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Plant sterols and sterolins: A review of their immune-modulating properties


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Beta-sitosterol (BSS) and its glycoside (BSSG) are sterol molecules which are synthesized by plants. When humans eat plant foods phytosterols are ingested, and are found in the serum and tissues of healthy individuals, but at concentrations orders of magnitude lower than endogenous cholesterol. Epidemiological studies have correlated a reduced risk of numerous diseases with a diet high in fruits and vegetables, and have concluded that specific molecules, including b-carotene, tocopherols, vitamin C, and flavonoids, confer some of this protective benefit. However, these epidemiologic studies have not examined the potential effect that phytosterols ingested with fruits and vegetables might have on disease risk reduction. In animals, BSS and BSSG have been shown to exhibit anti-inflammatory, anti-neoplastic, anti-pyretic, and immune-modulating activity. A proprietary BSS:BSSG mixture has demonstrated promising results in a number of studies, including in vitro studies, animal models, and human clinical trials. This phytosterol complex seems to target specific T-helper lymphocytes, the Th1 and Th2 cells, helping normalize their functioning and resulting in improved T-lymphocyte and natural killer cell activity. A dampening effect on overactive antibody responses has also been seen, as well as normalization of the DHEA:cortisol ratio. The re-establishment of these immune parameters may be of help in numerous disease processes relating to chronic immune-mediated abnormalities, including chronic viral infections, tuberculosis, rheumatoid arthritis, allergies, cancer, and auto-immune diseases.
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Page 170 Alternative Medicine Review
Volume 4, Number 3 1999
Copyright©1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
Plant Sterols and Sterolins: A Review of Their
Immune-Modulating Properties
Patrick J.D. Bouic, PhD and Johan H. Lamprecht, MD
Beta-sitosterol (BSS) and its glycoside (BSSG) are sterol molecules which are
synthesized by plants. When humans eat plant foods phytosterols are ingested, and
are found in the serum and tissues of healthy individuals, but at concentrations orders
of magnitude lower than endogenous cholesterol. Epidemiological studies have corre-
lated a reduced risk of numerous diseases with a diet high in fruits and vegetables, and
have concluded that specific molecules, including b-carotene, tocopherols, vitamin C,
and flavonoids, confer some of this protective benefit. However, these epidemiologic
studies have not examined the potential effect that phytosterols ingested with fruits
and vegetables might have on disease risk reduction. In animals, BSS and BSSG have
been shown to exhibit anti-inflammatory, anti-neoplastic, anti-pyretic, and immune-
modulating activity. A proprietary BSS:BSSG mixture has demonstrated promising re-
sults in a number of studies, including
in vitro
studies, animal models, and human
clinical trials. This phytosterol complex seems to target specific T-helper lymphocytes,
the T
1 and T
2 cells, helping normalize their functioning and resulting in improved T-
lymphocyte and natural killer cell activity. A dampening effect on overactive antibody
responses has also been seen, as well as normalization of the DHEA:cortisol ratio.
The re-establishment of these immune parameters may be of help in numerous dis-
ease processes relating to chronic immune-mediated abnormalities, including chronic
viral infections, tuberculosis, rheumatoid arthritis, allergies, cancer, and auto-immune
(Altern Med Rev 1999;4(3):170-177)
Beta-sitosterol (BSS) is the major phytosterol in higher plants, and is found in the serum
and tissues of healthy individuals at concentrations 800-1000 times lower than that of endogenous
cholesterol. Its glycoside, β-sitosterol glycoside (BSSG), is also present in serum in even lower
These molecules are synthesized in plants; whereas animals obtain them through
diet. Many epidemiological studies of groups consuming diets rich in vegetables and fruits
have indicated a reduced incidence of various types of cancer, cardiovascular disease, diabetes,
and other chronic diseases.
Many of these studies have concentrated on the protective effects
of well-characterized molecules such as b-carotene, tocopherols, vitamin C, and flavonoids.
P.J.D. Bouic, Ph.D and Johan H. Lamprecht, M.D. - Departments of Medical Microbiology and Pharmacology, Medical Faculty,
University of Stellenbosch.
Correspondence address: P.O. Box 19063, Tygerberg 7505, South Africa. E-mail:
Copyright©1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
Sterols & Sterolins
Alternative Medicine Review
Volume 4, Number 3 1999 Page 171
However, such studies have ignored the
relative importance of fats in the plants
The scientific literature is replete with
reports of the biological activities of sterols or
their glycosides in various animal models. For
instance, BSS and its glycoside have been
shown to reduce carcinogen-induced cancer
of the colon in rats,
as well as exhibiting anti-
and insulin-releasing effects.
A proprietary mixture of BSS and
BSSG (BSS:BSSG) was studied and found to
have profound immune modulating activities.
Initial in vitro studies were followed by clini-
cal trials in patients with chronic infectious dis-
eases (tuberculosis, HIV, Human Papilloma
Virus [HPV]) and non-infectious conditions,
such as allergies and rheumatoid arthritis. The
trials confirmed the importance of BSS:BSSG
in the management of such conditions.
The Functioning of the Immune
The immune system is an intricate net-
work of cells and soluble factors released by
these cells. B-lymphocytes produce antibod-
ies in response to antigenic stimulation. T-lym-
phocytes induce either a humoral or cellular
response depending on the subset of T cells
that are primed upon initial contact with the
T cells are made up of two
distinct subsets, the CD4 helper
cell and the CD8 cytotoxic/sup-
pressor cells. Within the CD4
subset there are two types of
helper cells. One is the T
which releases interleukin-2 (IL-
2) and gamma interferon (IFN-γ).
These cytokines bind to and acti-
vate the CD8 cytotoxic cells to
become effective killers. This
type of cellular response is vital
to clearing the host of pathogens
which use the intracellular milieu to survive
attack by the immune response. Should this
cellular response fail, the infection becomes
chronic. The second type of helper cell is the
2-type, which secretes IL-4, IL-6, and IL-
10, cytokines which are involved in B-lym-
phocyte differentiation (Table 1). The antibody
response is capable of limiting the damage
induced by most extracellular organisms.
