The specification and commitment of lateral root founder cells (LRFCs) from postembryonic pericycle cells are critical steps in LR development, yet their earliest molecular determinants remain unclear. Using single-cell transcriptomics, we resolved transcriptional transitions guiding LRFC fate in Arabidopsis thaliana and identified five distinct phases of transcriptional progression during LRFC specification. Through differentially expressed gene analysis and phenotypic observation, we showed that application of exogenous GA (20 and 50 μM) promoted the nuclear migration and division in LRFCs independently of DELLA signaling, and revealed that Gibberellic acid-stimulated Arabidopsis 1 (GASA1) functions as a key mediator of gibberellin (GA) to accelerate the LRFC progression. Further histochemical staining and cytological observations demonstrated that GASA1 mediated the GA-triggered reactive oxygen species (ROS) accumulation to reinforce the LRFC commitment. The GA-GASA1-ROS module is evolutionarily conserved, with GA-ROS-driven LRFC commitment being fundamental across angiosperms. Notably, GASA1 emerged with root evolution in early land plants and diversified alongside lateral and shoot-borne root systems, revealing a conserved GA-ROS axis in plant organogenesis.

Higher grain weight and stronger seed dormancy are key objectives for improving rice (Oryza sativa) yield and inhibiting pre-harvest sprouting. Therefore, identifying genes that coordinately regulate grain weight and seed dormancy is an urgent priority. Here, we report that knocking out miR1866 (KO1866) increased grain weight and reinforced dormancy. We identified the transcript of ubiquitin-specific processing protease 7 (OsUBP7), which encodes a protein with deubiquitination activity in vitro, as the primary target of miR1866. Consistent with miRNA-directed repression, OsUBP7 transcript abundance generally showed a spatiotemporal pattern opposite to miR1866 accumulation during rice development. Overexpression of native OsUBP7 (UBP7-OE) or a miR1866-resistant form (mUBP7-OE) phenocopied KO1866 by producing heavier grains with stronger dormancy. The miR1866-OsUBP7 module also altered the expression of genes associated with sucrose and starch metabolism, cell-cycle control, grain development, and abscisic acid (ABA) biosynthesis and signaling. Accordingly, KO1866, UBP7-OE, and mUBP7-OE plants contained more ABA and responded more sensitively to exogenous ABA than wild type. OsUBP7 interacted with OsDA1 (encoded by Os06g0182500) and UBIQUITIN-CONJUGATING ENZYME (OsUCE1; encoded by Os02g0833300), thereby affecting hull cell division and ABA signaling and ultimately regulating grain weight and seed dormancy, respectively. Our results indicate that the miR1866-OsUBP7 module regulates grain weight and seed dormancy in rice, highlighting its potential for engineering crops with improved yields and stronger seed dormancy.

Abscisic acid (ABA) regulates diverse aspects of plant growth, particularly adaptive responses to abiotic stress. Although the ubiquitin-proteasome system is recognized as a pivotal pathway for degrading key components of ABA signaling, the mechanisms governing 26S proteasome activity during ABA responses remain largely unclear. Here, we show that Arabidopsis proteasome regulator 1 (PTRE1) modulates ABA signaling by regulating proteasome activity. Phenotypic analyses reveal heightened ABA sensitivity in the ptre1 mutant. Mechanistically, ABA stabilizes the PTRE1 protein, thereby enhancing 26S proteasome activity. Sucrose nonfermenting 1-related kinase 2.6 (SnRK2.6), a key kinase activated by ABA, directly interacts with and phosphorylates PTRE1, which is essential for PTRE1 stability and its function in ABA responses. Notably, loss of PTRE1 leads to increased accumulation of the ABA-insensitive 5 (ABI5) protein, and the ptre1 mutation partially suppresses the ABA-insensitive phenotype of the abi5 mutant. Collectively, these findings establish an SnRK2.6-PTRE1 module that fine-tunes proteasome activity, providing new insights into the coordinated regulation of ABA signaling through SnRK2.6-mediated dual phosphorylation of ABI5 and PTRE1.

