Plant Physiology and Biochemistry 148 (2020) 80–89

Contents lists available at ScienceDirect

Plant Physiology and Biochemistry

journal homepage: www.elsevier.com/locate/plaphy

Review

The effect of developmental and environmental factors on secondary T

metabolites in medicinal plants
Yanqun Lia,b,c,1, Dexin Konga,1, Ying Fub, Michael R. Sussmand, Hong Wua,b,c,∗
a
State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou, 510642, China
b
Guangdong Key Laboratory for Innovative Development and Utilization of Forest Plant Germplasm, South China Agricultural University, Guangzhou, 510642, China
c
Guangdong Technology Research Center for Traditional Chinese Veterinary Medicine and Natural Medicine, South China Agricultural University, Guangzhou, 510642,
China
d
Biotechnology Center, University of Wisconsin, Madison, WI, 53706, USA

A R T I C LE I N FO A B S T R A C T

Keywords: Secondary metabolites (SMs) of medicinal plants are the material basis of their clinically curative effects. They
Medicinal plant are also important indicators for evaluating the quality of medicinal materials. However, the synthesis and
Secondary metabolites accumulation of SMs are very complex, which are affected by many factors including internal developmental
Growth and development genetic circuits (regulated gene, enzyme) and by external environment factors (light, temperature, water, sali-
Environmental factors
nity, etc.). Currently, lots of literatures focused on the effect of environmental factors on the synthesis and
accumulation of SMs of medicinal plants, the effect of the developmental growth and genetic factors on the
synthesis and accumulation of SMs still lack systematic classification and summary. Here, we have given the
review base on our previous works on the morphological development of medicinal plants and their secondary
metabolites, and systematically outlined the literature reports how different environmental factors affected the
synthesis and accumulation of SMs. The results of our reviews can know how developmental and environmental
factors qualitatively and quantitatively influence SMs of medicinal plants and how these can be integrated as
tools to quality control, as well as on the improvement of clinical curative effects by altering their genomes, and/
or growth conditions.

1. Introduction component of a ‘systems’ approach towards biology, i.e., with genomics

(DNA), transcriptomics (RNA) and proteomics being the other three.
Plants are living chemical factories for the biosynthesis of a huge Thus, in this context secondary metabolites are a subset of the meta-
array of the secondary metabolites (SMs) and in fact, it is these meta- bolome of plants, and are generally considered to be that group of small
bolites that form the basis for many commercial pharmaceutical drugs, molecules separate from the many common metabolites required for
as well as herbal remedies derived from medicinal plants. The different life in all organisms (e.g., mitochondrial TCA cycle or glycolysis, etc).
chemical constituents in medicinal plants possess biological activities Second, mass spectrometry has emerged as the workhorse of all studies
that can improve human health via the pharmaceutical and food in- aimed at identifying and quantifying the metabolome, including sec-
dustries, but they also represent important value in perfume, agro- ondary metabolites, and the reader is referred to recent reviews on this
chemical, cosmetic industries (Hassan, 2012). Many SMs such as alka- very powerful technology in current use (Wang et al., 2019). Finally, a
loids, terpenoids, and phenylpropanoids are being considered for drug key and often the most challenging aspect of research on medicinal
development (Sanchita and Sharma, 2018). plants is the assay used to quantitatively measure the bioactivity of the
Before discussing how the plant regulates its secondary metabolites, extracts. Since these extracts are incredibly complicated and most as-
a few brief more general comments are in order concerning new tech- says are not sufficiently high throughput to bio-analyze more than a few
nologies that are being used and are needed, to advance the science of dozen fractions at a time, it is clear that if more than one compound is
medicinal plants. First, the word ‘metabolome’ is now being used to needed to elicit an effect, our current capabilities are severely limited in
describe ALL of the small molecules in a cell, and is the fourth terms of connecting a particular chemical structure with a particular

∗
Corresponding author. State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou,
510642, China.
E-mail address: wh@scau.edu.cn (H. Wu).
1
These authors contributed equally to this work.

https://doi.org/10.1016/j.plaphy.2020.01.006
Received 4 June 2019; Received in revised form 12 December 2019; Accepted 4 January 2020
Available online 07 January 2020
0981-9428/ © 2020 Elsevier Masson SAS. All rights reserved.
Y. Li, et al. Plant Physiology and Biochemistry 148 (2020) 80–89

clinical effect. For example, while recent developments in high accumulation of active components with important medicinal value. In
throughput model organisms with brain like neural structures (e.g., root and stem herbs, the accumulation of active components is mainly
Drosophila) may provide the best opportunity for such comprehensive affected by growth periods, growth seasons and growth years. Some
analyses, there is no guarantee that the results are relevant to human medicinal plants accumulate abundant of SMs mainly during their re-
effects observed from ingesting medicinal plants. This latter limitation, productive growth period. For example, the root and rhizome of 2-year-
of a high throughput assay that can be coupled to state of the art old Echinacea purpurea have higher yields of cichoric acid in the fruiting
chemical analyses, represents a particularly imposing bottleneck in stage (Xu et al., 2014). During fruiting, Astragalus compactus Lam.
research on medicinal plants that will require the creativity and hard (Fabaceae) have a higher total phenolic content than during vegetative
work of future scientists to solve. and flowering stages of (Naghiloo et al., 2012b). The main flavonoids in
Biosynthesis of SMs starts from basic pathways, such as the glyco- the roots of Scutellaria baicalensis Georgi accumulate rapidly before the
lysis or shikimic acid pathways, and subsequently diversifies, largely full-bloom stage (Xu et al., 2018). However, there are also some med-
depending on cell type, developmental stage and environmental cues icinal plants with higher SMs content in vegetative growth period than
(Patra et al., 2013), these compounds are widely distributed in different in reproductive growth period. For example, oleanolic acid and ec-
plants cells, tissues and organs. However, different cells, tissues and dysterone in the root of Achyranthes bidentata are both higher in the
organs of medicinal plants may possess different medicinal properties at vegetative growth period than in reproductive growth period (Li and
different developmental stages (Bartwal et al., 2013). Because the de- Hu, 2009). In addition to quantitative changes, variations in the quality
velopmental factors influence the initiation and subsequent differ- of different components in the same plant are also obviously different.
entiation of particular cellular structures involved in the biosynthesis For example, the content of total flavonoids in the root of Scutellaria
and storage of SMs (Broun et al., 2006). In addition, the plant growth baicalensis Georgi is stable during the whole growth stage, but the
and development are usually elicited or inhibited by different en- content of baicalin increases and then gradually decreases (Hu et al.,
vironmental conditions. Therefore, the adaptation of plant morphology, 2012).
anatomy, and physiological functions to the changes in biotic and Due to the obvious difference in life cycle of different plants, a large
abiotic may influence the accumulation of secondary metabolites (Ma number of SMs often occur at a certain stage of plant growth. In gen-
and Zhang, 2010). The SM pathways and their regulation are highly eral, with the growth of perennial herbs, the content and yield of SMs
susceptible to environmental variations because the expression of genes are higher and higher. For example, saponins have the highest content
involved in SM pathways are altered by different stresses (Borges et al., in the root of three year old Panax notoginseng (Hong et al., 2005). The
2017; Sanchita and Sharma, 2018). The SMs exert long-term effects on saponin content of 1–5 year-old Panax ginseng also increases with the
plant growth and survival under stressful environments (Kurepin et al., increase of growth years (Shi et al., 2007). However, the opposite si-
2017). About 100,000 SMs are present in the plant kingdom confined to tuation has also been reported, e.g., the content of triterpene decreases
specific taxonomic groups. There are three major groups of SMs in when Codonopsis pilosula is older (Zhu et al., 2014). In perennial woody
plants based on their biosynthetic pathway including nitrogen-con- medicinal plants, the SMs generally increase with ages, or stop in-
taining compounds (cyanogenic glycosides, alkaloids, and glucosino- creasing and then decrease after reaching a certain degree. For ex-
lates), phenolic compounds (flavonoids and phenylpropanoids), and ample, Geng et al. (2011) studied 5-12 year-old Cinnamomum cassia
terpenes (isoprenoids) (Fang et al., 2011). Currently, although the SMs stem bark essential oils and found that the content of essential oil in-
biosynthesis and accumulation research are progressed, the reports on creased with increased years, and the oil content of C. cassia stem bark
the developmental and environmental factors influenced on the was the highest (2.61%, w/w) in 12 year old plants. In contrast, the
synthesis and accumulation of SMs of medicinal plants still rarely. Here, content of trans-cinnamaldehyde in 1–12 year-old plant stem bark
we have given the review base on our previous works and recent pro- showed a trend of increasing first and then decreasing. Moreover, dif-
gress reports on different environmental factors affected the synthesis ferent components in the same plant also show different time courses.
and accumulation of SMs. and discussing how some developmental and Chlorogenic acid, hyperin and quercetin are the highest in 13-year-old
environmental factors qualitatively and quantitatively influence SMs of plants, rutin and quercitrin are the highest in 7-year-old plants, and
medicinal plants and how these can be integrated as tools to quality magnolol is in 10-year-old plants of Magnolia officinalis bark (Yang
control, as well as on the improvement of clinical curative effects by et al., 2012).
altering their genomes, and/or growth conditions. The stimulating of Much of SMs are derivatives of primary metabolites produced by
biosynthesis on SMs in medicinal plants by control and optimization of plants because of diverse physiological changes (Zandalinas et al.,
external and internal factors may be applied to develop the bio- 2017). Therefore, both species and tissue specificity determined by
technologies of high quality drug production. genetic factors are all affected the synthesis and accumulation of SMs in
medicinal plants. If we want to obtain better medicinal parts and op-
2. Growth and development of plants influences the production of timal harvest time in a certain organ, we need to study the organs and
secondary metabolites tissues specificity of certain medicinal components in medicinal plants,
discussing the relationship between the morphogenesis and the synth-
According to the mainly synthesis, accumulation and distribution esis and accumulation of these components in medicinal plants. It is
patterns of secondary metabolites products in medicinal plants, the appropriate to choose a longer growth period for the harvest of per-
medicinal parts could be classified into 4 different types: (1) roots and ennial herbs and woody medicinal plants, because plants at these
stems, (2) leaves, (3) flowers, (4) fruits and seeds. In addition, because growth period show more vigorous growth and metabolism, as well as
the SMs are complex and diversity in different parts of medicinal plants, increased plant height, stem diameter, root diameter and biomass all
the different SMs may synthesize through special regulatory path way increase with the increasing growth period, concurrent with the in-
and special transport route in certain organs, tissues, and cells (Belkheir creased content and yield of effective components. However, for med-
et al., 2016). Therefore, the SMs biosynthesis and accumulation are icinal plants that contain special components, the biomass and com-
show the organ or tissue specificity. The following parts we will detailly positions should be comprehensively studied to determine the optimal
review the recent progress of SMs biosynthesis and accumulation in harvesting period for those specific compounds. In addition, the
different parts in medicinal plants. planting and production costs in agriculture and the curative effects in
the medical clinic should be primary considerations. In addition, al-
2.1. Root and stem though more chemical component biosynthesis path way have been
already revealed, the SMs synthesis are very complex, which were af-
Plant roots and stems are the main organs responsible for the fected by organs and tissues specificity of medicinal plants. In other

