Anti-Obesity Effects of Medicinal and Edible Mushrooms

Abstract

Obesity is a group of metabolic disorders caused by multiple factors, including heredity, diet, lifestyle, societal determinants, environment, and infectious agents, which can all lead to the enhancement of storage body fat. Excess visceral fat mass in adipose tissue generate several metabolic disorders, including cardiovascular diseases with chronic inflammation based pathophysiology. The objective of the current review is to summarize the cellular mechanisms of obesity that attenuate by antioxidant potentials of medicinal and edible mushrooms. Studies have showed that mushrooms potentially have antioxidant capacities, which increase the antioxidant defense systems in cells. They boost anti-inflammatory actions and thereby protect against obesity-related hypertension and dyslipidemia. The practice of regular consumption of mushrooms is effective in the treatment of metabolic syndrome, including obesity, and thus could be a good candidate for use in future pharmaceutical or nutraceutical applications.

Full text

molecules
Review
Anti-Obesity Effects of Medicinal and
Edible Mushrooms
Kumar Ganesan and Baojun Xu *
Food Science and Technology Program, Beijing Normal University—Hong Kong Baptist University United
International College, 2000, Jintong Road, Tangjiawan, Zhuhai 519087, China; kumarg@hku.hk
*Correspondence: baojunxu@uic.edu.hk; Tel.: +86-756-3620-636; Fax: +86-756-3620-882
Academic Editors: Min-Hsiung Pan and Filomena Conforti
Received: 27 September 2018; Accepted: 2 November 2018; Published: 5 November 2018


Abstract:
Obesity is a group of metabolic disorders caused by multiple factors, including heredity,
diet, lifestyle, societal determinants, environment, and infectious agents, which can all lead to the
enhancement of storage body fat. Excess visceral fat mass in adipose tissue generate several metabolic
disorders, including cardiovascular diseases with chronic inflammation based pathophysiology.
The objective of the current review is to summarize the cellular mechanisms of obesity that attenuate
by antioxidant potentials of medicinal and edible mushrooms. Studies have showed that mushrooms
potentially have antioxidant capacities, which increase the antioxidant defense systems in cells.
They boost anti-inflammatory actions and thereby protect against obesity-related hypertension and
dyslipidemia. The practice of regular consumption of mushrooms is effective in the treatment
of metabolic syndrome, including obesity, and thus could be a good candidate for use in future
pharmaceutical or nutraceutical applications.
Keywords:
medicinal and edible mushrooms; cholesterol-lowering effects; antioxidants;
anti-inflammatory; anti-obesity
1. Introduction
Obesity is a group of disorders defined as a body mass index (BMI) of more than 30 kg/m
2
,
in which enhancement of storage body fat deposited in the adipose tissue can cause deleterious
health effects. The complications of obesity (e.g., diabetes, cardiovascular diseases (CVD), pulmonary
diseases, obstructive sleep apnea, cancer, osteoarthritis etc.) are usually caused by a combination of
high food intake, sedentary lifestyles, lack of physical activity and a genetic predisposition. Hence,
obesity is a metabolic syndrome that reflects an imbalance between energy intake and expenditure [
1
,
2
].
It is measured by excess stored fat and high lipid content in the plasma. The quantity of total mass
of fat is enhanced by the availability of adipocytes and proliferation and cell differentiation that
results in both augmented number and size of fat cell [
1
]. Adipose tissue is a significant organ
that contributes energy balance in the body. High-fat accumulation causes an unusual progress of
white adipose tissue that contributes to obesity in humans [
2
]. The primary management of obesity
involves diet, exercise, and surgical intervention. In addition, there are treatment strategies such as
the prevention of high-calorie intake, suppression of appetite, and the therapeutic drugs which affect
mobilization and consumption of lipids [
3
]. Nevertheless, a successful result is also confirmed only
in a trivial number of the population. Therapeutic drugs for obesity, such as orlistat (Xenical
®
) and
sibutramine (Reductil), are found to cause many complications that include emesis, insomnia, headache,
myocardial infarction, stomach pain and constipation [
4
]. In the growing medical field, clinicians often
face main complications of multiple risk factor syndrome, including diabetes, pulmonary diseases,
osteoarticular diseases, CVD (atherosclerosis, elevated blood pressure, stroke, dyslipidemia) and some
Molecules 2018,23, 2880; doi:10.3390/molecules23112880 www.mdpi.com/journal/molecules

