Acute kidney injury (AKI) induced by cisplatin (CP), a first-line anticancer drug for chemotherapy, is common. To date, there is an urgent need to find effective treatments to reduce the nephrotoxicity caused by CP. Meanwhile, the restoration of mitochondrial dysfunction shows potential to be used as an adjunct to conventional therapeutic strategies. This study found that liquiritigenin can ameliorate mitochondrial dysfunction and acute kidney injury induced by CP in mice. The intraperitoneal injection of 15 mg/kg body weight liquiritigenin for 2 days markedly protected against CP-induced mitochondrial dysfunction, restored renal tubule and mitochondrial morphology, decreased blood Scr and BUN levels, and decreased cell apoptosis. Furthermore, the elevated expression of SIRT3 induced by liquiritigenin, which can be upregulated by NRF2, was confirmed in vivo and in vitro. The underlying protective mechanisms of liquiritigenin in CP-induced nephrotoxicity were then investigated. Molecular docking results showed that liquiritigenin has potent binding activities to KEAP1, GSK-3β and HRD1. Further results showed that liquiritigenin induced the nuclear translocation of NRF2 and increased the levels of mitochondrial bioenergetics-related protein such as PGC-1α, and TFAM, which are related to NRF2 activity and mitochondrial biogenesis. In addition, liquiritigenin was found to possibly reverse the decrease in BCL2/BAX ratio induced by CP in live cultured renal tubule epithelial cells. Collectively, these results indicated that liquiritigenin could be used as a potential nephroprotective agent to protect against cisplatin-induced acute kidney injury in a NRF2-dependent manner by improving mitochondria function.

Licorice (Gan-Cao, licorice) is a natural antioxidant and roasted licorice is the most common processing specification used in traditional Chinese medicine prescriptions. Traditional Chinese medicine theory deems that the honey-roasting process can promote the efficacy of licorice, including tonifying the spleen and augmenting “Qi” (energy). The antioxidant activity and mechanisms underlying roasted licorice have not yet been reported. In this study, we found that roasted licorice could relieve the oxidative stress injury induced by metronidazole (MTZ) and could restrain the production of excessive reactive oxygen species (ROS) induced by 2,2′-azobis (2-methylpropionamidine) dihydrochloride (AAPH) in a zebrafish model. It was further found that roasted licorice could exert its oxidative activity by upregulating the expression of key genes such as heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), glutamate–cysteine ligase modifier subunit (GCLM), and glutamate–cysteine ligase catalytic subunit (GCLC) in the nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway both in vivo and in vitro. Furthermore, consistent results were obtained showing that rat serum containing roasted licorice was estimated to reduce cell apoptosis induced by H₂O₂. Then, the UHPLC-Q-Exactive Orbitrap MS analysis results elucidated the chemical composition of rat plasma containing roasted licorice extracts, including ten prototype chemical components and five metabolic components. Among them, six compounds were found to have binding activity with Kelch-like ECH-associated protein 1 (KEAP1), which plays a crucial role in the transcriptional activity of NRF2, using a molecular docking simulation. The results also showed that liquiritigenin had the strongest binding ability with KEAP1. Immunofluorescence further confirmed that liquiritigenin could induce the nuclear translocation of NRF2. In summary, this study provides a better understanding of the antioxidant effect and mechanisms of roasted licorice, and lays a theoretical foundation for the development of a potential antioxidant for use in clinical practice.

Honey is a natural sweet substance produced by bees from nectar and plant secretions, which is abundant in nutrients and exhibits excellent biological activities. However, owing to deficiencies in the quality control index system, prominent issues such as honey adulteration and improper processing are prevalent in the current market, resulting in a severe decline in honey quality. Therefore, this study focuses on acacia honey, one of the four major honey varieties in China, by screening its characteristic components and analyzing the correlation between these components and immunomodulatory activity, aiming to provide targeted theoretical basis and indicator support for resolving the aforementioned practical issues. The results demonstrated that natural acacia honey (NAH) had significant advantages over commercial acacia honey (CAH) in key quality indices (total flavonoids, total phenols, proline content, amylase activity, etc.) and quality consistency, with significantly higher immunomodulatory activity. Combined with machine learning and chemometric analyses, hesperetin and pinocembrin were confirmed as the characteristic components of NAH from the 50 components identified via ultra‐performance liquid chromatography‐quadrupole‐electrostatic field orbitrap mass spectrometry (UPLC‐QE‐MS) analysis. In vitro experiments demonstrated that both components at 50 μM effectively promoted mouse splenic lymphocyte proliferation, reduced NO and TNF‐α secretion in LPS‐induced RAW264.7 macrophages, and showed no obvious cytotoxicity, indicating their potential as characteristic markers for evaluating NAH quality and functional activity. Further network pharmacology and molecular docking studies indicated that hesperetin and pinocembrin could mediate immunomodulatory effects by regulating 10 core targets including MMP9, MMP2, BCL2, and SRC, as well as the PI3K‐AKT pathway, with the markers showing the strongest binding activity toward MMP2. This study established a characteristic marker identification system for NAH, and provided scientific indicator support for formulating acacia honey quality standards and improvement of processing technologies.