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1.
Article in Chinese | WPRIM | ID: wpr-1021826

ABSTRACT

BACKGROUND:Studies have shown that there is a close association between spinal cord injury and ferroptosis,and that tetramethylpyrazine has the function of regulating redox reactions. OBJECTIVE:To investigate the regulatory effect of tetramethylpyrazine on ferroptosis in rats with spinal cord injury and its mechanism. METHODS:Thirty-six female specific pathogen-free Sprague-Dawley rats were randomly divided into sham-operated group,model group and tetramethylpyrazine group,with 12 rats in each group.Animal models of spinal cord injury were established using the modified Allen's method in the latter two groups.No treatment was given in the sham-operated group,while rats in the model and tetramethylpyrazine groups were given intraperitoneal injection of normal saline and tetramethylpyrazine solution,once a day,for 28 days. RESULTS AND CONCLUSION:The Basso,Beattie&Bresnahan Locomotor Rating Scale score in the tetramethylpyrazine group was lower than that in the sham-operated group but higher than that in the model group after 14,21,and 28 days of treatment(P<0.05).After 28 days of treatment,hematoxylin-eosin staining showed that in the model group,the spinal cord tissue of rats showed cavity formation,necrotic tissue and inflammatory infiltration with fibrous tissue formation;in the tetramethylpyrazine group,the area of spinal cord tissue defects was smaller,and inflammatory infiltration and fibrous tissue formation were less than those in the model group.After 28 days of treatment,Prussian blue staining showed that a large amount of iron deposition was seen in the spinal cord tissue of rats in the model group,and less iron deposition was seen in the spinal cord tissue of rats in the tetramethylpyrazine group than in the model group.After 28 days of treatment,the levels of glutathione and superoxide dismutase in the rat spinal cord tissue were decreased(P<0.05)and the level of malondialdehyde was increased in the model group compared with the sham-operated group(P<0.05);the levels of glutathione and superoxide dismutase in the rat spinal cord tissue were increased(P<0.05)and the level of malondialdehyde was decreased in the tetramethylpyrazine group compared with the model group(P<0.05).After 28 days of treatment,qRT-PCR and western blot assay showed that the mRNA and protein levels of glutathione peroxidase 4,ferritin heavy chain,and ferroportin in the rat spinal cord tissue in the model group were decreased compared with those in the sham-operated group(P<0.05),while the mRNA and protein levels of glutathione peroxidase 4,ferritin heavy chain,and ferroportin in the rat spinal cord tissue in the tetramethylpyrazine group were increased compared with those in the model group(P<0.05).Immunofluorescence staining showed that after 28 days of treatment,the neuronal nuclei positive staining in the spinal cord of rats was the most in the sham-operated group and the least in the model group.To conclude,tetramethylpyrazine can improve motor function and play a neuroprotective role in rats with spinal cord injury by regulating ferroptosis.

2.
Article in Chinese | WPRIM | ID: wpr-1039094

ABSTRACT

ObjectiveIt was reported that the transthyretin (TTR) has a neuroprotective effect on Alzheimer’s disease (AD), which is manifested by the ability of TTR to inhibit the pathological aggregation of amyloid beta protein (Aβ). In this work, we investigated the mechanism of the interactions between TTR and Aβ at the molecular level to reveal the neuroprotective effect of TTR on AD. MethodsProtein-protein docking was used to explore the models of interaction between different structural forms of TTR and Aβ, and molecular dynamics simulation was further applied to investigate the dynamic process of the interaction between the two. ResultsBoth TTR tetramer and monomer can interact with Aβ monomer, and the thyroxine-binding channel of TTR tetramer is the main binding site of Aβ monomer. In addition, the EF helix and EF loop of TTR tetramer were also able to bind Aβ monomer. When the TTR tetramer dissociates, the hydrophobic site of the internal TTR monomer is exposed, which has a strong affinity for Aβ monomer. For the interaction between Aβ aggregates and TTR, a higher degree of aggregation can be formed between TTR monomer and Aβ aggregates due to the β-sheet-rich property of TTR monomer and Aβ aggregates, which may therefore reduce the cytotoxicity of Aβ aggregates. ConclusionBoth TTR tetramer and monomer can inhibit Aβ aggregation by “sequestering” Aβ monomer, while TTR monomer can reduce the cytotoxicity of Aβ aggregates by forming large co-aggregation with Aβ aggregates. This work can provide an important theoretical basis for the design and discovery of anti-AD drugs based on the neuroprotective effects of TTR.

