Therapeutic Effects of Aloe saponaria against Ulcerative Colitis Induced by Dextran Sulfate Sodium.

Aloe vera (A. vera) has been studied as a treatment option for ulcerative colitis (UC), but there is a lack of scientific evidence showing whether treatment with Aloe saponaria (A. saponaria) can also be beneficial. To investigate the therapeutic potential of A. saponaria as a treatment for UC, clinical symptoms, histopathological characteristics of the colon, inflammatory response, and toxicity were analyzed in dextran sulfate sodium (DSS)-induced UC mice after administration of aqueous extracts of A. saponaria (AAS) for 7 days. The total polyphenol and tannin content of AAS was 272 µg/g and 163 µg/g, respectively. AAS exhibited significant antioxidant activity. Several clinical symptoms, including body weight, colon length, and hematochezia, remarkably improved in the DSS+AAS treated group compared to the DSS+Vehicle-treated group. In addition, similar improvements were detected in the histopathological characteristics and mucin-secreting ability in the colon of DSS-induced UC mice after the administration of AAS. The levels of infiltrated inflammatory cells and cytokine expression were significantly decreased in a dose-dependent manner in the colon of the DSS+AAS-treated group. These alterations in inflammatory response were accompanied by a significant recovery of the protein kinase C/extracellular signal-regulated kinase (PKC/ERK) and phosphatidylinositol-3-kinase/serine-threonine protein kinase (PI3K/Akt) signaling pathways. However, the levels of key markers for hepatotoxicity and nephrotoxicity consistently remained between those of the DSS+AAS-treated and the No groups. Therefore, the results of the present study provide novel evidence that AAS may improve the clinical symptoms and attenuate the inflammatory response in DSS-induced UC mice and does not have any significant hepatotoxicity or nephrotoxicity.

Inhibition of Migration and Invasion in Melanoma Cells by ß-Escin via the ERK/NF-κB Signaling Pathway.

ß-Escin, a natural triterpene saponin was extracted from Aesculus hippocastanum seeds, which have been widely used to treat inflammation in traditional medicine. In an effort to study the possible anti-tumor effects of ß-escin, we performed wound healing, invasion, and adhesion assays to examine the effects of ß-escin on cell migration, invasion, and angiogenesis. Our results revealed that ß-escin inhibits cell migration as well as motility in B16F10 and SK-MEL5 cells in a dose-dependent manner. RT-PCR and Western blot analysis showed that ß-escin increased TIMP-1, -2 while significantly downregulated phosphorylated extracellular signal-regulated kinase (p-ERK) expression, and suppressing nuclear factor-kappa B (NF-κB) and inhibitor of nuclear factor-kappa B (IκB) expression. Overall, the data from the current study suggest that ß-escin has the potential for inhibiting both metastatic and angiogenic activities, and are the earliest evidence for the involvement of the NF-κB/IκB signaling in ß-escin-induced anti-tumor effects.

Gastroprotective efficacy and safety evaluation of scoparone derivatives on experimentally induced gastric lesions in rodents.

This study investigated the gastroprotective efficacy of synthesized scoparone derivatives on experimentally induced gastritis and their toxicological safety. Six scoparone derivatives were synthesized and screened for gastroprotective activities against HCl/ethanol- and indomethacin-induced gastric ulcers in rats. Among these compounds, 5,6,7-trimethoxycoumarin and 6,7,8-trimethoxycoumarin were found to have gastroprotective activity greater than the standard drug rebamipide; 6-methoxy-7,8-methylenedioxycoumarin, 6-methoxy-7,8-(1-methoxy)-methylenedioxycoumarin, 6,7-methylenedioxycoumarin, and 6,7-(1-methoxy)-methylenedioxycoumarin were found to be equipotent or less potent that of rebamipide. Pharmacological studies suggest that the presence of a methoxy group at position C-5 or C-8 of the scoparone's phenyl ring significantly improves gastroprotective activity, whereas the presence of a dioxolane ring at C-6, C-7, or C-8 was found to have decreased activity. In order to assess toxicological safety, two of the potent gastroprotective scoparone derivatives-5,6,7-trimethoxycoumarin and 6,7,8-trimethoxycoumarin-were examined for their acute toxicity in mice as well as their effect on cytochrome P450 (CYP) enzyme activity. These two compounds showed low acute oral toxicity in adult male and female mice, and caused minimal changes to CYP3A4 and CYP2C9 enzyme activity. These results indicate that compared to other scoparone derivatives, 5,6,7-trimethoxycoumarin and 6,7,8-trimethoxycoumarin can improve gastroprotective effects, and they have low toxicity and minimal effects on drug-metabolizing enzymes.

