Raddeanin A Protects the BRB Through Inhibiting Inflammation and Apoptosis in the Retina of Alzheimer's Disease.

Neuroinflammation and endothelial cell apoptosis are prominent features of blood-brain barrier (BBB) disruption, which have been described in Alzheimer's disease (AD) and can predict cognitive decline. Recent reports revealed vascular ß-amyloid (Aß) deposits, Muller cell degeneration and microglial dysfunction in the retina of AD patients. However, there has been no in-depth research on the roles of inflammation, retinal endothelial cell apoptosis, and blood-retinal barrier (BRB) damage in AD retinopathy. We found that Raddeanin A (RDA) could improve pathological and cognitive deficits in a mouse model of Alzheimer's disease by targeting ß-amyloidosis, However, the effects of RDA on AD retinal function require further study. To clarify whether RDA inhibits inflammation and apoptosis and thus improves BRB function in AD-related retinopathy. In vitro we used Aß-treated HRECs and MIO-M1 cells, and in vivo we used 3×Tg-AD mice to investigate the effect of RDA on BRB in AD-related retinopathy. We found that RDA could improve BRB function in AD-related retinopathy by inhibiting NLRP3-mediated inflammation and suppressing Wnt/ß-catenin pathway-mediated apoptosis, which is expected to improve the pathological changes in AD-related retinopathy and the quality of life of AD patients.

Penthorum chinense Pursh inhibits ferroptosis in cellular and Caenorhabditis elegans models of Alzheimer's disease.

BACKGROUND: Ferroptosis, a unique type of cell death triggered by iron-dependent lipid peroxidation, plays a critical role in the pathogenesis of Alzheimer's disease (AD), a debilitating condition marked by memory loss and cognitive impairment due to the accumulation of beta-amyloid (Aß) and hyperphosphorylated Tau protein. Increasing evidence suggests that inhibitors of ferroptosis could be groundbreaking in the treatment of AD. METHOD: In this study, we established in vitro ferroptosis using erastin-, RSL-3-, hemin-, and iFSP1-induced PC-12 cells. Using MTT along with Hoechst/PI staining, we assessed cell viability and death. To determine various aspects of ferroptosis, we employed fluorescence probes, including DCFDA, JC-1, C11 BODIPY, Mito-Tracker, and PGSK, to measure ROS production, mitochondrial membrane potential, lipid peroxidation, mitochondrial morphology, and intracellular iron levels. Additionally, Western blotting, biolayer interferometry technology, and shRNA were utilized to investigate the underlying molecular mechanisms. Furthermore, p-CAX APP Swe/Ind- and pRK5-EGFP-Tau P301L overexpressing PC-12 cells, along with Caenorhabditis elegans (C. elegans) strains CL4176, CL2331, and BR5270, were employed to examine ferroptosis in AD models. RESULTS: Here, we conducted a screening of our natural medicine libraries and identified the ethanol extract of Penthorum chinense Pursh (PEE), particularly its ethyl acetate fraction (PEF), displayed inhibitory effects on ferroptosis in cells. Specifically, PEF inhibited the generation of ROS, lipid peroxidation, and intracellular iron levels. Furthermore, PEF demonstrated protective effects against H2O2-induced cell death, ROS production, and mitochondrial damage. Mechanistic investigations unveiled PEF's modulation of intracellular iron accumulation, GPX4 expression and activity, and FSP1 expression. In p-CAX APP Swe/Ind and pRK5-EGFP-Tau P301L overexpressing PC-12 cells, PEF significantly reduced cell death, as well as ROS and lipid peroxidase production. Moreover, PEF ameliorated paralysis and slowing rate in Aß and Tau transgenic C. elegans models, while inhibiting ferroptosis, as evidenced by decreased DHE intensity, lipid peroxidation levels, iron accumulation, and expression of SOD-3 and gst-4. CONCLUSION: Our findings highlight the suppressive effects of PEF on ferroptosis in AD cellular and C. elegans models. This study helps us better understand how ferroptosis affects AD and emphasizes the potential of PCP as a candidate for AD intervention.

