Diabetic Liver Injury Research Articles

Ginsenoside Rg1 alleviates diabetic liver injury and fibrosis by inhibiting the PLC-NFAT2-NLRP3 signaling pathway in T2DM mice

Diabetic liver injury (DLI) is a complication that impairs the quality of life of diabetic patients. Ginsenoside Rg1 is hepatoprotective, but its role and mechanism in diabetic liver injury need further investigation. Therefore, using in vivo experiments, we investigated the implication of ginsenoside Rg1 on hepatic lipid deposition, hepatic injury, hepatic fibrosis, and associated inflammation using a type 2 diabetes mellitus (T2DM) mouse model. We observed that Rg1 significantly ameliorated hepatic lipid deposition and hepatic fibrosis in T2DM mice. Meanwhile, Rg1 significantly reduced the expression of CD36, p-PLC, CaN, and NFAT2 and inhibited the activation of the NLRP3 inflammasome. Molecular docking results indicated that Rg1 binds well to PLC. In vitro experiments also demonstrated that Rg1 can inhibit calcium overload by regulating PA + HG-induced PLC activation in HepG2 cells. These results suggest that Rg1 treatment prevents T2DM-induced liver injury by inhibiting hepatic lipid deposition and the PLC-NFAT2-NLRP3 signaling pathway.

Formononetin attenuates hepatic injury in diabetic mice by regulating macrophage polarization through the PTP1B/STAT6 axis

BackgroundFormononetin (FNT) is an isoflavone known for its anti-inflammatory properties and has been shown to reduce insulin resistance in Type 2 Diabetes Mellitus (T2DM). However, its effects and the underlying mechanisms in diabetic liver injury remain largely unexplored. MethodsWe established a T2DM-induced liver injury mouse model by feeding high-fat diet, followed by injecting streptozotocin. The mice were then treated with FNT and the liver function in these mice was assessed. Macrophage markers in FNT-treated T2DM mice or human THP-1 cells were evaluated using flow cytometry, RT-qPCR, and Western blotting. The expression of PTP1B and STAT6 in mouse liver tissues and THP-1 cells was analyzed. Molecular docking predicted the interaction between PTP1B and STAT6, which was validated via co-immunoprecipitation (Co-IP) and phos-tag analysis. Microscale thermophoresis (MST) assessed the binding affinity of FNT to PTP1B. ResultsFNT treatment significantly ameliorated blood glucose levels, hepatocyte apoptosis, inflammatory response, and liver dysfunction in T2DM mice. Moreover, FNT facilitated M2 macrophage polarization in both T2DM mice and high glucose (HG)-induced THP-1-derived macrophages. The PTP1B/STAT6 axis, deregulated in T2DM mice, was normalized by FNT treatment, which counteracted the T2DM-induced upregulation of PTP1B and downregulation of phosphorylated STAT6. Molecular docking and subsequent analyses revealed that PTP1B binds to and dephosphorylates STAT6 at the S325A site. In contrast, FNT strongly binds to PTP1B and influences its expression at the K116A site, promoting M2 polarization of THP-1 cells via downregulation of PTP1B. ConclusionFormononetin mitigates diabetic hepatic injury by fostering M2 macrophage polarization via the PTP1B/STAT6 axis.

Punicalagin Ameliorates Diabetic Liver Injury by Inhibiting Pyroptosis and Promoting Autophagy via Modulation of the FoxO1/TXNIP Signaling Pathway.

Diabetic liver injury (DLI) is one of the complications of diabetes mellitus, which seriously jeopardizes human health. Punicalagin (PU), a polyphenolic compound mainly found in pomegranate peel, has been shown to ameliorate metabolic diseases such as DLI, and the mechanism needs to be further explored. In this study, a HFD/STZ-induced diabetic mouse model is established to investigate the effect and mechanism of PU on DLI. The results show that PU intervention significantly improves liver histology and serum biochemical abnormalities in diabetic mice, significantly inhibits the expression of pyroptosis-related proteins such as NLRP3, Caspase1, IL-1β, and GSDMD in the liver of diabetic mice, and up-regulated the expression of autophagy-related proteins. Meanwhile, PU treatment significantly increases FoxO1 protein expression and inhibits TXNIP protein expression in the liver of diabetic mice. The above results are further verified in the HepG2 cell injury model induced by high glucose. AS1842856 is a FoxO1 specific inhibitor. The intervention of AS1842856 combined with PU reverses the regulatory effects of PU on pyroptosis and autophagy in HepG2 cells. In conclusion, this study demonstrates that PU may inhibit pyroptosis and upregulate autophagy by regulating FoxO1/TXNIP signaling, thereby alleviating DLI.