81
Y. Li, et al. Plant Physiology and Biochemistry 148 (2020) 80–89

words, the synthesis and accumulation patterns of different component et al., 2008). There were apparent differences in the contents of the
in different organs or even in same organ were showed the differences. volatile oils among the flower buds of Magnolia zenii at different growth
This phenomenon was closely related to the differences in biosynthetic stages. The yields of volatile oil first increased and later decreased with
metabolic pathways of different medicinal components and the ex- the growth of flower buds. The highest oil yield was obtained from the
pression patterns of key regulated genes in metabolic pathways (Dey buds in October (Hu et al., 2015). In contrast, Magnolia biondii flowers
et al., 1998). Currently, lots of SMs biosynthesis path ways are lacking had a higher dry weight, volatile oil yield and total content of medicinal
and should be pursued in details. ingredients in January and February, which was the best time for
harvesting high-quality raw materials (Hu et al., 2018). However, there
2.2. Leaf are also great differences of the variations in different components
during the growth of plants. The amounts of azulene decreased, while
Leaves are the main organs of plants for photosynthesis and play an the content of camphor and 1,8-cineole increased, with the develop-
important role in the life of plants. Leaves can also be used as a syn- ment of the flowers of Achillea millefolium (Figueiredo et al., 2008). The
thetic and storage organ for SMs. Leaf age (Vazquez-Leon et al., 2017), contents of elemene and ocimene rapidly increased on the 2nd day after
harvesting season (Gomes et al., 2019), and growth stage (Li et al., flowering, and decreased after reaching the peak on the 6th day of
2016c), all affect the content of SMs in medicinal plant leaves. It has Antirrhinum majus (Dudareva et al., 2003). These variations may be
been reported that the biosynthesis of some monoterpenes and sesqui- directly related to the developmental characteristics of flower organs,
terpenoids (such as pinene) has begun as early as in the first cotyledon the spatio-temporal expression characteristics of volatile chemical
of Melaleuca alternifolia (Southwell and Russell, 2002). Synthesis and composition biosynthesis regulatory genes and their encoded proteins
accumulation of the highest eugenol of essential oil of Cinnamomum (Lepelley et al., 2007; Gupta et al., 2011). Because of the specific ex-
verum are mainly in young 1-year-old leaf (Li et al., 2016c). However, pression of regulatory enzymes and related genes of SMs in plant tissues
the synthesis of some other compounds begin in the mature leaves. For and cells, SMs in plants are usually synthesized and released in specific
example, compounds associated with the sabinene hydrate–terpinen-4- plant tissues and organs at specific times (Belkheir et al., 2016). For
ol–γ-terpinene pathways seem to be formed at later stages of develop- example, in the flower of Antirrhinum majus, myrcene and ocimene
ment (Southwell and Russell, 2002). synthase mRNA first appeared in mature flower buds, then increased
Secretory structures, such as nectaries, resin ducts, secretory ve- continuously, reaching a peak on the 4th day of flowering. In addition,
sicles, salt glands, oil cells and secretory trichomes, are usually differ- mRNA levels of myrcene and ocimene synthase genes show rhythmic
entiated on the surface or inside of leaves (Fahn, 1988). Secretory expression, indicating that biosynthesis of SMs is regulated by devel-
structures are often one of the main sites for the synthesis and accu- opmental stages and by circadian rhythms (Nagegowda et al., 2008).
mulation of SMs (Figueiredo et al., 2008). There are obvious differences Recently, some reports about the accumulation dynamics of
in the secretions of different secretory structures, and the develop- chlorogenic acid and luteolin at different growth stages in Lonicera ja-
mental state also often affects the yield and quality of medicinal ma- ponica Thunb. indicate that the accumulation of main components first
terials (Verma and Shukla, 2015). Oil cells are the main sites for the increased and then decreased throughout the growth of L. japonica.
synthesis and accumulation of the essential oils in leaves, and the dis- Further analysis reveals that the accumulation dynamics of chlorogenic
tribution density and degree of development was significantly different acid during flower organ development of L. japonica are directly con-
with the leaf age (Li et al., 2013), thus resulting in variations in the trolled by the spatio-temporal expression characteristics of a key reg-
essential oil yields. For example, the leaves of a 2-year-old branch had ulatory gene (HQT) and enzymatic protein encoded by HQT (Li et al.,
the highest density of oil cells (6.91 n/mm2) and the maximum per- 2019). The content of luteolin is closely related to the expression
centage of oil cells at the oil saturation stage (48.05%), which coincided characteristics of its regulatory enzyme CHI during flower organ de-
with the highest oil yield (2.12%). The oils were less accumulated in the velopment (Kong et al., 2017a). In addition, the accumulation of CGA
1–4 leaves of annual branch and were mostly disintegrated in the leaves and luteoloside at different growth stages in L.japonica correlated with
of 4 year old branches, therefore the lower percentages of oil cells at oil variations in the initial activities of several other regulatory enzymes in
saturation stage (6.72 and 33.71%, respectively) resulted in the lower the phenylalanine metabolic pathway, including phenylalanine am-
oil yields (1.01 and 0.54%, respectively) (Li et al., 2013, 2016c). This monia-lyase (PAL), cinnamate 4-hydroxylase (C4H) and 4-coumarate
indicates that the yield of the essential oils is directly correlated with CoA ligase (4CL) (Kong et al., 2017b). Regulation of secondary meta-
the density of the oil cells and the degree of development of the oil cells. bolism can be achieved at different levels, starting with the transport
Indeed, developmental factors influence the initiation and subsequent and metabolism of extracellular nutrients, through precursor formation
differentiation of particular cellular structures involved in the bio- and accumulation. This may occur via the onset of transcription and
synthesis and storage of SMs (Broun et al., 2006). Furthermore, the post-transcriptional processes as well as translational and posttransla-
particular tissues as well as the developmental stages, influence the tional controls, and of course, targeting the enzymes involved in their
expression pattern of genes related to SMs biosynthesis (Sanchita and biosynthesis (Rokem et al., 2008). This leads to the fact that sometimes
Sharma, 2018). Understanding which genes they target will also be the expression characteristics of genes can only affect the synthesis and
important to obtain further information on the pathway and on cellular accumulation of metabolites through direct changes in the activity of
mechanisms leading to the production and accumulation of metabolites the enzyme protein encoded by the genes (Navarre et al., 2013). Thus,
in plant cells. This will also be useful in order to link aspects of plant synthesis-related SM enzymes are not only regulated at the transcrip-
differentiation such as the development of oil cells to the downstream tion level, but also regulated by post-transcriptional and post-transla-
metabolic events leading to metabolite accumulation. So a study of tional control mechanisms (Patra et al., 2013). Post-translational con-
changes in the expression pattern of genes especially responsible for the trol mechanisms have been implicated in terpenoid indole alkaloid,
regulation of secondary metabolism in medicinal plants is necessary to anthocyanin, nicotine and camalexin biosynthesis in plants (Patra et al.,
understand the ontogenic factors. 2013). The miRNAs (microRNAs are known to regulate gene expression
at the post-transcriptional level by transcriptional cleavage or transla-
2.3. Flower tion repression) have also been demonstrated to play an active role in
SM regulation (Singh and Sharma, 2017). In addition, the two major
Most of the flowers of plants have an aromatic smell mainly com- post-transcriptional regulators Hfq and RsmA in the Gram-negative
posed of terpenes and aromatic compounds, whose synthesis and ac- bacterium, Serratia 39006 were found to play a major role in regulating
cumulation dynamics are mainly regulated by different development prodigiosin production, and RsmA was investigated by performing
stages, circadian rhythm, biological and abiotic factors (Figueiredo RNA-seq on an rsmA mutant (Wilf, 2011). Tobias et al. (2016)

