Activated microglia-mediated neuroinflammation plays a key pathogenic role in neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and ischemia. Sulforaphane is an active compound produced after conversion of glucoraphanin by the myrosinase enzyme in broccoli (Brassica oleracea var) sprouts. Dietary broccoli extract as well as sulforaphane has previously known to mitigate inflammatory conditions in aged models involving microglial activation. Here, we produced sulforaphane-enriched broccoli sprouts through the pretreatment of pulsed electric fields in order to trigger the biological role of normal broccoli against lipopolysaccharide-activated microglia. The sulforaphane-enriched broccoli sprouts showed excellent potency against neuroinflammation conditions, as evidenced by its protective effects in both 6 and 24 h of microglial activation in vitro. We further postulated the underlying mechanism of action of sulforaphane in broccoli sprouts, which was the inhibition of an inflammatory cascade via the downregulation of mitogen-activated protein kinase (MAPK) signaling. Simultaneously, sulforaphane-enriched broccoli sprouts inhibited the LPS-induced activation of the NF-κB signaling pathway and the secretions of inflammatory proteins (iNOS, COX-2, TNF-α, IL-6, IL-1β, PGE2, etc.), which are responsible for the inflammatory cascades in both acute and chronic inflammation. It also upregulated the expression of Nrf2 and HO-1 in normal and activated microglia followed by the lowered neuronal apoptosis induced by activated microglia. Based on these results, it may exhibit anti-inflammatory effects via the NF-κB and Nrf2 pathways. Interestingly, sulforaphane-enriched broccoli sprouts improved the scopolamine-induced memory impairment in mice through Nrf2 activation, inhibiting neuronal apoptosis particularly through inhibition of caspase-3 activation which could lead to the neuroprotection against neurodegenerative disorders. The present study suggests that sulforaphane-enriched broccoli sprouts might be a potential nutraceutical with antineuroinflammatory and neuroprotective activities.

Cynanchum paniculatum KITAG. (Asclepiadaceae) is a vivacious plant distributed across all of Korea and also cultivated in China. The root of Cynanchum paniculatum is used as a Chinese traditional medicine. Recently, the plants of genus Cynanchum of Asclepiadaceae, e.g. Cynanchum atratum, Cynanchum auriculatum and Cynanchum paniculatum, were studied for their anticancer and analgesic effects. [1][2][3] In addition, Cynanchum paniculatum has been traditionally used for gastritis and relieving pain in China. In traditional medicine, the dried root of Cynanchum paniculatum relieves rheumatic arthralgia, lumbago, pain due to traumatic injuries, abdominal pain, toothache, and other kinds of pain, as well as skin diseases such as eczema, rubella, neurodermatitis and snake bite. 4) A number of chemical constituents such as cynapanosides A, B, and C, paeonol, and antopine have been identified from Cynanchum paniculatum, 3,5,6) of which paeonol had been found to have analgesic effects in mice. 6)These studies concentrated on its analgesic and anticancer effects, without investigating its anti-inflammatory effect. Therefore, the present study employed NSAIDs; indomethacin, which is a non-selective cyclooxygenase (COX) inhibitor, and phenidone, which is a dual blocker of COX and lipoxygenase (LOX), to compare the anti-inflammatory effects with EACP. Pentobarbital sodium was used to study the sedative effect. The present study was undertaken to further elucidate the anti-inflammatory and anti-nociceptive effects of Cynanchum paniculatum, using the ethyl acetate (EtOAc)-soluble portion of the 70% methanol extract of its roots. MATERIALS AND METHODS Plant MaterialThe roots of Cynanchum paniculatum were purchased from Young-chang Co., Seoul, Korea. This plant material was authenticated by Dr. D. Y. Kwon and a voucher specimen (No. 05-010) was deposited in the laboratory of herbology, College of Pharmacy, Wonkwang University, Iksan, Korea.Preparation of Fraction The roots of Cynanchum paniculatum (1 kg) were extracted with 70% MeOH three times for 2 h under heating mantle-reflux. The resultant extract was condensed to 1 l in a rotary vacuum evaporator (N-1000S, EYELA, Japan) and in succession was partitioned with hexane, EtOAc and 1-buthanol (BuOH). After each partition, the solutions were filtered and the solvents were evaporated in a rotary vacuum evaporator. The extract yielded hexane (13.0 g), EtOAc (9.85 g), BuOH (40.4 g) and water (103.7 g) soluble fractions. All of the samples were stored at Ϫ4°C. The samples of the fractions and reference drugs were suspended in 5% Tween 80.Animals Male Sprague-Dawley rats (100-120, 180-200 g) and male ICR mice (30Ϯ3 g) were purchased from SAMTAKO BIOKOREA, Korea and used in the experiments. All animals were kept in a temperature-controlled room with a 12 h light-12 h dark cycle. The animals had free access to commercial solid food (SCF Co., Ltd., Korea) and water ad libitum. They were acclimatized for at least 1 week before starting the experiments.Drugs and Chemicals Evans Blue, acetic...

