Medicinal properties of substances occurring in higher basidiomycetes mushrooms: current perspectives

Medicinal Properties of Substances Occurring in Higher
Basidiomycetes Mushrooms: Current Perspectives
International Journal of Medicinal Mushrooms, Vol 1, 47-50, (1999)
Solomon P. Wasser, Alexander L. Weis
International Center for Cryptogamic Plants and Fungi, Institute of Evolution, University of Haifa, Israel
International Myko Biologics, Inc., San Antonio, TX, USA
M.G. Kholodny Institute of Botany, National Academy of Sciences of Ukraine, Kiev, Ukraine

The major cause of death in the Western countries is coronary artery disease. A primary risk
factor is hypercholesterolelmia, which contributes to hardening of the arteries. In humans, 50% or more of the total cholesterol is derived from de novo synthesis (Rosenfeld, 1989; Steinberg et al., 1989). Clinical intervention studies have demonstrated the therapeutic importance of correcting the hypercholesterolemia. The initial step in lowering cholesterol is a special diet low in fat and saturated fatty acids and rich in crude fibers. Drug therapy is the next step. The best-known pharmacologic agent that was approved in 1987 is lovastatin (mevinolin) and its analogues (Endo, 1988). This low molecular weight substance is the competitive inhibitor of HMG Co A reductase, the key enzyme in cholesterol metabolism that catalyzes the reduction of HMG CoA into mevalonate. The best known organisms for potential producers of lovastatin from edible higher Basidiomycetes mushrooms are species of the genus Pleurotus (Gunde-Cimerman et al;., 1993a,b; Gunde-Cimerman and Cimerman, 1995). The presences of the inhibitor was determined in four species: P. ostreatus, P. cornucopiae, P. eryngii, and P. sapidus. The highest content of lovastatin was found in the fruiting bodies of the P. ostreatus. The appearance of the inhibitor during the development of the fruiting bodies was found in the vegetative mycelium, in the primordial, and in different parts of fruiting bodies of different sizes; less lovastatin was found in stipes when compared with pileus (fig. 5) or in nature stages in the lamellae and basidioiospores (Gund-Cimerman and Cimerman, 1995) It was shown that lovastatin at the beginning of mushroom growth is unfortunately distributed in small fruit bodies, and there are no substantial differences between the pileus and the stipe. During fruit body growth, the majority of lovastatin is first transferred to the pileus and later the lamellae. Mature fruiting bodies have a diameter of approximately 15 cm and disperse large amounts of basidiospores. These contain less lovastatin in the lamellae when compared with the smaller, 10 cm diameter; less mature mushrooms this transfer is still incomplete (Gunde-Cimerman and cimerman, 1995). In a series of experiments conducted by Bobek et al. (1991a,b, 1993), it has been found that the addition of 2% to 4% of P. ostreatus to the hyperlipidemic diet efficiently prevented accumulation of C and triacly-glycerols in both sera and livers of animals with exogenous, endogenous, or genetically induced hyperlipidemia. VLDL cholesterol had the dominant role in the reduction of serum C up to 80% induced by the whole mushroom pr its water and 30% of ethanol extracts. The authors attributed this effect to the fiber pulp complex of the oyster mushroom, which limits the resorption of C and gastrointestinal tract, and to an undefined substance which influences, as well, metabolisms outside the phase of resorption. (Bobek et al., 1991a,b, 1993). Ryong et al. (1989) have tested alcohol and water extracts of 20 different edible mushrooms in tissue primary culture of cells isolated from atherosclerotic action. Four mushrooms also decreased atherogenic effects by 20% to 40% in sera collected from coronary heart disease patients. In these experiments the effect of dietary fibers was excluded and the efficiency was attributed to an unknown active component (Ryong et al., 1989). Authors suggest that this unknown substance is lovastatin, which can be found in high quantities in the fruiting bodies of various cultured Pleurotus species. Therefore, mature fruiting bodies of P. ostreatus could be recommended for consumption as a natural cholesterol-lowering agent. Lovastatin appears early in the life cycle of the mushroom, in the mycelia from which primordial are being formed. It is known that Lentinus edodes is able to lower BSC via a factor known as eritadenine (also known as "Lentinacin" or "Lentysine") was isolated from an 80% ethanol extract of Shiitake mushroom fruiting bodies by absorption on a Amberlite IR-120 (H+) column, followed by elution with 4% NH 4 OH (chibata et al., 1969). A crystalline product had the following properties: mp 261-263° C, C9H11O4N5, MW 253, 261 .5 nm (E=14,508)m, Nasapt mp 266 –268 C (decomposition), {a} D + 45.5 (C=1, H2O). Hydrolyses in 6N HCI at 110 C for 72h yielded glycine and new amino acid. Eritadenine apparently reduces serum cholesterol in mice. Its action is not inhibition of cholesterol biosynthesis, but rather the acceleration of excretion of ingested cholesterol and its metabolic decompositions (Makita et al., 1972, cited in Mizuno, 1995a,b). Apparently, Eritadenine reduces BSC in mice, not by the inhibition of cholesterol biosynthesis but by the acceleration of the excretion of ingested cholesterol and its metabolic decomposition (S. Suzuki and Oshima, 1974, 1976; Higushi et al., 1978; Yagishita et al., 1977, 1978). Eritadenine has been shown to lower blood levels of cholesterol and lipids in animals (Yamamura and Cochran, 1976) Added to the diet of rats, Eritadenine (0.005%) caused a 25% decrease in total cholesterol in as little as one week (Chibata et al., 1969) The cholesterol-lowering activity of this substance is more pronounced in rats fed a high fat diet than those on a low-fat diet (Rokujo et al., 1969). Although feeding studies with humans have indicated a similar effect, further systematic research is needed. S. Suzuki and Ohshima (1974, 1976) have shown that dietary shiitake mushroom lowered BSC levels. Various studies have confirmed (Kimoto et al., 1976;m Kabir and Kmura, 1989) that shiitake mushroom can lower both blood pressure and free cholesterol in plasma, as well as accelerate accumulation of lipids in the liver, by removing them from circulation. Nucleic acid compound in L. edodes extract have been shown a strong platelet agglutination inhibitive effect (antithrombotic activity). An extract of L. edodes with antithrombotic activity was studied by high-performance liquid chromatography (HPLC). ATP, ADP, UDPG, 5'-GMP, 5'UMP, 5'-CMP, 5'-AMP, uridine, eritadenine, and deoxylentinacin were identified. More antithrombotic activity was shown by 5'-AMP, 5'GMP, eritadenine, and deoxylentinacin (Hokama and Hokama, 1981; Kabir and Kimura, 1989). Auriculari auricula-judae has shown the following effects and activities in studies on mice and rats: anticoagulation, lowered total cholesterol, triglyceride, and lipid levels (Chen, 1989; Sheng and Chen, 1990); and antiaggregatory activity on blood platelets, which might make it beneficial for coronary heart disease (Agarwal et al., 1982). This mushroom is traditionally used as an immune tonic. Tremella fuciformis polysaccharides and spore extracts have demonstrated antilipemic activity. T. fuciformis lowered the LDL- cholesterol in rats fed the preparation, which also contained butter sugar, and egg yolks, by 30% over controls (Nakajima, et al., 1989). T. fuciformis polysaccharides prolonged thrombus formation, reduced thrombus size, reduced blood platelet adherence, blood viscosity, and positively influenced other blood coagulation parameters of survival in mice (Sheng and Chen, 1990). Animal studies on Armillriella mellea demonstrated that it decreases heart rate, reduces peripheral and coronary vascular resistance, and increases cerebral blood flow (Chang and But, 1986). AMG-1-a compound isolated from this mushroom exhibits a cerebral-protective effect (Watanabe et al., 1990), and increases coronary oxygen efficiency without altering blood pressure (Y. Zhang et al., 1985) Grifola frondosa reduced blood pressure in rats without changing plasma HDL levels (Kyoto et al., 1988). Adachi and coworkers (1988) found a blood pressure lowering effect with the powder of G. frondosa fed to hypertensive rats in their normal food. The effect was of rapid onset, short lived and dose dependent. An aqueous extract of G. frondosa also reduced serum cholesterol levels in rats (Mizuno, 1977). A glycoprotein obtained from submerged cultured mycelial biomass of Trametes sp. showed activity (in animal and in vitro test). Against experimental hypertension and thrombosis. The protein inhibits blood platelet aggregation and is antihyperlipemic and antiarrhythmic. (Ikuzawa, 1985) Trametes versicolor has been shown to lower serum chooesterol in animals (Yagishita et al., 1977). PKS ( beta-glucan protein) from T. versicolor has been used in clinical studies. Tsukagoshi et al (1984) have reported that PSK causes a significant decrease in LDL cholesterol in hyperlipidemia (stage 11a ) patients. The Volvariella volvacea cardioactive proteins are know to lower blood pressure (Cochran, 1978; Yao et al., 1998).


