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As a traditional Chinese medicine (TCM), Allii Macrostemonis Bulbus (AMB) is a key herb for the treatment of thoracic paralytic cardiac pain, but its quality evaluation method has not yet been fully clarified. In this study, chromatographic fingerprints of AMB were developed using solid-phase extraction–high-performance liquid chromatography–evaporative light scattering detection (SPE-HPLC-ELSD) to evaluate the quality of AMB from various origins and processing methods. This was achieved by employing chemical pattern recognition techniques and verifying the feasibility and applicability of the quality evaluation of AMB through the quantitative analysis of multi-components via a single-marker (QAMS) method. Through the analysis of the fingerprints of 18 batches of AMB, 30 common peaks were screened, and 6 components (adenosine, syringin, macrostemonoside T, macrostemonoside A, macrostemonoside U, and macrostemonoside V) were identified. Moreover, three differential markers (macrostemonoside A, macrostemonoside T, and macrostemonoside U) were screened out using chemometrics techniques, including principal component analysis (PCA), hierarchical cluster analysis (HCA), and orthogonal partial least squares discriminant analysis (OPLS-DA). Subsequently, a QAMS method was established for macrostemonoside T and macrostemonoside U using macrostemonoside A as an internal reference. The results demonstrate the method’s accuracy, reproducibility, and stability, rendering it suitable for the quality evaluation of AMB. This study provides a theoretical basis for drug quality control and the discovery of quality markers for AMB.

Allii Macrostemonis Bulbus (AMB), a traditional Chinese edible and medicinal plant, is considered beneficial to health. In this study, we isolated and purified nine steroidal saponins (compounds 1–9) from AMB. Their structures were characterized using physicochemical properties, HR-ESI-MS, 1D and 2D NMR spectroscopy. Among these compounds, compounds 1–5 were newly discovered named macrostemonoside U-Y, respectively. We assessed the in vitro antioxidant properties of the nine steroidal saponins through free radical scavenging and reducing power assays. This provides options for developing natural antioxidants. Additionally, an HPLC-ELSD quantitative analysis method was developed for the nine saponins in 12 batches of AMB from different origins and processing methods. The results showed that the contents of the nine steroidal saponins in AMB varied greatly among different growing environments and processing methods.

As a foundation of life-science research and advancement, biobanking has played a critical role and made tremendous contributions to healthcare, biotechnology, disease control and prevention, as well as bio-conservation for the benefit of all humankind. This paper starts with a brief introduction of basic concepts, history, classification, and significance of biobanking, followed by a discussion on cryobiology fundamentals and key challenges faced by cryopreservation in biobanking. A special case discussion on the cryopreservation and biobanking of pathogenic microorganisms to meet both the unmet needs for biomedical research and the urgent demand for developing countermeasures against the ongoing coronavirus disease 2019 (COVID-19) pandemic is highlighted with insightful recommendations for future studies.

In the present work, we investigated the protective effect of schisandrin, a major and representative lignin from the fruits of Schisandra chinensis Baill., on streptozotocin combining with high fat diet (STZ/HFD)-induced diabetic nephropathy (DN) in mice. All mice were divided into five groups as follows: normal group, diabetes mellitus (DM) group, Metformin group, DM + schisandrin (10 and 20 mg/kg). Schisandrin were administered intragastrically to mice for 8 weeks. Schisandrin prevented DN-induced injuries as determined by significantly decreasing levels of fast blood glucose, advanced glycation end products (AGEs), lipid Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), creatinine (CRE), and blood urea nitrogen (BUN) and increasing level of high-density lipoprotein cholesterol (HDL-C), which correlated with inhibited TGF-β1 and α-SMA at protein and transcriptional levels. In addition, schisandrin treatment reduced protein expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX-2), suggesting a suppressed inflammatory response. This suppression was afforded by inhibiting nuclear factor-κB (NF-κB) and activating phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling. In summary, these findings highlight the nephroprotective effect of schisandrin against STZ/HFD-induced DN through inhibiting the renal inflammation and fibrosis in mice.

