Eucarbwenstols A-H, eight novel compounds from Eucalyptus robusta prevents MPC-5 injury via ROS modulation and regulation of mitochondrial membrane potential.

BACKGROUND: The damage of podocytes is a primary hallmark of lupus nephritis (LN). Therefore, finding an effective way to inhibit the podocyte injury is important for improving the survival and development of patients with LN. Eucalyptus robusta exhibits anti-inflammatory properties. However, whether Formyl phloroglucinol meroterpenoids (FPMs), which are specialized metabolites of the genus Eucalyptus, is an anti-inflammatory active ingredient of E. robusta remains to be determined. PURPOSE: This study asimed to identify novel FPMs from E. robusta and investigated their anti-inflammatory effects. METHODS: Various separation methods were used to isolate and identify the compounds in the PE extract of E. robusta. The structures of the isolates were determined using 1D/2D NMR data and electron circular dichroism (ECD) calculations. The level of mitochondrial reactive oxygen species (ROS) level and mitochondrial membrane potential (MMP) of the podocyte cell line, MPC-5, were assessed using a multifunctional microplate reader combined with flow cytometry and fluorescence microscopy. RESULTS: Eight novel FPMs (1-8, Eucarbwenstols A-H, Fig. 1) and 15 known FPMs (9-23) were purified from the PE extract of E. robusta. It is noteworthy that compound 1 possesses an unprecedented FPM carbon skeleton. Among these compounds, compounds 1, 2, 4 and 5 showed the most promising potential for protecting MPC-5 cells because pretreatment with pro-inflammatory cytokines TGF-ß, IFN-α and IL-6 decreased ROS production and ameliorated the mitochondrial state. CONCLUSIONS: Our research contributes to the characterization of E. robusta constituents and highlights the anti-inflammatory effects of FPMs.

[Pharmacokinetic study on five components in phthalide target areas of Chaxiong and its ß-CD inclusion compounds based on UPLC-MS/MS].

This study aims to establish a method for the determination of the concentration of five main components of phthalide target areas of Chaxiong(CPTA) and its inclusion of ß-CD in the plasma of rats, and determine the pharmacokinetic parameters, absolute bioavailability and relative bioavailability of CPTA/ß-CD inclusion compound in vivo. The plasma concentrations of senkyunolide A, N-butylphthalide, new osthol lactone, Z-ligustilide and butenyl phthalide were determined with UPLC-MS/MS. The content determination was conducted at the chromatographic conditions as follows: Shim-pack GIST C_(18)-AQ HP column(2.1 mm×100 mm, 3 µm), mobile phase of 0.1% formic acid solution(A)-acetonitrile(B), gradient elution, flow rate of 0.3 mL·min~(-1), column temperature of 35 ℃ and injection volume of 2 µL. The mass spectra were obtained with electrospray ion source(ESI), positive ion mode and multi reaction monitoring. CPTA/ß-CD inclusion compound was prepared by grinding method, DAS 2.0 software was used to model the data, and the absolute bioavailability of CPTA and relative bioavailability of inclusion compound were calculated. Finally, the methods for the determination of five components of senkyunolide A, N-butylphthalide, new osthol lactone, Z-ligustilide and butenyl phthalide in CPTA, were successfully established. The linear relationship among the five components was good within their respective ranges, r>0.99. The absolute bioavailability of the five components in rats was 22.30%, 16.32%, 21.90%, 10.16% and 12.43%, respectively. After CPTA/ß-CD inclusion was prepared, the relative bioavailability of the five components was 138.69%, 198.39%, 218.01%, 224.54% and 363.55%, respectively, significantly improved. This method is rapid, accurate and sensitive, so it is suitable for the pharmacokinetic study of extracts in traditional Chinese medicine and their preparations.

Comparison of the effects of selenomethionine and selenium-enriched yeast in the triple-transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a complex, multifactorial neurodegenerative disease that exhibits multiple pathogeneses and heterogeneity. Selenium (Se) is an essential trace element for human and animal nutrition. It has been shown that supplementation with two organic forms of Se, Se-enriched yeast (Se-yeast) and selenomethionine (Se-Met), could improve cognitive impairment, reverse synaptic deficits and mitigate tau pathology in triple-transgenic (3× Tg) AD mice. Se-yeast is well known for its high Se-Met content, which may mediate its anti-AD effects. In addition, a large amount of the physiological and biochemical mechanisms of these two Se drugs in the amelioration AD pathology remains unknown. In this study, the content of Se-yeast aside from Se was analyzed, and the effects of Se-Met and Se-yeast on 3× Tg-AD mice were investigated and compared. The results showed that both Se-Met and Se-yeast not only significantly increased the Se levels, enhanced the antioxidant capacity and improved the cognitive decline in the model, but also decreased the Aß and tau pathologies in the brain tissue of the AD mice. Moreover, the ability of Se-Met to increase the Se levels in different tissues of the AD mice was more significant than that of Se-yeast. However, the positive effect of Se-yeast on improving the cognitive ability of the AD mice was better than that of Se-Met, likely due to the various elements, vitamins and other nutrients in Se-yeast. Collectively, these results suggest that Se-yeast has potential as a clinical health product or drug for AD but that Se-Met, as a pure organic Se compound, is more suitable for studying the therapeutic mechanism of Se because of its comprehensive effects on AD.

