Gastroprotective Effect of Isoferulic Acid Derived from Foxtail Millet Bran against Ethanol-Induced Gastric Mucosal Injury by Enhancing GALNT2 Enzyme Activity.

Excessive alcohol consumption has led to the prevalence of gastrointestinal ailments. Alleviating gastric disorders attributed to alcohol-induced thinning of the mucus layer has centered on enhancing mucin secretion as a pivotal approach. In this study, foxtail millet bran polyphenol BPIS was divided into two components with MW < 200 D and MW > 200 D by molecular interception technology. Combined with MTT, cell morphology observation, and trypan blue staining, isoferulic acid (IFA) within the MW < 200 D fraction was determined as the effective constituent to mitigate ethanol-induced damage of gastric epithelial cells. Furthermore, a Wistar rat model with similar clinical features to alcohol-induced gastric mucosal injury was established. Then, gastric morphological observation, H&E staining, and assessments of changes in gastric hexosamine content and gastric wall binding mucus levels were carried out, and the results revealed that IFA (10 mg/Kg) significantly ameliorated alcohol-induced gastric mucosal damage. Finally, we applied techniques including Co-IP, molecular docking, and fluorescence spectroscopy and found that IFA inhibited the alcohol-induced downregulation of N-acetylgalactosamintransferase 2 (GALNT2) activity related to mucus synthesis through direct interaction with GALNT2 in gastric epithelial cells, thus promoting mucin synthesis. Our study lays a foundation for whole grain dietary intervention tailored to individuals suffering from alcoholic gastric mucosal injury.

Dietary fibre supplementation enhances radiotherapy tumour control and alleviates intestinal radiation toxicity.

BACKGROUND: Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts. RESULT: Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8+ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles. CONCLUSION: These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. Video Abstract.

Crystal Structure, Spectroscopic Characterization, Antioxidant and Cytotoxic Activity of New Mg(II) and Mn(II)/Na(I) Complexes of Isoferulic Acid.

The Mg(II) and heterometallic Mn(II)/Na(I) complexes of isoferulic acid (3-hydroxy-4-methoxycinnamic acid, IFA) were synthesized and characterized by infrared spectroscopy FT-IR, FT-Raman, electronic absorption spectroscopy UV/VIS, and single-crystal X-ray diffraction. The reaction of MgCl2 with isoferulic acid in the aqueous solutions of NaOH resulted in synthesis of the complex salt of the general formula of [Mg(H2O)6]⋅(C10H9O4)2⋅6H2O. The crystal structure of this compound consists of discrete octahedral [Mg(H2O)6]2+ cations, isoferulic acid anions and solvent water molecules. The hydrated metal cations are arranged among the organic layers. The multiple hydrogen-bonding interactions established between the coordinated and lattice water molecules and the functional groups of the ligand stabilize the 3D architecture of the crystal. The use of MnCl2 instead of MgCl2 led to the formation of the Mn(II)/Na(I) complex of the general formula [Mn3Na2(C10H7O4)8(H2O)8]. The compound is a 3D coordination polymer composed of centrosymmetric pentanuclear subunits. The antioxidant activity of these compounds was evaluated by assays based on different antioxidant mechanisms of action, i.e., with •OH, DPPH• and ABTS•+ radicals as well as CUPRAC (cupric ions reducing power) and lipid peroxidation inhibition assays. The pro-oxidant property of compounds was measured as the rate of oxidation of Trolox. The Mg(II) and Mn(II)/Na(I) complexes with isoferulic acid showed higher antioxidant activity than ligand alone in DPPH (IFA, IC50 = 365.27 µM, Mg(II) IFA IC50 = 153.50 µM, Mn(II)/Na(I) IFA IC50 = 149.00 µM) and CUPRAC assays (IFA 40.92 µM of Trolox, Mg(II) IFA 87.93 µM and Mn(II)/Na(I) IFA 105.85 µM of Trolox; for compounds' concentration 10 µM). Mg(II) IFA is a better scavenger of •OH than IFA and Mn(II)/Na(I) IFA complex. There was no distinct difference in ABTS•+ and lipid peroxidation assays between isoferulic acid and its Mg(II) complex, while Mn(II)/Na(I) complex showed lower activity than these compounds. The tested complexes displayed only slight antiproliferative activity tested in HaCaT human immortalized keratinocyte cell line within the solubility range. The Mn(II)/Na(I) IFA (16 µM in medium) caused an 87% (±5%) decrease in cell viability, the Mg salt caused a comparable, i.e., 87% (±4%) viability decrease in a concentration of 45 µM, while IFA caused this level of cell activity attenuation (87% ± 5%) at the concentration of 1582 µM (significant at α = 0.05).

