Caenorhabditis Elegans Model Research Articles

Inhibition of Staphylococcus epidermidis and Pseudomonas aeruginosa biofilms by grape and rice agroindustrial residues

Agroindustrial wastes are generated daily and seem to be rich in bioactive molecules. Thus, they can potentially be used as source of compounds able to control bacterial biofilms. We investigated the potential of extracts from the residues of rice and grape to combat clinically important bacterial biofilms. Extracts of grape pomace and rice bran were obtained using different extractive methodologies and subjected to the evaluation of its antimicrobial and antibiofilm activities. After the in vivo toxicity, the chemical characterization of the most promising extract was assessed. The mass spectrometry analysis revealed the presence of dipeptides, alkaloids and phenolic compounds. Most grape extracts presented antibiofilm and antimicrobial activities against Staphylococcus epidermidis ATCC 35984 and Pseudomonas aeruginosa PA14. The hydromethanolic grape pomace extract obtained by ultrasound assisted extraction (MeOH 80 UAE) presented the most promising activity, being able to inhibit in 99% and 80% the biofilm formation of S. epidermidis and P. aeruginosa, respectively. Against the gram-negative model, this extract eradicated the biofilm by 80%, induced the swarming motility and displayed a physical effect. It also did not present acute or chronic toxicity in Caenorhabditis elegans model. In this way, agroindustrial residues represent a promising source of molecules capable of controlling bacterial biofilms.

Sennosides A and B could contribute to the antimicrobial efficiency of Senna alexandrina Mill. against pathogenic bacteria in vitro and in vivo models

The search of new antimicrobial compounds is increasing in due with increasing bacterial infections. Discovering effective antibacterial medications is crucial for improving healthcare and combating bacterial infections. Senna alexandrina Mill. known as Tinnevelly senna, used as herbal extract in traditional medicine and found be rich in anthraquinone glycosides like sennoside A (SA) and sennoside B (SB), shows significant biological activity as a potential therapeutic agent. This study assessed the antibacterial effects of senna extracts on Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus bacteria, both in vitro and in vivo. HPLC analysis identified sennosides as the major compounds in senna extracts, with the highest concentration found in the leaves, followed by the pods, flowers, stems, and roots. The leaf extract showed the highest sennoside content (SA 27.21 mg/g and SB 29.1 mg/g) compared to other plant parts. FT-IR analysis confirmed the presence of sennosides through the detection of carboxylic acids and OH functional groups in S. alexandrina extracts. Extracts rich in sennosides displayed potent in vitro antibacterial activity (1000 µg/mL) by generating ROS, penetrating and becoming disruptive to bacterial functions. Similarly, in Caenorhabditis elegans model, they inhibited bacterial growth and colonization and enhanced physiological functions in the worms. Senna extract (1000 µg/mL) improved intestinal barrier's structural stability in C. elegans by outcompeting pathogenic bacteria and prolonged survival rates of those infected with P. aeruginosa and S. aureus to 56.6 % and 62.4 %, respectively, confirming the potent antibacterial efficacy of senna leaf methanolic extracts due to their high sennoside content in both in vitro and in vivo models.

A clustering-based survival comparison procedure designed to study the Caenorhabditis elegans model.

Caenorhabditis elegans is highly important in current research, serving as a pivotal model organism that has greatly advanced the understanding of fundamental biological processes such as development, cellular biology, and neurobiology, helping to promote major advances in various fields of science. In this context, the survival of a nematode under various conditions is commonly investigated via statistical survival analysis, which is typically based on hypothesis testing, providing valuable insights into the factors influencing its longevity and response to various environmental factors. The extensive reliance on hypothesis testing is acknowledged as a concern in the scientific analysis process, emphasizing the need for a comprehensive evaluation of alternative statistical approaches to ensure a rigorous and unbiased interpretation of research findings. In this work, we propose an alternative method to hypothesis testing for evaluating differences in nematode survival. Our approach relies on a clustering technique that takes into account the complete structure of survival curves, enabling a more comprehensive assessment of survival dynamics. The proposed methodology helps to identify complex effects on nematode survival and enables us to derive the probability that treatment induces a specific effect. To highlight the application and benefits of the proposed methodology, it is applied to two different datasets, one simple and one more complex.