In health, there is a delicate balance
maintained between the activity of T
1 and
2 helper cells in that the activity of T
1 cells
is directly cross-regulated by the T
2 cells, and
vice versa. However, under certain pathologi-
cal conditions, especially chronic viral and
bacterial diseases, the functioning of T
1 cells
may be superseded by that of the T
2 cells
leading to a humoral immune response (anti-
body production) at the expense of the more
protective cellular response. A similar imbal-
ance exists in other chronic conditions, such
as allergies and autoimmune disorders. Main-
taining the delicate balance between T
1 and
2 cells is vital. Many researchers are cur-
rently attempting to enhance the activity of T
helper cells in order to eradicate latent and
chronic pathogens.
BSS and BSSG as Immune
Initial observations using human pe-
ripheral blood lymphocytes showed a mixture
Cell Cytokine profile Function of TH subset
, IL2
IL4, IL6, IL10, IL5
Activation of cytotoxic cells
Antogonism of T
2 cells
Activation and maturation of B cells
Antogonism of T
1 cells
Table 1. The dichotomy of T helper cells based on their
defining cytokine profiles and functions
Page 172 Alternative Medicine Review
Volume 4, Number 3 1999
Copyright©1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
of BSS:BSSG in a ratio of 100:1 could influ-
ence the cellular proliferation of T-lympho-
cytes when these were activated by mitogens
in vitro. The in vitro results were confirmed in
a small pilot study in which volunteers took a
BSS:BSSG complex orally. The ex vivo test-
ing of lymphocyte proliferation showed a
greatly enhanced response to mitogens. In par-
allel the lytic ability of the natural killer cells
(NK cells) to a cancer cell line in vitro was
greatly increased in the presence of the
BSS:BSSG mixture.
When the profile of cytokine secretion
by activated T cells was measured it was dis-
covered that the BSS:BSSG mixture was se-
lective in the above-mentioned activities. Lym-
phokines belonging to T
1-type helper cells
were increased, whereas those associated with
2-type helper cells were inhibited or re-
mained unchanged. The BSS:BSSG mixture
enhanced the secretion of IL-2 and IFN-γ, but
inhibited the secretion of IL-4.
The specific-
ity toward certain T-helper cells indicates
BSS:BSSG could have important regulatory
and modulatory activities in diseases where
enhancement of the T
1-type helper cells is
vital for the effective clearance of particular
pathogens. Furthermore, since these plant con-
stituents are able to switch off the secretion of
IL-4 in conditions where an overt T
2 response
predominates, these natural substances should
reinstate balance in conditions such as aller-
gies and auto-immune diseases.
Further in vitro testing of physiologi-
cal concentrations of BSS:BSSG on monocyte
activity revealed anti-inflammatory properties,
via inhibition of both IL-6 and tumor necrosis
factor alpha (TNF-α), in a dose-dependent
manner (Figure 1). Diseases characterized by
elevated levels of TNF-α and IL-6, which in-
duce tissue damage, include rheumatoid arthri-
tis and systemic lupus erythematosus (SLE).
BSS:BSSG as an Adjuvant in the
Treatment of Patients with
Pulmonary Tuberculosis
A clinical study of BSS:BSSG com-
plex examined its effect in culture-proven pul-
monary tuberculosis (PTB). This was a
IL6 (pg/ml)
Medium Lipopoly-
Figure 1. IL6 Secretion in vitro.
Sterols & Sterolins
Alternative Medicine Review
Volume 4, Number 3 1999 Page 173
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blinded, randomized, placebo-controlled trial
in drug-sensitive PTB. Patients were hospital-
ized for the duration of treatment, and sputum
culture positivity, chest radiography, weight
gain, Mantoux test response, routine hematol-
ogy, and liver function were evaluated at
monthly intervals. Forty-seven patients were
enrolled in the six-month study, and all pa-
tients were treated with the standard anti-tu-
berculous regimen of isoniazid, rifampicin and
pyrazinamide. No significant differences ex-
isted between the variables of each group
evaluated at the time of entry into the study.
Sputum conversion in the patient
groups were very similar; by the end of the
first month of therapy, 58 percent in the treat-
ment group and 61 percent in the placebo
group were still sputum culture positive. By
the end of the second month, 11 percent of the
patients in each group were still positive, but
thereafter, no patients had positive sputum
cultures. An independent physician and radi-
ologist evaluated the radiological changes seen
on the chest radiographs. Although improve-
ment seemed to occur faster
in the sterol treated group
when compared to their pla-
cebo counterparts, the differ-
ences were difficult to quan-
tify. Therefore, this param-
eter was not included in the
final analysis of the data.
The most significant
differences observed be-
tween the groups were in the
hematological parameters,
including higher lymphocyte
(p=0.0001), eosinophil
(p=0.0001), and monocyte
counts in the BSS:BSSG
group. The placebo group
showed higher sedimenta-
tion rates when compared to
the study group (p = 0.0001).
Possibly the most remark-
able difference between the
two groups was the difference in weight gain
over the six-month period, with the sterol-
treated group demonstrating a faster and more
pronounced weight recovery.
This was the first study to find a ben-
eficial effect of BSS:BSSG complex in PTB
patients. Although the study was small, the sta-
tistically significant differences observed be-
tween the patient groups suggest further analy-
sis of the immune modulatory activities of
BSS:BSSG in multi-drug resistant tuber-
BSS:BSSG Complex in Felines: A
Model of HIV
Domestic cats infected with the
retrovirus FIV (considered equivalent to HIV
because it induces the same pathogenic
mechanisms of CD4 cell loss and opportunistic
infections) were examined. Infected cats
typically succumb to the infection due to
immunosuppression. A group of 33 infected
cats was divided into a treatment group (n=16)
05112337 49 62 74 87 99 113 125
Time (weeks)
Median CD4 cells
Gp 1: Rx (n=16)
Linear {Gp 1: Rx N=16)}
Gp 2: Placebo (n=17)
Linear {Gp 2: Placebo (n=17)}
Figure 2. FIV Pilot Study number 2.
