[FeIIICl(TMPPH2)][FeIIICl4]2: A Stand-Alone Molecular Nanomedicine That Induces High Cytotoxicity by Ferroptosis.

Developing clinically meaningful nanomedicines for cancer therapy requires the drugs to be effective, safe, simple, cheap, and easy to store. In the present work, we report that a simple cationic Fe(III)-rich salt of [FeIIICl(TMPPH2)][FeIIICl4]2 (Fe-TMPP) exhibits a superior anticancer performance on a broad spectrum of cancer cell lines, including breast, colorectal cancer, liver, pancreatic, prostate, and gastric cancers, with half maximal inhibitory concentration (IC50) values in the range of 0.098-3.97 µM (0.066-2.68 µg mL-1), comparable to the best-reported medicines. Fe-TMPP can form stand-alone nanoparticles in water without the need for extra surface modification or organic-solvent-assisted antisolvent precipitation. Critically, Fe-TMPP is TME-responsive (TME = tumor microenvironment), and can only elicit its function in the TME with overexpressed H2O2, converting H2O2 to the cytotoxic •OH to oxidize the phospholipid of the cancer cell membrane, causing ferroptosis, a programmed cell death process of cancer cells.

Infection dynamic of Micropterus salmoides rhabdovirus and response analysis of largemouth bass after immersion infection.

Largemouth bass (Micropterus salmoides) is an important economic freshwater aquaculture fish originating from North America. However, the frequent outbreaks of Micropterus salmoides rhabdovirus (MSRV) have seriously limited the healthy development of Micropterus salmoides farming industry. In the present study, a strain of MSRV was isolated and identified from infected largemouth bass by PCR, transmission electron micrograph observation and genome sequences analysis, and tentatively named MSRV-HZ01 strain. Phylogenetic analyses showed that the MSRV-HZ01 presented the highest similarity to MSRV-2021, followed by MSRV-FJ985 and MSRV-YH01. The various tissues of juvenile largemouth bass exhibited significant pathological damage following MSRV-HZ01 immersion infection, and the mortality reached 90%. We also found that intestine was the key organ for MSRV to enter the fish body initially by dynamic analysis of viral infection, and the head kidney was the susceptible tissue of virus. Moreover, the MSRV was also transferred to the external mucosal tissue in later stage of viral infection to achieve horizontal transmission. In addition, the genes of IFN γ and IFN I-C were significantly up-regulated after MSRV infection to exert antiviral functions. The genes of cGAS and Sting might play an important role in the regulation of interferon expression. In conclusion, we investigated the virus infection dynamics and fish response following MSRV immersion infection, which would promote our understanding of the interaction between MSRV and largemouth bass under natural infection.

Trehalose targets Nrf2 signal to alleviate d-galactose induced aging and improve behavioral ability.

As an important factor leading to aging and chronic diseases, oxidative stress has become a hot research topic. Trehalose is a natural sugar widely found in many edible plants, animals and natural microorganisms, and recent studies have suggested that trehalose is an antioxidant, although its underlying molecular mechanism is unclear. Therefore, we evaluated the protective mechanism of trehalose against oxidative stress-induced senescence. In the mouse model of d-galactose (D-gal) induced aging, we found that trehalose significantly reversed the learning and memory impairment caused by D-gal and improved the ability to explore unknown things, which was associated with a significant reduction in brain tissue damage. Further studies have shown that trehalose activates the expressions of downstream target genes HO-1, NQO1, SOD, GSH and CAT by promoting the nuclear translocation of Nrf2 in the liver. The detoxification ability of organs is increased, antioxidant enzyme activity is enhanced, lipid peroxidation is reduced, and the secretion of inflammatory factors TNF-α, IL-1ß, il-6 is decreased. In conclusion, trehalose play an anti-aging role by activating genes related to Nrf2 pathway.

Effects of phenolic constituents of daylily flowers on corticosterone- and glutamate-treated PC12 cells.