The rotavirus-induced diarrhea of human and animal neonates is a major public health concern worldwide. Until recently, no effective therapy is available to specifically inactivate the rotavirion particles within the gut. Passive immunotherapy by oral administration of chicken egg yolk antibody (IgY) has emerged of late as a fresh alternative strategy to control infectious diseases of the alimentary tract and has been applied in the treatment of diarrhea due to rotavirus infection. The purpose of this concise review is to evaluate evidence on the properties and performance of anti-rotavirus immunoglobulin Y (IgY) for prevention and treatment of rotavirus diarrhea in human and animal neonates. A survey of relevant anti-rotavirus IgY basic studies and clinical trials among neonatal animals (since 1994-2015) and humans (since 1982-2015) have been reviewed and briefly summarized. Our analysis of a number of rotavirus investigations involving animal and human clinical trials revealed that anti-rotavirus IgY significantly reduced the severity of clinical manifestation of diarrhea among IgY-treated subjects relative to a corresponding control or placebo group. The accumulated information as a whole depicts oral IgY to be a safe and efficacious option for treatment of rotavirus diarrhea in neonates. There is however a clear need for more randomized, placebo controlled and double-blind trials with bigger sample size to further solidify and confirm claims of efficacy and safety in controlling diarrhea caused by rotavirus infection especially among human infants with health issues such as low birth weights or compromised immunity in whom it is most needed.

1. The objectives of this study were to evaluate the pharmacokinetics and metabolism of fimasartan in rats. 2. Unlabeled fimasartan or radiolabeled [(14)C]fimasartan was dosed by intravenous injection or oral administration to rats. Concentrations of unlabeled fimasartan in the biological samples were determined by a validated LC/MS/MS assay. Total radioactivity was quantified by liquid scintillation counting and the radioactivity associated with the metabolites was analyzed by using the radiochemical detector. Metabolite identification was conducted by product ion scanning using LC/MS/MS. 3. After oral administration of [(14)C]fimasartan, total radioactivity was found primarily in feces. In bile duct cannulated rats, 58.8 ± 14.4% of the radioactive dose was excreted via bile after oral dosing. Major metabolites of fimasartan including the active metabolite, desulfo-fimasartan, were identified, yet none represented more than 7.2% of the exposure of the parent drug. Fimasartan was rapidly and extensively absorbed and had an oral bioavailability of 32.7-49.6% in rats. Fimasartan plasma concentrations showed a multi-exponential decline after oral administration. Double peaks and extended terminal half-life were observed, which was likely caused by enterohepatic recirculation. 4. These results provide better understanding on the pharmacokinetics of fimasartan and may aid further development of fimasartan analogs.

BACKGROUND/OBJECTIVESCitrus flavonoids have a variety of physiological properties such as anti-oxidant, anti-inflammation, anti-cancer, and anti-obesity. We investigated whether bioconversion of Citrus unshiu with cytolase (CU-C) ameliorates the anti-adipogenic effects by modulation of adipocyte differentiation and lipid metabolism in 3T3-L1 cells.MATERIALS/METHODSGlycoside forms of Citrus unshiu (CU) were converted into aglycoside forms with cytolase treatment. Cell viability of CU and CU-C was measured at various concentrations in 3T3L-1 cells. The anti-adipogenic and lipolytic effects were examined using Oil red O staining and free glycerol assay, respectively. We performed real time-polymerase chain reaction and western immunoblotting assay to detect mRNA and protein expression of adipogenic transcription factors, respectively.RESULTSTreatment with cytolase decreased flavanone rutinoside forms (narirutin and hesperidin) and instead, increased flavanone aglycoside forms (naringenin and hesperetin). During adipocyte differentiation, 3T3-L1 cells were treated with CU or CU-C at a dose of 0.5 mg/ml. Adipocyte differentiation was inhibited in CU-C group, but not in CU group. CU-C markedly suppressed the insulin-induced protein expression of CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ) as well as the mRNA levels of CEBPα, PPARγ, and sterol regulatory element binding protein 1c (SREBP1c). Both CU and CU-C groups significantly increased the adipolytic activity with the higher release of free glycerol than those of control group in differentiated 3T3-L1 adipocytes. CU-C is particularly superior in suppression of adipogenesis, whereas CU-C has similar effect to CU on stimulation of lipolysis.CONCLUSIONSThese results suggest that bioconversion of Citrus unshiu peel extracts with cytolase enhances aglycoside flavonoids and improves the anti-adipogenic metabolism via both inhibition of key adipogenic transcription factors and induction of adipolytic activity.