Protective Effect of Que Zui Tea on d-Galactose-Induced Oxidative Stress Damage in Mice via Regulating SIRT1/Nrf2 Signaling Pathway.

Que Zui tea (QT) is an important herbal tea in the diet of the 'Yi' people, an ethnic group in China, and it has shown significant antioxidant, anti-inflammatory, and hepatoprotective effects in vitro. This study aims to explore the protective effects of the aqueous-ethanol extract (QE) taken from QT against ᴅ-galactose (ᴅ-gal)-induced oxidative stress damage in mice and its potential mechanisms. QE was identified as UHPLC-HRMS/MS for its chemical composition and possible bioactive substances. Thus, QE is rich in phenolic and flavonoid compounds. Twelve compounds were identified, the main components of which were chlorogenic acid, quinic acid, and 6'-O-caffeoylarbutin. Histopathological and biochemical analysis revealed that QE significantly alleviated brain, liver, and kidney damage in ᴅ-gal-treated mice. Moreover, QE remarkably attenuated oxidative stress by activating the Nrf2/HO-1 pathway to increase the expression of antioxidant indexes, including GSH, GSH-Px, CAT, SOD, and T-AOC. In addition, QE administration could inhibit the IL-1ß and IL-6 levels, which suppress the inflammatory response. QE could noticeably alleviate apoptosis by inhibiting the expressions of Caspase-3 and Bax proteins in the brains, livers, and kidneys of mice. The anti-apoptosis mechanism may be related to the upregulation of the SIRT1 protein and the downregulation of the p53 protein induced by QE in the brain, liver, and kidney tissues of mice. Molecular docking analysis demonstrated that the main components of QE, 6'-O-caffeoylarbutin, chlorogenic acid, quinic acid, and robustaside A, had good binding ability with Nrf2 and SIRT1 proteins. The present study indicated that QE could alleviate ᴅ-gal-induced brain, liver and kidney damage in mice by inhibiting the oxidative stress and cell apoptosis; additionally, the potential mechanism may be associated with the SIRT1/Nrf2 signaling pathway.

Neuroprotective potential of Erigeron bonariensis ethanolic extract against ovariectomized/D-galactose-induced memory impairments in female rats in relation to its metabolite fingerprint as revealed using UPLC/MS.

Erigeron bonariensis is widely distributed throughout the world's tropics and subtropics. In folk medicine, E. bonariensis has historically been used to treat head and brain diseases. Alzheimer's disease (AD) is the most widespread form of dementia initiated via disturbances in brain function. Herein, the neuroprotective effect of the chemically characterized E. bonariensis ethanolic extract is reported for the first time in an AD animal model. Chemical profiling was conducted using UPLC-ESI-MS analysis. Female rats underwent ovariectomy (OVX) followed by 42 days of D-galactose (D-Gal) administration (150 mg/kg/day, i.p) to induce AD. The OVX/D-Gal-subjected rats received either donepezil (5 mg/kg/day) or E. bonariensis at 50, 100, and 200 mg/kg/day, given 1 h prior to D-Gal. UPLC-ESI-MS analysis identified 42 chemicals, including flavonoids, phenolic acids, terpenes, and nitrogenous constituents. Several metabolites, such as isoschaftoside, casticin, velutin, pantothenic acid, xanthurenic acid, C18-sphingosine, linoleamide, and erucamide, were reported herein for the first time in Erigeron genus. Treatment with E. bonariensis extract mitigated the cognitive decline in the Morris Water Maze test and the histopathological alterations in cortical and hippocampal tissues of OVX/D-Gal-subjected rats. Moreover, E. bonariensis extract mitigated OVX/D-Gal-induced Aß aggregation, Tau hyperphosphorylation, AChE activity, neuroinflammation (NF-κBp65, TNF-α, IL-1ß), and apoptosis (Cytc, BAX). Additionally, E. bonariensis extract ameliorated AD by increasing α7-nAChRs expression, down-regulating GSK-3ß and FOXO3a expression, and modulating Jak2/STAT3/NF-ĸB p65 and PI3K/AKT signaling cascades. These findings demonstrate the neuroprotective and memory-enhancing effects of E. bonariensis extract in the OVX/D-Gal rat model, highlighting its potential as a promising candidate for AD management.

Rutin attenuates D-galactose-induced oxidative stress in rats' brain and liver: molecular docking and experimental approaches.