Background: Hyperuricemia (HUA) is a metabolic disease caused by reduced excretion or increased production of uric acid. This research aims to study the practical components, active targets, and potential mechanism of the “Radix ginseng (RG)-Ziziphus jujube (ZJ)” herb pair through molecular docking, network pharmacology, and animal experiments.Methods: The potential targets of “Radix ginseng (RG)-Ziziphus jujube (ZJ)” herb pair were obtained from the TCMSP database. The therapeutic targets of HUA were acquired from the GendCards, OMIM, PharmGkb, and TTD databases. Protein-protein interaction network (PPI) was constructed in the STRING 11.0 database. The David database was used for enrichment analysis. Molecular Docking was finished by the AutoDock Vina. And we employed Radix ginseng and Ziziphus jujube as raw materials, which would develop a new functional food fresh ginseng paste (FGP) after boiling. In addition, benzbromarone (Ben) (7.8 mg/kg) and allopurinol (All) (5 mg/kg) were used as positive drugs to evaluate the hyperuricemia induced by FGP (400 and 800 mg/kg) potassium oxazine (PO) (100 mg/kg) and hypoxanthine (HX) (500 mg/kg) on mice.Results: The results showed that 25 targets in the “RG-ZJ” herb pair interacted with hyperuricemia. Then protein-protein interaction (PPI) analysis showed that TNF, IL-1β, and VEGFA were core genes. KEGG enrichment analysis showed that the Toll-like receptor signaling pathway and IL-17 signaling pathway were mainly involved. Meantime, animal experiments showed that FGP could improve the HUA status of mice by reducing serum UA BUN, XO, and liver XO levels (p < 0.05, p < 0.01). Furthermore, we analyzed the main ingredients of FGP by HPLC. We found that the main ingredients of FGP had solid binding activity to the core target of HUA by molecular docking.Conclusion: This study explored the active ingredients and targets of the “RG-ZJ” herb pair on HUA through network pharmacology, molecular docking, and animal experiments. It revealed the improvement of FGP in mice with HUA.

Background: Epimedii Folium, as a natural botanical medicine, has been reported to have protective effects on intestinal diseases by modulating multiple signaling pathways. This study aimed to explore the potential targets and molecular mechanisms of Epimedii Folium extract (EFE) against cisplatin-induced intestinal injury through network pharmacology, molecular docking, and animal experiments.Methods: Network pharmacology was used to predict potential candidate targets and related signaling pathways. Molecular docking was used to simulate the interactions between significant potential candidate targets and active components. For experimental validation, mice were intraperitoneally injected with cisplatin 20 mg/kg to establish an intestinal injury model. EFE (100, 200 mg/kg) was administered to mice by gavage for 10 days. The protective effect of EFE on intestinal injury was analyzed through biochemical index detection, histopathological staining, and western blotting.Results: Network pharmacology analysis revealed that PI3K-Akt and apoptosis signaling pathways were thought to play critical roles in EFE treatment of the intestinal injury. Molecular docking results showed that the active constituents of Epimedii Folium, including Icariin, Epimedin A, Epimedin B, and Epimedin C, stably docked with the core AKT1, p53, TNF-α, and NF-κB. In verified experiments, EFE could protect the antioxidant defense system by increasing the levels of glutathione peroxidase (GSH-Px) and catalase (CAT) while reducing the content of malondialdehyde (MDA). EFE could also inhibit the expression of NF-κB and the secretion of inflammatory factors, including TNF-α, IL-1β, and IL-6, thereby relieving the inflammatory damage. Further mechanism studies confirmed that EFE had an excellent protective effect on cisplatin-induced intestinal injury by regulating PI3K-Akt, caspase, and NF-κB signaling pathways.Conclusion: In summary, EFE could mitigate cisplatin-induced intestinal damage by modulating oxidative stress, inflammation, and apoptosis.

Abstract Cisplatin, as one of the most effective chemotherapeutic agents, its clinical use is limited by serious side effect of nephrotoxicity. Cisplatin‐induced nephrotoxicity is closely related to apoptosis induction and activation of caspase. The present study aimed to explore the potential protective effect of ginsenoside Rk1 (Rk1), a rare ginsenoside generated during steaming ginseng, on cisplatin‐induced nephrotoxicity and the underlying mechanisms in human embryonic kidney 293 (HEK‐293) cells. Our results showed that the reduced cell viability induced by cisplatin could significantly recover by Rk1. Furthermore, glutathione (GSH) as an oxidative index, was elevated and the lipid peroxidation product malondialdehyde (MDA) was significantly decreased after Rk1 treatment compared to the cisplatin group. Additionally, Rk1 can also decrease the ROS fluorescence expression and increase the protein levels of nuclear factor erythroid 2‐related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1) compared to the cisplatin group, which suggested a suppression of oxidative response. More importantly, the cisplatin‐induced elevated protein levels of Bax, cleaved caspase‐3, cleaved caspase‐9, and decreased protein level of Bcl‐2 were reversed after treatment with Rk1. Our results elucidated the possible protective mechanism of Rk1 for the first time, which may involve in its anti‐oxidation and anti‐apoptosis effects.

