A randomized, double-blind, placebo-controlled crossover clinical trial to evaluate the anti-diabetic effects of Allium hookeri extract in the subjects with prediabetes.

BACKGROUND: Allium hookeri is widely consumed as a vegetable and herbal medicine in Asia. A. hookeri has been reported anti-inflammatory, anti-obesity, osteoblastic, anti-oxidant, and anti-diabetic effects in animal studies. We investigated the anti-diabetic effects of A. hookeri aqueous extract (AHE) in the Korean subjects. METHODS: Prediabetic subjects (100 ≤ fasting plasma glucose (FPG) < 126 mg/dL) who met the inclusion criteria were recruited for this study. The enrolled subjects (n = 30) were randomly divided into either an AHE (n = 15, 486 mg/day) or placebo (n = 15) group. Outcomes were measurements of FPG, glycemic response to an oral glucose tolerance test (OGTT), insulin, C-peptide, hemoglobin A1c (HbA1c), total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol. The t-test was used to assess differences between the groups. A p-value < 0.05 was considered statistically significant. RESULTS: Eight weeks after AHE supplementation, HbA1c level was significantly decreased in the AHE group compared with the placebo group. No clinically significant changes in any safety parameter were observed. CONCLUSION: The findings suggest that AHE can be effective in reducing HbA1c, indicating it as an adjunctive tool for improving glycemic control. TRIAL REGISTRATION: The study protocol was retrospectively registered at www.clinicaltrials.gov ( NCT03330366 , October 30, 2017).

Allium hookeri root protects oxidative stress-induced inflammatory responses and ß-cell damage in pancreas of streptozotocin-induced diabetic rats.

BACKGROUND: Water extract from the root of Allium hookeri (AH) shows anti-inflammatory, antioxidant, and free radical scavenging effects. In this study, the ameliorating effects of AH on oxidative stress-induced inflammatory response and ß-cell damage in the pancreas of streptozotocin (STZ)-induced type 1 diabetic rats were investigated. METHODS: AH (100 mg/kg body weight/day) was orally administered every day for 2 weeks to STZ-induced diabetic rats. After the final administration of AH, biochemical parameters including glucose, insulin, reactive oxygen species levels, and protein expressions related to antioxidant defense system in the pancreas of STZ-induced diabetic rats. RESULTS: The diabetic rats showed loss of body weight and increased pancreatic weight, while the oral administration of AH attenuated body and pancreatic weight changes. Moreover, the administration of AH caused a slightly decrease in the serum glucose level and a significant increase in the serum and pancreatic insulin levels in the diabetic rats. AH also significantly reduced the enhanced levels of reactive oxygen species, oxidative stress biomarker, in the serum and pancreas. The diabetic rats exhibited a down-regulation of the protein expression related to antioxidant defense system in the pancreas, but AH administration significantly up-regulated the expression of the heme oxygenase-1 (HO-1). Furthermore, AH treatment was reduced the overexpression of nuclear factor-kappa B (NF-кB)p65 and NF-кBp65-induced inflammatory cytokines such as tumor necrosis factor-α and interleukin-6. In addition, AH treatment was less pancreatic ß-cell damaged compared with those of the diabetic rats. CONCLUSION: These results provide important evidence that AH has a HO-1 activity on the oxidative stress conditions showing pancreato-protective effects against the development of inflammation in the diabetic rats. This study provides scientific evidence that AH protects the inflammatory responses by modulated NF-кBp65 signaling pathway through activation of HO-1 in the pancreas of STZ-induced diabetic rats.

Changes in volatile flavor compounds in steam-dried Allium hookeri root.

This study was carried out to identify volatile flavor compounds in Allium hookeri root (AHR) and steam-dried AHR. The volatile compounds were extracted using a simultaneous steam distillation and extraction (SDE) method and identified by gas chromatography/mass spectrometry (GC/MS) analysis. Forty volatile compounds, present at a concentration of 76.10 mg/kg, were identified in AHR, with sulfur-containing compounds (96.8%) as the major volatile compounds. On the other hand, in two and four times steam-dried AHR, 34 volatile compounds present at 5.96 mg/kg and 28 compounds present at 4.23mg/kg were identified, respectively. This two and four times steam-dried AHR respectively contained sulfur-containing compounds (64.1 and 37.4%) and aldehydes (19.3 and 45.4%) as the dominant compounds. The sulfur-containing compounds decreased, whereas the aldehydes increased relative to levels in AHR with increased steam-drying time. This is the first report on volatile flavor compounds in AHR and steam-dried AHR.