Identification of functional compounds in baru (Dipteryx alata Vog.) nuts: Nutritional value, volatile and phenolic composition, antioxidant activity and antiproliferative effect.

This work aimed to contribute to the nutritional and functional characterization of roasted baru nuts, a seed widely consumed and produced in Brazil. Baru nut was characterized in terms of its nutritional value and volatile composition (SPME-GC-MS analysis). The ultrasound assisted extraction was used to extract free and bound phenolic compounds that were identified by LC-DAD-ESI-MS/MS method. Bioactivity assays were carried out to evaluate the antioxidant activity (ORAC and HOSC assay) and anticancer effect (inhibition of HT29 cell growth and targeting of cancer stemness) of baru nut extracts and phenolic compounds. Results showed that baru is a good source of protein and monounsaturated fatty acids, specifically oleic acid (47.20 g/100 g). The predominant volatile compounds are hexanal (71.18%) and 2,5-dimethyl-pyrazine (9.43%). The main phenolic compounds identified were gallic acid and its derivatives, such as gallic acid esters and gallotannins. Among all, gallic acid and methyl gallate seemed to be the main compounds responsible for the high antioxidant activity. The antiproliferative effect evaluated of baru extracts in HT29 cell line showed ability to impair cell growth in both monolayer and spheroid cultures and to reduce ALDH+ population. These results supply new information about the functional compounds presents in baru nut, which are important sources of natural antioxidants and antiproliferative compounds.

Isoferulic acid inhibits human leukemia cell growth through induction of G2/M­phase arrest and inhibition of Akt/mTOR signaling.

Hematologic malignancy is a serious disease that develops quickly and aggressively, severely threatening human health owing to its high mortality. The current study aimed to evaluate the antitumor effects of isoferulic acid (IFA) on leukemia cells and investigate the possible molecular mechanisms. Hematologic cancer cell lines (Raji, K562 and Jurkat) were treated with IFA in a dose­dependent manner and proliferation was measured by a cell proliferation assay. Cell cycle arrest was detected via flow cytometry using propidium iodide (PI) staining. Cell apoptosis and apoptosis­associated signal pathways were analyzed via Annexin V/PI staining and western blot assays, respectively. IFA inhibited cell viability, induced cell apoptosis and triggered cell cycle arrest in G2/M phase in Raji, K562, and Jurkat cells in a dose­dependent manner. In response to IFA treatment, the levels of cleaved poly(ADP­ribose) polymerase and cleaved caspase­3 were increased in Jurkat and K562 cells, which was associated with increased phosphorylation of Cdc2 and reduction of Cyclin B1 levels. IFA remarkably attenuated the phosphorylation of mTOR and Akt in Jurkat cells. Collectively, the present data suggested that IFA had therapeutic effects on Jurkat, K562, and Raji cells, indicating it as a promising candidate for the treatment of hematologic malignancy.

Isoferulic acid attenuates methylglyoxal-induced apoptosis in INS-1 rat pancreatic ß-cell through mitochondrial survival pathways and increasing glyoxalase-1 activity.