3.
Yao Xue Xue Bao ; (12): 2746-2753, 2023.
Article in Chinese | WPRIM | ID: wpr-999020

ABSTRACT

Fourteen compounds were isolated from the ethyl acetate fraction of 90% EtOH extracts of the dried fruits of Alpinia oxyphylla by silica gel, MCI, RP-18, Sephadex LH-20, TLC and semi-preparative HPLC column chromatography. Their structures were identified by HR-ESI-MS, UV, IR, NMR, ECD and X ray single crystal diffraction spectroscopic data as: (2R,5R,7R,10S)-2,7-dihydroxyl-eudesmane-3(4),11(12)-diene (1), α-rotunol (2), diketone I (3), (1S,4S,5R,7S)-1-hydroxyl-eremophilane-9(10),11(12)-diene-8-one (4), cyperusol A1 (5), (6R,9S,10S)-10-hydroxyl-11,12,13-trinor-cadinane-4(5)-ene-3-one (6), (2E,4E)-6-hydroxy-2,6-dimethylhepta-2,4-dienal (7), oxyphyllacinol (8), yakuchinone A (9), (5R)-5-hydroxy-1,7-diphenylhept-3-heptanone (10), (5S)-5-hydroxy-7-(4″-hydroxyphenyl)-1-phenylhept-3-heptanone (11), (5S)-5-hydroxy-7-(4″-hydroxyl-3″-methoxyphenyl)-1-phenyl-3-heptanone (12), 7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-3,5-heptadione (13), bis-(2-ethylhexyl) terephthalate (14). Compounds 1-6 were sesquiterpenoids in which compound 1 is a new eudesmane sesquiterpenoid and compound 7 was a monoterpenoid. Compounds 8-13 were diarylheptanoids, and compounds 2-6 and 14 were isolated from A.oxyphylla for the first time. The experiments on H2O2 induced SH-SY5Y cells showed that compounds 2, 6, 7, 12 and 13 had neuroprotective effects at low and medium concentrations. In particular, compound 6 showed obvious neuroprotective effect at low, medium and high concentrations whose cell viability was higher than that of the positive control.

4.
Article in Chinese | WPRIM | ID: wpr-1030746

ABSTRACT

Glucagon-like peptide 1 (GLP-1) is a kind of incretin produced in the intestinal with multiple pharmacological effects, which can stimulate insulin secretion effectively. Various GLP-1 analogues have been widely used in the treatment of type 2 diabetes mellitus. Alzheimer's disease (AD) is closely related to type 2 diabetes mellitus, with some common pathological features, such as insulin resistance, and epidemiological studies also showed that patients with type 2 diabetes mellitus have an increased risk of developing AD. GLP-1 analogues have shown beneficial effects in both preclinical animal research and clinical trials of AD. Therefore, the authors summarized the main characteristics of GLP-1 and AD, and analyzed the mechanisms of GLP-1 in preclinical AD studies of animal models. GLP-1 readily crosses the blood-brain barrier and exerts its neuroprotective effects by binding to and activating the widely distributed GLP-1 receptors (GLP-1Rs) in the brain, affecting multiple physiological and pathological processes including glucose metabolism, neuroinflammation, mitochondrial function, and cell proliferation. Insulin resistance and inflammation are key common pathways in AD and type 2 diabetes. GLP-1 may exert its neuroprotective effects by improving mitochondrial function and glycolysis, reducing oxidative stress levels, exerting anti-inflammatory and anti-apoptotic effects, inducing neurogenesis, and inhibiting glial cell proliferation. This paper maybe provide the reference for further study of GLP-1 analogues in AD, hoping to open new therapy venues for AD patients.

