Stigmasterol

Stigmasterol, also known as stigmasterin or wulzen antistiffness factor, is one of a

group of plant sterols which is used in multiple chemical processes designed to yield
synthetic and semisynthetic compounds in the pharmaceutical industry.

From: A Centum of Valuable Plant Bioactives, 2021

Related terms:

Cholesterol, Sterol, Phytosterol, Campesterol, Beta-Sitosterol, Sitosterol, Toco-

pherol, Lipids, Seed Oils, Fatty Acids

View all Topics

Stigmasterol
Rizwan Ashraf, Haq Nawaz Bhatti, in A Centum of Valuable Plant Bioactives, 2021

10.5.1 Anticancer activity

Stigmasterols likewise, other plant sterols have shown astonishing anticancer prop-
erties against various cancer cell lines through the different potential mechanisms
of actions. Stigmasterol has been reported for its anticancer properties against a
number of cancer cell lines including but not limited to lung, ovary, stomach, and
estrogen-dependent human breast cancers (Bradford & Awad, 2007). Although the
anticancer activity of stigmasterol has not been fully explored, some researchers have
suggested some theories that cancer could be controlled through stigmasterol by
scavenging cancer-causing substances. In this regard, stigmasterol can be studied
for its anticancer activity through parameters of the basement like the ability to scav-
enge oxidative stress, control of DNA damage, measurement of histopathological
changes, and sometimes monitoring of kidney and liver functions. Moreover, it has
been speculated that stigmasterol participates in avoidance of carcinogen produc-
tion, inhibiting cancer-cell multiplication, metastasis, and invasion, and sometimes
promotes cancer apoptosis (Guarneri et al., 2006). Some of these mechanisms of
action for anticancer activity of stigmasterol are discussed briefly.
Stigmasterol is an important plant sterol that can inhibit the development of various
cancerous cells by inhibiting the promotion and growth of apoptosis of cancer
cells. This inhibition could be due to the activation of caspase enzymes (enzymes
involved in cell regulatory networks that control cell death). Plant sterols, stig-
masterol, when incorporates in the cell membrane increased the caspase enzyme’s
activity by producing changes in membrane structure and fluidity by replacing
the cholesterol of the membrane. These changes in membrane structure increased
extra and intracellular protein efflux and affect the signal transduction pathway that
activates the caspase enzyme. The other pathway which helps in the avoidance of
cancer is the inhibition of cancer enhancing species or scavenging of free radicals.
These free radicals are reactive oxygen species (ROS) produced in the body by the
oxidation of stressed cells that can damage DNA, and consequently could initiate or
proliferate cancer in the body, and breakage of this chain could be helpful to control
cancer proliferation (Michelini et al., 2016).

A seminal study by Vivancos and Moreno (2005) reported that the antioxidant activity
of the enzyme can also be improved by the synergistic effect of stigmasterol that
increased the ability of glutathione peroxidase and superoxide dismutase. The was
conducted in cultured macrophage cells in which oxidative stress was induced
by phorbol (12-myristate 13-acetate) and antioxidant activity of stigmasterol was
measured through monitoring the avoidance of damage of macrophages cells which
indicated that phytosterols are very helpful in protection of damage from ROS. In
vivo study on albino mice was conducted to monitor the tumor volume of mice by
the use of stigmasterol, separated from aerial parts of Bacopamonnieri Linn., which
indicates the antitumor activity of stigmasterol when a reduction in tumor volume
viable cell count was observed. The life span of treated mice was compared with
negative control and a significant increase in the life of treated mice was observed,
which indicates the potential role of stigmasterol in tumor control. The antioxidant
role of stigmasterol was observed when a decreased in levels of lipid peroxidation
and an increase in levels of glutathione was found. Moreover, the histopathological
study of liver tissues also supports the claim of the protective effect of stigmasterol
for EAC-bearing mice (Ghosh, Maity, & Singh, 2011).

A histopathological study of skin that was treated with dimethylbenzanthracene

(DMBA) showed severe skin damage and the effect of stigmasterol on the repair
of skin damage was investigated. DMBA is an immunosuppressor and lab-scale
carcinogenic chemical that deliberately induced cancer and mostly used for the
study of in vitro anticancer potential. When skin damage of DMBA was treated with
stigmasterol which was extracted from A. indica, a repair in degenerated dermal and
epidermal layers of skin was observed. The histological changes observed in dermis
and hypodermis were associated with the antioxidant activity of stigmasterol. Al-
though the overall structure of stigmasterol showed astonishing antioxidant activity,
the presence of hydroxyl groups on the aromatic ring of stigmasterols was found
responsible for their antioxidant activity. The further effect was assessed through
Comet assay which showed that DMBA induced significant DNA damage in lym-
phocytes. These findings of different studies indicate that the anticancer potential
of stigmasterol might be due to its antigenotoxic and antioxidant properties (Ali et
al., 2015).