Methylglyoxal (MG) is a reactive precursor to advanced glycation end-products (AGEs), which exert deleterious effects on cells and tissues. MG also causes pancreatic ß-cell dysfunction and apoptosis. Isoferulic acid (IFA), a naturally occurring cinnamic acid derivative, is considered to be an antiglycating agent. However, the effect of IFA on MG-induced pancreatic ß-cell dysfunction remains unknown. The objective of this study was to determine the protective effect of IFA against MG-induced mitochrondrial dysfunction and apoptosis in INS-1 pancreatic ß-cells. The results showed that pretreatment of INS-1 cells with 100 µM IFA for 48 h prevented MG-induced decrease in cell viability and impairment of glucose-stimulated insulin secretion (GSIS). In addition, 100 µM IFA pretreatment also decreased MG-induced generation of reactive oxygen species (ROS) and upregulation of mitochondrial uncoupling protein 2 (Ucp2) mRNA expression. Furthermore, IFA pretreatment reduced MG-induced increase in caspase-3 activity, suggesting a reduction of apoptotic cell death. IFA (50-100 µM) itself markedly increased the activity of glyoxalase 1 (GLO1), a major enzyme for the detoxification of MG. The results showed that 100 µM IFA protected MG-induced loss of GLO1 activity in INS-1 cells. These findings suggest that IFA pretreatment attentuates MG-induced dysfunction and apoptosis in INS-1 pancreatic ß-cells through mitochondrial survival pathway and increasing GLO1 activity.

Anti-HIV activity of southern African plants: Current developments, phytochemistry and future research.

ETHNOPHARMACOLOGICAL RELEVANCE: The African continent is home to a large number of higher plant species used over centuries for many applications, which include treating and managing diseases such as HIV. Due to the overwhelming prevalence and incidence rates of HIV, especially in sub-Saharan Africa, it is necessary to develop new and affordable treatments. AIM OF THE STUDY: The article provides an extensive overview of the status on investigation of plants from the southern African region with ethnobotanical use for treating HIV or HIV-related symptoms, or the management of HIV. The review also provide an account of the in vitro assays, anti-viral activity and phytochemistry of these plants. MATERIALS AND METHODS: Peer-reviewed articles investigating plants with ethnobotanical information for the treatment or management of HIV or HIV-related symptoms from the southern African region were acquired from Science Direct, PubMed central and Google Scholar. The selection criteria was that (1) plants should have a record of traditional/popular use for infectious or viral diseases, HIV treatment or symptoms similar to HIV infection, (2) if not traditionally/popularly used, plants should be closely related to plants with popular use and HIV activity identified by means of in vitro assays, (3) plants should have been identified scientifically, (4) should be native to southern African region and (5) anti-HIV activity should be within acceptable ranges. RESULTS: Many plants in Africa and specifically the southern African region have been used for the treatment of HIV or HIV related symptoms and have been investigated suing various in vitro techniques. In vitro assays using HIV enzymes such as reverse transcriptase (RT), integrase (IN) and protease (PR), proteins or cell-based assays have been employed to validate the use of these plants with occasional indication of the selectivity index (SI) or therapeutic index (TI), with only one study, that progressed to in vivo testing. The compounds identified from plants from southern Africa is similar to compounds identified from other regions of the world, and the compounds have been divided into three groups namely (1) flavonoids and flavonoid glycosides, (2) terpenoids and terpenoid glycosides and (3) phenolic acids and their conjugated forms. CONCLUSIONS: An investigation of the plants from southern Africa with ethnobotanical use for the treatment of HIV, management of HIV or HIV-related symptoms, therefore provide a very good analysis of the major assays employed and the anti-viral compounds and compound groups identified. The similarity in identified anti-viral compounds worldwide should support the progression from in vitro studies to in vivo testing in development of affordable and effective anti-HIV agents for countries with high infection and mortality rates due to HIV/AIDS.