Page 174 Alternative Medicine Review
Volume 4, Number 3 1999
Copyright©1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
or a placebo group (n=17).
Linear regression
of the median CD4 cell numbers of the two
groups revealed that the treated group
maintained stable immune cell numbers over
a period of 168 weeks, whereas those who
received the placebo capsules showed disease
progression with the typical CD4 cell loss over
the same period of time (Figure 2). The end
point of such a model is the analysis of
mortality in both groups of cats. At present,
cats treated with BSS:BSSG complex have
exhibited 20 percent mortality compared to 75
percent in the non-treated group.
Use of BSS:BSSG for Management
of HIV Infected Patients
A clinical study (open-labeled trial) is
in progress in patients presenting at an infec-
tious disease clinic with a diagnosis of HIV.
Pregnant women and children were excluded
from the study. Surrogate markers include both
the number of CD4 cells (percentages and ab-
solute numbers) as well as other lymphocyte
markers, plasma viral loads, and body weight.
Basic hematological and chemical parameters
are also being monitored. The initial database
consisted of 80 patients who
were entered into the trial and
followed for 36 months. At the
time of this writing over 150
patients are enrolled, with a
follow-up period of at least 15
Irrespective of baseline CD4
cell numbers, the median CD4
cell count within the total
group of patients has shown
relative stability over the ana-
lytical period (Figure 3). The
data was compared to that ob-
tained from a group of patients
attending the same infectious
disease clinic but who were not
participating in the clinical
study. These patients exhibited
the classical decline in CD4 cell numbers. Sta-
tistical analysis has found no significant dif-
ferences between the CD4 counts at entry and
at other times during the study in the treated
patients, confirming that to date there has been
stability in the CD4 counts with no further pro-
gression of disease.
Similar positive results were obtained
when plasma levels of the pro-inflammatory
monokine IL-6 were compared at baseline and
again after six months. IL-6 levels decreased
significantly, indicating less inflammation,
which could explain the CD4 cell stability in
these individuals.
Plasma viral loads also gradually de-
clined over time.
Sterols and sterolins do not
have innate anti-viral properties; the decrease
in viral loads is attributable to enhanced ac-
tivity of the cell-mediated immune response
which controls viral replication.
Evaluation of a small participating
group found the T
1/ T
2 profile, after at least
12 months of therapy with BSS:BSSG, was
comparable to that observed in healthy HIV-
negative controls.
In contrast, a group of in-
fected patients not on any therapy exhibited
Time (months)
Median CD4 cells
Phytosterols Control Linear (Phytosterols) Linear (Control)
Figure 3. HIV Clinical trial (phytosterols vs. control).
Sterols & Sterolins
Alternative Medicine Review
Volume 4, Number 3 1999 Page 175
Copyright©1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
the typical predominance of T
2 responses
after in vitro activation of CD4 cells (Table
2). The ability to maintain a protective T
cellular response has long-term prognostic
value, as disease progression is attributed to a
failure of this response to control viral repli-
BSS:BSSG for Preventing Stress-
Induced Immune Suppression
Individuals participating in marathon
running or other endurance events are prone
to bacterial and viral respiratory infections.
Research has shown this susceptibility is due
to a transient, hormone-induced redistribution
in immune cells, as well as a decline in the
functionality of the cells.
The potential of BSS: BSSG complex
to inhibit immune suppression in a group of
volunteers participating in an ultra-
marathon event was investigated in
a double blind, placebo-controlled
study. The study found the hema-
tological changes which accom-
pany endurance exercise were more
pronounced in individuals who re-
ceived placebo than in those who
received the active capsules. The
placebo individuals demonstrated
neutrophilia with severe lymphope-
nia characterized by a profound
decrease in the total number of T
cells, especially the T helper (CD4
positive) subset. These abnormali-
ties were primarily negated or re-
versed in volunteers in the treat-
ment group.
Possibly the most dramatic
differences between the groups in the study
were the changes in serum IL-6 and the
cortisol:dehydroepiandrosterone sulfate
(DHEAs) ratio. Volunteers in the BSS:BSSG
group showed a decline in cortisol, with a par-
allel increase in serum DHEAs levels, and a
decline in IL-6.
Modulation of these hor-
mones has a direct impact on the redistribu-
tion of lymphocytes during stress episodes and
significantly affects the immune system’s abil-
ity to respond to potential or ongoing immune
challenges. Abnormally high levels of IL-6
(such as is seen in chronic inflammatory con-
ditions) and decreased levels of DHEAs (such
as is seen in HIV, SLE, and other autoimmune
conditions) characterize many pathological
On-Going Clinical Studies with
BSS:BSSG Complex
At present, new clinical studies of the
following conditions are being conducted:
• Rheumatoid arthritis: This chronic in-
flammatory and destructive autoimmune dis-
ease is typified by increased levels of IL-6
within the affected joints and an abnormal
regulation of immune cells, due to the pre-
dominance of T
2-type helper cells which pro-
mote inflammation and antibody synthesis.
• Cervical lesions induced by the
Human Papilloma Virus (as detected by
7 Hours 18 Hours
Healthy HIV-
HIV+ BSS:BSSG treated
HIV+ No treatment
15.8 9.5
30.7 24.6
5.6 5.0
Table 2. The maintenance of T
1 responses by HIV positive
patients receiving Sterinol™: Ratio of T
1 versus
2 CD4+ cells activated in vitro.
Page 176 Alternative Medicine Review
Volume 4, Number 3 1999
Copyright©1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
cytology): Current literature reports such
lesions are indicative of an abnormal clearance
of the virus and, if left untreated, can lead to
carcinoma requiring conization and possibly
hysterectomy. Many anecdotal cases of women
having used BSS:BSSG complex for this
condition have been reported.
