The constituents of licorice (Glycyrrhiza uralensis) differentially suppress nitric oxide production in interleukin-1β-treated hepatocytes

Abstract

Licorice (Glycyrrhizae radix) is the roots and stolons of Glycyrrhiza uralensis Fischer or Glycyrrhiza glabra Linnaeus in the Japanese Pharmacopoeia. Glycyrrhizae radix has been widely used as a sweetener and a traditional medicine. A Glycyrrhizae radix extract contains many constituents and has antispasmodic, antitussive, anti-ulcer, and anti-inflammatory effects. However, reports comparing the anti-inflammatory effects of these constituents are very few. Here, we purified several constituents from the roots and stolons of G. uralensis and examined and compared their anti-inflammatory effects by monitoring the levels of the inflammatory mediator, nitric oxide (NO), in interleukin (IL)-1β-treated rat hepatocytes. From the G. uralensis extract, we purified the main constituent glycyrrhizin and the constituents that are characteristic of G. uralensis (chalcones and flavanones). These constituents suppressed NO production in IL-1β-treated rat hepatocytes, and isoliquiritigenin showed the greatest suppression activity. Isoliquiritigenin, isoliquiritin, and liquiritigenin significantly decreased both protein and mRNA for the inducible nitric oxide synthase. These constituents reduced the levels of mRNAs encoding tumor necrosis factor α and IL-6. In contrast, although glycyrrhizin is abundant, it showed a 100-fold lower potency in NO suppression. Therefore, both glycyrrhizin and the minor constituents (isoliquiritigenin, isoliquiritin, and liquiritigenin) may be responsible for the anti-inflammatory effects of G. uralensis. It is also implied that these constituents may have a therapeutic potential for inflammatory hepatic disorders.

Cinnamomi Cortex and Scutellariae Radix in the Japanese herbal medicine Kampo saireito inhibit expression of iNOS through different mechanisms in hepatocytes

“…In previous studies, we have demonstrated that Glycyrrhizae Radix suppressed NO production in IL‐1β‐treated hepatocytes . The present study reveals that most of the crude drugs (except Pinelliae Tuber) in saireito depressed the NO production.…”

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

“…Furthermore, ILG and LG reduced the levels of both iNOS mRNA and protein in primary rat hepatocytes. Moreover, TNF-α and IL-6 mRNA levels were downregulated by ILG and LG, supporting anti-inflammatory effects in hepatocytes ( Tanemoto et al, 2015 ).…”

Isoliquiritigenin Pretreatment Induces Endoplasmic Reticulum Stress-Mediated Hormesis and Attenuates Cisplatin-Induced Oxidative Stress and Damage in LLC-PK1 Cells

“…IsoLQ is a flavonoid with anti-inflammatory, antitumoral, and antioxidant properties [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 16 , 59 ] that exerts protective effects in liver and kidney cells [ 3 , 4 , 9 , 16 , 17 , 18 ]. In addition, it has been demonstrated that IsoLQ does not interfere with CP antineoplastic activity [ 16 ].…”

“…The flavonoid 4,2′,4′-trihydroxichalcone, also known as isoliquiritigenin (IsoLQ) ( Figure 1 ), proceeds from the roots and rhizomes of licorice ( Glycyrrizha glabra ). It is used in Asia as an herbal medicine due to its anti-inflammatory, antimicrobial, antitumoral, and antioxidant properties [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. Regarding its antioxidant activity, it has been reported that IsoLQ scavenges reactive oxygen species (ROS), such as the superoxide anion (O 2 ●− ), hydroxyl radical, hydrogen peroxide, and singlet oxygen [ 4 , 7 ], and induces phase II cytoprotective enzymes’ expression [ 9 , 10 ].…”