Inhibition of ROS/caspase-3/GSDME-mediated pyroptosis alleviates high glucose-induced injury in AML-12 cells

Diabetic liver injury (DLI) is a chronic complication of the liver caused by diabetes, and its has become one of the main causes of nonalcoholic fatty liver disease (NAFLD). The gasdermin E (GSDME)-dependent pyroptosis signaling pathway is involved in various physiological and pathological processes; however, its role and mechanism in DLI are still unknown. This study was performed to investigate the role of GSDME-mediated pyroptosis in AML-12 cell injury induced by high glucose and to evaluate the therapeutic potential of caspase-3 inhibition for DLI. The results showed that high glucose activated apoptosis by regulating the apoptotic protein levels including Bax, Bcl-2, and enhanced cleavage of caspase-3 and PARP. Notably, some of the hepatocytes treated with high glucose became swollen, accompanied by GSDME-N generation, indicating that pyroptosis was further induced by active caspase-3. Moreover, the effects of high glucose on AML-12 cells could be partly reversed by a reactive oxygen scavenger (NAC) and caspase-3 specific inhibitor (Z-DEVD-FMK), which suggests high glucose induced GSDME-dependent pyroptosis in AML-12 cells through increasing ROS levels and activating caspase-3. In conclusion, our results show that high glucose can induce pyroptosis in AML-12 cells, at least in part, through the ROS/caspase-3/GSDME pathway，and inhibition of caspase-3 can ameliorate high glucose-induced hepatocyte injury, providing an important basis for clarifying the pathogenesis and treatment of DLI.

Theaflavin-3,3'-Digallate Protects Liver and Kidney Functions in Diabetic Rats by Up-Regulating Circ-ITCH and Nrf2 Signaling Pathway.

Theaflavin-3,3'-digallate (TFDG) in black tea has a strong antioxidant capacity. However, its effect on diabetic liver and kidney injury and the underlying mechanisms remain unclear. In the present study, our findings indicated that TFDG administration effectively lowers the fasting blood glucose and serum lipid concentrations and enhances the functionality and cellular architecture of the liver and kidney in rats with diabetes. The data also showed that TFDG mitigates oxidative harm in the liver and kidney of rats afflicted with diabetes. Additionally, metformin combined with TFDG was significantly more effective in reducing blood glucose and oxidative stress. Further studies suggested that TFDG upregulates the Nrf2 signal pathway and circ-ITCH (hsa_circ_0001141) expression. Silencing of circ-ITCH by transfection of the interfering plasmid apparently reduces the effects of TFDG on the Nrf2 signal pathway and oxidative stress in high-glucose-treated hepatic and renal cells. In conclusion, the present study highlights the great potential of TFDG in ameliorating diabetic liver and kidney injury by up-regulating circ-ITCH to promote the Nrf2 signal pathway and provides a potential option for the prevention and treatment of diabetic complications.

Krill Oil Ameliorates Liver Injury in Diabetic Mice by Activating Antioxidant Capacity and Inhibiting Ferroptosis.

Diabetic liver injury (DLI) has raised attention in recent years. Liver injury results from type 2 diabetes mellitus (T2DM), and in turn accelerates T2DM development by exacerbating insulin resistance. However, effective approaches for mitigating DLI are surprisingly rare. Krill oil (KO) is an alternative source of omega-3 polyunsaturated fatty acids, possessing antioxidant and anti-inflammatory capacities. Here we investigated the effect of KO supplementation on DLI in a mouse model of T2DM induced by streptozotocin and high-fat diet. The diabetic mice developed glucose intolerance, elevated serum alanine aminotransferase and aspartate aminotransferase, and hepatic pathological injuries such as vacuolation, lipid accumulation and fibrosis deposition, the effects of which were mitigated by KO. Further investigation showed that KO ameliorated the DM-induced expression of fibrotic and inflammatory genes. Notably, KO dramatically reduced hepatic oxidative gene expression, lipid peroxidation and ROS production, all of which are hallmarks of ferroptosis. The inhibitory effect of KO on ferroptosis was confirmed by the KO-decreased hepatic expression of GPX4, COX2 and ACSL4, as well as the KO-reduced hepatic iron deposition. Further, KO restored hepatic NRF2 antioxidant signaling which combats ferroptosis. The present study may provide KO supplementation as a viable approach for the intervention of DLI.