5.
Zhongguo Zhong Yao Za Zhi ; (24): 762-769, 2023.
Article in Chinese | WPRIM | ID: wpr-970546

ABSTRACT

This study aimed to explore the effect of Ganmai Dazao Decoction on the ethology of rats with posttraumatic stress disorder(PTSD) and study the related mechanism through the changes in magnetic resonance imaging and protein expression. Sixty rats were randomly divided into 6 groups, namely the normal group, the model group, the low(1 g·kg~(-1)), medium(2 g·kg~(-1)), and high-dose Ganmai Dazao Decoction groups(4 g·kg~(-1)), and the positive control group(intragastric administration with 10.8 mg·kg~(-1) of fluoxetine), with 10 rats in each group. Two weeks after inducing PTSD by single-prolonged stress(SPS) in rats, the positive control group was given fluoxetine hydrochloride capsule by gavage, the low, medium, and high-dose groups were given Ganmai Dazao Decoction by gavage, and both the normal group and the model group were given the same volume of normal saline by gavage, each for 7 days. The open field experiment, elevated cross elevated maze, forced swimming experiment, and new object recognition test were carried out for the behavioral test. Three rats in each group were selected to detect the expression of neuropeptide receptor Y1(NPY1R) protein in the hippocampus by Western blot. Then, the other three rats in each group were selected to use the 9.4T magnetic resonance imaging experiment to observe the overall structural changes in the brain region and the anisotropy fraction of the hippocampus. The results of the open field experiment showed that the total distance and central distance of rats in the model group were significantly lower than those in the normal group, and the total distance and central distance of rats in the middle and high-dose Ganmai Dazao Decoction groups were higher than those in the model group. The results of the elevated cross maze test showed that medium and high-dose Ganmai Dazao Decoction remarkably increased the number of open arm entries and the residence time of open arm of rats with PTSD. The results of the forced swimming experiment showed that the immobility time in the water of the model group rats was significantly higher than that of the normal group, and Ganmai Dazao Decoction hugely reduced the immobility time in the water of rats with PTSD. The results of the new object recognition test showed that Ganmai Dazao Decoction significantly increased the exploration time of new objects and familiar objects in rats with PTSD. The results of Western blot showed that Ganmai Dazao Decoction significantly reduced the expression of NYP1R protein in the hippocampus of rats with PTSD. The 9.4T magnetic resonance examination found that there was no significant difference in the structural image among the groups. In the functional image, the fractional anisotropy(FA value) of the hippocampus in the model group was significantly lower than that in the normal group. The FA value of the hippocampus in the middle and high-dose Ganmai Dazao Decoction groups was higher than that in the model group. Ganmai Dazao Decoction reduces the injury of hippocampal neurons by inhibiting the expression of NYP1R in the hippocampus of rats with PTSD, thereby improving the nerve function injury of rats with PTSD and playing a neuroprotective role.


Subject(s)
Animals , Rats , Ethology , Stress Disorders, Post-Traumatic , Fluoxetine , Hippocampus , Maze Learning
6.
Article in English | WPRIM | ID: wpr-1010975

ABSTRACT

Six new ent-abietane diterpenoids, abientaphlogatones A-F (1-6), along with two undescribed ent-abietane diterpenoid glucosides, abientaphlogasides A-B (7-8) and four known analogs were isolated from the aerial parts ofPhlogacanthus curviflorus (P. curviflorus). The structures of these compounds were determined using high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), one-dimensional and two-dimensional nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) spectra, and quantum chemical calculations. Notably, compounds 5 and 6 represented the first reported instances of ent-norabietane diterpenoids from the genus Phlogacanthus. In the β-hematin formation inhibition assay, compounds 2, 4, 7-10, and 12 displayed antimalarial activity, with IC50 values of 12.97-65.01 μmol·L-1. Furthermore, compounds 4, 5, 8, and 10 demonstrated neuroprotective activity in PC12 cell injury models induced by H2O2 and MPP+.


Subject(s)
Abietanes/pharmacology , Antimalarials , Hydrogen Peroxide , Biological Assay , Plant Components, Aerial
7.
Article in English | WPRIM | ID: wpr-982400

ABSTRACT

Over the past few decades, complementary and alternative treatments have become increasingly popular worldwide. The purported therapeutic characteristics of natural products have come under increased scrutiny both in vitro and in vivo as part of efforts to legitimize their usage. One such product is tea tree oil (TTO), a volatile essential oil primarily obtained from the native Australian plant, Melaleuca alternifolia, which has diverse traditional and industrial applications such as topical preparations for the treatment of skin infections. Its anti-inflammatory-linked immunomodulatory actions have also been reported. This systematic review focuses on the anti-inflammatory effects of TTO and its main components that have shown strong immunomodulatory potential. An extensive literature search was performed electronically for data curation on worldwide accepted scientific databases, such as Web of Science, Google Scholar, PubMed, ScienceDirect, Scopus, and esteemed publishers such as Elsevier, Springer, Frontiers, and Taylor & Francis. Considering that the majority of pharmacological studies were conducted on crude oils only, the extracted data were critically analyzed to gain further insight into the prospects of TTO being used as a neuroprotective agent by drug formulation or dietary supplement. In addition, the active constituents contributing to the activity of TTO have not been well justified, and the core mechanisms need to be unveiled especially for anti-inflammatory and immunomodulatory effects leading to neuroprotection. Therefore, this review attempts to correlate the anti-inflammatory and immunomodulatory activity of TTO with its neuroprotective mechanisms.


