D-galactose Induced Aging Model Research Articles

Structural characterization and antioxidant activity in aging mice of a homogenous polysaccharide isolated from Ecklonia kurome

In this study, the crude polysaccharide (EKP) was extracted from Ecklonia kurome and purified with gel filtration to obtain the homogeneous polysaccharide (EKP-I). At the same time, the structure of EKP-I was characterized by infrared spectroscopy (IR), nuclear magnetic resonance (NMR), mass spectrometry (MS) and methylation analysis. The results showed that EKP-I was mainly composed of T-D-Glcp(1→, →4)-D-Galp(1→, →3,6)-D-Glcp(1→, →3)-D-Manp(1→ and →3)-D-Araf(1→. In addition, the antioxidant capacity of EKP-I in vivo was evaluated by constructing D-galactose induced aging model mice. The experimental results showed that after EKP-I treatment, the oxidative stress indexes of mice were significantly improved. Compared with the MG group, SOD and DPPH activities was significantly increased, while MDA content was significantly decreased. In addition, EKP-I could significantly reduce the levels of LDL-C, AST and ALT in serum, and increase the level of HDL-C, which has a certain protective effect on the organs of aging mice. Moreover, EKP-I could increase the levels of pro-inflammatory factor of IL-12, IL-6 and TNF-α, and decrease the levels of anti-inflammatory factor of IL-10, so as to improve the inflammatory response of aging mice. Therefore, this results provide data support for the development of Ecklonia kurome polysaccharides in food and medicine.

Formulation Containing Phytosomes of Carotenoids from Nyctanthes arbor-tristis and Tagetes patula Protect D-galactose Induced Skin Aging in Mice

• Gel containing phytosomes of crocin rich extract(equivalent to crocin 1% w/w) obtained from Nyctanthes arbor-tristis and Lutein rich extract (equivalent to lutein 0.5%w/w) from Tagetes patula indicated • Entrapment of crocin and lutein was found to be (60.20% w/w) and (50.81% w/w) respectively. • Improved stability of crocin and lutein through preparation of Phytosomes • Significant (P<0.01) increase in thickness of dermal and epidermal layer • Significant increase (P<0.05) in glutathione level and decrease (P<0.01) in MDA level • Upregulation of expression of elastin and Collagen gene by 0.26 and 0.03 fold respectively : Carotenoids play important role in delay of aging process. Orange coloured tubular calyx of flowers of Nyctanthes arbor-tristis. contains crocin, an apocarotenoid which forms a major component of stigma of saffron. Due to presence of crocin in orange coloured tubular calyx of Nyctanthes arbor-tristis, it can be used as an economical substitute to saffron for its medicinal and cosmetic utilities. Lutein from flower petals of Tagetes patula L , is another popular carotenoid which has antioxidant effect and many health benefits. The carotenoids are highly unstable when exposed to atmosphere, hence in the present study crocin and lutein rich extracts were entrapped into phytosomes to improve stability and efficacy of topical preparation. : Oxidative stress is considered to be a major contributor to the process of aging. Carotenoids viz, Lutein and crocin, being powerful antioxidants, can delay aging of skin through upregulating col type I gene and elastin gene. The carotenoids have very low oxidation potential, due to which they get oxidized fast and protect oxidation of other compounds which make them highly unstable. One of the ways to improve stability of these phytoconstituents, is their entrapment in phytosomes. Preparation of phytosomes will have dual advantages of improving stability as well as bioavailability of molecule. : The phytosomes of Carotenoid rich extract of tubular calyx of Nyctanthes arbor-tristis L. and the petals of Tagetes patula L. (standardized for crocin and lutein content) were prepared using lipid film hydration technique and these phytosomes were then incorporated into gel base. The gel formulation was evaluated for stability as per ICH guidelines. Efficacy of formulation was evaluated by D-galactose induced aging model. Aging in skin was induced by administration of D-Galactose (100mg/kg b.w.s.c.) to albino mice for 42 days. The gel formulation was applied topically for 42 days. Then the effect of formulation on skin aging was evaluated by estimation of biochemical parameters viz. glutathione and malondialdehyde (MDA) and histopathological studies of treated skin samples. Also expression of COL type I and elastin genes was carried out from the skin samples by RT-PCR method. : Percent entrapment (%w/w) of crocin and lutein in phytosomes were found to be 60.20 and 50.81 respectively. Accelerated stability studies showed improvement in stability of carotenoids viz. crocin and lutein and the content of crocin and lutein in formulation was found in the range of 99.98 % w/w to 99.85%w/w at the end of three months. The formulation containing extract of Phytosomes of carotenoid rich extracts of Nyctanthes arbor-tristis L. and the petals of Tagetes patula L. exhibited potent antiaging activity through significant (p<0.05)increase in dermal and epidermal layers, and increase in GSH levels of skin as compared to the untreated group. The treatment with the gel formulation revealed upregulation of col type I and elastin genes. There was significant reduction in lipid peroxidation as revealed through reduction in MDA levels as compared to untreated group. : Crocin and lutein have potential to prevent skin aging via upregulation of COL type I gene and elastin gene. Upregulation of genes resulted into increase in the thickness of epidermal and dermal layer along with reduction in oxidative stress in skin. Entrapment of carotenoid rich extracts of Nyctanthes arbor-tristis and Tagetes patula in Phytosomes enhanced the stability and efficacy of the formulation.

