curcumin and baicalein

Excessive exposure to ultraviolet (UV) B radiation may lead to skin damage, photosensitivity, or even tumorigenesis via induction of oxidative stress. Naturally derived antioxidants could play significant roles in cancer therapy due to their multi-targeted actions and lack of substantial toxicity. Drug combinations target at diverse pathway of cells and make cells export meticulous biological outcomes through the multifaceted signaling network. The UVB protective effects of combinations of naturally derived antioxidants- curcumin, resveratrol, proanthocyanidins, baicalein, and beta-nicotinamide adenine dinucleotide (NADH) were investigated. An oxidative cell damage model was established to study the ultraviolet irradiation system. An orthogonal array composite design (OACD) was employed in the optimization of antioxidants combinations. Combination of resveratrol (0.1μM) and baicalein in medium concentration (0.2μM), with NADH in high concentration (0.8μM) was found to be the most efficacious combination among all the 30 runs performed using OACD. The findings suggested that UVB exposure-inflicted cell apoptosis can be significantly reduced by naturally-derived antioxidant combinations. These results provide an insight into the discovery of synergistic antioxidant combinations in skin cancer, using orthogonal array composite design (OACD). The results also have practical implications in the understanding of drug mechanisms in skin cancer, which can assist clinical practice by recommending better drug combinations.

Topics: Antioxidants; Cell Line; Cell Survival; Curcumin; DNA Fragmentation; Fibroblasts; Flavanones; Humans; Linear Models; Oxidative Stress; Proanthocyanidins; Reactive Oxygen Species; Resveratrol; Skin; Stilbenes; Ultraviolet Rays

Baicalein (B), a bioactive flavone isolated from the root of a traditional Chinese medicinal herb Scutellaria baicalensis Georgi, was found to undergo extensive intestinal Phase II metabolism during its absorption process. Compounds sharing the same metabolic pathways with B or being inhibitors of enzymes UGT and SULT are expected to interfere with the metabolism of B leading to alteration of the absorption of B. The present study aims to identify potential intestinal absorption and metabolism interactions between B and four selected compounds, namely acetaminophen (APAP), (-)-epicatechin (EC), piperine (PIP) and curcumin (CUR) using in vitro and in situ models.. Three in vitro and one in situ methods were employed to investigate the effect of selected compounds on the metabolism and absorption on B. Incubation studies using rat intestinal s9 and Caco-2 cell lysate were used to study the effect of selected compounds on glucuronidation and sulfation of B. Sigmoidal dose-response curves were plotted and IC(50) values were estimated. Apical to basolateral absorption study using Caco-2 cell monolayer model was also employed to study the effect of selected compounds on absorption of B. The most potent inhibitor identified was selected to further investigate its potential herb-drug interaction with B using in situ rat intestinal perfusion model. LC/MS/MS was used for the analysis of B and its metabolites in collected samples.. It was found that all the four selected compounds could produce a dose-dependent inhibition on the glucuronidation and sulfation of B. Moreover, the presence of CUR and high-dose EC demonstrated a subsequent increase in the absorption of B. In general, the order of potency on glucuronidation inhibition is: CUR>PIP>EC>APAP; while the potency order on sulfation inhibition is: CUR>EC>PIP>APAP. CUR was selected to further study its in vivo effect on B using in situ rat intestinal perfusion model. It was found that CUR could significantly increase the absorption of B via the inhibition on formation of its metabolites.. Our findings indicated that the intestinal metabolism of B could be inhibited by all the selected compounds with CUR being the most potent inhibitor, which could result in subsequent increase of absorption of B. The current study had significant implications for further investigation on the in vivo evaluations of the herb-drug and herb-herb interactions between B and selected compounds, especially CUR.

Topics: Acetaminophen; Administration, Oral; Alkaloids; Animals; Benzodioxoles; Biotransformation; Caco-2 Cells; Catechin; Chromatography, Liquid; Curcumin; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Flavanones; Glucuronides; Herb-Drug Interactions; Humans; Intestinal Absorption; Jejunum; Male; Medicine, Chinese Traditional; Perfusion; Piperidines; Plant Roots; Plants, Medicinal; Polyunsaturated Alkamides; Rats; Rats, Sprague-Dawley; Scutellaria baicalensis; Sulfates; Tandem Mass Spectrometry

Sixteen novel compounds; 3alpha-methoxyserrat-14-en-21beta-ol (1) and 3beta-methoxyserrat-14-en-21beta-ol (2) and their curcumin, kojic acid, quercetin, and baicalein conjugates (3)-(18) were designed, synthesized, and evaluated for in vitro anti-HIV-1 reverse transcriptase (RT) activity in infected C8166-CCR5 cells, a human CD4(+) T-lymphocyte cell line. Among them, kojic acid derivatives, 9-12 showed significant biological activity. In particular, the compound 13, the conjugate of two molecules of 3alpha-methoxyserrat-14-en-21beta-ol (1) and one molecule of kojic acid, exerted significant anti-HIV activity with an EC50 value of 0.12microg/mL.

Topics: Antiviral Agents; Cell Line; Cell Survival; Curcumin; Flavanones; HIV Infections; HIV-1; Humans; Molecular Structure; Pyrones; Quercetin; Reverse Transcriptase Inhibitors; RNA-Directed DNA Polymerase; T-Lymphocytes; Triterpenes; Viral Proteins

Baicalein, berberine, curcumin and hesperidin are the major components derived from Scutellaria baicalensis, Coptis japonica, Curcuma longa and Poncirus trifoliata, respectively. These plants have been used for the treatment of diverse chronic inflammatory diseases including respiratory disease in oriental medicine and their respective major components were reported to have various biological effects including anti-inflammatory activity. In the present study, we investigated whether these four natural products affect mucin release from airway goblet cells and compared the possible activities of these agents with the inhibitory action on mucin release by PLL and the stimulatory action by ATP. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled using 3H-glucosamine for 24 h and chased for 30 min in the presence of varying concentrations of each agent to assess the effects on 3H-mucin release. The results were as follows: (i) baicalein did not affect mucin release significantly; (ii) berberine, curcumin and hesperidin increased mucin release at the highest concentration (10 - 4 M); (iii) PLL inhibited and ATP increased mucin release. We conclude that berberine, curcumin and hesperidin can increase mucin release by directly acting on airway mucin-secreting cells and suggest that these agents be further studied for possible use as mild expectorants during the treatment of chronic airway diseases. Abbreviations. PLL:poly- L-lysine ATP:adenosine triphosphate HTSE:hamster tracheal surface epithelial DMSO:dimethylsulfoxide IL-12:interleukin-12 PBS:phosphate-buffered saline

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Berberine; Cell Line; Coptis; Cricetinae; Curcuma; Curcumin; Dose-Response Relationship, Drug; Flavanones; Flavonoids; Goblet Cells; Hesperidin; Male; Mucins; Phytotherapy; Plants, Medicinal; Poncirus; Scutellaria baicalensis; Trachea