Subject(s)
Tea Tree Oil/therapeutic use , Melaleuca , Neuroprotection , Drug Repositioning , Neuroinflammatory Diseases , Australia , Oils, Volatile , Anti-Inflammatory Agents/pharmacology
8.
Zhongguo Zhong Yao Za Zhi ; (24): 5032-5040, 2023.
Article in Chinese | WPRIM | ID: wpr-1008673

ABSTRACT

This study aimed to explore the possible effect of Xixin Decoction(XXD) on the learning and memory ability of Alzheimer's disease(AD) model senescence-accelerated mouse-prone 8(SAMP8) and the related mechanism in enhancing neuroprotective effect and reducing neuroinflammation. Forty SAMP8 were randomly divided into a model group(10 mL·kg~(-1)·d~(-1)), a probiotics group(0.39 g·kg~(-1)·d~(-1)), a high-dose group of XXD granules(H-XXD, 5.07 g·kg~(-1)·d~(-1)), a medium-dose group of XXD granules(M-XXD, 2.535 g·kg~(-1)·d~(-1)), and a low-dose group of XXD granules(L-XXD, 1.267 5 g·kg~(-1)·d~(-1)). Eight senescence-accelerated mouse-resistant 1(SAMR1) of the same age and strain were assigned to the control group(10 mL·kg~(-1)·d~(-1)). After ten weeks of intragastric administration, the Morris water maze was used to test the changes in spatial learning and memory ability of mice after treatment. Meanwhile, immunofluorescence staining was used to detect the positive expression of receptor for advanced glycation end products(AGER), Toll-like receptor 1(TLR1), and Toll-like receptor 2(TLR2) in the hippocampal CA1 region of mice. Western blot was employed to test the protein expression levels of silencing information regulator 2 related enzyme 1(SIRT1), AGER, TLR1, and TLR2 in the hippocampus of mice. Enzyme linked immunosorbent assay(ELISA) was applied to assess the levels of Aβ_(1-42) in the hippocampus of mice and the levels of nuclear factor κB p65(NF-κB p65), NOD-like receptor protein 3(NLRP3), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) in the serum and hippocampus of mice. Compared with the model group, XXD significantly improved the spatial learning and memory ability of SAMP8, increased the expression of neuroprotective factors in the hippocampus, decreased the levels of neuroinflammatory factors, and inhibited the expression of Aβ_(1-42). In particular, H-XXD significantly increased the expression of SIRT1 in the hippocampus of mice, reduced the expression levels of NF-κB p65, NLRP3, TNF-α, and IL-1β in the serum and hippocampus of mice, and decreased the expression of AGER, TLR1, and TLR2 in the hippocampus of mice(P<0.05 or P<0.01). XXD may improve the spatial learning and memory ability of AD model SAMP8 by enhancing the neuroprotective effect and inhibiting neuroinflammation.


Subject(s)
Humans , Neuroprotective Agents/therapeutic use , Sirtuin 1/metabolism , Toll-Like Receptor 2/metabolism , NF-kappa B/metabolism , Tumor Necrosis Factor-alpha/metabolism , Neuroinflammatory Diseases , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Toll-Like Receptor 1/metabolism , Alzheimer Disease/genetics , Hippocampus
9.
Article in Chinese | WPRIM | ID: wpr-940382