82
Y. Li, et al. Plant Physiology and Biochemistry 148 (2020) 80–89

demonstrated that the lack of Hfq impaired production of many of the However, lack of sunlight may reduce the absorption of light energy
SM in vitro, thus revealing a global regulation of SM synthesis at the and inhibit plant growth and yield by affecting net photosynthetic rate
post-transcriptional level. Moreover, Valverde (2017) revealed that (Gregoriou et al., 2007). There were the conspicuous effects of photo-
interplay between the post-transcriptional (Hfq-dependent) and tran- period and light intensity on the biosynthesis and storage of SMs for
scriptional (HexA-dependent) control of SM production in Photorhabdus different chemical components (Verma and Shukla, 2015; Zhang et al.,
luminiscens. These works opens a new avenue of future work in the field 2015; Kong et al., 2016; Li et al., 2018). Plants require an appropriate
of natural bioactive products, provided that derivative mutants affected intensity of light for photosynthesis, and this affects the quality and
in control of SM production, may be a source of novel SM or of higher accumulation of total alkaloids yields, hexadecanoic acid, total flavo-
levels for their production in vitro. noids, phenolic acids and spermine (Lavola et al., 2000; Kong et al.,
2016; Li et al., 2018). In some cases, the higher irradiance is helpful for
2.4. Fruits and seed plant growth and SMs production (Zhang et al., 2015). For instance, the
amount of scutellarin (flavone glycoside) was higher in sun-developed
The fruits and seeds are important medicinal materials of many leaves than in shade-developed leaves of Erigeron breviscapus (Zhou
plants, whose developmental stages also have a significant influence on et al., 2016). Similarly, the yield of essential oil is also increased in
the content and composition of components. Liang et al. (2006) re- response to high light intensities (Figueiredo et al., 2008; Kong et al.,
ported that volatile oils, which are the main active ingredient in Citrus 2016; Li et al., 2018). Occasionally, the opposite situation is reported.
fruits, are affected by the developing secretory cavity of fruit. Usually, For example, concentrations of camphene, sabinene, b-pinene, borneol,
when the fruit is light yellow, the volatile oil content is the highest, bornyl acetate, and Z-jasmone were higher for plants grown under
which can be used as a morphological index for harvesting. Wu et al. partial shade than fully irradiated control plants of Flourensia cernua
(2013) found that essential oils yields showed significantly increase (Estell et al., 2016). Thus, the light intensity and photoperiod have
during maturation process, and the content of α-thujone, carene, β- different effects on the accumulation of plant SMs in different plants.
pinene and γ-terpinene in Citrus medica L. var. sarcodactylis, varied These studies indicated that improving the yield and medicinal prop-
significantly during maturation stages. Similarly, the contents of mor- erties of plants might be achieved by appropriate adjustments of light
phine, codeine and thebaine were highest in capsules. Maximum mor- quality and quantity. Different plant species have their own optimal
phine content in capsule is reached at maturity of Papaver somniferum L light sets (quality and quantity), which manage to elicit maximal yield
roots (Shukla and Singh, 2001). Thus again, the content and composi- of SMs (Zhou et al., 2016).
tion of SMs are affected by the developmental stages of plant (Verma
and Shukla, 2015). 3.1.2. Ultraviolet radiation
Similarly, the synthesis and accumulation of SMs were closely as- The effect of ultraviolet (UV) light exposure on SMs is common in
sociated with the developmental stage of the medicinal plant seeds. The medicinal plants. For example, the concentrations of flavonoids and
content of coffee quinic acids is relatively stable in coffee, but the phenolic acids increased in response to increased UV-B radiation of
content of dicoffee quinic acids obviously decreases with the develop- Chrysanthemum (Ma et al., 2016). Reifenrath and Müller (2007) re-
mental stage of the seeds. The content of quinic acid (precursor sub- ported that compared to old leaves, young leaves were efficiently pro-
stance of chlorogenic acid synthesis) is high at the early developmental tected from UV light due to high flavonoid and glucosinolate amounts
stage of seeds, and obviously decreases at the later stage. These varia- in Sinapis alba, or enhanced flavonoid levels and myrosinase activities
tions are related to the expression characteristics of HQT gene, a key in Nasturtium officinale. An increase of total phenolic content could be
enzyme regulating phenolic acid biosynthesis (Lepelley et al., 2007). due to an increase in the amount of UV radiation associated with an
The effect of developmental stages on the content of SMs in plants is increase in solar radiation received by the plants (Naghiloo et al.,
displayed in Table 1. 2012b). Spitaler et al. (2006) demonstrated that the induction of phe-
nolics is a major factor in the reactive oxygen species (ROS) scavenging
3. Environmental factors influence the production of secondary system in genetically homogenous populations grown along an altitu-
metabolites dinal gradient, and most probably is linked with augmented UV-B light.
Takshak and Agrawal (2014) reported a similar study that the UV solar
The synthesis and proper accumulation of SMs are strictly con- radiation induces the production of ROS, and instigates protective ef-
trolled in a spatial and temporal manner and influenced by the chan- fects that promote the biosynthesis of UV-B absorbing alkaloids, an-
ging abiotic and biotic environment. In general, abiotic stress is re- thocyanins, carotenoids, flavonoids, lignin, phytosterols, saponins, and
sponsible for the decrease of production and yield of medicinal plants. tannins. However, plant SMs have not been fully studied with respect to
During growth and development, plants interact with the surrounding their relevant functions in plants under environmental stress. How plant
environment, where they come in contact with different abiotic com- SMs enable plants to avoid oxidative damage is an area of research that
ponents like water, light, temperature, soil and chemicals. Negative must be studied in detail. The expression and transcriptional level of
abiotic factors, such as drought or flooding, extremes of light and SM-regulated genes in plants are affected by UV. For instance, Eichholz
temperature and the presence of poor soil or toxic chemicals generate et al. (2012) reported that the concentration of flavonol quercetin-4′-O-
secondary stresses, and these trigger variation in the biosynthesis of monoglucoside increased with UV-B dose, which was accompanied
SMs (Verma and Shukla, 2015). Thus, environmental factors are crucial with a rise in activity of polyphenol-related enzymes (phenylalanine
determinants for the biosynthesis and fluctuations in plant SMs (Verma ammonialyase and peroxidase) in Asparagus officinalis L. cv. Gijnlim.
and Shukla, 2015). Moreover, higher artemisinin accumulation under low dose UV-B ex-
posure (3–4 h, 2.8 Wm-2) was shown to be a result of significant up-
3.1. Light and ultraviolet radiation regulation of HMGR, DXR, IPPi, FPS, ADS, CYP71AV1 and RED1 gene
transcripts (Pan et al., 2014), and the transcription levels of amorpha-
3.1.1. Light 4,11-diene synthase (ADS) and cytochrome P450 monooxygenase
Irradiance with photons of different wavelengths and intensity is an (CYP71AV1) genes were upregulated when compared with control
essential abiotic component required by the plants for photosynthesis, plants under UV light in Artemisia annua (Yin et al., 2008). In most case,
growth, and secondary metabolic product accumulation (Zhang et al., the effect of UV light exposure on SMs biosynthesis is positive, however,
2015; Li et al., 2018). Excessive irradiance may inactivate or impair the high doses of UV-B and UV-C radiation negatively affect growth, de-
photosynthetic reaction centres of the chloroplasts and cause photo- velopment, photosynthesis, and other important processes in plants
inhibition and may reduce plant growth (Szymańska et al., 2017). (Katerova et al., 2017). SMs accumulation is highly important from

83
Y. Li, et al. Plant Physiology and Biochemistry 148 (2020) 80–89

Table 1
Developmental stages change on the content of various plant SMs.
Metabolite Metabolite Name Concentration Change Developmental stages Plant Species Parts Refences
Class

