- Email: [email protected]
Biological Activities and Health Effects of Terpenoids from Marine Fungi
CHAPTER
26 Biological Activities and Health Effects of Terpenoids from Marine Fungi Se-Kwon Kim*,†,1 and Yong-Xin Li*
Contents
Abstract
I. Introduction II. Diversity of Terpenoids Derived from Marine Fungi III. Health Benefits and Biological Activities of Terpenoids from Marine Fungi IV. Concluding Remarks References
410 410 411 412 412
Recently, a great deal of interest has been developed by the consumers toward natural bioactive compounds as functional ingredients in the nutraceutical, cosmeceutical, and pharmaceutical products due to their various health beneficial effects. Hence, it can be suggested that bioactive functional ingredients from marine bioresources and their by-products are alternative sources for synthetic ingredients that can contribute to consumer’s well-being, as a part of nutraceuticals and functional foods. Marine-derived fungi produce a vast array of secondary metabolites including terpenes, steroids, polyketides, peptides, alkaloids, and polysaccharides. These secondary metabolites serve many biopharmaceutical purposes. This chapter discusses about marine fungi-derived terpenoids and presents an overview of their beneficial health effects.
* Department of Chemistry, Marine Biochemistry Laboratory, Pukyong National University, Busan, Republic { 1
of Korea Marine Bioprocess Research Center, Pukyong National University, Busan, Republic of Korea Corresponding author: Se-Kwon Kim, E-mail address: [email protected]
Advances in Food and Nutrition Research, Volume 65 ISSN 1043-4526, DOI: 10.1016/B978-0-12-416003-3.00026-3
#
2012 Elsevier Inc. All rights reserved.
409
410
Se-Kwon Kim and Yong-Xin Li
I. INTRODUCTION Recently, much attention has been paid by the consumers toward natural bioactive compounds as functional ingredients in the diet, pharmaceuticals, and cosmeceuticals. Especially, bioactive compounds derived from marine organisms have been served as a rich source of health-promoting components (Kim and Wijesekara, 2010; Wijesekara and Kim, 2010; Wijesekara et al., 2010, 2011). Terpenoids, including more than 35,000 well-defined molecules, probably constitute the natural product family with the greater structural diversity. All terpenoids are synthesized from two five-carbon building blocks. Based on the number of the building blocks, terpenoids are commonly classified as monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), and sesterterpenes (C25). Numerous of these compounds possess well-known applications as drugs, cosmetics, perfumes, flavors, insecticides, herbicides, phytohormones, and many others. In recent years, a number of advances in terpenoid research have led, for example, to the discovery of a second biosynthetic pathway, namely methyl-erythritol phosphate pathway, usually present in bacteria and plants. Marine organisms produce a wide array of fascinating terpenoid structures distinguished by characteristic structural features. Certain structural classes, for example, cembrane, chamigrene, amphilectane skeletons, and unusual functional groups such as isonitrile, isothiocyanate, isocyanate, dichloroimine, and halogenated functionalities, occur predominantly in marine metabolites (Gross and Konig, 2006). In past two decades, natural product bioprospecting from the marine environment has resulted in hundreds of terpenoids with novel structures and interesting bioactivities, with more to be discovered in the future. These terpenoids display a wide range of biological activities against cancer, malaria, inflammation, and a variety of infectious diseases (viral and bacterial). This chapter focuses on terpenoids from marine-derived fungi and presents an overview of their biological activities with potential medicinal benefits.