• Chronic rhinitis and sinusitis: A
small, placebo-controlled study in affected in-
dividuals indicates this allergic condition can
be controlled by BSS:BSSG complex.
• Hepatitis C virus carrier status: New
clinical data from physicians using BSS:BSSG
complex report control of liver damage, with
a concomitant improvement in liver function
and decline of virus within the plasma in these
The BSS:BSSG complex is a new,
natural immune modulator which has demon-
strated promising results in a number of clini-
cal trials. These important plant constituents
seem to specifically target T-helper cells, and
may help to restore balance between T
1 and
2 cells. The end result of this immune modu-
lation is an increase in T
1-related cytokines,
a decrease in T
2-related cytokines, increased
lymphocyte proliferation, and greater NK cell
activity. The BSS:BSSG complex has also
been shown to help normalize the
DHEA:cortisol ratio, which can have profound
positive results on the immune system. The
re-establishment of these immune parameters
may be of help in numerous disease processes
relating to chronic immune-mediated abnor-
malities, including chronic viral infections,
tuberculosis, rheumatoid arthritis, allergies,
cancer, and auto-immune diseases.
Acknowledgements: The authors wish
to thank Essential Sterolin Products (Pty) Ltd.,
of South Africa, the worldwide distributor of
Moducare™ Sterinol,™ the BSS:BSSG com-
plex used in the clinical studies mentioned
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... In this regard, Cheon et al., in 2006, reported that a phytosterol, guggulsterone, inhibited NF-κB signaling in a murine inflammation model by inhibiting I-κB kinase [142], and later studies showed that guggulsterone blocks apoptosis by decreasing the expressions of COX-2 and MMP-9 in many cell lines by acting on the NF-κB pathway [143]. Lupeol, a well-known phytosterol, has been shown to ameliorate dextran sulfate sodiuminduced colitis by suppressing the expressions of TNF-α, IL-2, and IL-6 [144], and mitigating inflammation by suppressing the NF-kB pathway in vitro and in vivo [145][146][147][148]. Furthermore, the consumption of β-sitosterol was reported to reduce the expression of Il-6 [130,149,150], while stigmasterol downregulated PGE2 and MMP-3 in IL-1β-treated cells without effecting IL-6 levels, suggesting that stigmasterol participates in the IL-1β-induced NF-κB pathway [151]. In line with this finding, β-sitosterol at 16 µM upregulated SHP-1 and IL-10 in murine J774A.1 macrophages, and thus, hindered the nuclear transfer of NF-κB [130]. ...
... Furthermore, phytosterols and phytosterol glucosides have immunomodulatory properties [129,131,150,[155][156][157][158], as they enhance T-cell generation and the activities of natural killer cells, and also cause TH1 shift by activating TLR2 receptor [157,[159][160][161]. 3-O-β-D-glucopyranosyl spinasterol, which is present in the leaves of Stewartia koreana, suppresses the production of CCL17 and CCL22 in keratinocytes [162,163], and inhibits the TNF-α mediated phosphorylation of JAK2 and p38 MAP kinases without activating ERK or JNK [164], thereby regulating Th2-type chemokines production. Furthermore, supplementation of a phytosterol mixture in ApoE lacking mice induced an intense immunomodulatory effect [165], and also regulated leukocyte function in murine inflammation models [166,167] and reduced prostaglandin release by cultured macrophages [134]. ...
Full-text available
Plant-derived sterols, phytosterols, are well known for their cholesterol-lowering activity in serum and their anti-inflammatory activities. Recently, phytosterols have received considerable attention due to their beneficial effects on various non-communicable diseases, and recommended use as daily dietary components. The signaling pathways mediated in brain by phytosterols have been evaluated, but little is known of their effects on neuroinflammation, and no clinical studies have been undertaken phytosterols of interest. In this review, we discuss the beneficial roles of phytosterols, including their attenuating effects on inflammation, blood cholesterol levels, and hallmarks of disease, and their regulatory effects on neuroinflammatory disease pathways. Despite recent advancements made in phytosterol pharmacology, some critical questions remain unanswered. Therefore, we have tried to highlight the potentials of phytosterols as viable therapeutics against neuroinflammation and to direct future research with respect to clinical applications.
... Several studies have demonstrated the actions of phytosterols as immunomodulatory compounds. The first studies that demonstrated this activity were reported by Bouic et al., who demonstrated that β-sitosterol and its glucoside derivative enhanced the cytotoxic activity of NK cells; proliferation of T lymphocytes, in particular the T H 1 population; secretion of IL-2 and IFN-γ; and inhibition of IL-4 secretion (Bouic et al., 1996;Bouic & Lamprecht, 1999). The ability to stimulate NK cell function in the presence of IL-12 was also found for (−)-β-sitosterol-3-O-β-D-(6-O-palmitoyl)glucopyranoside extracted from Phyllanthus songboiensis (Ren et al., 2015). ...
... Ex vivo exposure of T helper cells derived from the lamina propria of mice to cis-guggulsterone (10 μM) inhibited IL-2, IL-4 and IFN-γ production by these cells (Mencarelli et al., 2009). In addition, β-sitosterol and its glucoside derivative were found to exert anti-inflammatory effects on monocytes by inhibiting IL-6 and TNF-α production (Bouic & Lamprecht, 1999). The inhibition of TNF-α, IL-1β, IL-6, and IL-8 secretion and ROS generation was also demonstrated for β-sitosterol isolated from Moringa oleifera, which was used to treat stimulated keratinocytes and macrophages (P. ...
