• Journal of Nutrition and Health
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• v.52 no.2
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• pp.139-148
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• 2019

Purpose: Ulcerative colitis is a common inflammatory bowel disease. Prolonged colitis can be a risk factor for the development of colorectal cancer. Mulberry twig (MT, Sangzhi), a dry branch of Morus alba L., which is widely distributed throughout East Asia, has been shown to have anti-inflammatory activities in the cells. However, the effects of MT extracts on colitis in in vivo are limited. Therefore, in this study, we investigated the anti-inflammatory effects of MT extracts in the dextran sulfate sodium (DSS)-induced mouse colitis model. Methods: Six week-old, male ICR mice were divided into 3 groups: Control (n = 5), DSS (n = 7), and DSS+MT (n = 7) groups. Mice in the DSS and DSS+MT groups were administrated 3% DSS in drinking water for 5 days to induce colitis. At the same time, water extracts of MT (5 g/kg body weight/day) were orally administered to mice in the DSS+MT groups for 5 days. Results: The MT extracts significantly reduced the clinical and pathological characteristics of colitis. Disease activity index, mucosal thickness, and colonocyte proliferation were significantly reduced in the DSS+MT group compared with the DSS group. Furthermore, MT administration reduced the levels of plasma $TNF-{\alpha}$, IL-6, and the colonic myeloperoxidase activity as well as mRNA expression of $TNF-{\alpha}$, IL-6, Cox-2, and iNOS. Conclusion: Taken together, these results suggest that MT water extracts have potent anti-colitis activities in the mouse colitis model.

• The Korea Journal of Herbology
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• v.33 no.5
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• pp.89-103
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• 2018

Objectives : This study is aimed to compare the changes in Antioxidative capacity of Liriopis Tuber by steaming process and to compare the effects in hyperlipidemia induced rats fed high cholesterol diet between Simvastatin and Liriopis Tuber by steaming process. Methods : The SD rats were divided into six groups: normal diet (Nor), high cholesterol diet (Veh), high cholesterol diet plus Simvastatin 5 mg/kg (Sim), high cholesterol diet plus LT0 extract 200 mg/kg (LT0), high cholesterol diet plus LT6 extract 200 mg/kg (LT6) and high cholesterol diet plus LT9 extract 200 mg/kg (LT9). We compared the total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL) contents and reactive oxygen species (ROS) from each serums. Protein expression in liver tissues related to antioxidant and cholesterol was analyzed. Results : The Antioxidant activity of Liriopis Tuber increased by steaming process. In vivo, TC, TG, LDL-c, atherogenic index (AI) and cardiac risk factor (CRF) decreased and HDL-c increased with increasing steaming frequency. aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and blood urea nitrogen (BUN) decreased with increasing steaming frequency. ROS decreased only in LT9, and SOD, catalase and glutathione peroxidase (GPx) increased with increasing steaming frequency. phospho-AMP-activated protein kinase (p-AMPK) increased and sterol regulatory element-binding protein 2 (SREBP-2), Phospho-Acetyl-CoA Carboxylase (p-ACC) and HMG-CoA reductase (HMGCR) decreased with increasing steaming frequency. Liver staining showed a decrease in hepatic fat accumulation of LT9. LT9 showed significant results in all experiments. Conclusions : LT9 showed significance of anti-lipid effect and improved fatty liver of hyperlipemia induced rats fed on high cholesterol diet, In conclusion, LP9 can be effectively used for the treatment of hyperlipidemia.

• Biomolecules & Therapeutics
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• v.31 no.2
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• pp.227-239
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• 2023

Major depressive disorder is a leading cause of disability in more than 280 million people worldwide. Monoamine-based antidepressants are currently used to treat depression, but delays in treatment effects and lack of responses are major reasons for the need to develop faster and more efficient antidepressants. Studies show that ketamine (KET), a PCP analog, produces antidepressant effects within a few hours of administration that lasts up to a week. However, the use of KET has raised concerns about side effects, as well as the risk of abuse. 4 -F-PCP analog is a novel PCP analog that is also an NMDA receptor antagonist, structurally similar to KET, and might potentially elicit similar antidepressant effects, however, there has been no study on this subject yet. Herein, we investigate whether 4-F-PCP displays antidepressant effects and explored their potential therapeutic mechanisms. 4-F-PCP at 3 and 10 mg/kg doses showed antidepressant-like effects and repeated treatments maintained its effects. Furthermore, treatment with 4-F-PCP rescued the decreased expression of proteins most likely involved in depression and synaptic plasticity. Changes in the excitatory amino acid transporters (EAAT2, EAAT3, EAAT4) were also seen following drug treatment. Lastly, we assessed the possible side effects of 4-F-PCP after long-term treatment (up to 21 days). Results show that 4-F-PCP at 3 mg/kg dose did not alter the cognitive function of mice. Overall, current findings provide significant implications for future research not only with PCP analogs but also on the next generation of different types of antidepressants.