Black goji berry anthocyanins extend lifespan and enhance the antioxidant defenses in Caenorhabditis elegans via the JNK-1 and DAF-16/FOXO pathways.

The black goji berry (Lycium ruthenicum Murr.) is known for its abundance of high-quality natural antioxidants, particularly anthocyanins. Black goji berry anthocyanins (BGA) are receiving increasing attention because of their high safety and beneficial biological activities. Studies have shown that oxidative stress is a key factor affecting aging, whereas antioxidants are critical preventive and delaying strategies. In the present study, we investigated the potential anti-aging effects and mechanism of BGA using the Caenorhabditis elegans model. We found that BGA prolonged the mean lifespan of nematodes and improve their healthspan, including locomotion, pharyngeal pumping rate and stress resistance. Subsequently, we observed a significant decrease in reactive oxygen species and malondialdehyde levels in nematodes after administering BGA. Moreover, BGA enhanced the activities of the antioxidant enzymes superoxide dismutase and catalase, and elevated the glutathione disulfide/glutathione ratio. We confirmed that BGA exerted excellent antioxidative stress activity in nematodes, which may contribute substantially to its anti-aging effects. The health benefits of BGA in C. elegans might be closely related to petunidin-3-O-glucoside, the most abundant anthocyanin in BGA. Further mechanistic investigation revealed that the JNK-1 and DAF-16/FOXO pathways, rather than the calorie restriction pathway, were responsible for the antioxidant stress and life-prolonging effects of BGA in nematodes. Our research provides a theoretical foundation for studying the anti-aging effect of BGA and a basis for developing black goji berry and its anthocyanins as functional foods with anti-aging and antioxidative stress benefits. © 2024 Society of Chemical Industry.

Senolytics Enhance the Longevity of Caenorhabditis elegans by Altering Betaine Metabolism.

Aging triggers physiological changes in organisms that are tightly linked to metabolic changes. Senolytics targeting many fundamental aging processes are currently being developed. However, the host metabolic response to natural senescence and the molecular mechanism underlying the antiaging benefits of senolytics remain poorly understood. In this study, we investigated metabolic changes during natural senescence based on the Caenorhabditis elegans model and pinpointed potential biomarkers linked to the benefits of senolytics. These results suggest that age-dependent metabolic changes during natural aging occur in C elegans. Betaine was identified as a crucial metabolite in the natural aging process. We explored the metabolic effects of aging interventions by administering 3 antiaging drugs-metformin, quercetin, and minocycline-to nematodes. Notably, betaine expression significantly increased under the 3 antiaging drug treatments. Our findings demonstrated that betaine supplementation extends lifespan, primarily through pathways associated with the forkhead box transcription factor (FoxO) signaling pathway, the p38-mitogen-activated protein kinase (MAPK) signaling pathway, autophagy, the longevity regulating pathway, and the target of rapamycin (mTOR) signaling pathway. In addition, autophagy and free radicals are altered in betaine-treated nematodes. Overall, we found that betaine is a critical metabolite during natural aging and that senolytics extend the lifespan of nematodes by increasing betaine levels and promoting autophagy and antioxidant activity. This finding suggests that betaine could be a novel therapeutic target for promoting longevity.

Exploration of New Drug Candidate Derived from Antioxidants of Korean Native Halophytes: Control of Acinetobacter baumannii with Antipathogenic Activity

The rise of antibiotic-resistant bacteria poses a significant challenge to the treatment of bacterial infections, necessitating the development of novel antibiotics or strategies to preserve the efficacy of existing ones. This study investigates the role of oxidative stress modulation in the pathogenicity of multidrug-resistant (MDR) bacterial strains, aiming to identify potential avenues for new drug design. Specifically, the anti-biofilm effects of crude extracts and fractions from seven halophyte species native to Jeju Island, South Korea, were evaluated against Acinetobacter baumannii ATCC 17978. Notably, the 85% aqueous methanol fraction of Peucedanum japonicum Thunb. (Pj) and the n-hexane fraction of Lysimachia mauritiana Lam. (Lm) demonstrated significant anti-biofilm activity. Further assessments revealed that these fractions also exhibited notable antioxidant and anti-inflammatory properties, with the Pj fraction showing a lifespan extension effect in the Caenorhabditis elegans model. These findings suggest that Pj and Lm hold promise as potential candidates for the development of new therapeutic agents targeting MDR bacteria.