Molecules 2018,23, 2880 2 of 26
of the commonest forms of cancer [
5
]. These can lead to morbidity and mortality in which obesity is
the foremost cause of these syndromes.
2. Etiology of Obesity
A combination of excess nutrients and a lack of physical activity is the primary causative factor
in most cases of obesity. In addition, obesity is caused by hereditary, medications or mental illness
and endocrine disorders [
6
]. Sometimes high proportions of obesity are seen at a communal level
and persist due to readily accessible tastier food, changes the mode of transportation, and increasing
urbanization [
7
]. Further studies have shown that some of the potential contributors to elevated obesity
levels include hormonal disruptors, inadequate sleep, the variability of ambient temperature, smoking
habits, cravings, usage of medications (e.g., antipsychotic drugs), pregnancy at a later age, inherited
risk factors and elevated BMI [8,9].
2.1. Diet, Lifestyle, and Societal Determinants
The global rate of obesity increased more than threefold between 1980 and 2014. More than
600 million people were considered obese in 2014. Almost 40 percent of men and women 18 years
old and above were overweight. Over 41 million children (<5 years old) were overweight or obese in
Asia. It is predicted that 1.12 billion people will be obese around the world in 2030 [
10
]. In most of the
developed countries people die due to their overweight condition and obesity. This scenario is also
rising in lower-middle-income nations, mostly in urban backgrounds. Overweight or obesity rates
in Africa (1990–2014) increased by nearly double from 5.4 million to 10.6 million [
11
]. Overweight
is mostly caused by the consumption of energy-dense foods when the ingestion of carbohydrates is
higher than in a fat diet [
12
]. In addition, the lack of physical activity highly influences the rate of
enhancement of obesity. Presently, over
3
4
of the global population is found to exercise inadequately,
along with the increasing sedentary nature of daily tasks, laborsaving technology, altered modes of
transportation, and increasing urbanization. There is an increasing relationship between television
watching time and obesity threat in both adults and children [
13
]. WHO further specified global
populations are being less active in leisure pursuits, environmental and societal alterations connected
with the progress and deficiency of encouraging strategies in various sectors including education,
health, urban planning, farming, transport, environment, food, and advertising [
10
]. In developed
nation’s populations, those with higher incomes are more probable to have obesity than those with low
income. No significant relation is seen between obesity and education in men. Nevertheless, higher
income women have less obesity than low-income women. Furthermore, women with college degrees
are less probable to have obesity compared with less educated women [
12
]. Smoking is another societal
factor that influences overweight. Over ten years, those who quit smoking will increase in weight by
4.5 kg (men), and 5.0 kg (women), respectively [14].
2.2. Genetics
More than 70 percent of obesity is caused by heredity. This is a consequence of phenotypes, which
are linked to adipose tissue distribution and excess body fat [
2
]. Excessive adiposity and increase
with age are also influenced by heredity. According to Neel’s ‘thrifty gene’ hypothesis, genes that
predispose to obesity in populations that often experienced hunger [
15
]. Individuals who possess
these genes develop the ‘obesogenic’ environment and can become extremely obese. Nowadays, this is
predominantly seen in Pima Indians and Pacific Islanders [
15
]. Many genes involved in glucose and
lipid metabolism are subject to positive selection in Asian and African ethnic groups. The search for
genes that enhance the vulnerability to improve obesity has become progressively significant. There
have been several studies that have proved that the candidate genes are extremely associated with
obesity and elevated body weight [11].

