N-p-coumaroyloctopamine ameliorates hepatic glucose metabolism and oxidative stress involved in a PI3K/AKT/GSK3ß pathway.

Type 2 diabetes mellitus is regarded as a chronic metabolic disease characterized by hyperglycemia. Long-term hyperglycemia may result in oxidative stress, damage pancreatic ß-cell function and induce insulin resistance. Herein we explored the anti-hypoglycemic effects and mechanisms of action of N-p-coumaroyloctopamine (N-p-CO) in vitro and in vivo. N-p-CO exhibited high antioxidant activity, as indicated by the increased activity of SOD, GSH and GSH-Px in HL-7702 cells induced by both high glucose (HG) and palmitic acid (PA). N-p-CO treatment significantly augmented glucose uptake and glycogen synthesis in HG/PA-treated HL-7702 cells. Moreover, administration of N-p-CO in diabetic mice induced by both high-fat diet (HFD) and streptozotocin (STZ) not only significantly increased the antioxidant levels of GSH-PX, SOD and GSH, but also dramatically alleviated hyperglycemia and hepatic glucose metabolism in a dose-dependent manner. More importantly, N-p-CO upregulated the expressions of PI3K, AKT and GSK3ß proteins in both HG/PA-induced HL-7702 cells and HFD/STZ-induced mice. These findings clearly suggest that N-p-CO exerts anti-hypoglycemic and anti-oxidant effects, most probably via the regulation of a PI3K/AKT/GSK3ß signaling pathway. Thus, N-p-CO may have high potentials as a new candidate for the prevention and treatment of diabetes.

Anticancer efficacy triggered by synergistically modulating the homeostasis of anions and iron: Design, synthesis and biological evaluation of dual-functional squaramide-hydroxamic acid conjugates.

Targeting the homeostasis of anions and iron has emerged as a promising therapeutic approach for the treatment of cancers. However, single-targeted agents often fall short of achieving optimal treatment efficacy. Herein we designed and synthesized a series of novel dual-functional squaramide-hydroxamic acid conjugates that are capable of synergistically modulating the homeostasis of anions and iron. Among them, compound 16 exhibited the most potent antiproliferative activity against a panel of selected cancer cell lines, and strong in vivo anti-tumor efficacy. This compound effectively elevated lysosomal pH through anion transport, and reduced the levels of intracellular iron. Compound 16 could disturb autophagy in A549 cells and trigger robust apoptosis. This compound caused cell cycle arrest at the G1/S phase, altered the mitochondrial function and elevated ROS levels. The present findings clearly demonstrated that synergistic modulation of anion and iron homeostasis has high potentials in the development of promising chemotherapeutic agents with dual action against cancers.

Apigenin targets fetuin-A to ameliorate obesity-induced insulin resistance.

Fetuin-A, a hepatokine secreted by hepatocytes, binds to insulin receptors and consequently impairs the activation of the insulin signaling pathway, leading to insulin resistance. Apigenin, a flavonoid isolated from plants, has beneficial effects on insulin resistance; however, its regulatory mechanisms are not fully understood. In the present study, we investigated the molecular mechanisms underlying the protective effects of apigenin on insulin resistance. In Huh7 cells, treatment with apigenin decreased the mRNA expression of fetuin-A by decreasing reactive oxygen species-mediated casein kinase 2α (CK2α)-nuclear factor kappa-light-chain-enhancer of activated B activation; besides, apigenin decreased the levels of CK2α-dependent fetuin-A phosphorylation and thus promoted fetuin-A degradation through the autophagic pathway, resulting in a decrease in the protein levels of fetuin-A. Moreover, apigenin prevented the formation of the fetuin-A-insulin receptor (IR) complex and thereby rescued the PA-induced impairment of the insulin signaling pathway, as evidenced by increased phosphorylation of IR substrate-1 and Akt, and translocation of glucose transporter 2 from the cytosol to the plasma membrane. Similar results were observed in the liver of HFD-fed mice treated with apigenin. Collectively, our findings revealed that apigenin ameliorates obesity-induced insulin resistance in the liver by targeting fetuin-A.