> Read full chapter

Role of mangrove endophytic fungi in

diabetes mellitus
R. Nathiya, Gayathri Mahalingam, in Biotechnological Utilization of Mangrove Re-
sources, 2020

21.3.1.1 Avicennia sp
The secondary metabolites like stigmasterol, stigmasterol-3-O- -d galactopyra-
noside and three triterpenoids, lupeol, taraxerol, and betulinic acid, were obtained
from pneumatophores (aerial roots) of the mangrove plant A. marina. Among these
compounds, stigmasterol-3-O- -d galactopyranoside showed antiglycation prop-
erties with an inhibition percentage of 58.4% (Mahera et al., 2011). The ethanolic
extracts of the leaf and bark of A. officinalis L. were reported as having in vitro
antidiabetic activities ( -glucosidase, -amylase inhibitory), antimicrobial activities,
and antioxidant activities. These pharmacological activities of ethanolic leaf and bark
extracts of A. officinalis L. could be due to the synergetic effect of phenols, tannins,
and flavonoids (Das et al., 2018).

> Read full chapter

Ecdysteroid Chemistry and Biochem-

istry☆
R. Lafont, ... H.H. Rees, in Reference Module in Life Sciences, 2017

4.1.1 General scheme of cholesterol formation from phytos-

terols
A given species usually contains a complex sterol cocktail, with a few major com-
pounds and many minor ones. Sterol diversity concerns (1) the number of carbon
atoms (27 to 29) as discussed above and (2) the number and position of unsatura-
tions, classically termed ∆: mainly ∆5 and ∆7 on the steroid nucleus, and ∆22 and
∆24 on the side-chain (Fig. 9). In addition, sterols can be in free or conjugated form,
ie, sterol acyl esters with various fatty acids or sterol acylglucosides, where a sugar
moiety is linked both to the 3 -OH of the sterol and to a fatty acid (Eichenberger,
1977; Grunwald, 1980).

Fig. 9. Structures of cholesterol and of representative phytosterols.

Ingested sterols are subjected to the action of several types of enzymes: (1) hydrolytic
enzymes (esterases or glycosidases) from the insect gut (see Section 5), which
will release free sterols from their conjugates; (2) reductases and/or oxidases; and
(3) enzymes involved in the so-called “dealkylation process.” Reactions (2) and (3)
have been investigated extensively from the late 1960s by a combination of several
strategies: feeding experiments with diets containing one particular sterol; in vivo
metabolic studies with [1H] or [14C] labeled sterols allowing the isolation of labeled
intermediates; enzymatic studies using isolated tissues or cell-free preparations; and
observing the effects of various pharmacological inhibitors of reactions known in
mammals/humans (ie, hypocholesterolemic agents). All the biochemical pathways
have been fully elucidated, at least with regards to the metabolism of the most
common ∆5 plant sterols (reviews: Fujimoto et al., 1985b; Svoboda and Thompson,
1985; Svoboda and Feldlaufer, 1991; Svoboda and Weirich, 1995; Svoboda, 1999),
and are summarized in Fig. 10.
Fig. 10. From phytosterols to cholesterol: the dealkylation processes.

> Read full chapter

Terpenes
Christophe Wiart PharmD, PhD, in Lead Compounds from Medicinal Plants for the
Treatment of Cancer, 2013
Phytopharmacology
The plant is known to contain a series of campesterol, stigmasterol and sitosterol
derivatives,122 triterpenes such as lupeol and -amyrin-3-acetate,123 the tigliane-type
diterpenes 12-deoxy phorbol-13-hexadecanoate, 12-deoxyphorbol-13-acetate,-
124 langduin A, prostratin,125 12-deoxyphorbaldehyde-13-acetate, 12-deoxyphor-

baldehyde-13-hexadecacetate, 12-deoxyphorbol-13-(9Z)-octadecanoate-20-acetate,
12-deoxyphorbol-13-decanoate,126 fischerosides A-C,127 the ent-abietane diterpenes
langduin B, 17-acetoxyjolkinolide A and B, jolkinolide A and B, 17-hydroxyjolki-
nolide A and B,128 7 ,11 ,12 -trihydroxy-ent-abieta-8(14), 13(15)-dien-16,12-olide,
17-acetoxyjolkinolide B, 13-hydroxy-ent-abiet- 8(14)-en-7-one,126 the pimarane
diterpene 3 R,17-dihydroxy-ent-pimara-8(14), 15-diene126 unusual diterpenes of
which langduin C129 and D130 and some phenolics such as scopoletin, physcion and
2,4-dihydroxy-6- methoxy-1-acetophenone.123