The aim of the present study was designed to investigate that Platycodon grandiflorum saponins (PGS) exerted protective effects against testicular injury induced by scrotal hyperthermia. PGS (15, 30 mg/kg) were administered intragastrically to mice for 14 days, then exposed to a single scrotal heat treatment at 43 °C for 18 min on the 7th day. Heat stress (HS) induced spermatogenic damage was associated with a significant loss of leydig cells and the changes of serum testosterone, oxidative stress and apoptosis markers, and activated MAPK signaling pathway. In contrast, PGS treatment normalized HS-induced histopathological changes and prevented the activation of MAPK signaling pathway, which was contributed to oxidative stress and apoptosis in the testis of treated mice. In conclusion, our findings clearly demonstrated that PGS exhibited a significant protective effect against HS-induced testicular dysfunction, largely dependent upon the inhibition of oxidative stress associated apoptosis via partly regulation of MAPK signaling pathway.

Cisplatin, as an effective chemotherapeutic agent, is widely used to treat verious types of cancers. Nephrotoxicity induced by cisplatin seriously limits its clinical application. Icariin, a major and remarkable flavonoid isolated from Epimedium koreanum, has been reported to exert anti-oxidative stress and anti-inflammation actions. The purpose of this study is to explore the protective effect and possible mechanism of icariin on cisplatin-induced nephrotoxicity on HEK-293 cells. In this study, icariin pretreatment for 24 h significantly ameliorated cisplatin-induced oxidative stress by reducing levels of malondialdehyde (MDA) and reactive oxygen species (ROS), while increasing level of glutathione (GSH) in HEK-293 cells. Furthermore, icariin pretreatment reduced NF-κB phosphorylation and nuclear translocation in HEK-293 cells followed by decreased secretion of IL-1β, TNF-α, and iNOS, suggesting a suppression of inflammatory response. Moreover, icariin pretreatment significantly reduced cellular apoptosis via reduced levels of Bax, cleaved caspase-3/9, and increased anti-apoptotic protein Bcl-2 in the cells. Importantly, LY294002, a specific PI3K inhibitor, abrogated the anti-apoptosis effect of icariin, implicating the involvement of PI3K/Akt pathway. In summary, icariin prevents cisplatin-induced HEK-293 cell injury by inhibiting oxidative stress, inflammatory response, and cellular apoptosis partly via regulating NF-κB and PI3K/Akt signaling pathways. Icariin may serve as a potential therapeutic target against cisplatin-induced nephrotoxicity.

This study establishes a compartment model for the categorized COVID-19 risk area. In this model, the compartments represent administrative regions at different transmission risk levels instead of individuals in traditional epidemic models. The county-level regions are partitioned into High-risk (H), Medium-risk (M), and Low-risk (L) areas dynamically according to the current number of confirmed cases. These risk areas are communicable by the movement of individuals. An LMH model is established with ordinary differential equations (ODEs). The basic reproduction number R0 is derived for the transmission of risk areas to determine whether the pandemic is controlled. The stability of this LHM model is investigated by a Lyapunov function and Poincare–Bendixson theorem. We prove that the disease-free equilibrium (R0 < 1) is globally asymptotically stable and the disease will die out. The endemic equilibrium (R0 > 1) is locally and globally asymptotically stable, and the disease will become endemic. The numerical simulation and data analysis support the previous theoretical proofs. For the first time, the compartment model is applied to investigate the dynamics of the transmission of the COVID-19 risk area. This work should be of great value in the development of precision region-specific containment strategies.