Interaction of graphene oxide with tannic acid: computational modeling and toxicity mitigation in C. elegans.

Graphene oxide (GO) undergoes multiple transformations when introduced to biological and environmental media. GO surface favors the adsorption of biomolecules through different types of interaction mechanisms, modulating the biological effects of the material. In this study, we investigated the interaction of GO with tannic acid (TA) and its consequences for GO toxicity. We focused on understanding how TA interacts with GO, its impact on the material surface chemistry, colloidal stability, as well as, toxicity and biodistribution using the Caenorhabditis elegans model. Employing computational modeling, including reactive classical molecular dynamics and ab initio calculations, we reveal that TA preferentially binds to the most reactive sites on GO surfaces via the oxygen-containing groups or the carbon matrix; van der Waals interaction forces dominate the binding energy. TA exhibits a dose-dependent mitigating effect on the toxicity of GO, which can be attributed not only to the surface interactions between the molecule and the material but also to the inherent biological properties of TA in C. elegans. Our findings contribute to a deeper understanding of GO's environmental behavior and toxicity and highlight the potential of tannic acid for the synthesis and surface functionalization of graphene-based nanomaterials, offering insights into safer nanotechnology development.

Quinic acid protects against the development of Huntington’s disease in Caenorhabditis elegans model

BackgroundQuinic acid (QA), a cyclitol and cyclohexanecarboxylic acid, is a natural product that is present and can be isolated from edible herbals like tea, coffee and several fruits and vegetables. It was previously reported that QA exerted antioxidant and neuroprotective activity against dementia. However, it was not tested for its neuroprotective potential against Huntington’s disease (HD). Since aging related disorders are greatly linked to oxidative stress conditions, we focused on testing the oxidative stress resistant activity and protective effect of QA against the development of HD by using the multicellular Caenorhabditis elegans (C. elegans) worm model.MethodsFirstly, QA was tested for its oxidative stress resistant properties. In survival assay, wild type and mutant skn-1 and daf-16 worms were exposed to oxidative stress conditions by using H2O2. Activation of SKN-1 pathway and expression of its downstream genes gcs-1 and gst-4 were also tested. Secondly, the effect of QA was evaluated on HD by testing its ability to decrease the formation of polyQ150 aggregates. Furthermore, its effect on the accumulation of polyglutamine (polyQ35 and polyQ40 aggregates) was tested.ResultsHere we report that QA could improve the survival of C. elegans after exposure to oxidative stress caused by H2O2 while also exerting antioxidant effects through the activation of SKN-1/Nrf2 pathway. Moreover, QA could be a potential candidate to protect against HD due to its effects on decreasing the formation of polyQ150, polyQ35 and polyQ40 aggregates.ConclusionsThis study highlights the importance of QA as a natural compound in defending against oxidative stress and the development of neurodegenerative diseases like HD.

Study on HPLC fingerprint of Saposhnikovia divaricata lipophilic components and anti-aging effects

Saposhnikovia divaricata is commonly used in clinical practice as a heat-clearing and detoxifying traditional Chinese medicine. Current research on Saposhnikovia divaricata has mostly focused on chromones, while studies on its lipophilic parts remain scarce. In this study, samples of the lipophilic components of Saposhnikovia divaricata (SDL) from different regions in China were collected to establish an HPLC fingerprint. The quality of SDL was evaluated through chemical pattern recognition and multi-component content determination. Furthermore, using the Caenorhabditis elegans (C. elegans) model, the anti-aging ability of SDL was preliminarily studied. In the HPLC fingerprints of 11 batches of SDL, 19 common peaks were identified, and 4 components were characterized as follows: peak 14, linolenic acid (ALA); peak 15, docosahexaenoic acid (DHA); peak 16, linoleic acid (LA); peak 17, oleic acid (OA). The similarity of the fingerprint ranged from 0.704 to 0.929. The results indicate that the content of ALA, DHA, LA, and OA are 0.040–0.440 mg/g, 0.003–0.116 mg/g, 1.047–6.460 mg/g, and 0.040–0.294 mg/g, respectively. HCA analysis divided 11 batches of SDL into two categories, and PCA analysis extracted 6 principal components with a cumulative contribution rate of 85.91%. The anti-aging ability of the SDL was proved by measuring the lifespan, reproductive capacity, body length, mobility, lipofuscin content, and heat stress resistance of C. elegans. The combination of high-performance liquid chromatography fingerprint and chemical pattern recognition for multi-component content determination is a reliable, comprehensive, and promising evaluation of the quality of SDL. The confirmation of SDL’s anti-aging ability provides the possibility for the research of Saposhnikovia divaricata in the field of healthy food and cosmetics.