Suppressing inflammatory signals and apoptosis-linked sphingolipid metabolism underlies therapeutic potential of Qing-Jin-Hua-Tan decoction against chronic obstructive pulmonary disease.

Background: Qing-Jin-Hua-Tan decoction (QJHTD) is a classic traditional Chinese medicine (TCM) prescription that first appeared in the ancient book Yi-Xue-Tong-Zhi. QJHTD has shown effectiveness for treating chronic obstructive pulmonary disease (COPD), although its mechanisms of action are still perplexing. The molecular mechanisms underlying the curative effects of QJHTD on COPD is worth exploring. Methods: In vitro antiapoptotic and antiinflammatory activities of QJHTD were evaluated using cell viability, proliferation, apoptosis rate, and expression of IL-1ß and TNF-α in BEAS-2B and RAW264.7 cells challenged with cigarette smoke (CS) extract (CSE) and lipopolysaccharide (LPS). In vivo therapeutic activities of QJHTD were evaluated using respiratory parameters (peak inspiratory flow (PIFb) and peak expiratory flow (PEFb) values), histopathology (mean linear intercept, MLI), and proinflammatory cytokine (IL-1ß and TNF-α) and cleaved caspase-3 (c-Casp3) levels in the lung tissue of CS-LPS-exposed BALB/c mice. Network pharmacology-based prediction, transcriptomic analysis, and metabolic profiling were employed to investigate the signaling molecules and metabolites pertinent to the anti-COPD action of QJHTD. Results: Increased cell viability and proliferation with decreased apoptosis rate and proinflammatory cytokine expression were noted after QJHTD intervention. QJHTD administration elevated PEFb and PIFb values, reduced MLI, and inhibited IL-1ß, TNF-α, and c-Casp3 expression in vivo. Integrated network pharmacology-transcriptomics revealed that suppressing inflammatory signals (IL-1ß, IL-6, TNF, IκB-NF-κB, TLR, and MAPK) and apoptosis contributed to the anti-COPD property of QJHTD. Metabolomic profiling unveiled prominent roles for the suppression of apoptosis and sphingolipid (SL) metabolism and the promotion of choline (Ch) metabolism in the anti-COPD effect of QJHTD. Integrative transcriptomics-metabolomics unraveled the correlation between SL metabolism and apoptosis. In silico molecular docking revealed that acacetin, as an active compound in QJHTD, could bind with high affinity to MEK1, MEK2, ERK1, ERK2, Bcl2, NF-κB, and alCDase target proteins. Conclusion: The therapeutic effect of QJHTD on COPD is dependent on regulating inflammatory signals and apoptosis-directed SL metabolism. These findings provide deeper insights into the molecular mechanism of action of QJHTD against COPD and justify its theoretical promise in novel pharmacotherapy for this multifactorial disease.

Novel 18-norspirostane steroidal saponins: Extending lifespan and mitigating neurodegeneration through promotion of mitophagy and mitochondrial biogenesis in Caenorhabditis elegans.

Pharmacological strategies to delay aging and combat age-related diseases are increasingly promising. This study explores the anti-aging and therapeutic effects of two novel 18-norspirostane steroidal saponins from Trillium tschonoskii Maxim, namely deoxytrillenoside CA (DTCA) and epitrillenoside CA (ETCA), using Caenorhabditis elegans (C. elegans). Both DTCA and ETCA significantly extended the lifespan of wild-type N2 worms and improved various age-related phenotypes, including muscle health, motility, pumping rate, and lipofuscin accumulation. Furthermore, these compounds exhibited notable alleviation of pathology associated with Parkinson's disease (PD) and Huntington's disease (HD), such as the reduction of α-synuclein and poly40 aggregates, improvement in motor deficits, and mitigation of neuronal damage. Meanwhile, DTCA and ETCA improved the lifespan and healthspan of PD- and HD-like C. elegans models. Additionally, DTCA and ETCA enhanced the resilience of C. elegans against heat and oxidative stress challenges. Mechanistic studies elucidated that DTCA and ETCA induced mitophagy and promoted mitochondrial biogenesis in C. elegans, while genetic mutations or RNAi knockdown affecting mitophagy and mitochondrial biogenesis effectively eliminated their capacity to extend lifespan and reduce pathological protein aggregates. Together, these compelling findings highlight the potential of DTCA and ETCA as promising therapeutic interventions for delaying aging and preventing age-related diseases.

