The botanical origin and antioxidant, anti-BACE1 and antiproliferative properties of bee pollen from different regions of South Korea.

BACKGROUND: Bee pollen (BP) has been used as a traditional medicine and food diet additive due to its nutritional and biological properties. The potential biological properties of bee pollen vary greatly with the botanical and geographical origin of the pollen grains. This study was conducted to characterize the botanical origin and assess the antioxidant effects of ethanol extracts of 18 different bee pollen (EBP) samples from 16 locations in South Korea and their inhibitory activities on human ß-amyloid precursor cleavage enzyme (BACE1), acetylcholinesterase (AChE), human intestinal bacteria, and 5 cancer cell lines. METHODS: The botanical origin and classification of each BP sample was evaluated using palynological analysis by observing microscope slides. We measured the biological properties, including antioxidant capacity, inhibitory activities against human BACE1, and AChE, and antiproliferative activities toward five cancer cell lines, of the 18 EBPs. In addition, the growth inhibitory activities on four harmful intestinal bacteria, six lactic acid-producing bacteria, two nonpathogenic bacteria, and an acidulating bacterium were also assessed. RESULTS: Four samples (BP3, BP4, BP13 and BP15) were found to be monofloral and presented four dominant pollen types: Quercus palustris, Actinidia arguta, Robinia pseudoacacia, and Amygdalus persica. One sample (BP12) was found to be bifloral, and the remaining samples were considered to be heterofloral. Sixteen samples showed potent antioxidant activities with EC50 from 292.0 to 673.9 µg mL- 1. Fourteen samples presented potent inhibitory activity against human BACE1 with EC50 from 236.0 to 881.1 µg mL- 1. All samples showed antiproliferative activity toward the cancer cell lines PC-3, MCF-7, A549, NCI-H727 and AGS with IC50 from 2.7 to 14.4 mg mL- 1, 0.9 to 12.7 mg mL- 1, 5.0 to > 25 mg mL- 1, 2.7 to 17.7 mg mL- 1, and 2.4 to 8.7 mg mL- 1, respectively. In addition, total phenol and flavonoid contents had no direct correlation with antioxidant, anti-human BACE1, or antiproliferative activities. CONCLUSION: Fundamentally, Korean bee pollen-derived preparations could be considered a nutritional addition to food to prevent various diseases related to free radicals, neurodegenerative problems, and cancers. The botanical and geographical origins of pollen grains could help to establish quality control standards for bee pollen consumption and industrial production.

Therapeutic effect of intradermal needling combined with rehabilitation intervention on knee osteoarthritis in the middle and early stages / 中国针灸

OBJECTIVE@#To observe the effect of intradermal needing combined with rehabilitation intervention on middle and early knee osteoarthritis.@*METHODS@#Seventy patients were randomly divided into an observation group and a control group, 35 cases in each group. Excluding the dropping cases, finally, 34 cases in the observation group and 32 cases in the control group were included in the statistics. Intradermal needing combined with rehabilitation intervention were given in the observation group, the intradermal needing was applied at Dubi (ST 35), Neixiyan (EX-LE 8), Xuehai (SP 10), Liangqiu (ST 34), Yanglingquan (GB 34), point, and retained for 24 h; the simple conventional rehabilitation intervention was given in the control group. The visual analogue scale (VAS) was used to evaluate knee pain before treatment, the end of initial treatment, 1 month after treatment, and 3 months after treatment. The Western Ontario and McMaster Osteoarthritis index (WOMAC) was used to assess the joint function of the knee, the active knee flexion range (ROM) was used to assess the joint mobility of the knee before treatment and 1 month after treatment, and the efficacy of the two groups was evaluated.@*RESULTS@#At the end of the initial treatment, the VAS score in the observation group were significantly improved as compared with that before treatment and the control groups (0.05). After 1 month of treatment, the VAS score, WOMAC score and ROM measurement in the two groups were significantly improved as compared with those before treatment (<0.05), and the observation group was superior to the control group (<0.05); the total effective rate in the observation group was 97.1% (33/34), which was better than 81.3% (26/32) in the control group (<0.05). At the follow-up, the VAS scores in the two groups were slightly higher than those after 1 month of treatment, but the difference was still statistically significant as compared with those before treatment (<0.05), and the observation group was still superior to the control group (<0.05).@*CONCLUSION@#The combination of intradermal needing combined with rehabilitation intervention can effectively alleviate knee pain and improve joint function. It has a beneficial effect on the rehabilitation of middle and early knee osteoarthritis.