ABSTRACT

ObjectiveTo observe the protective effect of Chaihu Jia Longgu Mulitang (CLMT) on dopaminergic neurons in Parkinson's disease with depression (PDD) model rats, and to explore the mechanism based on adenosine monophosphate-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway. MethodAmong the 80 male SD rats, 10 were randomly selected as normal group and the rest were treated with long-term low-dose subcutaneous injection of rotenone in the neck and back combined with chronic unpredictable mild stress (CUMS) to establish PDD rat model. The successfully modeled PDD rats were randomly divided into model group, western medicine group (madopar 0.032 g·kg-1+fluoxetine hydrochloride 0.002 g·kg-1), CLMT low-dose, medium-dose and high-dose groups (5, 10 and 20 g·kg-1), 10 rats in each group. Normal group and model group were administrated with the same amount of normal saline by gavage for 4 consecutive weeks. Behavioral changes of rats in each group were evaluated by open field test and pole climbing test. The content of dopamine (DA) and 5-hydroxytryptamine (5-HT) in cerebrospinal fluid was determined by high performance liquid chromatography (HPCL). The pathological changes of dopaminergic neurons in substantia nigra of rats were observed by hematoxylin-eosin (HE) staining. The positive expression of tyrosine hydroxylase (TH) and expression of α-synuclein in substantia nigra were detected by immunohistochemistry (IHC) and immunofluorescence (IF), repsectively. The protein expression of microtubule-associated protein 1 light chain 3 (LC3), adenosine monophosphate-activated protein kinase (AMPK), phosphorylated AMPK (p-AMPK), mammalian target of rapamycin (mTOR) and phosphorylated mTOR (p-mTOR) was detected by Western blot. ResultCompared with the conditions in normal group, the total horizontal distance and the activity time in the central region in open field test and the content of DA and 5-HT in cerebrospinal fluid were decreased (P<0.05, P<0.01), and the time of pole climbing was shortened (P<0.01), with increased score (P<0.01) in model group. Compared with model group, CLMT high-dose group and western medicine group increased the total horizontal distance and activity time in the central region and the content of DA and 5-HT (P<0.05, P<0.01), and extended the time of climbing pole (P<0.05), with decreased score (P<0.05, P<0.01). Compared with those in normal group, the number of dopaminergic neurons in the substantia nigra was reduced, with narrowed and loosely arranged cell body. The fluorescence expression of α-synuclein was enhanced (P<0.01), and the positive expression of TH was decreased (P<0.01) in model group. Compared with model group, CLMT high-dose group and western medicine group showed elevated number of dopaminergic neurons in the substantia nigra, with enlarged cell body, and decreased fluorescence expression of α-synuclein, and enhanced the positive expression of TH (P<0.05, P<0.01). Compared with normal group, model group had lowered expression of LC3Ⅱ/Ⅰ, p-AMPK/AMPK in striatum (P<0.05, P<0.01) and increased expression of p-mTOR/mTOR (P<0.01). Compared with those in model group, LC3Ⅱ/Ⅰ and p-AMPK/AMPK expression were increased (P<0.05, P<0.01) and p-mTOR /mTOR expression was decreased (P<0.01) in CLMT high-dose group and western medicine group. ConclusionCLMT exerts a neuroprotective effect by inhibiting rotenone neurotoxicity. It enhances the level of DA, and thus improves the depression condition in rats with Parkinson's disease. The underlying mechanism may be related to the regulation of AMPK/mTOR signaling pathway, activation of autophagy, and promotion of degrading α-synuclein.

10.
Article in Chinese | WPRIM | ID: wpr-905918

ABSTRACT

Cerebral ischemia/reperfusion injury (CIRI) is a common feature and the main pathophysiological mechanism of ischemic stroke(IS), which is caused by a blood reperfusion injury in ischemic brain tissues. It can aggravate brain tissue injury and cause irreversible brain damage, seriously affecting the quality of life or even the life of patients. Hence, we must find out the exact mechanism as well as the effective therapeutic drugs and targets for CIRI. The Chinese medicine effective in Xingnao (restoring consciousness) and Kaiqiao (opening orifices) has been widely used in the treatment of CIRI and serves as a classic therapy for IS. In recent years, scholars have conducted extensive and in-depth studies on the mechanism and therapeutic targets of Chinese medicine in Xingnao and Kaiqiao. They found that those drugs could interfere with a series of changes after IS and achieve the remarkable curative effect. This study summarized the effect and mechanism of Chinese medicine in Xingnao and Kaiqiao in the treatment of CIRI, including reducing the inflammatory response and oxidative stress, alleviating brain edema and the toxicity of excitatory amino acids, reducing cell apoptosis, promoting angiogenesis and neurovascular remodeling, and improving blood-brain barrier injury. It is expected to provide references to clarify the mechanism and important targets of those drugs in resisting CIRI and ideas for the in-depth investigation and application of brain protection of Chinese medicine in Xingnao and Kaiqiao.