Modified Buyang Huanwu Decoction alleviates diabetic liver injury via inhibiting oxidative stress in db/db mice

Modified Buyang Huanwu Decoction alleviates diabetic liver injury via inhibiting oxidative stress in db/db mice

Protective effects of Huang-Qi-Ge-Gen decoction against diabetic liver injury through regulating PI3K/AKT/Nrf2 pathway and metabolic profiling

Ethnopharmacological relevanceHuang-Qi-Ge-Gen decoction (HGD) is a traditional Chinese medicine prescription that has been used for centuries to treat “Xiaoke” (the name of diabetes mellitus in ancient China). However, the ameliorating effects of HGD on diabetic liver injury (DLI) and its mechanisms are not yet fully understood. Aim of the studyTo elucidate the ameliorative effect of HGD on DLI and explore its material basis and potential hepatoprotective mechanism. Materials and methodsA diabetic mice model was induced by feeding a high-fat diet and injecting intraperitoneally with streptozotocin (40 mg kg−1) for five days. After the animals were in confirmed diabetic condition, they were given HGD (3 or 12 g kg−1, i. g.) for 14 weeks. The effectiveness of HGD in treating DLI mice was evaluated by monitoring blood glucose and blood lipid levels, liver function, and pathological conditions. Furthermore, UPLC-MS/MS was used to identify the chemical component profile in HGD and absorption components in HGD-treated plasma. Network pharmacology and molecular docking were performed to predict the potential pathway of HGD intervention in DLI. Then, the results of network pharmacology were validated by examining biochemical parameters and using western blotting. Lastly, urine metabolites were analyzed by metabolomics strategy to explore the effect of HGD on the metabolic profile of DLI mice. ResultsHGD exerted therapeutic potential against the disorders of glucose metabolism and lipid metabolism, liver dysfunction, liver steatosis, and fibrosis in a DLI model mice induced by HFD/STZ. A total of 108 chemical components in HGD and 18 absorption components in HGD-treated plasma were preliminarily identified. Network pharmacology and molecular docking results of the absorbed components in plasma indicated PI3K/AKT as a potential pathway for HGD to intervene in DLI mice. Further experiments verified that HGD markedly reduced liver oxidative stress in DLI mice by modulating the PI3K/AKT/Nrf2 signaling pathway. Moreover, 19 differential metabolites between normal and DLI mice were detected in urine, and seven metabolites could be significantly modulated back by HGD. ConclusionsHGD could ameliorate diabetic liver injury by modulating the PI3K/AKT/Nrf2 signaling pathway and urinary metabolic profile.

A 4D Printed Adhesive, Thermo-Contractile, and Degradable Hydrogel for Diabetic Wound Healing.

Chronic wound healing remains a substantial clinical challenge. Current treatments are often either prohibitively expensive or insufficient in meeting the various requirements needed for effective diabetic wound healing. A 4D printing multifunctional hydrogel dressing is reported here, which aligns perfectly with wounds owning various complex shapes and depths, promoting both wound closure and tissue regeneration. The hydrogel is prepared via digital light process (DLP) 3D printing of the mixture containing N-isopropylacrylamide (NIPAm), curcumin-loaded Pluronic F127 micelles (Cur-PF127), and poly(ethylene glycol) diacrylate-dopamine (PEGDA575-Do), a degradable crosslinker. The use of PEGDA575-Do ensures tissue adhesion and degradability, and cur-PF127 serves as an antibacterial agent. Moreover, the thermo-responsive mainchains (i.e., polymerized NIPAm) enables the activation of wound contraction by body temperature. The features of the prepared hydrogel, including robust tissue adhesion, temperature-responsive contraction, effective hemostasis, spectral antibacterial, biocompatibility, biodegradability, and inflammation regulation, contribute to accelerating diabetic wound healing in Methicillin-resistant Staphylococcus aureus (MRSA)-infected full-thickness skin defect diabetic rat models and liver injury mouse models, highlighting the potential of this customizable, mechanobiological, and inflammation-regulatory dressing to expedite wound healing in various clinical settings.