• Journal of Nutrition and Health
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• v.56 no.4
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• pp.361-376
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• 2023

Purpose: This study evaluates the potential protective effects of hemp (Cannabis sativa L.) seed oil supplementation in rats fed a high-cholesterol diet. Methods: Rats were fed a 1.25% cholesterol diet for 8 weeks, followed by oral administration of either of the two doses of hemp seed oil (HO) (0.5 mL/kg (HOL group) or 1 mL/kg (HOH group) body weight/day) or simvastatin at 10 mg/kg body weight/day. Oxidative stress, lipids, liver enzymes, and renal markers were measured in the serum. Western blot analysis was applied for evaluating the expressions of inflammatory makers. Results: Except for HDL-cholesterol, the altered levels of lipoproteins, aminotransferases, urea, and creatine kinases in hypercholesterolemic rats were significantly corrected by HO administration. Especially, compared to the HOH group, HOL treatment further reduced AST, ALT, creatinine, TC, and LDL-cholesterol levels. Moreover, both the atherogenic index and cardiac risk factor (CRF) in the HOL group were more restrained compared to the HOH group. Increased levels of p-AMPK coincided with the inhibition of SREBP-2 activation which subsequently suppressed the expression of HMGCR. Nuclear factor (NF)-κB activation coincided with the PI3K/Akt pathway activation and the increased phosphorylation of p38; these levels were significantly suppressed by HO treatment. In addition, HO treatment markedly reversed the changes in chemokines such as ICAM-1, VCAM-1, and MCP-1. Histological alterations induced by cholesterol overload in cardiac and hepatic tissues were ameliorated by HO supplementation. Conclusion: Taken together, our results indicate a low concentration of HO demonstrates improved dysfunctions caused by a high-cholesterol diet via inhibition of the PI3K/Akt/NF-κB signaling pathway.

• Korean Journal of Environmental Biology
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• v.41 no.1
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• pp.41-53
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• 2023

E171, a mixture of titanium dioxide, has been widely used as a food additive due to its whitening effect and low toxicity. However, it has been proven that E171 is no longer safe for public health. So far, there are insufficient studies on the toxic effects of E171 on organisms especially using standardized test methods. In this study, toxicity assessments of E171 to two aquatic species, water flea (Daphnia magna) and zebrafish (Danio rerio), were performed using modified standardized test methods based on the physicochemical properties of E171. The hydrodynamic diameter, polydispersity index, and turbiscan stability index (TSI) were measured to ensure the dispersion stability of E171 in exposure media during the test period. The EC₅₀ for immobilization of water flea was 141.7 mg L^-1 while zebrafish was not affected until 100 mg L^-1 of E171. Measurements of reactive oxygen species (ROS) and antioxidant enzyme activities confirmed that E171 induced oxidative stress, leading to the activation of superoxide dismutase and catalase in both water flea and zebrafish, although the expression of antioxidant enzyme genes differed between species. These results suggested the potential risk of E171 to aquatic organisms and provided toxicological insights into the impacts of E171 on the environment.