Acetylshikonin attenuates angiotensin II-induced proliferation and motility of human brain smooth muscle cells by inhibiting Wnt/ß-catenin signaling.

Cerebrovascular smooth muscle cell proliferation and migration contribute to hyperplasia in case of cerebrovascular remodeling and stroke. In the present study, we investigated the effects of acetylshikonin, the main ingredient of a Chinese traditional medicine Zicao, on human brain vascular smooth muscle cell (HBVSMCs) proliferation and migration induced by angiotensin II (AngII), and the underlying mechanisms. We found that acetylshikonin treatment significantly inhibited AngII-induced HBVSMCs proliferation and cell cycle transition from G1 to S phase. Wound-healing assay and Transwell assay showed that AngII-induced cell migration and invasion were markedly attenuated by acetylshikonin. In addition, AngII challenge significantly induced Wnt/ß-catenin signaling activation, as evidenced by increased ß-catenin phosphorylation and nuclear translocation and GSK-3ß phosphorylation. However, acetylshikonin treatment inhibited the activation of Wnt/ß-catenin signaling. Consequently, western blotting analysis revealed that acetylshikonin effectively reduced the expression of downstream target genes in AngII-treated cells, including c-myc, survivin and cyclin D1, which contributed to the inhibitory effect of acetylshikonin on HBVSMCs proliferation. Further, stimulation with recombinant Wnt3a dramatically reversed acetylshikonin-mediated inhibition of proliferation and cell cycle transition in HBVSMCs. Our study demonstrates that acetylshikonin prevents AngII-induced cerebrovascular smooth muscle cells proliferation and migration through inhibition of Wnt/ß-catenin pathway, indicating that acetylshikonin may present a potential option for the treatment of cerebrovascular remodeling.

Using UPLC-MS/MS for Characterization of Active Components in Extracts of Yupingfeng and Application to a Comparative Pharmacokinetic Study in Rat Plasma after Oral Administration.

Yupingfeng (YPF), a famous traditional Chinese medicine, which contains a large array of compounds, has been effectually used in health protection. A two-dimensional liquid chromatography (²D-LC) combined with quadrupole time-of-flight mass spectrometry (QTOF-MS) method was firstly established to separate and identify chemical components in YPF. A total of 33 compounds were identified, including 15 constituents (flavonoids and saponins) in Astragali radix; seven constituents (sesquiterpenoids and polysaccharide) in Atractylodis rhizoma; and 11 constituents (chromone and coumarins) in Saposhnikoviae radix. The corresponding fragmentation pathway of typical substances was investigated. Then, seven active constituents (astragaloside, calycosin, formononetin, cimicifugoside, 4-O-beta-d-glucosyl-5-O-methylvisamminol, sec-O-glucosylhamaudol, and atractylenolide II) derived from three medicinal plants were chosen to further investigate the pharmacokinetic behavior of YPF formula using ultrahigh-performance liquid chromatography with triple quadrupole mass spectrometry system. The method was sensitive, accurate and reliable. We also used the area under the plasma concentration-time curve from zero to infinity (AUC0-∞) as weighting factor to make an integrated pharmacokinetic curve. Results show that the constituents of Saposhnikoviae radix have the best absorption and pharmacokinetic behavior and may play important role in leading to the changes of overall therapeutic effects of YPF. Further study is needed to confirm the association between them.

Long-time Retaining of Intradermal Needles in Treating Pharyngeal Dysphagia after Cerebral Stroke / 上海针灸杂志

Objective To observe the clinical efficacy of long-time retaining of intradermal needles plus rehabilitation training in treating pharyngeal dysphagia after cerebral stroke.Method Sixty patients with pharyngeal dysphagia after cerebral stroke were randomized into treatment group 1,treatment group 2 and a control group,20 cases each.In addition to the basic treatment and nursing,the control group received rehabilitation (neuromuscular electrical stimulation plus swallowing training);treatment group 1 was given long-time retaining of intradermal needles based on the intervention given to the control group;treatment group 2 received electroacupuncture in addition to the intervention given to the control group.After 3-week treatment,the changes in Toshima Ichiro swallowing assessment of the three groups were observed,and the clinical efficacies were also compared.Result After the intervention,each group showed a significant change in the score of Toshima Ichiro swallowing assessment (P＜0.05).Treatment group 1 and group 2 were both significantly different from the control group in comparing the score of Toshima Ichiro swallowing assessment after the treatment (P＜0.05).The total effective rate was 95.0％ in treatment group 1,90.0％ in treatment group 2,and 60.0％ in the control group.The total effective rates in treatment group 1 and 2 were both significantly different from the rate in the control group (P＜0.05).There were no significant differences in comparing the score of Toshima Ichiro swallowing assessment and total effective rate between treatment group 1 and 2 after the intervention (P＞0.05).Conclusion Long-time retaining of intradermal needles plus rehabilitation is an effective approach in treating pharyngeal dysphagia after cerebral stroke,and its efficacy is equivalent to that of electroacupuncture.

