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Hepatoprotection by dandelion ( Taraxacum officinale ) and mechanisms

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The protection of the liver as an essential organ in the body against oxidative stress and deleterious compounds has been the subject of recent investigations. Among different compounds, medicinal plants play an important role due to their hepatoprotective effects. Taraxacum officinale or “common dandelion” is a popular plant that has been traditionally used for its hepatoprotective effects. Currently, there are limited clinical studies on its hepatoprotective effects. The aim of this review article is to evaluate the hepatoprotective effects of dandelion and its mechanism of action. We reviewed literature up to July 2019 on “Taraxacum officinale” or “dandelion” and hepatoprotection. Currently available pharmacological studies indicate that dandelion extracts have hepatoprotective effects against chemical agents due to its antioxidant and anti-inflammatory activities. The anti-inflammatory effects of dandelion, the prebiotic effects of its oligofructans, inhibitory effects against the release of lipopolysaccharides and fasting induced adipose factor, digestive enzymes, and enhancing effects of lipogenesis, reduce lipid accumulation and liver inflammation, which directly or indirectly improve the liver functions. Given emerging evidence on hepatoprotective effects of dandelion, designing large human clinical studies is essential.
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doi: 10.4103/2221-1691.273081 Impact Factor: 1.59
Hepatoprotection by dandelion (Taraxacum officinale) and mechanisms
Mohaddese Mahboubi, Mona Mahboubi
Medicinal Plants Research Department, Research and Development, TabibDaru Pharmaceutical Company, Kashan, Iran
ABSTRACT
The protection of the liver as an essential organ in the body against
oxidative stress and deleterious compounds has been the subject
of recent investigations. Among different compounds, medicinal
plants play an important role due to their hepatoprotective effects.
Taraxacum officinale or “common dandelion” is a popular plant that
has been traditionally used for its hepatoprotective effects. Currently,
there are limited clinical studies on its hepatoprotective effects.
The aim of this review article is to evaluate the hepatoprotective
effects of dandelion and its mechanism of action. We reviewed
literature up to July 2019 on Taraxacum officinaleor “dandelion”
and hepatoprotection. Currently available pharmacological
studies indicate that dandelion extracts have hepatoprotective
effects against chemical agents due to its antioxidant and anti-
inflammatory activities. The anti-inflammatory effects of dandelion,
the prebiotic effects of its oligofructans, inhibitory effects against
the release of lipopolysaccharides and fasting induced adipose
factor, digestive enzymes, and enhancing effects of lipogenesis,
reduce lipid accumulation and liver inflammation, which directly
or indirectly improve the liver functions. Given emerging evidence
on hepatoprotective effects of dandelion, designing large human
clinical studies is essential.
KEYWORDS: Dandelion; Hepatoprotective effects; Antioxidant;
Anti-inflammatory
1. Introduction
Liver is a vital organ with numerous functions in the body,
which transforms and cleans the body from chemical substances.
Although, the main function of liver is the body detoxification
from common toxins, chemicals and heavy metals, but liver is
affected by radical oxygen species (ROS) and oxidative stress
plays a critical role in initiation and progression of liver injuries.
Furthermore, liver is the metabolic organ for metabolism of
carbohydrates, lipids, proteins to produce the energy. Exogenous
(alcohol, drugs, environmental toxins, virus, and UV light), and
endogenous (obesity, insulin resistance, steatosis, hepatocellular
carcinoma, chronic hepatitis, fibrosis/cirrhosis) agents are the
main reasons for oxidative stress in the liver. Liver injuries by
oxidative stress cause irretrievable alteration in DNA, lipids and
proteins. Different types of liver diseases like zonal necrosis,
hepatitis, cholestasis, steatosis, granuloma, vascular lesions, and
neoplasm are involved in liver disorders[1]. Furthermore, drugs,
air pollution, inflammation, triglyceride accumulation, obesity,
insulin resistance and microorganisms play essential roles in liver
functions and related disorders. Medicinal plants are traditionally
used for their hepatoprotective effects[2] and Taraxacum officinale,
also known as “common dandelion”, is one important medicinal
plant as a hepatoprotective agent, which is used for treatment of
hepatobiliary problems[3]. Dandelion is a popular hepatoprotective
medicinal plant in different traditional medicines. The high content
of minerals, fibers, vitamins, and essential fatty acids make it
as a favorite food source[4]. Dandelion is a French word from
“dent de lion” with meaning of lion’s tooth. The scientific name
of dandelion comes from taraxis and akeomai, with meaning of
“benefit for inflammation”[5]. Dandelion roots are used in different
cuisines of at least 54 countries. Dandelion is used in folk medicine
of China, India and Russia as liver tonic[3]. Different traditional
systems including Ayurveda[6], Siddha and Unani recommended
using the dandelion for management of liver disorders such as
jaundice, liver and gallbladder’s disorders[7-9]. Dandelion roots
in combination with other plants are used in the powder form as
a sedative agent and for regulating the urine discharge and urine
burning sensation in India[10], and this combination is applied
as blood purifier and for treatment of hepatitis, jaundice, and
Asian Pacific Journal of Tropical Biomedicine 2020; 10(1): 1-10
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How to cite this article: Mahboubi M, Mahboubi M. Hepatoprotection by dandelion
(Taraxacum officinale) and mechanisms. Asian Pac J Trop Biomed 2020; 10(1): 1-10.