Momordica charantia polysaccharide ameliorates D-galactose-induced aging through the Nrf2/β-Catenin signaling pathway.

Aging is widely thought to be associated with oxidative stress. Momordica charantia (MC) is a classic vegetable and traditional herbal medicine widely consumed in Asia, and M. charantia polysaccharide (MCP) is the main bioactive ingredient of MC. We previously reported an antioxidative and neuroprotective effect of MCP in models of cerebral ischemia/reperfusion and hemorrhage injury. However, the role played by MCP in neurodegenerative diseases, especially during aging, remains unknown. In this study, we investigated the protective effect of MCP against oxidative stress and brain damage in a D-galactose-induced aging model (DGAM). The Morris water maze test was performed to evaluate the spatial memory function of model rats. The levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were measured and telomerase activity was determined. The results showed that MCP treatment attenuated spatial memory dysfunction induced by D-galactose. In addition, MCP increased antioxidant capacity by decreasing MDA and increasing SOD and GSH levels. MCP treatment also improved telomerase activity in aging rats. Mechanistically, MCP promoted the entry of both Nrf2 and β-Catenin into the nucleus, which is the hallmark of antioxidation signaling pathway activation. This study highlights a role played by MCP in ameliorating aging-induced oxidative stress injury and reversing the decline in learning and memory capacity. Our work provides evidence that MCP administration might be a potential antiaging strategy.

Impact of caffeic acid on the testicular damages in D-galactose-induced aging model in mice.

Objective(s):Aging is a biological phenomenon that causes various disorders and diseases in body systems such as the reproductive system. One of the important factors in aging is oxidative stress, which facilitates the aging process through various mechanisms. The aim of this study is the investigation of effects of caffeic acid on the testicular damages in Dgalactose induced aging model in mice. Materials and Methods:Forty male mice were randomly divided into 5 groups (n=8): 1) Control, 2) Sham, 3) Aging, 4) Aging + caffeic acid, and 5) Caffeic acid. Aging was induced through daily injection of D-Galactose (300 mg/kg, intraperitoneal) for 6 weeks. Caffeic acid (60 mg/kg, intraperitoneal) was injected daily for 6 weeks. One day after the last injection mice were killed and the testicle and epididymis were removed. Then, sperm parameters, factors of oxidative stress, and histopathological changes were evaluated. Results:The results showed that aging significantly decreased the count, motility, and viability of sperm, and increased abnormal sperm and sperm DNA fragmentation in contrast to the control group (P<0.05). In addition, MDA levels increased significantly in this group, and SOD, GPx, and TAC activity decreased (P<0.05). Histological studies also showed the destruction of seminiferous tubules, and Johnson’s score decreased (P<0.05). Caffeic acid administration significantly improved the above disarrays (P<0.05). Conclusion:The results showed that caffeic acid reduces the adverse effects of aging on spermatogenesis in mice by reducing oxidative stress and increasing antioxidant defenses.

Galactose-induced Aging Model in Rat Testicular Tissue.

