Primitive medical records indicate that extracts from many species of plants have been used for treating a variety of human health problems for perhaps the past 3500 years (Machlin, 1992; Pettit et al., 1993, 1995). In modern times the practice has continued, with numerous chemotherapeutic agents being isolated (Gabrielsen et al., 1992a). Until recently, however, no studies had investigated the effects of atmospheric CO2 enrichment on specific plant compounds of direct medicinal value.
This situation changed when Stuhlfauth et al. (1987) studied the individual and combined effects of atmospheric CO2 enrichment and water stress on the production of secondary metabolites in the woolly foxglove (Digitalis lanata EHRH), which produces the cardiac glycoside digoxin that is used in the treatment of cardiac insufficiency. Under controlled well-watered conditions, a near-tripling of the air's CO2 content increased plant dry weight production in this medicinal plant by 63%, while under water-stressed conditions the CO2-induced dry weight increase was 83%. In addition, the concentration of digoxin within the plant dry mass was enhanced by 11% under well-watered conditions and by 14% under conditions of water stress.
In a subsequent whole-season field experiment, Stuhlfauth and Fock (1990) obtained similar results. A near-tripling of the air's CO2 concentration led to a 75% increase in plant dry weight production per unit land area and a 15% increase in digoxin yield per unit dry weight of plant, which combined to produce an actual doubling of total digoxin yield per hectare of cultivated land.
In another study, Idso et al. (2000) evaluated the response of the tropical spider lily (Hymenocallis littoralis Jacq. Salisb.) to elevated levels of atmospheric CO2 over four growing seasons. This plant has been known since ancient times to possess anti-tumor activity; and in modern times it has been shown to contain constituents that are effective against lymphocytic leukemia and ovary sarcoma (Pettit et al., 1986). These same plant constituents have also been proven to be effective against the U.S. National Cancer Institute's panel of 60 human cancer cell lines, demonstrating greatest effectiveness against melanoma, brain, colon, lung and renal cancers (Pettit et al., 1993). In addition, it exhibits strong anti-viral activity against Japanese encephalitis and yellow, dengue, Punta Tora and Rift Valley fevers (Gabrielsen et al., 1992a,b).
The results of the Idso et al. study showed that a 75% increase in the air's CO2 concentration produced a 56% increase in the spider lily's belowground bulb biomass, where the disease-fighting substances are found. In addition, for these specific substances, they observed a 6% increase in the concentration of a two-constituent (1:1) mixture of 7-deoxynarciclasine and 7-deoxy-trans-dihydronarciclasine, an 8% increase in pancratistatin, an 8% increase in trans-dihydronarciclasine, and a 28% increase in narciclasine. Averaged together and combined with the 56% increase in bulb biomass, these percentage concentration increases resulted in a total mean active-ingredient increase of 75% for the plants grown in air containing 75% more CO2.
In another study, Zobayed and Saxena (2004) worked with St. Johns' wort, a perennial herb native to Europe and West Asia that has been used as a medicinal plant for the treatment of mild to moderate depression, inflammation and wound healing (Brolis et al., 1998; Stevinson and Ernst, 1999), and which has been reported to be a potential source for anticancer, antimicrobial and antiviral medicines (Schempp et al., 2002; Pasqua et al., 2003). More specifically, they grew shoots of the plant for 42 days under well watered and fertilized conditions in a greenhouse, where the air's CO2 concentration averaged 360 ppm during the photoperiod, and in computer-controlled environment chambers maintained at a mean photoperiod CO2 concentration of 1000 ppm, with all other environmental conditions being comparable between the two treatments.
On the final day of the study, the researchers determined that the net photosynthetic rates of the plants in the CO2-enriched chambers were 124% greater than those of the plants growing in ambient air, and that their dry weights were 107% greater. In addition, the extra 640 ppm of CO2 in the high-CO2 treatment increased plant concentrations of hypericin and pseudohypericin (two of the major health-promoting substances in the plants) by just over 100%. Consequently, the 180% increase in the air's CO2 content more than doubled the dry mass produced by the well-watered and fertilized St. John's wort plants, while it also more than doubled the concentrations of hypericin and pseudohypericen found in their tissues, which means that the CO2 increase more than quadrupled the total production of these two health-promoting substances.