The occurrence of immune effector cells in the tissue microenvironment during neoplastic progression is critical in determining tumor growth outcomes. On the other hand, tumors may also avoid immune system-mediated elimination by recruiting immunosuppressive leukocytes and soluble factors, which coordinate a tumor microenvironment that counteracts the efficiency of the antitumor immune response. Checkpoint inhibitor therapy results have indicated a way forward via activation of the immune system against cancer. Widespread evidence has shown that different compounds in foods, when administered as purified substances, can act as immunomodulators in humans and animals. Although there is no universally accepted definition of nutraceuticals, the term identifies a wide category of natural compounds that may impact health and disease statuses and includes purified substances from natural sources, plant extracts, dietary supplements, vitamins, phytonutrients, and various products with combinations of functional ingredients. In this review, we summarize the current knowledge on the immunomodulatory effects of nutraceuticals with a special focus on the cancer microenvironment, highlighting the conceptual benefits or drawbacks and subtle cell-specific effects of nutraceuticals for envisioning future therapies employing nutraceuticals as chemoadjuvants.
... The authors of this study (Kei et al., 2001) have concluded that ethyl gallate as the most selective inhibitor of Th2 cytokines among the studied derivatives. Phytosterols are also known to modulate immune function-b-sitosterol and one of its glycosides has been reported to target specific Thelper lymphocytes (Th1 and Th2) helping to normalize their function (Patrick and Lamprecht, 1999). It was also observed that they also normalize DHEA-cortisol ratio. ...
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Helicanthes elasticus (Desv.) Danser is a common type of mistletoes of Indian origin. In Indian traditional and folklore medicines the plant is claimed to possess a range of medicinal values such as immunomod-ulator, anti-diabetic and anti-microbial properties. However, there is no experimental proof for its therapeutic claim. The aqueous and alcoholic extracts of H. elastica were evaluated for its immuno-modulatory effect on antibody formation against sheep red blood cells and on cell mediated immunity of immunological paw edema model. Ethanolic and aqueous extracts have shown dose dependent elevation in the antibody titer value in comparison to control group at 14th and 21st day of sensitization (**p < 0.01). There is a mild to moderate elevation were observed in the immunological paw edema at highest dose (400 mg/kg) during 21st day after sensitization. The histopathological observation shows that there is an increase in the white pulp of spleen and increased cellularity and formation of distinct germinal cells in lymph node. H. elasticus extracts possess marked antibody formation propensity without significant modification on cell mediated immunity.
... Bouic and Lamprecht reported that this phytosterol complex seems to target specific T-helper lymphocytes, the Th1 and Th2 cells, helping normalize their functioning and resulting in improved T-lymphocyte and natural killer cell activity. The re-establishment of these immune parameters may be of help in numerous disease processes relating to chronic immune-mediated abnormalities, including chronic viral infections, tuberculosis, rheumatoid arthritis, allergies, cancer, and autoimmune diseases [17]. Bouic et al. concluded that phytosterols could be used to prevent the subtle immunosuppression associated with excessive physical stress [18]. ...
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As an extension to our recently published research work in Asian Journal of Pharmaceutical and Clinical Research, entitled “Β-Sitosterol: Isolation from Muntingia Calabura Linn. Bark Extract, Structural Elucidation, and Molecular Docking Studies as Potential Inhibitor of SARS-CoV-2 Mpro (COVID-19)”, we have investigated the role of β-sitosterol as an immunostimulant, antioxidant and inhibitory potential against Receptor Binding Domain (RBD) of SARS-CoV-2 Spike Glycoprotein with the aid of molecular docking. There are many studies which reveals the antioxidant and immune boosting role of β-sitosterol especially in viral infection including pneumoniae. This commentary emphasis on further potential of β-sitosterol in treatment of COVID-19 through molecular docking studies. We have targeted RBD of spike glycoprotein and performed molecular docking studies of β-sitosterol to find out its inhibitory potential of SARS-CoV-2. β-sitosterol have showed binding affinity - 7.8 kcal/mol with 0 RMSD lower and upper bound. It formed one hydrogen bond with Ala-B:419 with bond length of 2.16A0. β-sitosterol has formed five alkyl bonds with Pro-C:384 (5.0A0, 4.66A0, 5.23A0, 4.27A0) and with Lys-C:378 (4.66A0). From present commentary, we have concluded that β-sitosterol can be used to enhance immunity against the SARS-CoV-2 infection as well as to restrict the viral invasion into the host cell through angiotensin converting enzyme-2 (ACE-2) by inhibiting spike glycoprotein. If we can increase the dietary intake of β-sitosterol and other phytosterols it can modulate the immunity which is todays need to face COVID-19.
... It has been reported that sitosterol and sitosterol glycoside presented antiinflammatory, anti-neoplastic, anti-pyretic, and immune-modulatory activity. Their mixture seems to target specific T-helper lymphocytes, TH1 and TH2 cells, helping to normalize their function and resulting in improved T-lymphocyte and natural killer cell activity (Bouic et al., 1999). -Sitosterol--D-glucoside isolated from ...
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Ethnopharmacological relevance: Verbesina crocata (Cav.) Less. (Arnica or Capitaneja) is an endemic plant from Mexico restricted to the western part of the country. The aerial parts are used in traditional medicine for the treatment of wounds and burns. The objective of this investigation was to carry out a pharmacognostic study of V. crocata and establish markers that allow for the recognition of the characteristics of the plant and validate its traditional use. The study includes anatomical and chemical characteristics of the plant as well as evaluations of its antioxidant capacity and wound healing ability in a murine model. Materials and methods An anatomical study was performed on the middle part of the leaf and stem. A methanolic extract of V. crocata (VcME) was obtained by methanolic maceration of the aerial parts. Subsequently, a partition of the VcME was made to obtain a hexanic fraction (VcH). The phytochemical preliminary screening and characterization by high-performance liquid chromatography/mass spectrometry (HPLC-ESI/MS) of the VcME and VcH were performed. The antioxidant activity and total phenolic content were quantified. The wound healing capacity of the methanolic extract was determined in CD-1 mice by the healing rate, the tensiometric method, and histological analysis. Results The anatomical study of V. crocata showed the presence and absence of various types of secretory structures and their position on the leaves. In addition, the characteristics of the middle vein and trichomes are potentially useful for recognition of the species. Chemical compounds detected by HPLC-ESI/MS reveal the presence of sitosterol glycoside and catechin derivatives as principal constituents of V. crocata. The VcME showed low antioxidant capacity and total phenolic. V. crocata had a similar healing effect to Recoveron® in the tensiometric method, but the rate of healing was higher. According to the histological analysis, the treatment of V. crocata promoted the remodelling phase 15 days after the incisional wound. Conclusion This is the first pharmacognostic study of this species that covers the plant anatomy, chemical content and biological properties related to its traditional use. V. crocata favours wound healing according to physical and histological evaluations. In addition, the characteristics of the middle vein, trichomes and catechin glycosides are potentially useful for the recognition of this species.
