Today, diabetes is considered a growing global epidemic. In the diabetic environment, a large amount of reactive oxygen species are produced. This type of active oxygen causes severe damage to cell membranes, proteins, and DNA. Therefore, finding a solution to deal with and reduce this type of reactive oxygen is very important. One of the most effective ways to deal with oxidative damage and inflammation is the modulation of the nuclear factor erythroid 2 (Nrf2) signaling pathway. One of the useful natural substances that can be used for treatment in the signaling system is saffron. In this article, research evaluating the medicinal effects of saffron and its compounds and their mechanisms of action, especially the Nrf2 signaling pathway, have been investigated and studied. The results show that saffron and its components have the potential to treat diabetes due to their unique properties.

Exclusive enteral nutrition (EEN) is highly effective in achieving remission and improving nutritional status in pediatric Crohn's disease (CD), commonly associated with altered body mass composition (BC). Bioimpedance analysis (BIA) with phase angle (PA) assessment is a noninvasive, reliable tool in screening for BC alterations. In the present study we aimed to assess the PA's usefulness in the detection of malnutrition in newly diagnosed pediatric CD, ongoing EEN treatment, and during 1-year follow-up. Patients and study design: Fourty-three patients with CD, qualified for EEN, were enrolled in the study. Additionally, 22 healthy children, being in the same age category, served as controls. Fat-free mass (FFM), fat-free mass index (FFMI), and BIA-derived PA were assessed at diagnosis, after EEN completion, and at week 52. The same parameters were obtained in the control group once. The majority of patients presented with normal body mass index at diagnosis. PA values were lower than 5 degrees in 65% of the study group. FFMI deficiencies were observed in 74% of patients. After EEN completion, an increase in FFM ( < .001) was observed. The highest mean of FFM ( < .001) and PA ( < .001) were observed at week 52. A strong correlation between PA and FFM at CD diagnosis (Spearman's rho = 0.671, = 0.702, < .001), after EEN completion (Spearman's rho = 0.781, < .00) and at week 52 (Spearman's rho = 0.657, < .001) was present. PA has been observed as positively associated with albumin concentrations both at diagnosis and after EEN. Our study provides some support that PA may be a reliable tool for screening alteration in BC, especially FFM and lean tissue mass (LTM). Moreover, PA has been observed as positively associated with albumin levels at CD diagnosis, which provides some evidence that it may be considered as a risk indicator of malnutrition and protein deficiency in newly diagnosed CD pediatric patients.

This study investigated the behavioral responses of male Institute for Cancer Research (ICR) mice to intravenous caffeine exposure via a functional observation battery (FOB) test. Thirty-two experimental mice were randomly assigned to four groups ( = 8 per group) and received intravenous caffeine at a dose of 0, 5, 10, or 20 mg/kg. Functional behaviors were observed at 0, 0.25, 1.5, 6, and 24 h after intravenous caffeine administration. Among the hand-held observations, the ease of removal from the cage and the ease of handling were significantly altered in all caffeine-exposed mice in both a dose-dependent and a time-dependent manner. In terms of physiological responses, both stimulus responses and locomotor activities were significantly affected by intravenous caffeine exposure. Specifically, the tail pinch response was significantly impaired in half of the mice in the 10 mg/kg and 20 mg/kg groups. Moreover, the rearing count decreased in the 10 mg/kg group at 1.5 to 6 h and in the 20 mg/kg group at 1.5 h after intravenous caffeine exposure. Furthermore, locomotor activity was markedly increased 0.25 h after intravenous caffeine administration in the 20 mg/kg group. These findings clearly indicate that intravenous caffeine exposure significantly impacts functional behaviors, as assessed by an FOB test, which is consistent with widely accepted safety pharmacology testing guidelines.

This study examined the effects of prebiotic and probiotic (synbiotic) supplementation on weight loss and biochemical parameters in treating obesity. The study was conducted with 110 participants in Eskisehir Anadolu Hospital, Turkiye, between February 15, 2019 and February 15, 2020. Individuals with obesity, who were following a weight loss diet, were randomly assigned to two groups. While one group (the control group) followed the diet only, the other group received synbiotic tablets in the morning and evening, in addition to the diet. Anthropometric values and biochemical parameters of the patients were measured at the beginning of the study and 3 months after. A significant decrease was found in weight, body mass index (BMI), and waist circumference values compared with baseline in both groups (: .001; < .05). A significant decrease was found in fasting blood sugar and HOMA-IR values compared with baseline in both groups. Furthermore, there was a significant increase in vitamin B12 and vitamin D values in the group receiving synbiotics compared with their baseline values. As a result of our study, both groups experienced similar weight loss and a decrease in BMI values. The vitamin B12 and vitamin D values of the group that took supplements increased significantly. The HOMA-IR values were significantly lower in both groups, albeit more in the synbiotic group. Changes in vitamin B12, vitamin D, and HOMA-IR values are extremely important for improving the health parameters in the long term.