Identification of sedative-hypnotic compounds shared by five medicinal Polyporales mushrooms using UPLC-Q-TOF-MS/MS-based untargeted metabolomics.

BACKGROUND: Five Polyporales mushrooms, namely Amauroderma rugosum, Ganoderma lucidum, G. resinaceum, G. sinense and Trametes versicolor, are commonly used in China for managing insomnia. However, their active components for this application are not fully understood, restricting their universal recognition. PURPOSE: In this study, we aimed to identify sedative-hypnotic compounds shared by these five Polyporales mushrooms. STUDY DESIGN AND METHODS: A UPLC-Q-TOF-MS/MS-based untargeted metabolomics, including OPLS-DA (orthogonal projection of potential structure discriminant analysis) and OPLS (orthogonal projections to latent structures) analysis together with mouse assays, were used to identify the main sedative-hypnotic compounds shared by the five Polyporales mushrooms. A pentobarbital sodium-induced sleeping model was used to investigate the sedative-hypnotic effects of the five mushrooms and their sedative-hypnotic compounds. RESULTS: Ninety-two shared compounds in the five mushrooms were identified. Mouse assays showed that these mushrooms exerted sedative-hypnotic effects, with different potencies. Six triterpenes [four ganoderic acids (B, C1, F and H) and two ganoderenic acids (A and D)] were found to be the main sedative-hypnotic compounds shared by the five mushrooms. CONCLUSION: We for the first time found that these six triterpenes contribute to the sedative-hypnotic ability of the five mushrooms. Our novel findings provide pharmacological and chemical justifications for the use of the five medicinal mushrooms in managing insomnia.

Study of the Structure and Bioactivity of Polysaccharides from Different Parts of Stemona tuberosa Lour.

The polysaccharides from Stemona tuberosa Lour, a kind of plant used in Chinese herbal medicine, have various pharmacological activities, such as anti-inflammatory and antioxidant properties. However, the effects of the extraction methods and the activity of polysaccharides from different parts are still unknown. Therefore, this study aimed to evaluate the effects of different extraction methods on the yields, chemical compositions, and bioactivity of polysaccharides extracted from different parts of Stemona tuberosa Lour. Six polysaccharides were extracted from the leaves, roots, and stems of Stemona tuberosa Lour through the use of hot water (i.e., SPS-L1, SPS-R1, and SPS-S1) and an ultrasound-assisted method (i.e., SPS-L2, SPS-R2, and SPS-S2). The results showed that the physicochemical properties, structural properties, and biological activity of the polysaccharides varied with the extraction methods and parts. SPS-R1 and SPS-R2 had higher extraction yields and total sugar contents than those of the other SPSs (SPS-L1, SPS-L2, SPS-S1, and SPS-S2). SPS-L1 had favorable antioxidant activity and the ability to downregulate MUC5AC expression. An investigation of the anti-inflammatory properties showed that SPS-R1 and SPS-R2 had greater anti-inflammatory activities, while SPS-R2 demonstrated the strongest anti-inflammatory potential. The results of this study indicated that SPS-L1 and SPS-L2, which were extracted from non-medicinal parts, may serve as potent natural antioxidants, but further study is necessary to explore their potential applications in the treatment of diseases. The positive anti-inflammatory effects of SPS-R1 and SPS-R2 in the roots may be further exploited in drugs for the treatment of inflammation.

A novel donor-acceptor fluorescent probe for the fluorogenic/ chromogenic detection and bioimaging of nitric oxide.

