Danggui Buxue decoction ameliorates mitochondrial biogenesis and cognitive deficits through upregulating histone H4 lysine 12 acetylation in APP/PS1 mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Buxue decoction (DBD) is a classic herbal decoction consisting of Astragali Radix (AR) and Angelica Sinensis Radix (ASR) with a 5:1 wt ratio, which can supplement 'blood' and 'qi' (vital energy) for the treatment of clinical diseases. According to Traditional Chinese Medicine (TCM) theory, dementia is induced by Blood deficiency and Qi weakness, which causes a decline in cognition. However, the underlying mechanisms of DBD improving cognition deficits in neurodegenerative disease are no clear. AIM OF THE STUDY: This study aims at revealing the underlying mechanisms of DBD plays a protective role in the cognitive deficits and pathology process of Alzheimer's disease (AD). MATERIALS AND METHODS: The APP/PS1 (Mo/HuAPP695swe/PS1-dE9) double transgenic mice were adopted as an experimental model of AD. Qualitative and quantitative analysis of 3 compounds in DBT was analyzed by HPLC. Morris water maze test, Golgi staining and electrophysiology assays were used to evaluate the effects of DBD on cognitive function and synaptic plasticity in APP/PS1 mice. Western blot, immunofluorescence and Thioflavin S staining were used for the pathological evaluation of AD. Monitoring the level of ATP, mitochondrial membrane potential, SOD and MDA to evaluate the mitochondrial function, and with the usage of qPCR and CHIP for the changes of histone post-translational modification. RESULTS: In the current study, we found that DBD could effectively attenuate memory impairments and enhance long-term potentiation (LTP) with concurrent increased expression of memory-associated proteins. DBD markedly decreased Aß accumulation in APP/PS1 mice by decreasing the phosphorylation of APP at the Thr668 level but not APP, PS1 or BACE1. Further studies demonstrated that DBD restored mitochondrial biogenesis deficits and mitochondrial dysfunction. Finally, the restored mitochondrial biogenesis and cognitive deficits are under HADC2-mediated histone H4 lysine 12 (H4K12) acetylation at the peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) and N-methyl-D-aspartate receptor type 2B (GluN2B) promoters. CONCLUSIONS: These findings reveal that DBD could ameliorate mitochondrial biogenesis and cognitive deficits by improving H4K12 acetylation. DBD might be a promising complementary drug candidate for AD treatment.

Steroidal saponins and ecdysterone from Asparagus filicinus and their cytotoxic activities.

Two new spirostanoides, filiasparosides E (1) and F (2), one new furostanoside, filiasparoside G (3), and one new ecdysterone, stachysterone A-20, 22-acetonide (4), together with six known steroidal saponins, asparagusin A (5), filiasparoside A (6), filiasparoside B (7), aspafilioside A (8), aspafilioside B (9), and filiasparoside C (10) were isolated from the roots of Asparagus filicinus Buch.-Ham. Their structures were elucidated on the basis of spectroscopic and chemical evidence. Compounds 1-10 were investigated for their cytotoxicities against human breast adenocarcinoma MDA-MB-231 cell line and compounds 8-10 exhibited cytotoxic activities with IC(50) values ranging from 3.4 to 6.6microM.

Chemical components and tyrosinase inhibitors from the twigs of Artocarpus heterophyllus.

An HPLC method was developed and validated to compare the chemical profiles and tyrosinase inhibitors in the woods, twigs, roots, and leaves of Artocarpus heterophyllus . Five active tyrosinase inhibitors including dihydromorin, steppogenin, norartocarpetin, artocarpanone, and artocarpesin were used as marker compounds in this HPLC method. It was discovered that the chemical profiles of A. heterophyllus twigs and woods are quite different. Systematic chromatographic methods were further applied to purify the chemicals in the twigs of A. heterophyllus. Four new phenolic compounds, including one isoprenylated 2-arylbenzofuran derivative, artoheterophyllin A (1), and three isoprenylated flavonoids, artoheterophyllin B (2), artoheterophyllin C (3), and artoheterophyllin D (4), together with 16 known compounds, were isolated from the ethanol extract of the twigs of A. heterophyllus. The structures of compounds 1-4 were elucidated by spectroscopic analysis. However, the four new compounds did not show significant inhibitory activities against mushroom tyrosinase compared to kojic acid. It was found that similar compounds, such as norartocarpetin and artocarpesin in the twigs and woods of A. heterophyllus, contributed to their tyrosinase inhibitory activity.