Selenium-enriched yeast inhibited ß-amyloid production and modulated autophagy in a triple transgenic mouse model of Alzheimer's disease.

As the most common cause of progressive intellectual failure in elderly humans, Alzheimer's disease (AD) is pathologically featured by amyloid plaques, synaptic loss, and neurofibrillary tangles. The amyloid plaques are mainly aggregates of amyloid ß-peptide (Aß), a primary factor contributing to the pathogenesis of AD. Elimination or reduction of the level of Aß is considered an important strategy in AD treatment. The pharmacotherapeutic efficacy of selenium (Se), an essential biological trace element for mammalian species, has been confirmed in a number of experimental models of neurodegenerative diseases. Selenium-enriched yeast (Se-yeast) is commonly used as a nutritional supplement for Se. In this study, we investigated the effects and underlying mechanisms of Se-yeast on Aß pathology in a 4-month-old triple transgenic mouse model of AD (3×Tg-AD mice). The administration of Se-yeast attenuated the deposition of Aß in the brains of AD mice, which was concomitant with decreased levels of LC3II. The Se-yeast treatment decreased the level of amyloid-protein precursor (APP), downregulated the activity of AMP-activated protein kinase (AMPK) and upregulated the activity of AKT/mTOR/p70S6K. Furthermore, the levels of p62 also significantly decreased, and the cathepsin D levels increased, accompanied by increased turnover of Aß and APP in Se-yeast-treated AD mice. In addition to decreasing the generation of Aß, Se-yeast also inhibited the initiation of autophagy by modulating the AMPK/AKT/mTOR/p70S6K signaling pathway and enhanced autophagic clearance, thus reducing the burden of Aß accumulation in the brains of AD mice. Our results further highlight the potential therapeutic effects of Se-yeast on AD.

Long-Term Dietary Supplementation with Selenium-Enriched Yeast Improves Cognitive Impairment, Reverses Synaptic Deficits, and Mitigates Tau Pathology in a Triple Transgenic Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by multiple histopathological changes in the brain and by impairments in memory and cognitive function. Currently, there is no effective treatment that can halt or reverse the progression of this disease. Here, we explored the effects of 3 months of treatment with selenium-enriched yeast (Se-yeast), which is commonly used as a source of organic selenium (Se) for nutrition, on cognitive dysfunction and neuropathology in the triple transgenic mouse model of AD (3×Tg-AD mice). As the results revealed that Se-yeast significantly improved the spatial learning and memory retention of 3×Tg-AD mice, promoted neuronal activity, attenuated the activation of astrocytes and microglia, mitigated synaptic deficits, and reduced the levels of total tau and phosphorylated tau though inhibiting the activity of GSK-3ß, dietary supplementation with Se-yeast exerted multiple beneficial effects on the prevention or treatment of AD. These findings provide evidence of a potentially viable compound for AD treatment.

[Post-stroke dysphagia in chronic stage treated with magnetic-ball sticking therapy at the auricular points: a randomized controlled trial].