Background Gongxuening capsule (GXN) is a commonly used Chinese patent medicine for treating gynecological diseases in China. Currently, the available detection methods are constrained and inadequate due to the complex chemical composition of the capsule. The saponin components have a wide range of polarities and a weak response in low-band ultraviolet detection, which is compounded by numerous interference peaks. These factors make it difficult to accurately quantify the active ingredients. Objective This study aims to develop the chromatographic fingerprint of GXN using high-performance liquid chromatography in conjunction with a charged aerosol detector (HPLC-CAD) and quantitatively analyze its principal components. Methods A chromatographic separation was performed on an Acclaim C30 column (3 mm & times; 250 mm, 3 & micro;m) with a gradient elution program using a mixture of acetonitrile (A) and water (B) as mobile phase: (0-5 min, 40% A; 5-20 min, 40-45% A; 20-35 min, 45-50% A; 35-45 min, 50% A). The flow rate was maintained at 0.4 mL min(-1), and the column temperature was set at 10 degrees C. An injection volume of 1 mu L was used, and the sampling frequency was 5 Hz, with a filtration constant of 3.6 s, and an atomization temperature of 50 degrees C. Six batches of GXN were subjected to chromatographic fingerprinting to establish their similarity. Furthermore, the quantification of the principal components was conducted to determine their content. Results The HPLC chromatographic fingerprint of GXN was established, and 9 common peaks were identified with 6 batches of samples sharing a close similarity, which is greater than 0.960. Polyphyllin I (PPI), polyphyllin II (PPII), polyphyllin VII (PPVII), polyphyllin D (PPD), polyphyllin H (PPH) and gracillin had a good linearity with peak area within the corresponding concentration range. Correlation coefficients were >0.999, and the recovery of the method was in the range of 98.56-101.50%, with RSD values below 2.0%. Conclusion The developed method demonstrated broad applicability, high sensitivity, excellent repeatability, and strong reliability, making it suitable for detecting and controlling the quality of complex Rhizoma Paridis Saponins (RPS) in GXN.

The promising CMS-C/Rf system has not been applied on a large scale in maize hybrid breeding due to the unclear restoration mechanism for the primary restorer ZmRf4b. In CMS-C maize, the mitochondrial chimeric gene atp6c encodes a cytotoxic variant of ATP6 that over-accumulates and disrupts the assembly of mitochondrial complex V, leading to male sterility. Here, we report the map-based cloning and functional characterization of ZmRf4b, which encodes a SQUAMOSA promoter-binding protein-like (SPL) transcription factor. Through DAP-seq and yeast two-hybrid screening, we identified ZmMAP1D, a mitochondrion-targeted methionine aminopeptidase, as a direct downstream target of ZmRf4b. ZmRf4b functions as a transcriptional repressor that directly binds the ZmMAP1D promoter; in the restorer line, the relatively low expression level of ZmRf4b weakens its repression of ZmMAP1D, permitting moderate ZmMAP1D accumulation. ZmMAP1D is then imported to mitochondria, where it co-translationally removes the N-terminal methionine of ATP6C, thereby targeting excess ATP6C for degradation. The reduction of ATP6C to normal levels restores mitochondrial complex V assembly, alleviates reactive oxygen species accumulation and tapetal programmed cell death, and ultimately restores male fertility. This study reveals a previously unrecognized fertility restoration mechanism operating through co-translational protein turnover—rather than transcriptional or translational suppression of the CMS gene—providing new insights into nucleus-mitochondria communication and mitochondrial protein homeostasis.

Environmental stressors, including pathogens, substantially affect the growth of host plants. However, how non-adapted bacteria influence nonhost plants has not been reported. Here, we reveal that infection of Arabidopsis flowers by Xanthomonas oryzae pv. oryzae PXO99A, a bacterial pathogen causing rice blight disease, suppresses ovule initiation and reduces seed number without causing visible disease symptoms. TleB, secreted by the type VI secretion system (T6SS), interacts with plant E3 ligase PUB14 and disrupts the function of the PUB14-BZR1 module, leading to decreased ovule initiation and seed yield. On the other site, PUB14 concurrently promotes TleB’s degradation. Our findings indicate that bacterial infections in nonhost plants directly repress offspring production. The regulatory mechanism by effectors PUB14-BZR1 is widely present, suggesting that plants may balance reproduction and defense and produce fewer offspring to conserve resources, thus enabling them to remain in a standby mode prepared for enhanced resistance.

