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Involvement of a Novel Organic Cation Transporter in Paeonol Transport Across the Blood-Brain Barrier

  • Gyawali, Asmita;Krol, Sokhoeurn;Kang, Young-Sook
    • Biomolecules & Therapeutics
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    • v.27 no.3
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    • pp.290-301
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    • 2019
  • Paeonol has neuroprotective function, which could be useful for improving central nervous system disorder. The purpose of this study was to characterize the functional mechanism involved in brain transport of paeonol through blood-brain barrier (BBB). Brain transport of paeonol was characterized by internal carotid artery perfusion (ICAP), carotid artery single injection technique (brain uptake index, BUI) and intravenous (IV) injection technique in vivo. The transport mechanism of paeonol was examined using conditionally immortalized rat brain capillary endothelial cell line (TR-BBB) as an in vitro model of BBB. Brain volume of distribution (VD) of [$^3H$]paeonol in rat brain was about 6-fold higher than that of [$^{14}C$]sucrose, the vascular space marker of BBB. The uptake of [$^3H$]paeonol was concentration-dependent. Brain volume of distribution of paeonol and BUI as in vivo and inhibition of analog as in vitro studies presented significant reduction effect in the presence of unlabeled lipophilic compounds such as paeonol, imperatorin, diphenhydramine, pyrilamine, tramadol and ALC during the uptake of [$^3H$]paeonol. In addition, the uptake significantly decreased and increased at the acidic and alkaline pH in both extracellular and intracellular study, respectively. In the presence of metabolic inhibitor, the uptake reduced significantly but not affected by sodium free or membrane potential disruption. Similarly, paeonol uptake was not affected on OCTN2 or rPMAT siRNA transfection BBB cells. Interestingly. Paeonol is actively transported from the blood to brain across the BBB by a carrier mediated transporter system.

Review of the Antioxidant Effect of Herbal Material in In Vivo Parkinson's Disease Models (파킨슨병 in vivo 모델에서 한약재 및 기능성 식품의 항산화 효과에 대한 고찰)

  • Lee, Gi-hyang;Jeon, Sang-woo;Jeong, Min-jeong;Kim, Hong-jun;Jang, In-soo
    • The Journal of Internal Korean Medicine
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    • v.41 no.6
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    • pp.993-1014
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    • 2020
  • Objective: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Antioxidant stress and inflammatory reactions are important causes of neurodegenerative diseases and are major causes of PD. Many animal experiments have been aimed at treating PD using the antioxidant effects of various traditional medicines and dietary supplements. This review reports the research investigating the antioxidant effects of herbs in in vivo PD models. Methods: The study consisted of a database search for articles related to PD and herbal treatments using the OASIS, NDSL, KTKP, Korean KISS, PubMed, Science Direct, CNKI, Wanfang, and J-STAGE databases. The search period was limited from the start of the search engine application to November 14, 2019. Studies were selected to confirm the antioxidant effects of herbal medicines in an in vivo PD model. Results: Eighty-two studies were summarized for plant species, extracts (or compounds), animal models, neurotoxins, and functional results. The most frequently used herbal materials were Bacopa monnieri, Camellia sinensis, Centella asiatica, and Withania somnifera. MPTP and 6-OHDA were the most commonly used neurotoxins for inducing PD. Most studies confirmed an increased expression and activation of antioxidant enzymes and a decrease in oxidative stress. Herbal materials showed their antioxidant effects regardless of the order of treatment and confirmed their possible use as treatments for the prevention and treatment of neurodegeneration. Conclusion: Many herbal medicines have antioxidant effects and are likely to be effective in delaying neurodegenerative damage by inhibiting or reducing oxidative stress by expression of antioxidant enzymes.

