Sodium butyrate has context-dependent actions on dipeptidyl peptidase-4 and other metabolic parameters

Sodium butyrate (SB) has various metabolic actions. However, its effect on dipeptidyl peptidase 4 (DPP-4) needs to be studied further. We aimed to evaluate the metabolic actions of SB, considering its physiologically relevant concentration. We evaluated the effect of SB on regulation of DPP-4 and its other metabolic actions, both in vitro (HepG2 cells and mouse mesangial cells) and in vivo (high fat diet [HFD]-induced obese mice). Ten-week HFD-induced obese C57BL/6J mice were subjected to SB treatment by adding SB to HFD which was maintained for an additional 16 weeks. In HepG2 cells, SB suppressed DPP-4 activity and expression at sub-molar concentrations, whereas it increased DPP-4 activity at a concentration of 1,000 µM. In HFD-induced obese mice, SB decreased blood glucose, serum levels of insulin and IL-1β, and DPP-4 activity, and suppressed the increase in body weight. On the contrary, various tissues including liver, kidney, and peripheral blood cells showed variable responses of DPP-4 to SB. Especially in the kidney, although DPP-4 activity was decreased by SB in HFD-induced obese mice, it caused an increase in mRNA expression of TNF-α, IL-6, and IL-1β. The pro-inflammatory actions of SB in the kidney of HFD-induced obese mice were recapitulated by cultured mesangial cell experiments, in which SB stimulated the secretion of several cytokines from cells. Our results showed that SB has differential actions according to its treatment dose and the type of cells and tissues. Thus, further studies are required to evaluate its therapeutic relevance in metabolic diseases including diabetes and obesity.

Chemical Constituents from Leaves of Pileostegia viburnoides Hook.f.et Thoms

Phytochemical investigation on the leaves of Pileostegia viburnoides Hook.f.et Thoms led to the isolation of twenty-five compounds, and their structures were identified as n-dotriacontane (1), taraxeryl acetate (2), friedelin (3), epifriedelinol (4), canophyllal (5), stigmast-4-en-3-one (6), stigmasterol (7), (24R)-5A-stigmastane-3,6-dione (8), ursolic acid (9), pomolic acid (10), umbelliferone (11), 4-epifriedelin (12), n-octatriacontanol (13), β-amyrin (14), α-amyrin (15), taraxerol (16), nonadecanol (17), friedelane (18), arachic acid (19), protocatechuic acid (20), n-pentatriacontanol (21), hexadecanoic acid (22), vincosamide (23), daucosterol (24), and skimming (25), respectively. To our best knowledge, compounds 1, 2, 12, 13, 17 - 19 and 21-23 were new within Saxifragaceae family. Compounds 15, 16, and 20 were produced from this genus for the first time. Compounds 4, 14 and 25 were first obtained from species P. viburnoides and compounds 3, 5 - 11, and 24 were achieved from the leaves of P. viburnoides for the first time. Furthermore, the anti-neuroinflammatory activity of these isolates was evaluated.

Effects of Gastrodiae rhizoma on proliferation and differentiation of human embryonic neural stem cells

Objective: To investigate the effects of Gastrodiae rhizoma, a dried root of Gastrodia elata Blume, on proliferation and differentiation of human NSCs derived from embryonic stem cells. Methods: A 70% ethanol extract of Gastrodiae rhizoma (EEGR) was estimated with 4-hydroxybenzyl alcohol as a representative constituent by HPLC. Results: MTT assay showed that the treatment with EEGR increased the viability of NSCs in growth media. Compared to control, EEGR increased the number of dendrites and denritic spines extended from a differentiated NSC. Whereas EEGR decreased the mRNA expression of Nestin, it increased that of Tuj1 and MAP2 in NSCs grown in differentiation media. Immunocytochemical analysis using confocal microscopy also revealed the increased expression of MAP2 in dendrites of EEGR-treated NSCs. Furthermore, EEGR decreased mRNA expression of Sox2 in NSCs grown even in growth media. Conclusions: In conclusion, our study demonstrates for the first time that EEGR induced proliferation and neuronal differentiation of NSCs, suggesting its potential benefits on NSC-based therapies and neuroregeneration in various neurodegenerative diseases and brain injuries.