Microsoft word - vol8n15a5.doc

VAN WEEZEL, Alex. "El delito de infracción de una patente por equivalencia o por imitación". Polít. crim. Vol. 8, Nº 15 (Julio 2013), Art. 5, pp. 170 - 209. El delito de infracción de una patente por equivalencia o por imitación Prof. Dr. Alex van Weezel* Pontificia Universidad Católica de Chile Resumen La doctrina de los equivalentes y sus limitaciones configuran de un modo determinante el equilibrio entre la certeza de la protección que brinda una patente y la restricción de dicha protección que resulta indispensable para el bien común. Este equilibrio se encuentra en la base del sistema de la propiedad industrial y la tensión entre sus dos extremos caracteriza al bien jurídico protegido por los delitos de infracción de una patente. El presente trabajo procura mostrar, a la luz del derecho comparado, la relevancia de esta doctrina para la interpretación de los tipos penales previstos en el art. 52 de la Ley 19.039, concretamente en lo que respecta las expresiones "invento patentado", "procedimiento patentado" e "imiten un invento con solicitud de patente en trámite", cuando se trata contrastar el invento o procedimiento patentado (o con solicitud de patente en trámite) con un invento o procedimiento presuntamente infractor. Palabras clave Patente de invención, doctrina de los equivalentes, delitos contra la propiedad industrial, interpretación de reivindicaciones, arte previo. Abstract The doctrine of equivalents and its limitations are a determining element in the balance between the certainty of the protection granted by a patent and the restriction of such protection so far as it is convenient for the community. This balance is at the base of the industrial property system and the tension between its two ends characterizes the legally protected object in the crimes of patent infringement. This paper seeks to show, in the light of comparative law, the relevance of this doctrine for the interpretation of the crimes under Article 52 of Law Nr. 19.039, in particular as regards the terms "patented invention", "patented process" and "imitate an invention patent application pending" when it comes to contrast a patented (or patent application pending) invention or process with an allegedly infringing invention or process.


32_RODRIGUEZ MARADIAGA_pp_484-495.QXD_Layout 1 07/02/13 16:06 Pagina 484 The Global Quest for Tranquillitas Ordinis. Pacem in Terris, Fifty Years Later Pontifical Academy of Social Sciences, Acta 18, 2013 Aproximación geopolítica a la justiciaen un mundo globalizado