Oxidative stress results from the imbalance between reactive oxygen species (ROS) production and antioxidant defence and is primarily involved in aging. The current study investigated the antioxidant activity of rutin in aging in rats induced by D-galactose (D-gal) for 42 days. Rutin was orally used at doses of 50 and 100 mg kg-1 daily. Results showed that D-gal induced oxidative alterations in the brain and liver recognized via upregulation of aging and oxidative markers. In contrast, rutin ameliorated the oxidative stress induced by D-gal by enhancing antioxidant markers such as superoxide dismutase-1, glutathione peroxidase-1, and glutathione S-transferase-α. Also, rutin significantly decreased the accumulation of ß-galactosidase and reduced the expression of p53, p21, Bcl-2-associated X protein (Bax), caspase-3 (CASP3), and mammalian target of rapamycin (mTOR) in brain and hepatic tissues. Rutin potentially attenuated these aging-related oxidative alterations in a dose-dependent manner. Moreover, rutin markedly reduced the increased immunohistochemical expression of ß-galactosidase, 8-hydroxy-2'-deoxyguanosine, calcium-binding adapter molecule 1, glial fibrillary acidic protein, Bax, and interleukin-6 and significantly increased Bcl2, synaptophysin, and Ki67. Furthermore, a molecular docking study revealed that rutin exhibited high affinity to rat and human caspases, PI3K/AKT/mTOR, and the IL-6 receptor. Finally, we can conclude that rutin supplementation can be a promising natural protective compound that could delay aging and maintain health.

20(S)-protopanaxatriol inhibited D-galactose-induced brain aging in mice via promoting mitochondrial autophagy flow.

Previous reports have confirmed that saponins (ginsenosides) derived from Panax ginseng. C. A. Meyer exerted obvious memory-enhancing and antiaging effects, and the simpler the structure of ginsenosides, the better the biological activity. In this work, we aimed to explore the therapeutic effect and underlying molecular mechanism of 20(S)-protopanaxatriol (PPT), the aglycone of panaxatriol-type ginsenosides, by establishing D-galactose (D-gal)-induced subacute brain aging model in mice. The results showed that PPT treatment (10 and 20 mg/kg) for 4 weeks could significantly restore the D-gal (800 mg/kg for 8 weeks)-induced impaired memory function, choline dysfunction, and redox system imbalance in mice. Meanwhile, PPT also significantly reduced the histopathological changes caused by D-gal exposure. Moreover, PPT could increase TFEB/LAMP2 protein expression to promote mitochondrial autophagic flow. Importantly, the results from molecular docking showed that PPT had good binding ability with LAMP2 and TFEB, suggesting that TFEB/LAMP2 might play an important role in PPT to alleviate D-gal-caused brain aging.

Gouqizi () seed oil reduces D-galactose induced inflammation in testis of rats Janus kinase 1/signal transducerand activator of transcription 1/nuclear factor-κB and.

OBJECTIVE: To investigate the efficacy of Gouqizi () seed oil (FLSO) on D-gal induced inflammation in testis of rats and . METHODS: In aging Sertoli cells (TM4 cells) induced by D-galactose (D-gal), the expression of upregulated aging-related proteins. The number of cells counted by cell counting kit (CCK)-8 assay showed a high number of cells disposed with FLSO at 50, 100 and 150 µg/mL compared to that for the aging model. , male Sprague-Dawley rats ( = 50, 8-week-old, 230-255 g) were randomly categorized into control, aging model, and FLSO (low-, medium-, and high-dose) groups. The expression of nuclear factor-κB (NF-κB) and its upstream factors [Janus kinase 1 (JAK1) and signal transducerand activator of transcription 1 (STAT1)] was detected by Western blot and immunofluorescence, related inflammatory factors quantified by enzyme-linked immunosorbent assay. Evaluation of testicular tissue by Johnsen score, the spermatogenic function was explored. RESULTS: The expression of interleukin-1ß (IL-1ß) ( < 0.05), IL-6 ( < 0.001), and tumor necrosis factor α (TNF-α) ( < 0.05) was decreased significantly, while that of heme oxygenase-1 (HO-1) ( < 0.001) and IL-10 ( < 0.05) was increased in cells disposed with FLSO 100 µg/mL. FLSO inhibited the expression of NF-B and declined p-p65/p65 ( < 0.01), as detected by Western blotting. In, the levels in serum of IL-1ß ( < 0.001), IL-6 ( < 0.05), and TNF-( < 0.01) declined while IL-10 ( < 0.05) was upregulated post-FLSO treatment. In addition, the expression of JAK-1 and STAT1 increased significantly in testicular tissue of rats treated with FLSO as compared to the aging model of rats ( < 0.001), while the expression of NF-κB ( < 0.001) declined in the testis in the FLSO group, as assessed by immunofluorescence. The levels of inhibor B and testosterone in serum both increased (< 0.05). CONCLUSIONS: In conclusion, this study determined the protective effects of FLSO to tolerate inflammatory injury in the testis, indicating that FLSO alleviates inflammation JAK-1/STAT1/NF-κB pathway.

