• Journal of Korean Medicine for Obesity Research
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• v.16 no.2
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• pp.109-115
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• 2016

Objectives: The all anti-obesity drugs currently approved by the US Food and Drug Administration work by reducing energy intake. In fact, no approved drug targets energy expenditure. In Korean medicine, it is known to Qi or Yang invigorating therapy could increase energy metabolism. Aconitum carmichaeli Debx (ACD) is a Yang invigorating herb, often used for treat obesity in Korean medicine. In the present study, the authors investigated the regulatory effects of ACD in energy metabolism and mitochondrial biogenesis in C2C12 skeletal muscle cells. Methods: The water extract of ACD (0.2, 0.5 and 1.0 mg/ml) were treated in differentiated C2C12 cells. The protein or mRNA levels of target genes were analyzed and mitochondrial mass were investigated. Results: ACD activated the expressions of peroxisome proliferator-activated receptor gamma coactivator 1-alpha ($PGC-1{\alpha}$), nuclear respiratory factor 1 and TFAM and increased mitochondrial mass. ACD also increased adenosin monophosphate-activated protein kinase (AMPK), and acetyl-CoA carboxylase. Conclusions: This study suggests that ACD has the potential to increase energy metabolism and mitochondrial biogenesis by activating AMPK and $PGC1{\alpha}$.

• Archives of Pharmacal Research
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• v.20 no.6
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• pp.633-636
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• 1997

In the course of searching for PAF receptor antagonists, pregomisin (1) and chamigrenal (2) were isolated from the fruits of Schizandra chinensis Baill by the bioactivity-guided isolation. Both compounds showed PAF antagonistic activity and the $IC_{50}$ values were $4.8{\times}10^{-5} M and 1.2{\times}10^{-4}M,$ respectively. In addition, the $^{13}C$ NMR assignments of 1 and 2 using DEPT, HMQC, COLOC and HMBC were reported for the first time.

• BMB Reports
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• v.54 no.1
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• pp.2-11
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• 2021

Antibody-based therapeutics targeting the inhibitory receptors PD-1, PD-L1, or CTLA-4 have shown remarkable clinical progress on several cancers. However, most patients do not benefit from these therapies. Thus, many efforts are being made to identify new immune checkpoint receptor-ligand pathways that are alternative targets for cancer immunotherapies. Nectin and nectin-like molecules are widely expressed on several types of tumor cells and play regulatory roles in T- and NK-cell functions. TIGIT, CD226, CD96 and CD112R on lymphoid cells are a group of immunoglobulin superfamily receptors that interact with Nectin and nectin-like molecules with different affinities. These receptors transmit activating or inhibitory signals upon binding their cognate ligands to the immune cells. The integrated signals formed by their complex interactions contribute to regulating immune-cell functions. Several clinical trials are currently evaluating the efficacy of anti-TIGIT and anti-CD112R blockades for treating patients with solid tumors. However, many questions still need to be answered in order to fully understand the dynamics and functions of these receptor networks. This review addresses the rationale behind targeting TIGIT, CD226, CD96, and CD112R to regulate T- and NK-cell functions and discusses their potential application in cancer immunotherapy.

• Journal of Applied Biological Chemistry
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• v.65 no.1
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• pp.23-31
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• 2022

Oxidative stress and neuroinflammation play important roles in the pathogenesis of Alzheimer's disease (AD). This study investigated the protective effects of paeoniflorin (PF) against neuronal oxidative stress and neuroinflammation in lipopolysaccharide (LPS)-induced mice. The brains of LPS-injected control group showed significantly increased neuroinflammation by activating the nuclear factor kappa B (NF-κB) pathway and increasing inflammatory mediators. However, administration of PF significantly attenuated oxidative stress by inhibiting lipid peroxidation, nitric oxide levels, and reactive oxygen species production in the brain; PF at doses of 5 and 10 mg/kg/day downregulated the expression of NF-κB pathway-related proteins and significantly decreased inflammatory mediators including inducible nitric oxide synthase and cyclooxygenase-2. Moreover, the levels of brain-derived neurotrophic factor and its receptor, tropomycin receptor kinase B, were significantly increased in PF-treated mice. Furthermore, acetylcholinesterase activity and the ration of B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X were significantly reduced by PF in the brains of LPS-induced mice, resulting in the inhibition of cholinergic dysfunction and neuronal apoptosis. Thus, we can conclude that administration of PF to mice prevents the development of LPS-induced AD pathology through the inhibition of neuronal oxidative stress and neuroinflammation, suggesting that PF has a therapeutic potential for AD.

