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Metabolic-dysfunction-associated steatotic liver disease (MASLD, formerly known as NAFLD) is a global chronic liver disease, and no licensed drugs are currently available for its treatment. The incidence of MASLD is increasing, which could lead to a huge clinical and economic burden. As a multifactorial disease, MASLD involves a complex set of metabolic changes, and many monotherapies for it are not clinically effective. Therefore, combination therapies using multiple drugs are emerging, with the advantages of improving drug efficacy and reducing side effects. Peanut skin extract (PSE), geniposide (GEN), and isoquercitrin (IQ) are three natural antiaging components or compounds. In this study, the preventive effects of individual PSE, GEN, and IQ in comparison with the effects of their mixture (MPGI) were examined in a mouse model of high-fat-feed-induced MASLD. The results showed that MPGI could significantly reduce the body and liver weights of mice and improve hepatic steatosis and liver function indicators. Further mechanistic studies showed that PSE, GEN, and IQ worked together by reducing inflammation, modulating the intestinal flora, and regulating the TLR4/NF-κB, AMPK/ACC/CPT1, and AMPK/UKL1/LC3B signaling pathways. It is a promising therapeutic method for preventing MASLD. [ABSTRACT FROM AUTHOR]

Background: With the development of an aging sociality, aging-related diseases, such as Alzheimer's disease, cardiovascular disease, and diabetes, are dramatically increasing. To find small molecules from natural products that can prevent the aging of human beings and the occurrence of these diseases, we used the lifespan assay of yeast as a bioassay system to screen an antiaging substance. Isoquercitrin (IQ), an antiaging substance, was isolated from Apocynum venetum L., an herbal tea commonly consumed in Xinjiang, China. Aim of the Study: In the present study, we utilized molecular-biology technology to clarify the mechanism of action of IQ. Methods: The replicative lifespans of K6001 yeasts and the chronological lifespans of YOM36 yeasts were used to screen and confirm the antiaging effect of IQ. Furthermore, the reactive oxygen species (ROS) and malondialdehyde (MDA) assay, the survival assay of yeast under stresses, real-time polymerase chain reaction (RT-PCR) and Western blotting analyses, the replicative-lifespan assay of mutants, such as Δsod1, Δsod2, Δgpx, Δcat, Δskn7, Δuth1, Δatg32, Δatg2, and Δrim15 of K6001, autophagy flux analysis, and a lifespan assay of K6001 yeast after giving a mitophagy inhibitor and activator were performed. Results: IQ extended the replicative lifespans of the K6001 yeasts and the chronological lifespans of the YOM36 yeasts. Furthermore, the reactive nitrogen species (RNS) showed no change during the growth phase but significantly decreased in the stationary phase after treatment with IQ. The survival rates of the yeasts under oxidative- and thermal-stress conditions improved upon IQ treatment, and thermal stress was alleviated by the increasing superoxide dismutase (Sod) activity. Additionally, IQ decreased the ROS and MDA of the yeast while increasing the activity of antioxidant enzymes. However, it could not prolong the replicative lifespans of Δsod1, Δsod2, Δgpx, Δcat, Δskn7, and Δuth1 of K6001. IQ significantly increased autophagy and mitophagy induction, the presence of free green fluorescent protein (GFP) in the cytoplasm, and ubiquitination in the mitochondria of the YOM38 yeasts at the protein level. IQ did not prolong the replicative lifespans of Δatg2 and Δatg32 of K6001. Moreover, IQ treatment led to a decrease in Sch9 at the protein level and an increase in the nuclear translocation of Rim15 and Msn2. Conclusions: These results indicated that the Sch9/Rim15/Msn signaling pathway, as well as antioxidative stress, anti-thermal stress, and autophagy, were involved in the antiaging effects of IQ in the yeasts. [ABSTRACT FROM AUTHOR]

