• Korean Journal of Medicinal Crop Science
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• v.16 no.5
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• pp.313-319
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• 2008

Scutellaria barbata was examined to evaluate its modulatory effects on the functional activation of macrophages under lipopolysaccharide (LPS) treatment. To do this, hot water extract (Sb-HWE) was prepared from Scutellaria barbata and several inflammatory parameters such as nitric oxide (NO) production, phagocytosis, reactive oxygen species (ROS) determination and intracellular signaling pathway were selected to be tested. Sb-HWE strongly blocked NO production in LPS-activated RAW264.7 cells in a dose-dependent manner. However, it did not suppress inducible NO synthase (iNOS). In agreement, Sb-HWE did not diminish inflammatory signaling composed of NF-${\kappa}B$ and its upstream activation signaling enzymes such as Akt and $I{\kappa}B{\alpha}$. Sb-HWE protected RAW264.7 cells from LPS-induced cytotoxicity up to 80% at 400\;{\mu}g/ml$. Furthermore, this extract blocked phagocytic uptake of FITC-dextran, while sodium nitroprusside (SNP)-induced ROS generation in RAW264.7 cells was not decreased. Therefore, our data suggest that Sb-HWE may have differential immunoregulatory function depending on macrophage-mediated immune responses.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6549-6556
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• 2015

The PI3K-Akt-mTOR, $Wnt/{\beta}$-catenin and apoptosis signaling pathways have been shown to be involved in genesis of colorectal cancer (CRC). The aim of this study was to elucidate whether combination of Gelam honey and ginger might have chemopreventive properties in HT29 colon cancer cells by modulating the mTOR, $Wnt/{\beta}$-catenin and apoptosis signaling pathways. Treatment with Gelam honey and ginger reduced the viability of the HT29 cells dose dependently with $IC_{50}$ values of 88 mg/ml and 2.15 mg/ml respectively, their while the combined treatment of 2 mg/ml of ginger with 31 mg/ml of Gelam honey inhibited growth of most HT29 cells. Gelam honey, ginger and combination induced apoptosis in a dose dependent manner with the combined treatment exhibiting the highest apoptosis rate. The combined treatment downregulated the gene expressions of Akt, mTOR, Raptor, Rictor, ${\beta}$-catenin, $Gsk3{\beta}$, Tcf4 and cyclin D1 while cytochrome C and caspase 3 genes were shown to be upregulated. In conclusion, the combination of Gelam honey and ginger may serve as a potential therapy in the treatment of colorectal cancer through inhibiton of mTOR, $Wnt/{\beta}$ catenin signaling pathways and induction of apoptosis pathway.

• Preventive Nutrition and Food Science
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• v.7 no.2
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• pp.113-118
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• 2002

Alpha-lipoic acid is a known hypoglycemic agent that may be useful in the treatment of diabetes. The objective of this study was to investigate the fate of glucose in isolated muscles incubated with lipoic acid by determining its direct effects on specific metabolic and signaling pathways. Soleus muscles from healthy rats were incubated with lipoic acid in the absence or presence of insulin. Glucose transport, glycogen synthesis, glucose oxidation and lipid synthesis were determined and affects on major pathways associated with insulin signaling were evaluated. Glucose transport was not significantly altered by the addition of lipoic acid to the incubation medium. However, lipoic acid decreased glycogen synthesis in comparison to controls. Glucose oxidation was moderately increased while de-novo lipid synthesis from glucose was inhibited. Wortmannin repressed insulin stimulation of glucose incorporation into glycogen, an effect that was augmented by the combined treatment of wortmannin and lipoic acid. Basal and insulin-stimulated serine phosphorylation of Akt was not changed by the addition of lipoic acid to the incubation medium. These data show that in this in vitro model, lipoic acid did not significantly affect glucose uptake but dramatically modified pathways of glucose metabolism within muscle tissue.

