Flavonoids derived from licorice suppress LPS-induced acute lung injury in mice by inhibiting the cGAS-STING signaling pathway

Wen, Jincai; Qin, Shuanglin; Li, Yurong; Zhang, Ping; Zhan, Xiaoyan; Ming-xia, Fang; Chen, Shi; Mu, Wenqing; Kan, Wen; Zhao, Jia; Hui, Siwen; Hou, Manting; Li, Hui; Xiao, Xiaohe; Xu, Guang; Bai, Zhaofang

doi:10.1016/j.fct.2023.113732

Cited by 17 publications

(4 citation statements)

References 44 publications

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“…In addition to direct antiviral drugs, there is a growing interest in the role of immunity which consist of adaptive and innate immunity in the treatment of HBV. cGAS-STING pathway, one of the important antiviral pathways [ 38 , 39 ], has been reported to play an essential role in inhibiting HBV. SC, one of the main lignan of Schisandra chinensis (sovereign drug of LWWL), has been reported to facilitate the activation of cGAS-STING pathway in macrophages [ 32 ].…”

Section: Resultsmentioning

confidence: 99%

The combination of Schisandrin C and Luteolin synergistically attenuates hepatitis B virus infection via repressing HBV replication and promoting cGAS-STING pathway activation in macrophages

Wu,

Zhao,

et al. 2024

Chin Med

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Background HBV infection can result in severe liver diseases and is one of the primary causes of liver cell carcinoma-related mortality. Liuwei Wuling tablet (LWWL) is a traditional Chinese medicine formula, with a protecting liver and decreasing enzyme activity, usually used to treat chronic hepatitis B with NAs in clinic. However, its main active ingredients and mechanism of action have not been fully investigated. Hence, we aimed to screen the active ingredient and effective ingredient combinations from Liuwei Wuling tablet to explore the anti-herpatitis B virus activity and mechanism. Methods Analysis and screening of effective antiviral components in LWWL by network pharmacology, luteolin (Lut) may be a compound with significant antiviral activity. The mechanism of antiviral action of Lut was also found by real-time PCR detection and western blotting. Meanwhile, we established a co-culture model to investigate the antiviral mechanism of Schisandrin C (SC), one of the main active components of Schisandra chinensis fructus (the sovereign drug of LWWL). Next, HBV-infected mice were established by tail vein injection of pAAV-HBV1.2 plasmid and administered continuously for 20 days. And their antiviral capacity was evaluated by checking serum levels of HBsAg, HBeAg, levels of HBV DNA, and liver levels of HBcAg. Results In this study, we conducted network pharmacology analysis on LWWL, and through in vitro experimental validation and data analysis, we found that luteolin (Lut) possessed obviously anti-HBV activity, inhibiting HBV replication by downregulating hepatocyte nuclear factor 4α (HNF4α) via the ERK pathway. Additionally, we established a co-culture system and proved that SC promoted activation of cGAS-STINIG pathway and IFN-β production in THP-1 cells to inhibit HBV replication in HepG2.2.15 cells. Moreover, we found the combination of SC and Lut shows a greater effect in inhibiting HBV compared to SC or Lut alone in HBV-infected mice. Conclusion Taken together, our study suggests that combination of SC and Lut may be potential candidate drug for the prevention and treatment of chronic hepatitis B.

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Section: Resultsmentioning

confidence: 99%

The combination of Schisandrin C and Luteolin synergistically attenuates hepatitis B virus infection via repressing HBV replication and promoting cGAS-STING pathway activation in macrophages

Wu,

Zhao,

et al. 2024

Chin Med

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“…After adaptive feeding for six days, the 51 male mice were randomly divided into the normal group (n = 6), the GP group (n = 16), the GC group (n = 6), the XP group (n = 17) and the XC group (n = 6). According to previously described methods [14], the other two groups but not the normal group, GP group or XP group were forced to inhale 50 µL of 1 mg/mL LPS solution into the trachea on the rst, third, fth and seventh days, respectively (Fig. 1A).…”

Section: Animalsmentioning

confidence: 99%

Pneumonia activates renal antioxidant defense function to reduce the damage of aristolochic acid I through Keap1/Nrf2/NQO1 signaling pathway

Wang,

Li,

Qin

et al. 2024

Preprint

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Aristolochic acids (AAs) are a group of compounds widely found in Aristolochiaceae, and the main toxic component of AAs is aristolochic acid I (AAI). AAI causes severe direct nephrotoxicity and carcinogenicity. Plants containing AAI are widely used around the world; for example, Asari Radix et Rhizoma (ARR) contains trace amounts of aristolochic acid and is still included in the Chinese Pharmacopoeia. Based on the theory of therapy for syndrome differentiation in traditional Chinese medicine, we established a 7-day mouse model of pneumonia and observed that kidney damage in the pneumonia group was significantly lower than that in the healthy group after the same treatment. Subsequently, the carcinogenic metabolite aristolochic acid-DNA adduct standards were synthesized, and assays were established. No adduct formation was detected in our limit of quantification (500 pg/ml) in the ARR group, while the adduct formation in the Caulis Aristolochiae Manshuriensis (CAM) group, whose content of AAI is 900 times that of the ARR, was significantly lower than that in the healthy group in the pneumonia state. Here, we demonstrate that the safety risk of ARR is not high at normal doses. Western blot analysis revealed that the level of the AAI metabolic enzyme NQO1 in the pneumonia group was significantly lower than that in the healthy group. Combined with the transcriptomic results, we speculate that kidney injury and adduct production in the pneumonia group were lower than those in the healthy group because of the ROS-Keap1-Nrf2-NQO1 pathway.

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“…Glycyrrhizin has been shown to inhibit activation of the HMGB1/TLR9 pathway to alleviate sepsis-induced acute respiratory distress syndrome ( Zhao et al, 2016 ). In addition, licorice flavonoids, licorice extracts, Licochalcone B, and Glabridin have all been shown to have significant inhibitory effects on the cGAS-STING pathway and its mediated inflammatory disorders ( Wen et al, 2023a ; Wen et al, 2023b ; Luo et al, 2023 ; Luo et al, 2024 ). Therefore, we speculate that GUP, a major component of licorice, may also have an effect on the cGAS-STING pathway.…”

Section: Introductionmentioning

confidence: 99%

Glycyrrhiza uralensis polysaccharides ameliorates cecal ligation and puncture-induced sepsis by inhibiting the cGAS-STING signaling pathway

Hui,

Kan,

Qin

et al. 2024

Front. Pharmacol.

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Flavonoids derived from licorice suppress LPS-induced acute lung injury in mice by inhibiting the cGAS-STING signaling pathway

Cited by 17 publications

References 44 publications

The combination of Schisandrin C and Luteolin synergistically attenuates hepatitis B virus infection via repressing HBV replication and promoting cGAS-STING pathway activation in macrophages

The combination of Schisandrin C and Luteolin synergistically attenuates hepatitis B virus infection via repressing HBV replication and promoting cGAS-STING pathway activation in macrophages

Pneumonia activates renal antioxidant defense function to reduce the damage of aristolochic acid I through Keap1/Nrf2/NQO1 signaling pathway

Glycyrrhiza uralensis polysaccharides ameliorates cecal ligation and puncture-induced sepsis by inhibiting the cGAS-STING signaling pathway

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