Abstract Cisplatin, a potent anticancer drug, is usually causing nephrotoxicity; limiting its therapeutic application and efficiency. Maltol may be used to prevent such toxic effect. The aim of this study was to investigate the underlying protective mechanisms of maltol on nephrotoxicity by cisplatin using a cisplatin-treated mouse model and a cellular toxicity model of HEK293 cells. The blood urea nitrogen (BUN), creatinine (CRE) and neutrophil gelatinase-associated lipocalin (NGAL) levels in mice were increased by cisplatin but decreased to normal ranges by maltol pretreatment (50 and 100 mg/kg) for ten days. Besides, maltol pretreatment decreased oxidative stress, lipid peroxidation and apoptosis in cisplatin-treated mice. The inhibitory action of maltol on inflammatory responses was achieved by reducing the expressions in NF-κB, IL-1β, iNOS, and TNF-α in the mice in vivo. Additionally, maltol restored the reduction of PI3K/Akt and mTOR levels by cisplatin through increasing AMPK expression in cisplatin-treated HEK293 cells. Maltol also suppressed the expression of Bax and caspase 3 by inhibiting the p53 activity in HEK293 cells. Overall, maltol may serve as a valuable potential drug to prevent cisplatin-induced nephrotoxicity, and the underlying molecular mechanisms of maltol action may involve intracellular AMPK/PI3K/Akt and p53 signaling pathways.

Brevinins are a well-characterised, frog-skin-derived, antimicrobial peptide (AMP) family, but their applications are limited by high cytotoxicity. In this study, a wild-type des-Leu2 brevinin peptide, named brevinin-1OS (B1OS), was identified from Odorrana schmackeri. To explore the significant role of the leucine residue at the second position, two variants, B1OS-L and B1OS-D-L, were designed by adding L-leucine and D-leucine residues at this site, respectively. The antibacterial and anticancer activities of B1OS-L and B1OS-D-L were around ten times stronger than the parent peptide. The activity of B1OS against the growth of Gram-positive bacteria was markedly enhanced after modification. Moreover, the leucine-modified products exerted in vivo therapeutic potential in an methicillin-resistant Staphylococcus aureus (MRSA)-infected waxworm model. Notably, the single substitution of D-leucine significantly increased the killing speed on lung cancer cells, where no viable H838 cells survived after 2 h of treatment with B1OS-D-L at 10 μM with low cytotoxicity on normal cells. Overall, our study suggested that the conserved leucine residue at the second position from the N-terminus is vital for optimising the dual antibacterial and anticancer activities of B1OS and proposed B1OS-D-L as an appealing therapeutic candidate for development.

The current opioid epidemic in the US presents a great problem which calls for policy supervision and regulation. In this work, the opioid cases of five states were used for trend analysis and modeling for the estimation of potential policy effects. An evaluation model was established to analyze the severity of the opioid abuse based on the entropy weight method (EWM) and rank sum ratio (RSR). Four indexes were defined to estimate the spatial distribution of development and spread of the opioid crisis. Thirteen counties with the most severe opioid abuse in five states were determined using the EWM-RSR model and those indexes. Additionally, a forecast of the development of opioid abuse was given based on an autoregressive (AR) model. The RSR values of the thirteen counties would increase to the range between 0.951 and 1.226. Furthermore, the least absolute shrinkage and selection operator (LASSO) method was adopted. The previous indexes were modified, incorporating the comprehensive socioeconomic effects. The optimal penalty term was found to facilitate the stability and reliability of the model. By using the comprehensive model, it was found that three factors—VC112, VC114, VC115—related to disabled people have a great influence on the development of opioid abuse. The simulated policies were performed in the model to decrease the values of the indicators by 10%–50%. The corresponding RSR values can decline to the range between 0.564 and 0.606. Adopting policies that benefit the disabled population should inhibit the trend of opioid abuse.

Antibiotic resistance represents a tremendous contemporary clinical challenge. Given this challenge, antimicrobial peptides (AMPs) are regarded as one of the most promising new options for next-generation lead antibiotics. Here, we describe the antibacterial activities of a cationic peptide named DRP-AC4, obtained from frog skin secretion using shotgun cloning. Two modified peptides were derived by substituting the sequence of amino acids to complete the hydrophobic face (DRP-AC4b) and increase net charge (DRP-AC4a), respectively. The activity and cytotoxicity of these two peptides were compared. DRP-AC4a displayed significantly increased potency against bacteria compared to the natural peptide. It should be noted, however, that both analogue peptides demonstrated higher lytic ability than the natural peptide against the membranes of mammalian erythrocytes. At the same time, all three peptides displayed lower hemolytic activity compared to their antibacterial activity. Here, we demonstrate that AMPs have more complex activity mechanisms and faster bactericidal rates than traditional antibiotics, which may be one of the reasons why bacteria do not develop resistance to them. These discoveries provide interesting insights into the discovery and development of novel drugs from natural sources.