The microbial-gut-brain axis and oxidative stress may be important to the pathogenesis of Alzheimer's disease (AD). Tratt polysaccharides (RRTP) have a strong antioxidant effect and can affect the gut microbiota, and whether it can affect AD is unknown. So, AlCl and d-galactose were used to establish AD model rats, and RRTP was used as an intervention treatment. Morris water maze test was used to detect cognitive functions. The hippocampus was used to observe the pathological changes, and the cortex was used to measure antioxidant markers. The stool was collected for 16S rDNA sequencing. Morris water maze test showed that the learning ability and memory level of AD group rats were decreased, and RRTP intervention could mitigate the injury to a certain extent. In the AD group, hematoxylin-eosin staining revealed changes in the morphology of neurons, silver glycine staining revealed neurofibrillary tangles and Congo red staining revealed -amyloid. RRTP could ameliorate the above changes to some extent. The results of superoxide dismutase, malondialdehyde, and glutathione peroxidase showed that the antioxidant capacity in the RRTP intervention group was significantly higher than that in the AD group. 16S rDNA sequencing results showed that there were differences in the species composition of gut microbiota, and the ratio of to in the AD group was decreased. After RRTP intervention, the proportion of increased. In conclusion, RRTP may prevent AD pathology and cognitive functions in rats to a certain extent through the microbiota-gut-brain axis and oxidative stress.

This study aimed to investigate the hypoglycemic effects of different concentrations of black tea (BT) extracts and their underlying mechanisms in type 2 diabetic (T2DM) mice. Results indicated that BT extracts significantly mitigated weight loss, improved glucose and insulin tolerance, and modulated cytokine levels related to glucose and lipid metabolism in T2DM mice. Moreover, BT extracts ameliorated liver and pancreas damage resulting from high-sugar/high-fat diets and insulin resistance. Among the tested concentrations, low-concentration BT (BT-L) extract exhibited the most potent hypoglycemic ability. Furthermore, BT-L restored pancreatic function in hyperglycemic mice via activating the glucagon-like peptide-1 receptor-protein kinase A-pancreatic and duodenal homeobox-1-glucokinase cascade pathway. In terms of intestinal homeostasis, all BT-treated groups adjusted the gut microbiota structure by regulating the distribution and diversity of gut microbiota in T2DM mice. Among them, BT-L intervention specifically and significantly increased the levels of probiotic in the intestine of T2DM mice. Furthermore, BT-L intervention effectively promoted the synthesis of streptomycin by gut microbiota, thereby exerting anti-inflammatory effect. Comprehensively, the hypoglycemic effect of BT cannot show an absolute concentration-dependent relationship. Our findings highlight the potential of BT as an effective blood glucose regulator and provide valuable insights for BT-based functional food development.

Cancer is a significant cause of death worldwide. It has been suggested that the consumption of flavonoids decreases the risk for cancer by increasing phase II enzymes, such as Nicotinamide Adenine Dinucleotide Phosphate Hydrogen (NAD(P)H) quinone oxidoreductase 1 (NQO1), glutathione S-transferases, and Uridine 5'-diphospho- (UDP)-glucuronosyltransferases that assist in removing carcinogens from the human body. Flavonoids are bioactive compounds found in a variety of dietary sources, including fruits, vegetables, legumes, nuts, and teas. As such, it is important to investigate which flavonoids are involved in the metabolism of carcinogens to help reduce the risk of cancer. Therefore, the objective of this narrative review was to investigate the effects of commonly consumed flavonoids on NQO1 mRNA expression, protein, and activity in human cell and murine models. PubMed was used to search for peer-reviewed journal articles, which demonstrated that selected flavonoids (, quercetin, apigenin, luteolin, genistein, and daidzein) increase NQO1, and therefore, increase the excretion of carcinogens. However, more research is needed regarding the mechanisms by which flavonoids induce NQO1. Furthermore, it is suggested that future efforts focus on providing precise flavonoid recommendations to decrease the risk factors for chronic diseases.