The anticancer property of the plant is owed to the ent-abietane 17-acetoxyjolkino-

lide A and B.131,132

> Read full chapter

Nanoencapsulation of Enzymes, Bioac-

tive Peptides, and Biological Molecules
Muhammed Yusuf Çağlar, ... İbrahim Gülseren, in Nanoencapsulation of Food
Bioactive Ingredients, 2017

8.4 Phytosterols
Phytosterols are a group of phytochemicals that include compounds such as stig-
masterol, -sitosterol, and campesterol. Plant stanols, which are found naturally
at lower concentrations than sterols, can be produced by the hydrogenation of
phytosterols. Phytosterol concentrations in vegetable oils range from 0.1% to 1.0%
(Chaiyasit, Elias, McClements, & Decker, 2007) and typical phytosterol consumption
is in the range of 200 to 400 mg/day. The production of phytosterol fortified
foods has become popular due to the ability of phytosterols to decrease total and
low-density lipoprotein cholesterol in humans by inhibiting the absorption of dietary
cholesterol (Wong, 2001; Ostlund, 2004).

Daily intake of 1.6 g phytosterols was found to lead to an approximately 10% reduc-
tion in LDL cholesterol (Hallikainen, Sarkkinen, & Uusitupa, 2000). The intestinal
absorption of phytosterols is very low so dietary phytosterols do not have adverse ef-
fects on health. Phytosterol incorporation into food formulations is quite challenging
due to their high melting point and tendency to form insoluble crystals. However,
PUFA esterified phytosterols demonstrate a higher solubility. Upon ingestion of
phytosterols esters, lipases hydrolyze the fatty acid to produce free phytosterols.
Phytosterols have mostly been added to high fat foods (e.g., margarine) where
solublization and dispersion were relatively simple. Phytosterol introduction into
water-based foods require them either being suspended or emulsified. Phytosterol
oxidation products have been observed in model systems, oils, and food prod-
ucts (Bortolomeazzi, Cordaro, Pizzale, & Conte, 2003; Cercaci, Rodriguez-Estrada,
Lercker, & Decker, 2007; Dutta, 1997; Lambelet et al., 2003; Soupas, Juntunen,
Lampi, & Piironen, 2004). It is not clear whether oxidized phytosterols tend to
lose their bioactive properties or demonstrate any toxic effects in vivo in a manner
similar to oxidized cholesterol. As with other bioactive lipids that are susceptible
to oxidative reactions, nanoencapsulation of phytosterols could potentially increase
their oxidative stability and consequently render enhance their bioavailability.

> Read full chapter

Phytosterol Classes in Olive Oils and

their Analysis by Common Chromato-
graphic Methods
Sodeif Azadmard-Damirchi, Paresh C. Dutta, in Olives and Olive Oil in Health and
Disease Prevention, 2010

27.10.1 4-Desmethylsterols
From the 4-desmethylsterol class, cholesterol, campesterol, campestanol, stigmas-
terol, clerosterol, sitosterol, Δ5-avenasterol, Δ5,24-stigmastadienol, Δ7-stigmastenol
and Δ7-avenasterol can be detected in olive oil (Paganuzzi and Leoni, 1979; Ben-
itez-Sánchez et al., 2003; Azadmard-Damirchi et al., 2005). Sitosterol is predom-
inant, followed by Δ5-avenasterol and campesterol. Figure 27.5 shows the typical
GC chromatogram of 4-desmethylsterols of olive oil. Phytosterol composition and
content of olive oil are affected by cultivar, cropping year, degree of fruit ripeness,
storage time of fruits before oil extraction and method of oil extraction. Table 27.2
shows the 4-desmethylsterol levels according to International Olive Oil Council
trade standards (IOOC, 2003). Benitez-Sánchez et al. (2003) have reported the total
4-desmethylsterol content in European, North African and Turkish olive oils to
be ≥1000 ppm, 1800–2300 ppm and 1100–1700 ppm, respectively (Table 27.3).
Sitosterol is the predominant 4-desmethylsterol, followed by Δ5-avenasterol and
campesterol (Table 27.3).

