Cytotoxicity and Preliminary Analysis of the Pro-apoptotic and Cell Cycle Arrest Effects of Lantana ukambensis Against Colorectal Cancer Cells.

Lantana ukambensis (Vatke) Verdc. (Verbenaceae) is a seasonal herb widely spread in the West African region. The whole plant is used for the treatment of wounds, infections, and inflammatory pathologies. The purpose of this research is to evaluate the cytotoxicity and to analyze the probable pro-apototic, and cell cycle arrest effects of L. ukambensis methylene chloride extract and its fractions against HCT-116 and HT-29 colorectal cancer cells using preliminary tests in order to highlight the interest of this plant in the search of new anticancer molecules. The dried powder of the whole plant was extracted by methylene chloride maceration for 24 hours and the extract was divided into five fractions. The cytotoxicity of the crude extract and fractions were evaluated by the MTS assay. The most active fractions were subjected to some preliminary assays including crystal violet, Hoechst staining, cell cycle arrest, and annexin V/PI assays on the cancer cells to highlight the probable mechanism of action of these fractions. The methylene chloride, ethyl acetate, and 1-butanol fractions of L. ukambensis crude extract demonstrated significant antiproliferative effects on HCT-116 and HT-29 cell growth with IC50 values ranging between 2 to 15 μg/mL. 1-butanol and ethyl acetate fractions decreased the G1 phase by 20.53% and 28.47% and increased the G2/M by 23.47% and 25.90% respectively on HCT-116. Moreover, 1-butanol fraction increased the cumulative value of apoptotic cells by 49.77% on HCT-116 and ethyl acetate fraction increased this value by 53.37% at 15 μg/mL after 48 hours of exposure. The outcome of this study suggests the potential of 1-butanol and ethyl acetate fractions for the isolation of anticancer molecules against colorectal cancer

6,8-di-<i>C</i>-glycosyl flavones with <i>β</i>-furanoarabinose from <i>Scutellaria baicalensis</i> and their anti-inflammatory activities

<p>Two flavone di-<i>C</i>-glycosides, a pair of isomers, were isolated from <i>Scutellaria baicalensis</i>. The structures of compounds <b>1</b> and <b>2</b> were elucidated by means of physical data, including 1D and 2D NMR and HR-ESI-MS. Supporting theoretical calculations of the compound conformational landscape has also been conducted for geometry optimization. This is the first report of the natural occurrence of <i>β</i>-furanoarabinoside. In addition, the effects of compounds <b>1</b> and <b>2</b> on NO, pro-inflammatory cytokines, PGE2 and COX-2 levels were measured in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. The pair of isomers exhibited significant inhibitory effects on inflammation.</p

Metabonomic Profiling Reveals Cancer Chemopreventive Effects of American Ginseng on Colon Carcinogenesis in <i>Apc</i>^<i>Min/+</i> Mice

American ginseng (<i>Panax quinquefolius</i> L.) is one of the most commonly used herbal medicines in the West. It has been reported to possess significant antitumor effects that inhibit the process of carcinogenesis. However, the mechanisms underlying its anticancer effects remain largely unresolved. In this study, we investigated the cancer chemopreventive effects of American ginseng on the progression of high fat (HF) diet-enhanced colorectal carcinogenesis with a genetically engineered <i>Apc</i>^<i>Min/+</i> mouse model. The metabolic alterations in sera of experimental mice perturbed by HF diet intervention as well as the American ginseng treatment were measured by gas chromatography time-of-flight mass spectrometry (GC-TOFMS) and liquid chromatography time-of-flight mass spectrometry (LC-TOFMS) analysis. American ginseng treatment significantly extended the life span of the <i>Apc</i>^<i>Min/+</i> mouse. Significant alterations of metabolites involving amino acids, organic acids, fatty acids, and carbohydrates were observed in <i>Apc</i>^<i>Min/+</i> mouse in sera, which were attenuated by American ginseng treatment and concurrent with the histopathological improvement with significantly reduced tumor initiation, progression and gut inflammation. These metabolic changes suggest that the preventive effect of American ginseng is associated with attenuation of impaired amino acid, carbohydrates, and lipid metabolism. It also appears that American ginseng induced significant metabolic alterations independent of the <i>Apc</i>^<i>Min/+</i> induced metabolic changes. The significantly altered metabolites induced by American ginseng intervention include arachidonic acid, linolelaidic acid, glutamate, docosahexaenoate, tryptophan, and fructose, all of which are associated with inflammation and oxidation. This suggests that American ginseng exerts the chemopreventive effects by anti-inflammatory and antioxidant mechanisms

Polydopamine-Coated Magnetic Molecularly Imprinted Polymers with Fragment Template for Identification of <i>Pulsatilla</i> Saponin Metabolites in Rat Feces with UPLC-Q-TOF-MS

In this work, a modified pretreatment method using magnetic molecularly imprinted polymers (MMIPs) was successfully applied to study the metabolites of an important botanical with ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The MMIPs for glucoside-specific adsorption was used to identify metabolites of <i>Pulsatilla chinensis</i> in rat feces. Polymers were prepared by using Fe₃O₄ nanoparticles as the supporting matrix, d-glucose as fragment template, and dopamine as the functional monomer and cross-linker. Results showed that MMIPs exhibited excellent extraction performance, large adsorption capacity (5.65 mg/g), fast kinetics (60 min), and magnetic separation. Furthermore, the MMIPs coupled with UPLC-Q-TOF-MS were successfully utilized for the identification of 17 compounds including 15 metabolites from the <i>Pulsatilla</i> saponin metabolic pool. This study provides a reliable protocol for the separation and identification of saponin metabolites in a complex biological sample, including those from herbal medicines