Molecules 2018,23, 2880 3 of 26
2.3. Medical and Psychiatric Illness
Numerous psychiatric prescriptions are recognized as weight gain agents that cause obesity
in most psychiatric cases [
16
]. Weight gain is connected with the use of mood stabilizers (lithium,
valproate), antipsychotics (clozapine and olanzapine), and antidepressants (amitriptyline), which may
have serious long-term complications [
17
]. Medical sicknesses that threaten to augment obesity include
congenital (hypothyroidism, dwarfism, cretinism) or genetic syndromes (Cohen syndrome), and night
eating syndrome [
18
]. The menace of obesity is significantly higher in psychiatric patients than in
patients with non-psychiatric complaints and these adverse effects of medications vary with age and
sex [19].
2.4. Infectious Agents
The term “infectobesity” describes obesity of infectious origin. Infectious agents, especially
viruses, have been identified to cause obesity in various animal models [
20
]. Human Adv36 can
induce insulin sensitivity, obesity, and hepatic steatosis in chickens, mice, and monkeys. Canine
distemper virus and avian adenovirus were reported to cause growth failure, fatty liver, and obesity in
mice. An avian retrovirus (Rous-associated virus-7) in chicken, and Borna disease virus in rats caused
neuronal degeneration in the brain, obesity, hyperuricemia, and dyslipidemia. Scrapie agents were
also reported to induce obesity in mice and hamsters [
20
]. Infections may not be completely associated
with obesity as a causal factor; however, there may be a connection to the consequences of obesity [
21
].
It has found that overweight individuals are highly vulnerable to several types of contagion, due to the
weakening of the immune system. Moreover, in severe obesity cases, the course of infectious diseases
is more severe [20].
3. Pathophysiology of Obesity
Hormones like leptin and ghrelin are internal mediators in humans involved in feeding and
hunger. Leptin is a peptide hormone synthesized by adipocytes, which play a key role in the storage
of fat in the body, and regulates long-standing appetite. When the energy reserves are adequate, leptin
levels are increased and this would suppress further food ingestion. It is formed by the ‘ob’ gene in
mice [
22
]. Ghrelin is another peptide hormone synthesized by the fundus lining of the stomach and
epsilon cells of the pancreas, which regulates temporary appetite control. This peptide hormone plays
a chief function in the maintenance of energy balance and body weight by impeding food ingestion
and elevating energy expenditure through the hypothalamus [
23
]. Administration of leptin could
be a powerful treatment in obese, mainly leptin deficient, individuals. A majority of obese persons
are identified as leptin resistant and have been identified as having elevated leptin concentrations in
their blood [
24
]. Leptin resistance in overweight individuals, which is due to the extreme synthesis of
leptin with ineffective appetite control, is very common [
22
]. Although both leptin and ghrelin are
synthesized peripherally, they regulate cravings through the hypothalamus, which regulates the intake
of food and energy expenditure. The pro-opiomelanocortin (POMC) pathway in the hypothalamus is
the significant circuit that stimulates satiety and inhibit feeding. It is initiated by an arcuate nucleus,
lateral and ventromedial hypothalamus. The arcuate nucleus has another two functional neuron
units, namely neuropeptide Y (NPY) and agouti-related peptide (AgRP) that provoke responses in the
hypothalamus. Both induce feeding and inhibit satiety. Both units of the arcuate nucleus are mediated
by leptin and ghrelin. These hormones inhibit the NPY/AgRP group while eliciting the POMC group
and vice versa. Therefore, a deficiency of leptin signaling either via lacking leptin or leptin resistance
encourages to overeating and ultimately causes some heritable and acquired types of obesity [
22
]
(Figure 1).