Short-range magnetic order in La1-xBaxCoO3 cobaltites

  • Long, Phan The;Petrov, Dimitar N.;Cwik, J.;Dang, N.T.;Dongquoc, Viet
    • Current Applied Physics
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    • v.18 no.11
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    • pp.1248-1254
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    • 2018
  • Magnetization versus temperature and magnetic-field measurements, M(T, $H_a$), have been carried out to study the magnetic and critical properties of polycrystalline $La_{1-x}Ba_xCoO_3$ (x = 0.3 and 0.5) cobaltites. These compounds with the density of ${\sim}6.2g/cm^3$ crystallized in the $R{\bar{3}}c$ rhombohedral and $Pm{\bar{3}}m$ cubic structures, respectively. With an applied field $H_a=200Oe$, M(T) data have revealed that the samples with x = 0.3 and 0.5 exhibit the ferromagnetic-paramagnetic (FM-PM) phase transition at the Curie temperature points $T_C=202$ and 157 K, respectively. At 4.2 K, the saturation magnetization ($M_{sat}$) decreases from 35.9 emu/g for x = 0.3-26.1 emu/g for x = 0.5. Particularly, the critical-behavior analyses in the vicinity of $T_C$ reveal all samples undergoing a second-order phase transition, with critical exponent values (${\beta}=0.328$ and ${\gamma}=1.251$ for x = 0.3, and ${\beta}=0.331$ and ${\gamma}=1.246$ for x = 0.5) close to those expected for the 3D Ising model. This proves short-range magnetic order existing in $La_{1-x}Ba_xCoO_3$. We believe that magnetic inhomogeneities due to the mixture of hole-rich FM regions (confined in the trivalent-cobalt hole-poor anti-FM matrix) and uniaxial anisotropy prevent long-range order in $La_{1-x}Ba_xCoO_3$.

Ononis spinosa alleviated capsaicin-induced mechanical allodynia in a rat model through transient receptor potential vanilloid 1 modulation

  • Jaffal, Sahar Majdi;Al-Najjar, Belal Omar;Abbas, Manal Ahmad
    • The Korean Journal of Pain
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    • v.34 no.3
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    • pp.262-270
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    • 2021
  • Background: Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel implicated in pain sensation in response to heat, protons, and capsaicin (CAPS). It is well established that TRPV1 is involved in mechanical allodynia. This study investigates the effect of Ononis spinosa (Fabaceae) in CAPS-induced mechanical allodynia and its mechanism of action. Methods: Mechanical allodynia was induced by the intraplantar (ipl) injection of 40 ㎍ CAPS into the left hind paw of male Wistar rats. Animals received an ipl injection of 100 ㎍ O. spinosa methanolic leaf extract or 2.5% diclofenac sodium 20 minutes before CAPS injection. Paw withdrawal threshold (PWT) was measured using von Frey filament 30, 90, and 150 minutes after CAPS injection. A molecular docking tool, AutoDock 4.2, was used to study the binding energies and intermolecular interactions between O. spinosa constituents and TRPV1 receptor. Results: The ipsilateral ipl injection of O. spinosa before CAPS injection increased PWT in rats at all time points. O. spinosa decreased mechanical allodynia by 5.35-fold compared to a 3.59-fold decrease produced by diclofenac sodium. The ipsilateral pretreatment with TRPV1 antagonist (300 ㎍ 4-[3-Chloro-2-pyridinyl]-N-[4-[1,1-dimethylethyl] phenyl]-1-piperazinecarboxamide [BCTC]) as well as the β2-adrenoreceptor antagonist (150 ㎍ butoxamine) attenuated the action of O. spinosa. Depending on molecular docking results, the activity of the extract could be attributed to the bindings of campesterol, stigmasterol, and ononin compounds to TRPV1. Conclusions: O. spinosa alleviated CAPS-induced mechanical allodynia through 2 mechanisms: the direct modulation of TRPV1 and the involvement of β2 adrenoreceptor signaling.

Ginsenoside Rb1 inhibits monoiodoacetate-induced osteoarthritis in postmenopausal rats through prevention of cartilage degradation

  • Aravinthan, Adithan;Hossain, Mohammad Amjad;Kim, Bumseok;Kang, Chang-Won;Kim, Nam Soo;Hwang, Ki-Chul;Kim, Jong-Hoon
    • Journal of Ginseng Research
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    • v.45 no.2
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    • pp.287-294
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    • 2021
  • Background: Ginsenoside Rb1 (G-Rb1), one of the major active compounds in Panax ginseng, has already been shown to reduce inflammation in various diseases. Osteoarthritis (OA) has traditionally been considered a degenerative disease with degradation of joint articular cartilage. However, recent studies have shown the association of inflammation with OA. In the present study, we investigated whether Rb1 had an antiinflammatory effect on monoiodoacetate (MIA)-induced OA in ovariectomized rats as a model of postmenopausal arthritis. Methods: G-Rb1 at a dosage of 3 and 10 ㎍/kg body weight was administered every 3 days intraarticularly for a period of 4 weeks to observe antiarthritic effects. Diclofenac (10 mg/kg) served as a positive control. Results: The administration of Rb1 significantly ameliorated OA inflammatory symptoms and reduced serum levels of inflammatory cytokines. Furthermore, G-Rb1 administration considerably enhanced the expression of bone morphogenetic protein-2 and collagen 2A and reduced the levels of matrix metalloproteinase-13 genes, indicating a chondroprotective effect of G-Rb1. G-Rb1 also significantly reduced the expression of several inflammatory cytokines/chemokines (interferon gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP-1)/CCL-2, interleukin [IL]-1β, and IL-6). Histological analysis demonstrated that G-Rb1 significantly attenuated the pathological changes in MIA-induced OA in ovariectomized rats. Safranin O and toluidine blue staining further demonstrated that G-Rb1 effectively prevented the degradation of cartilage and glycosaminoglycans, respectively. Conclusion: Overall, our results suggest that G-Rb1 exerts cartilage protective effect on MIA-induced ovariectomized OA rats, by inhibiting inflammatory mediators such as IL-6, IL-1β, MCP-1/CCL-2, cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). These results shed a light on possible therapeutic application of G-Rb1 in OA.