Traditional uses, phytochemistry, pharmacology and toxicology of the genus Cimicifuga: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants of the genus Cimicifuga have long been used as an ethnomedicine in China, Europe, and North America for its high medicinal value and health benefits. Their dried rhizomes are widely used for treating wind-heat headache, toothache, aphtha, sore throat, measles, spot poison, archoptosis, and uterine prolapse. In addition, it is used as a dietary supplement for preventing women menopausal symptoms and osteoporosis. AIM OF THE REVIEW: This paper aims to provide up-to-date information on the genus Cimicifuga, including botanical characterization, medicinal resources, traditional medicinal uses, phytochemistry, quality control, pharmacological research as well as the toxicology. The possible structural-activity relationships and molecular mechanisms of the bioactive constituents are discussed in ways that contribute to the structural optimization and preclinical safety assessment for further drug design. MATERIALS AND METHODS: The relevant information on Cimicifuga was collected from scientific databases (such as Google Scholar, PubMed, SciFinder Scholar, Science Direct, CNKI, Baidu Scholar, Web of Science, China Knowledge Resource Integrated Database), Chinese herbal classics, ethnobotanical books, PhD and MSc dissertations, Chinese Pharmacopoeia, published articles in peer-reviewed journals, local magazines, and unpublished materials. In addition, the Plant List (TPL, www.theplantlist.org) was also used to validate the scientific names and synonyms of this plant. The literature cited in this review dated from 1953 to 2017. RESULTS: The majority of chemical constituents of this plant include triterpenoid glycosides, phenylpropanoids, nitrogenous compounds, chromones, flavonoids and 4α-methyl steroid. Among them, the primary bioactive constituents are believed to be present in the triterpene glycoside fraction. To date, investigation of seven Cimicifuga spp. plants led to the identification of more than 457 compounds. Years of pharmacological research proved that the crude extracts and certain pure compounds obtained from Cimicifuga exhibited menopausal syndrome-treatment, anti-osteoporosis, antiviral, antitumor, antioxidant and antiangiogenic activities. On the other hand, Cimicifuga plant-induced toxicities of liver, cardiovascular, central and peripheral nervous systems have also been reported. Therefore, safety consideration should be placed into a high priority for herbal medicine Cimicifuga therapy in the early stages of development and clinical trials. CONCLUSIONS: This review presents information on botany, medicinal resources, and traditional medicinal history of some Cimicifuga plants. Modern pharmacology researchers have validated many traditional uses of Cimicifuga species. As the quality control and safety assessment of Cimicifuga plants is still incomplete, only a small part of the plant is permitted to be used as medicines. Expansion of medicinal resources in Cimicifuga is urgently needed to enable its full use. Currently research primarily focuses on the triterpenoid glycosides but there are many other types of compounds which may possess new biological activities however the systematic studies of these compounds are lacking. Extensive study is required on Cimicifuga plant before it can be fully used in clinics as a potent drug candidate.

Fermentation and complex enzyme hydrolysis enhance total phenolics and antioxidant activity of aqueous solution from rice bran pretreated by steaming with α-amylase.

In this study, rice bran was successively steamed with α-amylase, fermented with lactic acid bacteria, and hydrolyzed with complex enzymes. The changes in phenolic profiles and antioxidant activities of the corresponding aqueous solutions from three stages were investigated. Compared to the first stage, fermentation and complex enzyme hydrolysis significantly increased the total phenolics, total flavonoids, total FRAP and ORAC values by 59.2%, 56.6%, 73.6% and 45.4%, respectively. Twelve individual phenolics present in free or soluble conjugate forms were also analyzed during the processing. Ferulic acid was released in the highest amount among different phenolics followed by protocatechuic acid. Moreover, a major proportion of phenolics existed as soluble conjugates. The results showed that fermentation and complex enzyme hydrolysis enhanced total phenolics and antioxidant activities of aqueous solution from rice bran pretreated by steaming with α-amylase. This research could provide basis for the processing of rice bran beverage rich in phenolics.