Molecules 2018,23, 2880 4 of 26
Molecules 2018, 23, x FOR PEER REVIEW 4 of 26
Figure 1. Pathophysiology of obesity and energy homeostasis—Melanin-concentrating hormone
(MCH) is a peptide hormone, synthesized by the neurons of the hypothalamus, which normally
stimulate food intake. These neurons are arbitrated by POMC as well as NPY/AGRP in an arcuate
nucleus. Leptin and insulin are peptide hormones that activate POMC while inhibiting NPY/AGRP,
consequently reduces body weight through energy expenditure or lipolysis and release free fatty
acids (FFA). In contrast, the hunger hormone, ghrelin provokes NPY/AGRP and enhances body
weight through the intake of food. MCH neurons are impeded by POMC cells, however, NPY/AGRP
neurons are known to have an antagonist effect. Weight loss reduces insulin and leptin amounts in
the blood while increasing ghrelin levels. This response is regulated by the arcuate nucleus (triggering
of NPY/AGRP and impeding of POMC) that ultimately activates MCH neurons.
4. Pathologies Associated with Obesity and Its Effects on Health
Obesity is an amplification of normal adiposity and is a central dogma in the pathophysiology
of diabetes, cancer, dyslipidemia, hypertension, and atherosclerosis. It largely affects health because
of the secretion of excessive adipokines [22,23]. Obesity is a key agent in metabolic malfunctions
involving lipid and glucose metabolism and influences organ dysfunction involving the heart, liver,
intestines, lungs, hormones, and reproductive functions. Obesity is coupled with numerous
pathological effects due to the extra body weight (i.e., worsening of osteoarthritis, sleep apnea, gout,
and pain of the vertebral column) [15,22]. Moreover, obesity is highly connected to the following
occurrence and pathologies.
Figure 1.
Pathophysiology of obesity and energy homeostasis—Melanin-concentrating hormone (MCH)
is a peptide hormone, synthesized by the neurons of the hypothalamus, which normally stimulate food
intake. These neurons are arbitrated by POMC as well as NPY/AGRP in an arcuate nucleus. Leptin and
insulin are peptide hormones that activate POMC while inhibiting NPY/AGRP, consequently reduces
body weight through energy expenditure or lipolysis and release free fatty acids (FFA). In contrast,
the hunger hormone, ghrelin provokes NPY/AGRP and enhances body weight through the intake of
food. MCH neurons are impeded by POMC cells, however, NPY/AGRP neurons are known to have an
antagonist effect. Weight loss reduces insulin and leptin amounts in the blood while increasing ghrelin
levels. This response is regulated by the arcuate nucleus (triggering of NPY/AGRP and impeding of
POMC) that ultimately activates MCH neurons.
4. Pathologies Associated with Obesity and Its Effects on Health
Obesity is an amplification of normal adiposity and is a central dogma in the pathophysiology of
diabetes, cancer, dyslipidemia, hypertension, and atherosclerosis. It largely affects health because of the
secretion of excessive adipokines [
22
,
23
]. Obesity is a key agent in metabolic malfunctions involving
lipid and glucose metabolism and influences organ dysfunction involving the heart, liver, intestines,
lungs, hormones, and reproductive functions. Obesity is coupled with numerous pathological effects
due to the extra body weight (i.e., worsening of osteoarthritis, sleep apnea, gout, and pain of
the vertebral column) [
15
,
22
]. Moreover, obesity is highly connected to the following occurrence
and pathologies.