II. DIVERSITY OF TERPENOIDS DERIVED FROM MARINE FUNGI Marine fungi contain a pronounced degree of structurally diversified terpenoids such as monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, triterpenes, steroids, and tetraterpenes. Meroterpenoids are most often isolated from fungi and marine organisms, but bacteria and higher plants produce such mixed biosynthesized products as well. Mixed
Health Effects of Terpenoids from Marine Fungi
411
polyketide–terpenoid-derived fungal natural products constitute the largest class of meroterpenoids, while those derived from orsellinic acid or its mono- and dimethyl derivatives are the most frequently isolated meroterpenoids from fungi, especially Penicillium and Aspergillus spp. Fungi, themselves, produce a range of interesting terpenoids including trichothecanes, the protoilludane group, cyathins, fussicoccanes, and many triterpenoids. Recent research into marine natural products has shown marine organisms are a prolific source of unusual terpenoids. Detailed reviews of marine natural products appear regularly, and a comprehensive review of terpenoids of marine invertebrates concentrates on their biological activity. Marine organisms continue to provide new carbon skeletons. Many substituents that are rarely found in natural products occur in marine terpenoids, for example, bromo- and chlorosubstituents in algal terpenoids and isonitrile and isothiocyanate substituents in sponge terpenoids. A chlorinated monoterpene has been found in marine-derived fungus, Tryblidiopycnis sp. (Huang et al., 2006). Sesquiterpenes have been reported from Dendryphiella sp., Penicillium sp., and Hansfordia sp. (Schneider et al., 1997). A marine-derived fungus Fusarium sp. secretes sesterterpenes as secondary metabolites (Renner et al., 1998). Moreover, triterpenes have been isolated from Phomopsis sp. (Li et al., 2008). In addition, steroids have been yielded by some marine-derived fungi, such as Rhizopus sp., Gymnascella sp., and Penicillium sp. (Ebel, 2010). The occurrence of tetraterpenoids or carotenoids has only rarely been studied for marine fungi, and the known carotenoids neurosporaxanthin, b-carotene, and torulene have been reported.
III. HEALTH BENEFITS AND BIOLOGICAL ACTIVITIES OF TERPENOIDS FROM MARINE FUNGI Antioxidants may have a positive effect on human health as they can protect human body against damage by reactive oxygen species (ROS), which attack macromolecules. Moreover, deterioration of some foods has been identified due to oxidation of lipids or rancidity and formation of undesirable secondary lipid peroxidation products. Lipid oxidation by ROS such as superoxide anion, hydroxyl radicals, and H2O2 also causes a decrease in nutritional value of lipid foods and affects their safety and appearance. Therefore, in food and pharmaceutical industries, many synthetic commercial antioxidants such as butylated hydroxytoluene, butylated hydroxyanisole, tert-butylhydroquinone, and propyl gallate have been used to retard the oxidation and peroxidation processes. However, the use of these synthetic antioxidants must be under strict regulation due to potential health hazards (Hettiarachchy et al., 1996). Hence, the search for natural antioxidants as safe alternatives is important in the food
412
Se-Kwon Kim and Yong-Xin Li
industry (Penta-Ramos and Xiong, 2001). Recently, there is a considerable interest in the food industry as well as pharmaceutical industry for the development of antioxidants from natural sources, such as marine flora and fauna. It has been demonstrated that marine fungi-derived terpenoids such as neurosporaxanthin, b-carotene, g-carotene, and torulene have potential antioxidant activity (Ebel, 2010). Antioxidant activity of terpenoid carotenoids have been determined by various methods such as 1,1-diphenyl-2picryl hydrazil radical scavenging, lipid peroxide inhibition, ferric reducing antioxidant power, nitric oxide scavenging, ABTS radical scavenging, and superoxide radical and hydroxyl radical scavenging assays. Marine fungiderived terpenoids could be used as a rich source of natural antioxidants with potential application in the food industry as well as in cosmetic and pharmaceutical areas. Several studies have reported that terpenoids derived from marine fungi have antiproliferative activity in several human cancer cell lines in vitro, as well as inhibitory activity of tumor growth in mice. In addition, they have antimetastatic activity by blocking the interactions between cancer cells and the basement membrane. Many species of marine-derived fungi contain significant quantities of complex structural terpenoids that have been shown to inhibit the proliferation of pathogenic microorganisms.
IV. CONCLUDING REMARKS Recent studies have provided evidence that terpenoids derived from marine fungi play a vital role in human health. The possibilities of designing new functional foods, pharmaceuticals, and cosmeceuticals reducing or regulating the chronic malfunctions are promising. Therefore, it can be suggested that due to valuable biological functions with medicinal beneficial effects, marine fungal-derived terpenoids have much potential as active ingredients for preparation of nutraceuticals and medicinal food products. Until now, most of the biological activities of marine-derived bioactive terpenoids have been observed in vitro or in mouse model systems. Therefore, further research studies are needed in order to investigate their activity in human subjects.
REFERENCES Ebel, R. (2010). Terpenes from marine-derived fungi. Mar. Drugs 8, 2340–2368. Gross, H. and Konig, G. M. (2006). Terpenoids from marine organisms: Unique structures and their pharmacological potential. Phytochem. Rev. 5, 115–141.