Belamcanda chinensis (L.) DC-An ethnopharmacological, phytochemical and pharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: Belamcanda chinensis (L.) DC is the sole species in the genus Belamcanda Adans. (Iridaceae), found mainly in Northeast Asia. Bombus chinensis has long been used in traditional Chinese medicine for its multiple therapeutic uses in the form of antipyretic agents, antidote, expectorant, antiphlogistic and analgesic. AIM OF THE REVIEW: This manuscript comprehensively summarizes the various studies published in recent years on the botany, ethnopharmacology, phytochemistry, biological activity and toxicology of B. chinensis. We hope to provide a foundation for future studies on the mechanism of action and development of better therapeutic agents based on B. chinensis. MATERIAL AND METHODS: All information available on B. chinensis was collected using electronic search engines, such as PubMed, SciFinder Scholar, CNKI, TPL (www.theplantlist.org), Google Scholar and Web of Science. RESULTS: The analysis shown that ethno-medical uses of B. chinensis have been recorded in China, Japan and Korea since a long time. Based on a phytochemical investigation, this plant contains flavonoids, terpenoids, quinones, phenolic compounds, ketones, organic acids, etc. Crude extracts and pure compounds isolated from B. chinensis exhibited various biological effects. CONCLUSIONS: In light of its long traditional use and the modern phytochemical and pharmacological studies summarized here, B. chinensis is known to be a promising medicinal plant with the isolated extracts and chemical components showing a wide range of biological activities. Thus, it is imperative that the necessary programs and value assessment of B. chinensis be established for further studies. It is also important that the synergistic or antagonistic effects of this traditional herbal medicine are investigated in depth to identify more bioactive components by bioactivity-guided isolation strategies, and to illustrate the mechanisms of action targeting on ethnomedical uses. Future clinical studies can also focus on the main therapeutic aspects, toxicity and adverse effects of B. chinensis.

Antioxidative free and bound phenolic constituents in botanical fractions of Indian specialty maize (Zea mays L.) genotypes.

Specialty maize genotypes viz. QPM (quality protein maize), Baby corn, Popcorn and Sweet corn, which are usually consumed in whole forms can be good supplements of phenolic antioxidants. Botanical fractions of these maize genotypes were analyzed to explore the distribution of free and bound phenolics. HPLC and ESI-MS/MS results indicated the presence of vanillic, syringic, p-hydroxybenzoic, caffeic, p-coumaric, ferulic and isoferulic acids along with cyanidin-3-O-glucoside, kaempferol and quercetin. Germs of maize samples contained significantly higher free phenolics than pericarps, whereas, pericarps contained 74-83% of bound ones. QPM and Popcorn contained only 3% free phenolics whereas, Baby corn and Sweet corn had 14-17%. Unlike in peroxide scavenging and reducing capacity, anti-radical capacity of free phenolics of germs was significantly higher than that of pericarps. Free phenolics contributed 0.2-1.65%, 2-5% and 42-49% in anti-radical, peroxide scavenging and reducing capacity, respectively. Among lipophilic tocochromanols γ-tocopherol was the most abundant isomer in the samples among which Sweet corn contained the most (84.2 µg/g). Data showed that specialty maize genotypes are rich sources of hydrophilic and lipophilic bioactives and are natural antioxidants.

Screening of effective ingredients of total salvianolic acids components based on in vitro blood-brain barrier model / 中草药

Objective: To establish a blood-brain barrier (BBB) model for screening the effective ingredients of total salvianolic acids components probably effecting central nervous system (CNS), so as to provide basis for the rapid high throughput screening of CNS drugs. Methods: The permeability parameters and transendothelial electrical resistance (TEER) values showed that the co-cultured human brain microvascular endothelial cells (HBMEC)/HA (human astrocytes) model was of integrity and vitality. The active components in total salvianolic acids were screened with this in vitro BBB model, and then analyzed by HPLC-MS. Results: HA induced HBMEC to produce higher TEER in the first 10 d up to 300 Ω/cm2, sodium fluorescein was used to detect the formation of tight junctions of endothelial cells, and the permeability coefficient of its cross-vitro BBB model was (2.659 ± 0.730) × 10-3 cm/min. We found that six compounds at least from total salvianolic acids could permeate across BBB model, in which danshensu, protocatechuic acid, caffeic acid, isoferulic acid, lithospermic acid, and rosmarinicacid were identified. Conclusion: The co-cultured HBMEC/HA model combined with HPLC-MS analysis is a potential tool for screening of BBB permeable drug candidates from plant-derived materials.