Strigolactones (SLs) significantly impact agricultural production due to their central role in regulating plant morphology. As switch controllers of SL signaling, the transcriptional repressors, suppressor of MAX2 1-like 6/7/8 (SMXL6/7/8), are ubiquitinated by the F-box E3 ligase, more axillary growth 2 (MAX2) for degradation through the 26S proteasome, which is mediated by the receptor DWARF14. However, post-translational modifications and regulatory mechanisms of SMXL6/7/8 proteins remain unknown. Here, we demonstrate that Arabidopsis seedlings deficient in or overexpressing an evolutionarily conserved, plant-specific protein kinase Arabidopsis EL1-like (AEL1-4) exhibit significantly reduced or enhanced branching, respectively. Biochemical assays reveal that AEL interacts with and phosphorylates SMXL6/7/8 proteins, inhibiting their interactions with MAX2 and suppressing their degradation, thereby negatively interfering with SL-regulated branching. Notably, SL signaling reduces the expression of AEL genes dependent on action of SMXL6/7/8 and diminishes AEL-SMXL protein interactions. In summary, this study reveals the importance of protein phosphorylation in regulating SL signaling and its effects, highlighting a fine-tuning mechanism of SL signaling through phosphorylation-mediated transition between active and inactive forms of SMXL6/7/8.

Uncontrolled cell proliferation drives tumorigenesis and malignant progression, making cell cycle regulation a promising strategy for cancer therapy. Phosphorylation plays pivotal roles in cancer initiation and metastasis by regulating the cancer-related proteins. Identifying key phosphorylation sites is essential for inhibiting tumor cell proliferation and optimizing therapy strategy. Here, this study reveals the strong association of oncogene Collaborator of ARF (CARF), a cell-division regulator interacting with p53, with prognosis and survival of lymphoma patients through pan-cancer analysis. In addition, this study finds that mammalian CARF shares homology with Kip-Related Protein6 (KRP6), a cell cycle inhibitor from higher plant Arabidopsis. KRP6 is regulated by casein kinase1 via phosphorylation at serines 75 and 109, which are conservative in CARF at serines 316 and 356. Systemic assays conducted with various B-cell lymphoma cell lines and a mouse xenograft model demonstrate that the non-phosphorylation variant of CARF inhibited cell proliferation and lymphoma formation more effectively than wild-type CARF, highlighting the crucial regulatory role of phosphorylation at these conserved sites in controlling B-cell lymphoma cell proliferation. A similar suppressive effect is observed with plant KRP6, suggesting a cross-species bioengineering application. These findings enlighten the application of phosphorylation-modified proteins as therapeutic targets in precise lymphoma treatments.

Auxin regulates various aspects of plant growth and development by modulating the transcription of target genes through the degradation of auxin/indole-3-acetic acid (Aux/IAA) repressors via the 26S proteasome. Proteasome regulator 1 (PTRE1), a positive regulator of proteasome activity, has been implicated in auxin-mediated proteasome suppression; however, the mechanism by which auxin modulates PTRE1 function remains unclear. Here, we demonstrate that auxin promotes the interaction between germin-like protein 1 (GLP1) and PTRE1, facilitating PTRE1 retention at the plasma membrane. The relocation of PTRE1 results in reduced nuclear 26S proteasome activity, and thus the attenuated Aux/IAA degradation and altered Aux/IAA homeostasis, ultimately resulting in suppressed auxin-mediated transcriptional regulation. Our findings uncover a previously uncharacterized regulatory axis in auxin signaling that controls Aux/IAA protein stability, functioning alongside the TIR1- and TRANSMEMBRANE KINASE 1 (TMK1)-mediated pathways, and highlight the coordination of auxin signaling from the cell surface to the nucleus via auxin-induced PTRE1 relocation, which fine-tunes Aux/IAA protein homeostasis and auxin responses.

Objectives: Bisphenol A (BPA), a prototypical environmental endocrine-disrupting chemical (EDC), is ubiquitously present in environmental matrices and biological fluids. Dietary ingestion and inhalation exposure to BPA can induce testicular oxidative stress and apoptosis. This study aimed to investigate the protective effects and underlying mechanisms of Pfaffia glomerata (Pg), a perennial herb of the Amaranthaceae family, against BPA-induced reproductive system injury. Methods: Potential targets and molecular mechanisms were predicted through network pharmacology. Physiological indicators, histopathological changes, serum biochemical parameters, and Western blot analysis were used to systematically evaluate the ameliorative effects of Pg and elucidate its mechanisms. Results: Our network pharmacology analysis identified core targets of Pg in attenuating reproductive system injury, including PTPN11, PIK3CA, JAK2, PIK3R1, PDGFRB, and others. GO enrichment and KEGG pathway analysis indicated that these key targets primarily regulate steroid metabolism, enhance antioxidant capacity, and modulate signaling pathways such as PI3K-AKT, Fc epsilon RI, and cAMP. In vivo studies demonstrated that all Pg dose groups showed significant improvement in BPA-induced histopathological injury to testicular tissues. BPA exposure increased serum levels of follicle-stimulating hormone (FSH) while decreasing testosterone (T), estradiol (E2), and progesterone (PROG) levels. Furthermore, BPA elevated serum levels of the testicular marker enzymes acid phosphatase (ACP) and lactate dehydrogenase (LDH) but reduced alkaline phosphatase (ALP) levels; all these effects were significantly reversed with Pg treatment. Western blot results showed that compared with the model group, high-dose Pg significantly upregulated the expression of phosphorylated AKT (p-AKT), phosphorylated PI3K (p-PI3K), and Bcl-2, while downregulating Cleaved Caspase-3 and Bax. Conclusions: Our findings indicate that Pg may attenuate BPA-induced reproductive system injury by activating the PI3K/AKT signaling pathway, upregulating the anti-apoptotic protein Bcl-2, and inhibiting the activation of the apoptotic effector Caspase-3. The study provides a new theoretical basis for the development of novel natural drugs or health products.