Review Article
Article history: Received 14 September 2019; Revision 5 November 2019; Accepted 5
December 2019; Available online 24 December 2019
To whom correspondence may be addressed. E-mail: mahboubi1357@yahoo.com
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fever[4]. Dandelion leaves or roots are used for liver complaints in
Himalaya region[11]. Oral administration of dandelion roots increases
the bile flow and is known as cholagogue[12]. Dandelion is one
ingredient of “Taemyeongcheong” and “kimchi” that is used for
liver complaints[13], and also eaten as food and salad by Germans,
French and Italian for its hepatoprotective effects[14]. Dandelion
leaves infusions are used in Mexico[15], Pakistan[16], Bolivia[17], and
Canada[18] for hepatic, biliary, kidney and spleen ailments. Moreover,
dandelion roots eliminate the toxins from liver and kidneys, dissolve
the gallstones, increase the appetite and stimulate the bile flow[19].
Although there are some review articles[20-22] on phytochemistry
of dandelion and its health benefit, due to traditional believes on
its hepatoprotective effects and its use in many hepatoprotective
products and limited review article on its effectiveness, this review
article is designed to focus on its hepatoprotective effects and its
related mechanism of actions.
At first, we conducted an investigation on chemical composition of
dandelion and its importance as a hepatoprotective agent.
2. Chemical composition of dandelion
The chemical composition of dandelion plays an important role
in its biological activities. Therefore, before evaluating the potency
of dandelion as a hepatoprotective agent, we consider the chemical
composition from different parts of dandelion.
The chemical composition of dandelion has been the subject
of different investigations. Dandelion plant is rich in vitamins,
inulin, phytosterols, amino acids, and minerals, particularly in
potassium[23,24], sesquiterpenes, triterpenes, phytosterols, and
phenolic compounds[5].
Oligofructans[25], chicoric acid and the related monocaffeyltartaric
acid, hydroxycinnamic acids, chlorogenic acid[23], triterpenoids[26],
lupane-, bauerane-, and euphane-type triterpenoids, 18β,19β-epoxy-
21β-hydroxylupan-3β-yl acetate, 21-oxolup-18-en-3β-yl acetate,
betulin, officinatrione, 11-methoxyolean-12-en-3-one, eupha-7,24-
dien-3-one, and 24-oxoeupha-7,24-dien-3β-yl acetate[27], taraxinic
acid derivatives[4], caffeic acids, p-hydroxyphenyl acetic acid[28],
rutin[29], apigenin, hesperidin, myricetin, sesquiterpene lactones,
hydroxyphenylacetic acid[30], synergic acid, vanillic acid[31] were
isolated from dandelion roots.
Flavonoid glycosides (luteolin 7-glucoside, luteolin 7-diglucosides),
coumarins, cichoriin, aesculin[23], sesquiterpenoid phytoalexin
(Lettucenin A)[32], 4-hydroxyphenylacetate inositol esters[21],
aesculin[4], caffeic acid, chlorogenic acids, apigenin, isovitexin[30],
chicoric acid[31] were identified in dandelion leaves. In addition,
dandelion flowers contained flavonoid glycosides, free luteolin and
chrysoeriol[23].
Polyphenols (hydroxycinnamic acid derivatives and flavonoid
glycosides) are abundant in dandelion aerial parts[33]. In one study,
the phenolic content of young leaf dandelion extract was higher
than that of its root[33]. The extraction by 50% and 80% hydro-
alcohol with or without formic acid at 60 for 3 h exhibited that
the phenolic and flavonoid content of hydro-alcohol 80% with
formic acid was higher than hydro-alcohol 80% without formic acid.
Extraction time and temperature had no effects on total flavonoid
and phenolic content of dandelion leaf extract. Total phenolic content
of leaf was higher than its stem, followed by flower and roots.
Total flavonoid content of leaf was higher than flower, followed by
stem and roots. Chicoric acid was identified as a major phenolic
Lettucenin A Chlorogenic acid
Aesculin
Luteolin
Chicoric acid
Betulin
Monocaffeyltartaric acid Chrysoeriol
Figure 1. The chemical components of dandelion.
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Mohaddese Mahboubi et al./ Asian Pacific Journal of Tropical Biomedicine 2020; 10(1): 1-10
compound in dandelion ethanol extract[31] (Figure 1).
The results of these investigations exhibited that the chemical
composition of each part of dandelion is changed by different parts,
extraction method, solvent, and temperature. Therefore, a direct
correlation can be found between the biological activity of dandelion
and its chemical compositions.
3. Hepatoprotective effects of dandelion against toxic
agents
Although dandelion is known as a hepatoprotective plant in
different traditional systems, the recent studies have been limited to
its protective effects against chemical toxic agent in animal studies.
There are different investigations that evaluated the efficacy of
dandelion against chemical agents. Carbon tetrachloride (CCL4)
as hepatotoxic haloalkane is capable to produce hepatocellular
fatty degeneration and centrilobular necrosis. CCL4 increased the
activities of liver enzymes [aspartate aminotransferase (AST),
alanine aminotransferase (ALT) and alkaline phosphatase (ALP)].
The liver weight and liver hydroxy proline content were increased
in the presence of CCL4 and the activity of hepatic copper zinc
superoxide dismutase (Cu/Zn SOD) was reduced[34]. Intra-peritoneal
administration of dandelion root hydro-alcoholic extract for 4 weeks
normalized the activity of ALP, Cu/Zn SOD enzymes and reduced
the hepatic hydroxyl proline level in CCL4-induced hepatic fibrosis
in mice. Dandelion root extract significantly reduced the enlargement
of liver, hepatic fibrinous deposits, and restored histological
architecture. Glial fibrillary acidic protein (GFAP) and α-smooth
muscle actin (α-SMA) expressions were reduced after treatment with
dandelion root extract, while metallothionein (MT) / expression
was increased in dandelion ethanol extract[29]. α-SMA and GFAP
expressions are responsible for fibrosis in chronic liver injury[34].