Mosaleeyanon et al. (2005) also studied St. John's wort, growing well watered and fertilized seedlings for 45 days in controlled environment chambers at low, medium and high light intensities (100, 300 and 600 µmol m-2 s-1, respectively) at atmospheric CO2 concentrations of 500, 1000 and 1500 ppm. On day 43, they measured net photosynthetic rates in all treatment combinations at plant growth conditions; and on day 45 the plants were harvested, and hypericin, pseudohypericin and hyperforin (another important health-promoting substance) were extracted from their leaves and quantified. Under all three light intensities employed in the study, the 1000-ppm increase in atmospheric CO2 concentration experienced in going from 500 to 1500 ppm produced total plant biomass increases of approximately 32%. Over this same CO2 range, hypericin concentrations rose by 78, 57 and 53%, respectively, under the low, medium and high light intensities, while corresponding increases in pseudohypericin were 70, 57 and 67%, and those in hyperforin were 102, 23 and 3%. Last of all, compared to results obtained from plants growing out-of-doors in air of 380 ppm CO2 and at light intensities on the order of 1770 µmol m-2 s-1, Mosaleeyanon et al. report that total plant biomass was fully 30 times greater in the high-light, high-CO2 treatment, while concentrations of hypericin and pseudohypericin were 30 and 41 times greater, respectively, in the high-light, high-CO2 treatment. Consequently, the researchers demonstrated that growing St. John's wort plants in CO2-enriched air in a controlled environment can enormously enhance the production of both plant biomass and total hypericin and pseudohypericin contents.
Introducing their study on the effects of elevated CO2 on broccoli, Schonhof et al. (2007) note that the glucosinolates found in broccoli comprise a group of bioactive compounds that are responsible for many physiological effects, including serving as feeding deterrents and protective compounds that help protect the plants against herbivore attack (Mewis et al., 2005), enhancing flavor for human consumers, and - perhaps most important of all - helping to prevent cancer in those who consume them (Mikkelsen et al., 2002).
In a set of three experiments conducted in a controlled greenhouse environment, Schonhof et al. grew well watered and fertilized broccoli (Brassica oleracea var. italica Plenck) cv Marathon plants in large soil-filled containers at ambient (430-480 ppm) and elevated (685-820 ppm) atmospheric CO2 concentrations to the stage where fully developed heads could be harvested for glucosinolate analyses. Results indicated that the roughly 65% increase in atmospheric CO2 concentration increased the fresh weight of the broccoli heads by approximately 7%, while it increased the total glucosinolate concentration of the broccoli inflorescences by 14%, due primarily to identical 37% increases in two methylsulfinylalkyl glucosinolates: glucoiberin and glucoraphanin. Based on these results Schonhof et al. concluded by saying that atmospheric CO2 enrichment "can enhance the health-promoting quality of broccoli because of induced glucosinolate content changes."
In a separate study, Ziska et al. (2005) grew well watered and fertilized tobacco and jimson weed plants from seed in controlled environment chambers maintained at atmospheric CO2 concentrations of either 294 ppm (reduced), 378 ppm (ambient) or 690 ppm (elevated) and mean air temperatures of either 22.1 or 27.1°C for 50 and 47 days after planting for tobacco and jimson weed, respectively, while sampling the plants at weekly intervals beginning at 28 and 16 days after planting for tobacco and jimson weed, respectively, to determine the effects of these treatments on the concentrations of three plant alkaloids possessing important pharmacological properties: nicotine, in the case of tobacco, and atropine and scopolamine, in the case of jimson weed. In following these protocols, they found that at the time of final harvesting, the elevated CO2 had increased the aboveground biomass production of tobacco by approximately 89% at 22.1°C and 53% at 27.1°C, and to have increased that of jimson weed by approximately 23% and 14% at the same respective temperatures. It was also found to have reduced the concentration of nicotine in tobacco, to have increased the concentration of scopolamine in jimson weed, but to have had no significant effect on the concentration of atropine in jimson weed. These changes (reduced nicotine in tobacco and increased scopolamine in jimson weed) would likely be characterized as positive; for the researchers report that nicotine is acknowledged to have significant negative impacts on human health, and that scopolamine is used as a sedative and as "an antispasmodic in certain disorders characterized by restlessness and agitation, (e.g., delirium tremens, psychosis, mania and Parkinsonism)."
With respect to the significance of their findings, Ziska et al. say "it can be argued that synthetic production of these secondary compounds alleviates any concern regarding environmental impacts on their production from botanical sources; however, developing countries (i.e., ~75% of the world population) continue to rely on ethno-botanical remedies as their primary medicine (e.g. use of alkaloids from jimson weed as treatment for asthma among native Americans and in India)," also noting that "for both developed and developing countries, there are a number of economically important pharmaceuticals derived solely from plants whose economic value is considerable (Raskin et al., 2002)."
