• Journal of Ginseng Research
• /
• v.48 no.1
• /
• pp.77-88
• /
• 2024

Background: Lung inflammation occurs in many lung diseases, but has limited effective therapeutics. Ginseng and its derivatives have anti-inflammatory effects, but their unstable physicochemical and metabolic properties hinder their application in the treatment. Panaxadiol (PD) is a stable saponin among ginsenosides. Inhalation administration may solve these issues, and the specific mechanism of action needs to be studied. Methods: A mouse model of lung inflammation induced by lipopolysaccharide (LPS), an in vitro macrophage inflammation model, and a coculture model of epithelial cells and macrophages were used to study the effects and mechanisms of inhalation delivery of PD. Pathology and molecular assessments were used to evaluate efficacy. Transcriptome sequencing was used to screen the mechanism and target. Finally, the efficacy and mechanism were verified in a human BALF cell model. Results: Inhaled PD reduced LPS-induced lung inflammation in mice in a dose-dependent manner, including inflammatory cell infiltration, lung tissue pathology, and inflammatory factor expression. Meanwhile, the dose of inhalation was much lower than that of intragastric administration under the same therapeutic effect, which may be related to its higher bioavailability and superior pharmacokinetic parameters. Using transcriptome analysis and verification by a coculture model of macrophage and epithelial cells, we found that PD may act by inhibiting TNFA/TNFAR and IL7/IL7R signaling to reduce macrophage inflammatory factor-induced epithelial apoptosis and promote proliferation. Conclusion: PD inhalation alleviates lung inflammation and pathology by inhibiting TNFA/TNFAR and IL7/IL7R signaling between macrophages and epithelial cells. PD may be a novel drug for the clinical treatment of lung inflammation.

• International Journal of Stem Cells
• /
• v.16 no.2
• /
• pp.191-201
• /
• 2023

Background and Objectives: O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung. Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice. Methods and Results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSC^cP1P), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSC^cP1P reduce inflammatory response in LPS exposed mice. hdMSC^cP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSC^cP1P treated mice. Conclusions: Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSC^cP1P provide a therapeutic potential for ALI/ARDS treatment.

• Herbal Formula Science
• /
• v.32 no.1
• /
• pp.51-61
• /
• 2024

Objectives : This study induced oxidative stress in HepG2 cells by treating them with AA+iron and investigated the effects of forsythia suspensa extract on this stress, as well as elucidated the molecular mechanisms underlying its hepatoprotective effects. Methods : To confirm the antioxidative effects of FSE, HepG2 cells were induced with AA+iron to induce oxidative stress, followed by MTT assay. Additionally, the effect of FSE in reducing the increased ROS levels and mitochondrial damage induced by AA+iron in HepG2 cells was confirmed using FACS. Furthermore, western blot analysis were conducted to investigate the molecular mechanisms underlying the hepatoprotective effects of FSE. Results : FSE increased the decreased cell viability induced by AA+iron. Additionally, FSE normalized the expression of apoptosis-related proteins induced by AA+iron. The elevated ROS levels in HepG2 cells induced by AA+iron were reduced by FSE, and the increase in Rh123-negative cells induced by AA+iron was attenuated by FSE. Moreover, FSE activated the protein expression of AMPK and its related phosphorylating enzymes, LKB1 and ACC. Furthermore, FSE activated YAP and its upstream phosphorylating enzyme, LATS1. Conclusions : These results demonstrate that FSE has an inhibitory effect on oxidative stress induced by AA+iron and may have potential hepatoprotective effects.

