Ellagic Acid Increases Stress Resistance via Insulin/IGF-1 Signaling Pathway in Caenorhabditis elegans

Ellagic acid is a natural polyphenol found in various fruits and vegetables. Numerous studies have shown that ellagic acid has beneficial effects on human health. In this study, we investigated the stress resistant action of ellagic acid in Caenorhabditis elegans (C. elegans). Notably, 50 μM ellagic acid prolonged the lifespan of C. elegans by 36.25%, 36.22%, 155.1%, and 79.07% under ultraviolet radiation stress, heat stress, oxidative stress, and Pseudomonas aeruginosa infection stress, respectively. Furthermore, the mechanism by which ellagic acid reduces the damage caused by ultraviolet radiation in C. elegans was explored. Ellagic acid could significantly induce the nucleus translocation of DAF-16 and, thereby, activate a series of target genes to resist ultraviolet radiation stress. Moreover, ellagic acid also significantly increased the expression of SOD-3 by 3.61 times and the activity of superoxide dismutase by 3.70 times to clean out harmful reactive oxygen species in C. elegans exposed to ultraviolet radiation stress. In both daf-16 mutant and daf-2; daf-16 double-mutant worms exposed to ultraviolet radiation, ellagic acid could no longer prolong their lifespan. These results indicate that ellagic acid plays an important role in resisting ultraviolet radiation stress in C. elegans, probably in an insulin/IGF-1 signaling pathway-dependent way.     

The potential antioxidant ability of hydroxytyrosol on Caenorhabditis elegans against oxidative damage via the insulin signaling pathway

Hydroxytyrosol (HY) deriving from olive leaves is a phenolic component which has been proven to possess a strong antioxidant ability. However, the underling mechanism is still unclear. To evaluate the antioxidant ability of HY comprehensively, assays in vitro and in vivo (Caenorhabditis elegans (C. elegans) was used as a model organism) were conducted. The results showed HY could scavenge 2,2-Diphenyl-1-picryl-hydrazyl (DPPH) radicals with a strong total reducing power. Pretreated with HY for 48 h, the cell viability of Chinese hamster ovary (CHO) cells was enhanced under oxidative stress by reducing the level of reactive oxygen species (ROS) and malondialdehyde (MDA). A suitable concentration of HY showed no side effects on the development, fertility, and movement of C. elegans. With the treatment of HY, the survival was enhanced by 15.79% under thermal stress. The ROS and MDA contents were also reduced, which might be associated with the increasing abilities of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the heat shock protein HSP-16.2. Nuclear localization of DAF-16 was greatly increased after treated with HY. More outcomes demonstrated HY exhibited an excellent antioxidant capacity via the insulin signaling pathway by upregulating daf-16 and sod-3 and downregulating the genes of age-1 and daf-2.     

Stress Buffering and Longevity Effects of Amber Extract on Caenorhabditis elegans (C. elegans)

Amber is a fossilized tree resin historically used in wound healing and stress relief. Unfortunately, there is no concrete scientific evidence supporting such efficacy. Here, the stress buffering and longevity effect of Amber extract (AE) in Caenorhabditis elegans (C. elegans) was investigated. Survival assays, health span assays, Enzyme-Linked Immunosorbent Assay (ELISA), Stress biomarker detection assays, Green Fluorescence Proteins (GFP), Real Time quantitative PCR (RT-qPCR) and C. elegans mutants were employed to investigate the stress buffering and longevity effect of AE. In the study, it was observed that AE supplementation improved health span and survival in both normal and stressed worms. Additionally, AE positively regulated stress hormones (cortisol, oxytocin, and dopamine) and decreased fat and reactive oxygen species (ROS) accumulation. Through the Insulin/IGF-1 signaling (IIS) pathway, AE enhanced the nuclear localization of DAF-16 and the expression of heat shock proteins and antioxidant genes in GFP-tagged worms and at messenger RNA levels. Finally, AE failed to increase the survival of daf-16, daf-2, skn-1 and hsf-1 loss-of-function mutants, confirming the involvement of the IIS pathway. Evidently, AE supplementation relieves stress and enhances longevity. Thus, amber may be a potent nutraceutical for stress relief.     

Preparation of Dendrobium officinale Flower Anthocyanin and Extended Lifespan in Caenorhabditis elegans

The Dendrobium officinale flower is a non-medicinal part of the plant, rich in a variety of nutrients and bioactive ingredients. The purpose of this article was to explore the preparation conditions of anthocyanins (ACNs) from the D. officinale flower. Subsequently, its anti-aging effects were evaluated with Caenorhabditis elegans. Results showed that the ACNs had antioxidant activities on scavenging free radicals (DPPH· and ABTS⁺·), and the clearance rate was positively correlated with the dose. Additionally, ACNs significantly increased the activity of superoxide dismutase (SOD) in C. elegans, which was 2.068-fold higher than that of the control. Treatment with ACNs at 150 μL extended the lifespan of C. elegans by 56.25%, and treatment with ACNs at 50 μL promoted fecundity in C. elegans. Finally, the protective effect of ACNs enhanced stress resistance, thereby increasing the survival numbers of C. elegans, which provided insights for the development and practical application of functional products.     