Effects of Gastrodiae rhizoma on proliferation and differentiation of human embryonic neural stem cells

OBJECTIVE@#To investigate the effects of Gastrodiae rhizoma, a dried root of Gastrodia elata Blume, on proliferation and differentiation of human NSCs derived from embryonic stem cells.@*METHODS@#A 70% ethanol extract of Gastrodiae rhizoma (EEGR) was estimated with 4-hydroxybenzyl alcohol as a representative constituent by HPLC.@*RESULTS@#MTT assay showed that the treatment with EEGR increased the viability of NSCs in growth media. Compared to control, EEGR increased the number of dendrites and denritic spines extended from a differentiated NSC. Whereas EEGR decreased the mRNA expression of Nestin, it increased that of Tuj1 and MAP2 in NSCs grown in differentiation media. Immunocytochemical analysis using confocal microscopy also revealed the increased expression of MAP2 in dendrites of EEGR-treated NSCs. Furthermore, EEGR decreased mRNA expression of Sox2 in NSCs grown even in growth media.@*CONCLUSIONS@#In conclusion, our study demonstrates for the first time that EEGR induced proliferation and neuronal differentiation of NSCs, suggesting its potential benefits on NSC-based therapies and neuroregeneration in various neurodegenerative diseases and brain injuries.

Viridicatol from Marine-derived Fungal Strain Penicillium sp. SF-5295 Exerts Anti-inflammatory Effects through Inhibiting NF-kappaB Signaling Pathway on Lipopolysaccharide-induced RAW264.7 and BV2 Cells

Viridicatol (1) has previously been isolated from the extract of the marine-derived fungus Penicillium sp. SF-5295. In the course of further biological evaluation of this quinolone alkaloid, anti-inflammatory effect of 1 in RAW264.7 and BV2 cells stimulated with lipopolysaccharide (LPS) was observed. In this study, our data indicated that 1 suppressed the expression of well-known pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and consequently inhibited the production of iNOS-derived nitric oxide (NO) and COX-2-derived prostaglandin E2 (PGE2) in LPS stimulated RAW264.7 and BV2 cells. Compound 1 also reduced mRNA expression of pro-inflammatory cytokines such as interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). In the further evaluation of the mechanisms of these anti-inflammatory effects, 1 was shown to inhibit nuclear factor-kappa B (NF-kappaB) pathway in LPS-stimulated RAW264.7 and BV2 cells. Compound 1 blocked the phosphorylation and degradation of inhibitor kappa B (IkappaB)-alpha in the cytoplasm, and suppressed the translocation of NF-kappaB p65 and p50 heterodimer in nucleus. In addition, viridicatol (1) attenuated the DNA-binding activity of NF-kappaB in LPS-stimulated RAW264.7 and BV2 cells.

Sulfuretin protects against cytokine-induced beta-cell damage and prevents streptozotocin-induced diabetes

NF-kappaB activation has been implicated as a key signaling mechanism for pancreatic beta-cell damage. Sulfuretin is one of the main flavonoids produced by Rhus verniciflua, which is reported to inhibit the inflammatory response by suppressing the NF-kappaB pathway. Therefore, we isolated sulfuretin from Rhus verniciflua and evaluated if sulfuretin could inhibit cytokine- or streptozotocin-induced beta-cell damage. Rat insulinoma RINm5F cells and isolated rat islets were treated with IL-1beta and IFN-gamma to induce cytotoxicity. Incubation of cells and islets with sulfuretin resulted in a significant reduction of cytokine-induced NF-kappaB activation and its downstream events, iNOS expression, and nitric oxide production. The cytotoxic effects of cytokines were completely abolished when cells or islets were pretreated with sulfuretin. The protective effect of sulfuretin was further demonstrated by normal insulin secretion of cytokine-treated islets in response to glucose. Treatment of mice with streptozotocin resulted in hyperglycemia and hypoinsulinemia, which was further evidenced by immunohistochemical staining of islets. However, the diabetogenic effects of streptozotocin were completely prevented when mice were pretreated with sulfuretin. The anti-diabetogenic effects of sulfuretin were also mediated by suppression of NF-kappaB activation. Collectively, these results indicate that sulfuretin may have therapeutic value in preventing beta-cell damage.