... Scientific studies on SIT have been considerably decreased in the current pace of research which comes up with its current status as an "orphan phytosterol" [21]. There are few scientific reviews on the useful outcomes of phytosterol on health [22][23][24] and selected diseases [25][26][27][28]. In this review, the characterization, sources and antioxidant and anti-diabetic activities of SIT are discussed which give a clear evidence of its potential on insulin resistance and metabolic disorder and it sets a new path for researchers to have a look on its efficacy on life threatening diseases such as diabetes in the future. ...
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Phytosterols are bioactive compounds that are naturally present in plant cell membranes with chemical structure similar to the mammalian cell- derived cholesterol. They are highly present in lipid-rich plant foods such as nuts, seed, legumes and olive oil. Among various phytosterols, β-sitosterol (SIT) is the major compound, found plentiful in plants. It has been evidenced in many in-vitro and in-vivo studies that SIT possesses various biological actions such as anxiolytic & sedative effects, analgesic, immunomodulatory, antimicrobial, anticancer, anti – inflammatory, lipid lowering effect, hepatoprotective, protective effect against NAFLD and respiratory diseases, wound healing effect, antioxidant and anti-diabetic activities. In this review, in order to compile the sources, characterization, biosynthesis, pharmacokinetics, antioxidant and anti-diabetic activities of SIT, classical and online-literature were studied which includes the electronic search (Sci Finder, Pubmed, Google Scholar, Scopus, and Web of Science etc) and books on photochemistry. The experimental studies on SIT gives a clear evidence that the potential phytosterol can be used as supplements to fight against life threatening diseases. High potential of this compound, classifies it as the notable drug of the future. Therefore, immense researches regarding its action at molecular level on life threatening diseases in humans are highly endorsed.
... Kaempferol is avonoid found in FF, LIF, EH, FBR, HH, and LI of LHQW capsule, and can protect against in ammation, virus infection, endothelial barrier dysfunction, and cytokines release [35][36][37][38]. Another important compounds, such as luteolin, naringenin, and beta-sitosterol, in LHQW capsule also have these protective effects [39][40][41][42] [43]. IL-17 signaling can not only activate downstream pathways that include NF-κB, MAPKs and C/EBPs to induce the expression of anti-microbial peptides, cytokines and chemokines, but also is critical for protection against a variety of fungal and bacterial infections [44,45]. ...
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Background The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) disease has led to a wide-spread global pandemic. There is no specific antiviral drug proven effective for the treatment of patients with COVID-19 at present. Combination of western and traditional Chinese medicine (TCM) is recommended, and Lian Hua Qing Wen (LHQW) capsule is a basic prescription and widely used to treat COVID-19 in China. However, the mechanisms of LHQW capsule treating COVID-19 are not clear. The aim of the study is to explore the mechanisms of LHQW capsule treating COVID-19 based on network pharmacy and molecular docking approach. Methods The active compounds and targets of LHQW capsule were obtained from traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). COVID-19 related target genes were obtained from GeneCards database and OMIM database. Protein–protein interaction (PPI) networks of LHQW capsule targets and COVID-19-related genes were visualized and merged to identify the candidate targets for LHQW capsule treating COVID-19. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also performed. The hub genes involved in the gene-related pathways were screened and their corresponding compounds were used for in vitro validation of molecular docking predictions. Results A total of 185 active compounds of LHQW capsule were screened out, and 263 targets were predicted. Third hundred and fifty-two COVID-19 related target genes were obtained from GeneCards database and OMIM database. GO functional enrichment analysis showed that the biological processes of LHQW capsule treating COVID-19 were closely linked with the regulation of inflammation, immunity, cytokines production, vascular permeability, oxidative stress and apoptosis. KEGG enrichment analysis revealed that the pathways of LHQW capsule treating COVID-19 were significantly enriched in AGE−RAGE signaling pathway in diabetic complications, Kaposi sarcoma−associated herpesvirus infection, TNF, IL−17, and Toll−like receptor (TLR) signaling pathway. The hub targets genes in the gene-related pathways analysis of LHQW capsule treating COVID-19 included MAPK1, MAPK3, RELA, IL-6 and CASP8, which closely associated with inflammation, cytokines storm and apoptosis. Finally, molecular docking showed that top 5 compounds of LHQW capsule also had good binding activities to the important targets in COVID-19. Conclusions The mechanisms of LHQW capsule treating COVID-19 may involve in inhibiting inflammatory response, cytokine storm and virus infection, and regulating immune reactions, apoptosis and endothelial barrier.
... From a treatment perspective, plant sterols, which are dietary constituents present in vegetable oils, nuts, grains, and fruit [18], seem promising due to their immune-modulatory properties [19][20][21][22][23][24][25][26][27]. Moreover, they have even shown to be anti-inflammatory in the liver of mice that developed non-alcoholic fatty liver disease (NASH) [28]. ...