11.
Article in Chinese | WPRIM | ID: wpr-906316

ABSTRACT

Notoginsenosides, the saponins extracted from Panax notoginseng, have many pharmacological effects, such as anti-inflammation, anti-oxidation, anti-tumor, nervous system and cardiovascular system protection, microcirculation improvement and calcium overload inhibition. At present, notoginsenosides are widely used clinically for treating many diseases with good efficacy, especially for nervous system diseases such as stroke, stroke sequelae and Alzheimer's disease. In recent years, the mechanism underlying their neuroprotective effect has been continuously explored. To advance the applied research on notoginsenosides in the prevention and treatment of central nervous system diseases, this paper, combined with the latest reports, summarizes their neuroprotective effect and mechanisms in terms of regulating voltage-gated ion channels, protecting nerve cells and neurovascular unit, inhibiting oxidative stress and inflammatory reaction, promoting angiogenesis and reducing excitatory neurotoxicity. Although the protective mechanism of notoginsenosides for the nervous system mainly involves the above several aspects, some of them still remain to be fully elucidated, which necessitates the further exploration of neuroprotective effect of notoginsenosides with molecular biology, metabolomics, proteomics and other technologies.

12.
Zhongguo Zhong Yao Za Zhi ; (24): 380-387, 2021.
Article in Chinese | WPRIM | ID: wpr-878984

ABSTRACT

One new and two known dammarane-type saponins were isolated from the leaves of Gynostemma pentaphyllum using various chromatographic methods. Their structures were identified by HR-ESI-MS,~( 1)H-NMR, ~(13)C-NMR, 2 D-NMR spectra as 2α,3β,12β,20,24(S)-tetrahdroxydammar-25-en-3-O-[β-D-glucopyranosyl(1→2)-β-D-glucopyranosyl]-20-O-β-D-xylopyranosyl(1→6)-β-D-glucopyranoside(1, a new compound, namely gypenoside J5) and 2α,3β,12β,20,24(R)-tetrahdroxydammar-25-en-3-O-[β-D-glucopyranosyl(1→2)-β-D-glucopyranosyl]-20-O-β-D-xylopyranosyl(1→6)-β-D-glucopyranoside(2) and 2α,3β,12β,20-tetrahydroxy-25-hydroperoxy-dammar-23-en-3-O-[β-D-glucopyranosyl(1→2)][β-D-glucopyranosyl]-20-O-[β-D-xylopyranosyl(1→6)]-β-D-glucopy-ranoside(3), respectively. Compounds 1 and 2 were a pair of C-24 epimers. All compounds showed weak cytotoxicity agxinst H1299, HepG2, PC-3, SH-SY5 Y cancer cell lines. However, they exerted protective effect against SH-SY5 Y cellular damage induced by H_2O_2 dose-dependently, of which compound 1 displayed the strongest antioxidant effect. The present study suggested that G. pentaphyllum has antioxidative potential and the saponins from G. pentaphyllum are considered as the active compounds with neuroprotecitve effect.


Subject(s)
Gynostemma , Molecular Structure , Neuroprotective Agents/pharmacology , Saponins/pharmacology , Triterpenes/pharmacology
13.
Yao Xue Xue Bao ; (12): 478-483, 2020.
Article in Chinese | WPRIM | ID: wpr-815849

ABSTRACT

Butylphthalide and ferulic acid exhibit excellent therapeutic effects in ischemic stroke. In this research, twelve 3-n-butylphthalide derivatives were designed by molecular hybridization strategy. The target compounds were obtained by nucleophilic substitution, reduction reaction, esterification reaction and elimination reaction, and the structure was confirmed by 1H NMR, 13C NMR and ESI-MS. All compounds were evaluated for neuroprotective activity against OGD/R-induced neurotoxicity in rat cortical neurons by MTT assay. The compounds with the best neuroprotective activity were biologically evaluated for their ability to inhibit platelet aggregation induced by arachidonic acid (AA) and adenosine diphosphate (ADP) via the Bron method.The results indicate that 7b exhibited potent neurocyte protective activity as well as prominent anti-platelet aggregation activity. Compound 7b has potential to be developed as a drug for ischemic stroke.

14.
Natural Product Sciences ; : 130-135, 2019.
Article in English | WPRIM | ID: wpr-760553

ABSTRACT

The purification of the MeOH extract from Impatiens balsamina by repeated column chromatography led to the isolation of one new tetrahydronaphthalene (1), together with eleven known compounds (2 – 12). The structure of the new compound (1) was determined by spectral data analysis (1H and 13C-NMR, 1H-1H COSY, HSQC, HMBC, NOESY, and HR-ESI-MS). Isolated compounds (1 – 12) were evaluated for their inhibitory effects on NO production in LPS-activated murine microglial BV-2 cells and their effects on NGF secretion from C6 glioma cells. Compounds 3, 7, and 10 reduced NO levels in LPS-activated murine microglial cells with IC50 values of 26.89, 25.59, and 44.21 µM, respectively. Compounds 1, 5, and 9 upregulated NGF secretion to 153.09 ± 4.66, 156.88 ± 8.86, and 157.34 ± 3.30%, respectively.