• Journal of Ginseng Research
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• v.48 no.1
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• pp.12-19
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• 2024

Skeletal muscle (SM) is the largest organ of the body and is largely responsible for the metabolism required to maintain body functions. Furthermore, the maintenance of SM is dependent on the activation of muscle satellite (stem) cells (MSCs) and the subsequent proliferation and fusion of differentiating myoblasts into mature myofibers (myogenesis). Natural compounds are being used as therapeutic options to promote SM regeneration during aging, muscle atrophy, sarcopenia, cachexia, or obesity. In particular, ginseng-derived compounds have been utilized in these contexts, though ginsenoside Rg1 is mostly used for SM mass management. These compounds primarily function by activating the Akt/mTOR signaling pathway, upregulating myogenin and MyoD to induce muscle hypertrophy, downregulating atrophic factors (atrogin1, muscle ring-finger protein-1, myostatin, and mitochondrial reactive oxygen species production), and suppressing the expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cachexia. Ginsenoside compounds are also used for obesity management, and their anti-obesity effects are attributed to peroxisome proliferator activated receptor gamma (PPARγ) inhibition, AMPK activation, glucose transporter type 4 (GLUT4) translocation, and increased phosphorylations of insulin resistance (IR), insulin receptor substrate-1 (IRS-1), and Akt. This review was undertaken to provide an overview of the use of ginseng-related compounds for the management of SM-related disorders.

• IMMUNE NETWORK
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• v.20 no.3
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• pp.21.1-21.10
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• 2020

TLRs are pattern recognition receptors (PRRs) whose cytoplasmic signalling domain is similar to that of IL-1. The extracellular domain of TLRs serve as the binding site of pathogen associated molecular patterns. TLRs are found on both plasma and endosomal membranes and they mainly exert their function by activating genes which lead to production of inflammatory factors. The latest TLR to be discovered, TLR10 is a unique TLR which exhibit anti-inflammatory properties. TLR10 is found on the plasma membrane with other TLRs namely TLR1, TLR2, TLR4, TLR5 and TLR6. Studies have revealed that TLR10 is found on the same gene cluster with TLR1 and TLR6 and is also a coreceptor of TLR2. Up to date, TLR10 is the only TLR which exhibit anti-inflammatory property. Previously, TLR10 was thought to be an "orphan receptor" but much recent studies have identified ligands for TLR10. Currently there is no review article on TLR10 that has been published. In this narrative review, we are going to give an account of TLR10, its functions mainly as an anti-inflammatory PRR and its possible applications as a target in therapeutics.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.6
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• pp.769-774
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• 1997

Non-neuronal high affinity binding sites for benzodiazepines have been found in many peripheral tissues including cardiac muscle and vascular smooth muscle, and have been designated as 'peripheral benzodiazepine receptor'. Benzodiazepines have been shown to induce relaxation of the ileal, vesical, and uterine smooth muscles. However, it is still unclear about possible involvement of peripheral benzodiazepine receptor on the contractility of trachealis muscle. This study was performed to investigate the role of the peripheral benzodiazepine receptor on the contractility of canine trachealis muscle. Canine trachealis muscle strips of 15 mm long were suspended in an isolated organ bath containing 1 ml of physiological salt solution maintained at $37^{\circ}C$, and aerated with $95%\;O_2/5%\;CO_2$. Isometric myography was performed, and the results of the experiments were as follows: Ro5-4684, FGIN-1-27 and clonazepam reduced a basal tone of isolated canine trachealis muscle strip concentration dependently, relaxant actions of RoS-4684 and FGIN-1-27 were antagonized by PK11195, a peripheral benzodiazepine receptor antagonist. Flumazenil, a central type antagonist, did not antagonize the relaxant action of Peripheral type agonists. Saturation binding assay of [3H]Ro5-4864 showed a high affinity$(Kd=5.33{\pm}1.27nM,\;Bmax=\;867.3{\pm}147.2\;fmol/mg\;protein)$ binding site on the canine trachealis muscle. Ro 5-4684 suppressed the bethanechol-, 5-hydroxyoyptamine- and histamine- induced contractions. Platelet activating factor (PAF) exerted strong and prolonged contraction in trachealis muscle strip. Strong tonic contraction by PAE was attenuated by Ro 5-4684, but not by WEB 2086, a PAF antagonist. Based on these results, it is concluded that the peripheral benzodiazepine receptor mediates the inhibitory regulation of contractilty of canine trachealis muscle.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.2
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• pp.201-208
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• 1997

