Radix Glycyrrhizae in Human Health and Disease Models

Simultaneous Determination and Pharmacokinetic Characterization of Glycyrrhizin, Isoliquiritigenin, Liquiritigenin, and Liquiritin in Rat Plasma Following Oral Administration of Glycyrrhizae Radix Extract

Advances in the development of imaging probes and aggregation inhibitors for alpha-synuclein

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