In models related to the “growth rate hypothesis,” plant defense chemistry is viewed as occurring in
a compensatory manner with plant growth. Here, the metabolic cost of replacing plant tissues consumed
by herbivores is considered in the context of the costs of plant secondary product metabolism [60]. Un-
der conditions of high resource availability where plant growth rates are high, levels of defensive sec-
ondary products would be expected to be low as the higher rate of growth would assure adequate survival
from herbivory. On the hand, in resource-limited environments where suboptimal growth occurs, pro-
duction of defensive secondary products would be elevated. Several studies have provided data in sup-
port of this model [60–63]. For example, in studies conducted by McKey [55], tree species grown in nu-
trient-poor soils that limited growth had higher levels of defensive phenolic compounds than the same
trees growing in nutrient-rich soils.
The “carbon-nutrient balance” model was developed by Bryant et al. [61] to explain the effects of
soil nutrient supply and light levels on secondary product metabolism. A central theme of this model is
that the carbon/nitrogen (C/N) ratio of the plant under a given set of environmental conditions will have
a strong bearing on the types and levels of secondary products generated by the plant. In this model, pro-
duction of “carbon-based” secondary products (e.g., phenolics, terpenes, and other chemicals having only
C, O, and H as part of their structure) would be directly proportional to the C/N ratio, whereas production
of nitrogen-based secondary products (e.g., alkaloids, cyanogenic glycosides, nonprotein amino acids)
would be inversely proportional to the C/N ratio. For example, under conditions of adequate light and low
nitrogen supply, the C/N ratio of the plant would increase and this would lead to increased production of
carbon-based secondary products. On the other hand, with conditions such as low light and adequate ni-
trogen that lead to a decrease in the plant C/N ratio, increased production of nitrogen-containing sec-
ondary products would be expected. As simple as this concept is, a substantial number of studies appear
to support the C/N balance model for regulation of secondary product metabolism. Several studies have
shown that soil fertilization tends to increase levels of nitrogen-based secondary products [64–66] and de-
crease levels of carbon-based secondary products [67–74]. Likewise, a decrease in light levels has been
shown to increase levels of nitrogen-based secondary products [75] and decrease levels of carbon-based
secondary products [76–80].
Although these models point to different relationships with factors governing production and distri-
bution of secondary metabolites, it is apparent that two of the three general models place strong empha-
sis on the growth environment in determining levels and patterns of plant secondary metabolite produc-
tion. These two models (growth rate hypothesis and carbon-nitrogen balance hypothesis) are also
amenable to experimental testing, and data in support of each have been presented. Although no single
model may be able to account for levels and patterns of secondary product production (see Ref. 54 for dis-
cussion), these results point to the importance of considering how the growth environment of a particular
medicinal plant could have an impact on phytomedicinal chemical production and hence the quality of a
botanical medicine.
VI. PERSPECTIVE AND OUTLOOK
Although medicinal plants have had long-standing use throughout human history and are of considerable
interest as alternatives to synthetic pharmaceuticals, there is a paucity of basic knowledge of the physiol-
ogy and biochemistry of these plants. With only a few exceptions, many widely used medicinal plants
have not received the extensive physiological, biochemical, and genetic characterization received by food
crops or model plant systems such as Arabidopsis. Although some active chemicals may have been iden-
tified in these plants, the pathways for their biosynthesis and the factors (biotic and abiotic) regulating
their biochemical production are, in many cases, unclear.
At present, a major concern about the use of phytomedicinals regards the maintenance of consistent
medicinal quality in botanical medicines [81]. Whereas the focus has tended to be on quality control in
herbal manufacturing practices (good manufacturing practices or GMPs), variation in phytomedicinal
content because of environmental effects on secondary plant metabolism in the plant material can also be
a significant factor in determining the quality of the plant material entering the botanical medicine pro-
duction process. In this respect, a set of guidelines for good agricultural practices” (GAPs) has been sug-
gested that takes into consideration the importance of standardizing growth conditions for optimal phy-
tomedicinal chemical production by a medicinal plant (see Ref. 82 for discussion). These guidelines
PHYTOMEDICINAL CHEMICAL PRODUCTION BY PLANTS 497