Camel whey protein improves diabetic liver injury by targeting ACMSD and promoting de novo NAD+ synthesis

Diabetic liver injury is a complication of diabetes without any specific medicine approved for its effective treatment or prevention. In this research, the effect of camel whey protein (CWP) on diabetic liver injury in T2DM rats (T2DM induced by a high-fat diet) and streptozotocin along with its possible mechanism were investigated by means of transcriptome and proteomics. The results demonstrated that CWP lowered fasting blood glucose and improved abnormal blood lipid profiles in T2DM rats. CWP reduced lipid accumulation, diminished oxidative stress, and effectively improved the pathological changes in the liver of T2DM rats. Further experiments indicated that CWP intake had adjusted mitochondrial dysfunction in the livers of T2DM rats and L-O2 cells induced by high glucose (HG)/palmitic acid (PA) by inhibiting α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) expression. In conclusion, CWP can ameliorate diabetic liver injury in T2DM rats by inhibiting the expression of ACMSD, promote de novo NAD+ synthesis and enhance mitochondrial function.

Engineering of cyanine-based nanoplatform with tunable response toward reactive species for ratiometric NIR-II fluorescent imaging in mice

High-quality second near-infrared (NIR-II) nanoprobes are of great significance for real-time bioimaging and medical diagnosis. Cyanine is an important class of fluorophores to construct activatable probes; however, there are still significant challenges hindering their biological applications, including weak fluorescence in aqueous solution, instability, and insufficient specificity. Herein, an integrated engineering strategy is conducted to develop the cyanine-based activatable NIR-II nanoplatforms with bright, stable emission and high specificity. Specifically, poly(styrene-co-maleic anhydride) (PSMA) is employed to encapsulate NIR-II fluorescent molecules (IR1048) to render the stable and bright NIR-II nanoparticles (PSMA@IR1048 NPs). By charge-modulated strategy, a series of cyanine-fluorophores are loaded on the surface of PSMA@IR1048 NPs and exhibit tunable response toward reactive species. Combing those two strategies, NIR-II ratiometric fluorescent nanoprobes (RNPs, including RNP1, RNP2, and RNP3) are constructed; among them, RNP2 displays hypochlorous acid (HClO) responsive performance and generates a higher NIR-II fluorescent ratio (FL2/FL1) signal. Such nanoprobe can reliably report the pathological HClO level in models of diabetic liver injury and lower limb ischemia–reperfusion (I/R) injury mice. Our study paves an engineering strategy to construct cyanine-based stable, bright, and specific NIR-II probes for bioimaging.

Protective effect of solanesol in glucose-induced hepatocyte injury: Mechanistic insights on oxidative stress and mitochondrial preservation

Solanesol is a tetra sesquiterpene enol with various biological activities. Modern medical studies have confirmed that solanesol has the function of lipid antioxidation and scavenges free radicals. This study aimed to investigate the protective effect of solanesol against oxidative damage induced by high glucose on human normal hepatocytes (L-02 cells) and its possible mechanism. The results showed that solanesol could effectively improve the decrease of cell viability induced by high glucose, decrease the contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) in the extracellular medium, increased the enzyme activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), balanced the level of reactive oxygen species (ROS) in cells, inhibited lipid peroxidation of all kinds of biological membranes, and restored mitochondrial membrane potential (MMP). In addition, Solanesol also inhibited the expression of Keap1, promoted the nuclear translocation of Nrf2 by hydrogen bonding with Nrf2, and activated the expression of downstream antioxidant factors NQO1 and HO-1. Altogether, these findings suggest that solanesol may be a potential protectant against diabetic liver injury.

Low‑dose ionizing radiation attenuates high glucose‑induced hepatic apoptosis and immune factor release via modulation of a miR‑155‑SOCS1 axis.