Another plant with a long history of medicinal use is the ginseng plant. Well known for its anti-inflammatory, diuretic and sedative properties, and acknowledged to be an effective healing agent (Gillis, 1997; Ali et al., 2005), ginseng is widely cultivated in China, South Korea and Japan, where it has been used for medicinal purposes since Greek and Roman times. Normally, four to six years are required for ginseng roots to accumulate the amounts of the various phenolic compounds that are needed to produce their health-promoting effects. Consequently, in an effort to develop an efficient culture system for the commercial production of ginseng root, Ali et al. (2005) investigated the consequences of growing ginseng roots in suspension culture in bioreactors maintained in equilibrium with air enriched to CO2 concentrations of 10,000 ppm, 25,000 ppm and 50,000 ppm for periods of up to 45 days.
Of most immediate concern in such an experiment are the effects of the ultra-high CO2 concentrations on root growth, whether or not they be toxic and lead to biomass reductions or even root death. According to the results, the answer was no. After 45 days of growth at 10,000 ppm CO2, root dry weight was increased by fully 37% relative to the dry weight of roots produced in bioreactors in equilibrium with ambient air, while root dry mass was increased by a lesser 27% after 45 days at 25,000 ppm CO2 and by a still smaller 9% after 45 days at 50,000 ppm CO2. Consequently, although the optimum CO2 concentration for ginseng root growth likely resides somewhere below 10,000 ppm, the concentration at which root growth is reduced below that characteristic of ambient air resides somewhere significantly above 50,000 ppm, for even at that extremely high CO2 concentration, root growth was still greater than it was in ambient air.
Almost everything else measured by Ali et al. was even more enhanced by the ultra-high CO2 concentrations they employed in their experiment. After 45 days of treatment, total root phenolic concentrations were 58% higher at 10,000 ppm CO2 than at ambient CO2, 153% higher at 25,000 ppm CO2 and 105% higher at 50,000 ppm CO2, as best as can be determined from the bar graphs of their results. Likewise, total root flavonoid concentrations were enhanced by 228%, 383% and 232%, respectively, at the same ultra-high CO2 concentrations, while total protein contents rose by 14%, 22% and 30%, non-protein thiol contents by 12%, 43% and 62%, and cysteine contents by 27%, 65% and 100% under the identical respective set of conditions. What is more, there were equally large CO2-induced increases in the activities of a large number of phenol biosynthetic enzymes.
With regard to the implications of their results, Ali et al. write that "the consumption of foodstuffs containing antioxidant phytonutrients such as flavonoids, polyphenolics, ascorbate, cysteine and non-protein thiol is advantageous for human health," citing Cervato et al. (2000) and Noctor and Foyer (1998). Hence, they conclude that their technique for the culture of ginseng roots in CO2-enriched bioreactors could be used for the large-scale production of an important health-promoting product that could be provided to the public in much greater quantities than is currently possible.
Another plant that serves as both an herbal ingredient and a food delicacy in China, Japan and Korea is the brown seaweed Hizikia fusiforme, which has been studied by Zou (2005), who collected specimens of it from intertidal rocks along the coast of Nanao Island, Shantou, China, and maintained them in glass aquariums in filtered natural seawater enriched with 60 µM NaNO3 and 6.0 µM NaH2PO4, where the plants were continuously aerated with either ambient air of 360 ppm CO2 or CO2-enriched air of 700 ppm CO2. Under these conditions, Zou measured the seaweed's relative growth and nitrogen assimilation rates, as well as its nitrate reductase activity. This work revealed that the slightly less than a doubling of the air's CO2 concentration increased the seaweed's mean relative growth rate by about 50%, its mean rate of nitrate uptake during the study's 12-hour light periods by some 200%, and its nitrate reductase activity by approximately 20% over a wide range of substrate nitrate concentrations.
In discussing the implications of these findings, Zou notes that "the extract of H. fusiforme has an immunomodulating activity on humans and this ability might be used for clinical application to treat several diseases such as tumors (Suetsuna, 1998; Shan et al., 1999)." He also reports that the alga is "becoming one of the most important species for seaweed mariculture in China, owing to its high commercial value and increasing market demand." As a result, the ongoing rise in the air's CO2 content bodes well for both of these applications. In addition, Zou says "the intensive cultivation of H. fusiforme would remove nutrients more efficiently with the future elevation of CO2 levels in seawater, which could be a possible solution to the problem of ongoing coastal eutrophication," which in turn suggests that rising atmospheric CO2 concentrations may also assist in the amelioration of this environmental problem.