• Journal of Life Science
• /
• v.20 no.4
• /
• pp.561-571
• /
• 2010

Colon cancer is one of the most common malignancies in the western world and the second leading cause of cancer death in Korea. Epidemiology studies have shown a reduced incidence of colon cancer among populations consuming a large quantity of ${\omega}3$-polyunsaturated fatty acids (${\omega}3$-PUFA) of marine origin. Recently, it has been found that ${\omega}3$-PUFA has an antineoplastic effect in several cancers. This study was designed to investigate the mechanism of the anti-invasive effect of ${\omega}3$-PUFA in colon cancer. ${\omega}3$-PUFA, docosahexaenoic acids (DHA) and eicosapentaenoic acid (EPA) treatment resulted in a dose-dependent inhibition of cell growth in SW480 human colon cancer cells. In contrast, arachidonic acid (AA), a ${\omega}6$-PUFA, exhibited no significant effect. This action likely involves apoptosis, given that DHA treatment increased apoptotic cells in TUNEL assay. Moreover, invasiveness of SW480 cells was inhibited following treatment of DHA in a dose-dependent manner; in contrast, AA had no effect. The levels of MMP-9 and MMP-2 mRNA decreased after DHA pretreatment. MMP-9 and MMP-2 promoter activities were also inhibited by DHA treatment. The levels of NF-kB and p-IkB protein were down-regulated by DHA pretreatment in a dose dependent manner. In addition, DHA inhibited NF-kB promoter reporter activities. These findings suggest that ${\omega}3$-PUFA may inhibit cancer cell invasion by inhibition of MMPs via reduction of NF-kB in colon cancer. In conclusion, ${\omega}3$-PUFA could be used for chemoprevention and treatment of human colon cancer.

• Tuberculosis and Respiratory Diseases
• /
• v.59 no.2
• /
• pp.142-150
• /
• 2005

Background : Continuous growth stimulation by various factors, as well as chronic oxidative stress, may co-exist in many solid tumors, such as lung cancer. A new family of antioxidant proteins, the peroxiredoxins (Prxs), have been implicated in the regulation of many cellular processes, including cell proliferation, differentiation and apoptosis. However, a real pathophysiological significance of Prx proteins, especially in lung disease, has not been sufficiently defined. Therefore, this study was conducted to investigate the distribution and expression of various Prx isoforms in lung cancer and other pulmonary conditions. Method : Patients diagnosed with lung cancer, and who underwent surgery at the Ajou Medical Center, were enrolled. The expressions of Prxs, Thioredoxin (Trx) and Thioredoxin reductase (TR) were analyzed using proteomic techniques and the subcellular localization of Prx proteins was studied using immunohistochemistry on normal mouse lung tissue. Result : Immunohistochemical staining has shown the isoforms of Prx I, II, III and V are predominantly expressed in bronchial and alveolar lining epithelia, as well as in the alveolar macrophages of the normal mouse lung. The isoforms of Prx I and III, and thioredoxin were also found to be over-expressed in the lung cancer tissues compared to their paired normal lung controls. There was also an increased amount of the oxidized form of Prx I, as well as a putative truncated form of Prx III, in the lung cancer samples when analyzed using 2-dimensional electrophoresis. In addition, a 43 kDa intermediate molecular weight protein band, and other high molecular weight bands of over 20 kDa, recognized by the anti-Prx I antibody, were present in the tissue extracts of lung cancer patients on 1-Dimensional electrophoresis, which require further investigation. Conclusion : The over-expressions of Prx I and III, and Trx in human lung cancer tissue, as well as their possible chaperoning function, may represent an attempt by tumor cells to adjust to their microenvironment in a manner advantageous to their survival and proliferation, while maintaining their malignant potential.