To examine whether the D-galactose induced aging model is an appropriate model for further aging research. Experimental study. Aziz Sancar Institute of Experimental Medicine, Istanbul University, Turkey, June 2015- June 2017. The study comprises 3 groups of rats. Group I is young control (YC) 5-month-old rats. Group II is 5-month- old rats, which were mimetically aged (MA) for 6 weeks via intraperitoneal D-galactose (60 mg/kg body weight/day, 0.5 mL) administration. Group III is naturally aged (NA) 24-month-old rats. Group I and III received intraperitoneal saline (0.9% 0.5 mL) for 6 weeks as vehicle. Group I and Group II received injections at 21 weeks age and Group III rats 6 weeks before 24 months age. Tissues were harvested when rats became 6.5-month-old (Group I and Group II) and 24-month-old (Group III). Quantitative biochemical analyses of proteins, lipids, DNA biomarkers and Cu, Zn-SOD were conducted. Statistical analysis of the data was conducted using ANOVA, followed by post-hoc Bonferroni test. Higher magnitude of oxidative damage and diminished antioxidant defence capacity were found in both mimetically aged and naturally aged testicular tissues. It is observed that D-galactose aging model group shares significant similarities in terms of impaired redox homeostasis with the naturally aged rats. D-galactose induced testicular aging model successfully mimics aging process. Therefore, D-galactose induced aging model may be used as an accelerated aging model to study the age related alterations and interventions.

Decrease of Auditory Evoked Delta, Alpha and Beta Oscillatory Responses in d-galactose Induced Aging Model: Effects of Rosmarinic Acid

Summary Background Age-related hearing impairment is one of the most common complaints among older people. It was reported that central neural processing deficits contribute this deficit and improving central auditory function might be beneficial for cognitive functions in elderly. In the present study, we examined the effect of rosmarinic acid (RA) on auditory evoked oscillations and lipid peroxidation in d -galactose induced rat aging model. Methods Wistar rats were randomly divided into four groups: sham (S); RA-treated (R); d -galactose-treated (DG); d -galactose + RA-treated (DGR). After eight weeks period, central auditory functions were evaluated by measuring the auditory evoked oscillations over temporal cortex. Thiobarbituric acid reactive substances (TBARS) assay was used to quantify lipid peroxidation levels of the temporal cortex. Results d -galactose treated rats exhibited attenuated auditory evoked delta, alpha and beta responses. Moreover, increased lipid peroxidation levels were detected in the d -galactose treated rats. Eight weeks RA (50 mg/kg) treatment significantly improved oscillatory alterations and lipid peroxidation as compared to DG group. Conclusion Thus, present study shows d -galactose induced oscillatory changes in auditory processing and highlights the protective effect of RA against d -galactose induced changes in auditory evoked oscillations and lipid peroxidation.

Effect of Dimethylaminoethano and Compound Amino Acid on Periostin and Dermatopontin Expression in the Skin of D-galactose Induced Aging Model in Rats

Effect of Dimethylaminoethano and Compound Amino Acid on Periostin and Dermatopontin Expression in the Skin of D-galactose Induced Aging Model in Rats

Effects of Vitex agnus-castus fruit on sex hormones and antioxidant indices in a d-galactose-induced aging female mouse model

BackgroundAging is associated with the loss of endocrine function. In this study, Vitex agnus-castus (Vitex), which has antioxidant effects and high levels of phytoestrogen, was investigated with regard to the hypothalamic-pituitary-gonadal axis and antioxidant indices in natural aging and in a d-galactose induced aging model in female mice. MethodsThe mice were subcutaneously injected with d-galactose (500 mg/kg/d for 45 days). Extract of Vitex (600 mg/kg/bid for 7 days by gavage) was used to treat d-galactose-induced aging and natural aging in mice. Seventy-two female NMRI mice (48 3-month-old normal mice and 24 18-24-month-old mice), weighing 30–35 g were randomly divided into six groups: control, Vitex, d-galactose, Vitex + d-galactose, Aging, and Vitex + Aging. The antioxidant indices and sex hormone levels were subsequently measured by enzyme-linked immunosorbent assay kits. ResultsBody weight and the levels of malondialdehyde (MDA), follicle-stimulating hormone, and luteinizing hormone levels were significantly increased in the d-galactose aging and natural aging groups, whereas catalase and superoxide dismutase (SOD) activity and estrogen level were significantly decreased in these same groups. d-Galactose can also disrupt the estrous cycle and damage the uterus and ovarian tissues. Vitex could effectively attenuate these alterations. ConclusionVitex improved some aging events in the reproductive system of female mice. Therefore, because of its apparent antiaging effects, Vitex can be suitable for some aging problems such as oxidative stress, female sex hormone deficiency, and an atrophic endometrium.