BACKGROUND: Daylily flowers, the flower and bud parts of Hemerocallis citrina or H. fulva, are well known as Wang-You-Cao in Chinese, meaning forget-one's sadness plant. However, the major types of active constituents responsible for the neurological effects remain unclear. This study was to examine the protective effects of hydroalcoholic extract and fractions and to identify the active fractions. METHODS: The extract of daylily flowers was separated with AB-8 resin into different fractions containing non-phenolic compounds, phenolic acid derivatives and flavonoids as determined using UPLC-DAD chromatograms. The neuroprotective activity was measured by evaluating the cell viability and lactate dehydrogenase release using PC12 cell damage models induced by corticosterone and glutamate. The neurological mechanisms were explored by determining their effect on the levels of dopamine (DA), 5-hydroxy tryptamine (5-HT), γ-aminobutyric acid (GABA), noradrenaline (NE) and acetylcholine (ACh) in the cell culture medium measured using an LC-MS/MS method. RESULTS: Pretreatment of PC12 cells with the extract and phenolic fractions of daylily flowers at concentrations ranging from 0.63 to 5 mg raw material/mL significantly reversed corticosterone- and glutamate-induced neurotoxicity in a dose-dependent manner. The fractions containing phenolic acid derivatives (0.59% w/w in the flowers) and/or flavonoids (0.60% w/w) exerted similar dose-dependent neuroprotective effect whereas the fractions with non-phenolic compounds exhibited no activity. The presence of phenolic acid derivatives in the corticosterone- and glutamate-treated PC12 cells elevated the DA level in the cell culture medium whereas flavonoids resulted in increased ACH and 5-HT levels. CONCLUSION: Phenolic acid derivatives and flavonoids were likely the active constituents of daylily flowers and they conferred a similar extent of neuroprotection, but affected the release of neurotransmitters in a different manner.

A Porphyrin-Based 3D Metal-Organic Framework Featuring [Cu8Cl6]10+ Cluster Secondary Building Units: Synthesis, Structure Elucidation, Anion Exchange, and Peroxidase-Like Activity.

Herein, we report a rare example of cationic three-dimensional (3D) metal-organic framework (MOF) of [Cu5Cl3(TMPP)]Cl5 ⋅ xSol (denoted as Cu-TMPP; H2TMPP=meso-tetrakis (6-methylpyridin-3-yl) porphyrin; xSol=encapsulated solvates) supported by [Cu8Cl6]10+ cluster secondary building units (SBUs) wherein the eight faces of the Cl--based octahedron are capped by eight Cu2+. Surface-area analysis indicated that Cu-TMPP features a mesoporous structure and its solvate-like Cl- counterions can be exchanged by BF4 -, PF6 -, and NO3 -. The polyvinylpyrrolidone (PVP) coated Cu-TMPP (denoted as Cu-TMPP-PVP) demonstrated good ROS generating ability, producing ⋅OH in the absence of light (peroxidase-like activity) and 1O2 on light irradiation (650 nm; 25 mW cm-2). This work highlights the potential of Cu-TMPP as a functional carrier of anionic guests such as drugs, for the combination therapy of cancer and other diseases.

Interleukin-1 beta (IL-1ß) as adjuvant enhances the immune effects of Aeromonas veronii inactivated vaccine in largemouth bass (Micropterus salmoides).

Largemouth bass (Micropterus salmoides) has emerged as a significant economic fish species, with a rise in Aeromonas veronii infections in farming. However, research on adjuvants for vaccines against A. veronii in largemouth bass remains scarce. In present study, recombinant largemouth bass IL-1ß (LbIL-1ß) was expressed to explore its adjuvant effect on the A. veronii inactivated vaccine. Following vaccination with recombinant LbIL-1ß (rLbIL-1ß) and the inactivated A. veronii, higher serum SOD levels and lysozyme activities were observed in largemouth bass from inactivated A. veronii + rLbIL-1ß vaccinated group. Furthermore, it was discovered that rLbIL-1ß was able to boost the serum-specific antibody levels induced by the inactivated A. veronii. The qRT-PCR analysis revealed that rLbIL-1ß also enhanced the expression of IgM, CD4, and MHC II in largemouth bass triggered by the inactivated A. veronii. After challenged with live A. veronii, the outcomes demonstrated that the relative percentage survival (RPS) for largemouth bass resulting from the inactivated A. veronii in combination with rLbIL-1ß was 76.67 %, surpassing the RPS of 60 % in the inactivated A. veronii group. Collectively, these findings indicate that rLbIL-1ß enhances the protective effect of the A. veronii inactivated vaccine on largemouth bass, showcasing potential as an adjuvant for further development.

A skeletal randomization strategy for high-performance quinoidal-aromatic polymers.