Carpesii fructus extract exhibits neuroprotective effects in cellular and Caenorhabditis elegans models of Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Despite extensive research, no definitive cure or effective disease-modifying treatment for PD exists to date. Therefore, the identification of novel therapeutic agents with neuroprotective properties is of utmost importance. Here, we aimed to investigate the potential neuroprotective effects of Carpesii fructus extract (CFE) in both cellular and Caenorhabditis elegans (C. elegans) models of PD. METHODS: The neuroprotective effect of CFE in H2O2- or 6-OHDA-induced PC-12 cells and α-synuclein-overexpressing PC-12 cells were investigated by determining the cell viability, mitochondrial damage, reactive oxygen species (ROS) production, apoptosis, and α-synuclein expression. In NL5901, BZ555, and N2 worms, the expression of α-synuclein, motive ability, the viability of dopaminergic neurons, lifespan, and aging-related phenotypes were investigated. The signaling pathway was detected by Western blotting and validated by employing small inhibitors and RNAi bacteria. RESULTS: In cellular models of PD, CFE significantly attenuated H2O2- or 6-OHDA-induced toxicity, as evidenced by increased cell viability and reduced apoptosis rate. In addition, CFE treatment suppressed ROS generation and restored mitochondrial membrane potential, highlighting its potential as a mitochondrial protective agent. Furthermore, CFE reduced the expression of α-synuclein in wide type (WT)-, A53T-, A30P-, or E46K-α-synuclein-overexpressing PC-12 cells. Our further findings reveal that CFE administration reduced α-synuclein expression and improved its induced locomotor deficits in NL5901 worms, protected dopaminergic neurons against 6-OHDA-induced degeneration in BZ555 worms, extended lifespan, delayed aging-related phenotypes, and enhanced the ability of stress resistance in N2 worms. Mechanistic studies suggest that the neuroprotective effects of CFE may involve the modulation of the MAPK signaling pathway, including ERK, JNK, and p38, whereas the interference of these pathways attenuated the neuroprotective effect of CFE in vitro and in vivo. CONCLUSION: Overall, our study highlights the potential therapeutic value of CFE as a neuroprotective agent in the context of PD. Furthermore, elucidation of the active compounds of CFE will provide valuable insights for the development of novel therapeutic strategies for PD.

The Protective Effects of Reineckia carnea Ether Fraction against Alzheimer's Disease Pathology: An Exploration in Caenorhabditis elegans Models.

Alzheimer's disease (AD) presents a significant challenge to global healthcare systems, with current treatments offering only modest relief and often bringing unwanted side effects, necessitating the exploration of more effective and safer drugs. In this study, we employed the Caenorhabditis elegans (C. elegans) model, specifically the AD-like CL4176 strain expressing the human Aß(1-42) protein, to investigate the potential of Reineckia carnea extract and its fractions. Our results showed that the Reineckia carnea ether fraction (REF) notably diminished the paralysis rates of CL4176 worms. Additionally, REF also attenuated the neurotoxicity effects prompted by Tau proteins in the BR5270 worms. Moreover, REF was observed to counteract the accumulation of Aß and pTau proteins and their induced oxidative stress in C. elegans AD-like models. Mechanistic studies revealed that REF's benefits were associated with the induction of autophagy in worms; however, these protective effects were nullified when autophagy-related genes were suppressed using RNAi bacteria. Together, these findings highlight Reineckia carnea ether fraction as a promising candidate for AD treatment, warranting further investigation into its autophagy-inducing components and their molecular mechanisms.

Mathematical modeling of climate and fluoride effects on sugarcane photosynthesis with silicon nanoparticles.