Potential Application of Tetrahydroxystilbene Glucoside in Treatment of Alzheimer’s Disease

Current treatment strategies for Alzheimer’s disease are mainly symptomatic, development of disease-modifying therapies is urgent needed. Polygonum Multiflorum has been used in Traditional Chinese Medicine for long history in the treatment of dementia. Pharmacological studies suggested Polygonum Multiflorum could improve learning and memory ability in the Alzheimer’s disease models, and inhibit β-amyloid production. 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucoside(TSG) is one main bioactive stillbene glycoside of Polygonum Multiflorum . The role of TSG in the Alzheimer’s disease treatment has been investigated. TSG might antagonize acetylcholine deficiency and cognitive performance impairment in the animal models of Alzheimer’s disease. By using β-amyloid precursor protein transgenic mice, TSG ameliorated learning and memory functions associated with reduced formation of senile plaques and β-amyloid deposition, and inhibition of γ- secretase and α-synuclein. In β-amyloid injection rat models, TSG increased cognitive behavior performance, and prevented β-amyloid deposition and synaptic degeneration. In the D-galactose induced aging model, TSG improved ability of learning and memory in the mice, inhibited β-amyloid precursor protein and β-amyloid expressions. Learning and memory deterioration in aged animals was reformed by TSG intervention; its effects might be exerted through β-amyloid precursor protein pathway. TSG was also shown to display antioxidant activity in vitro and in vivo. In conclusion, TSG has been demonstrated to improve cognitive performance of Alzheimer’s disease models through multiple targets strategies, and may be a future perspective in the development of Alzheimer’s disease therapy.

Effect of dimethylaminoethano and compound amino acid on collagens I and III mRNA expression in the skin of D-galactose induced aging model in rats

Objective To study the effect of dimethylaminoethano (DMAE) and compound amino acid injection (AA) by mesotherapy on collagen Ⅰ and collagen Ⅲ mRNA expression levels of D-galactose-induced chemical skin aging rats.Methods 80 rats were randomly divided into individual experimental group.At 18 days after D-gal induction,rats of aging treatment groups were treated with intradermal microinjection of 0.2％ DMAE+AA,0.1％ DMAE+AA,0.2％ DMAE,0.1％ DMAE,AA,and saline,respectively,once a week for 4 weeks.At 42 days after treatment,the skin wounds were harvested.HE,PCNA,hydroxyproline and collagen Ⅰ and collagen Ⅲ mRNA expression levels of every group skins were detected.Results Dermal thickness,hydroxyproline content and collagen type Ⅰ and Ⅲ mRNA expression levels of 0.1％ DMAE+ AA and 0.2 ％ DMAE+ AA groups were significantly improved (P＜0.05),but PCNA expression of sham control group was significantly higher than all of aging groups (P＞0.05).Conclusions Local co-injection of DMAE and compound AA directly into targeted tissue under mesotherapy has marked anti-aging effects on D-galactose induced skin aging model of rat by increasing the dermal thickness,collagen content and acceleration of collagen synthesis. Key words: Mesotherapy; Dimethylaminoethanol; Compound amino acid ; Anti-aging; Ⅰ and Ⅲ collagen; PCNA; D-galactose

Evaluation of Tissue Factor Activities and Sialic Acid Levels in D-Galactose Induced Aging Model

Evaluation of Tissue Factor Activities and Sialic Acid Levels in D-Galactose Induced Aging Model

Treatment of D-galactose induced mouse aging with &lt;i&gt;Lycium barbarum&lt;/i&gt; polysaccharides and its mechanism study

We evaluated the effects of Lycium barbarum polysaccharides LBP) on D-galactose aging model mouse, and explored its possible mechanism. Kunming mice were randomly divided into the control group, the model group, the high-dose LBP group, and the low-dose LBP group. Except the control group, D-galactose was used for modelling. The drug was administrated when modelling. Mouse behavioural, learning and memory changes were observed, and the contents of lipid peroxidation (LPO), lipofuscin (LF) and monoamine oxidase B (MAO-B) in mouse brain tissue and the weight of immune organs were measured after 6 weeks. Compared with the control group, mouse weight gain in the model group reduced significantly. Compared with model group, after mice drank LBP, the times of electric shock was less than aging mice (in which, the high-dose LBP group, P<0.05), and electric shock incubation period was longer (P<0.01). On Day 45 after modelling and drug administration, the contents of LPO, LF and MAO-B in mouse brain tissue in the model group increased significantly, while those in the drug administration groups decreased significantly. The thymus index in the aging model group decreased significantly; the thymus index and the spleen index in the high-dose LBP group and the low-dose LBP group rebounded significantly (P<0.01). We concluded that LBP has an anti-aging effect on D-galactose induced aging model mouse, and its mechanism may be related with the alleviation of glucose metabolism disorder and the resistance of the generation of lipid peroxide and other substances, which damage cell membrane lipid.