Health Effects of Terpenoids from Marine Fungi
413
Hettiarachchy, N. S., Glenn, K. C., Gnanasambandan, R., and Johnson, M. G. (1996). Natural antioxidant extract from fenugreek (Trigonella foenumgraecum) for ground beef patties. J. Food Sci. 61, 516–519. Huang, H. R., Xia, X. K., She, Z. G., Lin, Y. C., Vrijmoed, L. L. P., and Jones, E. B. G. (2006). A new chloro-monoterpene from the mangrove endophytic fungus Tryblidiopycnis sp. (4275). J. Asian Nat. Prod. Res. 8, 609–612. Kim, S. K. and Wijesekara, I. (2010). Development and biological activities of marine-derived bioactive peptides: A review. J. Funct. Foods 2, 1–9. Li, L. Y., Sattler, I., Deng, Z. W., Groth, I., Walther, G., Menzel, K. D., Peschel, G., Grabley, S., and Lin, W. H. (2008). A seco-oleane-type triterpenes from Phomopsis sp. (strain HK10458) isolated from the mangrove plant Hibiscus tiliaceus. Phytochemistry 69, 511–517. Penta-Ramos, E. A. and Xiong, Y. L. (2001). Antioxidative activity of whey protein hydrolysates in a liposomal system. J. Dairy Sci. 84, 2577–2583. Renner, M. K., Jensen, P. R., and Fenical, W. (1998). Neomangicols: Structures and absolute stereochemistries of unprecedented halogenated sesterterpenes from a marine fungus of the genus Fusarium. J. Org. Chem. 63, 8346–8354. Schneider, G., Anke, H., and Sterner, O. (1997). New secondary metabolites from a mycophilic Hansfordia species. Nat. Prod. Lett. 10, 133–138. Wijesekara, I. and Kim, S. K. (2010). Angiotensin-I-converting enzyme (ACE) inhibitors from marine resources. Mar. Drugs 8, 1080–1093. Wijesekara, I., Yoon, N. Y., and Kim, S. K. (2010). Phlorotannins from Ecklonia cava (Phaeophyceae): Biological activities and potential health benefits. Biofactors 36, 408–414. Wijesekara, I., Pangestuti, R., and Kim, S. K. (2011). Biological activities and potential health benefits of sulfated polysaccharides derived from marine algae. Carbohydr. Polym. 84, 14–21.
26 Biological Activities and Health Effects of Terpenoids from Marine Fungi Se-Kwon Kim*,†,1 and Yong-Xin Li*
Contents
Abstract
I. Introduction II. Diversity of Terpenoids Derived from Marine Fungi III. Health Benefits and Biological Activities of Terpenoids from Marine Fungi IV. Concluding Remarks References
410 410 411 412 412
Recently, a great deal of interest has been developed by the consumers toward natural bioactive compounds as functional ingredients in the nutraceutical, cosmeceutical, and pharmaceutical products due to their various health beneficial effects. Hence, it can be suggested that bioactive functional ingredients from marine bioresources and their by-products are alternative sources for synthetic ingredients that can contribute to consumer’s well-being, as a part of nutraceuticals and functional foods. Marine-derived fungi produce a vast array of secondary metabolites including terpenes, steroids, polyketides, peptides, alkaloids, and polysaccharides. These secondary metabolites serve many biopharmaceutical purposes. This chapter discusses about marine fungi-derived terpenoids and presents an overview of their beneficial health effects.
* Department of Chemistry, Marine Biochemistry Laboratory, Pukyong National University, Busan, Republic { 1
of Korea Marine Bioprocess Research Center, Pukyong National University, Busan, Republic of Korea Corresponding author: Se-Kwon Kim, E-mail address: [email protected]
Advances in Food and Nutrition Research, Volume 65 ISSN 1043-4526, DOI: 10.1016/B978-0-12-416003-3.00026-3