Background: Anti-apoptotic mechanism for cell protection on reperfusion may provide a new method to reduce reperfusion injury. Aims: The aim of the present study is to explore the effect of mitochondrial ATP sensitive potassium channel (Mito-KATP) opener diazoxide (DZ) preconditioning on hypoxia/ reoxygen (H/R) injury of rat myocardium microvascular endothelial cells (MMECs) against apoptosis and relation of PI3K/Akt pathway. Study Design: Animal experimentation. Methods: The rat MMECs were cultivated, and H/R model was made to imitate ischemia-reperfusion injury. The cells were seeds in 96-wellplates (100μL/hole) or in 6cm diameter dishes (2 mL/dish) with the density of 1×106/mL and randomly divided into 4 groups (n=6 each): control group (Group N), hypoxia-regoxygen group (Group H/R), Diazoxide preconditioning+H/R group (Group DZ) and Diazoxide preconditioning +mitochondrial KATP blocker 5-hydroxydecanoate (5-HD) + H/R group (Group DZ+5-HD). The cells were exposed to 2h hypoxia followed by 2h reoxygenation. Diazoxide 100μmol/L and diazoxide 100μmol/L+ 5-HD100μmol/L were added to the culture medium 2h before hypoxia in DZ and DZ+5-HD groups respectively. Each group was observed the proliferation in MTT, apoptotic rate in Annexin V-FITC/PI double standard, cell structure of Hoechst staining, and the levels of PI3K, Akt and p53 mRNA by RT-qPCR. Results: Compared with Group N, apoptotic rate of Group H/R increased (p

Maltol, a food-flavoring agent and Maillard reaction product formed during the processing of red ginseng (Panax ginseng, C.A. Meyer), has been confirmed to exert a hepatoprotective effect in alcohol-induced oxidative damage in mice. However, its beneficial effects on acetaminophen (APAP)-induced hepatotoxicity and the related molecular mechanisms remain unclear. The purpose of this article was to investigate the protective effect and elucidate the mechanisms of action of maltol on APAP-induced liver injury in vivo. Maltol was administered orally at 50 and 100 mg/kg daily for seven consecutive days, then a single intraperitoneal injection of APAP (250 mg/kg) was performed after the final maltol administration. Liver function, oxidative indices, inflammatory factors—including serum alanine and aspartate aminotransferases (ALT and AST), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), liver glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) were measured. Results demonstrated that maltol possessed a protective effect on APAP-induced liver injury. Liver histological changes and Hoechst 33258 staining also provided strong evidence for the protective effect of maltol. Furthermore, a maltol supplement mitigated APAP-induced inflammatory responses by increasing phosphorylated nuclear factor-kappa B (NF-κB), inhibitor kappa B kinase α/β (IKKα/β), and NF-kappa-B inhibitor alpha (IκBα) in NF-κB signal pathways. Immunoblotting results showed that maltol pretreatment downregulated the protein expression levels of the B-cell-lymphoma-2 (Bcl-2) family and caspase and altered the phosphorylation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) in a dose-dependent manner. In conclusion, our findings clearly demonstrate that maltol exerts a significant liver protection effect, which may partly be ascribed to its anti-inflammatory and anti-apoptotic action via regulation of the PI3K/Akt signaling pathway.