Also working with a marine alga - specifically, unicellular Nannochloropsis sp. - was Hoshida et al. (2005), who grew the alga in batch culture under normal (370 ppm) and elevated (3000 and 20,000 ppm) atmospheric CO2 concentrations in an attempt to learn how elevated CO2 impacted the alga's production of eicosapentaenoic acid (EPA), a major polyunsaturated omega-3 fatty acid that may play an important role in human health, including the prevention of cardiovascular diseases (e.g. atherosclerosis, thrombogenesis) and the inhibition of tumor growth and inflammation (Dyerberg et al., 1978; Hirai et al., 1989; Kinsella et al., 1990; Sanders, 1993). They also note that "Nitsan et al. (1999) showed that supplementing the diet of hens with Nannochloropsis sp. led to an increased content of n-3 fatty acids in the egg yolk, indicating an additional role in enhancing the nutritional value of eggs." Likewise, they indicate that "feeding Nannochloropsis sp. to rats caused a significant increase of the content of n-3 polyunsaturated fatty acids (Sukenik et al., 1994)," suggesting it may play an "important role as the source for n-3 polyunsaturated fatty acids in human nutrition."
What the Japanese scientists learned from their experiment was that "maximum EPA production was obtained when 20,000 ppm CO2 was supplied 12 hours prior to the end of the exponential growth," and that "the total EPA production during 4-day cultivation was about twice that obtained with ambient air." They also report that other researchers have obtained similar results, noting that EPA is mainly contained in thylakoid membranes (Sukenik et al., 1989; Hodgson et al., 1991), and that prior experiments have shown that "the amount of stroma thylakoid membrane increased in several plants under elevated CO2 concentrations (Griffin et al., 2001)." In addition, they say that "in Synechococcus lividus, reduction and synthesis of thylakoid membrane occurred by CO2 deprivation and elevation, respectively (Miller and Holt, 1977)," and that "in Chlorella vulgaris, altering the ambient CO2 concentration varied fatty acid composition (Tsuzuki et al., 1990)." Last of all, they say that "the effect of CO2 on fatty acid composition and/or fatty acid content was reported in algae and higher plants (Tsuzuki et al., 1990; Sergeenko et al., 2000; He et al., 1996; Radunz et al., 2000)," and that "increased EPA production caused by elevated CO2 concentration was reported in P. tricornutum (Yongmanitchai and Ward, 1991)." Consequently, as the atmosphere's CO2 concentration continues to rise, concentrations of omega-3 fatty acids should be widely enhanced in both aquatic and terrestrial plants, thereby benefiting much of the animal life of the planet.
With respect to the major staple crop of soybeans, Caldwell et al. (2005) write that "the beneficial effects of isoflavone-rich foods have been the subject of numerous studies (Birt et al., 2001; Messina, 1999)," and that "foods derived from soybeans are generally considered to provide both specific and general health benefits," presumably via these substances. Hence, the authors set out to determine how the isoflavone content of soybean seeds might be affected by the ongoing rise in the air's CO2 content.
The three researchers grew well watered and fertilized soybean plants from seed to maturity in pots within two controlled-environment chambers, one maintained at an atmospheric CO2 concentration of 400 ppm and one at 700 ppm. The chambers were initially kept at a constant air temperature of 25°C; but at the onset of seed fill air temperature was reduced to 18°C until seed development was complete, in order to simulate average outdoor temperatures at this stage of plant development. In a second experiment, this protocol was repeated, except that the temperature during seed fill was maintained at 23°C, with and without drought (a third treatment), while in a third experiment, seed-fill temperature was maintained at 28°C, with or without drought.
In the first experiment, where air temperature during seed fill was 18°C, the elevated CO2 treatment increased the total isoflavone content of the soybean seeds by 8%. In the second experiment, where air temperature during seed fill was 23°C, the extra CO2 increased total seed isoflavone content by 104%, while in the third experiment, where air temperature during seed fill was 28°C, the CO2-induced isoflavone increase was 101%. Then, when drought-stress was added as a third environmental variable, the extra CO2 boosted total seed isoflavone content by 186% when seed-fill air temperature was 23°C, while at a seed-fill temperature of 28°C, it increased isoflavone content by 38%. Under all environmental circumstances studied, therefore, enriching the air with an extra 300 ppm of CO2 increased the total isoflavone content of soybean seeds. In addition, the percent increases measured under the stress situations were always greater than the percent increase measured under optimal growing conditions.