#
2012 Elsevier Inc. All rights reserved.
409
410
Se-Kwon Kim and Yong-Xin Li
I. INTRODUCTION Recently, much attention has been paid by the consumers toward natural bioactive compounds as functional ingredients in the diet, pharmaceuticals, and cosmeceuticals. Especially, bioactive compounds derived from marine organisms have been served as a rich source of health-promoting components (Kim and Wijesekara, 2010; Wijesekara and Kim, 2010; Wijesekara et al., 2010, 2011). Terpenoids, including more than 35,000 well-defined molecules, probably constitute the natural product family with the greater structural diversity. All terpenoids are synthesized from two five-carbon building blocks. Based on the number of the building blocks, terpenoids are commonly classified as monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), and sesterterpenes (C25). Numerous of these compounds possess well-known applications as drugs, cosmetics, perfumes, flavors, insecticides, herbicides, phytohormones, and many others. In recent years, a number of advances in terpenoid research have led, for example, to the discovery of a second biosynthetic pathway, namely methyl-erythritol phosphate pathway, usually present in bacteria and plants. Marine organisms produce a wide array of fascinating terpenoid structures distinguished by characteristic structural features. Certain structural classes, for example, cembrane, chamigrene, amphilectane skeletons, and unusual functional groups such as isonitrile, isothiocyanate, isocyanate, dichloroimine, and halogenated functionalities, occur predominantly in marine metabolites (Gross and Konig, 2006). In past two decades, natural product bioprospecting from the marine environment has resulted in hundreds of terpenoids with novel structures and interesting bioactivities, with more to be discovered in the future. These terpenoids display a wide range of biological activities against cancer, malaria, inflammation, and a variety of infectious diseases (viral and bacterial). This chapter focuses on terpenoids from marine-derived fungi and presents an overview of their biological activities with potential medicinal benefits.
II. DIVERSITY OF TERPENOIDS DERIVED FROM MARINE FUNGI Marine fungi contain a pronounced degree of structurally diversified terpenoids such as monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, triterpenes, steroids, and tetraterpenes. Meroterpenoids are most often isolated from fungi and marine organisms, but bacteria and higher plants produce such mixed biosynthesized products as well. Mixed
Health Effects of Terpenoids from Marine Fungi
411
polyketide–terpenoid-derived fungal natural products constitute the largest class of meroterpenoids, while those derived from orsellinic acid or its mono- and dimethyl derivatives are the most frequently isolated meroterpenoids from fungi, especially Penicillium and Aspergillus spp. Fungi, themselves, produce a range of interesting terpenoids including trichothecanes, the protoilludane group, cyathins, fussicoccanes, and many triterpenoids. Recent research into marine natural products has shown marine organisms are a prolific source of unusual terpenoids. Detailed reviews of marine natural products appear regularly, and a comprehensive review of terpenoids of marine invertebrates concentrates on their biological activity. Marine organisms continue to provide new carbon skeletons. Many substituents that are rarely found in natural products occur in marine terpenoids, for example, bromo- and chlorosubstituents in algal terpenoids and isonitrile and isothiocyanate substituents in sponge terpenoids. A chlorinated monoterpene has been found in marine-derived fungus, Tryblidiopycnis sp. (Huang et al., 2006). Sesquiterpenes have been reported from Dendryphiella sp., Penicillium sp., and Hansfordia sp. (Schneider et al., 1997). A marine-derived fungus Fusarium sp. secretes sesterterpenes as secondary metabolites (Renner et al., 1998). Moreover, triterpenes have been isolated from Phomopsis sp. (Li et al., 2008). In addition, steroids have been yielded by some marine-derived fungi, such as Rhizopus sp., Gymnascella sp., and Penicillium sp. (Ebel, 2010). The occurrence of tetraterpenoids or carotenoids has only rarely been studied for marine fungi, and the known carotenoids neurosporaxanthin, b-carotene, and torulene have been reported.
III. HEALTH BENEFITS AND BIOLOGICAL ACTIVITIES OF TERPENOIDS FROM MARINE FUNGI Antioxidants may have a positive effect on human health as they can protect human body against damage by reactive oxygen species (ROS), which attack macromolecules. Moreover, deterioration of some foods has been identified due to oxidation of lipids or rancidity and formation of undesirable secondary lipid peroxidation products. Lipid oxidation by ROS such as superoxide anion, hydroxyl radicals, and H2O2 also causes a decrease in nutritional value of lipid foods and affects their safety and appearance. Therefore, in food and pharmaceutical industries, many synthetic commercial antioxidants such as butylated hydroxytoluene, butylated hydroxyanisole, tert-butylhydroquinone, and propyl gallate have been used to retard the oxidation and peroxidation processes. However, the use of these synthetic antioxidants must be under strict regulation due to potential health hazards (Hettiarachchy et al., 1996). Hence, the search for natural antioxidants as safe alternatives is important in the food
412
Se-Kwon Kim and Yong-Xin Li
industry (Penta-Ramos and Xiong, 2001). Recently, there is a considerable interest in the food industry as well as pharmaceutical industry for the development of antioxidants from natural sources, such as marine flora and fauna. It has been demonstrated that marine fungi-derived terpenoids such as neurosporaxanthin, b-carotene, g-carotene, and torulene have potential antioxidant activity (Ebel, 2010). Antioxidant activity of terpenoid carotenoids have been determined by various methods such as 1,1-diphenyl-2picryl hydrazil radical scavenging, lipid peroxide inhibition, ferric reducing antioxidant power, nitric oxide scavenging, ABTS radical scavenging, and superoxide radical and hydroxyl radical scavenging assays. Marine fungiderived terpenoids could be used as a rich source of natural antioxidants with potential application in the food industry as well as in cosmetic and pharmaceutical areas. Several studies have reported that terpenoids derived from marine fungi have antiproliferative activity in several human cancer cell lines in vitro, as well as inhibitory activity of tumor growth in mice. In addition, they have antimetastatic activity by blocking the interactions between cancer cells and the basement membrane. Many species of marine-derived fungi contain significant quantities of complex structural terpenoids that have been shown to inhibit the proliferation of pathogenic microorganisms.