Up-regulation of MT / expression had protective effects against
liver injury[35]. Dandelion extract showed hepatoprotective effects
against CCL4 induced hepatic fibrosis by reducing the α-SMA
and GFAP and inducing the MT / expression. Liver fibrosis
is associated with excessive accumulation of extracellular matrix
protein in the liver. Dandelion root extract reduced the collagen
deposits in necrotic area and reversed the hepatic fibrosis, which was
associated with reduction in GFAP and α-SMA and increase in the
Cu/Zn SOD activity, suggesting its hepatoprotective effect[29].
Ethanol increases ROS production and reduces the cell viability of
liver. Hot aqueous extract of dandelion root had protective effects
against alcohol-induced liver damage in ICR mice and HepG2/2E1
cell lines without any cytotoxic effects. Dandelion extract (1 g/kg
bw/day) significantly reduced the serum AST, ALT, ALP, lactate
dehydrogenase and malondialdehyde (MDA) levels. Dandelion also
significantly increased the hepatic antioxidant enzymes [catalase,
glutathione peroxidase (GPx), glutathione-S-transferase (GST),
glutathione reductase (GR) and glutathione (GSH)]. Reduction in
lipid peroxidation and increase in antioxidant enzymes were caused
by dandelion hot water extract. Ethanol induced the oxidative
stress that was associated with reduction in cell viability, whereas
dandelion aqueous extract increased the cell viability in the presence
of ethanol[36]. The result of the previous study exhibited that the
hepatoprotective effects of dandelion root extract are related to
its antioxidant activities. Dandelion root extract increased the
antioxidant enzymes and ameliorated the liver enzymes, therefore
protecting the liver against oxidative stress induced by ethanol.
The hepatoprotective effects of dandelion leaf extract were
confirmed against sodium dichromate induced liver injury in rats.
Oral daily administration of dandelion leaf hot water extract (500
mg/kg) for 30 d decreased the total cholesterol, triglycerides, AST,
ALT, lactate dehydrogenase, MDA and chromium concentration in
rat’s blood and liver. Thyroid-stimulating hormone level reached to
normal level in sodium dichromate treated animal after pretreatment
with dandelion leaf extract, which was associated with increase
in antioxidant enzymes activities (SOD, catalase, GPx levels)
and reduction in DNA fragmentation[37]. As the results of this
study confirmed, up-regulation of hepatic antioxidant enzymes
may be responsible for its hepatoprotective effects[38]. Other than
the antioxidant activities of dandelion, the anti-fibrotic effects
of dandelion aqueous extract have been confirmed. Dandelion
inactivates the hepatic stellate cells and enhances the hepatic
regenerative capabilities[39].
Dandelion is used in combination with other herbal extract as
hepato-protective agents and commonly is used in combination
with Silybum marianum (S. marianum). The protective effect of
oral dandelion extract (100 mg/kg/day) and its combination with
S. marianum extract (100 mg/kg/day) was evaluated in CCL4
treated female Wistar albino rats. Combination of dandelion and
S. marianum extracts in CCl4 treated animals decreased the serum
ALP and GGT enzyme activities and MDA level in the kidney
tissue, and increased the GSH level and GST enzyme activities. The
hepatoprotective effects of dandelion were a little weaker than S.
marianum extract[40]. The results of animal studies confirmed the
hepatoprotective effects of hot aqueous extracts of dandelion roots
and leave against chemical compounds and the extract improved
the liver, and antioxidant enzymes. Although the hepatoprotective
effects of dandelion were confirmed in animal studies, there is no
clinical study on its efficacy, it will be worthwhile, if the chemical
compounds responsible for its hepatoprotective effects will be known
and these compounds are chosen as standard for clinical trials.
4. Identified chemical compounds responsible for
hepatoprotective effects of dandelion
Among different parts of dandelion extracts, aqueous extracts
of dandelion roots and leaves have been used as hepatoprotective
agents. Different components may be responsible for its
hepatoprotective effects. Total phenolics, flavonoids, tannins,
polysaccharides and ascorbic acids are the main components of hot
aqueous extract of dandelion leaf with the ability to scavenge the free
radicals[37]. Dandelion extracts had effective reducing power and free
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radical scavenging effects[41]. It has been confirmed that dandelion
leaf extract (EC50: 1.9 µg/mL) had much higher antioxidant activity
than its root extracts (EC50: 12.6 µg/mL) and crude powdered roots
(EC50: 65 µg/mL). Taraxol, taraerol, laevulin, inulin are found in
dandelion extracts responsible for its hepatoprotective effects. Some
compounds isolated from dandelion leaf aqueous extracts, especially
its luteolin and polyphenol contents, had hepatoprotective effects
against CCL4-induced liver injury[42,43].
In addition, the dandelion’s polysaccharides reduced the oxidative
stress and liver inflammation. Oral administration of 304 and 92 mg/kg
polysaccharides (Top1 and Top2) for 7 d reduced the serum AST, and
ALT and thus was effective against CCL4-induced hepatitis in Sprague-
Dawley rats[43].
Polyphenols, flavonoids, and polysaccharides are responsible
compounds for hepatoprotective effects of dandelion. Therefore, the
dandelion extracts can be standardized on the basis of one of these
compounds.
5. Effects of dandelion on human condition related to
its hepatoprotective effects
Although there is no clinical study on hepatoprotective effects of
dandelion extracts, there is some evidence in human studies which
confirm its potency in protection of liver.
5.1. The role of oligofructans in dandelion and its effects on
liver functions
The prevalence of nonalcoholic fatty liver disease (NAFLD) is
associated with worldwide epidemic of obesity. There is a positive
correlation between intestinal microorganisms and development of
obesity and NAFLD. Portal venous system connects the liver and
gut, therefore the liver gets hurt by bacteria, bacteria endotoxin and
cytokines[44].