• Journal of Veterinary Clinics
• /
• v.29 no.4
• /
• pp.283-296
• /
• 2012

Allergic contact dermatitis (ACD) is an inflammatory skin disease and regarded as a prototype of T-cell mediated delayed-type hypersensitivity reactions. Poly-${\gamma}$-glutamic acid (PGA) is a biodegradable polymer that is produced by Bacillus subtilis. This study was performed to assess the effects of PGA in a canine model of ACD. ACD was induced on the back of dogs induced by sensitization and repeated application by 2,4-dinitro-1-chlorobenzene (DNCB). Topical treatment of PGA was applied once a day for 12 days and skin biophysical parameters including transepidermal water loss (TEWL), skin hydration, skin pH, skin thickness and erythema index, were measured every two days during experimental periods. Histopathology and immunohistochemistry were performed to evaluate the antiinflammatory effect. In skin biophysical parameters, TEWL, skin hydration, skin thickness and erythema index were significantly increased, with a maximum increase appeared on day 2 (p < 0.05). On the other hand, skin pH was significantly decreased, with a maximum decrease appeared on day 2 (p < 0.01). After the completion of PGA treatment, skin biophysical parameters were significantly reached those of baseline in a time-dependent manner (p < 0.05). In histopathology, marked increases of epidermal thicknesses were induced after DNCB challenge with numerous inflammatory cell infiltrations and edematous changes, decreases of connective tissue occupied regions in dermis. In addition, marked increases of cytokine - tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interferon-${\gamma}$ (IFN-${\gamma}$)-immunoreactivities in the dermis and of apoptotic markers - caspase-3 and PARP-immunoreactivities in the epidermis were observed in DNCB-PBS control as compared with intact control, respectively (p < 0.01). It means, the ACD and related apoptotic changes were induced by DNCB in the present study. However, these ACD induced by DNCB and related apoptosis in epidermis were significantly inhibited by treatment of PGA treated skin, the decreases of infiltrated inflammatory cells and related decreases of pro-inflammatory cytokine immunoreactivities were also observed (p < 0.01). Based on these findings, PGA may have anti-inflammatory and alleviatory effects in the allergic contact dermatitis.

• KOREAN JOURNAL OF CROP SCIENCE
• /
• v.53 no.1
• /
• pp.75-84
• /
• 2008

Colored potatoes are an excellent source of dietary polyphenols including anthocyanins. Generally, anthocyanins from fruits and vegetables exhibit anti-carcinogenesis and anti-cancer properties in vitro test. This experiment was conducted to know the effects of colored potato extracts contained anthocyanins on antimutagenic activity and anticancer activity to six human cancer cell lines containing LNCaP (androgen-dependent) prostate cancer cells. Extracts of three colored potatoes ('Hongyoung', 'Jayoung' and 'Jasim') and the white potato ('Superior') cultivars were used in this study. The extracts of three colored potatoes inhibited the mutagenicities induced by direct mutagen such as 4-nitro-quinoline-1-oxide (4-NQO) and another indirect mutagens of bezo(a)pyrene (BaP). Also, the extracts of 'Hoyoung' and 'Jayoung' showed higher antimutagenic activity than 'Jasim' and 'Superior' against to direct or indirect mutagen on both strains of TA98 and TA100. The activity of growth-inhibitory of extract of four potato cultivars were screened by SRB (sulphorhodamine B) method on diverse human cancer cells representing different types of cancers. Among the extract of four potato cultivars, the extract of 'Jasim' showed moderate inhibition on proliferation of LNCaP, ACHN and MOLT-4F cells and did not inhibit the proliferation of other cancer cells. On the other hand, extract of 'Superior' did not inhibit the proliferation of any tested cancer cell lines. However, the extracts of 'Hongyoung and Jayoung' inhibited the proliferation of cancer cells with $GI_{50}$ values ranging from 2.5 to $30\;{\mu}g/mL$. On the basis of the $GI_{50}$ values, it is clear that LNCaP cells were more sensitive to extracts of colored potato cultivars than other cancer cells. The extract of 'Jayoung' at $30\;{\mu}g/mL$ were more active and inhibited cell proliferation, and induced apoptosis in LNCaP cells. This result revealed that the extracts of colored potatoes are expected to be good candidate for development into source of antimutagenic and anticancer agent.