Study on establishment of kidney deficient aging model and comparison with D-galactose induced aging model

To establish a kidney deficient aging model (KDAM), assess it in antioxidant capacity, HPAT axis function and bone metabolism, and compare with D-galactose aging model. Aging rat model was established by injecting D-galactose solution, meanwhile dexamethasone solution was injected to establish kidney deficient aging model. Then these models were evaluated by serum MDA (malondialdehyde) and GSH-Px (glutathione peroxidase), liver SOD (superoxide dismutase), adrenal, thymus and spleen index, CD4(+), CD8(+), and serum COR (cortisol), BGP (bone Gla-protein), plasma ACTH (adrenocorticotropic hormone) and CRH (corticotropin-releasing hormone). Compared with the normal group, the aging model group and the kidney deficient aging group showed significant decrease in liver SOD activity (P < 0.01 on average) and significant increase in serum MDA content (P < 0.01 on average) , and the kidney deficient aging group revealed remarkable decline in plasma ACTH content (P < 0.05). Compared with the normal group and the aging model group, the kidney deficient aging model group's weight, serum GSH-Px decreased (P < 0.01, P < 0.05), adrenal index decreased (P < 0.05, P < 0.01), serum COR decreased (P < 0.05 on average), plasma CRH increased (P < 0.05, P < 0.01), serum BGP content significantly decreased (P < 0.01 on average), value of CD4(+), CD8(+) decreased (P < 0.05, P < 0.01), CD4(+)/CD8(+) increased, but without significant difference. The kidney deficient aging model shows significant decrease in antioxidant capacity, dysfunction of HPAT axis disorder and abnormal bone metabolism. However, D-galactose aging model only shows a significant difference in antioxidant capacity.

Protective Role of Salidroside against Aging in A Mouse Model Induced by D-galactose

To investigate the protective effects of putative AGEs (advanced glycation endproducts) inhibitor salidroside against aging in an accelerated mouse aging model induced by D-galactose. A group of 5-month-old C57BL/6J mice were treated daily with D-galactose, D-galactose combined with salidroside, salidroside alone, and control buffer for 8 weeks. At the end of the treatment, serum AGEs levels, neurological activities, expression of glial fibrillary acidic protein (GFAP) and neurotrophin-3 (NT-3) in the cerebral cortex, as well as lymphocyte proliferation and IL-2 production were determined. D-galactose induced mouse aging model was developed as described before. As expected, salidroside blocked D-galactose induced increase of serum AGEs levels. It also reversed D-galactose induced aging effects in neural and immune system, as evidenced by improving motor activity, increasing memory latency time, and enhancing lymphocyte mitogenesis and interleukin-2 (IL-2) production. Furthermore, elevated expression of GFAP and NT-3 in the aged model mice was also reduced upon salidroside treatment. Salidroside inhibits AGEs formation in vivo, which at least partially contributes to its anti-aging effect in D-galactose induced aging model.

Behavioural study of the d-galactose induced aging model in C57BL/6J mice

Rodent chronically injected with d-galactose ( d-gal) has been used as an animal aging model for brain aging or anti-aging pharmacology research. However, the dosage of d-gal used to establish this model in mice has been reported in a wide range. To study the dose-dependent effect of d-gal on rodent behaviour, we investigated the learning and memory ability of C57BL/6J (C57) mice after 8-week subcutaneous injection of d-gal at different doses by Morris water maze (MWM) and object recognition test (ORT). In addition, locomotor activity test (LAT) was also performed to examine the neuromuscular function. In comparison of vehicle (0.9% saline)-treated mice, d-gal-treated mice at dose of high (200 mg/kg per day) and middle (100 mg/kg per day) doses showed significant longer latency to platform and less target quadrant search time and distance in MWM In ORT, d-gal at high and middle doses reduced the discrimination index (DI) of mice more significantly than low dose (50 mg/kg per day), although all three doses of d-gal reduced the DI of mice significantly. Furthermore, d-gal at high and middle doses significantly decreased locomotor activity of the mice in LAT. Throughout three tests, d-gal induced behavioural impairments in C57 mice at high and middle doses tended to be in the same degree. These results indicate that d-gal can induce the behavioural impairment of C57 mice in a dose-dependent manner from 50 to 100 mg/kg, higher dose than 100 mg/kg cannot further deteriorate its behavioural performance.