Altered gut bacteria induce the release of LPS, fasting induced
adipose factor (FIAF), and endogenous ethanol that stimulate the
hepatic fat deposition and produce the inflammation in the liver
and damage the liver function (Fibrosis/Cirrhosis, steatohepatitis,
steatosis and NAFLD). The use of probiotics and prebiotics as diets
is for regulating the intestinal microbial ecosystems[45]. Prebiotics
act as the source of carbon and energy for stimulating the beneficial
intestinal bacteria. Dandelion roots are rich in oligofructans,
which are known as prebiotics[25]. High prebiotic fiber content of
dandelion acts as the source of carbon and energy for stimulating
the Bifidobacteria or other probiotics[25]. The bifidogenic effect
of dandelion root was confirmed against fourteen Bifidobacteria
strains[25]. Prebiotics are resistant to gastric acidity and mammalian
enzymes and they are fermented by gut bacteria. Prebiotics or non-
digestible fibers induce the growth or activity of intestinal beneficial
bacteria and influence on lipid metabolisms[46]. Reduction in growth
of gut dysbiosis is associated with reduction in release of LPS, FIAF,
and alcohol. In addition, prebiotic compounds induce the intestinal
beneficial bacteria that reduce the lipid accumulation[47] and
oxidative stress[48]. The results of preclinical studies confirmed that
the prebiotic effects of dandelion extracts reduced the inflammation
and oxidative stress in the body. Reduction in oxidative stress and
ethanol production in the liver is the main cause of reduction of liver
inflammation.
5.2. Anti-obesity effects of dandelion
Obesity is the most common background condition for development
of liver diseases with metabolic origin[49]. There are some documents
on anti-obesity effects of dandelion. Plants with inhibitory effects
against pancreatic lipase have potential to be used as an anti-obese
agent. The removal of fatty acids chains from triglycerides at the
positions of α and α’ is performed by pancreatic lipase, which produces
the lipolytic compounds. Inhibition of pancreatic lipase is an attractive
target for control the obesity[50]. Dandelion ethanol extract inhibited
the pancreatic lipase activity (IC50: 78.2 µg/mL) compared with orlistat
(IC50: 0.22 µg/mL), in in vitro condition[51,52]. The result of this study
was in accordance to the other study, in which young fresh dandelion
leave ethanol extract exhibited 90.2% pancreatic lipase inhibition
activity (IC50 = 78.2 µg/mL)[51]. However, the result of this study[51] was
in contrast to the other research that showed dandelion extract as a
weak pancreatic lipase inhibitory agent[53]. α-Glucosidase inhibitors
are used to develop the compounds for management of obesity and
related disorders. The inhibition of α-glucosidase suppresses the
cleavage of glucose from disaccharides and oligosaccharides[54].
Dandelion root and herb ethanol extract (100 µg/mL) exhibited
weak inhibitory effects against α-glucosidase activity (lower than
20%). Inhibition of angiotensin converting enzymes is important for
management of hypertension related to obesity[55]. Dandelion extract
showed weak xanthine oxidase, and ACE inhibitory effects[53]. The
results of above studies confirmed the acceptable inhibitory effects
of dandelion against pancreatic lipase activity.
Hypertrophy and hyperplasia of adipocytes are the other reasons
for obesity and identified by expanded adipose tissue, which is
associated with disruption in normal functions of adipose and
amplifying the secretome in the body. The systemic effects in the
liver lead to insulin resistance and hepatic lipid accumulation[56].
The positive role of dandelion roots and leaf on lipid metabolism,
adipogenesis and restoring the liver function is demonstrated.
Dandelion leaf and roots inhibited the lipogenesis and adipocyte
differentiation in 3T3-L1 pre-adipocytes[30]. Dandelion root
extract (400, 500, 600 µg/mL) reduced the size and the number
of adipocytes and increased the lipolysis activity. Leaf extract
and crude powdered roots of dandelion reduced the triglyceride
accumulation in mature adipocytes and the effect of leaf extract was
higher than the root extracts[41]. Dandelion root hydro-alcoholic
extract (30 µg/mL) for 10 and 20 d showed anti-adipogenic effects
on human primary visceral pre-adipocytes (P10, P20 and A7 cells).
Dandelion extract induced apoptosis (76.91%-81.00%) and inhibited
the adipogenesis in P10 and P20 cell lines, which increased the
release of free glycerol and decreased the triglyceride accumulation
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and lipogenesis[28]. Therefore, dandelion had anti-obesity effects by
different mechanisms, which is associated with reduction in liver
inflammation.
5.3. Beneficial effects of dandelion on type 2 diabetes
Insulin resistance is the primary cause of hyperglycemia and
the main pathogenesis of type 2 diabetes. There is an association
between high insulin resistance and hepatogenesis[57]. The anti-
diabetic effects of dandelion were the focus in some studies. The
result of a systemic review showed that among 20 animal and human
studies, only one diabetic rat study exhibited the hypoglycemic
effects of dandelion[58]. In other study, the anti-diabetic effect of 5
g dandelion leaf or root powder for 9 d was compared with placebo
on sixty type 2 diabetic patients. After taking the dandelion powder,
fasting blood glucose was monitored before and during the treatment
periods. The results showed that dandelion leaf and root powder
significantly reduced the fasting blood glucose levels of type 2
diabetic patients compared with placebo group[59].