Chlorogenic acid combined with epigallocatechin-3-gallate mitigates D-galactose-induced gut aging in mice.

Chlorogenic acid (CGA) and epigallocatechin-3-gallate (EGCG) are major polyphenolic constituents of coffee and green tea with beneficial health properties. In this study, we evaluated the gut protecting effect of CGA and EGCG, alone or in combination, on D-galactose-induced aging mice. CGA plus EGCG more effectively improved the cognition deficits and protected the gut barrier function, compared with the agents alone. Specifically, CGA plus EGCG prevented the D-galactose mediated reactive oxygen species accumulation by increasing the total antioxidant capacity, reducing the levels of malondialdehyde, and suppressing the activity of the antioxidant enzymes superoxide dismutase and catalase. In addition, supplementation of CGA and EGCG suppressed gut inflammation by reducing the levels of the proinflammatory cytokines TNFα, IFNγ, IL-1ß and IL-6. Moreover, CGA and EGCG modulated the gut microbiome altered by D-galactose. For instance, CGA plus EGCG restored the Firmicutes/Bacteroidetes ratio of the aging mice to control levels. Furthermore, CGA plus EGCG decreased the abundance of Lactobacillaceae, Erysipelotrichaceae, and Deferribacteraceae, while increased the abundance of Lachnospiraceae, Muribaculaceae, and Rikenellaceae, at the family level. In conclusion, CGA in combination with EGCG ameliorated the gut alterations induced by aging, in part, through antioxidant and anti-inflammatory effects, along with its gut microbiota modulatory capacity.

Inhibiting mitochondrial inflammation through Drp1/HK1/NLRP3 pathway: A mechanism of alpinetin attenuated aging-associated cognitive impairment.

Mitochondrial inflammation triggered by abnormal mitochondrial division and regulated by the Drp1/HK1/NLRP3 pathway is correlated with the progression of aging-associated cognitive impairment (AACI). Alpinetin is a novel flavonoid derived from Zingiberaceae that has many bioactivities such as antiinflammation and anti-oxidation. However, whether alpinetin alleviates AACI by suppressing Drp1/HK1/NLRP3 pathway-inhibited mitochondrial inflammation is still unknown. In the present study, D-galactose (D-gal)-induced aging mice and BV-2 cells were used, and the effects of alpinetin on learning and memory function, neuroprotection and activation of the Drp1/HK1/NLRP3 pathway were investigated. Our data indicated that alpinetin significantly alleviated cognitive dysfunction and neuronal damage in the CA1 and CA3 regions of D-gal-treated mice. Moreover, D-gal-induced microglial activation was markedly reduced by alpinetin by inhibiting the Drp1/HK1/NLRP3 pathway-suppressed mitochondrial inflammation, down-regulating the levels of p-Drp1 (s616), VDAC, NLRP3, ASC, Cleaved-caspase 1, IL-18, and IL-1ß, and up-regulating the expression of HK1. Furthermore, after Drp1 inhibition by Mdivi-1 in vitro, the inhibitory effect of alpinetin on Drp1/HK1/NLRP3 pathway was more evident. In summary, the current results implied that alpinetin attenuated aging-related cognitive deficits by inhibiting the Drp1/HK1/NLRP3 pathway and suppressing mitochondrial inflammation, suggesting that the inhibition of the Drp1/HK1/NLRP3 pathway is one of the mechanisms by which alpinetin attenuates AACI.

Cornuside, by regulating the AGEs-RAGE-IκBα-ERK1/2 signaling pathway, ameliorates cognitive impairment associated with brain aging.