Inhibitory activities of anthraquinones from Rubia akane on phosphatase regenerating liver-3.

The methanolic extract of the roots of Rubia akane (Rubiaceae) was found to show inhibitory activity on phosphatase of regenerating liver-3 (PRL-3). Bioassay-guided fractionation of the methanolic extract resulted in the isolation of two anthraquinone compounds, 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone-3-O-(6'-O-acetyl)-α-rhamnosyl(1→2)-ß-glucoside and 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone, as inhibitors on PRL-3. These compounds inhibited PRL-3 in a dose-dependent manner with IC50 values of 5.2 and 1.3 µg/mL, respectively.

Therapeutic effects of Baicalein on atopic dermatitis-like skin lesions of NC/Nga mice induced by dermatophagoides pteronyssinus.

The present study was conducted to investigate the effects of Baicalein (BE), which is hydrolyzed product of Baicalin (BA), on atopic dermatitis (AD). AD was induced in NC/Nga mice by DPE treatment. BE hydrogels treatment reduced the levels of skin severity scores. BE hydrogels treatment also decreased inflammatory cytokines such as TNF-alpha, IL-6, and its level in the serum. BE hydrogels treatment elevated IFN-gamma level in the spleenocyte culture supernatant. Cell numbers in the skin positive to CD3+/CD69+, CCR3+, CD11b+/Gr-1+, B220+/IgE+ all of which were up-regulated in AD-induced mice were decreased and returned to normal levels. Histological examination showed that infiltration levels of immune cells in the skin of AD-induced NC/Nga mice were much improved by BE hydrogels treatment. These results thus suggest that BE can regulate molecular mediators and immune cells that are functionally associated with atopic dermatitis induced in NC/Nga mice, and may play an important role in recovering AD symptoms.

Effects of isolated compounds from Catalpa ovata on the T cell-mediated immune responses and proliferation of leukemic cells.

Three compounds were isolated from the ethyl acetate soluble fraction of the methanolic extract of the leaves of Catalpa ovata (Bignoniaceae) through repeated column chromatography. We investigated the effects of these compounds on T cell-mediated responses for tumor surveillance and proliferation in U937, HL60, and Molt-4 leukemia cells. Compounds 1-3 inhibited proliferation of those cells in a dose-dependent manner. Compound 3 showed mild effect in Molt-4 cell cytotoxicity. Compound 3 enhanced gene expressions of p53 and IL-4, but decreased IL-2 and IFN-Gamma genes in Molt-4 cell. Our findings indicate that compound 3 may enhance T cell-mediated immune responses and anticancer properties.

Cytotoxic germacranolide sesquiterpenes from the bark of Magnolia kobus.

A new (3) and three known germacrane-type sesquiterpenoids were isolated from the chloroform-soluble fraction of the methanolic extract of the bark of Magnolia kobus (Magnoliaceae) through repeated silica gel and Sephadex LH-20 column chromatography. Their chemical structures were elucidated as costunolide (1), parthenolide (2), isobisparthenolidine (3), and bisparthenolidine (4) by spectroscopic analysis. Compounds 1-4 exhibited cytotoxicity against human A549, SK-OV-3, SK-MEL-2, and HCT15 tumor cells.

Farnesyl protein transferase inhibitory components of Polygonum multiflorum.

The methanolic extract of the roots of Polygonum multiflorum (Polygonaceae) was found to show inhibitory activity towards farnesyl protein transferase (FPTase). Bioassay-guided fractionation of the methanolic extract resulted in the isolation of two anthraquinone glycosides, as inhibitors of FPTase. These compounds inhibited the FPTase activity in a dose-dependent manner.

The effects of ketorolac tromethamine and baicalein on the levels of inflammatory factors in human synoviocytes.