In vitro and in vivo Antibacterial Activities of Cinnamomum cassia Extracts Against Helicobacter pylori / 한국실험동물학회지

Infection with Helicobacter pylori (H. pylori) is strongly associated with duodenal and gastric ulcers. Substantial epidemiological data has revealed that high rates of H. pylori infection might be related to high rates of gastric cancer and gastric adenocarcinoma. In this study, a medicinal herbal plant, Cinnamomum cassia, was examined and screened for anti-H. pylori activity. Seventy percent ethanol was used for herbal extraction. For anti-H. pylori activity screening, inhibitory zone tests as an in vitro assay and in vivo study using a Mongolian gerbil (Meriones unguiculatus) model were performed. Also, the safety of herbal compounds was evaluated by animal study. As a result of inhibitory zone test, Cinnamomum cassia extract demonstrated strong anti-H. pylori activities. Also, as results of in vivo animal studies, Cinnamomum cassia demonstrated strong therapeutic effects against H. pylori infection according to the criteria of histological examination and rapid urease test. As results of the safety study, after 28 days treatment of the Cinnamomum cassia extract, the animals were not detected any grossly and histological changes. These results demonstrate that it can be successfully cured against H. pylori infection and protected from H. pylori-induced pathology with Cinnamomum cassia. It could be a promising native herb treatment for patients with gastric complaints including gastric ulcer caused by H. pylori.

Antibacterial Activity of Sanguisorba officinalis against Helicobacter pylori / 한국실험동물학회지

In this study, a medicinal herbal plant, Sanguisorba officinalis, was examined and screened for anti-Helicobacter pylori (H. pylori) activity. Seventy percent ethanol was used for herbal extraction. For anti-H. pylori activity screening, inhibitory zone tests as an in vitro assay and in vivo study using a Mongolian gerbil (Meriones unguiculatus) model were performed. Also, the safety of herbal compounds was evaluated by animal study. As a result of inhibitory zone test, Sanguisorba officinalis extract demonstrated strong anti-H. pylori activities. Also, as results of in vivo animal studies, Sanguisorba officinalis extract demonstrated strong therapeutic effects against H. pylori infection according to the criteria of histological examination and rapid urease test. As results of the safety study, after 28 days treatment of the Sanguisorba officinalis extract, the animals were not detected any grossly and histological changes. These results demonstrate that it can be successfully cured against H. pylori infection and protected from H. pylori-induced pathology with Sanguisorba officinalis extract. It could be a promising candidate herb treatment for patients with gastric complaints including gastric ulcer caused by H. pylori.

Antibacterial Activity of Sanguisorba officinalis against Helicobacter pylori / 한국실험동물학회지

In this study, a medicinal herbal plant, Sanguisorba officinalis, was examined and screened for anti-Helicobacter pylori (H. pylori) activity. Seventy percent ethanol was used for herbal extraction. For anti-H. pylori activity screening, inhibitory zone tests as an in vitro assay and in vivo study using a Mongolian gerbil (Meriones unguiculatus) model were performed. Also, the safety of herbal compounds was evaluated by animal study. As a result of inhibitory zone test, Sanguisorba officinalis extract demonstrated strong anti-H. pylori activities. Also, as results of in vivo animal studies, Sanguisorba officinalis extract demonstrated strong therapeutic effects against H. pylori infection according to the criteria of histological examination and rapid urease test. As results of the safety study, after 28 days treatment of the Sanguisorba officinalis extract, the animals were not detected any grossly and histological changes. These results demonstrate that it can be successfully cured against H. pylori infection and protected from H. pylori-induced pathology with Sanguisorba officinalis extract. It could be a promising candidate herb treatment for patients with gastric complaints including gastric ulcer caused by H. pylori.

Roles of heme oxygenase-1 in curcumin-induced growth inhibition in rat smooth muscle cells

In vascular smooth muscle cells (VSMCs), induction of the heme oxygenase-1 (HO-1) confers vascular protection against cellular proliferation mainly via its up-regulation of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) that is involved in negative regulation of cellular proliferation. In the present study, we investigated whether the phytochemical curcumin and its metabolite tetrahydrocurcumin could induce HO-1 expression and growth inhibition in rat VSMCs and, if so, whether their antiproliferative effect could be mediated via HO-1 expression. At non-toxic concentrations, curcumin possessing two Michael-reaction acceptors induced HO-1 expression by activating antioxidant response element (ARE) through translocation of the nuclear transcription factor E2-related factor-2 (Nrf2) into the nucleus and also inhibited VSMC growth triggered by 5% FBS in a dose-dependent manner. In contrast, tetrahydrocurcumin lacking Michael-reaction acceptor showed no effect on HO-1 expression, ARE activation and VSMC growth inhibition. The antiproliferative effect of curcumin in VSMCs was accompanied by the increased expression of p21(WAF1/CIP1). Inhibition of VSMC growth and expression of p21(WAF1/CIP1) by curcumin were partially, but not completely, abolished when the cells were co- incubated with the HO inhibitor tin protoporphyrin. In human aortic smooth muscle cells (HASMCs), curcumin also inhibited growth triggered by TNF-alpha and increased p21(WAF1/CIP1) expression via HO-1-dependent manner. Our findings suggest that curcumin has an ability to induce HO-1 expression, presumably through Nrf2-dependent ARE activation, in rat VSMCs and HASMCs, and provide evidence that the antiproliferative effect of curcumin is considerably linked to its ability to induce HO-1 expression.