Gastroprotective activity of the hydroethanolic extract and isolated compounds from the leaves of Solanum cernuum Vell.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum cernuum Vell. (Solanaceae) is a Brazilian medicinal plant, traditionally known as "panaceia". Its folk name is probably due to its wide range of applications in traditional medicine including the treatment of ulcers. AIM OF THE STUDY: To evaluate the gastroprotective activities of the hydroethanolic extract (ESC) of S. cernuum and its major isolated compounds using in vivo gastric ulcer models. MATERIAL AND METHODS: The ESC extract was obtained by maceration followed by percolation of the dried and powdered leaves of S. cernuum in ethanol:water (7:3). The major compounds in the extract were isolated by applying various preparative chromatographic techniques. The gastroprotective activity was evaluated in mice using different gastric ulcer-induced models. The anti-Helicobacter pylori activity was performed using the agar-well diffusion and broth microdilution methods. RESULTS: The ESC extract showed gastroprotective effects in the assay of acute gastric ulcer-induced by HCl/EtOH, nonsteroidal anti-inflammatory drug, and acetic acid-induced chronic ulcer protocols. The results also demonstrated that the gastroprotection induced by ESC extract is related to the activity of nitric oxide and endogenous sulfhydryls, which are important gastroprotective factors. The ESC extract and the alkaloid cernumidine did not show activity against H. pylori in the concentrations tested. CONCLUSIONS: The present study showed that the crude extract of S. cernuum possessed gastroprotective activity which corroborating the traditional use of this plant for the treatment of gastric ulcers. The isolated flavonoids, quercitrin and afzelin as well as the phenylpropanoid, isoferulic acid are suggested to be the compounds responsible for the gastroprotective activity of S. cernuum extract.

Effect of degree of milling on phenolic profiles and cellular antioxidant activity of whole brown rice.

The impact of increasing degree of milling (DOM) on free and bound phenolics and flavonoids and on cellular antioxidant activity (CAA) of japonica and indica brown rice was investigated. As the average DOM increased from 0 to 2.67, 7.25 and 9.60%, the average total phenolic content decreased by 21.1, 42.6 and 55.6%, and the average total CAA value decreased by 37.4, 84.0 and 92.8%, respectively. Furthermore, the percentage contributions of bound forms to total phenolics and flavonoids decreased with increasing DOM. The contents of nine phenolic compounds significantly decreased with increasing DOM, including quercetin, ferulic and coumaric acids. Interestingly, as the DOM increased to 9.6%, free ferulic and coumaric acids were undetectable in japonica rice, while neither free nor bound caffeic acid was detectable in indica rice. These findings indicate that DOM should be carefully controlled for acceptable sensory quality and retention of phytochemicals during brown rice milling.

Inhibition screening method of microsomal UGTs using the cocktail approach.

A rapid method for the simultaneous determination of the in vitro activity of the 10 major human liver UDP-glucuronosyltransferase (UGT) enzymes was developed based on the cocktail approach. Specific substrates were first selected for each UGT: etoposide for UGT1A1, chenodeoxycholic acid for UGT1A3, trifluoperazine for UGT1A4, serotonin for UGT 1A6, isoferulic acid for UGT1A9, codeine for UGT2B4, azidothymidine for UGT2B7, levomedetomidine for UGT2B10, 4-hydroxy-3-methoxymethamphetamine for UGT2B15 and testosterone for UGT2B17. Optimal incubation conditions, including time-based experiments on cocktail metabolism in pooled HLMs that had been performed, were then investigated. A 45-min incubation period was found to be a favorable compromise for all the substrates in the cocktail. Ultra-high pressure liquid chromatography coupled to an electrospray ionization time-of-flight mass spectrometer was used to separate the 10 substrates and their UGT-specific glucuronides in less than 6 min. The ability of the cocktail to highlight the UGT inhibitory potential of xenobiotics was initially proven by using well-known UGT inhibitors (selective and nonselective) and then by relating some of the screening results obtained by using the cocktail approach with morphine glucuronidation (substrate highly glucuronidated by UGT 2B7). All the results were in agreement with both the literature and with the expected effect on morphine glucuronidation.