Monitoring of possible horizontal gene transfer from transgenic potatoes to soil microorganisms in the potato fields and the emergence of variants in Phytophthora infestans.

To examine the possibility of horizontal gene transfer between transgenic potatoes and microorganisms in potato fields, the gene flow from transgenic potatoes containing nucleoside diphosphate kinase 2 (NDPK2) gene to microorganisms in soils was investigated. The soil samples collected from the potato fields from March to October in 2007 were examined by PCR, Southern hybridization, and AFLP fingerprinting. The NDPK2 gene from soil genomic DNAs was not detected by both PCR and Southern hybridization, indicating that gene-transfer did not occur in the potato fields. In addition, no discrepancy was found in pathogenicity and noticeable changes for the appearance of variants of Phytophthora infestans in each generation when serial inoculations and the analysis of genomic DNAs by AFLP was conducted. Thus, these data suggest that transgenic potatoes do not give significant impacts on the communities of soil microorganisms and the emergence of variants although continued research efforts may be necessary to make a decisive conclusion.

Antiplatelet activities of newly synthesized derivatives of piperlongumine.

Piperlongumine, a pyridone alkaloid isolated from Piper longum L., exhibited a potential inhibitory effect on washed rabbit platelet aggregation induced by collagen, arachidonic acid (AA) and platelet activating factor (PAF), without any inhibitory effect on that induced by thrombin. Piperlongumine was used as a lead compound for the synthesis of new antiplatelet agents. Seven synthetic compounds were newly synthesized from 3,4,5-trimethoxycinnamic acid (TMCA). They were 1-piperidin-1-yl-3-(3,4,5-trimethoxy-phenyl)prop-2-en-1-one (1'), 1-morpholin-4-yl-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (2'), 1-(3,5-dimethylpiperidin-1-yl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (3'), 1-(2-methylpiperidin-1-yl)-3-(3,4,5-tri-methoxyphenyl)prop-2-en-1-one (4'), 1-(3-hydroxypiperidin-1-yl)-3-(3,4,5-trimethoxyphenyl)- prop-2-en-1-one (5'), 1-[3-(3,4,5-tri-methoxyphenyl) acryloyl]-piperidin-2-one (6') and ethyl 1-[3-(3,4,5-trimethoxyphenyl)-acryloyl]piperidine-4-carboxylate (7'). Among those seven synthetic derivatives, 1-(3,5-dimethylpiperidin-1-yl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (3') had the most inhibitory effect on platelet aggregation induced by collagen, AA and PAF.

A fraction of methylene chloride from Geum japonicum Thunberg inhibits tumor metastatic and angiogenic potential.

The plant Geum japonicum Thunberg (GjT) has been used as a diuretic in traditional medicine. Herein, we report that the GjT extract blocks both the spread of human umbilical vein endothelial cells (HUVECs) on matrigel and the migration of B16 cells. We used various assays to test for cell attachment, spreading, wound healing and angiogenesis. A reverse transcription-polymerase chain reaction (RT-PCR) and a mitogen-activated protein kinase (MAPK) assay were also carried out for the mechanistic study of GjT. Our results showed that a fraction of methylene chloride fraction from GjT inhibited B16 cells during cell attachment and migration and suppressed tube formation in a dose-dependent manner. An RT-PCR analysis showed that the methylene chloride extract decreased the mRNA expression of CD44 and TIMP-2. A Western blot analysis of the phosphorylation of MAPK kinases (ERK, JNK and p38) showed that the GjT fraction increased the expression of phospho-JNK, suggesting that GjT has the potential to alleviate metastatic and angiogenic activity, via a phospho-JNK signaling pathway.

Anti-tumor activity of Gastrodia elata Blume is closely associated with a GTP-Ras-dependent pathway.

