• 대한본초학회지
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• 제37권6호
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• pp.9-17
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• 2022

Objective : In modern society, liver diseases such as liver fibrosis are on the rise as inflammation and wound healing processes of the liver are repeated due to factors such as drinking, smoking, and stress. This study was conducted to evaluate the effect of Saenggangeonbi-tang (SGGBT) on thioacetamide (TAA)-induced liver fibrosis. Methods : The mice were divided into 4 groups for examination (n=6): Normal group (Nor), distilled water-treated liver fibrosis mice (Con), silymarin 50 mg/kg-treated liver fibrosis mice (Sily), SGGBT 200 mg/kg-treated liver fibrosis mice (S200). Liver fibrosis was established in the mice via TAA for 8 weeks (1 week 100 mg/kg, 2,3 weeks 200 mg/kg, 4-8 weeks 400 mg/kg, three times a week, intraperitoneal injection) and they were administered silymarin and SGGBT (every day, oral administration) with the TAA. Results : SGGBT significantly decreased the levels of aspartate aminotransferase, alanine aminotransferanse, ammonia, and myeloperoxidase in serum increased by liver fibrosis. As a result of confirming H&E and MT staining, it was confirmed that SGGBT reduced damage and inflammatory cell infiltration in liver tissue, and alleviated changes in collagen fiber deposition and histological fibrosis. Also, it was confirmed through PAS staining that it reduced glycogen deposition in liver tissue. In addition, SGGBT significantly decreased the NADPH oxidases as well as significantly modulated the expression of MMP-2 and TIMP-2. Conclusions : These results suggest that SGGBT regulates the expression of MMP/TIMP protein through inhibition of oxidative stress and alleviates liver fibrosis by reducing collagen and glycogen deposition in liver tissue.

• The Korean Journal of Physiology and Pharmacology
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• 제27권1호
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• pp.1-8
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• 2023

Hypothyroidism alone can lead to myocardial fibrosis and result in heart failure, but traditional hormone replacement therapy does not improve the fibrotic situation. Hydrogen sulfide (H₂S), a new gas signaling molecule, possesses anti-inflammatory, antioxidant, and anti-fibrotic capabilities. Whether H₂S could improve hypothyroidism-induced myocardial fibrosis are not yet studied. In our study, H₂S could decrease collagen deposition in the myocardial tissue of rats caused by hypothyroidism. Furthermore, in hypothyroidism-induced rats, we found that H₂S could enhance cystathionine-gamma-lyase (CSE), not cystathionine β-synthase (CBS), protein expressions. Finally, we noticed that H₂S could elevate autophagy levels and inhibit the transforming growth factor-β1 (TGF-β1) signal transduction pathway. In conclusion, our experiments not only suggest that H₂S could alleviate hypothyroidism-induced myocardial fibrosis by activating autophagy and suppressing TGF-β1/SMAD family member 2 (Smad 2) signal transduction pathway, but also show that it can be used as a complementary treatment to conventional hormone therapy.

• 대한한의학방제학회지
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• 제31권1호
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• pp.29-39
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• 2023

Objective : Gardeniae Fructus (GF) is the ripe fruit of Gardenia jasminoides Ellisa with a bitter taste and cold properties. Ingredient compounds including geniposide are known to have anti-inflammatory, antioxidant, and neuroprotective effects. The purpose of this study was to investigate the neuroprotective effect of GF on tBHP-induced PC12 cells. Methods : Cell viability was measured by the MTT assay, and apoptosis was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expression level of each protein was monitored by Western blot analysis, and reactive oxygen species (ROS) were analyzed using DCFH-DA. Results : In PC12 cells, tBHP induced cell death through apoptosis with caspase activation and PARP inactivation. Cells treated with tBHP showed an increase in intracellular ROS and depletion of GSH. Pretreatment with GF prevented tBHP-induced apoptosis, reduced ROS, and increased GSH. GF also maintained increased Nrf2 expression in the presence of tBHP. Phosphorylation of JNK and p38 MAPK was increased by tBHP, whereas phosphorylation of ERK was decreased. GF restored changes in ERK and p38 phosphorylation, but not JNK phosphorylation. Conclusion : These results indicate that GF has neuroprotective effects through anti-apoptotic and antioxidant effects mediated by regulation of Nrf2 expression and phosphorylation of ERK and p38. It also demonstrates the potential use of GF as a source of antioxidant and neuroprotective substances.