Comparative effects of curcuminoids on endothelial heme oxygenase-1 expression: ortho-methoxy groups are essential to enhance heme oxygenase activity and protection

Recently, it has been reported that curcumin, which is known as a potent antioxidant, acts as a non-stressful and non-cytotoxic inducer of the cytoprotective heme oxygenase (HO)-1. In this study, naturally occurring curcuminoids, such as pure curcumin, demethoxycurcumin (DMC) and bis-demethoxycurcumin (BDMC), were compared for their potential ability to modulate HO-1 expression and cytoprotective activity in human endothelial cells. All three curcuminoids could induce HO-1 expression and HO activity with differential levels. The rank order of HO activity was curcumin, DMC and BDMC. In comparison with endothelial protection against H2O2-induced cellular injury, cytoprotective capacity was found to be highest with curcumin, followed by DMC and BDMC. Interestingly, cytoprotective effects afforded by curcuminoids were considerably associated with their abilities to enhance HO activity. Considering that the main difference among the three curcuminoids is the number of methoxy groups (none for BDMC, one for DMC, and two for curcumin), the presence of methoxy groups in the ortho position on the aromatic ring was suggested to be essential to enhance HO-1 expression and cytoprotection in human endothelial cells. Our results may be useful in designing more efficacious HO-1 inducers which could be considered as promising pharmacological agents in the development of therapeutic approaches for the prevention or treatment of endothelial diseases caused by oxidative damages.

Effects of Cervi Parvum Cornu on Cell Cycle Regulation in Human Fetal Osteoblasts / 대한치주과학회지

Recently, many natural medicines, whose advantages are less side effects and possibility of long-term use, have been studied for their capacity, their anti-bacterial and anti-inflammatory effects and regenerative potential of periodontal tissues. Cervi Parvum Cornu(CPC) have been traditionally used as an hale, growth, hematogenous, anti-aging, back pain in Eastern medicine. The purpose of present study was to investigate the effects of CPC extract on cell cycle progression and its molecular mechanism in human fetal osteoblasts. CPC extracts (10 microgram/ml) increased cell proliferation in the human fetal osteoblasts as compared to non-supplemented control. There was no significant change in the G1 and S phase, but a increase in the G2/M phase in 10 microgram/ml and 100 microgram/ml of CPC extracts group as compared to non-supplemented control. The protein expression of cyclin E, cdk 2, cyclin D, cdk 4, and cdk 6 was higher than that of control group. The level of p21 was lower than that of control. But that of pRb and p16 was not distinguished from control. These results indicate that the increase of cell proliferation by CPC extracts may be due to the increased expression of cyclin E , cdk 2, cyclin D, cdk 4 and cdk 6, and the decreased expression of p21 in human fetal osteoblasts .

Effects of PCLS-2 in Regulation of Rabbit Corpus Cavernosum Smooth Muscle Tone / 대한비뇨기과학회지

PURPOSE: Relaxation of the penile cavernosum smooth muscle is a critical event in erection. Artemisia iwaymogi(AI) is a perennial herb growing in Korea. The aerial parts have been used in folk medicine. Bioassay-guided fractionation of an H2O extract of AI has furnished an inhibitory substance (PCLS-2). We investigated compound extracted in the rabbit corporal cavernosum smooth muscle. MATERIALS AND METHODS: Bioassay-guided fractionation of an H2O extract was used. A strip of rabbit corpus cavernosum was mounted in an organ chamber to measure the isometric tension. PCLS-2 compound induced relaxations were evaluated by in vitro study using muscarinic receptor blocker atropine (ATR), cyclo-oxygenase inhibitor indomethacin, nitric oxide synthase (NOS) ihibitor Nitro-L Arginine-Methyl Ester (NAME), guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin 1-one (ODQ), intrinsic neurotransmission inhibitor tetrodotoxin (TTX), or/and potassium channel blockers. RESULTS: PCLS-2 showed relaxation in a dose-dependent manner. Atropine, Indomethacin, NAME, ODQ, TTX, glibenclamide, tetraethylammonium, 4-aminopyridine, charybdotoxin, or apamin did not inhibit the relaxation induced by PCLS-2 compound. CONCLUSIONS: The present results suggest that the PCL-2 compound has effect of relaxation of corpus cavernosum smooth muscle and the relaxation was not involved muscarinic receptor, nitric oxide, prostaglandin, potassium channels and intrinsic neurotransmission. Other mechanisms may by involved in the PCLS-2 induced relaxation in the rabbit corpus cavernosum smooth muscle.