Figure 27.5. Chromatogram of 4-desmethylsterols of virgin olive oil (reproduced

from Casas et al., 2004). 1 = cholesterol, IS = -cholestanol (internal standard, IS);
2 = methylene cholesterol; 3 = campesterol; 4 = campestanol; 5 = stigmasterol; 6 =
Δ7-campesterol; 7 = clerosterol; 8 = sitosterol; 9 = sitostanol; 10 = Δ5-avenasterol,
11 = Δ5,24-stigmastadienol; 12 = Δ7-stigmastenol; 13 = Δ7-avenasterol.

Table 27.2. 4-Desmethylsterol composition (% total sterols) of olive oil according to

International Olive Oil Council trade standards (IOOC, 2003).

Sterol Limit
Cholesterol < 0.5
Brassicasterol < 0.1
Campesterol < 4.0
Stigmasterol < campesterol
Δ7-Stigmastenol < 0.5
Apparent -sitosterol ≥ 93.0%a

a Apparent -sitosterol comprises: -sitosterol, Δ5-avenasterol, Δ5,23-stigmas-

tadienol, clerosterol, sitostanol, Δ5,24-stigmastadienol.

Table 27.3. 4-Desmethylsterols content (parts per million) in olive oils from different
geographical origins.

Olive oil Campes- Stigmas- Sitosterol Δ5-Ave- Δ7-Stig- Δ7-- Total

terol terol nasterol masterol Avanas-
terol
European 25–114 5–67 683–2610 34–266 Nr Nr ≥ 1000
North 59–62 16–26 1545–1851 158–214 1–4 8–14 1800–2300
African
Turkish 33–74 26–17 1000–2025 30–218 2 5–30 1100–1700

Nr, not reported.

Data adapted from Benitez-Sánchez et al. (2003).

In virgin olive oil, there is a very good correlation between stability and concen-
tration of total sterols, -sitosterol and Δ5-avenasterol (Gutiérrez et al., 1999). The
4-desmethylsterol level does not vary substantially during ripening of olive fruits,
except for a reduction in total sterols and -sitosterol and an increase in Δ5-avenas-
terol level. The decrease in total sterols is because sterols form in the first phases of
ripening and as the oil content increases during this period, the sterols are therefore
diluted. The decrease in -sitosterol is exactly the same as the increase in Δ5-avenas-
terol, suggesting the presence of a desaturase enzyme that transforms -sitosterol
into Δ5-avenasterol (Gutiérrez et al., 1999). The influence of storage temperature of
olive fruits on sterol composition is more important than the influence of storage
time. The total sterol content increases gradually with olive storage time and this
increase is greater for olive fruits stored at ambient temperature than those stored
at low temperature (5 °C) (Gutiérrez et al., 2000). Stigmasterol is related to various
quality parameters of virgin olive oil. High levels of this compound are correlated
with high acidity and low organoleptic quality (Gutiérrez et al., 2000). Ranalli et al.
(2002) compared the phytosterol classes of seed, pulp and whole olive fruit oil. Seed
oil was found to have a higher content of total 4-desmethylsterols (2.3-fold higher),
sitosterol, campesterol, clerosterol, Δ5-24-stigmastadienol, Δ7-stigmastenol and
Δ7-avenasterol compared with the other extracted oils. Pulp and whole olive fruit
oil generally had the same amounts of 4-desmethylsterols.

> Read full chapter

Brassinosteroids
J. Li, in Brenner's Encyclopedia of Genetics (Second Edition), 2013