• Journal of Microbiology and Biotechnology
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• v.32 no.9
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• pp.1168-1177
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• 2022

Parkinson's disease (PD) is the second-most prevalent neurodegenerative disease and is characterized by dopaminergic neuronal death in the midbrain. Recently, the association between alterations in PD pathology and the gut microbiota has been explored. Microbiota-targeted interventions have been suggested as a novel therapeutic approach for PD. Agathobaculum butyriciproducens SR79^T (SR79) is an anaerobic bacterium. Previously, we showed that SR79 treatment induced cognitive improvement and reduced Alzheimer's disease pathologies in a mouse model. In this study, we hypothesized that SR79 treatment may have beneficial effects on PD pathology. To investigate the therapeutic effects of SR79 on PD, 6-hydroxydopamine (6-OHDA)-induced mouse models were used. D-Amphetamine sulfate (d-AMPH)-induced behavioral rotations and dopaminergic cell death were analyzed in unilateral 6-OHDA-lesioned mice. Treatment with SR79 significantly decreased ipsilateral rotations induced by d-AMPH. Moreover, SR79 treatment markedly activated the AKT/GSK3β signaling pathway in the striatum. In addition, SR79 treatment affected the Nrf2/ARE signaling pathway and its downstream target genes in the striatum of 6-OHDA-lesioned mice. Our findings suggest a protective role of SR79 in 6-OHDA-induced toxicity by regulating the AKT/Nrf2/ARE signaling pathway and astrocyte activation. Thus, SR79 may be a potential microbe-based intervention and therapeutic strategy for PD.

• BMB Reports
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• v.56 no.10
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• pp.545-550
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• 2023

Osteoporosis is a major public health concern, which requires novel therapeutic strategies to prevent or mitigate bone loss. Natural compounds have attracted attention as potential therapeutic agents due to their safety and efficacy. In this study, we investigated the regulatory activities of boeravinone B (BOB), a natural rotenoid isolated from the medicinal plant Boerhavia diffusa, on the differentiation of osteoclasts and mesenchymal stem cells (MSCs), the two main cell components responsible for bone remodeling. We found that BOB inhibited osteoclast differentiation and function, as determined by TRAP staining and pit formation assay, with no significant cytotoxicity. Furthermore, our results showing that BOB ameliorates ovariectomy-induced bone loss demonstrated that BOB is also effective in vivo. BOB exerted its inhibitory effects on osteoclastogenesis by downregulating the RANKL/RANK signaling pathways, including NF-κB, MAPK, and PI3K/Akt, resulting in the suppression of osteoclast-specific gene expression. Further experiments revealed that, at least phenomenologically, BOB promotes osteoblast differentiation of bone marrow-derived MSCs but inhibits their differentiation into adipocytes. In conclusion, our study demonstrates that BOB inhibits osteoclastogenesis and promotes osteoblastogenesis in vitro by regulating various signaling pathways. These findings suggest that BOB has potential value as a novel therapeutic agent for the prevention and treatment of osteoporosis.

• Biomolecules & Therapeutics
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• v.23 no.2
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• pp.149-155
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• 2015

Our previous study demonstrated that yuzu has an anti-platelet effect in rat blood. In the present study, we examined whether the anti-platelet effect of yuzu can be extended to human blood by investigating its ability to inhibit aggregations induced by various agonists in human platelet rich plasma (PRP). This study also investigated the underlying mechanism of yuzu focusing on ADP granule secretion, $TXB_2$ formations, and $PLC{\gamma}$/Akt signaling. The results from this study showed that ethanolic yuzu extract (YE), and its components, hesperidin and naringin, inhibited human platelet aggregation in a concentration-dependent manner. YE, hesperidin and naringin also inhibited $TXB_2$ formation and ADP release. The phosphorylation of $PLC{\gamma}$ and Akt was significantly inhibited by YE, heperidin and naringin. Furthermore, we demonstrated that YE, heperidin and naringin has anti-platelet effects in rat ex vivo studies, and lower side effects in mice tail bleeding time studies. The results from this study suggest that YE, hesperidin and naringin can inhibit human platelet aggregation, at least partly through the inhibition of $PLC{\gamma}$ and Akt, leading to a decrease in $TXB_2$ formation and granule secretion.