Antibiofilm and antivirulence potentials of iodinated fmoc-phenylalanine against Staphylococcus aureus

Staphylococcus aureus poses significant risks to public health due to its ability to form biofilm and produce virulence factors, contributing to the increase in antibiotic resistance and treatment complications. This emphasizes the urgent need for novel antimicrobial controls. Based on the premise that halogenation improves antimicrobial efficacy, this study investigated the ability of halogenated phenylalanine to effectively inhibit S. aureus biofilm formation and virulence activities. Among 29 halogenated compounds, Fmoc-4-iodo-phenylalanine (Fmoc-Iodo-Phe) displayed the highest antibiofilm effect against S. aureus, achieving 94.3 % reduction at 50 μg/mL. Microscopic studies confirmed its ability to prevent and disrupt mature biofilms. At 10 μg/mL, Fmoc-Iodo-Phe markedly inhibited virulence factors, such as cell surface hydrophobicity, hemolysin and slime production. It showed low propensity for resistance development and effectively inhibited biofilms formed by methicillin-resistant S. aureus (MRSA) and S. epidermidis, but was inactive against Gram-negative bacteria. Gene expression analysis complemented by molecular docking suggest that Fmoc-Iodo-Phe could target the AgrA quorum sensing cascade due to strong interactions with key residues at its DNA binding sites. Notably, it was non-cytotoxic in Caenorhabditis elegans model and satisfied drug-likeliness criteria based on ADMET prediction. Therefore, our findings position Fmoc-Iodo-Phe as a promising antimicrobial candidate against S. aureus infections, underscoring its potential as an alternative to traditional antibiotics.

Free long-chain fatty acids trigger early postembryonic development in starved Caenorhabditis elegans by suppressing mTORC1.

Postembryonic development of animals has long been considered an internally predetermined program, while macronutrients were believed to be essential solely for providing biomatters and energy to support this process. However, in this study, by using a nematode Caenorhabditis elegans (abbreviated as C. elegans hereafter) model, we surprisingly discovered that dietary supplementation of palmitic acid alone, rather than other abundant essential nutrients such as glucose or amino acid mixture, was sufficient to initiate early postembryonic development even under complete macronutrient deprivation. Such a development was evidenced by changes in morphology, cellular markers in multiple tissues, behaviors, and the global transcription pattern and it occurred earlier than the well-known early L1 nutrient checkpoint. Mechanistically, palmitic acid did not function as a biomatter/energy provider, but rather as a ligand to activate the nuclear hormone receptor NHR-49/80, leading to the production of an unknown peroxisome-derived secretive hormone in the intestine. This hormonal signal was received by chemosensory neurons in the head, regulating the insulin-like neuropeptide secretion and its downstream nuclear receptor to orchestrate global development. Additionally, the nutrient-sensing hub mTORC1 played a negative role in this process. In conclusion, our data indicate that free fatty acids act as a primary nutrient signal to launch the early development in C. elegans, which suggests that specific nutrients, rather than the internal genetic program, serve as the first impetus for postembryonic development.

Binding profiles for 961 Drosophila and C. elegans transcription factors reveal tissue-specific regulatory relationships.