Increased Stress Resistance and Lifespan in Chaenorhabditis elegans Wildtype and Knockout Mutants—Implications for Depression Treatment by Medicinal Herbs

Depression and anxiety disorders are widespread diseases, and they belong to the leading causes of disability and greatest burdens on healthcare systems worldwide. It is expected that the numbers will dramatically rise during the COVID-19 pandemic. Established medications are not sufficient to adequately treat depression and are not available for everyone. Plants from traditional medicine may be promising alternatives to treat depressive symptoms. The model organism Chaenorhabditis elegans was used to assess the stress reducing effects of methanol/dichlormethane extracts from plants used in traditional medicine. After initial screening for antioxidant activity, nine extracts were selected for in vivo testing in oxidative stress, heat stress, and osmotic stress assays. Additionally, anti-aging properties were evaluated in lifespan assay. The extracts from Acanthopanax senticosus, Campsis grandiflora, Centella asiatica, Corydalis yanhusuo, Dan Zhi, Houttuynia cordata, Psoralea corylifolia, Valeriana officinalis, and Withania somnifera showed antioxidant activity of more than 15 Trolox equivalents per mg extract. The extracts significantly lowered ROS in mutants, increased resistance to heat stress and osmotic stress, and the extended lifespan of the nematodes. The plant extracts tested showed promising results in increasing stress resistance in the nematode model. Further analyses are needed, in order to unravel underlying mechanisms and transfer results to humans.     

Neurorescue Effects of Frondoside A and Ginsenoside Rg3 in C. elegans Model of Parkinson’s Disease

Parkinson’s disease (PD) is a currently incurable neurodegenerative disorder characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta and α-synuclein aggregation. Accumulated evidence indicates that the saponins, especially from ginseng, have neuroprotective effects against neurodegenerative disorders. Interestingly, saponin can also be found in marine organisms such as the sea cucumber, but little is known about its effect in neurodegenerative disease, including PD. In this study, we investigated the anti-Parkinson effects of frondoside A (FA) from Cucumaria frondosa and ginsenoside Rg3 (Rg3) from Panax notoginseng in C. elegans PD model. Both saponins were tested for toxicity and optimal concentration by food clearance assay and used to treat 6-OHDA-induced BZ555 and transgenic α-synuclein NL5901 strains in C. elegans. Treatment with FA and Rg3 significantly attenuated DAergic neurodegeneration induced by 6-OHDA in BZ555 strain, improved basal slowing rate, and prolonged lifespan in the 6-OHDA-induced wild-type strain with downregulation of the apoptosis mediators, egl-1 and ced-3, and upregulation of sod-3 and cat-2. Interestingly, only FA reduced α-synuclein aggregation, rescued lifespan in NL5901, and upregulated the protein degradation regulators, including ubh-4, hsf-1, hsp-16.1 and hsp-16.2. This study indicates that both FA and Rg3 possess beneficial effects in rescuing DAergic neurodegeneration in the 6-OHDA-induced C. elegans model through suppressing apoptosis mediators and stimulating antioxidant enzymes. In addition, FA could attenuate α-synuclein aggregation through the protein degradation process.     

Review of FTIR microspectroscopy applications to investigate biochemical changes in C. elegans

Caenorhabditis elegans nematode has emerged as a model organism paving the ways for multidisciplinary research in biomedical, environmental toxicology, aging, metabolism, obesity, and drug discovery. The wide range of applications of this model organism are attributed to C. elegans’ unique features: C. elegans are inexpensive, easy to grow and maintain in a laboratory, has a short lifespan, and has a small body size. With this increased interest, the need for analytical techniques to assess the biochemical information on intact worms continues to grow. Fourier Transform Infrared (FTIR) microspectroscopy is considered as a powerful technique that can be used to determine the chemical structure and composition of various materials, including biological samples. Furthermore, the development of focal plane array detectors has made this technique attractive to study complex biological systems such as whole nematodes. This review focuses on the use of FTIR microspectroscopy to study C. elegans. The first published work on the use of FTIR microspectroscopy to study a complex whole animal was reported in 2004. Since then, very few other studies were carried out. The objective of this review is to summarize work conducted to date using FTIR microspectroscopy to study nematodes and to discuss the information that can be gained by using this technique. This could allow scientists to add this technique to the arsenal of techniques already in use for C. elegans studies.     