A second research team to study soybeans within this context and timeframe was that of Kim et al. (2005), who add that important flavoniods "are mainly found in the form of isoflavones in soybean seeds," including "phytoestrogens with various biological potentials such as antioxidative, pharmaceutical, oestrogenic and anticarcinogenic properties, with some acting as antiestrogens and being used as anticancer agents (Peterson and Barnes, 1991; Anderson et al., 1995; Anthony et al., 1996; Arjmandi et al., 1996; Holt, 1997, Chung et al., 2000)." In their study, well watered plants were grown from seed to maturity in pots of sandy loam soil within the closed-environment plant growth facility of the National Horticultural Research Institute of Korea, where the plants were exposed to either natural solar radiation and the natural daily course of ambient air temperature or elevated air temperature (= ambient + 5°C) with either no added nitrogen or added nitrogen equivalent to an extra 40 kg N/ha, and where they were maintained at either ambient CO2 (360 ppm) or elevated CO2 (650 ppm). Then, at the end of the growing season, the plants were harvested and their total biomass determined, while the concentrations of 12 different isoflavones found in their seeds were quantitatively analyzed. These isoflavones included three aglycons (daidzein, genistein, glycitein), three glucosides (diadzin, genistin, glycitin), three acetyl conjugates (6"-O-acetyldaidzin, 6"-O-acetylgenistin, 6"-O-acetylglycitin), and three malonyl conjugates (6"-O-malonyldaidzin, 6"-O-malonylgenistin and 6"-O-malonylglycitin).
The results of this study indicated that the CO2-induced increase in total plant biomass at normal ambient temperatures was 96% in the case of no added nitrogen and 105% in the case of added nitrogen, while at the warmer temperatures it was 59% in the case of no added nitrogen and 68% in the case of added nitrogen. With respect to seed isoflavone concentrations, the CO2-induced increases of all twelve isoflavones were fairly similar to each other. As a group, at normal ambient temperatures the mean increase was 72% in the case of no added nitrogen and 59% in the case of added nitrogen, while at the warmer temperatures it was 72% in the case of no added nitrogen and 106% in the case of added nitrogen. Irrespective of soil nitrogen status and air temperature, therefore, increases in the air's CO2 content produced large increases in soybean biomass, as well as soybean seed concentrations of twelve major isoflavones. Hence, as the above studies show, as the atmosphere's CO2 concentration continues to rise in the years and decades ahead, both the amount and potency of many important health-promoting substances produced in soybean seeds should be significantly enhanced.
Noting that "among medicinal plants, the therapeutic uses of opiate alkaloids from poppy (Papaver spp.) have long been recognized," Ziska (2008) set out to "evaluate the growth and production of opiates for a broad range of recent and projected atmospheric carbon dioxide concentrations using wild poppy (P. setigerum) as a surrogate for P. somniferum.
Well watered and fertilized plants were grown from seed (one plant per 2.6-liter pot filled with a 4:1:1 mixture of sphagnum, perlite and vermiculite) within growth chambers maintained at four different atmospheric CO2 concentrations - 300, 400, 500 and 600 ppm - for a period of 90 to 100 days, after which the authors quantified plant growth and the production of secondary compounds including the alkaloids morphine, codeine, papaverine and noscapine, which were derived from latex obtained from capsules produced by the plants. The data indicated that relative to the plants grown at 300 ppm CO2, those grown at 400, 500 and 600 ppm produced approximately 200, 275 and 390% more aboveground biomass, respectively, as best as can be determined from their bar graphs. In addition, the authors report that "reproductively, increasing CO2 from 300 to 600 ppm increased the number of capsules, capsule weight and latex production by 3.6, 3.0 and 3.7 times, respectively, on a per plant basis," with the ultimate result that "all alkaloids increased significantly on a per plant basis." Based on these results, Ziska et al. concluded that "as atmospheric CO2 continues to increase, significant effects on the production of secondary plant compounds of pharmacological interest (i.e. opiates) could be expected," which effects, in their words, "are commonly accepted as having both negative (e.g. heroin) and positive (e.g. codeine) interactions with respect to public health."
Ali, M.B., Hahn, E.J. and Paek, K.-Y. 2005. CO2-induced total phenolics in suspension cultures of Panax ginseng C.A. Mayer roots: role of antioxidants and enzymes. Plant Physiology and Biochemistry 43: 449-457.
Anderson, J.W., Johnstone, B.M. and Cook-Newell, M.E. 1995. Meta-analysis of the effects of soybean protein intake on serum lipids. New England Journal of Medicine 333: 276-282.
Anthony, M.S., Clarkson, T.B., Hughes, C.L., Morgan, T.M. and Burke, G.L. 1996. Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkeys. Journal of Nutrition 126: 43-50.