A catalog of transcription factor (TF) binding sites in the genome is critical for deciphering regulatory relationships. Here we present the culmination of the efforts of the Model Organism ENCyclopedia Of DNA Elements (modENCODE) and the model organism Encyclopedia of Regulatory Networks (modERN) consortia to systematically assay TF binding events in vivo in two major model organisms, Drosophila melanogaster (fly) and Caenorhabditis elegans (worm). These datasets comprise 605 TFs identifying 3.6M sites in the fly and 356 TFs identifying 0.9 M sites in the worm and represent the majority of the regulatory space in each genome. We demonstrate that TFs associate with chromatin in clusters termed "metapeaks", that larger metapeaks have characteristics of high occupancy target (HOT) regions, and that the importance of consensus sequence motifs bound by TFs depends on metapeak size and complexity. Combining ChIP-seq data with single cell RNA-seq data in a machine learning model identifies TFs with a prominent role in promoting target gene expression in specific cell types, even differentiating between parent-daughter cells during embryogenesis. These data are a rich resource for the community that should fuel and guide future investigations into TF function. To facilitate data accessibility and utility, all strains expressing GFP-tagged TFs are available at the stock centers for each organism. The chromatin immunoprecipitation sequencing data are available through the ENCODE Data Coordinating Center, GEO, and through a direct interface that provides rapid access to processed data sets and summary analyses, as well as widgets to probe the cell type-specific TF-target relationships.

Stress resistance, antiaging, and neuroprotective activities of baicalein 5,6-dimethyl ether and Alnus rugosa extract in Caenorhabditis elegans model.

The leaf extract of Alnus rugosa (AR) together with the isolated compound baicalein 5,6-dimethyl ether (BME) were investigated for their antioxidant, radical scavenging, antiaging, and neuroprotective properties using the Caenorhabditis elegans model. The stress resistance and antiaging potential of AR and BME were assessed in wild-type N2 and transgenic C. elegans strains CF1553, TJ356, and BA17. Transgenic CL4176 expressing the human amyloid-beta peptide (Aβ) was used as a model for Aβ toxicity, whereas transgenic AM141 expressing polyQ aggregates was employed as a model for Huntington's disease. An in silico molecular docking study using Discovery Studio 4.5 was performed to elucidate the putative binding mode of BME to the active sites of Daf-2 protein, involved in longevity and oxidative stress resistance in C. elegans. BME and AR significantly delayed the appearance of oxidative stress markers in wild-type N2 and transgenic strains TJ356 and CF1553, affecting the DAF-16/FOXO transcription factor subcellular distribution and inducing expression of the sod-3 antioxidative gene. Pretreatment with AR significantly reduced the aging marker lipofuscin accumulation in BA17 worms, its effect was greater than that of epigallocatechin gallate, suggesting a potential antiaging effect. Neuroprotective effects of AR and BME were confirmed in AM141 transgenic worms, inducing a significant reduction in the score of polyQ40::GFP aggregates. Moreover, BME (25 µg/mL) resulted in a significant delay in Aβ-induced paralysis in CL4176 worms. In silico molecular modeling revealed that BME exhibited good fitting scores within the active sites of the Daf-2 protein. AR and BME exert beneficial effects in the modulation of age-related markers and attenuation of neurotoxicity in neurodegenerative disorders. Hence, AR and BME could be recognized as promising antioxidant and neuroprotective natural drug candidates that could be included in neuro-nutraceuticals.

Low molecular weight polysaccharide of Tremella fuciformis exhibits stronger antioxidant and immunomodulatory activities than high molecular weight polysaccharide

Low molecular weight polysaccharides had higher bio-activity and bioavailability compared to ultra-high molecular weight polysaccharides, this study aimed to obtain low molecular weight polysaccharides from Tremella fuciformis (TFLP) by using high-temperature and high-pressure assisted hydrochloric acid method to degrade Tremella fuciformis polysaccharides (TFP), and the structural characteristics, in vivo antioxidant and immune enhancing activities of TFP and TFLP was explored through Caenorhabditis elegans (C. elegans) and mice model. It was found that TFP and TFLP were acidic polysaccharides with molecular weights of 2238 kDa and 3 kDa, respectively. The glycosidic bonding of TFP and TFLP was mainly composed of different configurations of mannopyranose. TFP and TFLP had excellent in vivo antioxidant activity and stress resistance by regulating the mRNA transcription level and metabolites in C. elegans. Results also showed that TFP and TFLP could enhance the antioxidant capacity and immunity of serum, spleen and small intestine tissues in normal mice and cyclophosphamide-induced immunosuppressive mice through regulating the relative transcription and expression levels of anti-inflammatory related signaling factors, and it has found that TFLP showed better immune enhancement and antioxidant activity than TFP. In addition, Akkermansia, Bacteroides and Alloprevotella were characteristic bacteria at the genus level in immunosuppressed mice intervened with TFLP, with a significant increase in relative abundance. The content of SCFAs significantly increased in immunosuppressed mice by TFLP. These results indicated that TFP and TFLP had potential in vivo antioxidant and immune enhancing activities.

