Mária Báthori

Phytoecdysteroids and anabolic-androgenic steroids--structure and effects on humans.

Phytoecdysteroids are structural analogs of the insect molting hormone ecdysone. Plants comprise rich sources of ecdysteroids in high concentration and with broad structural diversity. Ecdysteroids have a number of proven beneficial effects on mammals but the hormonal effects of ecdysteroids have been proven only in arthropods. Their structures are somewhat similar to those of the vertebrate steroid hormones but there are several structural differences between the two steroid groups. Despite of these essential structural differences, ecdysteroids exert numerous effects in vertebrates that are similar to those of vertebrate hormonal steroids, and they may serve as effective anabolic, hepatoprotective, immunoprotective, antioxidant and hypoglycemic agents. Ecdysteroids do not bind to the cytosolic steroid receptors, instead, they are likely to influence signal transduction pathways, like the anabolic steroids, possibly via membrane bound receptors. The application of phytoecdysteroids is a promising alternative to the use of anabolic-androgenic steroids because of the apparent lack of adverse effects. The prospective use of phytoecdysteroids may extend to treatments of pathological conditions where anabolic steroids are routinely applied. One of the most cited aspects of phytoecdysteroid application (on the Internet) is the increase of muscle size. However in this field too stringent research is needed as an adequate cytological explanation is not yet available for the anabolic. This paper reports on the most important structural differences between androgenic hormones, their synthetic analogs and ecdysteroids. The anabolic/hormonal effects and the possible mechanisms of action of these compounds are also discussed as concerns the skeletal muscle.

Phytoecdysteroids - From Isolation to Their Effects on Humans

An overview is given on both well-known and recently discovered phytoecdyteroids including a sophisticated isolation scheme and notable physiological and pharmacological effects of ecdysteroids on vertebrates. The isolation of pure ecdysteroids has been improved by the use of low-pressure reversed-phase chromatography. An optimized combination of preliminary purification and chromatographic separations results in pure ecdysteroids. Structural elucidation has been done using spectroscopic methods, however, the final proof of the steric structure is rendered using x-ray crystallography. Ecdysteroid containing preparations show a boom and both OTC products and numerous preparation techniques can be found using the Internet. This paper will give a review on the kaleidoscope of pharmacological effects attributed to the ecdysteroids, such as: An increase of protein synthesis (for body-building, AIDS, patients with neoplasm disease, etc.), and other body functions; Antidepressant effect; Shielding the body from stress, and improve the physical and sexual performance; Prevention from infections and certain diseases. A list of recent offers of ecdysteroid-containing products will also be given. The perspective use of ecdysteroids is promising in genetics. Steroid regulation of programmed cell death during development and differentiation has recently come to the limelight. Murine model of human diseases and its influencing with ecdysteroids are detailed.

Crystal structures of ecdysteroids: the role of solvent molecules in hydrogen bonding and isostructurality.

Three crystal forms of the steroid 20-hydroxyecdysone were identified by single-crystal X-ray diffraction analysis: a solvent-free modification, a methanol solvate hydrate and a trihydrate. The structure of a closely related steroid, polypodine B (the 5,20-dihydroxy derivative of ecdysone), was determined in its monohydrate form. Since the unit-cell volume of unsolvated 20-hydroxyecdysone was found to be considerably smaller than that of ecdysone [Huber & Hoppe (1965). Chem. Ber. 98, 2403-2424], a new structure determination of ecdysone was performed, which confirmed the unexpected difference between the unit-cell volumes. The crystals of ecdysone and 20-hydroxyecdysone are isostructural, while the mixed solvate of 20-hydroxyecdysone is homostructural with the hydrate of polypodine B. A detailed analysis of the hydrogen-bond networks in these closely related crystal pairs highlights their packing similarities, demonstrates the role of solvent molecules, and explains the unexpectedly small cell volume of 20-hydroxyecdysone.

Significant activity of ecdysteroids on the resistance to doxorubicin in mammalian cancer cells expressing the human ABCB1 transporter.

Multidrug resistance (MDR) is a major cause of failure of cancer chemotherapy. Fifty-eight ecdysteroids, herbal analogues of the insect molting hormone and their semisynthetic derivatives, were tested for their activity against L5178 mouse T-cell lymphoma cells (non-MDR) and their subcell line transfected with pHa MDR1/A retrovirus overexpressing the human ABCB1 efflux pump (MDR cell line). The compounds showed very low antiproliferative activities but modulated the efflux of rhodamine 123 mediated by the ABCB1 transporter. Roughly depending on the polarity, mild to strong synergism or antagonism was observed by combining ecdysteroids with doxorubicin, and specific structure-activity relationships were also found. Our results show the effect of ecdysteroids on MDR cancer cells for the first time. Less polar derivatives may serve as valuable leads toward a potent and safe resistance modulator. Biological significance of the resistance-increasing activity of the most abundant phytoecdysteroids including 20-hydroxyecdysone is yet to be clarified.