Glucose homeostasis is affected by oxidative stress, as the result
of auto-oxidation and protein glycation[60]. High lipid peroxides
and reduction of oxidative defense are associated with β-cell
dysfunction and impair the insulin secretion[61]. Dandelion extracts
stimulated the release of insulin in pancreatic β-cells, and exhibited
the hypoglycemia effects. Treatment of rat insulinoma cells (INS-
1E cells) with 40 µg/mL dandelion or glibenclamide in the presence
of glucose (6.0 mM) increased the insulin secretion in INS-1E
cells compared to normal glucose (3.0 mM)[62]. Dandelion as one
ingredient of SR2004, clinically decreased the HbA1c, fasting blood
glucose, lipid profile, and total cholesterol in patients with type 2
diabetes mellitus[63]. Oral administration of dandelion can improve
the insulin sensitivity in type 2 diabetic patients. Diabetic diseases
are associated with liver dysfunctions and improvement in diabetic
conditions is associated with correct liver functions.
5.4. Hypoglycemic effects of dandelion and improvement in
the oxidant condition in the body
Although there is a close relation between type 2 diabetes and
hyperglycemia, due to frequency of studies, this subject was
evaluated in a distinct part. There are studies which exhibited that
dandelion had hypoglycemic effects by improvement in the liver
and antioxidant enzymes. Feeding the hybrid grouper with basal
diet containing dandelion extract (0, 0.1%, 0.2%, 0.4% and 0.8%)
for 8 weeks had no significant impact on growth performance and
feed utilization. Dandelion extract reduced the whole body’s crude
lipid percent and increased the crude protein percent in muscle.
Dandelion extract increased the mRNA level of antioxidant enzymes
(catalase, GPx and GR) and improved the liver enzyme activities.
Reduction in whole body’s crude lipid was associated with reduction
in inflammatory condition in fish spleen and kidney. Furthermore,
dandelion extract increased the survival rate and total blood cell
count in CCL4 treated hybrids[64]. The results of this research in fish
exhibited that dandelion extract regulates lipid metabolism related
genes expression in fish, which is related to reduction in crude lipid
content in the whole body. The immunity status was improved in
dandelion treated fish by enhancing the antioxidant enzymes and
decreasing the inflammation in the kidney and spleen. Furthermore,
the plasma triglyceride levels were reduced in ICR mice after
consumption of dandelion ethanol extract which was attributed to the
pancreatic lipase inhibitory effects of flavonoids in dandelion[51,52].
Dandelion root and leaf (1%) had hypolipidemic and antioxidant
effects in rabbit fed high cholesterol diet. Dandelion root extract
reduced the AST, ALT, triglyceride and LDL-cholesterol and
increased the creatine kinase, and HDL-cholesterol. Dandelion leaf
and root extract significantly increased the GSH, GPX, SOD and
decreased the lipid peroxidation (TBARS), GST and formation
of atherosclerotic lesions. Dandelion root extract improved the
atherogenic index, and prevented the oxidative damage[65]. GSH
as the most abundant cellular thiol antioxidant enzyme protects the
liver from injuries[66]. Damage in body tissue or organs increases
the ALT and AST and lipid peroxidation in the body[67]. Dandelion
leaf extract had protective effect against liver injury in high fat diet
induced hepatic steatosis[68]. Steatosis is caused by triglyceride
accumulation in the liver[1]. C57BL/6 mice group fed a high
fat diet supplemented with dandelion leaf extract reduced lipid
accumulation, which was associated with reduction in liver and body
weights, triglyceride, total cholesterol, serum fasting glucose level
and insulin[68].
Fatty acids are metabolized by two pathways of mitochondrial
β-oxidation to produce ATP, or by esterification to produce
triglycerides and very low-density lipoproteins[69]. Reduction
in triglycerides and total cholesterol after dandelion leaf extract
supplementation exhibited the role of dandelion leaf extract in
controlling the fatty acid metabolism[68].
Plasma HDL acts as cholesterol translocator from peripheral tissue
to liver for catabolism. Therefore, dandelion extract improves the
liver enzymes and liver functions by inhibiting the pancreatic lipase,
decreasing the lipogenesis and reducing the inflammation in the
liver.
One important property of dandelion is its anti-inflammatory
and antioxidant effects. Dandelion methanol or aqueous extract
exhibited the antioxidant and anti-inflammatory activities in LPS-
stimulated RAW 264.7 cells. Nitric oxide (NO) production was
suppressed by dandelion methanol or aqueous extracts with IC50 of
79.9 and 157.5 µg/mL, respectively. Dandelion methanol extract
and aqueous extracts inhibited the MDA concentration. The GSH
content and anti-oxidant enzymes (catalase, SOD, GPx) were
increased after treatment by dandelion methanol or aqueous extracts
in a dose dependent manner. Catalase and SOD activities were
increased by methanol dandelion extract, which were higher than
its aqueous extract[70]. Among different kinds of dandelion extracts
(hot aqueous, aqueous, ethanol and methanol), hot aqueous and
methanol extracts of dandelion roots had higher antioxidant and anti-
inflammatory effects against LPS-induced macrophages, which was
associated with reduction in NO and MDA production. Luteolin and
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chicoric acid are responsible for antioxidant and anti-inflammatory
effects[42]. Betulin, 18β,19β-epoxy-21β-hydroxylupan-3β-yl acetate,
and 24-oxoeupha-7,24-dien-3β-yl acetate showed inhibitory effects
against NO in LPS activated mouse peritoneal macrophages without
any cytotoxic effects as same as L-NMMA, suggesting its anti-
inflammatory effects[27].
Dandelion methanol extract (100 µg/mL) had anti-inflammatory effect
in LPS stimulated human umbilical vein endothelial cells. Dandelion
methanol extract at 50, 100 and 200 µg/mL had no effect on viability of
human umbilical vein endothelial cells. In addition, its methanol extract
reduced the adherence of LPS induced THP-1 cells to baseline and LPS
induced monocyte adhesion to endothelial cells [71].
The antioxidant activity of dandelion leaf extract (hydro-
ethanol 50% with formic acid) was higher than root extracts.