Basic characterization and Alzheimer’s disease relieving property of a glucose riched polysaccharide from Cibotium barometz

The water-soluble polysaccharides from plants have attracted ever-increasing attention in the field of food and drug due to their various activities and low toxicity. CBP50-1, as a purified fraction of polysaccharide from the rhizome of Cibotium barometz (CBP), mainly consisted of glucose (55.45%) and xylose (25.27%). CBP50-1 showed excellent antioxidant activity for scavenging 2,2?Diphenyl?1?picryl?hydrazy (DPPH) radical and hydroxyl radical, further inhibiting lipid peroxidation. CBP50-1 significantly improved the survival rate of Caenorhabditis elegans under thermal and oxidative stress. Furthermore, CBP50-1 reduced the paralysis and oxidative damage induced by amyloid-beta (Aβ) and increased the antioxidant enzyme activity in Alzheimer’s disease (AD) model C. elegans CL4176 through c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) signal pathway. Thus, CBP50-1 had a potential application in health industries.     

Modulation of the lifespan of C. elegans by the controlled release of nitric oxide

The frontier of nitric oxide biology has gradually shifted from mechanism elucidation to biomanipulation, e.g. cell-proliferation promotion, cell-apoptosis induction, and lifespan modulation. This warrants biocompatible nitric oxide (NO) donating materials, whose NO release is not only controlled by a bioorthogonal trigger, but also self-calibrated allowing real-time monitoring and hence an onset/offset of the NO release. Additionally, the dose of NO release should be facilely adjusted in a large dynamic range; flux and the dose are critical to the biological outcome of NO treatment. Via self-assembly of a PEGylated small-molecule NO donor, we developed novel NO-donating nanoparticles (PEG-NORM), which meet all the aforementioned criteria. We showcased that a low flux of NO induced cell proliferation, while a high flux induced cell oxidative stress and, ultimately, death. Notably, PEG-NORM was capable of efficiently modulating the lifespan of C. elegans. The average lifespan of C. elegans could be fine-tuned to be as short as 15.87 ± 0.29 days with a high dose of NO, or as long as 21.13 ± 0.41 days with a low dose of NO, compared to an average life-span of 18.87 ± 0.46 days. Thus, PEG-NORM has broad potential in cell manipulation and life-span modulation and could drive the advancement of NO biology and medicine.

Schematic illustration of modulating the longevity of the C. elegans by PEG-NORM nanoparticles.     

Flavonoids from Lycium barbarum Leaves Exhibit Anti-Aging Effects through the Redox-Modulation

Lycium barbarum leaves are a kind of vegetable, and modern nutrition studies have found that they have an anti-aging function. Our study aims to investigate the anti-aging effects of Lycium barbarum leaf flavonoid (LBLF) extracts and its underlying molecular mechanism. LBLFs were purified using D101 and polyamide resin, characterized by ultraperformance liquid chromatography coupled with mass spectrometry, and administered to hydrogen peroxide (H₂O₂)-treated human umbilical vein endothelial cells (HUVECs) and Caenorhabditis elegans. Appropriate enrichment conditions were optimized through dynamic adsorption and desorption experiments, the content of flavonoids reached 909.84 mg/g, rutin and kaempferol being the main ones. LBLFs attenuated H₂O₂-induced HUVEC apoptosis, decreased reactive oxygen species and malondialdehyde production levels, increased superoxide dismutase, glutathione peroxidase and catalase activities. Furthermore, pre-treatment with LBLF increased mRNA expression of erythropoietin (EPO) and heme oxygenase-1 (HO-1) via the mitogen-activated protein kinase (MAPK) signaling pathway in HUVECs. Compared with 100 µM rutin monomer, LBLF prolonged the lifespan of Caenorhabditis elegans, enhanced their mobility in middle life stages and upregulated expression of sod-2, gcs-1 and skn-1 genes, which indicated that the anti-aging effects of LBLF were due to its redox-modulation.     

Effects of gamma irradiation on two heat resistant moulds: Aspergillus fumigatus and Paecilomyces variotii isolated from margarine

The present study was undertaken to evaluate the effect of gamma irradiation on two heat-resistant moulds, namely Aspergillus fumigatus and Paecilomyces variotii isolated from margarine samples. The irradiation process of these moulds was carried out in a ⁶⁰Co gamma (γ) irradiator at average absorbed doses of 1, 3, 5 and 7 kGy for exposure times of 52, 156, 260 and 364 min, respectively. The average D₁₀ value for A. fumigatus was 1.08±0.08 kGy while it was 0.59±0.10 kGy for P. variotii. Consequently, the sensitivity of P. variotii against γ irradiation was more than A. fumigatus.     