Phenols Cichoric acid Higher Fruiting stage Echinacea purpurea Root Xu et al. (2014)
Total phenolic Higher Fruiting stage Astragalus compactus Root Naghiloo et al. (2012b)
Chlorogenic acid, Highest 13-year-old Magnolia officinalis Bark Yang et al. (2012)
Magnolol Highest 10-year-old Magnolia officinalis Bark Yang et al. (2012)
Eugenol Highest 1-year-old Cinnamomum verum Leaf Li et al. (2016c)
Chlorogenic acid Increasing first and then Whole growth stage Lonicera japonica Flower Kong et al. (2017a); Li
decreasing et al. (2019)
Coffee quinic acids Stable Whole growth stage coffee Seed Lepelley et al. (2007)
Dicoffee quinic acids Decrease with the developmental coffee Seed Lepelley et al. (2007)
stage
Quinic acid High Early developmental stage coffee Seed Lepelley et al. (2007)
Flavonoids compounds Flavonoids Strong increase Before the full-bloom stage Scutellaria baicalensis Root Xu et al. (2018)
Total flavonoids Stable Whole growth stage Scutellaria baicalensis Root Hu et al. (2012)
Baicalin Increases and then Whole growth stage Scutellaria baicalensis Root Hu et al. (2012)
gradually decreases
Hyperin and quercetin Highest 13-year-old Magnolia officinalis Bark Yang et al. (2012)
Rutin, Quercitrin Highest 7-year-old Magnolia officinalis Bark Yang et al. (2012)
Luteolin Increasing first and then Whole growth stage Lonicera japonica Flower Kong et al. (2017a); Li
decreasing et al. (2019)
Terpenoids/Essential Triterpene Low Older tree Codonopsis pilosula Root Zhu et al. (2014)
Oils Essential oils Increase Increased years Cinnamomum cassia Stem bark Geng et al. (2011)
Essential oils Highest 2-year-old branch Cinnamomum cassia; Leaf Li et al. (2013)
Cinnamomum verum
Essential oils Highest October Magnolia zenii Flower bud Hu et al. (2015)
Camphor, 1,8-cineole Increase With the development of Achillea millefolium Flower Figueiredo et al. (2008)
the flowers
Myrcene, Ocimene Highest 4th day of flowering Antirrhinum majus Flower Nagegowda et al.
(2008)
Essential oils Highest Fruit is light yellow Citrus Fruit Liang et al. (2006)
Essential oils Significant increase Maturation process Citrus medica Fruit Wu et al. (2013)
Others Trans-cinnamaldehyde Increasing first and then 1-12 year-old Cinnamomum cassia Stem bark Geng et al. (2011)
decreasing
Saponins Highest 3 year old Panax notoginseng Root Hong et al. (2005)
Increase 1–5 year old Panax ginseng Root Shi et al. (2007)
Oleanolic acid, High Vegetative growth period Achyranthes bidentata Root Li and Hu (2009)
Ecdysterone
Azulene Decrease With the development of Achillea millefolium Flower Figueiredo et al. (2008)
the flowers

pharmacological point of view and researchers face the necessity to alterations in various physiochemical and molecular processes (cellular
study them including qualities of light exposure are essential in order to dehydration, water uptake, and metabolic reactions) that enable plants
obtain higher yield of these valuable compounds. The effect of light on to survive low temperature stress, a phenomenon known as cold ac-
the content of SMs in plants is displayed in Table 2. climation (Ashraf et al., 2018). On the basis of global gene regulation of
unsaturated fatty acid biosynthesis and jasmonic acid biosynthesis-re-
3.2. Temperature stress lated genes, unsaturated fatty acid biosynthesis and jasmonic acid
biosynthesis pathways were deduced to be involved in the low tem-
Plant growth and development are directly linked with temperature perature responses in C. japonica (Li et al., 2016a). In response to
ranges at which the plants are present. Low and high temperature temperature stresses, plants have shown a coordinated change at the
ranges may have a negative impact on plant growth and productivity transcriptional level. Thus transcriptional regulation plays an essential
(Yadav, 2010). Plants growing at elevated temperatures exhibit a de- role in the adaptation of cells against environmental challenges. In
cline in the photochemical efficiency of photosystem II, indicating in- Artemisia annua, upon exposure to chilling and heat shock, the tran-
creased stress (Maxwell and Johnson, 2000). The biosynthesis of SMs is scription levels of amorpha-4,11-diene synthase (ADS) and cytochrome
also correlated with high temperature in plants (Verma and Shukla, P450 monooxygenase (CYP71AV1) genes were upregulated when
2015). High-temperature stress usually increased the production of SMs compared with control plants (Yin et al., 2008). These are mostly the
(Naghiloo et al., 2012a), whereas some studies reported that SMs were genes responsible for the expression of osmoprotectants, detoxifying
decreased in plants under high-temperature stress (Shibata et al., enzymes, transporter, and regulatory proteins. These studies indicated
1988). Thus, the SMs increase or decrease in response to elevated that the concentration of SMs of different plants is associated with the
temperatures and this is dependent on the species and multiple factors. metabolic pathway of the particular SMs and temperature conditions,
High temperature downregulates or upregulates the responding genes and a plant's ability to function in a stressful environment depends to a
and affects the growth and development of plants (Li et al., 2016b). In large extent on their genetic program (Dodd et al., 2006). The precise
such conditions of heat stress, modification of physiological and bio- mechanisms, however, need to be further demonstrated and need to
chemical processes by gene expression changes slowly leads to the explore the functions of various plant SMs in plants grown under
development of heat tolerance in the form of acclimation or adaptation stressful conditions. Temperature factors that influence production of
of a plant to high temperature (Hasanuzzaman et al., 2017). Plant plant SMs should be studied. Unraveling the involvement of the SMs in
growth and the biosynthesis and the storage of SMs are also sig- stress signaling can help in enhancing the selective metabolites for their
nificantly hampered as a result of low-temperature stress (Verma and exploitation in stress tolerance. Strategies must be developed to im-
Shukla, 2015). Plants grown under low temperature exhibit significant prove the potential of plants for SM production. The effect of

84
Y. Li, et al. Plant Physiology and Biochemistry 148 (2020) 80–89

temperature on the content of plant SMs is shown in Table 3.

Reifenrath and Müller (2007)

Reifenrath and Müller (2007)

Takshak and Agrawal (2014)

Takshak and Agrawal (2014)

Takshak and Agrawal (2014)

Takshak and Agrawal (2014)
Naghiloo et al. (2012b)
3.3. Drought stress

Eichholz et al. (2012)

Spitaler et al. (2006)
Estell et al. (2016)

Estell et al. (2016)

Kong et al. (2016)
Zhou et al. (2016)
Ma et al. (2016)

Ma et al. (2016)
Drought stress decreases water absorption and water potentials in

Li et al. (2018)

Li et al. (2018)

Li et al. (2018)
plants, which thereby negatively influence various physiological pro-
Refences

cesses and can alter SM biosynthesis (Ashrafia et al., 2018). There are
many reports relating to the effect of drought stress on SMs of medicinal
plants. For example, the content of flavonoids and phenolics is elevated
under severe drought stress condition in plants (De Abreu and
Mazzafera, 2005; Azhar et al., 2011). The elevation of phenolic and
Flowering heads

flavonoid compounds is highly related to the balance between carbo-

Root and leaf

Root and leaf

Root and leaf

Root and leaf
Whole plant,
Whole plant

hydrate sources and sinks. It was reported that the accumulation of

Root, stem

soluble carbohydrates in plant cells is affected by the reduced transport

Flower

Flower
Parts

Leaf

Leaf

Leaf
Leaf

Leaf
Leaf

Leaf
Leaf
of soluble sugars under water stress (Jaafar et al., 2012). When stresses
act upon plants, changes in gene expression also take place (Kilian
et al., 2007). In low to moderate drought stress condition, the expres-
sion of many genes contributing in the synthesis pathway of phenolic
Mahonia breviracema

Mahonia breviracema
Astragalus compactus

Nasturtium officinale

Nasturtium officinale
Asparagus officinalis
Erigeron breviscapus
Withania somnifera

Withania somnifera

Withania somnifera
Withania somnifera

compounds such as phenylalanine ammonialyase (PAL) are elevated

Mahonia bodinieri

Mahonia bodinieri
Flourensia cernua
Arnica montana
Chrysanthemum

Chrysanthemum

and this requires high energy inputs, while in moderating to severe

Plant Species

stress condition these energy-intensive processes are more limited (Król

Tarbush

et al., 2014). Also, an appropriate degree of drought stress may promote

baicalin accumulation by stimulating the expression and activities of
the key enzymes (PAL), (C4H), (4CL) and (CHS) involved in baicalin
biosynthesis of Scutellaria baicalensis Georgi (Cheng et al., 2018). In
another study, imposition of drought stress resulted in improved quality
Concentration Change

of key SMs such as rutin, quercetin, and betulinic acid in Hypericum

brasiliense, and that of artemisinin in Artemisia (Verma and Shukla,
2015). The sterol C-4 methyl oxidase gene (SMO1) gene, which has
No effect

been identified in Artemisia annua, is responsible for the enhanced

Increase
Increase
Increase
Increase

Increase
Increase
Increase
Increase

Increase
Increase
Increase
Increase
Increase
Increase

production of sterols and tolerance against dehydration/drought stress

(Singh et al., 2002). Drought promoted the synthesis of glycyrrhizin, as
indicated by the increases in the expression of the glycyrrhizin bio-
synthesis pathway genes SQS1, SQS2, bAS, CYP88D6, CYP72A154 and
30 and 50% Full sunlight

UGT73, and increased the root concentrations of glycyrrhizin with

drought in some genotypes of licorice (Glycyrrhiza glabra L.) (Hosseini
Environment Factor

50% Full sunlight

et al., 2018). These studies indicated that drought responsive metabo-

lites are produced/consumed by different pathways/cycles; new tech-
Full sunlight

Full sunlight
50% shade

nological approaches such as transcriptomics and proteomics could

help us to identify and manipulate of drought-responsive pathways/
UV-B
UV-B

UV-B
UV-B

UV-B
UV-B

UV

cycles involved in establishment of enhanced drought tolerance

(Ashrafia et al., 2018). More research is needed to completely under-
stand the regulatory proteins and genes involved in the biosynthesis of
plant SMs so that these may be manipulated for improving plant tol-
Sabinene, b-pinene, Borneol, Bornyl acetate, Z-jasmone

erance to drought stresses. Moreover, the concentrations of SMs are

significantly increased under drought stress conditions in the present
literature. It may be a reduced production of biomass in the stressed
plants and the rate of biosynthesis of SMs is not changed, resulting in
Flavonol quercetin-4′-O-monoglucoside
Light quality change on the content of various plant SMs.

their concentration on dry or fresh weight basis simply will be elevated.