Nitric oxide (NO) plays an essential role in regulating various physiological and pathological processes. This has spurred various efforts to develop feasible methods for the detection of NO. Herein we designed and synthesized a novel donor-acceptor fluorescent probe Car-NO for the selective and specific detection of NO. Reaction of Car-NO with NO generated a new donor-acceptor structure with strong intramolecular charge transfer (ICT) effect, and led to remarkable chromogenic change from yellow to blue and dramatic fluorescence quenching. Car-NO exhibited high selectivity, excellent sensitivity, and rapid response for the detection of NO. In addition, the nanoparticles prepared from Car-NO (i.e., Car-NO NPs) showed strong NIR emission and high selectivity/sensitivity. Car-NO NPs was successfully employed to image both endogenous and exogenous NO in HeLa and RAW 264.7 cells. The present findings reveal that Car-NO is a promising probe for the detection and bioimaging of NO.

The shape function method of nonlinear thermal stress of granite fracture tips in a high-temperature environment.

Exposed rock masses in tunnel portals are susceptible to thermal deterioration in southern China, where temperatures are relatively high. The thermal stress field of rock masses is affected by fracture shape and distribution as fractures near the surface are channels for solar radiation energy to be converted into rock thermal energy. In this study, a function expression is developed for triangular heat sources of fractured rock masses in a tunnel portal in a high-temperature environment. By the function expression, the temperature field and thermal stress field are calculated, and the influence of fracture shape parameters and multi-fracture interaction is analyzed. The results are as follows: (1) the temperature field and thermal stress field of exposed rocks are redistributed by fractures. The internal temperature of the fractured rocks is higher than that of non-fractured rocks, and thermal stress near the fracture tip increases. (2) For triangular fractures of the same length, thermal stress increases as the apex angle increases. (3) When the spacing between parallel fractures or coplanar fractures is close, the superposition effect of thermal stress becomes significant. (4) In a high-temperature environment, temperature field and thermal stress field of a fractured rock are both nonlinear as temperature and thermal stress around fractures increase significantly. The results provide effective reference for stability evaluation of fractured rock masses in tunnel portals and offer theoretical foundation for thermal diseases analysis and protection measures of tunnel engineering in high-temperature environments of southern China.

Cooperative Active Learning-Based Dual Control for Exploration and Exploitation in Autonomous Search.

In this article, a multi-estimator based computationally efficient algorithm is developed for autonomous search in an unknown environment with an unknown source. Different from the existing approaches that require massive computational power to support nonlinear Bayesian estimation and complex decision-making process, an efficient cooperative active-learning-based dual control for exploration and exploitation (COAL-DCEE) is developed for source estimation and path planning. Multiple cooperative estimators are deployed for environment learning process, which is helpful to improving the search performance and robustness against noisy measurements. The number of estimators used in COAL-DCEE is much smaller than that of the particles required for Bayesian estimation in information-theoretic approaches. Consequently, the computational load is significantly reduced. As an important feature of this study, the convergence and performance of COAL-DCEE are established in relation to the characteristics of sensor noises and turbulence disturbances. Numerical and experimental studies have been carried out to verify the effectiveness of the proposed framework. Compared with the existing approaches, COAL-DCEE not only provides convergence guarantee but also yields comparable search performance using much less computational power.

Advances in the molecular mechanisms of statins in regulating endothelial nitric oxide bioavailability: Interlocking biology between eNOS activity and L-arginine metabolism.

Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A, are widely used to treat hypercholesterolemia. In addition, statins have been suggested to reduce the risk of cardiovascular events owing to their pleiotropic effects on the vascular system, including vasodilation, anti-inflammation, anti-coagulation, anti-oxidation, and inhibition of vascular smooth muscle cell proliferation. The major beneficial effect of statins in maintaining vascular homeostasis is the induction of nitric oxide (NO) bioavailability by activating endothelial NO synthase (eNOS) in endothelial cells. The mechanisms underlying the increased NO bioavailability and eNOS activation by statins have been well-established in various fields, including transcriptional and post-transcriptional regulation, kinase-dependent phosphorylation and protein-protein interactions. However, the mechanism by which statins affect the metabolism of L-arginine, a precursor of NO biosynthesis, has rarely been discussed. Autophagy, which is crucial for energy homeostasis, regulates endothelial functions, including NO production and angiogenesis, and is a potential therapeutic target for cardiovascular diseases. In this review, in addition to summarizing the molecular mechanisms underlying increased NO bioavailability and eNOS activation by statins, we also discuss the effects of statins on the metabolism of L-arginine.