• Journal of Life Science
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• v.34 no.6
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• pp.418-425
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• 2024

Solid tumors are heterogeneous populations of multiple cell types. While the majority of the cells that comprise cancer are unable to divide, cancer stem cells have self-renewal and differentiation properties. Normal stem cell pathways that control self-renewal are overactivated in cancer stem cells, making cancer stem cells important for cancer cell expansion and progression. Dick first proposed the definition of cancer stem cells in acute myeloid leukemia, according to which cancer stem cells can be classified based on the expression of cell surface markers. Cancer stem cells maintain their potential in the tumor microenvironment. Multiple cell types in the tumor microenvironment maintain quiescent cancer stem cells and serve as regulators of cancer growth. Since current cancer treatments target proliferative cells, quiescent state cancer stem cells that are resistant to treatment increase the risk of recurrence or metastasis. Various signals of the tumor microenvironment induce changes to become a tumor-supportive environment by remodeling the vasculature and extracellular matrix. To effectively treat cancer, cancer stem cells and the tumor microenvironment must be targeted. Therefore, it is important to understand how the tumor microenvironment induces reprogramming of the immune response to promote cancer growth, immune resistance, and metastasis. In this review, we discuss the cellular and molecular mechanisms that can enhance immunosuppression in the tumor microenvironment.

• Anatomy and Cell Biology
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• v.57 no.3
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• pp.431-445
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• 2024

Parkinson's disease (PD) affects about 8.5 million individuals worldwide. Oxidative and inflammatory cascades are implicated in the neurological sequels, that are mostly unresolved in PD treatments. However, proper nutrition offers one of the most effective and least costly ways to decrease the burden of many diseases and their associated risk factors. Moreover, prevention may be the best response to the progressive nature of PD, thus, the therapeutic novelty of honey and levodopa may be prospective. This study aimed to investigate the neuroprotective role of honey and levodopa against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced oxidative stress. Fifty-four adult male Swiss mice were divided into control and PD model groups of 27 mice. Each third of the control mice either received phosphate buffered saline, honey, or levodopa for 21 days. However, each third of the PD models was either pretreated with honey and levodopa or not pretreated. Behavioral studies and euthanasia were conducted 2 and 8 days after MPTP administration respectively. The result showed that there were significantly (P<0.05) higher motor activities in the PD models pretreated with the honey as well as levodopa. furthermore, the pretreatments protected the midbrain against the chromatolysis and astrogliosis induced by MPTP. The expression of antioxidant markers (glutathione [GSH] and nuclear factor erythroid 2-related factor 2 [Nrf2]) was also significantly upregulated in the pretreated PD models. It is thus concluded that honey and levodopa comparably protected the substantia nigra pars compacta neurons against oxidative stress by modulating the Nrf2 signaling molecule thereby increasing GSH level to prevent MPTP-induced oxidative stress.

• Journal of Chest Surgery
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• v.38 no.4 s.249
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• pp.263-270
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• 2005

In recent years, a combination of two demographic phenomena, an increased number of older people in the population and an increase in the incidence of lung cancer with age, has made it mandatory to develop therapeutic modalities with less toxicity for the treatment of inoperable elderly patients with lung cancer. Therefore, we investigated the correlation between COX-2 expression and cytotoxicity of Nimesulide, a specific COX-2 inhibitor. Material and Method: Immunohistochemical staining of COX-2 was performed. After exposure of Nimesulide, XTT analysis, FACS analysis and Hoechst staining were carried out. Result: COX-2 protein was expressed in non-treated A549 cells strongly, but not in H1299. Cytotoxicity of Nimesulide against A549 cell and H1299 cell were similar and $IC_{50}$ of Nimesulide in both cell lines were $70.9{\mu}M$ in A549 cell line and $56.5{\mu}M$ in H1299 cell line respectively. FACS analysis showed $G_0/G_1$ arrest in both cell lines and the S phase cell fraction was decreased. Morphologic assessment of apoptosis by Hoechst 33258 staining, many apoptotic cells were detected in both cell lines. Conclusion: Selective COX-2 inhibitor, Nimesulide, can inhibit the proliferation of non-small cell lung cancer cell lines in vitro. Inhibitory effect of Nimesulide are induction of apoptosis and $G_0/G_1$ arrest. There is no correlation between COX-2 expression and cytotoxicity of Nimesulide, a specific COX-2 inhibitor. Therefore, highly selective COX-2 inhibitors such as Nimesulide can be expected to lead to even greater efficacy of their use as adjuncts to various anticancer angents and radiation therapy for the treatment of high-risk patients.