So much more data on the biomass is required and thus the yields of
SMs per plant are available. The effect of drought on the content of SMs
Anthocyanins, lignin, tannins

in plants is displayed in Table 4.

3.4. Salinity stress

Hexadecanoic acid
Metabolite Name

Phenolic acids

Glucosinolate
Phytosterols
Essential oil

Soils with elevated levels of salt induce nutritional imbalances,

Scutellarin

Saponins,
Alkaloids
Alkaloids

hyper-osmotic stress and exhibit declines in photosynthesis, growth,

and uptake of nutrients in plants (Banerjee and Roychoudhury, 2017).
Plant SMs may undergo an increase or decrease in their concentration
in response to salinity-induced osmotic stress or specific ion toxicity
(Akula and Ravishankar, 2011). Plants growing under salinity stress
Metabolite Class

increase alkaloid and tannin concentration (Abd EL-Azim and Ahmed,

2009), phenolics (Verma and Shukla, 2015), saponins, flavonoids and
Alkaloids
Phenols

proline in Plantago ovata (Haghighi et al., 2012). A decrease in oil yields

Table 2

Others

during salt stress was reported in recent researches (Ali et al., 2008).
Moreover, many articles reported that the levels of the main

85
Y. Li, et al. Plant Physiology and Biochemistry 148 (2020) 80–89

Table 3
Temperature change on the content of various plant SMs.
Metabolite Metabolite Name Environment Factor Concentration Plant Species Parts Refences
Class Change

Sesquiterpene lactone Artemisinin A transient pre-chilling Increase Artemisia annua Whole plant Yin et al. (2008)
treatment
Phenols Phenolics High-temperature Increase Astragalus compactus Roots, leaf and Naghiloo et al.
flowers (2012a)
Anthocyanins High temperature Decrease Chrysanthemum Whole plant Shibata et al. (1988)
Fatty acid α-linolenic acid, Jasmonic Low temperature Increase Camellia japonica Leaf Li et al. (2016a)
acid

Table 4
Drought stress increases the concentration of various plant SMs.
Metabolite Metabolite Name Plant Species Parts Refences
Class

Phenols Total phenolics Hypericum brasiliense Shoots and roots De Abreu and Mazzafera (2005)
Trachyspermum ammi Leaf Azhar et al. (2011)
Labisia pumila Leaf Jaafar et al. (2012)
Baicalin Scutellaria baicalensis Whole plant Cheng et al. (2018)
Rutin, Quercetin, Hypericum brasiliense Verma and Shukla (2015)
Anthocyanins Labisia pumila Leaf Jaafar et al. (2012)
Pentacyclic triterpenoid Betulinic acid Hypericum brasiliense Verma and Shukla (2015)
Sesquiterpene lactone Artemisinin Artemisia Whole plant Verma and Shukla (2015)

compounds in essential oils of plants were differentially affected by salt content are often difficult to interpret as many abiotic conditions
stress (Neffati and Marzouk, 2008; Baatour et al., 2010). Salt stress usually interfere with complex internal factors. These studies may have
tolerance in plants is induced by multilevel changes in molecular re- a significant role in developing plants that are tolerant to multiple
sponses accompanied with alterations in the plant transcriptome, me- stresses. Hence, the optimum environmental conditions for plant
tabolome and proteome (Banerjee and Roychoudhury, 2018). These growth are very complex. There is a need for the development of broad-
transcription factors include various families, like AP2, ERF, bZIP, NAC, spectrum resistance (i.e., resistance to multiple stresses) in medicinal
MYB and WRKY which exhibit higher correlations with salinity (Kumar plants.
et al., 2017). Plant salt tolerance is controlled by a complex network Additionally, recent studies showed that the soil microbial com-
involving plant organ, tissue, physiology and molecule, and the changes munity plays an important role in promoting plant growth and health.
of stress-induced metabolites are also too complex. The biosynthesis of Studying the relationship between the composition of the soil microbial
SMs are undoubtedly influenced by different regulatory genes, en- community and the synthesis and accumulation of active constituents of
zymes, transcription factors and stresses caused by salinity leads to medicinal plants is expected to provide scientific guidance for the cul-
instability of accumulation or production of different SMs. The level of tivation and management of medicinal plants with the highest active
these SMs changes according to their need by the plants as defense ingredient content. SMs accumulation in plants in the course of plant-
molecules to survive them in unfavorable conditions. Moreover, the key soil microbial interaction definitely impels the development of attrac-
factor, receptor and mechanism of salinity stress should be pursued in tive strategies to bring medicinal plants cultivation into new era for
more details. Much more related research is required to elucidate the pharmaceutical purpose.
molecular coherences of this fascinating issue. Although transformation
of salt-tolerant gene have been done of some plants, the improvement
4. Conclusions and future prospects
of salt tolerance of transgenic plants is not very ideal and limited. On
the transgenic frontline, it should focus upon developing salt-tolerance
The content and composition of effective components, i.e., the SMs
in susceptible plant species and facilitate the introgression of salt-tol-
in medicinal plants are vary with changes in the growth seasons,
erant genes in susceptible species of medicinal plants. The effect of
growth years and environment. The SM content increases or decreases
salinity on the content of plant SM is shown in Table 5.
under developmental process or stress conditions in medicinal plants
with the same genetic background, because the gene expression or their
3.5. Other factors encoded protein activity involved in secondary metabolic pathways are
modified at different growth stages or in the presence of different
The synthesis and accumulation of SMs are also obviously influ- stresses. Therefore, to achieve a more precise understanding of the
enced by other environmental stresses such as soil type and composi- temporal and spatial patterns of synthesis and accumulation of active
tion, wounding, metal ions, circadian rhythm, geography (Verma and ingredients in specific organs, tissues and cells in plants, new technol-
Shukla, 2015). In recent years, there have been many reports on the ogies used to study genomics, transcriptomics and metabolomics will
effect of chemical stress (Verma and Shukla, 2015), nutrients (Dar et al., need to be applied. These can be used to reveal the molecular reg-
2016), metal ions (Ma et al., 2018) and geographical origins (Li et al., ulatory mechanisms of synthesis and metabolism of active constituents
2013) on SMs. In most cases, several environmental stresses jointly of medicinal plants at different growth stages and stress conditions.
cause drastic changes in the growth, physiology, and metabolism of Specifically, these may reveal changes in metabolic pathways of the
plants leading to the increased accumulation of SMs (Debnath et al., main active constituents of medicinal plants, which can provide im-
2011). The response of plants to multiple abiotic stresses is unique and portant theoretical foundations and technical support for the im-
cannot be directly speculated from simply studying one stress applied provement of medicinal plant varieties, protection of germplasm re-
individually. Plants with different genotypes might behave differen- sources, selection of suitable planting regions and synthesis of
tially under drought stress. Moreover, the differences in plant SM secondary metabolites.

86
Y. Li, et al. Plant Physiology and Biochemistry 148 (2020) 80–89

Contributions

Abd EL-Azim and Ahmed (2009)

Abd EL-Azim and Ahmed (2009)

Neffati and Marzouk (2008)

Neffati and Marzouk (2008)

Neffati and Marzouk (2008)

Neffati and Marzouk (2008)
H. Wu., conceived and designed the manuscript. Y.Q. Li., and D.X.

Haghighi et al. (2012)

Haghighi et al. (2012)

Kong., wrote the manuscript and contributed equally. Y. Fu., edited the

Baatour et al. (2010)

Baatour et al. (2010)

Baatour et al. (2010)
Ali et al. (2008) manuscript. M.R. Sussman., and H.Wu., performed the language editing

Ali et al. (2008)

and gave final approval of manuscript.
Refences

Declaration of competing interest

The authors declare that they have no competing interests.