Anti-Alzheimer's disease (AD) drugs can only change the symptoms of cognitive impairment in a short time but cannot prevent or completely cure AD. Thus, a more effective drug is urgently needed. Cornuside is extracted from Corni Fructus, a traditional Chinese medicine that plays an important role in treating dementia and other age-related diseases. Thus, the study aimed to explore the effects and mechanisms of Cornuside on the D-galactose (D-Gal) induced aging mice accompanied by cognitive decline. Initially, we found that Cornuside improved the learning and memory abilities of D-Gal-treated mice in behavioral experiments. Pharmacological experiments indicated that Cornuside acted on anti-oxidant and anti-inflammatory effects. Cornuside also reversed acetylcholin esterase (AChE) activity. Meanwhile, pathology tests showed that Cornuside had a protective effect on neuron damage. Cornuside increased the expression of brain-derived neurotrophic factor (BDNF), and down-regulated the expression of receptor for advanced glycosylation end products (RAGE), ionized calcium binding adapter molecule 1 (Iba1), and glial fibrillary acidic protein (GFAP) respectively. Further studies claimed that Cornuside had important effects on the expression of IκBα and extracellular signal-regulated kinases 1/2 (ERK1/2). These effects might be achieved through regulating the AGEs-RAGE-IκBα-ERK1/2 signaling pathway, among which, ERK1/2 might be the key protein. The study provides direct preclinical evidence for the research of Cornuside, which may become an excellent candidate drug for the treatment of aging-related AD.

S-adenosylmethionine improves cognitive impairment in D-galactose-induced brain aging by inhibiting oxidative stress and neuroinflammation.

Oxidative stress and neuroinflammation play crucial roles in aging. S-adenosylmethionine (SAM), a popular supplement, is a potential antioxidant and candidate therapy for depression. This study aimed to evaluate the neuroprotective effects of SAM on D-galactose-induced brain aging and explore its underlying mechanisms. Brain aging model was established with D-galactose (180 mg/kg/day) for 8 weeks. During the last 4 weeks, SAM (16 mg/kg) was co-administrated with D-galactose. Behavior tests were used to assess cognitive function and depression-like behaviors of rats. Results showed that cognitive impairment and depression-like behaviors were reversed by SAM. SAM reduced neuronal cell loss, increased brain-derived neurotrophic factor level in the hippocampus, inhibited amyloid-ß level and microglia activation, as well as pro-inflammatory factors levels in the hippocampus and serum. Further, SAM enhanced antioxidant capacity and attenuated cholinergic damage by reducing malondialdehyde levels, increasing acetylcholine levels, expression levels of α7 nicotinic acetylcholine receptor (α7nAChR), nuclear factor erythrocyte 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the hippocampus. Above all, SAM has a potential neuroprotective effect on ameliorating cognitive impairment in brain aging, which is related to inhibition of oxidative stress and neuroinflammation, as well as α7nAChR signals. DATA AVAILABILITY: Data will be made available on request.

In vivo antioxidant activity of Cinnamomum cassia leaf residues and their effect on gut microbiota of d-galactose-induced aging model mice.

BACKGROUND: To thoroughly explore the values of Cinnamomum cassia leaf residues (CcLR), their antioxidant activity in vivo and the relationship with gut microbiota were investigated using d-galactose-induced aging mice. RESULTS: Results showed that CcLR extract treatment exerted antioxidant activity by increasing the levels of superoxide dismutase (P < 0.01) and glutathione peroxidase (P < 0.05), as well as inhibiting the formation of malondialdehyde (P < 0.01). Meanwhile, the inflammatory response was also alleviated as the ratio of pro-inflammatory tumor necrosis factor-α (P < 0.01) and interleukin-1ß (P < 0.01))/anti-inflammatory cytokines (interleukin-10; P < 0.05) in serum was decreased and the contents of inflammatory markers (induced nitrogen monoxide synthase and nitric oxide) in brain and liver tissues (P < 0.01) were reduced. Moreover, through inhibiting acetylcholinesterase activity and improving choline acetyltransferase activity, the cholinergic system in aging mice recovered to levels comparable to the normal control group. In addition, 16S rRNA sequencing results demonstrated that CcLR extract promoted the growth of beneficial bacteria. In particular, Spearman correlation analysis revealed that the abundance of Colidextribacter was negatively correlated with serum superoxide dismutase (P < 0.05, R = -0.943), and Helicobacter displayed a positive correlation with the content of brain nitric oxide (P < 0.05, R = 0.899), suggesting that regulating gut microbiota might be one of the mechanisms for reducing oxidative stress, thus postponing the aging process. CONCLUSION: It is suggested that CcLR extract could be used as a novel antioxidant and anti-aging resource in the pharmaceutical and food industries. © 2022 Society of Chemical Industry.

Network Proximity Analysis Deciphers the Pharmacological Mechanism of Osthole against D-Galactose Induced Cognitive Disorder in Rats.