Fluoride (F-) stress is one of the major environmental pollutant, affecting plant growth, development and production, globally. Acquisition of eco-friendly F- stress reliever seems to be the major concern these days. Consequently, application of engineered nanomaterials (ENMs) has been increasing to improve agri-economy. However, the impact of silicon nanoparticles (Si NPs) on mitigation of F- stress has not been investigated yet. Thus, the present study was conducted to compare their protective roles against F- stress by improving diurnal photosynthetic efficiency of sugarcane plant leaves. An ability of sugarcane (Saccharum officinarum cv. GT44) plants to ameliorate F- toxicity assessed through soil culture medium. After an adaptive growth phase, 45 days old plants select to examine F- mitigative efficacy of silicon nanoparticles (SiNPs: 0, 100, 300 and 500 ppm) on sugarcane plants, irrigated by F- contaminated water (0, 100, 200 and 500 ppm). Our results strongly favour that SiNPs enhanced diurnally leaf photosynthetic gas exchange viz., photosynthesis (∼1.0-29%), stomatal conductance (∼3.0-90%), and transpiration rate (∼0.5-43%), significantly, as revealed by increments in photochemical chlorophyll fluorescence efficiency of PS II linked with performance index and photosynthetic pigments during F- stress. To the best of our knowledge, this is the first investigation to explore the impact of SiNPs improving and/or maintaining the diurnal photosynthetic responses in sugarcane plants in response to F- stress. It may also precisely unlayer action of molecular mechanism(s) mediated by SiNPs, found essential for mitigation of F--toxicity to explore nano-phytoremediation approach for crop improvement and agri-economy as well.

Poly (ADP-ribose) polymerase 1 and neurodegenerative diseases: Past, present, and future.

Poly (ADP-ribose) polymerase 1 (PARP1) is a first responder that recognizes DNA damage and facilitates its repair. Neurodegenerative diseases, characterized by progressive neuron loss driven by various risk factors, including DNA damage, have increasingly shed light on the pivotal involvement of PARP1. During the early phases of neurodegenerative diseases, PARP1 experiences controlled activation to swiftly address mild DNA damage, thereby contributing to maintain brain homeostasis. However, in late stages, exacerbated PARP1 activation precipitated by severe DNA damage exacerbates the disease condition. Consequently, inhibition of PARP1 overactivation emerges as a promising therapeutic approach for neurodegenerative diseases. In this review, we comprehensively synthesize and explore the multifaceted role of PARP1 in neurodegenerative diseases, with a particular emphasis on its over-activation in the aggregation of misfolded proteins, dysfunction of the autophagy-lysosome pathway, mitochondrial dysfunction, neuroinflammation, and blood-brain barrier (BBB) injury. Additionally, we encapsulate the therapeutic applications and limitations intrinsic of PARP1 inhibitors, mainly including limited specificity, intricate pathway dynamics, constrained clinical translation, and the heterogeneity of patient cohorts. We also explore and discuss the potential synergistic implementation of these inhibitors alongside other agents targeting DNA damage cascades within neurodegenerative diseases. Simultaneously, we propose several recommendations for the utilization of PARP1 inhibitors within the realm of neurodegenerative disorders, encompassing factors like the disease-specific roles of PARP1, combinatorial therapeutic strategies, and personalized medical interventions. Lastly, the encompassing review presents a forward-looking perspective along with strategic recommendations that could guide future research endeavors in this field.

Lychee seed polyphenol ameliorates DR via inhibiting inflammasome/apoptosis and angiogenesis in hRECs and db/db mice.

Blood retinal barrier (BRB) damage is an important pathogenesis of diabetic retinopathy, and alleviating BRB damage has become a key target for DR treatment. We previously found that Lycopene seed polyphenols (LSP) maintained BRB integrity by inhibiting NLRP3 inflammasome-mediated inflammation. However, it is still unknown whether LSP inhibits retinal neovascularization with abnormal capillaries and its mechanism of action. Here, we employed db/db mice and hRECs to find that LSP increases the level of glycolipid metabolism, maintains the morphology of retinal endothelial cells and inhibits acellular capillary neogenesis. Mechanistic studies revealed that LSP inhibits the NLRP3 inflammasome, reduces cell apoptosis in retinal tissue, increases tight junction protein (TJ) expression, and reduces vascular endothelial growth factor (VEGF) and Ve-Cadherin in vivo and in vitro. Collectively, this study finds that LSP inhibits inflammation and angiogenesis to improve BRB function to ameliorate DR.