MicroRNAs (miRNAs) play crucial regulatory roles in multiple developmental processes of animals and plants. Serrate (SE) is essential for miRNA processing and RNA metabolism; however, post-translational modification of SE remains largely unexplored. Casein kinase 1 (CK1) plays vital roles in both plants and mammals by phosphorylating distinct substrates. Here, we demonstrate that Arabidopsis early flowering 1-like (AELs; a plant CK1) regulates miRNA metabolism through phosphorylating SE. miRNA-seq reveals a decreased abundance of miRNAs under AEL4 overexpression, suggesting that AELs suppress miRNA biogenesis. AELs phosphorylate SE at Thr21 and Ser355, enhancing its affinity with the 20S core proteasome α subunit G1 (PAG1) for degradation and reducing SE's binding affinity to hyponastic leaves 1 (HYL1) to suppress microprocessor complex assembly. This study elucidates the crucial roles of CK1/AEL-mediated phosphorylation in regulating SE accumulation and consequently miRNA metabolism, providing insights into the regulation of miRNA homeostasis at the post-translational level.

This study investigated the protective effect of Dai Bai Jie (DBJ) extract against acute alcoholic liver injury (AALI) and elucidated its potential mechanism. The total saponin level in the DBJ extracts was measured using vanillin–chloroform acid colorimetry. To observe the preventive and protective effects of DBJ on AML-12 cells in an ethanol environment, the effective components of DBJ were identified. An alcohol-induced AALI mouse model was used to evaluate the efficacy of DBJ against AALI. For this purpose, alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) levels were assessed, liver function indices and oxidative and inflammatory markers were determined, and histopathological examinations were performed. Mechanistic investigations were conducted using RT-qPCR assays and immunohistochemical analysis to determine the protective effects of DBJ. The samples (DBJ-1, DBJ-2, and DBJ-3) were obtained by extracting DBJ with water, 50% ethanol, and 95% ethanol, yielding total saponin contents of 5.35%, 6.64%, and 11.83%, respectively. DBJ-3 was isolated and purified, and its components were identified by Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS). DBJ-3 had the greatest effect on cell viability in an ethanol environment. Moreover, DBJ-3 reduced inflammatory infiltration, liver cell degeneration, and hemorrhage, while increasing ADH and ALDH levels in liver tissues. Additionally, DBJ-3 considerably decreased the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triglyceride (TG) levels. DBJ-3 reduced malondialdehyde (MDA), reactive oxygen species (ROS), and inflammatory factors, such as tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin 6 (IL-6), while increasing superoxide dismutase (SOD) and glutathione S-transferase (GST) activities. Furthermore, DBJ-3 significantly increased alcohol dehydrogenase 1b (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) expression at the gene and protein levels within alcohol metabolism pathways and reduced the nuclear factor kappa-B (NF-κB) gene and protein levels. These findings suggest that DBJ-3 can prevent AALI by enhancing alcohol metabolism via the regulation of ADH1B and ALDH2 and the modulation of the NF-κB pathway to improve antioxidant and anti-inflammatory effects.