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Chorioamnionitis can lead to inflammation and injury of the liver and gut, thereby predisposing patients to adverse outcomes such as necrotizing enterocolitis (NEC). In addition, intestinal bile acids (BAs) accumulation is causally linked to NEC development. Plant sterols are a promising intervention to prevent NEC development, considering their anti-inflammatory properties in the liver. Therefore, we investigated whether an intra-amniotic (IA) Ureaplasma parvum (UP) infection affected the liver and enterohepatic circulation (EHC) and evaluated whether an IA administered plant sterol mixture dissolved in β-cyclodextrin exerted prophylactic effects. An ovine chorioamnionitis model was used in which liver inflammation and the EHC were assessed following IA UP exposure in the presence or absence of IA prophylactic plant sterols (a mixture of β-sitosterol and campesterol dissolved in β-cyclodextrin (carrier)) or carrier alone. IA UP exposure caused an inflammatory reaction in the liver, histologically seen as clustered and conflated hepatic erythropoiesis in the parenchyma, which was partially prevented by IA administration of sterol + β-cyclodextrin, or β-cyclodextrin alone. In addition, IA administration of β-cyclodextrin prior to UP caused changes in the expression of several hepatic BAs transporters, without causing alterations in other aspects of the EHC. Thereby, the addition of plant sterols to the carrier β-cyclodextrin did not have additional effects.
... All the sterols which are produced in the plant body are β-sitosterol and its glycosidic derivatives. These moieties reveal antineoplastic, antipyretic, anti-inflammatory, and immunemodulating activity in vivo (Bouic and Lamprecht 1999). The mixture of β-sitosterol and its glycosidic derivatives targets specific Th1 and Th2 cells (T-helper lymphocytes) thereby developing natural killer cell and T-lymphocyte activity. ...
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The naturally occurring phytochemicals produced by plants are biologically sound and integrated to lower the threat of various human diseases. The history of the use of phytochemicals as conventional medicine or functional food is, perhaps, as old as the history of man. Secondary metabolites are not crucial for the development of the plant and their propagation, but they play an important role in its biotic and abiotic domain. These phytoconstituents are categorized into three important divisions – terpenoids, phenols, and alkaloids. Constituents of these classes are produced from the precursors of the same division obtained from the primary phytoconstituents. Both polyphenols and phenols are obtained from aromatic amino acids. Similarly, terpenoids are obtained from several intermediates of glycolysis. Alkaloids are chemically a more sundry class of N-heterocycles, which are structured from three aromatic amino acids, namely, glutamate, aspartate, and glycine. Maximum plant-obtained compounds used as food are either phenols or terpenoids. Hydroxybenzoic acids, curcuminoids, and phenylpropanoids including coumarins and flavonoids are the main constituents of phenolic groups. On the other hand, terpenoids comprise of mono-, sesqui-, and diterpenes. A compact figure of apposite constituents may not be allocated to terpenoids and phenols, and they are amino acids, glycosides, vitamins, and proteins. These metabolites give protection against UV radiation and scavenge the free radicals. They also provide defense against phytopathogenic bacteria, different fungi, and viruses and also against the attraction of pollinators. Throughout the approximate era of 1990, the main research was on the cytotoxic chemicals of plants, but the interest in the scientific validation of its traditional uses was very low. In the last decade, traditional uses of these phytoconstituents in pharmaceuticals have gained lots of interest. In vitro and in vivo animal models of analgesic and antipyretic, anticonvulsant, anticancer, immunomodulatory, anti-inflammatory, antibacterial, and antifungal effects have shown great promise. Here in this chapter, the functional information about these important phytoconstituents or secondary metabolites, which are widely used in various pharmaceuticals, has been explored and expressed.
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Tuberculosis (TB) is a contagious disease that has affected mankind. The anti-TB treatment has been used from ancient times to control symptoms of this disease but these medications produced some serious side effects. Herbal products have been successfully used for the treatment of TB. Gold is the most biocompatible metal among all available for biomedical purposes so Gold nanoparticles (GNPs) have sought attention as an attractive biosynthesized drug to be studied in recent years for bioscience research. GNPs are used as better catalysts and due to unique small size, physical resemblance to physiological molecules, biocompatibility and non-cytotoxicity extensively used for various applications including drug and gene delivery. Greenly synthesized GNPs have much more potential in different fields because phytoconstituents used in GNP synthesis itself act as reducing and capping agents and produced more stabilized GNPs. This review is devoted to a discussion on GNPs synthesis with herbs for TB. The main focus is on the role of the natural plant bio-molecules involved in the bioreduction of metal salts during the GNPs synthesis with phytoconstituents used as antitubercular agents. © 2021 Tabriz University of Medical Sciences. All rights reserved.
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Recent studies of vegetarian diets and their effects on morbidity and mortality are reviewed. Vegetarian diets are heterogeneous as are their effects on nutritional status, health, and longevity. Mortality rates are similar or lower for vegetarians than for nonvegetarians. Risks of dietary deficiency disease are increased on vegan but not on all vegetarian diets. Evidence for decreased risks for certain chronic degenerative diseases varies. Both vegetarian dietary and lifestyle practices are involved. Data are strong that vegetarians are at lesser risk for obesity, atonic constipation, lung cancer, and alcoholism. Evidence is good that risks for hypertension, coronary artery disease, type II diabetes, and gallstones are lower. Data are only fair to poor that risks of breast cancer, diverticular disease of the colon, colonic cancer, calcium kidney stones, osteoporosis, dental erosion, and dental caries are lower among vegetarians. Reduced risks for chronic degenerative diseases can also be achieved by manipulations of omnivorous diets and lifestyles.