Platycodon grandiflorus - an ethnopharmacological, phytochemical and pharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: Platycodon grandiflorus (Jacq.) A. DC., the sole species in genus Platycodon A. DC. (Campanulaceae) has a long history of use as a traditional herbal medicine for the treatments of cough, phlegm, sore throat, lung abscess, chest pain, dysuria, and dysentery. As a legal medicine and dietary supplement, it is also frequently used as an ingredient in health foods and vegetable dishes. The aim of this review is to provide up-to-date information on the botanical characterization and distribution, ethnopharmacology, phytochemistry, pharmacology, and toxicity of Platycodon grandiflorus based on literature published in recent years. It will build a foundation for further study of the mechanism of action and the development of better therapeutic agents and healthy products from Platycodon grandiflorus. MATERIAL AND METHODS: All of the available information on Platycodon grandiflorus was collected via electronic search (using PubMed, SciFinder Scholar, CNKI, TPL (www.theplantlist.org), Google Scholar, Baidu Scholar, and Web of Science). RESULTS: A comprehensive analysis of the literature obtained through the above-mentioned sources confirmed that ethno-medical uses of Platycodon grandiflorus have been recorded in China, Japan, Mongolia, and Korea for thousands of years. A phytochemical investigation revealed that this product contains steroidal saponins, flavonoids, polyacetylenes, sterols, phenolics, and other bioactive compounds. Crude extracts and pure compounds isolated from Platycodon grandiflorus exhibited significant anti-inflammatory and immunostimulatory effects. They also showed valuable bioactive effects, such as anti-tumor, anti-oxidant, anti-diabetic, anti-obesity, hepatoprotective and cardiovascular system effects, among others. CONCLUSIONS: In light of its long traditional use and the modern phytochemical and pharmacological studies summarized here, Platycodon grandiflorus has been demonstrated to show a strong potential for therapeutic and health-maintaining uses. Both the extracts and chemical components isolated from the plant showed a wide range of biological activities. Thus, more studies on the pharmacological mechanisms of its main active compounds (e.g., platycodin D, D2) need to be conducted. In addition, as one of the most popular traditional herbal medicines, clinical studies of the main therapeutic aspects, toxicity and adverse effects of Platycodon grandiflorus will also undoubtedly be the focus of future investigation.

Effects of Different Processing Methods on Contents of Isoferulic Acid in Cimicifuga heracleifolia / 中国中医药信息杂志

Objective To investigate the effects of different processing methods on contents of main chemical components isoferulic acid in Cimicifuga heracleifolia. Methods Cimicifuga heracleifolia from the same batch were prepared by processing method. HPLC were used to determine the contents of isoferulic acid in crudes samples, wine-prepared samples, vinegar-prepared samples, and carbonized samples. Results The contents of isoferulic acid of crudes samples and the three different processed products were in the order as follows:carbonized samples (0.404 7%)>vinegar-prepared samples (0.302 3%)>wine-prepared samples (0.262 4%)>crudes samples (0.231 3%). Conclusion Different processing methods had certain effects on the content of isoferulic acid in Cimicifuga heracleifolia.

Search for novel histone deacetylase inhibitors. Part II: design and synthesis of novel isoferulic acid derivatives.