Background: Aging is an important pathogenic factor of age-related diseases and has brought huge health threat and economic burden to the society. Dendrobium nobile Lindl., a valuable herb in China, promotes longevity according to the record of ancient Chinese materia medica. This study aimed to discover the material basis of D. nobile as an anti-aging herb and elucidate its action mechanism. Methods: K6001 yeast replicative lifespan assay was used to guide the isolation of D. nobile. The chronological lifespan assay of YOM36 yeast was further conducted to confirm the anti-aging activity of dendrobine. The mechanism in which dendrobine exerts anti-aging effect was determined by conducting anti-oxidative stress assay, quantitative real-time PCR, Western blot, measurements of anti-oxidant enzymes activities, determination of nuclear translocation of Rim15 and Msn2, and replicative lifespan assays of Δsod1, Δsod2, Δcat, Δgpx, Δatg2, Δatg32, and Δrim15 yeasts. Results: Under the guidance of K6001 yeast replicative lifespan system, dendrobine with anti-aging effect was isolated from D. nobile. The replicative and chronological lifespans of yeast were extended upon dendrobine treatment. In the study of action mechanism, dendrobine improved the survival rate of yeast under oxidative stress, decreased the levels of reactive oxygen species and malondialdehyde, and enhanced the enzyme activities and gene expression of superoxide dismutase and catalase, but it failed to elongate the replicative lifespans of Δsod1, Δsod2, Δcat, and Δgpx yeast mutants. Meanwhile, dendrobine enhanced autophagy occurrence in yeast but had no effect on the replicative lifespans of Δatg2 and Δatg32 yeast mutants. Moreover, the inhibition of Sch9 phosphorylation and the promotion of nuclear translocation of Rim15 and Msn2 were observed after treatment with denrobine. However, the effect of dendrobine disappeared from the Δrim15 yeast mutant after lifespan extension, oxidative stress reduction, and autophagy enhancement. Conclusions: Dendrobine exerts anti-aging activity in yeast via the modification of oxidative stress and autophagy through the Sch9/Rim15/Msn2 signaling pathway. Our work provides a scientific basis for the exploitation of D. nobile as an anti-aging herb. [ABSTRACT FROM AUTHOR]

Gentirigeoside B (GTS B) is a dammaren-type triterpenoid glycoside isolated from G. rigescens Franch, a traditional Chinese medicinal plant. In the present study, the evaluation of the anti-aging effect and action mechanism analysis for this compound were conducted. GTS B significantly extended the replicative lifespan and chronological lifespan of yeast at doses of 1, 3 and 10 μM. Furthermore, the inhibition of Sch9 and activity increase of Rim15, Msn2 proteins which located downstream of TORC1 signaling pathway were observed after treatment with GTS B. Additionally, autophagy of yeast was increased. In addition, GTS B significantly improved survival rate of yeast under oxidative stress conditions as well as reduced the levels of ROS and MDA. It also increased the gene expression and enzymatic activities of key anti-oxidative enzymes such as Sod1, Sod2, Cat and Gpx. However, this molecule failed to extend the lifespan of yeast mutants such as ∆cat, ∆gpx, ∆sod1, ∆sod2, ∆skn7 and ∆uth1. These results suggested that GTS B exerts an anti-aging effect via inhibition of the TORC1/Sch9/Rim15/Msn signaling pathway and enhancement of autophagy. Therefore, GTS B may be a promising candidate molecule to develop leading compounds for the treatment of aging and age-related disorders. [ABSTRACT FROM AUTHOR]

Abstract: Asexual and sexual reproduction are the most important biological events in the life cycle of phytopathogenic and toxigenic Fusarium and are responsible for disease epidemics. However, the signaling molecules which induce the asexual reproduction of Fusarium are unknown. Herein we describe the structure elucidation, including the absolute configuration, of Fusarium asexual reproduction inducer (FARI), a new sesquiterpene derivative, by spectroscopic analysis, total synthesis, and conidium‐inducing assays of synthetic isomers. We have also uncovered the universality of FARI among Fusarium species. Moreover, a mechanism‐of‐action study suggested that the Gpmk1 and LaeA signaling pathways are required for conidium formation induced by FARI; conversely, the Mgv1 of mitogen‐activated protein kinase is not involved in conidium formation. FARI exhibited conidium‐inducing activity at an extremely low dose and high stereoselectivity, which may suggest the presence of a stereospecific target. [ABSTRACT FROM AUTHOR]