Protective effects of Radix Stellariae extract against Alzheimer's disease via autophagy activation in Caenorhabditis elegans and cellular models.

Enhancing the clearance of proteins associated with Alzheimer's disease (AD) emerges as a promising approach for AD therapeutics. This study explores the potential of Radix Stellariae, a traditional Chinese medicine, in treating AD. Utilizing transgenic C. elegans models of AD, we demonstrated that a 75% ethanol extract of Radix Stellariae (RSE) (at 50 µg/mL) effectively diminishes Aß and Tau protein expression, and alleviates their induced impairments including paralysis, behavioral dysfunction, neurotoxicity, and ROS accumulation. Additionally, RSE enhances the stress resistance of C. elegans. Further investigations revealed that RSE promotes autophagy, a critical cellular process for protein degradation, in these models. We found that inhibiting autophagy-related genes negated the neuroprotective effects of RSE, suggesting a central role for autophagy in the actions of RSE. In PC-12 cells, we observed that RSE not only inhibited Aß fibril formation but also promoted the degradation of AD-related proteins and reduced their cytotoxicity. Mechanistically, RSE was found to induce autophagy via modulating PI3K/AKT/mTOR and AMPK/mTOR signaling pathways. Importantly, inhibiting autophagy counteracted the beneficial effects of RSE on the clearance of AD-associated proteins. Moreover, we identified Dichotomine B, a ß-carboline alkaloid, as a key active constituent of RSE in mitigating AD pathology in C. elegans at concentrations ranging from 50 to 1000 µM. Collectively, our study presents novel discoveries that RSE alleviates AD pathology and toxicity primarily by inducing autophagy, both in vivo and in vitro. These findings open up new avenues for exploring the therapeutic potential of RSE and its active component, Dichotomine B, in treating neurodegenerative diseases like AD.

Ameliorative effect of Luffa cylindrica fruits on Caenorhabditis elegans and cellular models of Alzheimer's disease-related pathology via autophagy induction.

BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder without an effective cure. Natural products, while showing promise as potential therapeutics for AD, remain underexplored. AIMS: This study was conducted with the goal of identifying potential anti-AD candidates from natural sources using Caenorhabditis elegans (C. elegans) AD-like models and exploring their mechanisms of action. MATERIALS & METHODS: Our laboratory's in-house herbal extract library was utilized to screen for potential anti-AD candidates using the C. elegans AD-like model CL4176. The neuroprotective effects of the candidates were evaluated in multiple C. elegans AD-like models, specifically targeting Aß- and Tau-induced pathology. In vitro validation was conducted using PC-12 cells. To investigate the role of autophagy in mediating the anti-AD effects of the candidates, RNAi bacteria and autophagy inhibitors were employed. RESULTS: The ethanol extract of air-dried fruits of Luffa cylindrica (LCE), a medicine-food homology species, was found to inhibit Aß- and Tau-induced pathology (paralysis, ROS production, neurotoxicity, and Aß and pTau deposition) in C. elegans AD-like models. LCE was non-toxic and enhanced C. elegans' health. It was shown that LCE activates autophagy and its anti-AD efficacy is weakened with the RNAi knockdown of autophagy-related genes. Additionally, LCE induced mTOR-mediated autophagy, reduced the expression of AD-associated proteins, and decreased cell death in PC-12 cells, which was reversed by autophagy inhibitors (bafilomycin A1 and 3-methyladenine). DISCUSSION: LCE, identified from our natural product library, emerged as a valuable autophagy enhancer that effectively protects against neurodegeneration in multiple AD-like models. RNAi knockdown of autophagy-related genes and cotreatment with autophagy inhibitors weakened its anti-AD efficacy, implying a critical role of autophagy in mediating the neuroprotective effects of LCE. CONCLUSION: Our findings highlight the potential of LCE as a functional food or drug for targeting AD pathology and promoting human health.