This study examined the effects of ketorolac tromethamine (KT) and baicalein (BE) on the levels of inflammatory factors in human synoviocytes. The fibroblast-like synoviocytes (FLS) cells were used to determine the possible regulatory effects of KT and BE (KTBE) on the levels of inflammatory factors in FLS cells. In addition, the levels of TNF-alpha, IL-6, and IL-1beta mRNA expression in FLS cells induced by a TNF-alpha and IL-1beta co-treatment were largely inhibited by a KTBE treatment. The level of FLS cells proliferation was increased by IL-1beta and TNF-alpha, and strongly inhibited by KTBE treatment. The production of oxygen species (ROS) was inhibited by KTBE in FLS cells. KTBE appears to regulate the levels of mRNA that are important for regulating RA progression.

Cytotoxic components from the dried rhizomes of Zingiber officinale Roscoe.

Five compounds were isolated from the chloroform-soluble fraction of the methanolic extract of the dried rhizomes of Zingiber officinale (Zingiberaceae) through repeated column chromatography. Their chemical structures were elucidated as 4-, 6-, 8-, and 10-gingerols, and 6-shogaol using spectroscopic analysis. Among the five isolated compounds, 6-shogaol exhibited the most potent cytotoxicity against human A549, SK-OV-3, SK-MEL-2, and HCT15 tumor cells. 6-shogaol inhibited proliferation of the transgenic mouse ovarian cancer cell lines, C1 (genotype: p53(-/-), c-myc, K-ras) and C2 (genotype: p53(-/-), c-myc, Akt), with ED(50) values of 0.58 microM (C1) and 10.7 microM (C2).

Prostaglandin E2-mediated dysregulation of proinflammatory cytokine production in pristane-induced lupus mice.

Systemic lupus erythematosus (SLE) is characterized by inflammatory and dysregulatory immune responses including overactive B cells, overproduction of proinflammatory cytokines, and T cell hyperactivity. PGE(2) modulates a variety of immune processes at sites of inflammation, including production of inflammatory cytokines. However, the role of PGE(2) in dysregulatory inflammatory and immune responses in lupus remains unclear. We investigated whether PGE(2) mediates production of inflammatory cytokines in pristane-induced lupus BALB/c mice. Our results showed that levels of serum and BAL PGE(2) and LPS-stimulated production of PGE(2) by peritoneal macrophages were remarkably increased in pristane-induced lupus mice compared to healthy controls. Exogenous PGE(2) enhanced production of IL-6, IL-10, and NO but decreased TNF-alpha by macrophages and augmented IFN-gamma, IL-6, and IL-10 by splenocytes from pristane-induced lupus mice compared to healthy controls. Exogenous PGE(2) also enhanced production of IFN-gamma, IL-6, and IL-10 by thymocytes from pristane-induced lupus mice. Indomethacin (Indo), a PGE(2) synthesis inhibitor, greatly inhibited LPS-induced production of IL-6 and IL-10 by macrophages from pristane-induced lupus mice, while enhanced TNF-alpha. Indo remarkably inhibited Con A-increased production of IFN-gamma, IL-6, and IL-10 by splenocytes and thymocytes from pristane-induced lupus mice. Therefore, our findings suggest that endogenous PGE(2) may mediate dysregulation of production of proinflammatory cytokines, such as IL-6, IL-10, and IFN-gamma, and NO in pristane-induced lupus mice.

Anti-hyperalgesic and anti-inflammatory effects of ketorolac tromethamine gel using pulsed ultrasound in inflamed rats.

The aim of this study was to determine if a ketorolac tromethamine (KT) gel solution could be administered in vivo via phonophoretic transdermal delivery using pulsed ultrasound by examining its anti-hyperalgesic and anti-inflammatory effects in a rat carrageenan inflammation model. 1% carrageenan was injected into the plantar surface of the right hindpaw of a rat, and anti-hyperalgesic and anti-inflammatory effects of KT via phonophoretic transdermal delivery were examined. The changes in the mechanical and thermal hyperalgesia, nociceptive flexor reflex (NFR), as well as the swelling changes were determined. According to the anti-hyperagesia and anti-inflammation tests, which were used to determine the change in the pain threshold, NFR and swelling showed that the group given the phonophoretic transdermal delivery of KT exhibited significantly more noticeable anti-hyperalgesic and anti-inflammatory effects than those treated with the simple application of a KT gel. The transdermal application of KT gel using phonophoresis had significant anti-hyperalgesic and anti-inflammatory effects. These findings suggest that the transdermal administration of a KT gel using phonophoresis using pulsed ultrasound might be useful for treating acute inflammation and pain.