• Biomedical Science Letters
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• v.24 no.1
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• pp.15-22
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• 2018

Pristimerin is a triterpene compound isolated from plant extracts that reportedly possesses antitumor, antioxidant, and anti-inflammatory activities. The current study was designed to evaluate the antitumor effects of pristimerin on human colon cancer cells. Treatment of the human colon cancer cells, HCT116 and SW480, with pristimerin led to a dose-dependent decrease in cell proliferation. Flow cytometry experiments showed that pristimerin increased cell apoptotic rate and decreased the mitochondrial membrane potential in HCT116 and SW480 cells. Western blot assay showed that pristimerin induced increased cleavage of caspase-3, -7, -8, and poly ADP ribose polymerase. Treatment with pristimerin also caused a marked decrease in the expression of Bcl-2 and Bcl-xL. Additionally, the levels of phosphorylated AKT and forkhead box O3a (FOXO3a) were decreased in pristimerin-treated colon cancer cells. Taken together, our study illustrated that pristimerin promoted apoptosis via the AKT/FOXO3a signaling pathway in colon cancer cells, elucidating that it might be considered as a potential agent for colon cancer therapy.

• Molecules and Cells
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• v.28 no.6
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• pp.583-588
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• 2009

The peroxiredoxin family of peroxidase has six mammalian members (Prx 1-6). Considering their frequent up-regulation in cancer cells, Prxs may contribute to cancer cells' survival in face of oxidative stress. Here, we show that Prx 6 promotes the invasiveness of lung cancer cells, accompanied by an increase in the activity of phosphoinositide 3-kinase (PI3K), the phosphorylation of p38 kinase and Akt, and the protein levels of uPA. Functional studies reveal that these components support Prx 6-induced invasion in the sequence p38 kinase/PI3K, Akt, and uPA. The findings provide a new understanding of the action of Prx 6 in cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.221-225
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• 2015

As metformin can inhibit endometrial carcinoma (EC) cell growth and the insulin growth factor (IGF) system is active in EC, the question of whether it can regulate endometrial carcinoma cell secretion of IGF-1 or expression of IGF-1 receptor (IGF-1R) is of interest. In this study, serum IGF-1 levels in EC patients were found to be comparable with that in the non EC patients (p>0.05). However, the IGF-1 level in the medium of cultured cells after treatment with metformin was decreased (p<0.05). IGF-1R was highly expressed in human endometrial carcinoma paraffin sections, but IGF-1R and phosphor-protein kinase B/protein kinase B (p-Akt/Akt) expression was down-regulated after metformin treatment (p<0.05). In summary, metformin can reduce the secretion of IGF-1 by Ishikawa and JEC EC cell lines and their expression of IGF-1R to deactivate downstream signaling involving the PI-3K/Akt pathway to inhibit endometrial carcinoma cell growth.

• Korean Journal of Veterinary Research
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• v.45 no.4
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• pp.537-544
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• 2005

We have examined distribution and expression of caveolin-3 (cav-3), one of three caveolin isoforms from 16-wks-old spontaneously hypertensive rats (SHR) compared with age-matched control wistar-kyoto (WKY) rats. The expression of cav-3 was increased, whereas expression of PKB/Akt and calcineurin (Cn) was not changed in cardiac tissues of SHR compared to WKY rats. Interestingly, expression of cav-3, PKB/Akt and Cn were decreased in plasma membrane fraction in SHR compared to WKY rats. In H9c2 cardiomyoblast cells treated with phenylephrine ($50{\mu}M$, 48hr) or isoproterenol ($10{\mu}M$, 48hr), the expression of cav-3 was markedly enhanced compared to nontreated cells. Upon immunofluorescence analysis, cav-3 was localized in plasma membrane of control H9c2 cells. However phenylephrine or isoproterenol treatment caused translocation of cav-3 to perinuclear region. These results suggest that cav-3 plays as positive regulators in the development of hypertrophy in cardiac tissues of SHR rats.