• Tuberculosis and Respiratory Diseases
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• v.53 no.5
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• pp.485-496
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• 2002

Background : Nonsteroidal anti-inflammatory drugs (NSAIDs) are useful in the chemoprevention of colon cancers. Continuous NSAID use results in a 40% to 50% reduction in the relative risk of colorectal cancer. The precise mechanism by which NSAIDs prevent and/or cause the regression of colorectal tumors is not known. Some investigators have reported that certain NSAIDs induce apoptosis and alter the expression of the cell cycle regulatory genes in some carcinoma cells when administered at a relatively high concentration. However, the possibility of NSAIDs application as chemopreventive agents in lung cancers remains to be elucidated. To address this question, the human lung cancer cell line NCI-H1299 was used to investigate whether or not NSAIDs might induce the apoptotic death of NCI-H1299 cells. Methods : A viability test was carried out using a MTT assay. Apoptosis was measured by flow cytometric analysis and unclear staining(DAPI). The talytic activity of the caspase family was measured by the fluirigenic cleavage of biosubstrates. To define the mechanical basis of apoptosis, western blot was performed to analyze the expression of the death substrates(PARP and ICAD). Results : NaSaL significantly decreased the viability of the NCI-H1299 cells, which was revealed as apoptosis characterized by an increase in the $subG_0/G_1$ population and unclear fragmentation. The catalytic activity of caspase-3 protease began to increase after 24 Hr and reached a peak 30 Hr after treatment with 10 mM NaSaL. In contrast, caspase-6, 8, and 9 proteases did not have a significantly altered enzymatic activity. Consistent with activation of caspase-3 protease, NaSaL induced the cleavage of the protease biosubstrate. Conclusion : NaSaL induces the apoptotic death of NCI-H1299 human lung cancer cells via the activation of caspase-3 protease.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7633-7640
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• 2015

Background: Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and it is responsible for most cases of cervical uterine cancer. Although HPV infections of the cervix do not always progress to cancer, 90% of cervical cancer cases have been found to be associated with high risk HPV (HR-HPV) infection. HPV DNA testing is widely used, along with Papanicolaou (Pap) testing, to screen for cervical abnormalities. However, there are no data on the prevalence of genotype-specific HPV infections assessed by measuring HPV E6/E7 mRNA in women representative of the Chinese population across a broad age range. Materials and Methods: In the present study, we compared the results with the CervicGen HPV RT-qDx assay, which detects 16 HR-HPV genotypes (Alpha-9: HPV 16, 31, 33, 35, 52, and 58; Alpha-7: HPV 18, 39, 45, 51, 59, and 68; and Alpha-5, 6: HPV 53, 56, 66, and 69), and the REBA HPV-ID assay, which detects 32 HPV genotypes based on the reverse blot hybridization assay (REBA) for the detection of oncogenic HPV infection according to cytological diagnosis. We also investigated the prevalence and genotype distribution of HPV infection with a total of 324 liquid-based cytology samples collected in western Shandong province, East China. Results: The overall HPV prevalences determined by HPV DNA and HPV E6/E7 mRNA assays in this study were 79.9% (259/324) and 55.6% (180/324), respectively. Although the positivity of HPV E6/E7 mRNA expression was significantly lower than HPV DNA positivity, the HPV E6/E7 mRNA assay showed greater specificity than the HPV DNA assay (88.6% vs. 48.1%) in normal cytology samples. The prevalence of Alpha-9 (HPV 16, 31, 33, 35, 52, and 58) HPV infection among these women accounted for up to 80.3% and 76.1% of the high-grade lesions detected in the HPV mRNA and DNA tests, respectively. The HR-HPV genotype distribution, based on HPV DNA and E6/E7 mRNA expression by age group in patients with cytologically confirmed lesions, was highest in women aged 40 to 49 years (35.9% for cytologically confirmed cases, Pearson correlation r value=0.993, p<0.001) for high-grade lesions. Among the oncogenic HR-HPV genotypes for all age groups, there was little difference in the distribution of HPV genotypes between the HPV DNA (HPV -16, 53, 18, 58, and 33) and HPV E6/E7 mRNA (HPV -16, 53, 33, 58, and 18) assays. HPV 16 was the most common HPV genotype among women with high-grade lesions. Conclusions: Our results suggest that the HPV E6/E7 mRNA assay can be a sensitive and specific tool for the screening and investigation of cervical cancer. Furthermore, it may provide useful information regarding the necessity for early cervical cancer screenings and the development of additional effective HPV vaccines, such as one for HPV 53 and 58. Additionally, gaining knowledge of HPV distribution may also inform us about ecological changes in HPV after the vaccination.