• BMB Reports
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• v.55 no.1
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• pp.11-19
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• 2022

The coronavirus disease 2019 (COVID-19) is an ongoing global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe COVID-19 exhibit hyper-inflammatory responses characterized by excessive activation of myeloid cells, including monocytes, macrophages, and neutrophils, and a plethora of pro-inflammatory cytokines and chemokines. Accumulating evidence also indicates that hyper-inflammation is a driving factor for severe progression of the disease, which has prompted the development of anti-inflammatory therapies for the treatment of patients with COVID-19. Corticosteroids, IL-6R inhibitors, and JAK inhibitors have demonstrated promising results in treating patients with severe disease. In addition, diverse forms of exosomes that exert anti-inflammatory functions have been tested experimentally for the treatment of COVID-19. Here, we briefly describe the immunological mechanisms of the hyper-inflammatory responses in patients with severe COVID-19. We also summarize current anti-inflammatory therapies for the treatment of severe COVID-19 and novel exosome-based therapeutics that are in experimental stages.

• Molecules and Cells
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• v.42 no.1
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• pp.1-7
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• 2019

Macrophage is an important innate immune cell that not only initiates inflammatory responses, but also functions in tissue repair and anti-inflammatory responses. Regulating macrophage activity is thus critical to maintain immune homeostasis. Tyro3, Axl, and Mer are integral membrane proteins that constitute TAM family of receptor tyrosine kinases (RTKs). Growing evidence indicates that TAM family receptors play an important role in anti-inflammatory responses through modulating the function of macrophages. First, macrophages can recognize apoptotic bodies through interaction between TAM family receptors expressed on macrophages and their ligands attached to apoptotic bodies. Without TAM signaling, macrophages cannot clear up apoptotic cells, leading to broad inflammation due to over-activation of immune cells. Second, TAM signaling can prevent chronic activation of macrophages by attenuating inflammatory pathways through particular pattern recognition receptors and cytokine receptors. Third, TAM signaling can induce autophagy which is an important mechanism to inhibit NLRP3 inflammasome activation in macrophages. Fourth, TAM signaling can inhibit polarization of M1 macrophages. In this review, we will focus on mechanisms involved in how TAM family of RTKs can modulate function of macrophage associated with anti-inflammatory responses described above. We will also discuss several human diseases related to TAM signaling and potential therapeutic strategies of targeting TAM signaling.

• Journal of Ginseng Research
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• v.44 no.3
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• pp.373-385
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• 2020

Inflammation is an immune response that protects against pathogens and cellular stress. The hallmark of inflammatory responses is inflammasome activation in response to various stimuli. This subsequently activates downstream effectors, that is, inflammatory caspases such as caspase-1, 4, 5, 11, and 12. Extensive efforts have been made on developing effective and safe anti-inflammatory therapeutics, and ginseng has long been traditionally used as efficacious and safe herbal medicine in treating various inflammatory and inflammation-mediated diseases. Many studies have successfully shown that ginseng plays an anti-inflammatory role by inhibiting inflammasomes and inflammasome-activated inflammatory caspases. This review discusses the regulatory roles of ginseng on inflammatory caspases in inflammatory responses and also suggests new research areas on the anti-inflammatory function of ginseng, which provides a novel insight into the development of ginseng as an effective and safe anti-inflammatory herbal medicine.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.6 no.1
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• pp.1-13
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• 1993

Experimental studies were done to research the clinical effects of Sopoongyangjetang on the Anti-allergic effect, Analgesic action and Anti-inflammatory action. The results obtained as follows ; 1. In effect of Sopoongyangjetang on vascular permeability responses to intradermal serotonin, it had tendency to decrease, but was none significant effect. 2. In effect of Sopoongyangjetang on vascular permeability responses to intradermal histamine, it revealed significant effect. 3. In the homologous PCA provoked by the IgE-like antibody against white egg albumin, Sopoonyangjetang showed significant effect. 4. In the delayed type hypersensitivity responses to picryl chloride, Sopoongyangjetang was proved significant effect. 5. In the delayed type hypersensitivity responses to SRBC, Sopoongyangjetang revealed significant effect. 6. In analgesic action by acetic acid method, Sopoongyangjetang was recognized significantly. 7. In Anti-inflammatory action by carrageenine method, Sopoongyangjetang showed significant effect.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.4
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• pp.449-456
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• 2017