Arjmandi, B.H., Lee, A., Hollis, B.W., Amin, D., Stacewicz-Saounizakis, M., Guo, P. and Kukreja, S.C. 1996. Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis. Journal of Nutrition 126: 161-167.
Barbale, D. 1970. The influence of the carbon dioxide on the yield and quality of cucumber and tomato in the covered areas. Augsne un Raza (Riga) 16: 66-73.
Birt, D.F., Hendrich, W. and Wang, W. 2001. Dietary agents in cancer prevention: flavonoids and isoflavonoids. Pharmacology & Therapeutics 90: 157-177.
Brolis, M., Gabetta, B., Fuzzati, N., Pace, R., Panzeri, F. and Peterlongo, F. 1998. Identification by high-performance liquid chromatography-diode array detection-mass spectrometry and quantification by high-performance liquid chromatography-UV absorbance detection of active constituents of Hypericum perforatum. Journal of Chromatography A 825: 9-16.
Caldwell, C.R., Britz, S.J. and Mirecki, R.M. 2005. Effect of temperature, elevated carbon dioxide, and drought during seed development on the isoflavone content of dwarf soybean [Glycine max (L.) Merrill] grown in controlled environments. Journal of Agricultural and Food Chemistry 53: 1125-1129.
Cervato, G., Carabelli, M., Gervasio, S., Cittera, A., Cazzola, R.. and Cestaro, B. 2000. Antioxidant properties of oregano (Origanum vulgare) leaf extracts. Journal of Food Biochemistry 24: 453-465.
Chung, I.M., Kim, K.H., Ahn, J.K., Chi, H.Y. and Lee, J.O. 2000. Screening for antioxidative activity in soybean local cultivars in Korea. Korean Journal of Crop Science 45: 328-334.
Dyerberg, J., Bang, H.O., Stoffersen, E., Moncada, S. and Vane, J.R. 1978. Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis. Lancet 2: 117-119.
Gabrielsen, B., Monath, T.P., Huggins, J.W., Kefauver, D.F., Pettit, G.R., Groszek, G., Hollingshead, M., Kirsi, J.J., Shannon, W.F., Schubert, E.M., Dare, J., Ugarkar, B., Ussery, M.A., Phelan, M.J. 1992a. Antiviral (RNA) activity of selected Amaryllidaceae isoquinoline constituents and synthesis of related substances. Journal of Natural Products 55: 1569-1581.
Gabrielsen, B., Monath, T.P., Huggins, J.W., Kirsi, J.J., Hollingshead, M., Shannon, W.M., Pettit, G.R. 1992b. Activity of selected Amaryllidaceae constituents and related synthetic substances against medically important RNA viruses. In: Chu, C.K. and Cutler, H.G. (Eds.), Natural Products as Antiviral Agents. Plenum Press, New York, NY, pp. 121-35.
Gillis, C.N. 1997. Panax ginseng pharmacology: a nitric oxide link? Biochemical Pharmacology 54: 1-8.
Griffin, K.L., Anderson, O.R., Gastrich, M.D., Lewis, J.D., Lin, G., Schuster, W., Seemann, J.R., Tissue, D.T., Turnbull, M.H. and Whitehead, D. 2001. Plant growth in elevated CO2 alters mitochondrial number and chloroplast fine structure. Proceedings of the National Academy of Sciences, USA 98: 2473-2478.
He, P., Radunz, A., Bader, K.P. and Schmid, G.H. 1996. Quantitative changes of the lipid and fatty acid composition of leaves of Aleurites montana as a consequence of growth under 700 ppm CO2 in the atmosphere. Zeitschrift fur Naturforscher 51 C: 833-840.
Hirai, A., Terano, T., Tamura, Y. and Yoshida, S. 1989. Eicosapentaenoic acid and adult diseases in Japan: Epidemiological and clinical aspects. Journal of Internal Medicine, Supplement 225: 69-75.
Hodgson, P.A., Henderson, R.J., Sargent, J.R. and Leftley, J.W. 1991. Patterns of variation in the lipid class and fatty acid composition of Nannochloropsis oculata (Eustigmatophyceae) during batch culture. I. The growth cycle. Journal of Applied Phycology 3: 169-181.
Holt, S. 1997. Soya: the health food of the next millennium. Korean Soybean Digest 14: 77-90.
Hoshida, H., Ohira, T., Minematsu, A., Akada, R. and Nishizawa, Y. 2005. Accumulation of eicosapentaenoic acid in Nannochloropsis sp. in response to elevated CO2 concentrations. Journal of Applied Phycology 17: 29-34.