• Journal of the Korean Applied Science and Technology
• /
• v.37 no.3
• /
• pp.448-462
• /
• 2020

Dietary nutrition is a critical lifestyle factor that can reduce the risk of future cognitive impairments caused by dementia. Accumulating evidence suggests that dietary supplementation with Sulforaphane may help the prevention of cognitive impairments and dementia. Thus, Sulforaphane-enriched broccoli extract would hold promise to improve cognitive impairments of dementia patients. Here, we have used broccoli extracts, prepared from broccoli cultivated in Magma Seawater, to test if the broccoli extracts can be dietary supplement to improve cognitive impairments. Magma Seawater originated from Jeju Island, Korea is unique in terms of containing high concentrations of usable minerals (Zinc, Vanadium and Germanium etc.). Broccoli, grown in Magma Seawater, would contain Sulforaphane and the extra amount of usable minerals. The chemical compositions of the broccoli extracts were analyzed using LC-Q-orbitrap to detect Sulforaphane and Glucoraphanin. Analysis method based on HPLC was developed for measurement of sulforaphane levels in the broccoli extracts. We have tested if the broccoli extracts have anti-apoptotic and anti-inflammatory effects on neuron-like SH-SY5Y cells. In addition, we examined if the broccoli extracts are able to upregulate expression of synaptic plasticity-associated proteins (BDNF and phospho-CREB) and to inhibit acetylcholine esterase (AchE) activity. We have shown that the broccoli extracts inhibited the apoptotic pathway and inflammatory responses. Finally, we present evidence showing that AchE activity was inhibited by the broccoli extracts, but expression of BDNF and phospho-CREB was upregulated. Taken together, these findings suggest that the broccoli extracts from Magma Seawater-grown broccoli would be a good source of dietary nutrition to improve cognitive impairments in the future.

• Korean Journal of Food Science and Technology
• /
• v.44 no.4
• /
• pp.428-433
• /
• 2012

Probiotics and their products, such as yogurt and cheese have been widely consumed in many countries with proven health benefits including anti-microbial activity and anti-diarrheal activity. LHFM (Lactobacillus helveticus - fermented milk) is a processed skim milk powder, fermented by a probiotics, L. helveticus IDCC3801. In the present study, we aimed to investigate the neuroprotective effects and the cognitive improvements of LHFM. LHFM itself did not show any cytotoxicity to the human neuroblastoma cell line, SH-SY5Y; however, it dose-dependently protected against glutamate-induced neuronal cell death. LHFM also attenuated scopolamine-induced memory deficit in Y-maze and Morris-water maze. In the analysis of hippocampus after a behavior test, LHFM significantly increased the acetylcholine level and also inhibited acetylcholine esterase activity. Therefore, the raised acetylcholine release partially contributes to the improvement of learning and memory by a treatment with LHFM. These results suggest that LHFM is an effective material for prevention or improvement of cognitive impairments caused by neuronal cell damage and central cholinergic dysfunction.

• Journal of Life Science
• /
• v.28 no.2
• /
• pp.240-246
• /
• 2018

Efferent and afferent sympathetic nerves are closely related to the development of hypertension and heart failure. Catheter-based renal sympathetic denervation (RDN) is implemented as a strategy to treat resistant hypertension. We investigated whether RDN procedure causes inflammatory damage on myocardium in the early phase of sympathetic denervation. Twenty-five female swine were divided into 3 groups: normal control (Normal, n=5), sham-operated control (Sham, n=5), and RDN groups (RDN, n=15). The RDN group was further subdivided into 3 subgroups according to the time of sacrifice: immediately (RDN-0, n=5), 1 week (RDN-1, n=5), and 2 weeks (RDN-2, n=5) after RDN. There were no significant changes in the clinical parameters between the normal control and sham-operated group using contrast-media. In the myocardium, inflammatory cytokines, $IL-1{\beta}$ and $TNF-{\alpha}$ increased at the first week, and then decreased at the second week after RDN. Anti-inflammatory cytokine, IL-10 increased immediately, and then decreased at the second week after RDN. Caspase-1 activity and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) expression increased immediately after RDN until the second week. However, nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing protein 3 (NLRP3) expression did not show any significant differences among the groups. The RDN can cause acute myocardial inflammation through activation of caspase-1 and $IL-1{\beta}$. We should pay attention to protecting against early inflammatory myocardial damage after RDN.