Dandelion extract suppressed ROS in HT-29 cells and LPS induced
inflammatory signaling NF-κB p65 and COX-2 activity. Dandelion
extract also inhibited LRR, PYD, caspase-1, NLRP3 inflammasome
mediated IL-1β, and IL-8. The inflammasome activation was
suppressed through scavenging ROS and inhibiting inflammation[31].
Dandelion leaf aqueous extract (100 and 200 µg/mL) exhibited
the anti-inflammatory effects in rat mammary micro-vascular
endothelial cells. Endothelia ICAM-1 was increased during the
inflammation, which regulates the adhesion of effector cells to
endothelium. Dandelion aqueous extract significantly inhibited
TNF-α and ICAM-1. In addition, dandelion aqueous extract reduced
the expression of TNF-α and ICAM-1 in Staphylococcus aureus
induced mastitis in mammary gland tissues[72]. Dandelion phenolic
extracts showed better antioxidant activity than that of flavonoids
extracts[73]. The extracts with high content of hydroxycinnamic acid
showed the highest radical scavenging effects in DPPH system and
higher anti-coagulant effects[21]. Dandelion ethanol extracts also
demonstrated protective effects against glutamate-induced oxidative
damage by inducing the Nrf2/heme oxygenase 1 (HO-1) pathways
in HT22 cells. Moreover, dandelion ethanol extract (50-400 µg/mL)
had no significant effects on cell viability of HT22 cell lines. Its
ethanol extract increased the expression of HO-1 in a dose dependent
manner. Besides, dandelion ethanol extract increased the expression
of Nrf2 and inhibited the glutamate induced cytotoxicity and ROS
generation by inducing the HO-1 expression[74].
Taraxasterol inhibited the production of LPS induced TNF-α, IL-
1β and NF-κB activation in BV2 microglia cells. The formation of
lipid rafts was disrupted, which was associated with inhibition of
TLR4 translocation in lipid rafts. LXRα-ABCA1 signaling pathway
and cholesterol efflux were activated by taraxasterol (a pentacyclic
triterpene compound)[75]. Taraxasterol inhibited the iNOS and
COX-2 expression in LPS-stimulated RAW264.7 cells[76], as well
as IL-1β-induced NO and PGE2 production in human osteoarthritic
chondrocytes[77]. The anti-inflammatory and anti-oxidant effects of
dandelion play an important role in its hepatoprotective effects.
5.5. Effect of dandelion on blood properties
The main action of liver is purifying the blood. Dandelion is known
as blood purifier and its fresh leaves are rich in irons, so it is used in
salad or sometimes with egg and for anemia in Slovenia[78]. Injection
of dandelion ethanol extract (50, 100 and 200 mg/kg) to adult
female (Balb/C) mice for 20 d significantly increased the number of
RBC, WBC, lymphocytes and hemoglobin level rate[79]. Therefore,
dandelion can be used as blood purifier by increasing the number of
RBC.
6. Molecular mechanism of hepatoprotective effects of
dandelion
The molecular mechanism of hepatoprotective effects of dandelion
is explained in Figure 2. AMPK as energy sensor and one important
metabolic pathway decreases fatty acid synthase and acetyl CoA
carboxylase (ACC) by suppressing SREBP-1c. AMPK is activated
upon depletion of ATP and adipocyte derivative hormones such as
adiponectin, resistin and leptin. Lipid accumulation was suppressed
by treatment with dandelion leaf ethanol extract, which was
associated with reduction in insulin resistance and lipid via AMPK
pathway. A significant increase in activation of liver adenosine
monophosphate activated protein kinase (AMPK) and muscle
protein was observed after treatment with dandelion leaf extract,
which inhibited the liver’s lipid accumulation and decreased the
insulin resistance. Glucose uptake and phosphorylation of AMPK
(pAMPK)/ACC increased in C2C12 myotubes after treatment with
dandelion extract[68].
Dandelion ethanol extract reduced the serum insulin, fasting
glucose level and homeostatic model assessment for insulin
resistance in high fat diet induced mice, which was associated with
improvement in insulin sensitivity.
Dandelion (Tops polysaccharides) reduced the CCL4 induced hepatic
lesions in mice, which was associated with reduction in NF-κB, iNOS,
COX-2, TNF-α, and IL-1β (regulatory inflammatory mediators) and
up-regulation of antioxidant enzymes and GSH level. The free radical
scavenging effects of Tops were exhibited by reduction in TBARS
concentration[43]. It has been found that NO production and iNOS
expression were inhibited by Top2 in a dose dependent manner[80].
Although COX-2 expression was inhibited by Top2[43], the results
of other study exhibited[80], COX-2 was not suppressed by Top
treatment. Top, especially Top2, inhibited the production of TNF-α
in LPS induced RAW 264.7 cells. NF-κB regulates the expression
of iNOS, COX-2, and TNF-α. Nrf2 and NF-κB are regulated by
MAPK and PI3K/Akt. Top suppressed the phosphorylation levels
of IκBα, p65, and Akt, while had no effect on ERK, JNK and p38,
which was associated with inhibition of inflammatory cytokines.
Tops initiated partly the cell recovery following the cell mortality by
tert-butyl hydroperoxide, which showed other relevant mechanisms
rather than PI3K/Akt and HO-1 were responsible for Tops initiated
cell recovery[80]. HO-1 expression was induced in RAW 264.7 cells
in the presence of Top1 and Top2. Nrf2 nuclear accumulation was
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7
Mohaddese Mahboubi et al./ Asian Pacific Journal of Tropical Biomedicine 2020; 10(1): 1-10
also induced in the presence of Tops in a dose dependent manner.