Targeting autophagy to discover the Piper wallichii petroleum ether fraction exhibiting antiaging and anti-Alzheimer's disease effects in Caenorhabditis elegans.

BACKGROUND: With population aging, the incidence of aging-related Alzheimer's disease (AD) is increasing, accompanied by decreased autophagy activity. At present, Caenorhabditis elegans (C. elegans) is widely employed to evaluate autophagy and in research on aging and aging-related diseases in vivo. To discover autophagy activators from natural medicines and investigate their therapeutic potential in antiaging and anti-AD effects, multiple C. elegans models related to autophagy, aging, and AD were used. METHOD: In this study, we employed the DA2123 and BC12921 strains to discover potential autophagy inducers using a self-established natural medicine library. The antiaging effect was evaluated by determining the lifespan, motor ability, pumping rate, lipofuscin accumulation of worms, and resistance ability of worms under various stresses. In addition, the anti-AD effect was examined by detecting the paralysis rate, food-sensing behavior, and amyloid-ß and Tau pathology in C. elegans. Moreover, RNAi technology was used to knock down the genes related to autophagy induction. RESULTS: We discovered that Piper wallichii extract (PE) and the petroleum ether fraction (PPF) activated autophagy in C. elegans, as evidenced by increased GFP-tagged LGG-1 foci and decreased GFP-p62 expression. In addition, PPF extended the lifespan and enhanced the healthspan of worms by increasing body bends and pumping rates, decreasing lipofuscin accumulation, and increasing resistance to oxidative, heat, and pathogenic stress. Moreover, PPF exhibited an anti-AD effect by decreasing the paralysis rate, improving the pumping rate and slowing rate, and alleviating Aß and Tau pathology in AD worms. However, the feeding of RNAi bacteria targeting unc-51, bec-1, lgg-1, and vps-34 abolished the antiaging and anti-AD effects of PPF. CONCLUSION: Piper wallichii may be a promising drug for antiaging and anti-AD. More future studies are also needed to identify autophagy inducers in Piper wallichii and clarify their molecular mechanisms.

The Application of Biomaterials in Spinal Cord Injury.

The spinal cord and the brain form the central nervous system (CNS), which is the most important part of the body. However, spinal cord injury (SCI) caused by external forces is one of the most difficult types of neurological injury to treat, resulting in reduced or even absent motor, sensory and autonomic functions. It leads to the reduction or even disappearance of motor, sensory and self-organizing nerve functions. Currently, its incidence is increasing each year worldwide. Therefore, the development of treatments for SCI is urgently needed in the clinic. To date, surgery, drug therapy, stem cell transplantation, regenerative medicine, and rehabilitation therapy have been developed for the treatment of SCI. Among them, regenerative biomaterials that use tissue engineering and bioscaffolds to transport cells or drugs to the injured site are considered the most promising option. In this review, we briefly introduce SCI and its molecular mechanism and summarize the application of biomaterials in the repair and regeneration of tissue in various models of SCI. However, there is still limited evidence about the treatment of SCI with biomaterials in the clinic. Finally, this review will provide inspiration and direction for the future study and application of biomaterials in the treatment of SCI.

Folium Hibisci Mutabilis extract, a potent autophagy enhancer, exhibits neuroprotective properties in multiple models of neurodegenerative diseases.