Investigational agents for treatment of traumatic brain injury.

INTRODUCTION: Traumatic brain injury (TBI) is a major cause of death and disability worldwide. To date, there are no pharmacologic agents proven to improve outcomes from TBI because all the Phase III clinical trials in TBI have failed. Thus, there is a compelling need to develop treatments for TBI. AREAS COVERED: The following article provides an overview of select cell-based and pharmacological therapies under early development for the treatment of TBI. These therapies seek to enhance cognitive and neurological functional recovery through neuroprotective and neurorestorative strategies. EXPERT OPINION: TBI elicits both complex degenerative and regenerative tissue responses in the brain. TBI can lead to cognitive, behavioral, and motor deficits. Although numerous promising neuroprotective treatment options have emerged from preclinical studies that mainly target the lesion, translation of preclinical effective neuroprotective drugs to clinical trials has proven challenging. Accumulating evidence indicates that the mammalian brain has a significant, albeit limited, capacity for both structural and functional plasticity, as well as regeneration essential for spontaneous functional recovery after injury. A new therapeutic approach is to stimulate neurovascular remodeling by enhancing angiogenesis, neurogenesis, oligodendrogenesis, and axonal sprouting, which in concert, may improve neurological functional recovery after TBI.

Emerging treatments for traumatic brain injury.

BACKGROUND: This review summarizes promising approaches for the treatment of traumatic brain injury (TBI) that are in either preclinical or clinical trials. OBJECTIVE: The pathophysiology underlying neurological deficits after TBI is described. An overview of select therapies for TBI with neuroprotective and neurorestorative effects is presented. METHODS: A literature review of preclinical TBI studies and clinical TBI trials related to neuroprotective and neurorestorative therapeutic approaches is provided. RESULTS/CONCLUSION: Nearly all Phase II/III clinical trials in neuroprotection have failed to show any consistent improvement in outcome for TBI patients. The next decade will witness an increasing number of clinical trials that seek to translate preclinical research discoveries to the clinic. Promising drug- or cell-based therapeutic approaches include erythropoietin and its carbamylated form, statins, bone marrow stromal cells, stem cells singularly or in combination or with biomaterials to reduce brain injury via neuroprotection and promote brain remodeling via angiogenesis, neurogenesis, and synaptogenesis with a final goal to improve functional outcome of TBI patients. In addition, enriched environment and voluntary physical exercise show promise in promoting functional outcome after TBI, and should be evaluated alone or in combination with other treatments as therapeutic approaches for TBI.

Mice lacking catalase develop normally but show differential sensitivity to oxidant tissue injury.

Catalase plays a major role in cellular antioxidant defense by decomposing hydrogen peroxide, thereby preventing the generation of hydroxyl radical by the Fenton reaction. The degree of catalase deficiency in acatalasemic and hypocatalasemic mice varies from tissue to tissue. They therefore may not be suitable for studying the function of this enzyme in certain models of oxidant-mediated tissue injury. We sought to generate a new line of catalase null mice by the gene targeting technique. The mouse catalase (Cat or Cas1) gene was disrupted by replacing parts of intron 4 and exon 5 with a neomycin resistance cassette. Homozygous Cat knockout mice, which are completely deficient in catalase expression, develop normally and show no gross abnormalities. Slices of liver and lung and lenses from the knockout mice exhibited a retarded rate in decomposing extracellular hydrogen peroxide compared with those of wild-type mice. However, mice deficient in catalase were not more vulnerable to hyperoxia-induced lung injury; nor did their lenses show any increased susceptibility to oxidative stress generated by photochemical reaction, suggesting that the antioxidant function of catalase in these two models of oxidant injury is negligible. Further studies showed that cortical injury from physical impact caused a significant decrease in NAD-linked electron transfer activities and energy coupling capacities in brain mitochondria of Cat knockout mice but not wild-type mice. The observed decrease in efficiency of mitochondrial respiration may be a direct result of an increase in mitochondrion-associated calcium, which is secondary to the increased oxidative stress. These studies suggest that the role of catalase in antioxidant defense is dependent on the type of tissue and the model of oxidant-mediated tissue injury.