2,2′-Dimethoxy-4,4′-[rel-(2R,3S)-2,3-di­methylbutane-1,4-diyl]diphenol

The title mol­ecule, C20H26O4, commonly known as meso-dihydro­guaiaretic acid, is a naturally occurring lignan extracted from Larrea tridentata and other plants. The mol­ecule has a noncrystallographic inversion center situated at the midpoint of the central C—C bond, generating the meso stereoisomer. The central C—C—C—C alkyl chain displays an all-trans conformation, allowing an almost parallel arrangement of the benzene rings, which make a dihedral angle of 5.0 (3)°. Both hydr­oxy groups form weak O—H⋯O—H chains of hydrogen bonds along [100]. The resulting supra­molecular structure is an undulating plane parallel to (010)

A microfluidic-FCS platform for investigation on the dissociation of Sp1-DNA complex by doxorubicin

The transcription factor (TF) Sp1 is a well-known RNA polymerase II transcription activator that binds to GC-rich recognition sites in a number of essential cellular and viral promoters. In addition, direct interference of Sp1 binding to DNA cognate sites using DNA-interacting compounds may provide promising therapies for suppression of cancer progression and viral replication. In this study, we present a rapid, sensitive and cost-effective evaluation of a GC intercalative drug, doxorubicin (DOX), in dissociating the Sp1–DNA complex using fluorescence correlation spectroscopy (FCS) in a microfluidic system. FCS allows assay miniaturization without compromising sensitivity, making it an ideal analytical method for integration of binding assays into high-throughput, microfluidic platforms. A polydimethylsiloxane (PDMS)-based microfluidic chip with a mixing network is used to achieve specific drug concentrations for drug titration experiments. Using FCS measurements, the IC(50) of DOX on the dissociation of Sp1–DNA complex is estimated to be 0.55 μM, which is comparable to that measured by the electrophoretic mobility shift assay (EMSA). However, completion of one drug titration experiment on the proposed microfluidic-FCS platform is accomplished using only picograms of protein and DNA samples and less than 1 h total assay time, demonstrating vast improvements over traditional ensemble techniques

Lignans: quantitative analysis of the research literature

The current study provides a comprehensive overview and analysis of the lignan literature. Data for the current study were extracted from the electronic Web of Science Core Collection database via the search string TOPIC = (lignan*) and processed by the VOSviewer software. The search yielded 10,742 publications. The ratio of original articles to reviews was 14.6:1. Over 80% of the analyzed papers have been published since the year 2000 and nearly 50% since the year 2010. Many of the publications were focused on pharmacology, chemistry, and plant sciences. The United States and Asian countries, such as China, Japan, South Korea, and India, were the most productive producers of lignan publications. Among the 5 most productive institutions was the University of Helsinki in Finland, the country that ranked 9th. Nineteen journals collectively published 3,607 lignan publications and were considered as core journals. Their impact factor did not correlate with the proportion of uncited papers. Highly cited publications usually mentioned phytoestrogen, isoflavone, daidzein, enterodiol, enterolactone, equol, genistein, and isoflavonoid. Cancer (e.g., breast cancer), cardiovascular disease, and antioxidation were the major themes. Clinical trials were estimated to contribute to 0.21.1% of the analyzed body of literature, so more of them should be conducted in the future to substantiate the beneficial effects and optimal dose of lignan intake in humans. Moreover, researchers can refer to these findings for future research directions and collaborations.AA acknowledges the support by the Polish KNOW (Leading National Research Centre) Scientific Consortium “Healthy Animal—Safe Food,” decision of the Ministry of Science and Higher Education No. 05-1/KNOW2/2015. EN and AS acknowledge the support of the research project Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D18000140007.info:eu-repo/semantics/publishedVersio

Antiallergic activity of Tylophora sylvatica

Tylophora sylvatica is a medicinal plant successfully used in African folk medicine for the management of various allergic conditions. This plant was investigated using screening methods suitable for the isolation of the active constituents which inhibit the release of chemical mediators of allergic reactions. Chromatographic studies led to the characterization of two classes of active principles: known fatty acids (oleic, linoleic and linolenic acids) with 0.064% yield; two novel glycosides, tylophoroside and acetyltylophoroside, having 0.008% and 0.0113% yields, respectively. Mild acidic hydrolysis of these glycosides generated an aglycone termed tylogenin which appears to be a biodegraded steroid. The antiallergic activity of these compounds was further assessed for inhibition of antigen-induced mediator release by the rabbit basophil-dependent serotonin release(B08R) and human leukocyte-dependent histamine release(LDHR) assay systems. The activity of tylogenin was found to increase with the incubation time. In the B08R assay, at optimal incubation time, tylogenin with a geom mean IC₅₀ of 38.9 μM, (geom SD=1.3, n=5), exhibited an activity similar to that of the fatty acids. This activity differed significantly (p<0.05) from that of the standard corticosteroids, dexamethasone (geom mean IC50=912 μM, geom 80=2.8, n=5) and prednisolone (geom mean IC₅₀=1071.5 μM, geom 80=3.2, n=4). In the LOHR assay, the activity of tylogenin (geom mean IC₅₀=49.0 μM, geom 80=1.6, n=5) significantly exceeded that of dexamethasone (geom mean IC₅₀=257 μM geom 80=8.1), (p<0.05). Tylophora compounds were also investigated for a potential cardiac activity based on their structural similarity with cardiac glycosides. In the Na+/K+ ATPase assay, Tylophora compounds displayed a dose-dependent inhibitory activity of the sodium pump enzyme. However, these compounds were 100 times less active than ouabain (gem meanIC₅₀=2.3 μM, geom SD=1.4, n=5). Additional studies indicated that the standard cardenolides had no antiallergic activity at concentrations ranging from 0.1 nM to 300 μM, and standard corticosteroids had no ATPase inhibitory activity. Thus, Tylophora compounds were shown to possess an apparently unique dual activities. These compounds were also found to be devoid of cytotoxicity by dye exclusion and may represent a new class of agents with dual antiallergic and cardiac activities

Creosote bush lignans for human disease treatment and prevention: Perspectives on combination therapy

The medicinal properties of the most successful plant in the deserts of the western hemisphere, the creosote bush (Larrea tridentata), are evidenced by the long traditional usage of the plants by the Native Americans Indian tribes in Southwestern North America and the Amerindians from South America. The plant is rich in simple bisphenyl lignans and tricyclic lignans known as cyclolignans. These compounds are responsible for many of the pharmacological activities of extracts of the plants. Some of these activities, namely antiherpes, antioxidant, antifungal, and anti-inflammatory, were known a century ago. Only recently have further studies revealed other crucial activities of the same plant molecules as powerful agents against human immunodeficiency virus, human papillomavirus, cancer, neurodegenerative diseases, and symptoms of aging. Molecular mechanisms underlying the antiviral and anticancer activities have been elucidated and involve the inhibition of SP1 dependent gene transcription. This review summarizes the recent findings on creosote bush lignans. We introduce the concept of a cocktail of safe well-characterized natural products from the creosote bush that would represent a bridge between oriental herbal medicines and Western drug-based therapies