Gardenia jasminoides Extract GJ-4 Alleviates Memory Deficiency of Vascular Dementia in Rats through PERK-Mediated Endoplasmic Reticulum Stress Pathway.

Endoplasmic reticulum stress (ERS) is involved in the pathological process of vascular dementia (VD). GJ-4 is extracted from Gardenia jasminoides J. Ellis and has been reported to have protective roles in ischemia-related brain damage. However, the role of GJ-4 in ERS has not been elucidated. We established a VD rat model through bilateral common carotid arteries occlusion (2-VO). The rats were intragastrically administrated with GJ-4 (10, 25, and 50[Formula: see text]mg/kg) and nimodipine (10[Formula: see text]mg/kg). Data from a Morris water maze test showed that GJ-4 could significantly alleviate learning and memory deficits in VD rats. Nissl and cleaved caspase-3 staining revealed that GJ-4 can inhibit apoptosis and thus exert a protective role in the brain of 2-VO rats. Western blot results suggested that GJ-4 significantly reduced ERS-related protein expression and inhibited apoptosis through suppression of the PERK/eIF2[Formula: see text]/ATF4/CHOP signaling pathway. For in vitro studies, the oxygen-glucose deprivation (OGD) SH-SY5Y model was employed. Western blot and Hoechst 33342/PI double staining were utilized to explore the effects of crocetin, the main active metabolite of GJ-4. Like GJ-4 in vivo, crocetin in vitro also decreased ERS-related protein expression and inhibited the activation of the PERK/eIF2[Formula: see text]/ATF4/CHOP signaling pathway. Thus, crocetin exerted similar protective roles on OGD challenged SH-SY5Y cells in vitro. In summary, GJ-4 and crocetin reduce the ERS in the brain of VD rats and SY5Y cells subjected to OGD and inhibit neuronal apoptosis through suppression of the PERK/eIF2[Formula: see text]/ATF4/CHOP pathway, suggesting that GJ-4 may be useful for the treatment of VD.

The Protective Effects of Gardenia jasminoides (Fructus Gardenia) on Amyloid-ß-Induced Mouse Cognitive Impairment and Neurotoxicity.

Alzheimer's disease (AD) is the most common neurodegenerative disease in the world. Although the exact causes of AD have not yet been fully elucidated, cholinergic dysfunction, mitochondrial damage, oxidative stress and neuroinflammation have been recognized as influential factors. Current drugs that are designed to address only a single target are unable to mitigate or prevent the progression of this complicated disease, so new disease-modifying drugs are urgently needed. Chinese herbs with thousand years of effective usage might be a good source for potential drugs. Gardenia jasminoides J. Ellis (Fructus Gardenia) is a common traditional Chinese medicine with tranquilizing effects, which is an important component of widely-used traditional Chinese medicine for dementia. GJ-4 is crocin richments extracted from Gardenia jasminoides J. Ellis. In our study, we attempted to observe the effects of GJ-4 on learning and memory injury induced by amyloid-[Formula: see text] 25-35 (A[Formula: see text] injection in mice. Treatment with GJ-4 dose-dependently enhanced the memory and cognition ability of A[Formula: see text]-injected mice. Preliminary mechanistic studies revealed the protective effect of GJ-4 was related to its protection of neurons and cholinergic dysfunction. The mechanistic results also indicated that GJ-4 could enhance antioxidant capacity and attenuate neuroinflammation. Our results implied that GJ-4 might be a promising drug to improve cognitive and memory impairment, with multiple targets.

Anti-inflammatory pentacyclic triterpenes from the stems of Euonymus carnosus.

Three new lupane-type triterpenoids (1-3), three new oleane-type triterpenoids (4-6), as well as two known compounds (7-8) were isolated from Euonymus carnosus. The structures of the compounds were elucidated on the basis of spectroscopic data analyses, including UV, IR, MS, and NMR experiments. The inhibitory on LPS-induced NO production in microglia BV2 cells of compounds 1-8 were also evaluated. Compounds 1 and 2 showed moderate abilities to inhibit NO production, with IC50 values of 5.99 and 8.47µM, respectively.

[Research progress in the study of protective effect of tanshinone IIA on cerebral ischemic stroke].

Danshen is one of the traditional Chinese herbal medicines and nas a long history or being used clinically in the treatment of cardiovascular and cerebrovascular conditions such as coronary heart disease and angina pectoris. Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen. It has been reported to be the major bioactive compound of Danshen and has diverse biological effects. Recent studies demonstrated that tanshinone IIA had neuroprotective effects on experimental ischemic stroke through its antiinflammatory, anti-oxidant, anti-apoptosis effects and its inhibitory effect on excitatory amino acid toxicity. In this review, we summarized all the recent progresses on the protective effect of tanshinone IIA on cerebral ischemic stroke. Hopefully, this article will throw some light on further study and application of tanshinone IIA.

Bioactive carbazole alkaloids from the stems of Clausena lansium.

Seven new carbazole alkaloids, claulansines L-R (1-7), and six known analogues (8-13) were isolated from the stems of Clausena lansium. Their structures were elucidated on the basis of spectroscopic analyses, including UV, IR, and NMR experiments (HSQC, HMBC, and NOE experiment). Compound 7 showed moderate anti-inflammatory activities. Compounds 3, 5, 6, 8, and 12 exhibited moderate hepatoprotective activities.

Anti-inflammatory amide alkaloids from the stems of Clausena emarginata.