Idso, S.B., Kimball, B.A., Pettit III, G.R., Garner, L.C., Pettit, G.R. and Backhaus, R.A. 2000. Effects of atmospheric CO2 enrichment on the growth and development of Hymenocallis littoralis (Amaryllidaceae) and the concentrations of several antineoplastic and antiviral constituents of its bulbs. American Journal of Botany 87: 769-773.
Kim, S.-H., Jung, W.-S., Ahn, J.-K., Kim, J.-A. and Chung, I.-M. 2005. Quantitative analysis of the isoflavone content and biological growth of soybean (Glycine max L.) at elevated temperature, CO2 level and N application. Journal of the Science of Food and Agriculture 85: 2557-2566.
Kimball, B.A., Mitchell, S.T. 1981. Effects of CO2 enrichment, ventilation, and nutrient concentration on the flavor and vitamin C content of tomato fruit. HortScience 16: 665-666.
Kinsella, J.E., Lokesh, B. and Stone, R.A. 1990. Dietary n-3 polyunsaturated fatty acids and amelioration of cardiovascular diseases: Possible mechanisms. American Journal of Clinical Nutrition 52: 10-28.
Machlin, L.G. 1992. Introduction. In: Sauberlich, H.E. and Machlin, L.J. (Eds.), Beyond deficiency: New views on the function and health effects of vitamins. Annals of the New York Academy of Science 669: 1-6.
Madsen, E. 1971. The influence of CO2-concentration on the content of ascorbic acid in tomato leaves. Ugeskr. Agron. 116: 592-594.
Madsen, E. 1975. Effect of CO2 environment on growth, development, fruit production and fruit quality of tomato from a physiological viewpoint. In: P. Chouard and N. de Bilderling (Eds.), Phytotronics in Agricultural and Horticultural Research. Bordas, Paris, pp. 318-330.
Messina, M.J. 1999. Legumes and soybeans: overview of their nutritional profiles and health effects. American Journal of Clinical Nutrition 70(S): 439s-450s.
Mewis, I., Appel, H.M., Hom, A., Raina, R. and Schultz, J.C. 2005. Major signaling pathways modulate Arabidopsis thaliana (L.) glucosinolate accumulation and response to both phloem feeding and chewing insects. Plant Physiology 138: 1149-1162.
Mikkelsen, M.D., Petersen, B., Olsen, C. and Halkier, B.A. 2002. Biosynthesis and metabolic engineering of glucosinolates. Amino Acids 22: 279-295.
Miller L.S. and Holt, S.C. 1977. Effect of carbon dioxide on pigment and membrane content in Synechococcus lividus. Archives Microbiologie 115: 185-198.
Mosaleeyanon, K., Zobayed, S.M.A., Afreen, F. and Kozai, T. 2005. Relationships between net photosynthetic rate and secondary metabolite contents in St. John's wort. Plant Science 169: 523-531.
Nitsan, Z., Mokady, S. and Sukenik, A. 1999. Enrichment of poultry products with omega 3 fatty acids by dietary supplementation with the alga Nannochloropsis and mantur oil. Journal of Agricultural and Food Chemistry 47: 5127-5132.
Noctor, G. and Foyer, C.H. 1998. Ascorbate and glutathione: keeping active oxygen under control. Annual Review of Plant Physiology and Plant Molecular Biology 49: 249-279.
Pasqua, G., Avato, P., Monacelli, B., Santamaria, A.R. and Argentieri, M.P. 2003. Metabolites in cell suspension cultures, calli, and in vitro regenerated organs of Hypericum perforatum cv. Topas. Plant Science 165: 977-982.
Peterson, G. and Barnes, S. 1991. Genistein inhibition of the growth of human breast cancer cell: independence from estrogen receptors and the multi-drug resistance gene. Biochemistry and Biophysical Research Communications 179: 661-667.
Pettit, G.R., Gaddamidi, V., Herald, D.L., Singh, S.B., Cragg, G.M., Schmidt, J.M., Boettner, F.E., Williams, M. and Sagawa, Y. 1986. Antineoplastic agents, 120. Pancratium littorale. Journal of Natural Products 49: 995-1002.
Pettit, G.R., Pettit III, G.R., Backhaus, R.A., Boyd, M.R., Meerow, A.W. 1993. Antineoplastic agents, 256. Cell growth inhibitory isocarbostyrils from Hymenocallis. Journal of Natural Products 56: 1682-1687.
Pettit, G.R., Pettit III, G.R., Groszek, G., Backhaus, R.A., Doubek, D.L., Barr, R.J. 1995. Antineoplastic agents, 301. An investigation of the Amaryllidaceae genus Hymenocallis. Journal of Natural Products 58: 756-759.