Acknowledgements
Root and shoot

Root and shoot

Whole plant

Whole plant

Aerial part
Aerial part
This study was supported by the Science and Technology Innovation
Shoots
Shoot

Shoot
Parts

Fund Project on Forestry of Guangdong Province (2017KJ-CX006), the

Leaf
Leaf

Leaf
Leaf

Nature Science Foundation of China (31870172), Technology and

Development Project of Finance Department of Guangdong Province,
China ([2015]639).
Coriandrum sativum
Coriandrum sativum

Coriandrum sativum
Coriandrum sativum
Achillea fragratissima

Achillea fragratissima

Origanum majorana

Origanum majorana
Origanum majorana
Ricinus communis

Ricinus communis

References
Plantago ovata

Plantago ovata
Plant Species

Abd EL-Azim, W.M., Ahmed, S.T.h., 2009. Effect of salinity and cutting date on growth
and chemical constituents of Achillea fragratissima Forssk, under Ras Sudr conditions.
Res. J. Agric. Biol. Sci. 5 (6), 1121–1129.
Akula, R., Ravishankar, G.A., 2011. Influence of abiotic stress signals on secondary me-
tabolites in plants. Plant Signal. Behav. 6 (11), 1720–1731.
Ali, R.M., Elfeky, S.S., Abbas, H., 2008. Response of salt stressed Ricinus communis L. to
25 and 50 mM NaCl

exogenous application of glycerol and/or aspartic acid. J. Biol. Sci. 8 (1), 171–175.
Ashraf, M.A., Iqbal, M., Rasheed, R., Hussain, I., Riaz, M., Arif, M.S., 2018. Environmental
100 Mm NaCl
Environment

High salinity

Stress and Secondary Metabolites in Plants: an Overview. Plant Metabolites and

Regulation under Environmental Stress. pp. 153–167.
Salinity

Salinity

Salinity
Salinity

Ashrafia, M., Azimi-Moqadama, M.R., Moradib, P., MohseniFarda, E., Shekaria, F.,
Factor

NaCl

NaCl
NaCl

NaCl
NaCl
NaCl

Kompany-Zareh, M., 2018. Effect of drought stress on metabolite adjustments in

drought tolerant and sensitive thyme. Plant Physiol. Biochem. 132, 391–399.
Azhar, N., Hussain, B., Ashraf, Y.M., Abbasim, K.Y., 2011. Water stress mediated changes
in growth, physiology and secondary metabolites of desi ajwain (Trachyspermum
ammi). Pak. J. Bot. 43 (9), 15–19.
Concentration Change

Baatour, O.R., Kaddour, W., Wannes, A., Lachaal, M., Marzouk, B., 2010. Salt effects on
the growth, mineral nutrition, essential oil yield and composition of marjoram
(Origanum majorana). Acta Physiol. Plant. 32 (1), 45–51.
Banerjee, A., Roychoudhury, A., 2017. Effect of Salinity Stress on Growth and Physiology
Decrease

Decrease
Decrease

of Medicinal Plants. Medicinal Plants and Environmental Challenges. pp. 177–188.

Increase
Increase
Increase
Increase
Increase

Increase

Increase
Increase

Banerjee, A., Roychoudhury, A., 2018. Effect of Salinity Stress on Growth and Physiology
of Medicinal Plants. Plant Metabolites and Regulation under Environmental Stress.
pp. 153–167.
Bartwal, A., Mall, R., Lohani, P., Guru, S.K., Arora, S., 2013. Role of secondary metabo-
lites and brassinosteroids in plant defense against environmental stresses. J. Plant
cis-Sabinene Hydrate; Linalyl acetate; Terpinene-4-ol

Growth Regul. 32 (1), 216–232.

Belkheir, A.K., Gaid, M., Liu, B., Hänsch, R., Beerhues, L., 2016. Benzophenone synthase
and chalcone synthase accumulate in the Mesophyll of Hypericum perforatum Leaves
at different developmental stages. Front. Plant Sci. 7, 921. https://doi.org/10.3389/
fpls.2016.00921.
Borges, C.V., Minatel, I.O., Gomez-Gomez, H.A., Lima, G.P.P., 2017. Medicinal Plants:
Trans-sabinene Hydrate; γ-Terpinene

Influence of Environmental Factors on the Content of Secondary Metabolites.

Medicinal Plants and Environmental Challenges. pp. 259–277.
Octanal; Borneol; (E)-2-Nonenal

Broun, P., Liu, Y., Queen, E., Schwarz, Y., Abenes, M.L., Leibman, M., 2006. Importance of
transcription factors in the regulation of plant secondary metabolism and their re-
Soil salinity change on the content of various plant SMs.

levance to the control of terpenoid accumulation. Phytochem. Rev. 5 (1), 27–38.

α-Pinene; (Z)-Myroxide

Cheng, L., Han, M., Yang, L.M., Yang, L., Sun, Z., Zhang, T., 2018. Changes in the phy-
siological characteristics and baicalin biosynthesis metabolism of Scutellaria baica-
Recinine alkaloids

Saponins, Proline
Metabolite Name

lensis Georgi under drought stress. Ind. Crops Prod. 122, 473–482.
Dar, T.A., Uddin, M., Khan, M.M.A., Ali, A., Varshney, L., 2016. Modulation of alkaloid
Oil contents

Oil contents
Flavonoids

content, growth and productivity of Trigonella foenum-graecum L. using irradiated

Alkaloid

sodium alginate in combination with soil applied phosphorus. J. Appl. Res. Med.
Tannin

Aromat. Plants 3 (4), 200–210.

De Abreu, I.N., Mazzafera, P., 2005. Effect of water and temperature stress on the content
of active constituents of Hypericum brasiliense Choisy. Plant Physiol. Biochem. 43 (3),
241–248.
Debnath, M., Pandey, M., Bisen, P.S., 2011. An omics approach to understand the plant
Monoterpenes/Essential Oils

abiotic stress. OMICS 15 (11), 739–762.

Dey, M., Kalia, S., Ghosh, S., Guha-Mukherjee, S., 1998. Biochemical and molecular basis
Flavonoids compounds

of differentiation in plant tissue culture. Curr. Sci. 74, 591–596.

Dodd, A.N., Jakobsen, M.K., Baker, A.J., Telezerow, A., Hos, S.W., Laplaze, L., Barrot, L.,
Poething, R.S., Haselhoff, J., Webb, A.A.R., 2006. Time of day modulates low-tem-
perature Ca2+ signals in Arabidopsis. Plant J. 48 (6), 962–973.
Metabolite

Dudareva, N., Martin, D., Kish, C.M., Kolosova, N., Gorenstein, N., Fäldt, J., Miller, B.,
Phenolics
Alkaloids

Bohlmann, J., 2003. (E)-beta-ocimene and myrcene synthase genes of floral scent
Table 5

Others
Class

biosynthesis in snapdragon: function and expression of three terpene synthase genes

of a new terpene synthase subfamily. Plant Cell 15, 1227–1241.