Effects of Sophorae Radix Extracts on the Expression of Cell Cycle Regulatory Proteins in Human Gingival Fibroblasts / 대한치주과학회지

Fibroblasts are major cellular components of gingiva and periodontal ligament. They regulate the healing process after surgery or injury. Recently, many natural medicines, whose advantages are less side effects and possibility of long-term use, have been studied for their capacity, their anti-bacterial and anti-inflammatory effects and regenerative potential of periodontal tissues. Sophorae radix have been traditionally used as an antibacterial and anti-inflammatory drug in oriental medicine. The purpose of present study was to investigate the effects of Sophorae radix extract on cell cycle progression and its molecular mechanism in human gingival fibroblasts. Sophorae radix extracts(100microgram/ml) notably increased cell proliferation and cell activity in the human gingival fibroblasts as compared to non-supplemented controls. There was an increase in the S phase and a decrease in the G1 phase in 100microgram/ml of Sophorae radix extracts group as compared to non-supplemented controls. The level of cyclin E and cdk 2 protein in test group was higher than that of control groups. But that of cyclin D, cdk 4, and cdk 6 was not distinguished from controls. The level of p53 protein in test group was lower than that of controls, whereas that of p21 was not different. The level of pRB protein in test group was higher than that of controls, whereas that of p16 was lower. These results indicate that the increase of cell proliferation by Sophorae radix extracts may be due to the increased expression of cyclin E and cdk 2, and the decreased expression of p53 and p16 in human gingival fibroblasts.

Effects of Tetrandrine on the Nitric Oxide Production by Vascular Smooth Muscle Cells of the Rat / 대한면역학회지

No abstract available.

Effects of the Isolated Extracts from Safflower Seeds on Mineralization of Periodontal Ligament Cells and Osteoblastic Cells / 대한치주과학회지

The aim of periodontal treatments is the complete restoration of the structure and function of damaged periodontal tissues. Although it is very difficult to attain this goal, recent advances in periodontal wound healing concepts encourage hope reaching it. Safflower seeds has been used for the treatment of blood stasis, bone fracture and osteoporosis in traditional Korean medicine. The purpose of this study is to examine effects of the isolated extracts from Safflower seeds on mineralization of periodontal ligament cells and osteoblastic cells. Periodontal ligament cells were primarily obtained from a extracted premolars with non-periodontal diseases. Osteoblastic cells were obtained from calvariae of a fetal rat. Cells were cultured with DMEM at 37degrees C with 5% CO2 in 100% humidity incubator. Safflower seeds were isolated into the H2O layer and the butanol layer. MTT assay and alkaline phosphatase(ALP) level were examined. Also the number of bone calcification nodules were evaluated. The obtained results were as follows: 1. The cellular activity of periodontal ligament cells was significantly increased in 10(-3)g/ml, 10(-6)g/ml of both H2O layer and butanol layer of Safflower seeds. 2. The cellular activity of osteoblastic cells was significantly increased in 10(-3)g/ml, 10(-6)g/ml of H2O layer of Safflower seeds. 3. ALP level of periodontal ligament cells was significantly increased in 10-3g/ml of both H2O layer and butanol layer of Safflower seeds. 4. ALP level of osteoblastic cells was significantly increased in 10(-3)g/ml, 10(-6)g/ml of H2O layer and especilly more increaton was showed in 10(-3)g/ml of H2O layer. 5. Calcification nodules of periodontal ligament cells slightly increased in 10(-3)g/ml of both H2O layer and butanol layer of Safflower seeds. 6. Calcification nodules of osteoblastic cells slightly increased in 10(-3)g/ml, 10(-6)g/ ml of H2O layer of Safflower seeds. These results indicate that H2O layer and butanol layer of the isolated extracts from Safflower seeds has excellent effects on mineralization of periodontal cells and osteoblastic cells.