Enhancing the solution-processability of conjugated polymers (CPs) without diminishing their thin-film crystallinity is crucial for optimizing charge transport in organic field-effect transistors (OFETs). However, this presents a classic "Goldilocks zone" dilemma, as conventional solubility-tuning methods for CPs typically yield an inverse correlation between solubility and crystallinity. To address this fundamental issue, a straightforward skeletal randomization strategy is implemented to construct a quinoid-donor conjugated polymer, PA4T-Ra, that contains para-azaquinodimethane (p-AQM) and oligothiophenes as repeat units. A systematic study is conducted to contrast its properties against polymer homologues constructed following conventional solubility-tuning strategies. An unusually concurrent improvement of solubility and crystallinity is realized in the random polymer PA4T-Ra, which shows moderate polymer chain aggregation, the highest crystallinity and the least lattice disorder. Consequently, PA4T-Ra-based OFETs, fabricated under ambient air conditions, deliver an excellent hole mobility of 3.11 cm2 V-1 s-1, which is about 30 times higher than that of the other homologues and ranks among the highest for quinoidal CPs. These findings debunk the prevalent assumption that a random polymer backbone sequence results in decreased crystallinity. The considerable advantages of the skeletal randomization strategy illuminate new possibilities for the control of polymer aggregation and future design of high-performance CPs, potentially accelerating the development and commercialization of organic electronics.

A Three-in-One Hybrid Strategy for High-Performance Semiconducting Polymers Processed from Anisole.

The development of semiconducting polymers with good processability in green solvents and competitive electrical performance is essential for realizing sustainable large-scale manufacturing and commercialization of organic electronics. A major obstacle is the processability-performance dichotomy that is dictated by the lack of ideal building blocks with balanced polarity, solubility, electronic structures, and molecular conformation. Herein, through the integration of donor, quinoid and acceptor units, an unprecedented building block, namely TQBT, is introduced for constructing a serial of conjugated polymers. The TQBT, distinct in non-symmetric structure and high dipole moment, imparts enhanced solubility in anisole-a green solvent-to the polymer TQBT-T. Furthermore, PTQBT-T possess a highly rigid and planar backbone owing to the nearly coplanar geometry and quinoidal nature of TQBT, resulting in strong aggregation in solution and localized aggregates in film. Remarkably, PTQBT-T films spuncast from anisole exhibit a hole mobility of 2.30 cm2 V-1 s-1, which is record high for green solvent-processable semiconducting polymers via spin-coating, together with commendable operational and storage stability. The hybrid building block emerges as a pioneering electroactive unit, shedding light on future design strategies in high-performance semiconducting polymers compatible with green processing and marking a significant stride towards ecofriendly organic electronics.

Microbial transformation of asiatic acid.

Asiatic acid (1), a major pentacyclic triterpene of Centella asiatica, was subjected to transformation by Penicillium lilacinum ACCC 31890, Fusarium equiseti CGMCC 3.3658, and Streptomyces griseus CGMCC 4.18 strains. Incubation of asiatic acid with P. lilacinum ACCC 31890 and F. equiseti CGMCC 3.3658 gave an identical product: 2α,3ß,15α,23-tetrahydroxyurs-12-en-28-oic acid (2). Biotransformation of asiatic acid by S. griseus CGMCC 4.18 resulted in three derivatives: 2α,3ß,21ß,23-tetrahydroxyurs-12-en-28-oic acid (3), 2α,3ß,23-trihydroxyurs-12-en-28, 30-dioic acid (4), and 2α,3ß,23,30-tetrahydroxyurs-12-en-28-oic acid (5). The structures of those derivatives were deduced from their spectral data. Products (2), (3), and (4) were new compounds. In addition, the in vitro cytotoxicities of those derivatives along with 1 were evaluated with several human cancer cell lines.

Deep Data Analysis-Based Agricultural Products Management for Smart Public Healthcare.

Agricultural is an indispensably public healthcare industry for human beings at any time and smart management of it is of great significance. Since substantial technical advance relies on long-term efforts and continuous progress, reasonably scheduling the distribution of agricultural products acts as a key aspect of smart public healthcare. The most intuitive factor affecting the distribution of agricultural products is its dynamic price. Forecasting price fluctuations in advance can optimize the distribution of agricultural products and pave the way to smart public healthcare. Most researchers study the prices of various agricultural products separately, without considering the interaction of different agricultural products in the time dimension. This study introduces a typical deep learning model named graph neural network (GNN) for this purpose and proposes deep data analysis-based agricultural products management for smart public healthcare (named GNN-APM for short). The highlight of GNN-APM is to take latent correlations among multiple types of agricultural products into consideration when modeling evolving rules of price sequences. A case study is set up with the use of real-world data of the agricultural products market. Simulative results reveal that the designed GNN-APM functions well.