IV. CONCLUDING REMARKS Recent studies have provided evidence that terpenoids derived from marine fungi play a vital role in human health. The possibilities of designing new functional foods, pharmaceuticals, and cosmeceuticals reducing or regulating the chronic malfunctions are promising. Therefore, it can be suggested that due to valuable biological functions with medicinal beneficial effects, marine fungal-derived terpenoids have much potential as active ingredients for preparation of nutraceuticals and medicinal food products. Until now, most of the biological activities of marine-derived bioactive terpenoids have been observed in vitro or in mouse model systems. Therefore, further research studies are needed in order to investigate their activity in human subjects.
REFERENCES Ebel, R. (2010). Terpenes from marine-derived fungi. Mar. Drugs 8, 2340–2368. Gross, H. and Konig, G. M. (2006). Terpenoids from marine organisms: Unique structures and their pharmacological potential. Phytochem. Rev. 5, 115–141.
Health Effects of Terpenoids from Marine Fungi
413
Hettiarachchy, N. S., Glenn, K. C., Gnanasambandan, R., and Johnson, M. G. (1996). Natural antioxidant extract from fenugreek (Trigonella foenumgraecum) for ground beef patties. J. Food Sci. 61, 516–519. Huang, H. R., Xia, X. K., She, Z. G., Lin, Y. C., Vrijmoed, L. L. P., and Jones, E. B. G. (2006). A new chloro-monoterpene from the mangrove endophytic fungus Tryblidiopycnis sp. (4275). J. Asian Nat. Prod. Res. 8, 609–612. Kim, S. K. and Wijesekara, I. (2010). Development and biological activities of marine-derived bioactive peptides: A review. J. Funct. Foods 2, 1–9. Li, L. Y., Sattler, I., Deng, Z. W., Groth, I., Walther, G., Menzel, K. D., Peschel, G., Grabley, S., and Lin, W. H. (2008). A seco-oleane-type triterpenes from Phomopsis sp. (strain HK10458) isolated from the mangrove plant Hibiscus tiliaceus. Phytochemistry 69, 511–517. Penta-Ramos, E. A. and Xiong, Y. L. (2001). Antioxidative activity of whey protein hydrolysates in a liposomal system. J. Dairy Sci. 84, 2577–2583. Renner, M. K., Jensen, P. R., and Fenical, W. (1998). Neomangicols: Structures and absolute stereochemistries of unprecedented halogenated sesterterpenes from a marine fungus of the genus Fusarium. J. Org. Chem. 63, 8346–8354. Schneider, G., Anke, H., and Sterner, O. (1997). New secondary metabolites from a mycophilic Hansfordia species. Nat. Prod. Lett. 10, 133–138. Wijesekara, I. and Kim, S. K. (2010). Angiotensin-I-converting enzyme (ACE) inhibitors from marine resources. Mar. Drugs 8, 1080–1093. Wijesekara, I., Yoon, N. Y., and Kim, S. K. (2010). Phlorotannins from Ecklonia cava (Phaeophyceae): Biological activities and potential health benefits. Biofactors 36, 408–414. Wijesekara, I., Pangestuti, R., and Kim, S. K. (2011). Biological activities and potential health benefits of sulfated polysaccharides derived from marine algae. Carbohydr. Polym. 84, 14–21.