Osthole, a natural coumarin found in various medicinal plants, has been previously reported to have neuroprotective effects. However, the specific mechanism by which Osthole alleviates dysmnesia associated with Alzheimer's disease (AD) remains unclear. This study aimed to investigate the neuroprotective properties of Osthole against cognitive impairment in rats induced by D-galactose and elucidate its pharmacological mechanism. The rat model was established by subcutaneously injecting D-galactose at a dose of 150 mg/kg/day for 56 days. The effect of Osthole on cognitive impairment was evaluated by behavior and biochemical analysis. Subsequently, a combination of in silico prediction and experimental validation was performed to verify the network-based predictions, using western blot, Nissl staining, and immunofluorescence. The results demonstrate that Osthole could improve memory dysfunction induced by D-galactose in Sprague Dawley male rats. A network proximity-based approach and integrated pathways analysis highlight two key AD-related pathological processes that may be regulated by Osthole, including neuronal apoptosis, i.e., neuroinflammation. Among them, the pro-apoptotic markers (Bax), anti-apoptotic protein (Bcl-2), the microgliosis (Iba-1), Astro-cytosis (GFAP), and inflammatory cytokines (TNF-R1) were evaluated in both hippocampus and cortex. The results indicated that Osthole significantly ameliorated neuronal apoptosis and neuroinflammation in D-galactose-induced cognitive impairment rats. In conclusion, this study sheds light on the pharmacological mechanism of Osthole in mitigating D-galactose-induced memory impairment and identifies Osthole as a potential drug candidate for AD treatment, targeting multiple signaling pathways through network proximity and integrated pathways analysis.

[Yigong Powder regulates CXCL12/CXCR4 signaling to reduce glutamate release and prevent cognitive decline in mouse model of aging].

This study aims to explore the effect of preventive administration of Yigong Powder on the learning and memory abilities of the mouse model of aging induced by D-galactose and decipher the underlying mechanism, so as to provide a basis for the application of Yigong Powder in the prevention and treatment of cognitive decline. Forty KM mice were randomized into control, model, donepezil(1.5 mg·kg~(-1)), and high-dose(7.5 g·kg~(-1)) and low-dose(3.75 g·kg~(-1)) Yigong Powder groups. The mice in other groups except the control group were injected with D-galactose(200 g·kg~(-1)) at the back of the neck for the modeling of aging. At the same time, the mice were administrated with corresponding drugs by gavage for one month. Morris water maze was used to examine the learning and memory abilities of the mice. Hematoxylin-eosin staining was employed to observe the pathological and morphological changes of the hippocampus. The immunofluorescence assay was employed to detect the expression of ionized calcium-binding adapter molecule 1(IBA1), glial fibrillary acidic protein(GFAP), chemokine C-X-C-motif ligand 12(CXCL12), chemokine C-X-C-motif receptor 4(CXCR4) in the hippocampus and observe the positional relationship between IBA1, GFAP, and CXCR4. Western blot was employed to determine the protein levels of extracellular regulated kinase(ERK), p-ERK, and tumor necrosis factor receptor 1(TNFR1). Enzyme-linked immunosorbent assay was employed to measure the levels of glutamate and tumor necrosis factor(TNF-α) in the brain tissue and the level of TNF-α in the serum and spleen. Yigong Powder significantly shortened the escape latency, increased the times crossing platforms, and prolonged the cumulative time in quadrants of the aging mice. It alleviated the nerve cell disarrangement, increased intercellular space, and cell degeneration or death in the hippocampus and reduced the pathology score of the damaged nerve. Moreover, Yigong Powder reduced the positive area of IBA1 and GFAP, reduced the levels of TNF-α in the brain tissue, serum, and spleen, and decreased spleen index. Furthermore, Yigong Powder decreased the average fluorescence intensity of CXCL12 and CXCR4, reduced CXCR4-positive astrocytes and microglia, down-regulated the protein levels of p-ERK/ERK and TNFR1, and lowered the level of glutamate in the brain tissue. This study showed that the preventive administration of Yigong Powder can ameliorate the learning and memory decline of the D-galactose-induced aging mice by regulating the immune function of the spleen and the CXCL12/CXCR4 signaling in the brain to reduce glutamate release. However, the mechanism of Yigong San in preventing and treating dementia via regulating spleen and stomach function remains to be studied.

Protective effects of Dendrobium huoshanense polysaccharide on D-gal induced PC12 cells and aging mice, in vitro and in vivo studies.