Three Isomeric Non-Fullerene Acceptors Comprising a Mono-Brominated End-Group for Efficient Organic Solar Cells.

Non-fullerene acceptors (NFAs) carrying a 1,1-dicyanomethylene-3-indanone (IC) end-group are the most powerful ones to boost the power conversion efficiency of organic solar cells (OSCs). However, the well-known Knoevenagel condensation of the mono-halogenated IC end-group will result in an NFA isomeric effect, a chemical issue that needs to be addressed. Herein, facile preparations and separations of three well-defined mono-brominated isomers BTzIC-2Br-δ, BTzIC-2Br-γ, and BTzIC-2Br-δγ via column chromatography with a well-chosen mixing solvent were demonstrated for Knoevenagel condensation, and their structures were verified by NMR spectra and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) mass spectra. It is the first time that an asymmetric isomer BTzIC-2Br-δγ is reported, and the regioisomeric effect on optoelectronic properties can be investigated based on all three isomers. Moreover, the single-crystal structure was successfully achieved for the symmetric molecule BTzIC-2Br-γ. With benzodithiophene (BDT)-free PFBT4T-T20 as an easily accessible and low-cost polymer donor, the three isomers could show differentiated device performances, with a power conversion efficiency order of BTzIC-2Br-γ (16.00%) > BTzIC-2Br-δγ (15.81%) > BTzIC-2Br-δ (15.29%). The best efficiency of 16.00% achieved with BTzIC-2Br-γ is among the highest ones for binary OSCs based on the low-cost BDT-free donors. The facile and complete synthesis of isomeric NFAs with mono-halogenated IC end-groups would promote the elucidation of the structure-property relationship.

[Tiaohe Yinyang acupotomy for knee osteoarthritis: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of Tiaohe Yinyang acupotomy (acupotomy for regulating and harmonizing yin and yang) for knee osteoarthritis (KOA). METHODS: A total of 88 patients with KOA were randomized into a acupotomy group and a sham-acupotomy group, 44 cases in each group. In the acupotomy group, acupotomy was applied at yin side (4-5 high stress points i.e. pes anserinus and terminal of popliteus) and yang side (1-2 high stress points i.e. stimulation point of infrapatellar ligament and suprapatellar bursa) of knee joint. In the sham-acupotomy group, sham-acupotomy was applied at the same points as the acupotomy group. The treatment was given once a week for 2 weeks in the two groups. Before and after treatment, the Western Ontario and McMaster Universities arthritis index (WOMAC) score, visual analogue scale (VAS) score, thickness of medial and lateral collateral ligaments of knee joint, motion range of knee joint and plantar pressure distribution were observed in the two groups. In the follow-up of 3 months after treatment, the WOMAC and VAS scores were recorded in the acupotomy group. RESULTS: After treatment, the sub item scores (pain, stiffness and function) and total scores of WOMAC and VAS scores were decreased in the both groups (P<0.05), pain score, function score and total score of WOMAC and VAS score in the acupotomy group were lower than those in the sham-acupotomy group (P<0.05). Before and after treatment, there were no statistical differences in thickness of medial and lateral collateral ligaments of knee joint and motion range of knee joint between the two groups (P>0.05). After treatment, the plantar medial pressure was increased while the plantar lateral pressure was decreased (P<0.05), and the plantar force line moved medially in the acupotomy group. In the follow-up, the sub item scores and total score of WOMAC and VAS score were lower than those before and after treatment in the acupotomy group (P<0.05). CONCLUSION: Tiaohe Yinyang acupotomy can improve the clinical symptoms of knee joint in patients with KOA by changing the local biological stress.

Pheophorbide co-encapsulated with Cisplatin in folate-decorated PLGA nanoparticles to treat nasopharyngeal carcinoma: Combination of chemotherapy and photodynamic therapy.