Divergent synthesis of difluoromethylated indole-3-carbinols, bisindolylmethanes and indole-3-methanamines.

Indole-3-carbinol, bisindolylmethanes (BIMs) and indole-3-methanamines exhibit diverse therapeutic activities. Fluorinated molecules are widely used in pharmaceuticals. Herein we report a facile and straightforward method for the successful synthesis of difluoromethylated indole-3-carbinols, bisindolylmethanes and indole-3-methanamines by a Friedel-Crafts reaction. The reaction involves the in situ generation of difluoroacetaldehyde from difluoroacetaldehyde ethyl hemiacetal in the presence of a base or an acid. This protocol is distinguished by its good to excellent yields, broad substrate compatibility, good functional group tolerance and scalability.

Combined inhibition of pyruvate dehydrogenase kinase 1 and hexokinase 2 induces apoptsis in non-small cell lung cancer cell models.

Many cancer cells exhibit enhanced glycolysis, which is seen as one of the hallmark metabolic alterations, known as Warburg effect. Substantial evidence shows that upregulated glycolytic enzymes are often linked to malignant growth. Using glycolytic inhibitors for anticancer treatment has become appealing in recent years for therapeutic intervention in cancers with highly glycolytic characteristic, including non-small cell lung cancer (NSCLC). In this work, we studied the anticancer effects and the underlying mechanisms of combination of benzerazide hydrocholoride (Benz), a hexokinase 2 (HK2) inhibitor and 64, a pyruvate dehydrogenase kinase 1 (PDK1) inhibitor, in several NSCLC cell lines. We found that combination of Benz and 64 exhibited strong synergistic anticancer effects in NCI-H1975, HCC827, NCI-H1299 and SK-LU-1 cell lines. With this combination treatment, we observed changes of certain mechanistic determinants associated with metabolic stress caused by glycolysis restriction, such as mitochondrial membrane potential depolarization, overproduction of reactive oxygen species [1], activation of AMPK and down-regulation of mTOR, which contributed to enhanced apoptosis. Moreover, Benz and 64 together significantly suppressed the tumor growth in HCC827 cell mouse xenograft model. Taken together, our study may suggest that combined inhibition of HK2 and PDK1 using Benz and 64 could be a viable anticancer strategy for NSCLC.

Design, Synthesis, and Antitumor Efficacy of Substituted 2-Amino[1,2,4]triazolopyrimidines and Related Heterocycles as Dual Inhibitors for Microtubule Polymerization and Janus Kinase 2.

Preclinical and clinical studies have demonstrated the synergistic effect of microtubule-targeting agents in combination with Janus kinase 2 (JAK2) inhibitors, prompting the development of single agents with enhanced therapeutic efficacy by dually inhibiting tubulin polymerization and JAK2. Herein, we designed and synthesized a series of substituted 2-amino[1,2,4]triazolopyrimidines and related heterocycles as dual inhibitors for tubulin polymerization and JAK2. Most of these compounds exhibited potent antiproliferative activity against the selected cancer cells, with compound 7g being the most active. This compound effectively inhibits both tubulin assembly and JAK2 activity. Furthermore, phosphorylated compound 7g (i.e., compound 7g-P) could efficiently convert to compound 7g in vivo. Compound 7g, whether it was administered directly or in the form of a phosphorylated prodrug (i.e., compound 7g-P), significantly inhibited the growth of A549 xenografts in nude mice. The present findings strongly suggest that compound 7g represents a promising chemotherapeutic agent with high antitumor efficacy.

Identification of 1,3,4-oxadiazolyl-containing ß-carboline derivatives as novel α-glucosidase inhibitors with antidiabetic activity.