Nutritional composition of various insects and potential uses as alternative protein sources in animal diets

  • Shah, Assar Ali;Totakul, Pajaree;Matra, Maharach;Cherdthong, Anusorn;Hanboonsong, Yupa;Wanapat, Metha
    • Animal Bioscience
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    • v.35 no.2_spc
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    • pp.317-331
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    • 2022
  • The aim of the present investigation is to determine the nutritional composition of various insects and their potential uses as alternative protein sources in animal diets. The feeding industry requires production systems that use accessible resources, such as feed resources, and concentrates on the potential impacts on production yield and nutritional quality. Invertebrate insects, such as black soldier flies, grasshoppers, mealworms, housefly larvae, and crickets, have been used as human food and as feed for nonruminants and aqua culture while for ruminants their use has been limited. Insects can be mass-produced, participating in a circular economy that minimizes or eliminates food- and feed-waste through bioconversion. Although the model for formula-scale production of insects as feed for domestic animals has been explored for a number of years, significant production and transformation to being a conventional protein resource remains to be deeply investigated. This review will focus on the nutritional composition of various insects and their potential use as alternative protein sources, as well as their potential use to promote and support sustainable animal production. Furthermore, nutritional compositions, such as high protein, lauric acid omega 6, and omega 3, and bioactive compounds, such as chitin, are of great potential use for animal feeding.

Extracts and Enzymatic Hydrolysates Derived from Sea Cucumber Stichopus japonicas Ameliorate Hepatic Injury in BisphenolA-treated Mice (비스페놀A 유도 간 손상 마우스에서 해삼(Stichopus japonicas) 추출물 및 가수분해물의 간 기능 개선 효과)

  • Sejeong, Kim;Yun-Ho, Jo;Bi-Oh, Park;Dae-Seok, Yoo;Doo-Ho, Kim;Min-Jung, Kim;Youn-Gil, Kwak;Jin-Seong, Kim
    • Journal of Marine Bioscience and Biotechnology
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    • v.14 no.2
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    • pp.61-68
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    • 2022
  • This study aimed to investigate the hepatoprotective activities of the sea cucumber products, including extracts and hydrolysates, in vitro and in vivo. Dried sea cucumber, produced on the western coast of Korea, was boiled in water or 70% ethanol at 85℃ or 100℃ for 18 or 24 h, respectively, to extract bioactive compounds. The enzymatic hydrolysates were prepared by reacting the dried sea cucumber with pepsin or neutral protease (PNL) under optimal enzyme conditions. The anti-inflammatory effect of the samples was investigated using RAW 264.7 cells treated with lipopolysaccharide (LPS). The amount of nitric oxide (NO) was produced from the cells treated with LPS and each sample was compared. Therefore, the pepsin hydrolysate treatment decreased NO production compared to LPS sole treatment. Furthermore, the effects of the samples on cell injury in the hepatic cell line and bisphenolA-induced hepatic injury mouse model were investigated. The water extracts and the pepsin hydrolysates of sea cucumber significantly inhibited cell injury generated in the hepatocytes without cytotoxicity (p < 0.05), whereas the ethanol extracts were cytotoxic. However, these results indicate that the extracts and the enzymatic hydrolysates derived from sea cucumber can be used as beneficial materials for inhibiting liver damage.