The adverse effect and drug resistance of Cisplatin (CDDP) could be potential reduced by delivering in targeted nanoparticles and by combining with adjuvant therapy such as photodynamic therapy. In this study, F/CDPR-NP was formulated and characterized for all the physicochemical, biological and in vivo analysis. The results obtained from various in vitro and biological studies showed that encapsulation of CDDP and PBR in PLGA nanoparticles results in controlled release of encapsulated drugs and exhibited significantly low cell viability in CNE-1 and HNE-1 cancer cells. F/CDPR-NP significantly prolonged the blood circulation of the encapsulated drugs. The AUC of CDDP from F/CDPR-NP (4-fold) was significantly higher compared to that of free CDDP and similarly significantly higher t1/2 for CDDP from F/CDPR-NP was observed. F/CDPR-NP in the presence of laser irradiation showed significant reduction in the tumor burden with low tumor cell proliferations compared to either CDPR-NP or free CDDP indicating the potential of targeted nanoparticles and photodynamic therapy. Overall, combination of treatment modalities and active targeting approach paved way for the higher antitumor activity in nasopharyngeal carcinoma model. The positive results from this study will show new horizon for the treatment of other cancer models.

Red yeast rice increases excretion of bile acids in hamsters.

OBJECTIVE: To investigate the hypocholesterolemic activity of red yeast rice (RYR) and its underlying mechanism. METHODS: Three groups of hamsters were fed either the control diet or one of the two experimental diets containing by weight 0.1% RYR (0.1RYR) or 0.3% RYR (0.3RYR). Blood (0.5 mL) was collected from the retro-orbital sinus into a heparinized capillary tube at the end of week 0, 3, and 6. Plasma lipoproteins were measured using enzymatic kits, while fecal neutral and acidic sterols were quantified using a gas-liquid chromatography. RESULTS: Plasma total cholesterol was reduced by 12% in 0.1RYR group and by 18% in 0.3RYR group compared with the control value. Similarly, plasma triacylglycerol was decreased by 11% in 0.1RYR group and by 24% in 0.3RYR group. Western blotting analysis demonstrated that RYR had no effect on sterol regulatory element binding protein 2, liver X receptor, 3-hydroxy-3-methylglutary-CoA reductase, LDL receptor, and cholesterol-7alpha-hydroxylase. HPLC analysis confirmed that RYR contained 0.88% monacolin K. It was recently found that RYR supplementation increased excretion of fecal acidic sterols by 3-4 folds compared with the control value. CONCLUSION: Hypocholesterolemic activity of RYR is mediated at least partially by enhancement of acidic sterol excretion.

Antioxidant activities of extracts and subfractions from Inonotus Obliquus.

The ethanolic crude extracts and three subfractions (ethyl acetate fraction, n-butanol fraction, and aqueous fraction) from Inonotus Obliquus were obtained by sequential partitioning and their antioxidant activities were investigated in the present study. The methods of the total antioxidant capacity measured by the ferric-reducing antioxidant power assay, reducing power assay, scavenging activities towards DPPH, superoxide anion and hydroxyl radical employed in this study were established in in vitro systems. The amounts of total phenolics and total flavonoids were also determined by spectrophotometer. The results showed that the crude extracts and subfractions exhibited antioxidant activities in different evaluating system. The decreasing order of antioxidant activities is ethyl acetate fraction >n-butanol fraction >crude extract>aqueous fraction. A similar order of the amounts of phenolics and flavonoids in extract and subfractions was found. The results showed that the extent of antioxidant activities is in accordance with the amounts of phenolics and flavonoids existing in extracts and subfractions.

Application of the molecular combing technique to starch granules.

The molecular combing technique was used to dissociate the nanostructural units of starch granules from the starch fragments after a gelatinization process. With the help of atomic force microscopy (AFM), we observed that some nanostructural chains were just flowing out of the granules. It proves that there are substantive nanostructural units in the starch granules, a phenomenon not previously observed, so these nanostructural units were defined as suspected intermediates. Furthermore, we conclude that blocklets of starch granules are formed through twisting or distortion of nanochains.

Potential Correlation between Dietary Fiber-Suppressed Microbial Conversion of Choline to Trimethylamine and Formation of Methylglyoxal.

Dietary interventions alter the formation of the disease-associated metabolite, trimethylamine (TMA), via intestinal microbial TMA lyase activity. Nevertheless, the mechanisms regulating microbial enzyme production are still unclear. Sequencing of the gut bacteria 16S rDNA demonstrated that dietary intervention changed the composition of the gut microbiota and the functional metagenome involved in the choline utilization pathway. Characterization of the functional profile of the metagenomes and metabonomics analysis revealed that a series of Kyoto Encyclopedia of Genes and Genomes orthologous groups and enzyme groups related to accumulation of methylglyoxal (MG) and glycine were enriched in red meat diet-fed animals, whereas fiber-rich diet suppressed glycine formation via the MG-dependent pathway. Our observations suggest associations between choline-TMA lyase expression and MG formation, which are indicative of a novel role of the gut microbiota in choline metabolism and highlight it as a potential target for inhibiting TMA production.