Salmonella biofilm formation diminishes bacterial proliferation in the C. elegans intestine

Non-typhoidal Salmonella serovars are a significant global cause of foodborne infections, owing their transmission success to the formation of biofilms. While the role of these biofilms in Salmonella's persistence outside the host is well understood, their significance during infection remains elusive. In this study, we investigated the impact of Salmonella biofilm formation on host colonization and virulence using the nematode model Caenorhabditis elegans. This infection model enables us to isolate the effect of biofilm formation on gut colonization and proliferation, as no gut microbiome is present and Salmonella cannot invade the intestinal tissue of the nematode. We show that a biofilm-deficient ΔcsgD mutant enhances gut proliferation compared to the wild-type strain, while the pathogen's virulence, the host's immune signaling pathways, and host survival remain unaffected. Hence, our work suggests that biofilm formation does not significantly contribute to Salmonella infection in C. elegans. However, complementary assays in higher-order in vivo models are required to further characterize the role of biofilm formation during infection and to take into account the impact of biofilm formation on competition with gut microbiome and epithelial invasion.

Pentagalloyl glucose enhanced the stress resistance to delay aging process in Caenorhabditis elegans

Aging is a complex biological process characterized by gradual and irreversible functional deterioration, strongly associated with oxidative stress. Pentagalloyl glucose (PGG) has attracted increasing attention due to its potent antioxidant and anti-stress properties. This study investigated the potential of PGG to mitigate the aging process under stress in RAW 264.7 cells and Caenorhabditis elegans models. The expression of vital genes associated with stress was also measured to explain the action mechanism of PGG in C. elegans. The findings showed that PGG supplementation not only significantly enhanced the stress tolerance of RAW 264.7 cells, but also prolonged lifespan and reduced the ROS and lipofuscin accumulation in C. elegans induced by stress. Meanwhile, the improvement effect of PGG on delaying aging development was also manifested in the protection of mitochondrial function and neuronal integrity. Moreover, daf-16 nuclear translocation and sod-3 expression were significantly enhanced by PGG to delay the aging process. Mechanistically, PGG might alleviate aging by improving daf-16, sod-3, ctl-1, and gst-4 levels in the DAF-16/FOXO pathway and upregulating skn-1 and gst-4 expression in the SKN-1/Nrf2 pathway. Our study provided novel insights into the role of PGG in combating stress-induced aging.

Hispidol Regulates Behavioral Responses to Ethanol through Modulation of BK Channels: A Novel Candidate for the Treatment of Alcohol Use Disorder.

Alcohol use disorder (AUD) is the most common substance use disorder and poses a significant global health challenge. Despite pharmacological advances, no single drug effectively treats all AUD patients. This study explores the protective potential of hispidol, a 6,4'-dihydroxyaurone, for AUD using the Caenorhabditis elegans model system. Our findings demonstrate that hispidol-fed worms exhibited more pronounced impairments in thrashes, locomotory speed, and bending amplitude, indicating that hispidol exacerbated the detrimental effects of acute ethanol exposure. However, hispidol significantly improved ethanol withdrawal behaviors, such as locomotory speed and chemotaxis performance. These beneficial effects were absent in slo-1 worms (the ortholog of mammalian α-subunit of BK channel) but were restored with the slo-1(+) or hslo(+) transgene, suggesting the involvement of BK channel activity. Additionally, hispidol increased fluorescence intensity and puncta in the motor neurons of slo-1::mCherry-tagged worms, indicating enhanced BK channel expression and clustering. Notably, hispidol did not alter internal ethanol concentrations, suggesting that its action is independent of ethanol metabolism. In the mouse models, hispidol treatment also demonstrated anxiolytic activity against ethanol withdrawal. Overall, these findings suggest hispidol as a promising candidate for targeting the BK channel in AUD treatment.

Components in SLPE Alleviate AD Model Nematodes by Up-Regulating Gene gst-5.