It is becoming increasingly clear that the inflammatory reaction can be ascribed to a complex array of mediators generated and released from activated phagocytes. In this study, the effect of PAF on interleukin-1(IL-1) activity by rat alveolar macrophages(AM) was examined using thymocyte proliferation assay in the supernate of sample obtained after 24 hr culture. When AM were cultured with PAF alone, no change in IL-1 activity was observed. However, the combined addition of PAF and muramyl dipeptide(MDP) or lipopolysaccharide(LPS) to AM cultures markedly enhanced IL-1 activity by 2-3 fold compared with AM cultures with the stimulant alone in a concentration dependent fashion. The peack effect was found at $10^{-8}$ M PAF with MDP and $10^{-14}$ M PAF with LPS. the effect of PAF was also tested in silica, toxic respirable dust, -added AM cultures as well as in the cultures containing bacterial compounds. Although silica did not stimulate the IL-1 activity, PAF could enhance IL-1 activity by 2 fold above the value of the silica-treated AM cultures with the peak response at $10^{-12}$ M PAF. Optimal enhancement of IL-1 activity occured when MDP and PAF were present together at the initiation of the 24 hr AM cultures. Additionaly, the biologically inactive precursor/metabolite of PAF, lyso-PAF failed to induce enhancement of IL-1 activity. When the specific, but structurally different PAF receptor antagonists, BN 52021($10^{-5}$ M) and CV 3988($10^{-5}$ M) was treated 15 min before addition of PAF($10^{-8}$ M) and MDP$(10\;{\mu}g/ml)$ to the AM cultures, it markedly inhibited the enhancement of IL-1 activity induced by PAF. The effects of these PAF antagonists were also observed in LPS$(10\;{\mu}g/ml)$-stimulated cells. Collectively, these data suggest that PAF enhances IL-1 activity by interaction with a specific receptor.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.6
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• pp.311-316
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• 2003

Endothelins secreted from keratinocytes are intrinsic mitogens and melanogens of human melanocytes in UVB-induced hyperpigmentation. To elucidate the cellular mechanism of antimelanogenic activity of bamboo extract, the effects of three ingredients of bamboo extract on endothelin 1 (ET-1)-induced $Ca^{2+}$ mobilization were investigated in cultured human melanocytes. ET-1 receptors in human melanocytes were characterized by using specific antagonist, and ET-1 was found to increase intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) by activating ET-B receptor. SM709 (1,2-O-diferulyl-glycerol), an ingredient of bamboo extract, inhibited ET-1-induced $[Ca^{2+}]_i$ increase in a concentration- and time-dependent manner, although another ingredients SM707 and SM708 had no effect on ET-1-induced $[Ca^{2+}]_i$ increase in human melanocytes. SM709 ($100{\mu}M$), however, did not affect $[Ca^{2+}]_i$ increase induced by thapsigargin and caffeine, suggesting that SM709 has no effect on the $Ca^{2+}$ store in melanocytes. Furthermore, SM709 did not affect $[Ca^{2+}]_i$ increase induced by LPA or ATP, known as G protein-mediated PLC activators like ET-1. Taken together, it is suggested that SM709 antagonizes ET-1-induced transmembrane signaling through ET-B receptor, which maybe a possible underlying mechanism of antimelanogenic activity of bamboo extract in human melanocytes.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.2
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• pp.37-43
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• 2007

Adenosine has been reported to provide cytoprotection in the central nervous systems as well as myocardium by activating cell surface adenosine receptors. However, the exact target and mechanism of its action still remain controversial. The present study was performed to examine whether adenosine has a protective effect against $A{\beta}$-induced injury in neuroglial cells. The astrocyte-derived human neuroglioma cell line, A172 cells, and $A{\beta}_{25{\sim}35}$ were employed to produce an experimental $A{\beta}$-induced glial cell injury model. Adenosine significantly prevented $A{\beta}$-induced apoptotic cell death. Studies using various nucleotide receptor agonists and antagonists suggested that the protection was mediated by $A_1$ receptors. Adenosine attenuated $A{\beta}$-induced impairment in mitochondrial functional integrity as estimated by cellular ATP level and MTT reduction ability. In addition, adenosine prevented $A{\beta}$-induced mitochondrial permeability transition, release of cytochrome c into cytosol and subsequent activation of caspase-9. The protective effect of adenosine disappeared when cells were pretreated with 5-hydroxydecanoate, a selective blocker of the mitochondrial ATP-sensitive $K^+$ channel. In conclusion, therefore we suggest that adenosine exerts protective effect against $A{\beta}$-induced cell death of A172 cells, and that the underlying mechanism of the protection may be attributed to preservation of mitochonarial functional integrity through opening of the mitochondrial ATP-sensitive $K^+$ channels.