Diabetic liver injury (DLI) can result in several diseases of the liver, including steatohepatitis, liver fibrosis, cirrhosis, and liver cancer. Low‑dose ionizing radiation (LDIR) has hormetic effects in normal/disease conditions. However, whether LDIR has a beneficial effect on DLI has not been assessed previously. MicroRNA (miR)‑155 and its target gene suppressor of cytokine signaling 1 (SOCS1) play critical roles in modulating hepatic proliferation, apoptosis, and immunity. However, whether a miR‑155‑SOCS1 axis is involved in high glucose (HG) induced hepatic damage remains to be determined. In the present study, mouse hepatocyte AML12 cells were treated with 30mM glucose (HG), 75 mGy X‑ray (LDIR), or HG plus LDIR. The expression levels of miR‑155 and SOCS1 were determined by reverse transcription‑quantitative PCR and western blotting. Additionally, apoptosis was measured using flow cytometry. The release of inflammatory factors, including TNF‑α, IL‑1β, IL‑6, IL‑10, and IFN‑γ, after HG and/or LDIR treatment was detected by ELISA. The results showed that HG may induce hepatic apoptosis by upregulating the levels of miR‑155 and downregulating the levels of SOCS1. HG also stimulated the secretion of TNF‑α, IL‑1β, IL‑6, and IL‑10. However, LDIR blocked the HG‑induced activation of a miR‑155‑SOCS1 axis and suppressed the release of inflammatory factors. These results indicated that a miR‑155‑SOCS1 axis plays a role in HG‑induced liver injury, and LDIR may exert a hepatoprotective effect by regulating the miR‑155‑SOCS1 axis.

A near-infrared aggregation-induced emission probe for imaging lipid droplet and in vivo visualization of diabetes-related viscosity variations

As a pivotal parameter of microenvironment, viscosity is closely related to many diseases and dysfunction in vivo. Lipid droplets, as organelles that store and metabolize lipids, are involved in various physiological processes related to metabolism in cells. Diabetes is one of the metabolic diseases that may lead to dysfunction of organs, which is associated with abnormal viscosity changes. It is of great significance for the study of related diseases to clarify the relationship between viscosity variations in vivo and monitor the changes of lipid droplets. Here, a near-infrared fluorescent probe DPX ((E)− 6-(dimethylamino)− 4-(4-(diphenylamino)benzylidene)− 9-methyl-1,2,3,4-tetrahydroxanthylium) with AIE characteristics was designed, which shows an “off-on” fluorescence response to viscosity based on twisting intramolecular charge transfer (TICT) mechanism. The probe DPX features excellent mitochondria and lipid droplets targeting, and sensitively monitor accumulation of LDs induced by oleic acid and mitochondrial viscosity variations in HeLa cells. More importantly, DPX has been successfully applied to visualize viscosity changes of diabetic liver injury in vivo, which may be benefit for development of diabetes related clinical research.

Liposome-Encapsulated Berberine Alleviates Liver Injury in Type 2 Diabetes via Promoting AMPK/mTOR-Mediated Autophagy and Reducing ER Stress: Morphometric and Immunohistochemical Scoring.

In the advanced stages of type 2 diabetes mellitus (T2DM), diabetic liver damage is a common complication that can devastate a patient's quality of life. The present study investigated the ability of liposomal berberine (Lip-BBR) to aid in ameliorating hepatic damage and steatosis, insulin homeostasis, and regulating lipid metabolism in type 2 diabetes (T2DM) and the possible pathways by which it does so. Liver tissue microarchitectures and immunohistochemical staining were applied during the study. The rats were divided into a control non-diabetic group and four diabetic groups, which are the T2DM, T2DM-Lip-BBR (10 mg/kg b.wt), T2DM-Vildagliptin (Vild) (10 mg/kg b.wt), and T2DM-BBR-Vild (10 mg/kg b.wt + Vild (5 mg/kg b.wt) groups. The findings demonstrated that Lip-BBR treatment could restore liver tissue microarchitectures, reduce steatosis and liver function, and regulate lipid metabolism. Moreover, Lip-BBR treatment promoted autophagy via the activation of LC3-II and Bclin-1 proteins and activated the AMPK/mTOR pathway in the liver tissue of T2DM rats. Lip-BBR also activated the GLP-1 expression, which stimulated insulin biosynthesis. It decreased the endoplasmic reticulum stress by limiting the CHOP, JNK expression, oxidative stress, and inflammation. Collectively, Lip-BBR ameliorated diabetic liver injury in a T2DM rat model with its promotion activity of AMPK/mTOR-mediated autophagy and limiting ER stress.