Constipation represents a common gastrointestinal disorder that has various adverse effects on the gastrointestinal tract. As a result, various civilizations have developed phytomedicines in order to treat and relieve its symptoms. In the current study, we evaluated the effect of L. leaves decoction extract (CALDE) against loperamide (LOP)-induced constipation in rats. For 3 days, treated rats were administered LOP (3 mg/kg, .) and CALDE (50, 100, and 200 mg/kg, ) or yohimbine (2 mg/kg, .). The gastric emptying test or intestinal transit time was calculated. The oxidative status was studied and evaluated using biochemical colorimetric methods. Results showed that CALDE administration improves gastric emptying and accelerates gastrointestinal transit. Pretreatment with LOP altered the defecation parameters and generated an oxidative status in healthy rats. In contrast, CALDE coadministration protected against the deregulation of intestinal motor function and frequency of defecation and significantly re-established oxidative marker levels. CALDE treatment demonstrated significant protection against experimental oxidative stress and constipation induced by LOP. Therefore, it can be considered a pharmacological drug to treat these gastrointestinal troubles.

Skin aging, accelerated by oxidative stress from environmental factors, results in the breakdown of collagen and elastin, causing visible signs like wrinkles and inflammation. Natural antioxidants such as nicotinamide mononucleotide (NMN), decursin, and l-cysteine have shown potential in combating oxidative damage and inflammation. This study explored the effects of a formulated mixture of these compounds on skin aging and atopic dermatitis (AD) through a combination of , , and methods. Using human keratinocyte cells, we assessed cytotoxicity via a cell viability assay, confirming NMN and l-cysteine were nontoxic up to 100 µM, while decursin exhibited toxicity above 10 µM. The intracellular oxidative stress measurement demonstrated that mixtures A and B, composed of the same concentrations of decursin and l-cysteine but differing in NMN levels (low in mixture A and moderate in mixture B), significantly reduced oxidative stress levels induced by 2,2'-azobis(2-amidinopropane) dihydrochloride, whereas mixture C, which contained the highest NMN concentration, was ineffective. Mixture B further reduced senescence-associated heterochromatin foci formation under oxidative stress, while mixture C caused cell structure disruptions. In the dinitrochlorobenzene-induced AD model in BALB/c mice, both, mixture-L and mixture-H treatments reduced epidermal thickness, scratching behavior, and transepidermal water loss, with mixture-L also lowering dermal thickness and mast cell infiltration. Gene expression analysis confirmed that mixture B decreased proinflammatory cytokines like and , while network pharmacology predicted key antioxidant pathways, validated through restored gene expression. Overall, the findings highlight the potential of these compound mixtures to mitigate oxidative stress and inflammation, offering a promising approach for skin aging and dermatitis management, though further validation is needed to optimize efficacy and safety.

(), which is an indigenous herb in China, is gathered and consumed by nomads in Xinjiang due to its medicinal value. Only a few studies have evaluated its possible pharmacological activity. This study aims to examine and compare the ways in which two bulb polysaccharide fractions (ESBP and E1P) alleviate airway remodeling based on apoptosis and autophagy. In a mouse model of chronic asthma produced by ovalbumin, the anti-asthmatic effects of E1P and ESBP were investigated. The expression levels of the proteins linked to autophagy and apoptosis (cleaved-caspase 3, Beclin1, LC3B, Bad, and Bax) as well as the activity of the PI3K/Akt/mTOR signaling pathway were assessed. Airway remodeling was alleviated by E1P and ESBP. While E1P could only prevent the increase in PI3K, ESBP was capable of inhibiting the PI3K/Akt/mTOR signaling pathway. Furthermore, ESBP decreased the levels of cleaved-caspase 3, Beclin1, LC3B, Bad, and Bax protein expressions. By modifying signaling pathways linked to autophagy and apoptosis, bulb polysaccharides successfully improved the airway remodeling of asthma. Additionally, ESBP exhibited more potent inhibitory effects on asthmatic defective autophagy than E1P.