The leptin gene was transferred into the liver of streptozocin- and high fat diet-induced type 2 diabetic (T2D) mice by hydrodynamic-based gene delivery. The food intake, water consumption, glucose concentration, and triglyceride and total cholesterol levels of T2D mice were significantly decreased. Meanwhile, plasma leptin was remarkably increased after gene transfer for 2, 3, 5, and 7 days, while plasma adiponectin was also significantly increased at day 2. To understand the mechanism of action of leptin on T2D mice, gene expressions related to glycometabolism and energy metabolism in the liver, epididymal adipose tissue, hypothalamus, and muscle were measured. The mRNA expression levels of adiponectin receptor 1 ( ADR1), glucose transporter 4 ( GLUT4), glucose-6-phosphase, and peroxisome proliferator-activated receptor γ in the liver, leptin, adiponectin, and hormone-sensitive lipase in adipose tissue, leptin, leptin-receptor, ADR1 in the hypothalamus, and ADR1, GLUT4, and insulin 1 in the gastrocnemius significantly increased. Moreover, the hepatic glycogen of the leptin-gene-treated group was significantly increased in comparison to the control group. Meanwhile, the significant decrease of forkhead box O1, adiponectin receptor 2, and peroxisome proliferator-activated receptor α in the liver, and agouti-related protein and proopiomelanocortin genes in the hypothalamus were also observed. In fat tissue and hypothalamus, leptin and adiponectin protein levels were also significantly increased, whereas the neuropeptide Y protein level was significantly decreased. These results indicated that the leptin gene transfer could improve the symptoms of T2D mice by regulating the leptin-hypothalamus signaling pathway and improving the insulin resistance of the peripheral tissues of T2D mice. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance G. rigescens Franch (Long Dan Cao in Chinese) is a well-known TCM herb. It is clinically used with other drugs for the treatment of brain diseases such as epilepsy, postherpetic neuralgia in China. Aim of study In our previous study, the 11 dihydroxybenzoates compounds with NGF mimicking activity from G. rigescens Franch were found. In the present study, the neurogenesis and neuroprotection of a mixture of benzoates ( n-GS) were investigated in animal level. Materials and methods The NGF mimicking activity of n-GS from G. rigescens Franch was examined in PC12 cells. The neurogenesis effects of n-GS were investigated in ICR mice with 5-bromo-2-deoxyuridine (BrdU) and neuronal neclei (NeuN) double immunostaining. Furthermore, the neuroprotection effects of n-GS on the memory in a scopolamine (SCO)-induced mouse model were evaluated with animal behavior tests. Results The NGF-mimicking function and neurogenesis of n-GS were observed in PC12 cells and in normal mice. Subsequently, we investigated the effects of n-GS on the memory in a SCO-induced mouse model. In Y-maze test, SCO significantly lowered the alternation. This finding was reversed by n-GS and donepezil (DONE). SCO significantly impaired the mice's performance in novel object recognition (NOR) and Morris water maze (MWM) tests. The time spent to explore the novel object was longer in the n-GS- and DONE-treated groups than in the SCO control group. In the MWM test, the escape latency of n-GS- and DONE-treated groups was shorter than that of the SCO control group. Mechanism study showed that SCO significantly reduced superoxide dismutase (SOD) but increased the activities of acetylcholinesterase (AChE) and the levels of malondialdehyde (MDA) in the hippocampus and cerebral cortex, which all can be improved by n-GS and DONE. Additionally, the phosphorylation of type 1 insulin-like growth factor (IGF-1) receptor, extracellular signal-regulated kinase (ERK), and cAMP responsive element-binding (CREB) protein in the hippocampus was significantly up-regulated in the treatment group compared with that in the SCO group. Conclusions n-GS could alleviate impaired memory of the SCO-induced mice model by inhibiting AChE activity and oxidative stress, and regulating the IGF-1R/ERK signaling pathway. [ABSTRACT FROM AUTHOR]