• 대한약침학회지
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• 제25권4호
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• pp.326-343
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• 2022

Neurological disorders represent a substantial healthcare burden worldwide due to population aging. Acorus gramineus Solander (AG) and Acorus tatarinowii Schott (AT), whose major component is asarone, have been shown to be effective in neurological disorders. This review summarized current information from preclinical and clinical studies regarding the effects of extracts and active components of AG and AT (e.g., α-asarone and β-asarone) on neurological disorders and biomedical targets, as well as the mechanisms involved. Databases, including PubMed, Embase, and RISS, were searched using the following keywords: asarone, AG, AT, and neurological disorders, including Alzheimer's disease, Parkinson's disease, depression and anxiety, epilepsy, and stroke. Meta-analyses and reviews were excluded. A total of 873 studies were collected. A total of 89 studies were selected after eliminating studies that did not meet the inclusion criteria. Research on neurological disorders widely reported that extracts or active components of AG and AT showed therapeutic efficacy in treating neurological disorders. These components also possessed a wide array of neuroprotective effects, including reduction of pathogenic protein aggregates, antiapoptotic activity, modulation of autophagy, anti-inflammatory and antioxidant activities, regulation of neurotransmitters, activation of neurogenesis, and stimulation of neurotrophic factors. Most of the included studies were preclinical studies that used in vitro and in vivo models, and only a few clinical studies have been performed. Therefore, this review summarizes the current knowledge on AG and AT therapeutic effects as a basis for further clinical studies, and clinical trials are required before these findings can be applied to human neurological disorders.

• Biomolecules & Therapeutics
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• 제31권1호
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• pp.40-47
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• 2023

Activation of the NLRP3 inflammasome is a necessary process to induce fibrosis in nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH) is a kind of NAFLD that encompasses the spectrum of liver disease. It is characterized by inflammation and ballooning of hepatocytes during steatosis. We tested whether inhibiting the NLRP3 inflammasome could prevent the development and pathology of NASH. We identified loganin as an inhibitor of the NLRP3 inflammasome and investigated whether in vivo administration of loganin prevented NASH symptoms using a methionine-choline deficient (MCD) diet model in mice. We found that loganin inhibited the NLRP3 inflammasome activation triggered by ATP or nigericin, as shown by suppression of the production of interleukin (IL)-1β and caspase-1 (p10) in mouse primary macrophages. The speck formation of apoptosisassociated speck-like protein containing a caspase recruitment domain (ASC) was blocked by loganin, showing that the assembly of the NLRP3 inflammasome complex was impaired by loganin. Administration of loganin reduced the clinical signs of NASH in mice fed the MCD diet, including hepatic inflammation, fat accumulation, and fibrosis. In addition, loganin reduced the expression of NLRP3 inflammasome components in the liver. Our findings indicate that loganin alleviates the inflammatory symptoms associated with NASH, presumably by inhibiting NLRP3 inflammasome activation. In summary, these findings imply that loganin may be a novel nutritional and therapeutic treatment for NASH-related inflammation.

• Fisheries and Aquatic Sciences
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• 제26권2호
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• pp.158-168
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• 2023

The global output of Pyropia yezoensis (dried seaweed or laver, also called 'Gim' in Korea) has been reduced over the half-decade due to the wide spread of red rot disease, a serious algal disease affecting P. yezoensis. Recently, Gold 1 (G1), which is a resistant strain of P. yezoensis to red rot disease, was developed and commercialized in South Korea, yet its physiological activity has not been investigated. In this study, a comparative study was performed on G1 and commercially available strain of P. yezoensis (CP) for their antioxidative activities. Aqueous extract of G1 showed more marked 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity compared to that of CP. In 293T cells, antioxidant activity against H₂O₂-induced reactive oxygen species (ROS) formation was only observed in G1 extract. In addition, G1 extract showed more potent inhibitory effect on H₂O₂-induced apoptotic cell death than CP extract, as examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and fluorescence microscopy. Expression levels of various apoptosis-related genes, including B-cell lymphoma 2-associated X protein, p53, capase-3, and inflammatory cytokines, in H₂O₂-treated cells were significantly decreased by the treatment of G1. Taken together, the present study suggests that a new strain of red seaweed G1 can recover oxidative stress effectively by improving the imbalance of ROS generation and has a potential to be used a functional ingredient as an antioxidant source.

• Journal of Veterinary Science
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• 제24권3호
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• pp.37.1-37.14
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• 2023

Background: Toll-like receptor (TLR) agonists have been used as adjuvants to modulate immune responses in both animals and humans. Objectives: The objective of this study was to evaluate the combined effects of the TLR 4 agonist monophosphoryl lipid A (MPL) and the TLR 3 agonist polyinosinic:polycytidylic acid (Poly I:C) on equine peripheral blood mononuclear cells (PBMCs), monocyte-derived dendritic cells (MoDCs), and bone marrow-derived mesenchymal stromal cells (BM-MSCs). Methods: The PBMCs, MoDCs, and BM-MSCs collected from three mixed breed horses were treated with MPL, Poly I:C, and their combination. The mRNA expression of interferon gamma (IFN-γ), interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-12p40, tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1) was determined using real-time polymerase chain reaction. Results: The combination of MPL and Poly I:C significantly upregulated immunomodulatory responses in equine cells/ without cytotoxicity. The combination induced greater mRNA expression of pro-inflammatory cytokines IFN-γ and IL-6 than MPL or Poly I:C stimulation alone in PBMCs. In addition, the combination induced significantly higher mRNA expression of IL-1β, IL-6, and IL-12p40 in MoDCs, and IL-8, MCP-1, and VEGF in BM-MSCs compared to stimulation with a single TLR agonist. Conclusions: The combination of MPL and Poly I:C can be used as a potential adjuvant candidate for vaccines to aid in preventing infectious diseases in horses.