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In this article, emphasis was placed on the relationship between exercise and upper respiratory tract infection (URTI) in humans, experimentally induced infections in animals subjected to varying levels of exertion, and potential changes in the immune system that might explain the altered risk of infection. With regard to induced infections in animals, the influence of any exercise intervention appears to be pathogen specific, and dependent on the species, age, and sex of the animals selected for study, and the type of exercise paradigm. In general, although further research with larger subject pools and improved study designs is needed, published data at this time support a "J" curve relationship between risk of URTI and increasing exercise workloads. For example, individuals exercising moderately may lower their risk of URTI while those undergoing heavy exercise regimens may have higher than normal risk. Although researchers have investigated changes in immune function that might provide a biological rationale for the "J" curve model of infection and exercise, the wide variety of research designs, exercise protocols, subject characteristics, and methodologies combined with the innate complexity of the immune system have made interpretation of published findings equivocal. T and NK cell function, for example, is often reported to be decreased during recovery from high-intensity exercise. However, when adjustments are made for exercise-induced perturbations in blood lymphocyte subsets, any link to decreased host protection is unlikely.
Sitosterol, the principal phytosterol in most higher plants and hence in plant-derived food products, is found in the serum and tissues of healthy humans in concentrations 800-1000 times less than the endogenous cholesterol. The glucoside of sitosterol (sitosterolin) is present in mammalian serum at even lower concentrations. In many animals, sitosterol and sitosterolin concentrations relative to cholesterol are considerably higher than in humans. Only plants can synthesise these compounds and humans and animals obtain them from their diet. Even though their absorption efficiency is low (~1/10 and ~1/50 for sitosterol and sitosterolin , respectively, relative to cholesterol), their apparent synergystic stimulatory effect on the immune system and prophylactic effect on a variety of diseases of civilisation indicates their importance in human and animal nutrition. Since modern food processing tends to reduce their concentration in processed plant-food products, and eating habits also affect their consumption adversely, it is desirable to eat sufficient unrefined or processed plant foods or resort to food supplements containing sitostero land sitosterolin.
There is much interest in the factors that control the cytokine profile of T-helper (Th) lymphocytes, and attention has focused on feedback from the cytokines themselves. In general, Th1 cytokines promote Th1 activity and inhibit Th2 activity, and vice versa. Both Th1 and Th2 responses should therefore be stable. However, in vivo, many responses start predominantly as Th1 and then shift to Th2. Why do they do this? As discussed here, an important influence on this shift that has been largely ignored in in vitro work is the endocrine system.
Several phytosterols, stigmasterol, campesterol and β-sitosterol, were shown to have potent anti-complementary activities. Stigmasterol was the most potent. A marked consumption of C4 was observed to have occurred when serum was incubated with these phytosterols, and β-sitosterol and stigmasterol showed higher C4 consumption than campesterol. After the incubation of serum with these phytosterols in the absence of Ca2+ ions, cleavage of C3 in the serum was detected by immunoelectrophoresis. Stigmasterol caused greater C3 cleavage than the other two compounds. Stigmasterol also showed higher consumption of complement than campesterol and β-sitosterol when rabbit erythrocytes were used in the assay system in the absence of Ca2+ ions. These results indicate that these phytosterols activate complement via both the alternative and classical pathways.
Diets rich in vegetables are associated with a low incidence of colon cancer. Since plant sterols are plentiful in vegetarian diets, we studied the effect of beta-sitosterol on colon tumor formation in rats treated with the carcinogen N-methyl-N-nitrosourea. We demonstrated that beta-sitosterol nullified in part the effect of this direct-acting carcinogen on the colon. We suggest that plant sterols may have a protective dietary action action to retard colon tumor formation. The beneficial effects of vegetarian diets may be enhanced because of the presence of these compounds.
The phytosterols, beta-sitosterol (BSS), and its glucoside (BSSG) enhance the in vitro proliferative response of T-cells stimulated by sub-optimal concentrations of phytohaemagglutinin (PHA) several fold at extremely low concentrations (femtogram level). A 100:1 (mass:mass) ratio of BSS:BSSG (termed essential sterolin formulation, ESF) showed higher stimulation than the individual sterols at the same concentration. In vivo activity of ESF was also demonstrated when volunteers ingested ESF for 4 weeks. Proliferation of their T-cells, stimulated maximally with PHA, was significantly enhanced (20-920%) when compared to baseline values. In vitro, ESF (1 was able to significantly enhance the expression of CD25 and HLA-Dr activation antigens on T-cells and increased the secretion, into the medium, of IL-2 and gamma interferon. NK-cell activity was also increased by BSS and BSSG alone, but with EST a higher activity was always found at different effector:target ratios (100:1 12:1).
To evaluate the adjuvant effect of beta-sitosterol and its glucoside in the treatment of culture proven pulmonary tuberculosis (PTB). A blinded randomised placebo-controlled trial in culture proven drug sensitive PTB. Patients were hospitalised for the duration of treatment and evaluated at monthly intervals with regard to sputum culture positivity, chest radiography, weight gain, Mantoux test response, routine haematology and liver functions. STATISTICAL EVALUATION: General linear models for repeated measures (SAS GLM package) compared the interaction effects, group effects and time effects of findings in 19 patients receiving sitosterols with those in 18 patients receiving a placebo (talcum powder). Absolute values and change from baseline values were evaluated, although only the latter are reported. Weight gain was significantly greater in the sitosterol group (mean weight gain 8.9 kg) than the placebo group (mean gain 6.1 kg) (P = 0.0023 group effects; P = 0.0001 for time effects). Speed of achieving culture negativity, radiological improvement and induration on Mantoux testing was similar in the two groups. Change in lymphocyte counts from baseline was significantly higher in the sitosterol group (P = 0.0001 and P = 0.0001 for group and time effects) as was the increase in eosinophil counts (P = 0.0001 and P = 0.0137 for group and time effects). The study has shown significantly improved weight gain and higher lymphocyte and eosinophil counts in PTB patients receiving sitosterols in addition to an efficacious antituberculosis regimen. Sitosterols and their possible mode of action should now be evaluated in larger numbers of tuberculosis patients and in diseases with a similar immunopathogenesis.