Toosendan Fructus ameliorates the pancreatic damage through the anti-inflammatory activity in non-obese diabetic mice

  • Roh, Seong-Soo;Kim, Yong-Ung
    • The Korea Journal of Herbology
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    • v.30 no.2
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    • pp.1-9
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    • 2015
  • Objectives : The present study was conducted to examine whether Toosendan Fructus has an ameliorative effect on diabetes-induced alterations such as oxidative stress and inflammation in the pancreas of non-obese diabetic (NOD) mice, a model of human type I diabetes. Methods : Extracts of Toosendan Fructus (ETF) were administered to NOD mice at three doses (50 mg/kg, 100 mg/kg and 200 mg/kg). Mice at 18 weeks of age were measured glucose tolerance using intraperitoneal glucose tolerance test. After 28 weeks of ETF treatment, glucose, total cholesterol (TC), triglyceride (TG), and proinflammatory cytokines in serum, western blot analyses and a histopathological examination in pancreas tissue, and on the onset of diabetes were investigated. Results : The results showed that levels of glucose, glucose tolerance, TC, TG, interferon-${\gamma}$, interleukin (IL)-1 ${\beta}$, IL-6, and IL-12 in serum were down-regulated, while IL-4, IL-10, SOD, and catalase significantly increased. In addition, ETF improved protein expression of proinflammatory mediaters (such as cyclooxygenase-2, and inducible nitric oxide synthase) and a proapoptotic protein (caspase-3) in the pancreatic tissue. Also, in the groups treated with ETF (100 mg/kg or 200 mg/kg), insulitis and infiltration of granulocytes were alleviated. Conclusions : Based on these results, the anti-diabetic effect of ETF may be due to its anti-inflammatory and antioxidant effect. Our findings support the therapeutic evidence for Toosendan Fructus ameliorating the development of diabetic pancreatic damage via regulating inflammation and apoptosis. Our future studies will be focused on the search for active compounds in these extracts.

Antidiabetic Effect of Standardized Chrysanthemum rubellum Hydroethanolic Extract by Targeting α-Glucosidase and the PTP-1B Signaling Pathway for Alleviating Diabetes in Experimental Model

  • Bichitrananda Tripathy;Nityananda Sahoo;Sudhir Kumar Sahoo
    • Journal of Pharmacopuncture
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    • v.26 no.4
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    • pp.319-326
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    • 2023
  • Objectives: The study's goal was to find out whether Chrysanthemum rubellum extract has anti-diabetic properties by concentrating on α-glucosidase and the PTP-1B signaling pathway. C. rubellum flowers were used for extraction using Methanol/water (80/20) as solvent. Methods: LC-MS techniques was used to check the presence of phytoconstituents present in C. rubellum extract. In vitro antidiabetic activity was evaluated using α-glucosidase inhibitory activity and PTP-1B signaling pathway. On Streptozotocin (STZ)-induced rats with diabetes, the in vivo antidiabetic efficacy was assessed using a test for oral glucose tolerance. Results: The phytoconstituents identified in the extract of C. rubellum were apigenin, diosmin, myricetin, luteolin, luteolin-7-glucoside, and Quercitrin as compound 1-6, respectively. Results showed that diosmin exhibited highest α-glucosidase inhibitory activity i.e. 90.39%. The protein level of PTP-1B was lowered and the insulin signalling activity was directly increased by compounds 1-6. The maximum blood glucose levels were seen in all groups' OGTT findings at 30 minutes following glucose delivery, followed by gradual drops. In comparison to the control group, the extract's glucose levels were 141 mg/dL at 30 minutes before falling to 104 mg/dL after 120 minutes. The current study has demonstrated, in summary, that extract with phytoconstituents reduce blood sugar levels in rats. Conclusion: This finding suggests that extract may reduce the chance of insulin resistance and shield against disorders like hyperglycemia.

Improving Production of Value-added Materials by a Detoxification of Plant Derivatives (식물 유래 물질 해독화를 통한 고부가가치 소재 생산)

  • Sungmin Hwang;Jung Up Park;Bohyun Yun;Ji-Won Park;WonWoo Lee
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2023.04a
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    • pp.12-12
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    • 2023
  • Plant biomass, or lignocellulose, is one of the most abundant natural resources on earth. Lignocellulosic biomass, such as agricultural and forestry residue, serves as a renewable feedstock for microbial cell factories due to its low price and abundant availability. However, the recalcitrance of lignocellulosic biomass requires a pretreatment process prior to microbial fermentation, from which fermentable sugars including xylose and glucose are generated along with various inhibitory compounds. The presence of furan derivatives, such as 5-hydroxymethyl-2-furaldehyde and 2-furaldehyde (furfural), hampers the microbial conversion of lignocellulosic biomass into value-added commodities. In this study, furfural tolerance was improved by investigating the detoxification mechanism in non-model yeast. The genes encoding aldehyde dehydrogenases were overexpressed to enhance furfural tolerance and resulted in improving cell growth and lipid production that can be converted into biofuel. Taken together, this approach contributes to the understanding of the reducing toxicity mechanism of furfural by the aldehyde dehydrogenases and provides a promising strategy that the use of microorganism as an industrial workhorse to treat efficiently lignocellulosic biomass as sustainable plant derivatives.

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