Two new amide alkaloids, clauemaramide A (1) and clauemaramide B (2), and three known analogs were isolated from the stems of Clausena emarginata. Their structures were determined on the basis of spectroscopic analyses. The absolute configurations of 1 and 2 were confirmed by CD spectroscopy. Compound 3 showed moderate inhibitory effects on LPS-induced NO production (IC59 value = 4.9 µM).

Lupane triterpenoids from the stems of Euonymus carnosus.

Fifteen new lupane-type triterpenoids (1-15) and 10 known triterpenoids (16-25) were isolated from the stems of Euonymus carnosus. The structures of the new compounds were elucidated on the basis of spectroscopic analyses, and the absolute configuration of compound 1 was confirmed by X-ray crystallographic analysis using anomalous scattering of Cu Kα radiation. In addition, the compounds were tested for their cytotoxic activity against five human cancer cell lines and their ability to inhibit LPS-induced nitric oxide production in the murine microglia BV2 cell line. Compound 11 exhibited moderate cytotoxicity against several human cancer cell lines, and compounds 1, 2, 4, 5, 20, and 25 showed neuritis inhibitory activity against microglial inflammation factor, with IC50 values of 7.39, 7.48, 7.80, 3.48, 2.54, and 6.09 µM, respectively.

Bisindole alkaloids with neural anti-inflammatory activity from Gelsemium elegans.

Three new trace bisindole alkaloids geleganimines A and B (1, 2) and geleganamide (3) were isolated from the aerial parts of Gelsemium elegans. Their structures were elucidated by spectroscopy, particularly from their carbon-proton coupling constants, and electronic circular dichroism. Compounds 1-3 are the first bisindole alkaloids discovered from the genus Gelsemium. Geleganimine B exhibited anti-inflammatory activity indirectly by suppressing lipopolysaccharide-induced pro-inflammatory factors in BV2 microglial cells with an IC50 value of 10.2 µM. These findings confirm the importance of bioactive trace components in medicinal plant research.

FLZ alleviates the memory deficits in transgenic mouse model of Alzheimer's disease via decreasing beta-amyloid production and tau hyperphosphorylation.

Alzheimer's disease (AD) is the most common cause of dementia worldwide and mainly characterized by the aggregated ß-amyloid (Aß) and hyperphosphorylated tau. FLZ is a novel synthetic derivative of natural squamosamide and has been proved to improve memory deficits in dementia animal models. In this study, we aimed to investigate the mechanisms of FLZ's neuroprotective effect in APP/PS1 double transgenic mice and SH-SY5Y (APPwt/swe) cells. The results showed that treatment with FLZ significantly improved the memory deficits of APP/PS1 transgenic mice and decreased apoptosis of SH-SY5Y (APPwt/swe) cells. FLZ markedly attenuated Aß accumulation and tau phosphorylation both in vivo and in vitro. Mechanistic study showed that FLZ interfered APP processing, i.e., FLZ decreased ß-amyloid precursor protein (APP) phosphorylation, APP-carboxy-terminal fragment (APP-CTF) production and ß-amyloid precursor protein cleaving enzyme 1 (BACE1) expression. These results indicated that FLZ reduced Aß production through inhibiting amyloidogenic pathway. The mechanistic study about FLZ's inhibitory effect on tau phosphorylation revealed t the involvement of Akt/glycogen synthase kinase 3ß (GSK3ß) pathway. FLZ treatment increased Akt activity and inhibited GSK3ß activity both in vivo and in vitro. The inhibitory effect of FLZ on GSK3ß activity and tau phosphorylation was suppressed by inhibiting Akt activity, indicating that Akt/GSK3ß pathway might be the possible mechanism involved in the inhibitory effect of FLZ on tau hyperphosphorylation. These results suggested FLZ might be a potential anti-AD drug as it not only reduced Aß production via inhibition amyloidogenic APP processing pathway, but also attenuated tau hyperphosphoylation mediated by Akt/GSK3ß.

[Neurodegenerative conformational disease and heat shock proteins].

Many major neurodegenerative diseases are associated with proteins misfolding and aggregation, which are also called "neurodegenerative conformational disease". The interaction of gene mutation and environmental factors are probably primary events resulting in oligomer and aggregate formations of proteins. Moreover, the dysfunctions of protein control systems, i.e. the ubiquitin-proteasome system and autophagy-lysosomal system, also contribute to the neurodegenerative process. The present review mainly summarizes protein misfolding and aggregation in the development of neurodegenerative conformational disease and the underling mechanisms, as well as upregulation of heatshock proteins as a promising treatment method for this kind of disease.

[Effects of Tiaoxin and Zishen prescription on hippocampus neurotransmitters in Alzheimer's disease rats].

AIM: A method of stereotaxic apparatus was employed to damage the nucleus basalis of Meynert, and the effects of Tiao-xinzishen prescriptions on neurotransmitters such as ACh, 5-HT and NE in hippocampus were observed. METHODS: Rats were placed on the brain stereotaxic apparatus and received a bilateral lesion of Meynert by IA injection, according to the atlas of Daxinos and Watson. After seven days of lesion, AD rats were selected. Rats were treated with Tiaoxin or/and Zishen prescription for 20 days, respectively. Hippocampus ACh was measured by spectrophotometer and 5-HT and NE by high performance liquid chromatography (HPLC). RESULTS: The contents of hippocampus ACh, 5-HT and NE of AD rats were significantly increased after the treatment with the three prescriptions, respectively. CONCLUSION: These prescriptions had some up regulating effects on hippocampus neurotransmitters in rats, which had already decreased due to dementia.