Beauvericin (BEA), a cyclic hexadepsipeptide produced by the fungus Beauveria bassiana, is known to have anti-cancer, anti-inflammatory, and anti-microbial actions. However, how BEA suppresses macrophage-induced inflammatory responses has not been fully elucidated. In this study, we explored the anti-inflammatory properties of BEA and the underlying molecular mechanisms using lipopolysaccharide (LPS)-treated macrophage-like RAW264.7 cells. Levels of nitric oxide (NO), mRNA levels of transcription factors and the inflammatory genes inducible NO synthase (iNOS) and interleukin (IL)-1, and protein levels of activated intracellular signaling molecules were determined by Griess assay, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), luciferase reporter gene assay, and immunoblotting analysis. BEA dose-dependently blocked the production of NO in LPS-treated RAW264.7 cells without inducing cell cytotoxicity. BEA also prevented LPS-triggered morphological changes. This compound significantly inhibited nuclear translocation of the $NF-{\kappa}B$ subunits p65 and p50. Luciferase reporter gene assays demonstrated that BEA suppresses MyD88-dependent NF-${\kappa}B$ activation. By analyzing upstream signaling events for $NF-{\kappa}B$ activation and overexpressing Src and Syk, these two enzymes were revealed to be targets of BEA. Together, these results suggest that BEA suppresses $NF-{\kappa}B$-dependent inflammatory responses by suppressing both Src and Syk.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.7 no.1
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• pp.1-13
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• 1994

The Effects of Hoichunyanggyuksan on the Anti-allergic Effect, Analgesic Action, Anti-inflammatory Action and Antipyretic Action. Experimental studies were done to research the clinical effects of Hoichunyanggyuksan on the Anti-allergic effect, Analgesic action, Anti-inflammatory action and Antipyretic action. The results obtained as follows; 1. On vascular permeability responses to intradermal histamine, Hoichnyanggyuksan showed significant effect. 2. In the homologous PCA provoked by the IgE-like antibody against white egg albumin, Hoichunyanggyuksan showed the decreasing tendency, but was none significant effect. 3. In the delayed type hypersensitivity responses to Picryl chloride, Hoichunyanggyuksan was proved significant effect. 4. In the delayed type hypersensitivity resposes to SRBC, Hoichunyanggyuksan revealed significant effect. 5. In Anti-pyretic action by yeast method, Hoichunyanggyuksan showed significant effect. 6. In Anti-inflammatory action by carrageenin method, Hoichunyanggyuksan showed significant effect. 7. In analgesic action by acetic acid method, Hoichunyanggyuksan was recognized significantly.

• Natural Product Sciences
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• v.6 no.4
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• pp.170-178
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• 2000

Flavonoids are natural polyphenolic compounds widely distributed in plant kingdom. Although many flavonoids were found to show anti-inflammatory activity in vitro and in vivo, the potency of anti-inflammatory activity was not enough for a clinical trial. Thus, a search for finding potential flavonoid molecules is continuing. In this review, in vivo anti-inflammatory activity of various flavonoid derivatives is summarized mainly based on the results obtained in authors' laboratories. Among them, several biflavonoids such as amentoflavone and ginkgetin were found to possess anti-inflammatory activity on animal models of acute/chronic inflammation comparable to nonsteroidal and steroidal anti-inflammatory drugs currently used. In respect of their action mechanisms, the effects on arachidonic acid metabolism and nitric oxide production were described. Some flavonoids directly inhibit cyclooxygenase and/or lipoxygenase. Biflavones such as ochnaflavone and ginkgetin are inhibitors of phospholipase $A_2$. In recent studies, certain flavonoids were also found to suppress cyclooxygenase-2 and inducible nitric oxide synthase expression induced by inflammatory stimuli. Therefore, it is suggested that anti-inflammatory activity of the certain flavonoids (mainly flavones, flavonols and biflavonoids) may be mediated by direct inhibition of arachidonic acid metabolizing enzymes as well as suppression of the enzyme expression involved in inflammatory responses.