The traditional medicinal plant is commonly used in Chinese and Ayurvedic medicine due to its vast range of therapeutic properties. Previously, the ethanolic leaf extract was subjected to silica column fractionation, and the C3 fraction was obtained. We investigated the antioxidant and anti-proliferative effects of C3 in human embryonic kidney (HEK293) cells. In HEK293 cells, C3 cytotoxicity was assessed (viability assay; 24 h; [0.2-3 mg/mL]), and a half maximal inhibitory concentration (IC) was determined. Malondialdehyde (MDA), lactate dehydrogenase (LDH) (spectrophotometry), mitochondrial depolarization (), intracellular reactive oxygen species (flow cytometry), glutathione (GSH), oxidized glutathione (GSSG) concentrations, caspase activities, ATP levels (luminometry), and fragmentation of DNA (SCGE assay) were evaluated. Protein expressions were assessed by western blotting. Gene expressions were quantified by qPCR. Cell viability in HEK293 cells was decreased in a dose-dependent manner by C3. MDA, , LDH, caspase activities, and DNA fragmentation ( < .0004) were significantly increased by C3. Nuclear factor erythroid 2-related factor 2 (Nrf-2) protein expression, GSH, and GSSG concentrations were increased, whereas antioxidant (, , and ) gene expression was significantly decreased by C3 ( < .001). C3 decreased both Bax and Bcl-2 protein expression ( < .03). Gene expression of was significantly increased, whereas was significantly reduced by C3 ( < .05). C3 reduced antioxidant gene expression, increased antioxidant levels, and elevated anti-proliferative effects in HEK293 cells, suggesting that high concentrations of C3 are potentially toxic to kidney cells, thus rendering cause for concern with its human use.

The aim of this study was to determine the anti-inflammatory and anti-endoplasmic reticulum (ER) stress effects of var. (ADK) extract on ARPE-19 cells. Pretreatment with ADK effectively mitigated thapsigargin (Tg)-induced increases in vascular endothelial growth factor protein secretion and intracellular calcium levels. Furthermore, pretreatment with ADK suppressed ocular ER stress-related protein expression in a dose-dependent manner, inhibited the loss of tight junctions, and suppressed interleukin-6 gene expression. Moreover, ADK pretreatment significantly prevented lipopolysaccharide-inducible proinflammatory cytokine gene expression at the transcription level and the phosphorylation of proteins involved in the mitogen-activated protein kinase-nuclear factor kappa-light-chain-enhancer of activated B cells (NFB) axis at the posttranslational level. Additionally, ADK extract enhanced antioxidant activity, as evidenced by increased heme oxygenase-1 protein expression and increased 2,2-diphenyl-1-picrylhydrazyl radical scavenging and ferric-reducing antioxidant power. In conclusion, ADK extract effectively protected ARPE-19 cells from ocular ER stress, inflammation, and oxidative stress, demonstrating its potential as a nutraceutical intervention for ocular diseases.

Chronic stress in the central nervous system can lead to neurological dysfunction characterized by spontaneous neuronal cell death. This study investigated the neuroprotective potential of an aqueous extract of Thunberg (ELL) against corticosterone (CORT)-induced pathophysiology in PC12 cells. To assess the neuroprotective effects of ELL, PC12 cells were pretreated with 50 g/mL of ELL before being exposed to CORT. ELL significantly prevented CORT-induced neuronal cell death by attenuating pro-apoptotic protein expression, lactate dehydrogenase release, and reactive oxygen species generation, while maintaining intact adenosine triphosphate levels. Furthermore, ELL significantly mitigated CORT-induced endoplasmic reticulum (ER) stress responses by attenuating the elevation of unfolded protein responses, intracellular calcium levels, opening of mitochondrial permeability transition pores, and loss of mitochondrial membrane potential. In conclusion, ELL exerts neuroprotective effects by inhibiting apoptosis through the mitigation of CORT-induced ER stress and mitochondrial dysfunction, suggesting that ELL may prevent neuronal damage associated with chronic stress-induced neurotoxicity.

Skeletal muscle health is essential for metabolic homeostasis, and dysregulated apoptosis in muscle cells can lead to muscle wasting and degenerative diseases. Although soybean-derived peptides are known for their bioactive properties, including antioxidant and anti-apoptotic effects, their impact on apoptosis regulation in skeletal muscle cells remains underexplored. This study aims to investigate the effects of low-molecular-weight soy peptide hydrolysate (SPH) on apoptosis and related markers in C2C12 myoblasts. SPH was prepared by enzymatic hydrolysis, and its antioxidant and anti-apoptotic activities were analyzed through assays (i.e., ABTS, DPPH). Cellular studies were used to evaluate SPH effects on ROS scavenging and apoptosis. Results show that SPH enhanced antioxidant activity, reduced ROS levels, and promoted cell proliferation in a dose-dependent manner. SPH notably decreased apoptosis under oxidative stress by down-regulating p53, c-Caspase-3, and Cyto-c, while promoting HO-1 expression, likely via AMPK activation. Importantly, SPH had no significant impact on inflammation-related proteins or MAPK activation. These findings suggest that SPH may have therapeutic potential against oxidative stress and apoptosis in muscle cells through intrinsic pathways, contributing to muscle health maintenance.