Background: Although kidney injury caused by cisplatin has attracted much attention, cisplatin-induced cardiotoxicity is elusive. Our previous studies have confirmed that saponins (ginsenosides) from Panax quinquefolius can effectively reduce acute renal injuries. Our current study aimed to identify the potential effects of saponins from leaves of P. quinquefolius (PQS) on cisplatin-evoked cardiotoxicity. Methods: Mice were intragastrically with PQS at the doses of 125 and 250 mg/kg daily for 15 days. The mice in cisplatin group and PQS + cisplatin groups received four times intraperitoneal injections of cisplatin (3 mg/kg) two days at a time from the 7th day, respectively. All mice were killed at 48 h following final cisplatin injection. Body weights, blood and organic samples were collected immediately. Results: Our results showed that cisplatin-challenged mice experienced a remarkable cardiac damage with obvious histopathological changes and elevation of lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB) and cardiac troponin T (cTnT) concentrations and viabilities in serum. Cisplatin also impaired antioxidative defense system in heart tissues manifested by a remarkable reduction in reduced glutathione (GSH) content and superoxide dismutase (SOD) activity, demonstrating the overproduction of reactive oxygen species (ROS) and oxidative stress. Interestingly, PQS (125 and 250 mg/kg) can attenuate cisplatin-evoked changes in the above-mentioned parameters. Additionally, PQS administration significantly alleviated the oxidation resulted from inflammatory responses and apoptosis in cardiac tissues via inhibition of overexpressions of TNF-α, IL-1β, Bax, and Bad as well as the caspase family members like caspase-3, and 8, respectively. Conclusion: Findings from our present research clearly indicated that PQS exerted significant effects on cisplatin-induced cardiotoxicity in part by inhibition of the NF-κB activity and regulation of PI3K/Akt/apoptosis mediated signaling pathways.

The purpose of this research was to evaluate whether maltol could protect from hepatic injury induced by carbon tetrachloride (CCl4) in vivo by inhibition of apoptosis and inflammatory responses. In this work, maltol was administered at a level of 100 mg/kg for 15 days prior to exposure to a single injection of CCl4 (0.25%, i.p.). The results clearly indicated that the intrapulmonary injection of CCl4 resulted in a sharp increase in serum aspartate transaminase (AST) and alanine transaminase (ALT) activities, tumor necrosis factor-α (TNF-α), irreducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB) and interleukin-1β (IL-1β) levels. Histopathological examination demonstrated severe hepatocyte necrosis and the destruction of architecture in liver lesions. Immunohistochemical staining and western blot analysis suggested an accumulation of iNOS, NF-κB, IL-1β and TNF-α expression. Maltol, when administered to mice for 15 days, can significantly improve these deleterious changes. In addition, TUNEL and Hoechst 33258 staining showed that a liver cell nucleus of a model group diffused uniform fluorescence following CCl4 injection. Maltol pretreatment groups did not show significant cell nuclear condensation and fragmentation, indicating that maltol inhibited CCl4-induced cell apoptosis. By evaluating the liver catalase (CAT), glutathione (GSH), superoxide dismutase (SOD) activity, and further using a single agent to evaluate the oxidative stress in CCl4-induced hepatotoxicity by immunofluorescence staining, maltol dramatically attenuated the reduction levels of hepatic CAT, GSH and SOD, and the over-expression levels of CYP2E1 and HO-1. In the mouse model of CCl4-induced liver injury, we have demonstrated that the inflammatory responses were inhibited, the serum levels of ALT and AST were reduced, cell apoptosis was suppressed, and liver injury caused by CCl4 was alleviated by maltol, demonstrating that maltol may be an efficient hepatoprotective agent.

Acetaminophen overdose-induced hepatotoxicity is the most common cause of acute liver failure in many countries. Previously, alpha-mangostin (α-MG) has been confirmed to exert protective effects on a variety of liver injuries, but the protective effect on acetaminophen-induced acute liver injury (ALI) remains largely unknown. This work investigated the regulatory effect and underlying cellular mechanisms of α-MG action to attenuate acetaminophen-induced hepatotoxicity in mice. The increased serum aminotransferase levels and glutathione (GSH) content and reduced malondialdehyde (MDA) demonstrated the protective effect of α-MG against acetaminophen-induced hepatotoxicity. In addition, α-MG pretreatment inhibited increases in tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) caused by exposure of mice to acetaminophen. In liver tissues, α-MG inhibited the protein expression of autophagy-related microtubule-associated protein light chain 3 (LC3) and BCL2/adenovirus E1B protein-interacting protein 3 (BNIP3). Western blotting analysis of liver tissues also proved evidence that α-MG partially inhibited the activation of apoptotic signaling pathways via increasing the expression of Bcl-2 and decreasing Bax and cleaved caspase 3 proteins. In addition, α-MG could in part downregulate the increase in p62 level and upregulate the decrease in p-mTOR, p-AKT and LC3 II /LC3 I ratio in autophagy signaling pathways in the mouse liver. Taken together, our findings proved novel perspectives that detoxification effect of α-MG on acetaminophen-induced ALI might be due to the alterations in Akt/mTOR pathway in the liver.