In this study, we designed and synthesized a novel class of 1,3,4-oxadiazolyl-containing ß-carboline derivatives, i.e., compounds f1∼f35 as potential α-glucosidase inhibitors. All the synthesized compounds possessed outstanding α-glucosidase inhibitory activity with the IC50 values in the range of 3.07-15.49 µM, representing that they are 36∼183-fold more active than a positive control, acarbose (IC50 = 564.28 µM). Among them, compound f26 exhibited the highest α-glucosidase inhibitory activity (IC50 = 3.07 µM) and was demonstrated to function as a reversible and noncompetitive inhibitor. Mechanistic studies by means of 3D fluorescence spectra, CD spectra and molecular docking suggested that complexation of compound f26 with α-glucosidase through hydrogen bonds and hydrophobic interactions, led to changes in the conformation and secondary strictures of α-glucosidase and further the inhibition of the enzymatic activity. In vivo results showed that oral administration of compound f26 (50 mg/kg/day) could obviously reduce the levels of fasting blood glucose and improve glucose tolerance and dyslipidemia in diabetic mice. The present findings suggest that compound f26 is exploitable as a potential lead compound for the development of new α-glucosidase inhibitors with antidiabetic activity.

Carboxymethyl Chitosan/Sodium Alginate/Chitosan Quaternary Ammonium Salt Composite Hydrogel Supported 3J for the Treatment of Oral Ulcer.

Oral ulcer is a common inflammatory disease of oral mucosa, causing severe burning pain and great inconvenience to daily life. In this study, compound 3J with anti-inflammatory activity was synthesized beforehand. Following that, an intelligent composite hydrogel supported 3J was designed with sodium alginate, carboxymethyl chitosan, and chitosan quaternary ammonium salt as the skeleton, and its therapeutic effect on the rat oral ulcer model was investigated. The results show that the composite hydrogel has a dense honeycomb structure, which is conducive to drug loading and wound ventilation, and has biodegradability. It has certain antibacterial effects and good anti-inflammatory activity. When loaded with 3J, it reduced levels of TNF-α and IL-6 in inflammatory cells by up to 50.0%. It has excellent swelling and water retention properties, with a swelling rate of up to 765.0% in a pH 8.5 environment. The existence of a large number of quaternary ammonium groups, carboxyl groups, and hydroxyl groups makes it show obvious differences in swelling in different pH environments, which proves that it has double pH sensitivity. It is beneficial to adapt to the highly dynamic changes of the oral environment. Compared with single hydrogel or drug treatment, the drug-loaded hydrogel has a better effect on the treatment of oral ulcers.

Epigallocatechin gallate circumvents drug-induced resistance in non-small-cell lung cancer by modulating glucose metabolism and AMPK/AKT/MAPK axis.

Upon prolonged use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC), acquired drug resistance inevitably occurs. This study investigates the combined use of EGFR-TKIs (gefitinib or osimertinib) with epigallocatechin gallate (EGCG) to overcome acquired drug resistance in NSCLC models. The in vitro antiproliferative effects of EGFR-TKIs and EGCG combination in EGFR-mutant parental and resistant cell lines were evaluated. The in vivo efficacy of the combination was assessed in xenograft mouse models derived from EGFR-TKI-resistant NSCLC cells. We found that the combined use of EGFR-TKIs and EGCG significantly reversed the Warburg effect by suppressing glycolysis while boosting mitochondrial respiration, which was accompanied by increased cellular ROS and decreased lactate secretion. The combination effectively activated the AMPK pathway while inhibited both ERK/MAPK and AKT/mTOR pathways, leading to cell cycle arrest and apoptosis, particularly in drug-resistant NSCLC cells. The in vivo results obtained from mouse tumor xenograft model confirmed that EGCG effectively overcame osimertinib resistance. This study revealed that EGCG suppressed cancer bypass survival signaling and altered cancer metabolic profiles, which is a promising anticancer adjuvant of EGFR-TKIs to overcome acquired drug resistance in NSCLC.