Radunz, A., Alfermann, K. and Schmid, G.H. 2000. State of the lipid and fatty acid composition in chloroplasts of Nicotiana tabacum under the influence of an increased CO2 partial pressure of 700 p.p.m. Biochemical Society Transactions 28: 885-887.
Raskin, I., Ribnicky, D.M., Komarnytsky, S. et al. 2002. Plants and human health in the twenty-first century. Trends in Biotechnology 20: 522-531.
Sanders, T.A.B. 1993. Marine oils: Metabolic effects and role in human nutrition. Proceedings of the Nutrition Society 52: 457-472.
Schempp, C.M., Krikin, V., Simon-Haarhaus, G., Kersten, A., Kiss, J., Termeer, C.C., Gilb, B., Kaufmann, T., Borner, C., Sleeman, J.P. and Simon, J.C. 2002. Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St. John's wort that acts by induction of apoptosis. Oncogene 21: 1242-1250.
Schonhof, I., Klaring, H.-P., Krumbein, A. and Schreiner, M. 2007. Interaction between atmospheric CO2 and glucosinolates in broccoli. Journal of Chemical Ecology 33: 105-114.
Sergeenko, T.V., Muradyan, E.A., Pronina, N.A., Klyachko-Gurvich, G.L., Mishina, I.M. and Tsoglin, L.N. 2000. The effect of extremely high CO2 concentration on the growth and biochemical composition of microalgae. Russian Journal of Plant Physiology 47: 632-638.
Shan, B.E., Yoshida, Y., Kuroda, E. and Yamashita, U. 1999. Immunomodulating activity of seaweed extract on human lymphocytes in vitro. International Journal of Immunopharmacology 21: 59-70.
Stevinson, C. and Ernst, E. 1999. Hypericum for depression: an update of the clinical evidence. European Neuropsychopharmacology 9: 501-505.
Stuhlfauth, T., Fock, H.P. 1990. Effect of whole season CO2 enrichment on the cultivation of a medicinal plant, Digitalis lanata. Journal of Agronomy and Crop Science 164: 168-173.
Stuhlfauth, T., Klug, K. and Fock, H.P. 1987. The production of secondary metabolites by Digitalis lanata during CO2 enrichment and water stress. Phytochemistry 26: 2735-2739.
Suetsuna, K. 1998. Separation and identification of angiotensin I-converting enzyme inhibitory peptides from peptic digest of Hizikia fusiformis protein. Nippon Suisan Gakkaishi 64: 862-866.
Sukenik, A., Cameli, Y. and Berner, T. 1989. Regulation of fatty acid composition by irradiance level in the eustigmatophyte Nannochloropsis sp. Journal of Phycology 25: 686-692.
Sukenik, A., Takahashi, H. and Mokady, S. 1994. Dietary lipids from marine unicellular algae enhance the amount of liver and blood omega-3 fatty acids in rats. Annals of Nutrition and Metabolism 38: 85-96.
Tajiri, T. 1985. Improvement of bean sprouts production by intermittent treatment with carbon dioxide. Nippon Shokuhin Kogyo Gakkaishi 32(3): 159-169.
Tsuzuki, M., Ohnuma, E., Sato, N., Takaku, T. And Kawaguchi, A. 1990. Effects of CO2 concentration during growth on fatty acid composition in microalgae. Plant Physiology 93: 851-856.
Yongmanitchai, W. and Ward, O.P. 1991. Growth of and omega-3 fatty acid production by Phaeodactylum tricornutum under different culture conditions. Applied Environmental Microbiology 57: 419-425.
Ziska, L.H., Emche, S.D., Johnson, E.L., George, K., Reed, D.R. and Sicher, R.C. 2005. Alterations in the production and concentration of selected alkaloids as a function of rising atmospheric carbon dioxide and air temperature: implications for ethno-pharmacology. Global Change Biology 11: 1798-1807.
Ziska, L.H., Panicker, S. and Wojno, H.L. 2008. Recent and projected increases in atmospheric carbon dioxide and the potential impacts on growth and alkaloid production in wild poppy (Papaver setigerum DC.). Climatic Change 91: 395-403.
Zobayed, S. and Saxena, P.K. 2004. Production of St. John's Wort plants under controlled environment for maximizing biomass and secondary metabolites. In Vitro Cellular and Developmental Biology - Plant 40: 108-114.
Zou, D. 2005. Effects of elevated atmospheric CO2 on growth, photosynthesis and nitrogen metabolism in the economic brown seaweed, Hizikia fusiforme (Sargassaceae, Phaeophyta). Aquaculture 250: 726-735.