Phytobacteria play diverse roles in plant biology, ranging from promoting health to causing diseases that threaten global food security and the economy. In contrast to the extensive studies of phytopathogens targeting leaves and roots, their impact on plant reproductive processes has been largely overlooked. Here, we demonstrate that a bacterial effector TleB of the type VI secretion system in Xanthomonas oryzae can modulate seed production of Arabidopsis thaliana. Using biochemical, structural, and physiological analyses, we determined TleB as a phospholipase that mediates interspecies microbial competition in X. oryzae. Additionally, TleB plays a key role in the infection of inflorescences by X. oryzae, which leads to significantly reduced seed production. Lipidomic and biochemical assays show that TleB binds to a number of anionic phospholipids that are key signaling molecules. A fluorescence reporter for auxin distribution showed TleB-mediated diminished signals in planta. Additionally, transgenic plants expressing TleB exhibited significantly altered seed counts. These findings introduce a novel paradigm in which phytopathogens can affect plant reproduction in a traditionally non-susceptible host, prompting a reevaluation of diverse phytobacteria-host interactions in reproductive processes and offering new insights into plant health and crop protection.IMPORTANCEPhytobacteria are typically identified as pathogens based on visible effects on leaves and roots; those lacking such phenotypes are often considered nonpathogenic. Similarly, plant hosts that show no phenotypic changes are considered nonhosts and, thus, less studied. Our research challenges this classification by highlighting that bacteria-plant interactions on inflorescences, though less apparent and more delayed, can cause profound impacts on seed production. This discovery not only shifts the focus from the more commonly studied vegetative and root infections to the reproductive aspects of plant-pathogen interactions but also necessitates a reevaluation of host-pathogen dynamics with an emphasis on long-term effects such as seed production.

Vacuolar acidification is crucial for the homeostasis of intracellular pH and the recycling of proteins and nutrients in cells, thereby playing important roles in various physiological processes related to vacuolar function. The key factors regulating vacuolar acidification and underlying mechanisms remain unclear. Here, we report that Arabidopsis phospholipase Dζ2 (PLDζ2) promotes the acidification of the vacuolar lumen to stimulate autophagic degradation under phosphorus deficiency. The pldζ2 mutant massively accumulates autophagic structures while exhibiting premature leaf senescence under nutrient starvation. Impaired autophagic flux, lytic vacuole morphology, and lytic degradation in pldζ2 indicate that PLDζ2 regulates autophagy by affecting the vacuolar function. PLDζ2 locates in both tonoplast and cytoplasm. Genetic, structural, and biochemical studies demonstrate that PLDζ2 directly interacts with vacuolar-type ATPase (V-ATPase) subunit D (VATD) to promote vacuolar acidification and autophagy under phosphorus starvation. These findings reveal the importance of V-ATPase and vacuolar pH in autophagic activity and provide clues in elucidating the regulatory mechanism of vacuolar acidification.

Phosphatidic acid (PA) functions as a cell membrane component and signaling molecule in plants. PA metabolism has multiple routes, in one of which PA is converted into cytidine diphosphate diacylglycerol (CDP-DAG) by CDP-DAG synthases (CDSs). CDS genes are highly conserved in plants. Here, we found that knock-down of the CDS gene enhanced the resistance of Arabidopsis thaliana to multiple pathogens, with a growth penalty. When Arabidopsis leaves were treated with chitin or flg22, reactive oxygen species (ROS) production in cds mutants was significantly higher than that in the wild-type (WT). Similarly, phosphorylation of mitogen-activated protein kinases (MAPKs) in the cds1cds2 double mutant was significantly increased compared to the WT. By integrating lipidomics, transcriptomics, and metabolomics data, PA accumulation was observed in mutants cds1cds2, activating the jasmonic acid (JA) and salicylic acid (SA) signaling pathway, and increasing transcript levels of plant defense-related genes. Significant accumulation of the downstream metabolites including serotonin and 5-methoxyindole was also found, which plays important roles in plant immunity. In conclusion, our study indicated the role of CDSs in broad-spectrum disease resistance in Arabidopsis and that CDSs are involved in plant metabolic regulation.

Tiller angle is a key agronomic trait that influences plant architecture and thus grain yield by optimizing rice planting density. Although great progress has been made in understanding the LAZY1-dependent pathway mediating rice tiller angle, the genetic regulatory network of rice tiller angle remains to be elucidated. Here, we identified a new tiller angle gene LAZY5 (LA5) that encodes a member of the ATP binding cassette transporter G subfamily (ABCG) transporter. We found LA5 can interact with OsPIN3t to regulate lateral auxin transport (LAT), shoot gravitropism, and thus tiller angle. Further genetic analysis demonstrated that LA5 acts in a novel LA1-independent pathway to modulate LAT and rice tiller angle. Up-regulation of LA5 not only enlarges tiller angle but also increases tiller number in rice. Moreover, LA5 was strongly selected during rice domestication, with haplotype differentiations happened within the indica rice population. Our study not only uncovers a novel LA1-independent pathway controlling LAT and shoot gravitropism, but also provides a potential molecular target for high-yield breeding via synergistically regulating rice tiller angle and tiller number.