Dendrobium huoshanense C. Z. Tang et S. J. Cheng polysaccharide (DHP) is the essential active ingredient of D.huoshanense and has high medicinal value. A high dose of D-galactose (D-gal) is commonly utilized in the aging model establishment. In this study, we explored whether DHP shields PC12 cells and aging mice from D-gal caused damage and the possible mechanism. In vitro experiments, D-gal induced PC12 cells were used to investigate, and then DHP was used for treatment. In vivo experiments, 72 SPF ICR male mice were randomly divided into six groups (control: normal saline; model: D-gal (400 mg/kg); VE group: VE (50 µg/ml); DHP groups: D-gal + DHP (15.6 mg/ml; 31.2 mg/ml; 62.4 mg/ml)). The results showed that DHP could enhance the viability of D-gal injured PC12 cells and prevent cell apoptosis. DHP effectively promoted the transition from phase G0/G1 to phase S and inhibited cell cycle arrest. DHP has a potential neuroprotective effect on D-gal caused cognitive and memory disorders in mice. On the one hand, DHP protects the antioxidant enzymes SOD, GSH-PX, and CAT from excessive ROS buildup. On the other hand, DHP was demonstrated to block the expression of the P53/P21 signaling pathway-related proteins P53, P21, and P16. These results imply that DHP could be a potential neuroprotective agent against aging. PRACTICAL APPLICATIONS: Cognitive and memory decline caused by aging problems has become a problem in recent years. There are many theories about aging, among which oxidative stress is considered to be one of the important pathophysiological parts of various diseases in the aging process. In this study, DHP could not only improve the damage of D-Gal to PC12 cells, but also improve the cognitive and memory impairment caused by D-Gal in mice. In conclusion, this study verified the anti-aging effect of DHP from in vitro and in vivo experiments, and its mechanism may involve the P53/P21 pathway. Therefore, this study indicated that polysaccharides from Dendrobium huoshanense, a traditional Chinese medicine of homologous medicine and food, had potential and industrial value as potential anti-aging drugs.

Epigallocatechin-3-gallate alleviates galactose-induced aging impairment via gut-brain communication.

The study aimed to determine whether gut-brain communication could be modulated by epigallocatechin-3-gallate (EGCG) in a mouse aging model that was established by daily injection of D-galactose (D-gal) for 10 weeks. Our results showed that EGCG could improve aging-associated changes by increasing the immune organ indexes, brain index, and learning and memory ability in vivo. EGCG-triggered aging prevention was associated with the reduction of lipid peroxidation and elevation of enzymatic and non-enzymatic antioxidant activities in the brain. Concomitantly, treatment of D-gal-induced aging in mice with EGCG significantly reduced corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosterone, suggesting that EGCG-exerted protection of the aging brain was involved in the inhibition of the hypothalamic-pituitary-adrenal (HPA) axis. Further data concerning intestinal function showed that EGCG could enhance fecal moisture in vitro and reduce the pH value of feces in aging mice when compared to the D-gal group, suggesting that EGCG played beneficial roles in the intestine of aging mice. Moreover, short-chain fatty acids (SCFAs), the mediators of gut-brain communication, were significantly increased in the intestinal contents of aging mice by treatment with EGCG. Therefore, the tea polyphenol EGCG showing anti-aging properties was demonstrated to be implicated in modulating gut-brain communication by attenuating the HPA axis and enhancing the content of SCFAs.

Lactobacillus plantarum Combined with Galactooligosaccharides Supplement: A Neuroprotective Regimen Against Neurodegeneration and Memory Impairment by Regulating Short-Chain Fatty Acids and the c-Jun N-Terminal Kinase Signaling Pathway in Mice.

Probiotics and prebiotics have received attention in alleviating neurodegenerative diseases. Lactobacillus plantarum (L. plantarum) 69-2 was combined with galactooligosaccharides (GOS) and supplemented in a d-galactose (d-gal)-induced neurodegeneration and memory impairment mice model to explore its effects on the brain and the regulation of short-chain fatty acids. The results showed that the L. plantarum-GOS supplementation inhibited d-gal-induced oxidative stress and increased the brain's nuclear factor erythroid 2-related factor 2 (Nrf2) levels. Butyrate, a metabolite of the gut microbiota regulated by L. plantarum combined with GOS, inhibits p-JNK expression, downregulates pro-apoptotic proteins expression and the activation of inflammatory mediators, and upregulates synaptic protein expression. This might be a potential mechanism for L. plantarum 69-2 combined with GOS supplementation to alleviate d-gal-induced neurodegeneration and memory impairment. This study sheds new light on the development of aging-related neuroprotective dietary supplements based on the gut-brain axis.

Anti-Aging Effect of Momordica charantia L. on d-Galactose-Induced Subacute Aging in Mice by Activating PI3K/AKT Signaling Pathway.