Biosynthesis and Metabolism

Brassinosteroids are synthesized from three major phytosterols: campesterol, sitos-
terol, and stigmasterol, all of which are C24-alkylated cholesterols functioning main-
ly as common constituents of cellular membranes. The conversion of these phy-
tosterols to biologically active brassinosteroids involves the following key reactions:
(1) reduction of the Δ5 double bond involving the DET2 steroid 5 -reductase, (2)
addition of -oriented vicinal hydroxyl groups at C22 and C23, (3) epimerization of
a 3 -hydroxyl group to a 3 -hydroxyl group, (4) formation of the 2 -hydroxyl group,
and (5) oxidation of C6 and the subsequent Baeyer–Villiger-type oxidation to form
an alcohol/ketone and a lactone function at C6, respectively (Figure 2). Depending
on when the C22 hydroxylation (before or after the Δ5 reduction) and C6 oxidation
(right after the Δ5 reduction or at the third to last step) first occur, the brassinosteroid
biosynthetic routes are termed the early and late C22 or C6 oxidation pathways that
involve the same set of enzymes, most of which are members of the cytochrome
P450 superfamily, acting on C22-non-hydroxylated or hydroxylated or C6 deoxo or
oxo brassinosteroid intermediates (Figure 1). The homeostasis of brassinosteroids
is controlled largely by transcriptional regulation of genes that encode rate-limiting
enzymes of the brassinosteroid biosynthetic pathways, such as the C22 hydroxylase,
and brassinosteroid-inactivating or brassinosteroid-conjugating enzymes, includ-
ing C25/C26 hydroxylases, 22-O-sulfotransferases, and 23-O-glucosyltransferases.
Figure 2. A current model of the brassinosteroid signal transduction pathway (see
section Signaling Mechanism for details). P, phophorylated proteins.
> Read full chapter

Chemistry of pulses—micronutrients
Anamika Tripathi, ... Ashish Rawson, in Pulse Foods (Second Edition), 2021

4.2.7 Phytosterols
Pulses contain small quantities of phytosterols, of which sitosterol (most abundant),
stigmasterol, and campesterol are the major phytosterols present in pulses (Singh
et al., 2017) (Fig. 4.1). These compounds are also abundant as sterol glucosides and
esterified sterol glucosides, with -sitosterol representing 83% of the glycolipids
in defatted chickpea flour (Sánchez-Vioque et al., 1998). Ryan et al. (2007) reported
that the total phytosterol content in the pulses ranged from 134 mg 100 g−1 (kidney
beans) to 242 mg 100 g−1 (peas), while total -sitosterol content ranged from 160 mg
100 g−1 (chickpeas) to 85 mg 100 g−1 (butter beans). Chickpeas and peas contained
high levels of campesterol (21.4 and 25.0 mg 100 g−1, respectively). Stigmasterol
content is higher in butter beans (86 mg 100 g−1) as is the squalene content in peas
(1.0 mg 100 g−1).

> Read full chapter

Epigenetic drug development for au-

toimmune and inflammatory diseases
Hammad Ullah, Haroon Khan, in Histone Modifications in Therapy, 2020

16.3.2.8 Phytosterols
More than 200 sterols have been identified in plants. The most abundantly occurring
phytosterols are stigmasterol, -sitosterol, and campesterol. Dietary sources of
phytosterols are nuts, seeds, fruits, vegetables, vegetable oils, and cereals. Average
daily intake of phytosterol is about 250 mg. The chemical skeleton contains fused
cyclopentanophenanthrine and an alcohol moiety. Phytosterols can be divided in two
classes based on the degree of saturation: sterols (double bond at C-5) and stanols
(saturated sterols). Sterols are more abundant in nature and are effectively absorbed
compared to stanols.

Chemically, phytosterols resemble naturally occurring cholesterols. The major ther-

apeutic benefit of phytosterols is the management of hypercholesterolemia. Oth-
 er pharmacological effects include anticancer, antioxidant, antiinflammatory, im-
munomodulatory, and antiinfective activities. While combating inflammatory re-
sponses, phytosterols modify prostaglandin pathways and also T-helper cell medi-
ated immune response. However, steroidal compounds of natural origin such as
cholesterol are closely related to epigenetic modifications, but epigenetics regulating
effects of phytosterols have not yet been explored.

> Read full chapter

Soybean Oil Processing Byproducts and

Their Utilization
John B. Woerfel, in Practical Handbook of Soybean Processing and Utilization, 1995

Utilization of Deodorizer Distillate: Sterols

Table 17.5 (3) shows soybean distillate to be 18% sterols, of which 4.4% is stigmas-
terol. Distribution of sterol components for soybean oil is reported to approximate
20% campesterol, 20% stigmasterol, 53% -sitosterol, 4% -avenasterol, and 3%
-stigmasterol (28). This indicates soybean oil to be a good source of sterols,
stigmasterol in particular.

Sterols are used in the manufacture of pharmaceuticals. Stigmasterol from soybean

oil is used in the manufacture of progesterone and corticoids, whereas -sitosterol
is used to produce estrogens, contraceptives, diuretics, and male hormones (28).

> Read full chapter

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