Design and synthesis of 28-hydroxy protopanaxadiol as a novel probe template

<p>To explore the antitumour mechanism of 20(<i>S</i>)-protopanaxadiol (PPD) while maintaining its uncovered pharmacological active site 3-hydroxyl, 28-hydroxy protopanaxadiol (<b>17</b>), a small molecular probe template of PPD was first designed and synthesised based on the Baldwin’s reaction. Thus, 28-hydroxyl of <b>17</b> was built successfully as a derivatized site of molecular probe’s functional and report groups. The important intermediates and final product were confirmed by ESI-MS and nuclear magnetic resonance spectra with good yield. These studies provided a valuable basis for probe research of PPD.</p

The Efficacy and Safety of Chinese Herbal Medicine Jinlida as Add-On Medication in Type 2 Diabetes Patients Ineffectively Managed by Metformin Monotherapy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial

<div><p>Background</p><p>Metformin plays an important role in diabetes treatment. Studies have shown that the combined use of oral hypoglycemic medications is more effective than metformin monotherapy. In this double-blind, randomized, placebo-controlled, multicenter trial, we evaluated whether Jinlida, a Chinese herbal medicine, enhances the glycemic control of metformin in type 2 diabetes patients whose HbA1c was ineffectively controlled with metformin alone.</p><p>Methods</p><p>A total of 186 diabetes patients were enrolled in this double-Blind, randomized, placebo-controlled, multicenter trial. Subjects were randomly allocated to receive either Jinlida (9 g) or the placebo TID for 12 consecutive weeks. All subjects in both groups also continuously received their metformin without any dose change. During this 12-week period, the HbA1c, FPG, 2h PG, body weight, BMI were assessed. HOMA insulin resistance (HOMA-IR) and β-cell function (HOMA- β) were also evaluated.</p><p>Results</p><p>At week 12, compared to the HbA1c level from week 0, the level of the Jinlida group was reduced by 0.92 ± 1.09% and that of the placebo group was reduced by 0.53 ± 0.94%. The 95% CI was 0.69 - 1.14 for the Jinlida group vs. 0.34 - 0.72 for the placebo group. There was a very significant HbA1c reduction between the two groups after 12 weeks (p < 0.01). Both FG and 2h PG levels of the Jinlida group and placebo group were reduced from week 0. There were a very significant FG and 2h PG level reductions between the two groups after 12 weeks (both p < 0.01). The Jinlida group also showed improved β-cell function with a HOMA-β increase (p < 0.05). No statistical significance was observed in the body weight and BMI changes. No serious adverse events were reported.</p><p>Conclusion</p><p>Jinlida significantly enhanced the hypoglycemic action of metformin when the drug was used alone. This Chinese herbal medicine may have a clinical value as an add-on medication to metformin monotherapy.</p><p>Trial Registration</p><p>Chinese Clinical Trial Register <a href="http://www.chictr.org/en/proj/show.aspx?proj=4531" target="_blank">ChiCTR-TRC-13003159</a></p></div

TU-100 (Daikenchuto) and Ginger Ameliorate Anti-CD3 Antibody Induced T Cell-Mediated Murine Enteritis: Microbe-Independent Effects Involving Akt and NF-κB Suppression

<div><p>The Japanese traditional medicine daikenchuto (TU-100) has anti-inflammatory activities, but the mechanisms remain incompletely understood. TU-100 includes ginger, ginseng, and Japanese pepper, each component possessing bioactive properties. The effects of TU-100 and individual components were investigated in a model of intestinal T lymphocyte activation using anti-CD3 antibody. To determine contribution of intestinal bacteria, specific pathogen free (SPF) and germ free (GF) mice were used. TU-100 or its components were delivered by diet or by gavage. Anti-CD3 antibody increased jejunal accumulation of fluid, increased TNFα, and induced intestinal epithelial apoptosis in both SPF and GF mice, which was blocked by either TU-100 or ginger, but not by ginseng or Japanese pepper. TU-100 and ginger also blocked anti-CD3-stimulated Akt and NF-κB activation. A co-culture system of colonic Caco2BBE and Jurkat-1 cells was used to examine T-lymphocyte/epithelial cells interactions. Jurkat-1 cells were stimulated with anti-CD3 to produce TNFα that activates epithelial cell NF-κB. TU-100 and ginger blocked anti-CD3 antibody activation of Akt in Jurkat cells, decreasing their TNFα production. Additionally, TU-100 and ginger alone blocked direct TNFα stimulation of Caco2BBE cells and decreased activation of caspase-3 and polyADP ribose. The present studies demonstrate a new anti-inflammatory action of TU-100 that is microbe-independent and due to its ginger component.</p></div

Flow diagram of participant screening, randomization, and treatment.

<p>Four subjects in the Jinlida group and 2 subjects in the placebo group were excluded from the study due to various reasons listed.</p

Changes in HOMA-IR and HOMA-β after 12 weeks treatment in the Jinlida group and placebo group.

<p>(A) Left: The mean HOMA-IR decreased somewhat in both groups between the baseline and after treatment. Right: Changes in HOMA-IR of the two groups. (B) Left: The mean HOMA-β increased very signigicantly in the Jinlida group between the baseline and after treatment. Right: There was a significant statistical difference in the change between the two groups. Data presented as mean ± S.E. * p < 0.05. **p < 0.01.</p

Subject characteristics at the baseline.

<p>Subject characteristics at the baseline.</p