This study investigates the protective effects of CGK012 [(7S)-(+)-cyclopentyl carbamic acid 8,8-dimethyl-2-oxo-6,7-dihydro-2H,8H-pyrano[3,2-g]chromen-7-yl-ester], a small-molecule inhibitor targeting the Wnt/β-catenin signaling pathway, against inflammatory responses elicited by lipopolysaccharide (LPS). The study evaluated the influence of CGK012 on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) expressions in LPS-stimulated human endothelial cells. It examined its effects on iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β in LPS-challenged mice. CGK012 treatment resulted in increased HO-1 production, inhibited nuclear factor-kappa B activation, and decreased the levels of COX-2/PGE2 and iNOS/NO. Additionally, CGK012 reduced signal transducer and activator of transcription-1 phosphorylation and facilitated Nrf2 nuclear translocation and binding to antioxidant response elements, culminating in reduced IL-1β production in LPS-exposed human umbilical vein endothelial cells. Notably, the inhibitory effect of CGK012 on iNOS/NO was reversed upon HO-1 knockdown via RNA interference. In vivo, CGK012 markedly attenuated iNOS expression in lung tissue and decreased TNF-α levels in bronchoalveolar lavage fluid. These findings underscore the anti-inflammatory potential of CGK012, suggesting its therapeutic promise for conditions characterized by pathological inflammation.

The purpose of this study was to investigate the antioxidant effects of leaf polysaccharide extract (ALPE) against oxidative stress induced by hydrogen peroxide (HO) in H9c2 myoblasts. The cells showed a cell viability of around 70% following exposure to 150 μM HO. In addition, ALPE was noncytotoxic to H9c2 myoblasts at 10-1000 μg/mL concentrations. As confirmed by MTT analysis and Annexin V/propidium iodide staining, ALPE treatment was found to protect H9c2 myoblasts exposed to HO. This protection is achieved by inhibiting reactive oxygen species levels and inducing superoxide dismutase and catalase activity. Furthermore, ALPE downregulated the activation of Bax, caspase-3, -8, and -9 but upregulated Bcl-2, thereby preventing HO-stimulated cytotoxicity in H9c2 myoblasts. ALPE activated the Nrf2/heme oxygenase-1 signaling cascade. Collectively, ALPE treatment decreased HO-induced oxidative stress. Therefore, ALPE can potentially be used as a natural resource with antioxidant properties.

Drinking tea is an important cultural and sensory activity in modern society. However, tea consumption may influence biological functions because of its high polyphenol and methylxanthine content. Theophylline is a methylxanthine that plays a significant role in respiratory physiology and is used clinically as a bronchodilator. In this study, we assessed the pharmacological safety of theophylline by investigating its effects on the respiratory responses of experimental rodents. Six-week-old male Sprague-Dawley rats were intravenously administered 0, 2.5, 5, or 10 mg/kg theophylline. After systemic theophylline exposure, the respiratory rate, tidal volume, and minute volume were monitored and statistically analyzed. There was a significant increase in respiratory rate and minute volume with no change in tidal volume at theophylline doses of >5 mg/kg. Changes in respiratory rate and minute volume peaked at 0.25 h after exposure; the respiratory rate increased by 58.2% and 88.9%, and the minute volume increased by 50.5% and 72.8% with the 5 and 10 mg/kg doses, respectively, compared with the vehicle control. These results provide fundamental scientific data that can be used in clinical applications.