• Natural Product Sciences
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• v.20 no.4
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• pp.301-305
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• 2014

The aim of our study is to investigate the anti-nociceptive and anti-inflammatory properties of an ethanol extract of the leaf and stem of Aralia cordata. Writhing responses induced by acetic acid, tail immersion test, and formalin-induced paw pain response for nociception and formalin-induced paw edema for inflammation were evaluated in mice. A. cordata (50 - 200 mg/kg, p.o.) and ibuprofen (100 mg/kg, p.o.), a positive non-steroidal anti-inflammatory drugs (NSAIDs), inhibited the acetic acid-induced writhing response, but they did not protect the thermal nociception in tail immersion test. However, morphine (5 mg/kg, s.c.) used as positive opioid control alleviated both the acetic acid-induced writhing response and thermal nociception in tail immersion test. In the formalin test, A. cordata (50 - 200mg/kg) and ibuprofen (200mg/kg) inhibited the second phase response (peripheral inflammatory response), but not the first phase response (central response), whereas morphine inhibited both phase pain responses. Both A. cordata (100 mg/kg) and ibuprofen (200 mg/kg) significantly alleviated the formalin-induced increase of paw thickness, the index of inflammation. These results show for the first time that the leaf and stem of A. cordata has a significant anti-nociceptive effect that seems to be peripheral, but not central. A. cordata also displays an anti-inflammatory activity in an acute inflammation model. The present study supports a possible use of the leaf and stem of A. cordata to treat pain and inflammation.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.10a
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• pp.104-104
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• 2019

Licorice species (Glycyrhiza species) are perennial plants belonging to the Leguminosae family. Licorice is world-widely distributed in Asia, Europe, and the Americas. The licorice species, such as Glycyrhiza uralensis (G. uralensis) and G. glabra, have been widely used in traditional oriental medicine. G. uralensis is found in Central Asia to the northeastern part of China and G. glabra is distributed from southern Europe to the northwestern part of China. These licorice species are characterized by having various pharmacological activities, including anti-oxidant, anti-inflammatory, immune improvement, and anti-tumor effects. In this study, we investigated the comparative anti-inflammatory effects of four licorice varieties (G. glabra L., G. uralensis FISCH., Shinwongam, and Wongam) on LPS-induced inflammatory responses in RAW 264.7 macrophage cell line. We evaluated the cytotoxicity of licorices at various concentrations. In addition, the nitric oxide (NO) production was elucidated by the treatment of licorice.

• Natural Product Sciences
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• v.25 no.1
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• pp.64-71
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• 2019

The present study was conducted to investigate anti-nociceptive and anti-inflammatory effects of the leaves of Ilex latifolia Thunb (I. latifolia) in in vivo and in vitro. Writhing responses induced by acetic acid and formalin- and thermal stimuli (tail flick and hot plate tests)-induced pain responses for nociception were evaluated in mice. I. latifolia (50 - 200 mg/kg, p.o.) and ibuprofen (100 mg/kg, p.o.), a positive non-steroidal anti-inflammatory drug (NSAID), inhibited the acetic acid-induced writhing response and the second phase response (peripheral inflammatory response) in the formalin test, but did not protect against thermal nociception and the first phase response (central response) in the formalin test. These results show that I. latifolia has a significant anti-nociceptive effect that appears to be peripheral, but not central. Additionally, I. latifolia (50 and $100{\mu}g/mL$) and 3,5-di-caffeoyl quinic acid methyl ester ($5{\mu}M$) isolated from I. latifolia as an active compound significantly inhibited LPS-induced NO production and mRNA expression of the pro-inflammatory mediators, iNOS and COX-2, and the pro-inflammatory cytokines, IL-6 and $IL-1{\beta}$, in RAW 264.7 macrophages. These results suggest that I. latifolia can produce antinociceptive effects peripherally, but not centrally, via anti-inflammatory activity and supports a possible use of I. latifolia to treat pain and inflammation.