BACKGROUND: Protein aggregates are considered key pathological features in neurodegenerative diseases (NDs). The induction of autophagy can effectively promote the clearance of ND-related misfolded proteins. OBJECTIVE: In this study, we aimed to screen natural autophagy enhancers from traditional Chinese medicines (TCMs) presenting potent neuroprotective potential in multiple ND models. METHODS: The autophagy enhancers were broadly screened in our established herbal extract library using the transgenic Caenorhabditis elegans (C. elegans) DA2123 strain. The neuroprotective effects of the identified autophagy enhancers were evaluated in multiple C. elegans ND models by measuring Aß-, Tau-, α-synuclein-, and polyQ40-induced pathologies. In addition, PC-12 cells and 3 × Tg-AD mice were employed to further validate the neuroprotective ability of the identified autophagy enhancers, both in vitro and in vivo. Furthermore, RNAi bacteria and autophagy inhibitors were used to evaluate whether the observed effects of the identified autophagy enhancers were mediated by the autophagy-activated pathway. RESULTS: The ethanol extract of Folium Hibisci Mutabilis (FHME) was found to significantly increase GFP::LGG-1-positive puncta in the DA2123 worms. FHME treatment markedly inhibited Aß, α-synuclein, and polyQ40, as well as prolonging the lifespan and improving the behaviors of C. elegans, while siRNA targeting four key autophagy genes partly abrogated the protective roles of FHME in C. elegans. Additionally, FHME decreased the expression of AD-related proteins and restored cell viability in PC-12 cells, which were canceled by cotreatment with 3-methyladenine (3-MA) or bafilomycin A1 (Baf). Moreover, FHME ameliorated AD-like cognitive impairment and pathology, as well as activating autophagy in 3 × Tg-AD mice. CONCLUSION: FHME was successfully screened from our natural product library as a potent autophagy enhancer that exhibits a neuroprotective effect in multiple ND models across species through the induction of autophagy. These findings offer a new and reliable strategy for screening autophagy inducers, as well as providing evidence that FHME may serve as a possible therapeutic agent for NDs.

Chlorogenic acid delays the progression of Parkinson's disease via autophagy induction in Caenorhabditis elegans.

OBJECTIVES: Parkinson's disease (PD) is the second most common neurodegenerative disease. Chlorogenic acid (CGA) is a polyphenolic substance derived from various medicinal plants. Although CGA is reported to have potential anti-PD effect, the beneficial effect and the underlying mechanism remain unclear. In this study, we aimed to further investigate the protective effect and clarify the mechanism of action of CGA in Caenorhabditis elegans (C. elegans) models of PD. METHODS: Measurements of a-synuclein aggregation, movement disorders, and lipid, ROS and malondialdehyde (MDA) contents were observed in NL5901 nematodes. Determinations of dopamine (DA) neuron degeneration, food perception, and ROS content were performed in 6-OHDA-exposed BZ555 nematodes. The autophagy activation of CGA was monitored using DA2123 and BC12921 nematodes. Meanwhile, RNAi technology was employed to knockdown the autophagy-related genes and investigate whether the anti-PD effect of CGA was associated with autophagy induction in C. elegans. RESULTS: CGA significantly reduced α-synuclein aggregation, improved motor disorders, restored lipid content, and decreased ROS and MDA contents in NL5901 nematodes. Meanwhile, CGA inhibited DA neuron-degeneration and improved food-sensing behavior in 6-OHDA-exposed BZ555 nematodes. In addition, CGA increased the number of GFP::LGG-1 foci in DA2123 nematodes and degraded p62 protein in BC12921 nematodes. Meanwhile, CGA up-regulated the expression of autophagy-related genes in NL5901 nematodes. Moreover, the anti-PD effect of CGA was closely related to autophagy induction via increasing the expression of autophagy-related genes, including unc-51, bec-1, vps-34, and lgg-1. CONCLUSIONS: The present study indicates that CGA exerts neuroprotective effect in C. elegans via autophagy induction.

Therapeutic potential of Polygala saponins in neurological diseases.