Tops regulated Nrf2 mediated HO-1 expression in RAW 264.7 cells
by PI3K/Akt signaling cascade. PI3K/Akt is the upstream signaling
molecules in modulation of NF-κB and Nrf2. Treatment of Akt and
JNK using LY294002 and SP600125 abrogated Top induced HO-1
protein expression[80]. The anti-oxidative effects of Tops were caused
through Nrf2 transcription factor and PI3K/Akt signaling pathway,
and led to production of HO-1 in RAW 264.7 cells. HO-1 exhibited
protective effects against oxidative and inflammatory stimuli.
Therefore, Tops inactivated the NF-κB pathway and reduced the
LPS induced inflammatory mediators. In addition, up-regulation of
Nrf2-mediated HO-1 increased the cyto-protective effects in murine
macrophages. Top mediated anti-inflammatory effect in RAW 264.7
cells was associated with reduction in iNOS and TNF-α expression
and up-regulation of HO-1 protein.
Dandelion methanol and water extracts inhibited iNOS gene
expression and NF-κB in a dose dependent manner. Nitric oxide
synthase controls the production of NO and the iNOS expression
and is regulated by TNF-κB[70]. Mononuclear cell adhesion is
caused by endothelial VCAM-1. Dandelion methanol extract
reduced the VCAM-1, pro-inflammatory cytokines and monocyte
chemo-attractant protein 1. LPS induced nuclear translocation of
NF-κB was suppressed by dandelion without any effect on MAPK
activation. Dandelion extract also reduced the VCAM-1 and MCP-1
mRNA, TNF-α, IL-1β, and IL-6 expression, and also inhibited the
phosphorylation of IκBα, which was associated with inhibition of
NF-κB nuclear translocation and suppression of NF-κB pathway[71].
7. Daily dose of dandelion in traditional medicine
Dandelion is used in “materia medica for the relief of famines” as
dietary and edible vegetable. It is used single or in combination with
other plants as granule, hard shelf capsule, tablet or injection for
heat relief, inflammation and detoxification of the body. In Chinese
Pharmacopeia, the typical daily dose of dandelion is 10-15 g[20]. The
daily dose of dandelion as a whole herb and its roots is 4-10 g raw
material equivalent[81]. Moreover, dandelion leaf of 3-5 g is used as a
diuretic and choleretic agent in British Herbal Pharmacopeia, while
its roots are used for hepatic function. The daily dose for leaf tincture
is 5-10 mL, which is used twice daily. For cholelithiasis or gall stone
disease, 4-10 g dried leaf or 2-8 g dried root is used three times a day.
Dandelion tea is prepared with 4-10 g dried leaf or 2-8 g dried root
in 150 mL boiling water for 10-150 min and one cup is used three
times a day. Five to ten mL tincture (1:5) used three times a day are
recommended[82]. In other text, 4-10 g/day crude dried leaves or 50 g
fresh dandelion are recommended. In USA, 3-5 mL dandelion tincture
is used three times a day. The LD50 of dandelion is greater than 20 g/kg
body weight[18]. So, dandelion is generally recognized for its safety and
is well tolerated without any negative effects in human[83].
Dandelion extract
Figure 2. Molecular mechanism of hepatoprotective effects of dandelion.
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8 Mohaddese Mahboubi et al./ Asian Pacific Journal of Tropical Biomedicine 2020; 10(1): 1-10
8. Conclusion
Dandelion is a popular hepatoprotective plant in different medicinal
systems. It is named piss-a-bed in old European texts and known as a
laxative agent. Dandelion is diuretic, and is used for kidney and liver
disorders[36,84]. Their actions are bitter tonic, and choleretic. The
diuretic effects of dandelion leaf are stronger than dandelion roots[54].
Dandelion is also used in wine with good taste[85]. Whole herb of
dandelion is recommended for appetite loss and dyspepsia. Its roots
had benefical effect on bile flow disturbance and urine obstruction
apart from appetite loss and dyspepsia[81]. Current animal studies
exhibited the efficacy of dandelion against the cytotoxic effects of
CCL4, ethanol and sodium dichromate by improvement of liver and
antioxidant enzymes. Improvement in liver function is associated
with restoring histopathology of the liver cells. Polysacharides
(Top1, Top2), flavonoids, phenolic, tannins, ascorbic acids, taraxol,
taraerol, laevulin, inulin and luteolin are chemical compounds that
are responsible for hepatoprotective effects of dandelion. Different
mechanisms may be responsible for hepatoprotective effects of
dandelion. Oligofructans as prebiotic compounds of dandelion
induce the growth of intestinal probiotics and inhibit the release
of LPS and FIAF and lipid accumulation in the body. Dandelion
has anti-obesity effects via inhibition of digestive enzymes, lipid
metabolism and adipogenesis. The lipogenesis effects of dandelion
are associated with reduction of inflammation in the body and liver
and improvement of insulin resistance and anti-oxidant condition.
Although different documents confirmed the hepatoprotective
effects of dandelion, preparing standard extracts of dandelion with
high contents of effective compounds and designing large clinical
studies with standard extracts are required for further evaluating the
hepatoprotective effects of dandelion.
Conflict of interest statement
There is no conflict of interest.
Acknowledgments
The authors are thankful for the manager of Tabib Daru
Pharmaceutical Company, Mr. Ali Reza Mazaheri for spiritual help.
Authors contributions
Mohaddese Mahboubi has written, revised and approved the final
manuscript and Mona Mahboubi helped to gather the information
from reliable sources.