Lipase immobilized on HOOC-MCF： A highly enantioselective catalyst for transesterification resolution of （R,S）-1-phenylethanol

Pseudomonas cepacia lipase (PSL) immobilized on the carboxyl-functionalized meso-cellular foams (HOOC-MCF) was used for the transesterification resolution of (R,S)-1-phenylethanol in organic solvent.The results showed that the ee value of (S)-1- phenylethanol and (R)-1-phenylethyl acetate reached 99% with 50% conversion of 1-phenylethanol using toluene as solvent. Furthermore,it was found that PSL/HOOC-MCF exhibited high enantioselectivity in organic solvent with log P≤2 such as toluene and hexane.     

iso-Fatty Acid Metabolism in Caenorhabditis elegans’ Ceramide Biosynthesis

Ceramide biosynthesis and its connection to iso-fatty acid metabolism in the model organism Caenorhabditis elegans was investigated using a combination of reverse genetics and comparative ESI-(+)-HR-MS^e ceramide profiling along with incorporation experiments with bacterial mutants specifically enriched with isotopically labeled branched-chain amino acids or branched-chain fatty acids. Incorporation of a l -leucine-derived isovalerate unit into the conserved d17 : 1iso sphingosine building block proceeds through elo-5 dependent chain elongation and depends on peroxisomal β-oxidation by the 3-ketoacyl-CoA thiolase daf-22, although ceramide profiles of N2 wildtype and daf-22(ok693) are indistinguishable. Biosynthesis of the homologous N-iso-acyl moieties also depends on l -leucine and isovalerate chain elongation but proceeds independently of elo-5 and daf-22. Biosynthesis of the dominating N-docosanoyl moiety depends on elo-3-catalyzed chain elongation of bacteria-derived palmitic acid, whereas the N-tetracosanoyl moiety is derived from de novo lipogenesis.     

Sugar Containing Compounds and Biological Activities of Lagochilus setulosus

Phytochemical investigation of the methanolic extract obtained from the aerial parts of Lagochilus setulosus (Lamiaceae) afforded the new compound 1-methoxy-3-O-β-glucopyranosyl-α-l-oliose (1) together with five known glycosides, namely sitosterol-3-O-β-glucoside (2), stigmasterol-3-O-β-glucoside (3), pinitol (4), 6β-hydroxyl-7-epi-loganin (5), and chlorotuberoside (6). The structures of these compounds were elucidated by extensive spectroscopic analyses, especially HR-MS, 1D and 2D NMR spectroscopy. The in vitro cytotoxic activity of the methanolic extract and the isolated compounds was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and crystal violet (CV) staining assays. In addition, the antifungal activities of the components were evaluated against Botrytis cinerea, Septoria tritici, and Phytophthora infestans. The anthelmintic potential was determined against Caenorhabditis elegans nematodes. Neither the extract nor the isolated compounds showed promising activity in all the bioassays.     

Chemical composition,antioxidant, antimicrobial and antiproliferative activity of Laureliopsis philippiana essential oil of Chile,study in vitro and in silico

Chilean Laureliopsis philippiana has been used in traditional medicine by the Mapuche and their ancestors. To evaluate its pharmacological activity, Laureliopsis philippiana leaf essential oil extract (LP_EO) was chemically and biologically characterized in the present study. In vitro antioxidant potential was analyzed, and antitumor activity was evaluated in non-tumor and tumor cell culture lines. Caenorhabditis elegans was used as a model for evaluating toxicity, and the chemical composition of the essential oil was analyzed using gas chromatography–mass spectrometry. The oil contains six major monoterpenes: eucalyptol (27.7 %), linalool (27.6 %), isozaphrol (19.5 %), isohomogenol (12.6 %), α-terpineol (7.7 %), and eudesmol (4.8 %). Based on quantum mechanical calculations, isosafrole and isohomogenol conferred in vitro antioxidant and antimicrobial activity to LP_EO. In addition, LP_EO showed antimicrobial activity against clinical Helicobacter pylori isolates (MIC 64 and MBC > 128 μg·mL^?1), Staphylococcus aureus (MIC 32 and MBC > 64 μg·mL^?1), Escherichia coli (MIC 8 and MBC 16 μg·mL^?1) and Candida albicans (MIC 64 and > 128 μg·mL^?1). LP_EO could selectively inhibit the proliferation of epithelial tumor cell lines but showed low toxicity against Caenorhabditis elegans (0.39 to 1.56 μg·mL^?1). Therefore, LP_EO may be used as a source of bioactive compounds in novel pharmacological treatments for veterinary and human application, cosmetics, or sanitation.