Anti-aging is a challenging and necessary research topic. Momordica charantia L. is a common edible medicinal plant that has various pharmacological activities and is often employed in daily health care. However, its anti-aging effect on mice and the underlying mechanism thereof remain unclear. Our current study mainly focused on the effect of Momordica charantia L. on d-galactose-induced subacute aging in mice and explored the underlying mechanism. UHPLC-Q-Exactive Orbitrap MS was applied to qualitatively analyze the chemical components of Momordica charantia L. ethanol extract (MCE). A subacute aging mice model induced by d-galactose (d-gal) was established to investigate the anti-aging effect and potential mechanism of MCE. The learning and memory ability of aging mice was evaluated using behavioral tests. The biochemical parameters, including antioxidant enzyme activity and the accumulation of lipid peroxides in serum, were measured to explore the effect of MCE on the redox imbalance caused by aging. Pathological changes in the hippocampus were observed using hematoxylin and eosin (H&E) staining, and the levels of aging-related proteins in the PI3K/AKT signaling pathway were assessed using Western blotting. The experimental results demonstrated that a total of 14 triterpenoids were simultaneously identified in MCE. The behavioral assessments results showed that MCE can improve the learning and memory ability of subacute mice. The biochemical parameters determination results showed that MCE can improve the activity of antioxidant enzymes and decrease the accumulation of lipid peroxides in aging mice significantly. Furthermore, aging and injury in the hippocampus were ameliorated. Mechanistically, the results showed a significant upregulation in the protein expression of P-PI3K/PI3K and P-AKT/AKT (p < 0.01), as well as a significant reduction in cleaved caspase-3/caspase-3, Bax and P-mTOR/mTOR (p < 0.01). Our results confirm that MCE could restore the antioxidant status and improve cognitive impairment in aging mice, inhibit d-gal-induced apoptosis by regulating the PI3K/AKT signaling pathway, and rescue the impaired autophagy caused by mTOR overexpression, thereby exerting an anti-aging effect.

Impact of different processing methods on the phenolics and neuroprotective activity of Fragaria ananassa Duch. extracts in a D-galactose and aluminum chloride-induced rat model of aging.

Age-related diseases, including dementia, are a major health concern affecting daily human life. Strawberry (Fragaria ananassa Duch.) is the most eaten fruit worldwide due to its exceptional aroma and flavor. However, it's rapid softening and decay limit its shelf-life. Freezing and boiling represent the well-known conservation methods to extend its shelf-life. Therefore, we aimed to discover the phytochemical content differences of fresh and processed strawberries associated with investigating and comparing their neuroprotective effects in a rat model of aging. Female Wistar rats were orally pretreated with fresh, boiled, and frozen F. ananassa methanolic extracts (250 mg kg-1) for 2 weeks, and then these extracts were concomitantly exposed to D-galactose [65 mg kg-1, subcutaneously (S/C)] and AlCl3 (200 mg kg-1, orally) for 6 weeks to develop aging-like symptoms. The results of UPLC/ESI-MS phytochemical profiling revealed 36 secondary metabolites, including phenolics, flavonoids, and their glycoside derivatives. Compared with boiled and frozen extracts, the fresh extract ameliorated the behavioral deficits including anxiety and cognitive dysfunction, upregulated brain HO-1 and Nrf2 levels, and markedly reduced caspase-3 and PPAR-γ levels. Moreover, LDH and miRNA-9, 124 and 132 protein expressions were reduced. The histological architecture of the brain hippocampus was restored and glial fibrillary acidic protein (GFAP) immunoexpression was downregulated. In conclusion, the fresh extract has neuroprotective activity that could have a promising role in ameliorating age-related neurodegeneration.

Flaxseed oil ameliorates aging in d-galactose induced rats via altering gut microbiota and mitigating oxidative damage.