• Journal of Ginseng Research
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• 제47권4호
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• pp.543-551
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• 2023

Background: Panax ginseng Meyer is a representative Chinese herbal medicine with antioxidant and anti-inflammatory activity. 20(S)-Protopanaxadiol (PPD) has been isolated from ginseng and shown to have promising pharmacological activities. However, effects of PDD on pulmonary fibrosis (PF) have not been reported. We hypothesize that PDD may reverse inflammation-induced PF and be a novel therapeutic strategy. Methods: Adult male C57BL/6 mice were used to establish a model of PF induced by bleomycin (BLM). The pulmonary index was measured, and histological and immunohistochemical examinations were made. Cell cultures of mouse alveolar epithelial cells were analyzed with Western blotting, coimmunoprecipitation, immunofluorescence, immunohistochemistry, siRNA transfection, cellular thermal shift assay and qRT-PCR. Results: The survival rate of PPD-treated mice was higher than that of untreated BLM-challenged mice. Expression of fibrotic hallmarks, including α-SMA, TGF-β1 and collagen I, was reduced by PPD treatment, indicating attenuation of PF. Mice exposed to BLM had higher STING levels in lung tissue, and this was reduced by phosphorylated AMPK after activation by PPD. The role of phosphorylated AMPK in suppressing STING was confirmed in TGF-b1-incubated cells. Both in vivo and in vitro analyses indicated that PPD treatment attenuated BLM-induced PF by modulating the AMPK/STING signaling pathway. Conclusion: PPD ameliorated BLM-induced PF by multi-target regulation. The current study may help develop new therapeutic strategies for preventing PF.

• Molecules and Cells
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• 제46권4호
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• pp.245-255
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• 2023

This study aimed to exploring the pathophysiological mechanism of 7α,25-dihydroxycholesterol (7α,25-DHC) in osteoarthritis (OA) pathogenesis. 7α,25-DHC accelerated the proteoglycan loss in ex vivo organ-cultured articular cartilage explant. It was mediated by the decreasing extracellular matrix major components, including aggrecan and type II collagen, and the increasing expression and activation of degenerative enzymes, including matrix metalloproteinase (MMP)-3 and -13, in chondrocytes cultured with 7α,25-DHC. Furthermore, 7α,25-DHC promoted caspase-dependent chondrocyte death via extrinsic and intrinsic pathways of apoptosis. Moreover, 7α,25-DHC upregulated the expression of inflammatory factors, including inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E₂, via the production of reactive oxygen species via increase of oxidative stress in chondrocytes. In addition, 7α,25-DHC upregulated the expression of autophagy biomarkers, including beclin-1 and microtubule-associated protein 1A/1B-light chain 3 via the modulation of p53-Akt-mTOR axis in chondrocytes. The expression of CYP7B1, caspase-3, and beclin-1 was elevated in the degenerative articular cartilage of mouse knee joint with OA. Taken together, our findings suggest that 7α,25-DHC is a pathophysiological risk factor of OA pathogenesis that is mediated a chondrocyte death via oxiapoptophagy, which is a mixed mode of apoptosis, oxidative stress, and autophagy.

• The Korean Journal of Physiology and Pharmacology
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• 제27권4호
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• pp.375-381
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• 2023

Numerous studies have revealed the importance of tumor-derived exosomes in rectal cancer (RC). This study aims to explore the influence of tumor-derived exosomal integrin beta-1 (ITGB1) on lung fibroblasts in RC along with underlying mechanisms. Exosome morphology was observed using a transmission electron microscope. Protein levels of CD63, CD9, ITGB1, p-p65 and p65 were detected using Western blot. To determine ITGB1's mRNA expression, quantitative real-time polymerase chain reaction was used. Moreover, levels of interleukin (IL)-8, IL-1β, and IL-6 in cell culture supernatant were measured via commercial ELISA kits. ITGB1 expression was increased in exosomes from RC cells. The ratio of p-p65/p65 as well as levels of interleukins in lung fibroblasts was raised by exosomes derived from RC cells, while was reduced after down-regulation of exosomal ITGB1. The increased ratio of p-p65/p65 as well as levels of pro-inflammatory cytokines caused by exosomes from RC cells was reversed by the addition of nuclear factor kappa B (NF-κB) inhibitor. We concluded that the knockdown of RC cells-derived exosomal ITGB1 repressed activation of lung fibroblasts and the NF-κB pathway in vitro.