BACKGROUND: There are many types of neurological diseases with complex etiologies. At present, most clinical drugs can only relieve symptoms but cannot cure these diseases. Radix Polygalae, a famous traditional Chinese medicine from the root of plants of the genus Polygala, has the traditional effect of treating insomnia, forgetfulness, and palpitation and improving intelligence and other symptoms of neurological diseases. Saponins are important bioactive components of plants of the genus Polygala and exhibit neuroprotective effects. PURPOSE: This review aimed to summarize the traditional use of Polygala species and discuss the latest phytochemical, pharmacological, and toxicological findings, mainly with regard to Polygala saponins in the treatment of neurological disorders. METHODS: Literature was searched and collected using databases, including PubMed, Science Direct, CNKI, and Google Scholar. The search terms used included "Polygala", "saponins", "neurological diseases", "Alzheimer's disease", "toxicity", etc., and combinations of these keywords. A total of 1202 papers were retrieved until August 2022, and we included 135 of these papers on traditional uses, phytochemistry, pharmacology, toxicology and other fields. RESULTS: This literature review mainly reports on the traditional use of the Polygala genus and prescriptions containing Radix Polygalae in neurological diseases. Phytochemical studies have shown that plants of the genus Polygala mainly include saponins, flavonoids, oligosaccharide esters, alkaloids, coumarins, lignans, flavonoids, etc. Among them, saponins are the majority. Modern pharmacological studies have shown that Polygala saponins have neuroprotective effects on a variety of neurological diseases. Its mechanism of action involves autophagic degradation of misfolded proteins, anti-inflammatory, anti-apoptotic, antioxidative stress and so on. Toxicological studies have shown that Polygala saponins trigger gastrointestinal toxicity, and honey processing and glycosyl disruption of Polygala saponins can effectively ameliorate its gastrointestinal side effect. CONCLUSION: Polygala saponins are the major bioactive components in plants of the genus Polygala that exhibit therapeutic potential in various neurological diseases. This review provides directions for the future study of Polygala saponins and references for the clinical use of prescriptions containing Radix Polygalae for the treatment of neurological diseases.

The Therapeutic Potential of Plant Polysaccharides in Metabolic Diseases.

Plant polysaccharides (PPS) composed of more than 10 monosaccharides show high safety and various pharmacological activities, including immunoregulatory, antitumor, antioxidative, antiaging, and other effects. In recent years, emerging evidence has indicated that many PPS are beneficial for metabolic diseases, such as cardiovascular disease (CVD), diabetes, obesity, and neurological diseases, which are usually caused by the metabolic disorder of fat, sugar, and protein. In this review, we introduce the common characteristics and functional activity of many representative PPS, emphasize the common risks and molecular mechanism of metabolic diseases, and discuss the pharmacological activity and mechanism of action of representative PPS obtained from plants including Aloe vera, Angelica sinensis, pumpkin, Lycium barbarum, Ginseng, Schisandra chinensis, Dioscorea pposite, Poria cocos, and tea in metabolic diseases. Finally, this review will provide directions and a reference for future research and for the development of PPS into potential drugs for the treatment of metabolic diseases.

Concurrent severe hepatotoxicity and agranulocytosis induced by Polygonum multiflorum: A case report.

BACKGROUND: Various types of drug-induced liver injury are induced by Polygonum multiflorum (PM); however, it rarely causes neutropenia. Herein, we report the case of a 65-year-old woman with concurrent severe hepatotoxicity and agranulocytosis induced by PM. CASE SUMMARY: A 65-year-old woman reported with severe hepatotoxicity and agranulocytosis 17 d after ingestion of PM. The results of the Roussel Uclaf Causality Assessment Method demonstrated a highly probable relationship between hepatotoxicity and PM, with a total score of 10. The Naranjo algorithm results indicated that agranulocytosis had a probable relationship with PM, with an overall score of 6. Granulocyte colony-stimulating factor (for once), a steroid, compound glycyrrhizin, and polyene phosphatidylcholine therapy were initiated. After 15 d of treatment, there was a gradual improvement in liver biochemistry, leukocytes, and neutrophils levels. CONCLUSION: Concurrent hepatotoxicity and agranulocytosis are rare and critical adverse drug reactions of PM, which should be highly valued.

Genetic engineering: an efficient approach to mitigating biotic and abiotic stresses in sugarcane cultivation.

Abiotic stresses are the foremost limiting factors for crop productivity. Crop plants need to cope with adverse external pressure caused by various environmental conditions with their intrinsic biological mechanisms to keep their growth, development, and productivity. Climate-resilient, high-yielding crops need to be developed to maintain sustainable food supply. Over the last decade, understanding of the genetic complexity of agronomic traits in sugarcane has prompted the integrated application of genetic engineering to address specific biological questions. Genes for adaptation to environmental stress and yield enhancement traits are being determined and introgressed to develop elite sugarcane cultivars with improved characteristics through genetic engineering approaches. Here, we discuss the advancement to provide a reference for future sugarcane (Saccharum spp.) genetic engineering.