Gymnemic acid alleviates inflammation and insulin resistance via PPARδ- and NFκB-mediated pathways in db/db mice.

Gymnemic acid (GA) is a naturally occurring herbal ingredient that improves glucose metabolism in patients with diabetes mellitus. In this study, we evaluated the ameliorative effects of GA on obesity-induced inflammation and insulin resistance (IR), and identified the mechanisms for these effects in db/db mice. In these mice, GA effectively lowered fasting blood glucose concentrations from 26.3 ± 4.09 to 17.4 ± 3.38 mmol L-1, and improved oral glucose and insulin tolerance. Furthermore, GA treatment accelerated lipid transport and promoted fatty acid oxidation, which reduced lipid accumulation and inhibited expression of inflammatory cytokines, including those involved in the proliferator-activated receptor δ (PPARδ)- and nuclear factor κB (NFκB)-mediated signaling pathways. In addition, the anti-inflammatory effects increased the ratio of insulin to glucagon. It also regulated the insulin signal transduction with reduced phosphorylation of IRS-1 (Ser) and increased phosphorylation of IRS (Tyr) in liver, skeletal muscle and adipose tissue. In summary, we demonstrated in db/db mice that GA induces fatty acid oxidation, and alleviates inflammation and IR in liver, skeletal muscle and adipose tissue through PPARδ- and NFκB-mediated signaling pathways.

Gymnemic Acid Ameliorates Hyperglycemia through PI3K/AKT- and AMPK-Mediated Signaling Pathways in Type 2 Diabetes Mellitus Rats.

Gymnemic acid (GA) isolated from Gymnema sylvestre (Retz.) Schult. has been shown to have antihyperglycemic activity; however, the molecular mechanisms governing these effects are unclear. In this study, GA (40 and 80 mg kg-1 day-1) was evaluated by type 2 diabetes mellitus (T2DM) rats to explore its hypoglycemic activity and underlying mechanisms of action. The results indicated that GA decreased fasting blood glucose (FBG) concentrations by 26.7% and lowered insulin concentrations by 16.1% after oral administration of GA at a dose of 80 mg kg-1 day-1 for 6 weeks in T2DM rats. Our data showed that real-time polymerase chain reaction and western blot indicated that GA upregulated the level of phosphatidylinositol-3-kinase (PI3K) and glycogen synthesis (GS) and promoted the phosphorylation of protein kinase B (Akt) while downregulated the expression of glycogen synthesis kinase-3ß (GSK-3ß) in T2DM rats. In addition, key proteins involved in adenosine monophosphate (AMP)-activated protein kinase (AMPK)-mediated gluconeogenesis [such as phosphoenolpyruvate carboxy kinase (PEPCK) and glucose-6-phosphatase (G6Pase)] were downregulated in GA-treated T2DM rats. In summary, the hypoglycemic mechanisms of GA may be related to promoting insulin signal transduction and activating PI3K/Akt- and AMPK-mediated signaling pathways in T2DM rats.

Gymnemic Acid Alleviates Type 2 Diabetes Mellitus and Suppresses Endoplasmic Reticulum Stress in Vivo and in Vitro.

Gymnemic acid (GA) is an herbal ingredient that can improve glucose metabolism in patients with diabetes mellitus. In this study, we evaluated the ameliorative effects of GA on insulin resistance (IR) and identified the mechanisms in type 2 diabetes mellitus (T2DM) rats and IR HepG2 cells. GA effectively enhanced glucose uptake in IR HepG2 cells from 11.9 ± 1.09 to 14.7 ± 1.38 mmol/L and lowered fasting blood glucose (blood glucose levels in groups treated with GA at 40 and 80 mg/kg/day were reduced by 15.2% and 26.7%, respectively) and oral glucose tolerance. Both in vivo and in vitro, GA downregulated the expression of endoplasmic reticulum (ER) stress indicator proteins such as ORP150, p-c-Jun, p-PERK, and p-eIF2α. In addition, the improvement of ER stress regulated the insulin signal transduction proteins, reducing p-IRS-1(ser) levels and increasing p-IRS-1(tyr) in GA-treated T2DM rats and IR HepG2 cells. In summary, the mechanism underlying the hypoglycemic effects of GA may be associated with alleviation of ER stress and facilitation of insulin signal transduction in T2DM rats and IR HepG2 cells.