Visualizing Detection of Diabetic Liver Injury by a Biomarker-Activatable Probe via NIR-II Fluorescence Imaging.

Diabetes characterized by hyperglycemia is a chronic metabolic disease with increasing prevalence worldwide, and over time it leads to damage to various organs including the liver. As the liver is the major organ for glucose metabolism, patients with diabetes are prone to liver injuries or damages; and without timely and effective treatment, diabetic liver injury may further deteriorate into serious or life-threatening complications including liver cancer or liver failure. Hence, the accurate detection of diabetic liver injury is of great significance for diabetic patients in terms of improving quality of life. Herein, a fluorescent probe (TTX-P) has been developed for in situ detection and imaging of diabetic liver injury in the near-infrared second-window (NIR-II) region. In routine clinical practice, alkaline phosphatase (ALP) is one of the most commonly assayed enzymes, and thus serving as an important diagnostic biomarker for liver dysfunction or injury. The probe TTX-P responds in situ to the overexpressed ALP in liver and thus giving out strong NIR-II fluorescence as the reporting signals for detection and imaging. The NIR-II probe TTX-P consists of the NIR-II chromophore TTX-OH as the fluorophore and phosphate group as the responsive unit. Without the presence of ALP, the probe TTX-P displays weak fluorescence because the electron-withdrawing phosphate group weakens the electron-pushing capability of the electron-donor side of the NIR-II fluorophore. While in the presence of ALP, the phosphate group is cleaved by the enzyme and consequently the fluorophore emits evident NIR-II fluorescence. The probe TTX-P has been applied in imaging liver injury in diabetic mice. The approach provides a utilitarian means for visualizing detection of diabetic liver injury in mice with NIR-II fluorescence imaging.

FTY-720 alleviates diabetes-induced liver injury by inhibiting oxidative stress and inflammation.

We aimed to investigate the protective effect of FTY-720 on liver injury and explore its potential mechanism in diabetic mice. The diabetic mouse model was induced with streptozotocin and FTY-720 was administered for 12 weeks. We assayed biocharacters and liver function, and used histopathology staining to evaluate the protective effects of FTY-720 against diabetic liver injury. Levels of oxidative stress and inflammation in the liver were observed. mRNA and protein levels of essential enzymes for glucose metabolism were quantified in the liver and the protein expression of TLR4, HIF1α, and NF-κB was determined. In vivo results revealed that FTY-720 significantly lowered blood glucose and lipids, and improved liver function and alleviated liver fibrosis in diabetic mice. FTY-720 reduced oxidative stress and inflammation, with the increased catalase activity and reduced levels of malondialdehyde, myeloperoxidase, IL-1β, IL-6, TNF-α, TGF-β and MCP1. Furthermore, FTY-720 modulated glucose metabolism in liver and elevated the ATP production, showing the promotion of glycogenesis and glycolysis and inhibition of gluconeogenesis. Moreover, FTY-720 inhibited the expression of TLR4 and HIF1α, contributing to restoration of liver function. In conclusion, FTY-720 ameliorates diabetes-induced liver injury and improves glucose homeostasis by inhibiting oxidative stress and inflammation, and may be a promise drug for treatment of liver disease.

Linarin Ameliorates Diabetic Liver Injury by Alleviating Oxidative Stress and Inflammation through the Inhibition of AKR1B1.