Salvia leucantha is a perennial herb of the genus Salvia in the family Labiatae, which has a wide range of biological activities, mainly including inhibition of acetylcholinesterase, antibacterial, and anti-inflammatory activity. To explore the protective effects and mechanism of action of S. leucantha on Alzheimer's disease (AD), the anti-AD activity of SLE (extracts of S. leucantha) was determined by using a transgenic Caenorhabditis elegans (C. elegans) model (CL4176). Analyses included paralysis assay, phenotypic experiments, transcriptome sequencing, RNA interference (RNAi), heat shock assays, and gas chromatography-mass spectrometry (GC-MS). SLPE (S. leucantha petroleum ether extract) could significantly delay CL4176 paralysis and extend the longevity of C. elegans N2 without harmful effects. A total of 927 genes were significantly changed by SLPE treatment in C. elegans, mainly involving longevity regulatory pathways-nematodes, drug metabolism-cytochrome P450, and glutathione metabolic pathways. RNAi showed that SLPE exerted its anti-AD activity through up-regulation of the gene gst-5; the most abundant compound in SLPE analyzed by GC-MS was 2,4-Di-tert-butylphenol (2,4-DTBP), and the compound delayed nematode paralysis. The present study suggests that active components in S. leucantha may serve as new-type anti-AD candidates and provide some insights into their biological functions.

Hederagenin inhibits mitochondrial damage in Parkinson’s disease via mitophagy induction

BackgroundParkinson's disease (PD) is a neurodegenerative disorder marked by the loss of dopaminergic neurons and the formation of α-synuclein aggregates. Mitochondrial dysfunction and oxidative stress are pivotal in PD pathogenesis, with impaired mitophagy contributing to the accumulation of mitochondrial damage. Hederagenin (Hed), a natural triterpenoid, has shown potential neuroprotective effects; however, its mechanisms of action in PD models are not fully understood. MethodWe investigated the effects of Hed on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity in SH-SY5Y cells by assessing cell viability, mitochondrial function, and oxidative stress markers. Mitophagy induction was evaluated using autophagy and mitophagy inhibitors and fluorescent staining techniques. Additionally, transgenic Caenorhabditis elegans (C. elegans) models of PD were used to validate the neuroprotective effects of Hed in vivo by focusing on α-synuclein aggregation, mobility, and dopaminergic neuron integrity. ResultsHed significantly enhanced cell viability in 6-OHDA-treated SH-SY5Y cells by inhibiting cell death and reducing oxidative stress. It ameliorated mitochondrial damage, evidenced by decreased mitochondrial superoxide production, restored membrane potential, and improved mitochondrial morphology. Hed also induced mitophagy, as shown by increased autophagosome formation and reduced oxidative stress; these effects were diminished by autophagy and mitophagy inhibitors. In C. elegans models, Hed activated mitophagy and reduced α-synuclein aggregation, improved mobility, and mitigated the loss of dopaminergic neurons. RNA interference targeting the mitophagy-related genes pdr-1 and pink-1 partially reversed these benefits, underscoring the role of mitophagy in Hed's neuroprotective actions. ConclusionHed exhibits significant neuroprotective effects in both in vitro and in vivo PD models by enhancing mitophagy, reducing oxidative stress, and mitigating mitochondrial dysfunction. These findings suggest that Hed holds promise as a therapeutic agent for PD, offering new avenues for future research and potential drug development.

A novel method in radish processing: Augmented flavor and health benefits revealed through Caenorhabditis elegans model

This study investigates the preparation of black radish using a cyclic method involving alternating 75 °C baking and 100 °C steam treatment for 10 cycles. Compared to fresh radish, black radish contains higher concentrations of quinolines and amino acids, giving it a rich taste and caramel aroma. Black radish extract contains quinoline and ornithine levels that are 198.92 times and 94.48 times greater, respectively, than those in fresh radish extract. Black radish extract demonstrates superior performance in reducing fat accumulation and enhancing antioxidant capacity. At a concentration of 10 μg/mL, black radish extract reduces the relative Oil Red O intensity in Caenorhabditis elegans to 13.42%. At a concentration of 1000 μg/mL, black radish extract achieves a 24.93% inhibition rate of reactive oxygen species. Additionally, the black radish extract does not exhibit significant toxic effects on various physiological functions of C. elegans and notably enhances their lifespan.