Previously, we described the discovery of potent ferulic acid-based histone deacetylase inhibitors (HDACIs) with halogeno-acetanilide as novel surface recognition moiety (SRM). In order to improve the affinity and activity of these HDACIs, twenty seven isoferulic acid derivatives were described herein. The majority of title compounds displayed potent HDAC inhibitory activity. In particular, IF5 and IF6 exhibited significant enzymatic inhibitory activities, with IC50 values of 0.73 ± 0.08 and 0.57 ± 0.16 µM, respectively. Furthermore, these compounds showed moderate antiproliferative activity against human cancer cells. Especially, IF6 displayed promising profile as an antitumor candidate with IC50 value of 3.91 ± 0.97 µM against HeLa cells. The results indicated that these isoferulic acid derivatives could serve as promising lead compounds for further optimization.

Acylated glucosinolates with diverse acyl groups investigated by high resolution mass spectrometry and infrared multiphoton dissociation.

With the aim of developing a procedure for detecting and identifying intact acylated glucosinolates (a-GLSs) found in trace quantities in natural plant samples, extracts of Barbarea vulgaris seeds were analyzed by reversed-phase liquid chromatography coupled with electrospray ionization and Fourier-transform ion cyclotron resonance mass spectrometry (RPLC-ESI FTICR MS). After a preliminary optimization of fragmentation conditions, based on a non-acylated parent glucosinolate (glucobarbarin) and three previously identified a-GLSs (the 6'-isoferuloyl esters of glucobarbarin, gluconasturtiin and glucobrassicin), infrared multiphoton dissociation (IRMPD) was employed for a tandem MS-based elucidation of the molecular structures of novel a-GLSs. As a result, three acylated derivatives of glucobarbarin, esterified at the thioglucose moiety with a coumaric acid isomer, sinapic acid or an isomer and a dimethoxycinnamic acid isomer, were identified. In addition, a further acylated glucosinolate was tentatively identified as the isoferuloyl ester of an unidentified hydroxylic derivative of glucobarbarin. This is the first demonstration of diversity in the acyl moieties of thioglucose-acylated glucosinolates, which may reflect the substrate specificity of the endogenous acyl transferase. As expected, 6'-isoferuloyl-glucobarbarin was detected as the main acylated GLS in extracts of B. vulgaris seeds. A quantitative estimate suggested that non-isoferuloyl substituted glucobarbarins correspond to ca. 0.026% of the level of 6'-isoferuloyl glucobarbarin. The formation of an uncommon distonic radical anion, most likely generated in the gas phase upon methyl radical (CH3·) loss from the isoferuloyl anion, is demonstrated.

Downregulation of NO and PGE2 in LPS-stimulated BV2 microglial cells by trans-isoferulic acid via suppression of PI3K/Akt-dependent NF-κB and activation of Nrf2-mediated HO-1.

Little is known about whether trans-isoferulic acid (TIA) regulates the production of lipopolysaccharide (LPS)-induced proinflammatory mediators. Therefore, we examined the effect of TIA isolated from Clematis mandshurica on LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in BV2 microglial cells. We found that TIA inhibited the production of LPS-induced NO and PGE2 without accompanying cytotoxicity in BV2 microglial cells. TIA also downregulated the expression levels of specific regulatory genes such as inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) by suppressing LPS-induced NF-κB activity via dephosphorylation of PI3K/Akt. In addition, we demonstrated that a specific NF-κB inhibitor PDTC and a selective PI3K/Akt inhibitor, LY294002 effectively attenuated the expression of LPS-stimulated iNOS and COX-2 mRNA, while LY294002 suppressed LPS-induced NF-κB activity, suggesting that TIA attenuates the expression of these proinflammatory genes by suppressing PI3K/Akt-mediated NF-κB activity. Our results showed that TIA suppressed NO and PGE2 production through the induction of nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent heme oxygenase-1 (HO-1). Taken together, our data indicate that TIA suppresses the production of proinflammatory mediators such as NO and PGE2, as well as their regulatory genes, in LPS-stimulated BV2 microglial cells, by inhibiting PI3K/Akt-dependent NF-κB activity and enhancing Nrf2-mediated HO-1 expression.