Synthesis, in vitro assay, and molecular modeling of new piperidine derivatives having dual inhibitory potency against acetylcholinesterase and Abeta1-42 aggregation for Alzheimer's disease therapeutics.

With the goal of developing Alzheimer's disease therapeutics, we have designed and synthesized new piperidine derivatives having dual action of acetylcholinesterase (AChE) and beta-amyloid peptide (Abeta) aggregation inhibition. For binding with the catalytic site of AChE, an ester with aromatic group was designed, and for the peripheral site, another aromatic group was considered. And for intercalating amyloid-beta oligomerization, long and linear conformation with a lipophilic group was considered. The synthetic methods employed for the structure with dual action depended on alcohols with an aromatic ring and the substituted benzoic acids, which are esterificated in the last step of the synthetic pathway. We screened these new derivatives through inhibition tests of acetylcholinesterase, butyrylcholinesterase (BChE), and Abeta(1-42) peptide aggregation, AChE-induced Abeta(1-42) aggregation. Our results displayed that compound 12 showed the best inhibitory potency and selectivity of AChE, and 29 showed the highest selectivity of BChE inhibition. Compounds 15 and 12 had inhibitory activities against Abeta(1-42) aggregation and AChE-induced Abeta aggregation. In the docking model, we confirmed that 4-chlorobenzene of 12 plays the parallel pi-pi stacking against the indole ring of Trp84 in the bottom gorge of AChE. Because the benzyhydryl moiety of 12 covered the peripheral site of AChE in a funnel-like shape, 12 showed good inhibitory potency against AChE and could inhibit AChE-induced Abeta(1-42) peptide aggregation.

Anesthetic effects of lidocaine hydrochloride gel using low frequency ultrasound of 0.5 MHz.

PURPOSE: Low-frequency ultrasound has a significant effect on the transdermal permeation of high molecular weight drugs. However, the rate of permeation in pulsed mode is quite low necessitating considerable time to apply the ultrasound. 0.5 MHz ultrasound, which is a relatively higher frequency in the low-frequency range, can be applied in high intensity in continuous mode. METHODS: A transducer was used to administer an anesthetic drug transdermally on healthy volunteers. The anesthetic effect was measured following administration on placebo, lidocaine HCl alone and lidocaine HCl with 0.5 and 1.0 MHz ultrasound (n=8/group). RESULTS: In surface anesthesia, the phonophoresis group showed a significantly higher pain threshold than the other groups but there was no significant difference between the phonophoresis groups according to the ultrasound frequency. In conduction anesthesia, the 0.5 MHz phonophoresis group showed a significant change in their pain threshold and amplitude of sensory nerve action potential (SNAP) compared with the other groups. CONCLUSIONS: Although there are limitations in applying 0.5 MHz ultrasound in phonophoresis for conduction anesthesia using lidocaine hydrochloride for a nerve block, it is more effective than the 1 Mhz that is widely used in clinical situations. Carbamazepine is a poor water soluble drug and its bioavailability is limited by dissolution rate. Dissolution, serum concentration and anticonvulsive effect of the drug have been evaluated after cogrinding with microcrystalline cellulose. A cogrinding technique was used to increase the dissolution, serum concentrations and anticonvulsive effect of the drug. A novel deconvolution technique of in vitro-in vivo correlation was evaluated.

A new cytotoxic prenylated chalcone from Sophora flavescens.

We have isolated a new prenylated chalcone from the roots of Sophora flavescens (Leguminosae). We determined that structure of this compound is 7,9,2',4'-tetrahydroxy-8-isopentenyl-5-methoxychalcone (1) on the basis of spectroscopic analysis (1D and 2D NMR data). Compound 1 exhibited potent cytotoxicity against human acute promyelocytic (HL60), mouse lymphocytic (L1210) and human histiocytic (U937) leukemia cells.