Fibroblast Activation Protein Targeting Probe with Gly-Pro Sequence for PET of Glioblastoma.

As an important cancer-associated fibroblast-specific biomarker, fibroblast activation protein (FAP) has become an attractive target for tumor diagnosis and treatment. However, most FAP-based radiotracers showed inadequate uptake and short retention in tumors. In this study, we designed and synthesized a novel FAP ligand (DOTA-GPFAPI-04) through assembling three functional moieties: a quinoline-based FAP inhibitor for specifically targeting FAP, a FAP substrate Gly-Pro as a linker for increasing the FAP protein interaction, and a 2,2',2″,2‴-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) chelator for radiolabeling with different radionuclides. The FAP targeting ability of DOTA-GPFAPI-04 was investigated by molecular docking studies. DOTA-GPFAPI-04 was then radiolabeled with 68Ga to give [68Ga]Ga-DOTA-GPFAPI-04 for positron emission tomography (PET) imaging of glioblastoma. [68Ga]Ga-DOTA-GPFAPI-04 exhibited a purity of >98% and high stability analyzed by radio-HPLC in saline and mouse serum. Cell uptake studies demonstrated the targeting specificity of the probe. Further in vivo pharmacokinetic studies in normal mice demonstrated the quick clearance of the probe. Moreover, compared with the widely studied [68Ga]Ga-FAPI-04, [68Ga]Ga-DOTA-GPFAPI-04 showed much higher U87MG tumor uptake values (4.467 ± 0.379 for [68Ga]Ga-DOTA-GPFAPI-04 and 1.267 ± 0.208% ID/g for [68Ga]Ga-FAPI-04 at 0.5 h post-injection, respectively). The area under the curve based on time-activity curve (TAC) analysis for tumor radioactivity in small animal models was 422.5 for [68Ga]Ga-DOTA-GPFAPI-04 and 98.14 for [68Ga]Ga-FAPI-04, respectively, demonstrating that the former had longer tumor retention time. The tumor-to-muscle (T/M) ratio for [68Ga]Ga-DOTA-GPFAPI-04 reached 9.15 in a U87MG xenograft animal model. PET imaging and blocking assays showed that [68Ga]Ga-DOTA-GPFAPI-04 had specific tumor uptake. In summary, this study demonstrates the successful synthesis and evaluation of a novel FAPI targeting probe, [68Ga]Ga-DOTA-GPFAPI-04, with a Gly-Pro sequence. It shows favorable in vivo glioblastoma imaging properties and relatively long tumor retention, highlighting DOTA-GPFAPI-04 as a promising molecular scaffold for developing FAP targeting tumor theranostic agents.

Synthesis of a Golgi-targeting fluorescent probe for the selective detection of chloride anions.

In this paper, we describe the synthesis and properties of a Golgi-targeting fluorescent probe for the selective detection of chloride anions. Specifically, we have synthesized one quaternized quinoline derivative bearing a sulfanilamido group and found that this compound is able to primarily target the Golgi apparatus and detect the changes in the concentration of cellular chloride anions.

Facile access to 2-hydroxy-2-substituted indole-3-ones via a copper-catalyzed oxidative cyclization of 2-arylethynylanilines.

This paper reports a practical and versatile oxidative cyclization of 2-arylethynylanilines towards 2-hydroxy-2-substituted indol-3-ones via a copper-catalyzed radical approach in the presence of O2. The transformation of 2-hydroxy-2-arylindol-3-ones to 3-hydroxy-3-arylindol-2-ones proceeds well with good yields and highlights the practicability and utility of this catalytic system. Mechanistic investigations showed that the acetyl substituent on 2-arylaethynylanilines played an important role in the formation of the cyclic products and the reaction proceeded via an N-center radical-based 5-endo-dig aza-cyclization pathway.