Simultaneous determination of three phytoecdysteroids in the roots of four medicinal plants from the genus Asparagus by HPLC.

INTRODUCTION: The genus Asparagus is known to contain phytoecdysteroids that have been shown to exhibit many beneficial pharmacological properties such as improving lipid metabolism, modulating immunological responses, etc. Currently, knowledge about the contents of phytoecdysteroids in the roots of Asparagus species is limited and HPLC methods for their analyses are unsatisfactory. OBJECTIVE: To develop an HPLC method for the simultaneous determination of three phytoecdysteroids, 20-hydroxyecdysone, ecdysone and ajugasterone C, in the roots of four Asparagus species. METHODOLOGY: Reference standards of phytoecdysteroids were isolated from the roots of Asparagus filicinus by open column chromatography. HPLC analysis was performed on an Alltima C(18) column with gradient elution using aqueous 0.2% formic acid solution containing 0.2% isopropanol and acetonitrile. RESULTS: All calibration curves showed good linear correlation coefficients (r(2) > 0.9994) within the tested ranges. Limits of detection (S/N = 3) and quantification (S/N = 10) for the three analytes were less than 2.7 and 9.9 ng, respectively. Intra- and inter-day RSDs of retention times and peak areas were less than 2.61%. The recoveries were between 93.2 and 107.5%, and the RSDs were less than 3.83% for the root samples of A. filicinus. CONCLUSION: The HPLC method established is appropriate for the efficient quantitative and qualitative analyses of important phytoecdysteroids in Asparagus species. This study showed that A. filicinus is rich in phytoecdysteroids, especially 20-hydroxyecdysone. However the three studied phytoecdysteroids were not detected in A. cochinchinensis, A. officinalis and A. setaceus.

Iridoids from Neopicrorhiza scrophulariiflora and their hepatoprotective activities in vitro.

Four new non-glycosidic iridoids, piscrocins D (1), E (2), F (6), and G (7), as well as two new iridoid glycosides, piscrosides A (8) and B (9), were isolated from the roots of Neopicrorhiza scrophulariiflora (Scrophulariaceae), together with seven known iridoids. The structures of the isolated compounds were established by means of 1D and 2D NMR spectroscopy and chemical methods. The hepatoprotective activities of these compounds were evaluated by measuring their effects on CCl(4)-induced hepatocytes damage in vitro, and the structure-activity relationships were also discussed.

Antioxidative phenylethanoid and phenolic glycosides from Picrorhiza scrophulariiflora.

One new phenylenthanoid glycoside, scroside D (2), was isolated from the roots of Picrorhiza scrophulariiflora (Scrophulariaceae), together with nine known phenylethanoid and phenolic glycosides: 2-(3,4-dihydroxyphenyl)-ethyl-O-beta-D-glucopyranoside (1), 2-(3-hydroxy-4-methoxyphenyl)-ethyl-O-beta-D-glucopyranosyl (1-->3)-beta-D-glucopyranoside (3), scroside B (4), hemiphroside A (5), plantainoside D (6), scroside A (7), androsin (8), piceoside (9), and 6-O-feruloyl-beta-D-glucopyranoside (10). The structures of these compounds were elucidated using spectroscopic methods. The antioxidative activities of these isolated compounds were evaluated based on their scavenging effects on hydroxyl radicals and superoxide anion radicals, respectively. Compounds 1, 2, and 6 showed potent antioxidative effects as those of ascorbic acid and the structure-activity relationship is discussed.

Three new cyclopentanoid monoterpenes from Picrorhiza scrophulariiflora.

Three new cyclopentanoid monoterpenes, named piscrocins A , B and C, were isolated from the roots of Picrorhiza scrophulariiflora (Scrophulariaceae). The structures of these new compounds were established by 1D and 2D NMR spectroscopic techniques ( (1)H- (1)H COSY, HMQC, HMBC, and NOESY) in combination with X-ray crystallographic analysis.