OBJECTIVE: To assess the effectiveness and safety on post-stroke dysphagia in chronic stage treated with magnetic-ball sticking therapy at the auricular points. METHODS: Ninety cases of post-apoplexy dysphagia in chronic stage were randomized into an auricular points group and an acupuncture group. In the auricular points group, the magnetic-ball sticking therapy was applied to subcortex (pizhixia, AT4), brainstem (naogan, AT(3,4i)), mouth (kou, CO1), cheek (mianjia, LO(5,6i)), tongue (she, LO2) and throat (yanhou, TG3) on one ear each time, and were changed on the other ear once every 3 days. In the acupucnture group, acupuncture was applied to Feng-chi (GB 20), Yifeng (TE 17), Shanglianquan (Extra), Jinjin (EX-HN 12), Yuye (EX-HN 13), Shuigou (GV 26) and Tongli (TH 5), etc. The needles were retained for 30 min in each treatment. The treatment was gi-yen once a day in the two groups and the treatment of 6 days made one session. There was 1 day at an interval among the sessions. Totally, 3 sessions of treatment were required. The video fluoroscopic swallowing study (VFSS) was performed for 4 kinds of food with different properties and shapes in each patient. The main indices were Rosenbek penetration-aspiration score, oral-retaining score and throat-retaining score. The efficacy, and the incidences of aspiration pneumonia and malnutrition were compared between the two groups. The nutrition indices were compared before and after treatment between the two groups, such as the skinfold thickness of triceps brachii muscle, serum albumin and peralbumin. RESULTS: In 21 days of treatment, in the auricular points group, the 1 mL liquid loversol Rosenbek penetration-aspiration score (1.51 +/- 0.69), oral-retaining score (1.17 +/- 0.38) and throat-retaining score (1.30 +/- 0.66) were all lower than those (2.51 +/- 0.67, 1.63 +/- 0.72, 1.67 +/- 0.7) in the acupuncture group separately. The 10 mL liquid loversol Rosenbek penetration-aspiration score (2.27 +/- 0.65), oral-retaining score (1.60 +/- 0.50) and throat-retaining score (1.49 +/- 0.51) were all lower than those (4.19 +/- 0.73, 2.30 +/- 0.51, 2.41 +/- 0.50) in the acupuncture group separately. The 10 mL paste loversol Rosenbek penetration-aspiration score (1.68 +/- 0.81), oral-retaining score (1.11 +/- 0.31) and throat-retaining score (1.10 +/- 0.31) were all lower than those (3.91 +/- 0.68, 1.63 +/- 0.76, 1.60 +/- 0.76) in the acupuncture group separately. The 1/4 cake-form loversol Rosenbek penetration-aspiration score (2.60 +/- 0.65), oral-retaining score (1.40 +/- 0.50) and throat-retaining score (1.74 +/- 0.49) were all lower than those (4.14 +/- 1.10, 2.40 +/- 0.73, 2.30 +/- 0.83) in the acupuncture group separately. The incidence of aspiration pneumonia was 14.9% (7/47) in the auricular points group, which was lower than 55.0% (22/40) in the acupuncture group (P < 0.01). The incidence of malnutrition was 8. 5% (4/47) in the auricular points group, which was lower than 50.0% (20/40) in the acupuncture group (P < 0.01). In 21 days of treatment, the results of the skinfold thickness of triceps brachii muscle and serum albumin in the auricular points group were better than those in the acupuncture group (both P < 0.05). CONCLUSION: The magnetic-ball sticking therapy at auricular points achieves the definite efficacy on post-stoke dysphagia in chronic stage and decreases the incidences of aspiration pneumonia and malnutrition. The efficacy of this therapy is better than acupuncture.

[Post-stroke shoulder-hand syndrome treated with acupuncture and rehabilitation: a randomized controlled trial].

OBJECTIVE: To assess the clinical efficacy on post-stroke shoulder-hand syndrome (SHS) treated with acupuncture and rehabilitation and the impacts on patients' nailfold microcirculation. METHODS: One hundred and twenty patients were randomized into an acupuncture rehabilitation group and a simple rehabilitation group, 60 cases in each one. In the simple rehabilitation group, OT (comprehensive rehabilitation therapy) training was adopted. In the acupuncture rehabilitation group, on the basis of the treatment as the simple rehabilitation, acu puncture was added at Taiyuan (LU 9), Zusanli (ST 36), Xuanzhong (GB 39), Waiguan (TE 5), Shousanli (LI 10), Quchi (LI 11) and Jianyu (LI 15). Acupuncture was given once a day, 7 days made one session. Totally, 4 sessions of treatment were required. Fugl-Meyer score, upper limb pain score, the score of nerve function defect and the items of nailfold microcirculation of patients were assessed in the the two groups before and after treatment. The efficacy was compared between the two groups. RESULTS: (1) The upper limb pain, the systematic motor function of the upper limbs, the nerve function defect, nailfold microcirculation and clinical symptoms were all improved after treatment in either the acupuncture rehabilitation group or the simple rehabilitation group as compared with those before treatment, indicating the significant difference (P<0. 05, P<0. 01). (2) The im provements in the upper limb pain (0. 90+/-0.71 vs 1. 80+/-0. 66), the systematic motor function of the upper limbs (42. 43 13. 57 vs 29. 98+/-15. 11), the nerve function defect (8. 60+/-11. 61 vs 13. 0+/-1. 74), nailfold microcirculation (total score 3. 18+/-1.32 vs 4.34+/-1.23) and clinical symptoms in the acupuncture rehabilitation group after treatment were different significantly as compared with those in the simple rehabilitation group (PO0. 05,P-O. 01), and the results in the acupuncture rehabilitation group were superior to the simple rehabilitation group. (3) In the acupuncture rehabilitation group, the markedly effective rate was 50. 0% (30/60) and the total effective rate was 93.3% (56/60), which was better than 16.7% (10/60) and 63. 3% (38/60) respectively in the simple rehabilitation group (all P<0. 05). CONCLUSION: Both the combined therapy of acupuncture and rehabilitation and the simple rehabilitation training are effective in the treatment of post-stroke SHS, and promote the status of nailfold microcirculation, the efficacy of the combined therapy is better than that of the latter.