Application of combined chromatographic techniques in the screening and purification of ecdysteroids

SummaryPlants were found to contain ecdysteroids in concentrations in the order of 0.1% which are higher than those of the insects, and are adequate for the preparative production of ecdysteroids.A TLC screening method is elaborated for the qualitative and semiquantitative analysis of the ecdysteroid content of plants. The combined TLC method differentiates several characteristic ecdysteroids ranging from the apolar 2-deoxyecdysone to the polar 20,26-dihydroxyecdysone. A preparative purification method was developed consisting of solvent extraction, precipitation, crystallization and column liquid chromatography; these procedures permit the isolation of the main ecdysteroids in gram quantities. In some cases, droplet counter-current chromatography was also applied.Altogether, the isolation of thirteen ecdysteroids from five different plant species was accomplished by using a fast, simple and low-cost procedure, resulting in pure substances.

26-Hydroxylated Ecdysteroids from Silene viridiflora

Four new 26-hydroxylated phytoecdysteroids, 2-deoxy-5,20,26-trihydroxyecdysone (1), 5,20,26-trihydroxyecdysone 20,22-acetonide (2), 2-deoxy-5,20,26-trihydroxyecdysone 20,22-acetonide (3), and 20,26-dihydroxyecdysone 20,22-acetonide (4), were isolated from the herb Silene viridiflora, and their structures were elucidated by means of one- and two-dimensional NMR and mass spectrometry.

Two-dimensional thin-layer chromatography of plant ecdysteroids

SummaryTwo-dimesional thin-layer chromatography has been used to screen plant samples for ecdysteroids. Satisfactory separations were obtained even in the presence of substantial impurities and for mixtures containing many ecdysteroids. Normal-phase silica and octadecyl silica plates were used to differntiate apolar and polar ecdysteroids, respectively. The major advantages of thin-layer chromatography are multiple detection, which enables specific detection of the ecdysteroids. Use of a small amount of water in the mobile phase in the fist dimension, the a water-free mobile phase in the second dimension, can afford favorable separations.

Phytoecdysteroids and Vitamin D Analogues - Similarities in Structure and Mode of Action

Phytoecdysteroids are plant steroids with identical or analogue structures to the molting hormone in arthropods. The ecdysteroids exert several beneficial effects on mammals, from which the most cited and deeply examined one is the increase of muscle size and strength. This shows similarities with the mode of action of the androgenic steroids but the ecdysteroids do not bind to the cytoplasmic/nuclear receptor of the mammalian steroids. These findings led to the hypothesis that ecdysteroids possibly bind to membrane bound receptors and they are likely to influence signal transduction pathways. Probably because of their closely related chemical structures, ecdysteroids exert some similar effects in vertebrates to those of the hormone 1 alpha,25-dihydroxyvitamin D3 (1,25D) which is produced in the kidney from 25-hydroxyvitamin D3, after being converted in the liver from Vitamin D3. 1,25D generates biological responses via both genomic and rapid, nongenomic mechanisms. Structure-activity relationship studies with different Vitamin D analogues could open the possibility to show that the two ways of action (genomic and nongenomic) can be influenced separately. The connection between the Vitamin D status and muscle function is already well-described in clinical studies, and several efforts have been made to evaluate the effect of Vitamin D deficiency or supplementation on muscle morphological changes and the underlying molecular mechanisms. This paper aims to summarize the main structural commonalities between the ecdysteroids, 1,25D and other Vitamin D analogues. The similarities in their effects and pathways that might be involved in the mechanism of action of these compounds will also be discussed.

Three new steroids from the roots of Serratula wolffii

Investigation of the methanol extract of the roots of Serratula wolffii resulted in an ecdysone-related compound, 2beta,3beta,20R,22R,25-pentahydroxy-5beta-cholest-6,8(14)-dien (1), a new ecdysteroid, 24-methylene-shidasterone (2), the known compound stachysterone B (3) and its 14,15-alpha-epoxide (4), a novel natural product. The structures of compounds 1-4 were established by spectral analysis ((1)H NMR, (13)C NMR, COSY, NOESY, HMQC, HMQC-TOCSY and HMBC).

Metabolic Effects of Mulberry Leaves: Exploring Potential Benefits in Type 2 Diabetes and Hyperuricemia

The leaves of Morus alba L. have a long history in Traditional Chinese Medicine and also became valued by the ethnopharmacology of many other cultures. The worldwide known antidiabetic use of the drug has been suggested to arise from a complex combination effect of various constituents. Moreover, the drug is also a potential antihyperuricemic agent. Considering that type 2 diabetes and hyperuricemia are vice-versa in each others important risk factors, the use of mulberry originated phytotherapeutics might provide an excellent option for the prevention and/or treatment of both conditions. Here we report a series of relevant in vitro and in vivo studies on the bioactivity of an extract of mulberry leaves and its fractions obtained by a stepwise gradient on silica gel. In vivo antihyperglycemic and antihyperuricemic activity, plasma antioxidant status, as well as in vitro glucose consumption by adipocytes in the presence or absence of insulin, xanthine oxidase inhibition, free radical scavenging activity, and inhibition of lipid peroxidation were tested. Known bioactive constituents of M. alba (chlorogenic acid, rutin, isoquercitrin, and loliolide) were identified and quantified from the HPLC-DAD fingerprint chromatograms. Iminosugar contents were investigated by MS/MS, 1-deoxynojirimycin was quantified, and amounts of 2-O-alpha-D-galactopyranosyl-1-deoxynojirimicin and fagomine were additionally estimated.