87
Y. Li, et al. Plant Physiology and Biochemistry 148 (2020) 80–89

Eichholz, I., Rohn, S., Gamm, A., Beesk, N., Herppich, W.B., Kroh, L.W., Ulrichs, C., PCR expression of HCT, HQT, C3H1, and CCoAOMT1 genes during grain development
Huyskens-Keil, S., 2012. UV-B-mediated flavonoid synthesis in white asparagus in C. canephora. Plant Sci. 172 (5), 978–996.
(Asparagus officinalis L.). Food Res. Int. 48 (1), 196–201. Li, J.T., Hu, Z.H., 2009. Accumulation and dynamic trends of triterpenoid saponin in
Estell, R.E., Fredrickson, E.L., James, D.K., 2016. Effect of light intensity and wavelength vegetative organ of Achyranthus bidentata. J. Integr. Plant Biol. 51, 122–129.
on concentration of plant secondary metabolites in the leaves of Flourensia cernua. Li, K.H., Huang, W., Wang, G.L., Wu, Z.J., Zhuang, J., 2016b. Expression profile analysis
Biochem. Syst. Ecol. 65, 108–114. of ascorbic acid-related genes in response to temperature stress in the tea plant,
Fahn, A., 1988. Secretory tissues in vascular plants. New Phytol. 108 (3), 229–257. Camellia sinensis (L.) O. Kuntze. Genet. Mol. Res. 15, 1–10.
Fang, X., Yang, C.M.A.Q., Yang, L., Chen, X., 2011. Genomics grand for diversified plant Li, Q., Lei, S., Du, K., Li, L., Pang, X., Wang, Z., Wei, M., Fu, S., Hu, L., Xu, L., 2016a. RNA-
secondary metabolites. Plant Divers. Resour. 33, 53–64. seq based transcriptomic analysis uncovers a-linolenic acid and jasmonic acid bio-
Figueiredo, A.C., Barroso, J.G., Pedro, L.G., Scheffer, J.J.C., 2008. Factors affecting sec- synthesis pathways respond to cold acclimation in Camellia japonica. Sci. Rep. UK 6,
ondary metabolite production in plants: volatile components and essential oils. 36463. https://doi.org/10.1038/srep36463.
Flavour Fragrance J. 23 (4), 213–226. Li, Y.Q., Kong, D.X., Bai, M., He, H.J., Wang, H.Y., Wu, H., 2019. Correlation of the
Geng, S.L., Cui, Z.X., Huang, X.C., Chen, Y.F., Xu, D., Xiong, P., 2011. Variations in es- temporal and spatial expression patterns of HQT with the biosynthesis and accu-
sential oil yield and composition during Cinnamomum cassia bark growth. Ind. Crops mulation of chlorogenic acid in Lonicera japonica flowers. Hortic. Res. 6, 73. https://
Prod. 33 (1), 248–252. doi.org/10.1038/s41438-019-0154-2.
Gomes, A.F., Almeida, M.P., Leite, M.F., Schwaiger, S., Stuppner, H., Halabalaki, M., Li, Y.Q., Kong, D.X., Huang, R.S., Liang, H.L., Xu, C.G., Wu, H., 2013. Variations in vo-
Amaral, J.G., David, J.M., 2019. Seasonal variation in the chemical composition of latile oil yields and compositions of Cinnamomum cassia leaves at different develop-
two chemotypes of Lippia alba. Food Chem. 273, 186–193. mental stages. Ind. Crops Prod. 47, 92–101.
Gregoriou, K., Pontikis, K., Vemmos, S., 2007. Effects of reduced irradiance on leaf Li, Y.Q., Kong, D.X., Liang, H.L., Wu, H., 2018. Alkaloid content and essential oil com-
morphology, photosynthetic capacity, and fruit yield in olive (Olea europaea L.). position of Mahonia breviracema cultivated under different light environments. J.
Photosynthetica 45, 172–181. Appl. Bot. Food Qual. 91, 171–179.
Gupta, N., Sharma, S.K., Rana, J.C., Chauhan, R.S., 2011. Expression of flavonoid bio- Li, Y.Q., Kong, D.X., Lin, X.M., Xie, Z.H., Bai, M., Huang, S.S., Nian, H., Wu, H., 2016c.
synthesis genes vis-à-vis rutin content variation in different growth stages of Quality evaluation for essential oil of Cinnamomum verum leaves at different growth
Fagopyrum species. J. Plant Physiol. 168 (17), 2117–2123. stages based on GC–MS, FTIR and microscopy. Food Anal. Methods 9 (1), 202–212.
Haghighi, Z., Modarresi, M., Mollayi, S., 2012. Enhancement of compatible solute and Liang, S.J., Wu, H., Lun, X., Lu, D.W., 2006. Secretory cavity development and its re-
secondary metabolites production in Plantago ovata Forsk. by salinity stress. J. Med. lationship with the accumulation of essential oil in fruits of Citrus medica L. var.
Plants Res. 6 (18), 3495–3500. sarcodactylis (Noot.) Swingle. J. Integr. Plant Biol. 48 (5), 573–583.
Hasanuzzaman, M., Nahar, K., Anee, T.I., Fujita, M., 2017. Glutathione in plants: bio- Ma, C.H., Chu, J.Z., Shi, X.F., Liu, C.Q., Yao, X.Q., 2016. Effects of enhanced UV-B ra-
synthesis and physiological role in environmental stress tolerance. Physiol. Mol. Biol. diation on the nutritional and active ingredient contents during the floral develop-
Plants 23 (2), 249–268. ment of medicinal chrysanthemum. J. Photochem. Photobiol., B 158, 228–234.
Hassan, A.R.B., 2012. Medicinal plants (importance and uses). Pharm. Anal. Acta 3, e139. Ma, Z.Q., Zhang, S.S., 2010. Light intensity affects growth, photosynthetic capability, and
https://doi.org/10.4172/2153-2435.1000e139. total flavonoid accumulation of Anoectochilus plants. HortScience 45, 863–867.
Hong, D.Y.Q., Lau, A.J., Yeo, C.L., Liu, X.K., Yang, C.R., Koh, H.L., Hong, Y., 2005. Ma, S.J., Zhu, G.W., Yu, F.L., Zhu, G.H., Wang, D., Wang, W.Q., Hou, J.L., 2018. Effects of
Genetic diversity and variation of saponin contents in Panax notoginseng roots from a manganese on accumulation of Glycyrrhizic acid based on material ingredients dis-
single farm. J. Agric. Food Chem. 53 (22), 8460–8467. tribution of Glycyrrhiza uralensis. Ind. Crops Prod. 112, 151–159.
Hosseini, M.S., Samsampoura, D., Ebrahimib, M., Abadíac, J., Khanahmadi, M., 2018. Maxwell, K., Johnson, G.N., 2000. Chlorophyll fluorescence-A practical guide. J. Exp. Bot.
Effect of drought stress on growth parameters, osmolyte contents, antioxidant en- 345, 659–668.
zymes and glycyrrhizin synthesis in licorice (Glycyrrhiza glabra L.) grown in the field. Nagegowda, D.A., Gutensohn, M., Wilkerson, C.G., Dudareva, N., 2008. Two nearly
Phytochemistry 156, 124–134. identical terpene synthases catalyze the formation of nerolidol and linalool in
Hu, M.L., Bai, M., Ye, W., Wang, Y.L., Wu, H., 2018. Variations in volatile oil yield and snapdragon. Plant J. 55 (2), 224–239.
composition of "Xin-yi" (Magnolia biondii Pamp. Flower Buds) at different growth Naghiloo, S., Movafeghi, A., Delazar, A., Nazemiyeh, H., Asnaashari, S., Dadpour, M.R.,
stages. J. Oleo Sci. 67 (6), 779–787. 2012a. Ontogenetic variation of total phenolics and antioxidant activity in roots:
Hu, M.L., Li, Y.Q., Bai, M., Wang, H., Wu, H., 2015. Variations in volatile oil yields and leaves and flowers of Astragalus compactus Lam. (Fabaceae). Bioimpacts 2 (2),
compositions of Magnolia zenii Cheng flower buds at different growth stages. Trees 105–109.
Struct. Funct. 29 (6) 1694–1660. Naghiloo, S., Movafeghi, A., Delazar, A., Nazemiyeh, H., Asnaashari, S., Dadpour, M.R.,
Hu, G.Q., Yuan, Y., Wu, C., Jiang, C., Wang, Z.Y., Lin, S.F., Wu, Z.G., 2012. Effects of 2012b. Ontogenic variation of volatiles and antioxidant activity in leaves of
different development stages on growth and accumulation of active components of Astragalus compactus Lam. (Fabaceae). Excli. J. 11, 436–443.
scutellaria baicalensis. China J. Chin. Mater. Med. 37, 3793–3798. Navarre, D.A., Payyavula, R.S., Shakya, R., Knowles, N.R., Pillai, S.S., 2013. Changes in
Jaafar, H.Z., Ibrahim, M.H., Mohamad, F.N.F., 2012. Impact of soil field water capacity on potato phenylpropanoid metabolism during tuber development. Plant Physiol.
secondary metabolites, phenylalanine ammonia-lyase (PAL), maliondialdehyde Biochem. 65, 89–101.
(MDA) and photosynthetic responses of Malaysian kacip fatimah (Labisia pumila Neffati, M., Marzouk, B., 2008. Changes in essential oil and fatty acid composition in
Benth). Molecules 17 (6), 7305–7322. coriander (Coriandrum sativum L.) leaves under saline conditions. Ind. Crops Prod. 28,
Katerova, Z., Todorova, D., Sergiev, I., 2017. Plant Secondary Metabolites and Some Plant 137–142.
Growth Regulators Elicited by UV Irradiation, Light And/or Shade. Medicinal Plants Patra, B., Schluttenhofer, C., Wu, Y.M., Pattanaik, S., Ling, Y., 2013. Transcriptional
and Environmental Challenges. pp. 97–121. regulation of secondary metabolite biosynthesis in plants. BBA Gene Regul. Mech.
Kilian, J., Whitehead, D., Horak, J., Wanke, D., Weinl, S., Batistic, O., Angelo, C., 1829 (11), 1236–1247.
Bornberg-Bauer, E., Kudla, J., Harter, K., 2007. The AtGenExpress global stress ex- Pan, W.S., Zheng, L.P., Tian, H., Li, W.Y., Wang, J.W., 2014. Transcriptome responses
pression data set: protocols, evolution and model data analysis of UV-B light, drought involved in artemisinin production in Artemisia annua L. under UV-B radiation. J.
and cold stress responses. Plant J. 50 (2), 347–363. Photochem. Photobiol., B 140, 292–300.
Kong, D.X., Li, Y.Q., Bai, M., Deng, Y.L., Liang, G.X., Wu, H., 2017b. A comparative study Reifenrath, K., Müller, C., 2007. Species-specific and leaf-age dependent effects of ul-
of the dynamic accumulation of polyphenol components and the changes in their traviolet radiation on two Brassicaceae. Phytochemistry 68 (6), 875–885.
antioxidant activities in diploid and tetraploid Lonicera japonica. Plant Physiol. Rokem, J.S., Lantz, A.E., Nielsen, J., 2008. Systems biology of antibiotic production by
Biochem. 112, 87–96. microorganisms. Nat. Prod. Rep. 24, 1262–1287.
Kong, D.X., Li, Y.Q., Bai, M., He, H.J., Liang, G.X., Wu, H., 2017a. Correlation between Sanchita, Sharma, A., 2018. Gene Expression Analysis in Medicinal Plants under Abiotic
the dynamic accumulation of the main effective components and their associated Stress Conditions. Plant Metabolites and Regulation under Environmental Stress. pp.
regulatory enzyme activities at different growth stages in Lonicera japonica. Thunb. 407–414.
Ind. Crop. Prod. 96, 16–22. Shi, W., Wang, Y., Li, J., Zhang, H., Ding, L., 2007. Investigation of ginsenosides in dif-
Kong, D.X., Li, Y.Q., Wang, M.L., Bai, M., Zou, R., Tang, H., Wu, H., 2016. Effects of light ferent parts and ages of Panax ginseng. Food Chem. 102 (3), 664–668.
intensity on leaf photosynthetic characteristics, chloroplast structure, and alkaloid Shibata, M., Amano, M., Kawata, J., Uda, M., 1988. Breeding process and characteristics
content of Mahonia bodinieri (Gagnep.) Laferr. Acta Physiol. Plant. 38 (5), 120. of ‘Summer Queen’, a spray-type chrysanthemum. Bull. Natl. Res. Inst. Veg.
Król, A., Amarowicz, R., Weidner, S., 2014. Changes in the composition of phenolic Ornamental Plants Tea Ser. A 2, 245–255.
compounds and antioxidant properties of grapevine roots and leaves (Vitis vinifera L.) Shukla, S., Singh, S.P., 2001. Alkaloid profile in relation to different developmental stages
under continuous of long-term drought stress. Acta Physiol. Plant. 36 (6), 1491–1499. of Papaver somniferum L. Phyton Ann. Rei Bot. A 41 (1), 87–96.
Kumar, J., Singh, S., Singh, M., Srivastava, P.K., Mishra, R.K., Singh, V.P., Prasad, S.M., Singh, K.B., Foley, R.C., Onate-Sanchez, L., 2002. Transcription factors in plant defense
2017. Transcriptional regulation of salinity stress in plants: a short review. Plant and stress responses. Curr. Opin. Plant Biol. 5 (5), 430–436.
Gene 11, 160–169. Singh, N., Sharma, A., 2017. Turmeric (Curcuma longa): miRNAs and their regulating
Kurepin, L.V., Ivanov, A.G., Zaman, M., Pharis, R.P., Hurry, V., Hüner, N.P.A., 2017. targets are involved in development and secondary metabolite pathways. CR Biol.
Interaction of Glycine betaine and plant hormones: protection of the photosynthetic 340 (11–12), 481–491.
apparatus during abiotic stress. In: Hou, H.J.M., Najafpour, M.M., Moore, G.F., Southwell, I.A., Russell, M.F., 2002. Volatile oil comparison of cotyledon leaves of che-
Allakhverdiev, S.I. (Eds.), Photosynthesis: Structures, Mechanisms, and Applications. motypes of Melaleuca alternifolia. Phytochemistry 59 (4), 391–393.
Springer International Publishing, Cham, pp. 185–202. Spitaler, R., Schlorhaufer, P.D., Ellmerer, E.P., Merfort, I., Bortenschlager, S., Stuppner,
Lavola, A., Julkunen-Tiitto, R., de la Rosa, T.M., Lehto, T., Aphalo, P.J., 2000. Allocation H., Zidorn, C., 2006. Altitudinal variation of secondary metabolite profiles in flow-
of carbon to growth and secondary metabolites in birch seedlings under UV-B ra- ering heads of Arnica montana cv. ARBO. Phytochemistry 67 (4), 409–417.
diation and CO2 exposure. Physiol. Plant. 109 (3), 260–267. Szymańska, R., Ślesak, I., Orzechowska, A., Kruk, J., 2017. Physiological and biochemical
Lepelley, M., Cheminade, G., Tremillon, N., Simkin, A., Caillet, V., McCarthy, J., 2007. responses to high light and temperature stress in plants. Environ. Exp. Bot. 139,
Chlorogenic acid synthesis in coffee: an analysis of CGA content and real-time RT- 165–177.