Breast cancer remains a leading cause of malignancy-related mortality among women, with rising global incidence. While surgical intervention is effective for early-stage breast cancer, drug therapy is indispensable, particularly for triple-negative breast cancer, where treatment options are still limited. Actaea vaginata, a traditional Chinese medicinal herb, has been historically applied for inflammatory conditions, including pharyngitis and stomatitis. However, its antitumor potential remains under-reported. In this study, a cycloartane triterpene saponin, beesioside O (BO), was isolated from this plant. Its antitumor activity was evaluated in vitro. Its potential therapeutic mechanisms were elucidated through network pharmacology. BO exhibited substantial potency in inhibiting breast cancer cells. Network pharmacology analysis uncovered 179 potential pharmacological targets of BO, which were predominantly concentrated in pathways, such as pathways in cancer, the PI3K-Akt signaling pathway, and chemical carcinogenesis receptor activation. Molecular docking analysis indicated that STAT3 exhibited minimal binding energy with BO. Additionally, molecular dynamics simulations verified the conformational stability of the BO-STAT3 complex. Western blot analysis demonstrated that STAT3 was downregulated following administration. These results imply that BO may exhibit a multi-target, synergistic therapeutic effect against breast cancer, with STAT3 recognized as a pivotal target. This study demonstrates the potential of BO for development as a chemotherapeutic agent for breast cancer treatment. It lays the groundwork for further exploration of BO’s bioactivity and provides valuable insights into its molecular mechanisms in breast cancer therapy.

The ability to make a timely decision between being dormant and germinating is critical for pollen to achieve a selection advantage. Genetic pathways controlling developmental and environmental-controlled pollen dormancy remain largely unclear. We report here that four Arabidopsis AGC kinases, PDK1.1/PDK1.2 and AGC1.5/AGC1.7, form a kinase cascade to maintain pollen dormancy. Both agc1.5 agc1.7 and pdk1.1 pdk1.2 show precocious pollen germination; the role of AGC1.5 and 3-phosphoinositide-dependent protein kinase-1 (PDK1) in pollen dormancy depends on their kinase activity. By pharmacological, molecular, and genetic approaches, we demonstrate that AGC1.5 kinases mediate JINGUBANG (JGB)-dependent inhibition of jasmonic acid biosynthesis. Functional loss of the genetic pathway, that is in the pdk1.1 pdk1.2 or agc1.5 agc1.7 double mutants, results in hypersensitivity to high humidity. Results presented uncover a PDK1-AGC1.5-JGB module mediating developmental and environmental-controlled pollen dormancy.

Acute alcoholic liver disease (ALD) resulting from short-term heavy alcohol consumption has become a global health concern. Moreover, anthocyanins have attracted much attention for their ability to prevent oxidation and inflammation. The present work evaluates the protective effects of Lycium ruthenicum Murray (LRM) against ALD and explores the possible underlying mechanism involved. The total anthocyanin content in LRM was 43.64 ± 9.28 Pt g/100 g dry weight. Mice were orally administered 50, 125, or 375 mg LRM/kg body weight (BW) for 21 days. On days 18–21, mice were orally administered 15 mL of ethanol/kg BW. Markers of liver damage, oxidative stress, and inflammation were examined. Furthermore, the modulatory effect of LRM on Nrf2/HO-1/NF-κB pathway molecules was evaluated through quantitative reverse transcription polymerase chain reaction (RT‒qPCR) and immunohistochemistry analyses. The difference between the groups indicated that LRM improved liver histopathology and the liver index, decreased aspartate transaminase, alanine transaminase, malondialdehyde, reactive oxygen species, IL-6, TNF-α, and IL-1β expression, but elevated superoxide dismutase, catalase, and glutathione-s-transferase levels. Moreover, LRM upregulated Nrf2 and Ho-1 but downregulated Nf-κb and Tnf-α genes at the transcript level. In summary, LRM alleviated ethanol-induced ALD in mice by reducing oxidative damage and associated inflammatory responses. LRM protects against ALD by reducing damage factors and enhancing defense factors, especially via the Nrf2/HO-1/NF-κB pathway. Thus, LRM has application potential in ALD prophylaxis and treatment.