A tri-herb formulation protects against ethanol-induced mouse liver injury and downregulates mitogen-activated protein kinase phosphatase 1.

BACKGROUND: A tri-herb formulation comprising Ganoderma (the dried fruiting body of Ganoderma lucidum), Puerariae Thomsonii Radix (the dried root of Pueraria thomsonii) and Hoveniae Semen (the dried mature seed of Hovenia acerba) -GPH for short- has been using for treating liver injury; however, the pharmacological basis of this application of GPH is unknown. This study aimed to investigate the liver protective effects and mechanisms of action of an ethanolic extract of GPH (GPHE) in mice. METHODS: To control the quality of GPHE, the contents of ganodermanontriol, puerarin and kaempferol in the extract were quantified by ultra-performance liquid chromatography. An ethanol (6 ml/kg, i.g.)-induced liver injury ICR mouse model was employed to investigate the hepatoprotective effects of GPHE. RNA-sequencing analysis and bioassays were performed to reveal the mechanisms of action of GPHE. RESULTS: The contents of ganodermanontriol, puerarin and kaempferol in GPHE were 0.0632%, 3.627% and 0.0149%, respectively. Daily i.g. administration of 0.25, 0.5 or 1 g/kg of GPHE for 15 consecutive days suppressed ethanol (6 ml/kg, i.g., at day 15)-induced upregulation of serum AST and ALT levels and improved histological conditions in mouse livers, indicating that GPHE protects mice from ethanol-induced liver injury. Mechanistically, GPHE downregulated the mRNA level of Dusp1 (encoding MKP1 protein, an inhibitor of the mitogen-activated protein kinases JNK, p38 and ERK), and upregulated expression and phosphorylation of JNK, p38 and ERK, which are involved in cell survival in mouse liver tissues. Also, GPHE increased PCNA (a cell proliferation marker) expression and reduced TUNEL-positive (apoptotic) cells in mouse livers. CONCLUSION: GPHE protects against ethanol-induced liver injury, and this effect of GPHE is associated with regulation of the MKP1/MAPK pathway. This study provides pharmacological justifications for the use of GPH in treating liver injury, and suggests that GPHE has potential to be developed into a modern medication for managing liver injury.

Life Table Study of Fall Armyworm (Spodoptera frugiperda) (Lepidoptera: Noctuidae) on Three Host Plants under Laboratory Conditions.

After being discovered in Taiwan for the first time in June 2019, the polyphagous invasive fall armyworm (FAW), Spodoptera frugiperda (Lepidoptera: Noctuidae), has since spread throughout the entire nation. In Taiwan, this insect has a significant impact on the quality and output of wheat, corn, sorghum, and millet. It may further infest more crops in Taiwan due to its diverse range of hosts and alternate hosts. Maize and other staple crops have already been the subject of several study. The biology of FAW has not yet been studied in relation to the alternative hosts, particularly those commonly found in Taiwanese farmlands. Therefore, this study proposed to investigate the effects of napier grass (Pennisetum purpureum), natal grass (Melinis repens), and sunn hemp (Crotalaria juncea) on the development, reproduction, survivorship, and population growth of FAW under laboratory conditions. According to the results, the developmental duration was considerably the shortest when FAW was reared on sunn hemp while the longest on natal grass. Furthermore, female adults reared on napier grass had a longer adult pre-oviposition period, total pre-oviposition period, oviposition period, longevity, highest fecundity, and highest net reproductive rate (Ro: 465.12). Among the tested three alternative host plants evaluated, sunn hemp had the highest intrinsic rate of increase (r: 0.1993), finite rate of increase (λ: 1.2206), and shortest mean generation time (T: 29.98). Therefore, this study suggests that all hosts plants can contribute to the development and outbreak of this pest in the absence of its primary host; however, sunn hemp was a relatively more suitable host plant for this insect. The possibilities for the FAW's growth and development vary depending on the host plant. Thereby, all potential host plants in the area should be extensively examined while developing an IPM program against FAW.