Cancer cachexia, defined by the gradual depletion of muscle and fat mass, is a complex multifactorial syndrome affecting up to 80% of cancer patients. This study investigated the effects of extract (CXE) and xanthorrhizol (XAN) in ameliorating cancer-induced muscle atrophy in BALB/c mice. Treatment with CXE and XAN reversed muscle mass loss, grip strength decline, and decrease in myofiber size induced by cancer. In gastrocnemius muscle tissue, CXE and XAN downregulated the expression of nuclear factor kappa-beta (NF-κB), reducing the expression levels of proinflammatory cytokines. They also suppressed catabolic factors, including myostatin and ubiquitin-proteasome E3 ligases, and the nuclear translocation of forkhead box O3a. Furthermore, CXE and XAN promoted skeletal muscle anabolism by stimulating myogenesis and activating the phosphoinositide 3-kinase/protein kinase B signaling pathway. This activation subsequently upregulated the mammalian target of rapamycin and its downstream molecules. Overall, CXE and XAN effectively mitigated skeletal muscle catabolism induced by cancer cachexia and may serve as an intervention for inhibiting muscle atrophy in affected cancer patients if efficacy can be confirmed in human trials.

Black cumin ( L.) (family Ranunculaceae) is a largely utilized therapeutic herb worldwide. This comprehensive review discusses the pharmacological benefits of black cumin seed oil, focusing on its bioactive component thymoquinone (TQ). The review is structured as follows: First, we examine the antimicrobial properties of black cumin oil, followed by an analysis of its antioxidant capabilities. Finally, we explore its therapeutic potential, particularly in neurodegenerative diseases and COVID-19. Phytochemicals from have exhibited potential for developing novel preventive and therapeutic strategies against jaundice, gastrointestinal disorders, skin diseases, anorexia, conjunctivitis, dyspepsia, intrinsic hemorrhage, amenorrhea, paralysis, anorexia, rheumatism, diabetes, hypertension, fever, influenza, eczema, asthma, cough, bronchitis, and headache. The broader spectrum of application for and its essential bioactives have certainly enhanced the commercial value of this seed oil. TQ, a major constituent of black cumin seed oil, has numerous beneficial properties. Researchers have extensively studied black cumin seed oil and its major component, TQ. These studies have revealed a wide range of pharmacological properties, including anticancer, immunomodulatory, analgesic, antimicrobial, antidiabetic, and anti-inflammatory effects. Additionally, TQ has shown neuroprotective, spasmolytic, bronchodilatory, hepatoprotective, renoprotective, gastroprotective, and antioxidant activities.

Recent studies show that inorganic arsenic (As) exerts a toxic effect on the intestinal epithelium, causing a significant increase in its permeability. This disruption of the epithelial barrier may favor the entry of contaminants or toxins into the systemic circulation, thus causing toxicity not only at the intestinal level but possibly also at the systemic level. The present study conducts an evaluation of the protective effect of various dietary supplements and plant extracts against the intestinal toxicity of inorganic As. Some of these compounds were found to exert a protective effect. A significant decrease was observed in intracellular reactive oxygen/nitrogen species (10-31%), as well as a lower secretion of the pro-inflammatory cytokine IL-8 (25-41%) in the intestinal monolayers treated with the supplements and extracts, compared with those exposed only to As(III). The most effective supplements (glutathione/cysteine/vitamin C and lipoic acid) also normalized the distribution of tight junction protein zonula occludens-1, with partial restoration of the paracellular permeability and cell regeneration capacity of the intestinal epithelial cells. The results obtained show that dietary supplements and plant extracts can reduce the intestinal barrier disruption caused by inorganic As, and this may have a positive impact at both local and systemic levels.

Disturbances of the intestinal barrier enabling bacterial translocation exacerbate alcoholic liver disease (ALD). GG (LGG) has been shown to exert beneficial effects in gut dysbiosis and chronic liver disease. The current study assessed the combined effects of LGG and metformin, which play roles in anti-inflammatory and immunoregulatory processes, in alcohol-induced liver disease mice. A diet comprising 5% alcohol for 4 weeks was employed to develop an alcohol-induced liver injury model. Mice were orally administered LGG, metformin, or their combination on alternate days. Tight junction (TJ) proteins, gut microbiome composition, inflammatory cytokines, Jun N-terminal kinase (JNK), and p38 signals were assessed. When compared with treatment with LGG or metformin alone, combined LGG and metformin treatment substantially lowered the symptoms of inflammation, steatosis, and elevated liver enzymes caused by alcohol administration. Combination treatment significantly improved intestinal microecology, evidenced by the recovery of intestinal flora, TJ proteins, and intestinal villi. Combination treatment reduced hepatic inflammation by blocking p38 and JNK phosphorylation. The combination of LGG and metformin corrected immune-response dysregulation and improved ALD by enhancing the intestinal microbiome, restoring mucosal barrier integrity, modulating immune function, and decreasing liver injury. These results provide information for the development of intestinal microbiota-based preventive and therapeutic agents against ALD.