88
Y. Li, et al. Plant Physiology and Biochemistry 148 (2020) 80–89

Takshak, S., Agrawal, S.B., 2014. Secondary metabolites and phenylpropanoid pathway Xu, C.G., Tang, T.X., Chen, R., Liang, C.H., Liu, X.Y., Wu, C.L., Yang, Y.S., Yang, D.P., Wu,
enzymes as influenced under supplemental ultraviolet-B radiation in Withania som- H., 2014. A comparative study of bioactive secondary metabolite production in di-
nifera Dunal, an indigenous medicinal plant. J. Photochem. Photobiol., B 140, ploid and tetraploid Echinacea purpurea (L.) Moench. Plant Cell Tissue Organ Cult.
332–343. 116 (3), 323–332.
Tobias, N.J., Heinrich, A.K., Eresmann, H., Wright, P.R., Neubacher, N., Backofen, R., Xu, J.Y., Yu, Y.L., Shi, R.Y., Xie, G.Y., Zhu, Y., Wu, G., Qin, M.J., 2018. Organ-specific
Bode, H.B., 2016. Photorhabdus‐nematode symbiosis is dependent on hfq‐mediated metabolic shifts of flavonoids in Scutellaria baicalensis at different growth and de-
regulation of secondary metabolites. Environ. Microbiol. 19 (1). https://doi.org/10. velopment stages. Molecules 23 (2), 428.
1111/1462-2920.13502. Yadav, S.K., 2010. Cold stress tolerance mechanisms in plants. A review. Agron. Sustain.
Valverde, C., 2017. Who's the boss here? The post‐transcriptional global regulator Hfq Dev. 30 (3), 515–527.
takes over control of secondary metabolite production in the nematode symbiont Yang, Z.N., Lu, S.Q., Yu, Z.W., 2012. Comparison analysis of bioactive compunds of
Photorhabdus luminiscens. Environ. Microbiol. 19 (1), 21–24. Mignolia Rehd. et Wils from different growth ages. Heilongjiang Med. J. 25 (4),
Vazquez-Leon, L.A., Paramo-Calderon, D.E., Robles-Olvera, V.J., Valdes-Rodriguez, O.A., 553–555.
Perez Vazquez, A., Garcia-Alvarado, M.A., Rodriguez-Jimenes, G.C., 2017. ariation in Yin, L., Zhao, C., Huang, Y., Yang, R.Y., Zeng, Q.P., 2008. Abiotic stress-induced ex-
bioactive compounds and antiradical activity of Moringa oleifera leaves: influence of pression of artemisinin biosynthesis genes in Artemisia annua L. Chin. J. Appl.
climatic factors, tree age, and soil parameters. Eur. Food Res. Echnol. 243, Environ. Biol. 14 (1), 1–5.
1593–1608. Zandalinas, S.I., Mittler, R., Balfagón, D., Arbona, V., Gómez-Cadenas, A., 2017. Plant
Verma, N., Shukla, S., 2015. Impact of various factors responsible for fluctuation in plant adaptations to the combination of drought and high temperatures. Physiol. Plant.
secondary metabolites. J. Appl. Res. Med. Aromat. Plants 2 (4), 105–113. https://doi.org/10.1111/ppl.12540.
Wang, X.J., Ren, J.L., Zhang, A.H., Sun, H., Yan, G.L., Han, Y., Liu, L., 2019. Novel ap- Zhang, L.X., Guo, Q.S., Chang, Q.S., Zhu, Z.B., Liu, L., Chen, Y.H., 2015. Chloroplast
plications of mass spectrometry-based metabolomics in herbal medicines and its ultrastructure, photosynthesis and accumulation of secondary metabolites in
active ingredients: current evidence. Mass Spectrom. Rev. https://doi.org/10.1002/ Glechoma longituba in response to irradiance. Photosynthetica 53 (1), 144–153.
mas.21589. Zhou, R., Su, W.H., Zhang, G.F., Zhang, Y.N., Guo, X.R., 2016. Relationship between
Wilf, N.M., 2011. The role of post-transcriptional regulators in pathogenesis and sec- flavonoids and photoprotection in shade-developed Erigeron breviscapus transferred to
ondary metabolite production in Serratia sp. ATCC 39006. http://www.repository. sunlight. Photosynthetica 54 (2), 201–209.
cam.ac.uk/handle/1810/245284. Zhu, Y., Xu, C.H., Huang, J., Li, G.Y., Liu, X.H., Sun, S.Q., Wang, J.H., 2014. Rapid dis-
Wu, Z., Li, H., Yang, Y., Zhan, Y., Tu, D.W., 2013. Variation in the components and crimination of cultivated Codonopsis lanceolata in different ages by FT-IR and 2DCOS-
antioxidant activity of Citrus medica L. var. sarcodactylis essential oils at different IR. J. Mol. Struct. 1069, 272–279.
stages of maturity. Ind. Crops Prod. 46, 311–316.

89