Subject(s)
Balsaminaceae , Chromatography , Glioma , Impatiens , Inhibitory Concentration 50 , Nerve Growth Factor , Neuroprotective Agents , Statistics as Topic
15.
International Eye Science ; (12): 275-279, 2019.
Article in Chinese | WPRIM | ID: wpr-713013

ABSTRACT

@#AIM: To study glucagon-like peptide-1(GLP-1)analogues(liraglutide)in patients with mild to moderate nonproliferative diabetic retinopathy(NPDR)and the clinical efficacy of retinal neuroprotection.<p>METHODS: Sixty patients with type 2 diabetes mellitus with mild or moderate NPDR were treated in our department of endocrinology. They were randomly divided into two groups. Patients in the experimental group used metformin, insulin combined with liraglutide to regulate blood glucose, while the control group used metformin, insulin for hypoglycemia. Comparing the two groups of patients before and after the treatment, including HbA1c and pattern visual evoked potential(P-VEP)P100 amplitude and P100 latency, full field electroretinogram(F-ERG)oscillatory potentials(Ops)total amplitude, and light and dark adaptation 3.0 the amplitude of the a-, b-wave varies.<p>RESULTS: After 6mo treatment, the total amplitude of Ops in the experimental and control groups increased compared with that before treatment. The difference was statistically significant(all <i>P</i><0.01). And the total amplitude of Ops in the experimental group was higher than that of the control group, the difference was statistically significant(<i>P</i>=0.049). Meanwhile the b-wave amplitudes of the light and dark adaptation 3.0 in the experimental group were higher than those in the control group(<i>P</i>=0.001, <i>P</i>=0.014); however, there was no statistical significance in a-wave amplitude between the light and dark adaptation 3.0 in both groups after treatment(<i>P</i>=0.505, 0.441, 0.193, respectively). the b-wave amplitudes of the experimental group with dark and light adaptation 3.0 increased compared with that before treatment, and the difference was statistically significant(<i>P</i><0.01, <i>P</i>=0.019). The a-wave amplitude of light and dark adaptation in the experimental group increased compared with that before treatment, but the difference was not statistically significant(<i>P</i>=0.130, 0.147). <p>CONCLUSION: GLP-1 analogues can improve the function of retinal neurons in patients with mild to moderate NPDR to a certain extent, and have a positive effect on the prognosis of DR.

16.
Article in Chinese | WPRIM | ID: wpr-801934

ABSTRACT

Objective: To establish a model for the injury of human neuroblastoma cell (SH-SY5Y) induced by sodium glutamate, and to observe the protective effect of syringaresinol on cell damage from Viscum liquidambaricolum hayataon, and to explore its mechanism. Method: Construction of SH-SY5Y cell injury model using sodium glutamate.The experiment was divided into normal cell group, injury model group (sodium glutamate 50 mmol·L-1, sodium glutamate 50 mmol·L-1 + DMSO),syringaresinol experimental group (6.25, 12.5, 25 μmol·L-1), by cell counting, cell morphology observation, Annexin V-FITC/PI apoptosis detection, ROS reactive oxygen species detection, mitochondrial membrane potential, and Western blot, evaluation of syringaresinol on glutamate-induced neuronal excitability injury neuroprotective activity. Result: Compared with normal group, the cell survival rate of the model group was significantly decreased (PPPPP-1) showed a concentration-dependent increase in cells. Survival rate (PPPPPConclusion: Syringaresinol has significant protective activity against excitatory damage induced by sodium glutamate in SH-SY5Y neurons, the mechanism may be through anti-oxidative stress, repairing mitochondrial function and DNA damage to significantly reduce sodium glutamate-induced neuronal apoptosis.

17.
Acta Pharmaceutica Sinica B ; (6): 805-817, 2018.
Article in English | WPRIM | ID: wpr-690862

ABSTRACT

The EtOH extracts of the whole plants of afforded 17 new jatrophane diterpenoid esters, helioscopianoids A-Q (-), along with eight known compounds (-). Their structures were elucidated by extensive spectroscopic methods and Mo(OAc)-induced ECD analysis, and the structures of compounds , , and were confirmed by X-ray crystallography. Compounds - were evaluated for inhibitory effects on P-glycoprotein (P-gp) in an adriamycin (ADM)-resistant human breast adenocarcinoma cell line (MCF-7/ADR) and neuroprotective effects against serum deprivation-induced and rotenone-induced PC12 cell damage. Compounds and increased the accumulation of ADM in MCF-7/ADR cells by approximately 3-fold at a concentration of 20 μmol/L. Compound could attenuate rotenone-induced PC12 cell damage, and compounds , , and showed neuroprotective activities against serum deprivation-induced PC12 cell damage.