The study aims to find a new functional additive for diabetic liver injury. It is well-established that type 2 diabetes mellitus (T2DM) is a metabolic disease with multiple complications and places a significant health and economic burden on modern society. Linarin is a natural flavonoid isolated from Asteraceae and Lamiaceae, which has beneficial effects in preventing and treating metabolic diseases such as nonalcoholic steatohepatitis and diabetes. We aimed to investigate the pharmacological effect and underlying mechanism of linarin on T2DM-associated liver injury in vivo and in vitro. Using a high-glucose and high-palmitic acid-induced hepatocyte injury model and a type 2 diabetic rat model. Following linarin treatment, serum biochemical parameters, liver histology, and lipid profiles of rats were examined. Oxidative stress index and inflammatory response were detected in vivo and in vitro. The expression level of AKR1B1 in rat liver tissues and in vitro cells was detected by western blot and by real-time fluorescent quantitative PCR. The present study found that linarin could prevent oxidative stress and inflammation. In high-fat-fed diabetic rats, linarin administration (15, 30, and 60 mg/kg/day) reduced hepatic lipid accumulation, oxidative stress, and inflammation. Linarin (20 μM) significantly alleviated oxidative stress, inflammation, and apoptosis induced by high glucose combined with palmitic acid in LX-2 cells. Western blotting and overexpression experiments showed that these effects were related to AKR1B1 inhibition in vivo and in vitro. This study indicated that linarin could protect against liver injury in T2DM by alleviating oxidative stress and inflammation mediated by AKR1B1 and may be a promising additive for diabetic liver injury therapy.

Potential therapeutic effect of medium chain triglyceride oil in ameliorating diabetic liver injury in a streptozotocin-induced diabetic murine model.

Diabetes mellitus is one of the most commonly arising endocrine conditions. The disorder gives rise to enduring damage to a number of body tissues and viscera as a result of related macrovascular and microvascular complications. In patients who are unable to maintain their nutritional status independently, medium-chain triglyceride (MCT) oil is frequently added as a supplement to parenteral nutrition. The aim of the present research is to establish whether MCT oil has a therapeutic influence on the hepatic damage occurring in male albino rats as a result of streptozotocin (STZ)-induced diabetes. 24 male albino rats were randomized into four cohorts, i.e., controls, STZ-diabetic, metformin-treated and MCT oil-treated. The rodents were fed a high-fat diet for 14 days; a low dose of intraperitoneal STZ was then administered in order to induce diabetes. The rats were subsequently treated for 4 weeks with metformin or MCT oil. Analysis included an appraisal of liver histology and biochemical indices, i.e., fasting blood glucose (FBG), hepatic enzymes and glutathione (GSH), the latter obtained from hepatic tissue homogenate. A rise in FBG and hepatic enzymes was observed, but in the STZ-diabetic cohort, hepatic GSH levels were diminished. Treatment with either metformin or MCT oil led to a decline in FBG and hepatic enzyme titers whereas GSH concentrations increased. Liver histology findings were notable amongst rodents within control, STZ-diabetic and metformin-treated groups. The majority of histological changes were resolved following therapy with MCT oil. The anti-diabetic and antioxidant characteristics of MCT oil have been substantiated by this work. MCT oil led to a reversal of the hepatic histological changes seen in STZ-induced diabetes in rats.

Mechanistic Insights of Rutin against Metabolic Disorders

Rutin, a quercetin glycoside comes under the class flavonol. The aglycone part of rutin is known as quercetin. It is found in numerous fruits and plants, especially apricots, buckwheat, cherries, grapefruit, grapes, oranges, and plums. Rutin shows cardioprotective, neuroprotective, and nephroprotective effects mediated via its antioxidant mechanism. The neuroprotective effect of rutin is utilized in the treatment of Parkinson’s disease. It has been documented in the scientific literature that rutin improves obesity through brown fat activation, modulates DNA damage signaling in cancer cells, reduces inflammation by inhibiting eicosanoid biosynthesis, lipoxygenase, cyclooxygenase, and phospholipase A2 activities, enhances insulin release as well as decreases the expression of resistin along with increases the expression of PPAR γ in diabetic patients, increases total cholesterol, high-density lipoprotein and very low-density lipoprotein levels, whereas low-density lipoprotein level decreases resulting into antilipidemic activity, inhibits diabetic liver injury and diabetic cardiomyopathy. Repurposing of rutin was also done against SARS-CoV-2. Our study aims to survey the most recent progress with emphasis on how rutin adapts intracellular signaling cascades to treat different metabolic disorders. However, the precise cellular and molecular mechanisms of rutin are known and more clinical studies are required to provide a novel therapeutic approach for the treatment of metabolic disorders.