BACKGROUND: Aging causes decreased antioxidant capacity and chronic inflammation and may even elevate cancer risks. Previous studies reported that flaxseed oil (FO) can alleviate age-related diseases, including improving alcoholic liver disease, atherosclerosis and diabetes. However, whether the intestinal microbiota accountable for this alleviation is still unknown. This study aims to study the antioxidant effects of FO in an aging rat model and the underlying mechanism between the intestinal microbiota and aging. RESULTS: Our results presented that serum and liver antioxidant capacities in FO group were up-regulated, and liver inflammation in FO group was reduced. The 16S rDNA sequencing showed that FO regulated the microbial community, including up-regulation of four families of Lactobacillus and six families of Clostridium. In addition, FO had also adjusted the relative abundance of several genera such as Ruminococcaceae_UCG-005 and Prevotella_9, which may be the key bacteria associated with the aging process. Colonic transcriptome analysis showed that there were 1679 differentially expressed genes (DEGs) in the Model group and the FO group (134 up-regulated and 1545 down-regulated). Gene set enrichment analysis (GSEA) revealed FO down-regulates the expression of the upstream genes Ptprc, Lck, Zap70, Lat and Lcp2 in the T cell receptor signaling pathway. CONCLUSION: In conclusion, FO improved antioxidant capacity and reduced intestinal microbial disturbances caused by aging damage, indicating that dietary FO has the potential to fight aging damage. This study provides a more comprehensive view of dietary intervention to improve aging. © 2022 Society of Chemical Industry.

[Ershiwuwei Shanhu Pills regulate Akt/mTOR/GSK-3ß signaling pathway to alleviate Alzheimer's disease mice].

The present study investigated the mechanism of the Tibetan patent medicine Ershiwuwei Shanhu Pills(ESP) in alleviating Alzheimer's disease in mice via Akt/mTOR/GSK-3ß signaling pathway. BALB/c mice were randomly assigned into a blank control group, a model group, low(200 mg·kg~(-1)), medium(400 mg·kg~(-1)) and high(800 mg·kg~(-1)) dose groups of ESP, and donepezil hydrochloride group. Except the blank control group, the other groups were given 20 mg·kg~(-1) aluminum chloride by gavage and 120 mg·kg~(-1) D-galactose by intraperitoneal injection for 56 days to establish Alzheimer's disease model. Morris water maze was used to detect the learning and memory ability of mice. The level of p-tau protein in mouse hippocampus and the levels of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in hippocampus and serum were detected. Hematoxylin-eosin staining and Nissl staining were performed for the pathological observation of whole brain in mice. TdT-mediated dUTP nick-end labeling(TUNEL) staining was employed for the observation of apoptosis in mouse cortex. Western blot was adopted to detect the protein levels of p-mTOR, p-Akt, and GSK-3ß in the hippocampus. Compared with the model group, the ESP groups showcased alleviated pathological damage of the whole brain, decreased TUNEL positive cells, reduced level of p-tau protein in hippocampus, and risen SOD, CAT, and T-AOC levels and declined MDA level in hippocampus and serum. Furthermore, the ESP groups had up-regulated protein levels of p-mTOR and p-Akt while down-regulated protein level of GSK-3ß in hippocampus. Therefore, ESP can alleviate the learning and memory decline and oxidative damage in mice with Alzheimer's disease induced by D-galactose combined with aluminum chloride, which may be related to Akt/mTOR/GSK-3ß signaling pathway.

Hyperbaric oxygen therapy improves age induced bone dyshomeostasis in non-obese and obese conditions.

AIMS: To investigate the effects of hyperbaric oxygen therapy (HBOT) on metabolic disturbance, aging and bone remodeling in D-galactose-induced aging rats with and without obesity by determining the metabolic parameters, aging and oxidative stress markers, bone turnover markers, bone microarchitecture, and bone biomechanical strength. MATERIALS AND METHODS: Male Wistar rats were fed either a normal diet (ND; n = 18) or a HFD (n = 12) for 22 weeks. At week 13, vehicle (0.9% NaCl) was injected into ND-fed rats (NDV; n = 6), while 150 mg/kg/day of D-galactose was injected into 12 ND-fed rats (NDD) and 12 HFD-fed rats (HFDD) for 10 weeks. At week 21, rats were treated with either sham (NDVS, NDDS, or HFDDS; n = 6/ group) or HBOT (NDDH, or HFDDH; n = 6/group) for 14 days. Rats were then euthanized. Blood samples, femora, and tibiae were collected. KEY FINDINGS: Both NDD and HFDD groups developed aging as indicated by increased AGE level, increased inflammation and oxidative stress as shown by raised serum TNF-α and MDA levels, impaired bone remodeling as indicated by an increase in levels of CTX-1, TRACP-5b, and impaired bone structure/strength, when compared with those of the NDVS group. HFD aggravated these indicators of bone dyshomeostasis in D-galactose-treated rats. HBOT restored bone remodeling and bone structure/strength in the NDD group, however HBOT ameliorated bone dyshomeostasis in the HFDD group. SIGNIFICANCE: HBOT is a potential intervention to decrease the risk of osteoporosis and bone fracture in aging with or without obesity.