Gastrodia elata Blume (GEB) is an important medicinal plant in Korea. In order to confirm the anti-tumor activities of GEB extracts, we carried out various in vitro anti-tumor assays, including a wound assay and an invasion assay using an ethyl ether extract of GEB. The results showed that the GEB extract exhibits potent anti-tumor activity in vitro in a dose-dependent manner. The expression of CD44, cdc42, Timp-2 or RhoA mRNA did not change by GEB treatment, compared to that of the control. GTP-Ras, an active form of a G-coupled protein family, however, is associated with the anti-tumor activity of GEB extracts. We examined various molecular markers related to metastasis by reverse transcriptase-polymerase chain reaction with the extract of GEB-treated B16 cells. There was an increase in GTP-Ras expression by the Gastrodia elata Blume extract. Together, these results suggest that the Gastrodia elata Blume extract could have potential in alleviating tumorigenesis, by a GTP-Ras-dependent pathway; although the precise molecular mechanisms are still being examined.

Inhibitory effect on proliferation of vascular smooth muscle cells and protective effect on CCl(4)-induced hepatic damage of HEAI extract.

The effects of methanol extract from Hericium erinaceus cultivated with Artemisia iwayomogi (HEAI) on proliferation of vascular smooth muscle cells and CCl(4)-induced hepatic damage were evaluated. HEAI was shown to have a potent inhibitory effect on the proliferation of vascular smooth muscle cells (VSMCs). Interestingly, a methanol extract of Hericium erinaceus showed no inhibitory effect on the proliferation of VSMCs, while a methanol extract of Artemisia iwayomogi possessed strong inhibitory effects on the proliferation of VSMCs. Therefore, the inhibitory effects of HEAI may be caused by the changes of chemical components in the culture broth after the addition of Artemisia iwayomogi in the HEAI growth media. HEAI also had a strong protective effect on CCl(4)-induced hepatic damage in rats. The activity was evaluated using biochemical parameters such as glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and alkaline phosphatase (ALP). HEAI treatment caused a significant reduction in the activity of GOT but not of GPT and ALP in comparison with CCl(4) treatment alone. Histopathological studies showed that liver samples treated with HEAI were significantly different when compared to non-treated animals after CCl(4) exposure.

Monoterpenes from thyme (Thymus vulgaris) as potential mosquito repellents.

Five monoterpenes (carvacrol, p-cymene, linalool, alpha-terpinene, and thymol) derived from the essential oil of thyme (Thymus vulgaris) were examined for their repellency against the mosquito Culex pipiens pallens. All 5 monoterpenes effectively repelled mosquitoes based on a human forearm bioassay. Alpha-terpinene and carvacrol showed significantly greater repellency than a commercial formulation, N,N-diethyl-m-methylbenzamide (deet), whereas thymol showed similar repellency to that of deet. The duration of repellency after application for all these monoterpenes was equal to or higher than that of deet. These findings indicate that a spray-type solution containing 2% alpha-terpinene may serve as an alternative mosquito repellent.

Repellent activities of essential oils and monoterpenes against Culex pipiens pallens.

Essential oils of Eulcalyptus globulus, Lavender officinalis, Rosemarinus officinalis, and Thymus vulgaris were examined for their repellent activities against Culex pipiens pallens. All 4 essential oils effectively repelled adult mosquitoes on hairless mice. Essential oil of T. vulgaris (thyme) had potent repellent activity within the tested materials, with a protection rate of 91% at a concentration of 0.05% topical treatment. Thyme essential oil significantly extended the duration of protection until 3 bites by mosquitoes. With gas chromatography-mass spectrometry analysis, thyme essential oil was a rich source of 5 monoterpenes, including in descending order thymol, p-cymene, carvacrol, linalool, and alpha-terpinene. These 5 monoterpenes also were assessed to determine their repellent activities to the mosquitoes. alpha-Terpinene had a potent repellent activity with a protection rate of 97% at a concentration of 0.05% topical treatment. Additionally, carvacrol and thymol showed an equivalent level of repellency. A spray-type solution containing 2% alpha-terpinene was tested for its repellent activity against Cx. pipiens. This solution showed stronger repellent activity than the currently used repellent N,N-diethyl-m-methylbenzamide (deet).