Cytotoxic isoquinoline alkaloids from the aerial parts of Corydalis incisa.

Three known isoquinoline alkaloids were isolated from the chloroform-soluble fraction of the methanolic extract of the aerial parts of Corydalis incisa (Papaveraceae) through repeated column chromatography. Their chemical structures were elucidated as corynoline (1), corynoloxine (2) and 6-oxocorynoline (3) using spectroscopic analysis. Compounds 1-3 exhibited cytotoxicity against human A549, SK-OV-3, SK-MEL-2 and HCT15 tumor cells.

Transdermal delivery system of triamcinolone acetonide from a gel using phonophoresis.

Triamcinolone acetonide (TA) is a corticosteroid that is used in the systemic and topical treatment of many inflammatory diseases. In this study, a phonophoretic drug delivery system was designed to enhance the TA permeability and the influence of ultrasound was examined. In order to establish the transdermal delivery system for TA, a hydrophilic carbopol gel containing TA was prepared after adopting phonophoresis. A permeation study through mouse skin was performed at 37 degrees C using a Franz diffusion cell, and the ultrasound treatment was carried out for 10 h. The level of TA permeation through the skin was evaluated under various ultrasound conditions including the frequency (1.0, 3.0 MHz), intensity (1.0, 2.5 W/cm2), and duty cycle (continuous, pulse mode) using a 0.5% TA gel. The highest permeation was observed under the ultrasound treatment conditions of low frequency, high intensity, and in continuous mode.

Guaiane sesquiterpenoids from Torilis japonica and their cytotoxic effects on human cancer cell lines.

A new compound 2 and two known guaiane-type sesquiterpenoids were isolated from the methylene chloride-soluble fraction of the methanolic extract of the fruits of Torilis japonica (Umbelliferae) through repeated silica gel and Sephadex LH-20 column chromatography. Their chemical structures were elucidated as torilin (1), 11-acetoxy-8-angeloyloxy-1beta-hydroxy-4-guaien-3-one (1beta-hydroxytorilin, 2), and 11-acetoxy-8-angeloyloxy-1alpha-hydroxy-4-guaien-3-one (1alpha-hydroxytorilin, 3) by spectroscopic analysis. Compounds 1-3 exhibited cytotoxicity against human A549, SK-OV-3, SK-MEL-2, and HCT15 tumor cells.

Inhibitory activity of 6-O-angeloylprenolin from Centipeda minima on farnesyl protein transferase.

The methanolic extract of the aerial parts of Centipeda minima was found to show inhibitory activity on farnesyl protein transferase (FPTase). Bioassay-guided fractionation of the methanolic extract resulted in the isolation of 6-O-angeloylprenolin, as an inhibitor on FPTase. This compound inhibited FPTase activity in a dose-dependent manner, and the IC50 value of 6-O-angeloylprenolin was 18.8 microM.

Anti-inflammatory effects by transdermal application of triamcinolone acetonide gel using phonophoresis in rats.

The present study was carried out to determine the feasibility of using gel formulations for the transdermal delivery of triamcinolone acetonide (TA), which is one of the synthetic glucocorticoids, in conjunction with phonophoresis, and to develop the carbopol gels of TA. For this purpose, the anti-inflammatory effects of the gel containing TA after the adoption of ultrasound were evaluated by investigating the in vivo change in the serum creatine phosphokinase (CPK) and histological findings. Following a muscle injury, the serum CPK activity decreased significantly in the TA gel group with phonophoresis, comparing with that in the control group and the commercial gel group given ultrasound. In the gross finding, after a muscle injury, the TA gel group with phonophoresis showed rapid moderation of the injury compared with the three other groups. The histological findings showed that the inflammation was relieved within 72 h after the injury from the TA gel group with phonophoresis. These effects were considerably higher in the phonophoresis group than in the other three groups. Overall, a TA gel using phonophoresis might be used as a new transdermal delivery technique providing enhanced anti-inflammatory effects.