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Chapter 11 Oxidative Stress as a Crucial Factor in Liver Associated Disorders: Potential Therapeutic Effect of Antioxidants Hanaa A. Hassan Faculty of Science, Taibah University, Al-Ula, Kingdom of Saudi Arabia; Faculty of Science, Mansoura University, Mansoura, Egypt Summary Points • Human diseases appear to be increased; part of this increase may be due to our frequent contact with chemicals and other environmental pollutants. • The use of synthetic drugs in controlling diseases result in undesirable side effects, especially when used for long terms. So, nowadays, there is uprising awareness for going back to nature and getting away as much as possible from synthetic drugs as a target for therapy of some diseases and as a protection from environmental pollutants. • Liver is a major vital organ of vertebrates and some other animals that plays a major role in metabolism with numerous functions in the human body, including regulation of glycogen storage, decomposition of red blood cells, plasma protein synthesis, hormone production, and detoxification. • It is affected by reactive oxygen species (ROS) resulting in oxidative stress, which plays a critical role in liver diseases and other chronic and degenerative disorders resulting impair cellular functions and render hepatocytes more susceptible to the effects of endogenous and exogenous peroxides. • Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury and promotes several disorders of metabolic pathways and a depletion of antioxidant defense mechanisms. • The oxidative stress not only triggers hepatic damage by inducing irretrievable alteration of lipids, proteins, and DNA contents and more importantly, modulating pathways that control normal biological functions. • Recent trends suggest the use of several natural endogenous and exogenous antioxidants rather than synthetic ones in scavenging produced free radicals species tend to prefer compounds use that induced cellular damage to control and treating of various diseases, including liver. • Several natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as antiinflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. • Supplementation with natural antioxidants may help in safe application in medicine as well as in many other aspects of nowadays life. This effect is probably through its various nutritional constituents due, at least in part, to their synergistic antioxidant capacity. • Therefore it is recommended that antioxidant-enriched diets should be added to diets regimens to develop a new therapeutic strategy for the treatment of diseases associated with free radicals generation. However, the fractionation and bioavailability of the main constituents of the natural extracts which are responsible for the antioxidant activity will be an important area in the future.
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The study investigated the effects of dietary supplementation with dandelion extracts (DE) on growth performance, feed utilization, body composition, serum biochemical, liver histology, immune-related gene expression and CCl 4 resistance of hybrid grouper (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀). A basal diet supplemented with DE at 0% (diet 0%), 0.1% (diet 0.1%), 0.2% (diet 0.2%), 0.4% (diet 0.4%) and 0.8% (diet 0.8%) were fed to hybrid grouper for 8 weeks. The results revealed that dietary DE had not a significant impact on growth performance and feed utilization (P > 0.05), but it could decrease the percent of crude lipids in whole body and increase the percent of crude protein in muscle (P < 0.05). Dietary DE increased the mRNA levels of antioxidant enzymes (catalase, glutathione peroxidase and glutathione reductase) and reduced inflammatory factor in the spleen and head-kidney of fish (P < 0.05), but reduced the expression of the liver antioxidant gene except for glutathione reductase (P < 0.05). Dietary supplementation with 0.2%–0.4% DE could effectively improve liver health. After injection of CCL 4 by 72 h, fish fed Diet0.2% and Diet0.4% showed regular hepatocyte morphology while fish fed Diet 0%, Diet 0.1% and Diet 0.8% showed hepatocyte damage. Higher survival rate and total blood cell count was observed in fish fed 0.1%–0.4% dietary DE (P < 0.05). In conclusion, DE could be used as a functional feed additive to enhance liver function of farmed fish. The best level of it should be between 0.2% and 0.4%.
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Taraxaci Herba (Taraxacum mongolicum and other species) has been used in traditional Chinese medicine and dietary application for a long history in China, and Taraxacum officinale has been applied in medicinal and food use in other regions and cultures around the globe. In this review, the phytochemical constituents of dandelion (particularly from T. mongolicum and T. officinale) were summarized. Recent published health benefits of dandelion, such as anti-oxidant activity, anti-inflammatory activity, blood sugar and lipids regulation and hepatoprotective activity, as well as its safety data were highlighted. The limited human clinical study and pharmacokinetics information lead to the thought that well-designed human clinical study should be the focus and opportunity for the future research area to truly understand efficacy function and health benefit of dandelion for its application in medicine and health food area.
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Lactobacillus gasseri BNR17 is a probiotic strain isolated from human breast milk. Animal studies reported that BNR17 inhibited increases in body weight and adipose tissue weights. The purpose of this study was to evaluate the antiobesity effects of BNR17 in humans. In a randomized, double-blind, placebo-controlled trial, 90 volunteers aged 20-75 years with body mass index (BMI) from 25 to 35 kg/m2 were randomized to receive a placebo, low-dose BNR (BNR-L, 109 CFU/day), or high-dose BNR (BNR-H, 1010 CFU/day) for 12 weeks. Body weight, BMI, waist and hip circumferences, waist-to-hip ratio, abdominal adipose tissue areas, body fat mass, lean body mass, and biochemical parameters were assessed at the beginning and end of the trial. Visceral adipose tissue (VAT) was significantly decreased in the BNR-H group compared with the placebo group (P = .038). Difference of VAT areas of the BNR-H group compared with the placebo group after 12-week consumption of BNR17 was significant (-21.6 cm2, P = .012). Waist circumferences were significantly decreased in both the BNR-L and BNL-H groups (P = .045 and .012, respectively) compared with the baseline values, but not in the placebo group. Biochemical parameters were not significantly different among the groups. These findings suggest that daily consumption of BNR17 may contribute to reduced visceral fat mass in obese adults.
Chapter
This chapter considers ethnobotany, the study of the relationship between plants and people. It includes study of the uses of plants by humans and the relationship between humans and vegetation. In addition, it examines our dependence on plants and our effects on them. The chapter aims to understand the many ways weeds can be used and to encourage thought about the importance of doing research to find uses for weeds.