18.
Article in Chinese | WPRIM | ID: wpr-692567

ABSTRACT

Neonatal hypoxic-ischemic encephalopathy (HIE) is a leading cause of infant morbidity and mortality,often causing irreversible brain damage,and eventually leading to neurodevelopmental and cognitive dysfunction.Previous studies have shown that some commonly used inhaled anesthetics has certain neuroprotective effects on hypoxic-ischemic brain damage(HIBD),but its mode of action and the mechanisms are not clear.In this review,the protective effect of inhaled anesthetics on HIBD in neonates and its related mechanisms are described.

19.
Article in English | WPRIM | ID: wpr-713832

ABSTRACT

BACKGROUND/OBJECTIVE: Oxidative stress plays a key role in neuronal cell damage, which is associated with neurodegenerative disease. The aim of present study was to investigate the neuroprotective effects of perilla oil (PO) and its active component, alpha-linolenic acid (ALA), against hydrogen peroxide (H₂O₂)-induced oxidative stress in SH-SY5Y neuronal cells. MATERIALS/METHODS: The SH-SY5Y human neuroblastoma cells exposed to 250 µM H₂O₂ for 24 h were treated with different concentrations of PO (25, 125, 250 and 500 µg/mL) and its major fatty acid, ALA (1, 2.5, 5 and 25 µ/mL). We examined the effects of PO and ALA on H₂O₂-induced cell viability, lactate dehydrogenase (LDH) release, and nuclear condensation. Moreover, we determined whether PO and ALA regulated the apoptosis-related protein expressions, such as cleaved-poly ADP ribose polymerase (PARP), cleaved caspase-9 and -3, BCL-2 and BAX. RESULTS: Treatment of H₂O₂ resulted in decreased cell viability, increased LDH release, and increase in the nuclei condensation as indicated by Hoechst 33342 staining. However, PO and ALA treatment significantly attenuated the neuronal cell death, indicating that PO and ALA potently blocked the H₂O₂-induced neuronal apoptosis. Furthermore, cleaved-PARP, cleaved caspase-9 and -3 activations were significantly decreased in the presence of PO and ALA, and the H₂O₂-mediated up-regulated BAX/BCL-2 ratio was blocked after treatment with PO and ALA. CONCLUSIONS: PO and its main fatty acid, ALA, exerted the protective activity from neuronal oxidative stress induced by H₂O₂. They regulated apoptotic pathway in neuronal cell death by alleviation of BAX/BCL-2 ratio, and down-regulation of cleaved-PARP and cleaved caspase-9 and -3. Although further studies are required to verify the protective mechanisms of PO and ALA from neuronal damage, PO and ALA are the promising agent against oxidative stress-induced apoptotic neuronal cell death.


Subject(s)
Humans , Adenosine Diphosphate Ribose , alpha-Linolenic Acid , Apoptosis , Caspase 9 , Cell Death , Cell Survival , Down-Regulation , Hydrogen Peroxide , Hydrogen , L-Lactate Dehydrogenase , Neuroblastoma , Neurodegenerative Diseases , Neurons , Neuroprotective Agents , Oxidative Stress , Perilla
20.
Zhongcaoyao ; Zhongcaoyao;(24): 3411-3418, 2018.
Article in Chinese | WPRIM | ID: wpr-851847

ABSTRACT

Dihydromyricetin (DMY) is the main flavonoid compound in Ampelopsis grossedentata. It is popular for various biological and pharmacological activities including antiflammatory, antibacterial, antitumor, regulating blood fat, hypolipidemic, and protecting liver function. Recently studies have suggested that DMY works as neuroprotective molecular, ameliorating neurological abnormal symptoms in the Alzheimer’s disease, Parkinson’s disease, alcohol addiction, major depression disorder and so on. This paper reviewed various pharmacological effects of DMY and analyzed detailedly its interactions with the neuropsychiatric drugs and chemotherapeutics in the metabolism and pharmacodynamics perspectives in the last decade. We further elucidate the role of DMY in the combined medication, aiming to provide scientific reference for its potential in clinic.

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