Molecules 2018,23, 2880 5 of 26
4.1. Chronic Inflammation and Endothelial Dysfunction
Over one billion adipocytes are present in humans, where they have the functions of storage of
triglycerides in fat depots and supplying energy. In addition, they act as a major endocrine organ
that regulates adipocyte hormones like leptin, adiponectin, and visfatin. Accompanying pancreatic
hormones (insulin), these adipocyte hormones help normalize body-fat mass [
25
]. These body fat
depots release inflammatory adipokines including cytokines (TNF-
α
, IL-1, and IL-6), complement
proteins and growth factors, which generate local steatonecrosis in the vascular system and cause
inflammation and endothelial dysfunction [
25
]. Studies have also demonstrated that the biomarkers
of inflammation and endothelial dysfunction are connected with CVD, atherosclerosis, hypertension,
and insulin resistance [26].
4.2. Hypertension and Atherosclerosis
The incidence of hypertension and atherosclerosis are substantially higher in individuals with
obesity (>60%) which affects different proportions of men (78%) and women (64%) [
27
]. The occurrence
of hypertension enhances BMI dependence in both genders with increasing age [
28
]. Obesity affects
individuals progressively, and later leads to morbidity and mortality. The incorporation of obesity,
hypertension, and atherosclerosis has two key complications [
29
]. Initially, this combination is most
dangerous for patients with obesity and high blood pressure that have elevated incidence of CVD,
including coronary artery disease, carditis, cardiomyopathy, cardiac arrhythmia, end-stage renal disease,
stroke, and obstructive sleep apnea [
30
]. Furthermore, obesity enhances the threat of treatment-resistant
arterial blood pressure; as a result, several medications and equipment therapy like renal sympathetic
denervation are needed [
31
]. Hormonal studies of the adipose tissue also found a connection between
obesity, atherosclerosis, and hypertension, likely to cause adiposity dysfunction due to excess secretion
of bioactive molecules and immunomodulators [
32
]. The impairment of adiposity in individuals with
obesity causes insulin resistance, malfunctioning in the renin-angiotensin-aldosterone system as well as
the sympathetic and parasympathetic nervous system [
33
]. These hormones are important to regulate
the structure and functions of the kidney (Figure 2).
Obesity can cause an upsurge in the risk of endometrial cancer through endocrine pathways.
Obesity is related with augmented insulin levels, which may lead to elevated insulin-like growth
factor 1 and synthesis of androgens that ultimately cause progesterone deficiency [
27
]. Lack of
progesterone progresses to cause anovulation and consequently appears to be the most significant
physiological risk factor for endometrial cancer in premenopausal women. Elevated adiposity
normally provokes aromatase activity in postmenopausal women, leading to enhanced bioavailable
oestrogen levels, endometrial cell propagation and stimulated production of IGF1 in endometrial
tissue. After menopause (absence of exogenous oestrogen production), when ovarian progesterone
synthesis has ceased completely, the more central risk factor appears to be obesity-related endometrial
cancer development [
28
]. Adipocyte normally synthesizes aromatase along with 17
β
-HSD. In obese
persons, there is elevated transformation of the androgens
∆
4-
∆
4A and T into the estrogens, E1 and E2,
respectively, by an enzyme, aromatase. 17
β
-HSD catalyzes the conversion of
∆
4A and E1 into T and
E2 respectively. The circulating levels of sex-hormone-binding globulin helps elevate the amounts of
E2 and T that can readily diffuse across to target cells through binding with estrogen and androgen
receptors. Ultimately, they inhibit apoptosis and promote cellular proliferation in the breast epithelium
and endometrium [
29
]. Obesity leads to hyperinsulinemia and diabetes, which in turn to produce
AGE causing a pro-inflammatory state by NF-
χ
B, protein kinase, and intracellular adhesion molecules.
Based on the reduction of NO and more leucocyte infiltration in the vessels this causes endothelial
and microvascular dysfunction, which are influenced by oxidative stress (ROS), eventually causing
atherosclerosis and hypertension [
30
,
32
]. In addition, obesity elevates excess glucose and fatty acid
oxidation levels that lead to lipid peroxidation and ROS generation, which facilitate lipoprotein toxicity
and enhances the rate of hypertension and formation of plaque in blood vessels [27–30].

Molecules 2018,23, 2880 6 of 26
Molecules 2018, 23, x FOR PEER REVIEW 6 of 26
Figure 2. Physiological disorders related to obesity and its impact on human health. Endometrial
cancer: Obesity elevates the threat of endometrial cancer via endocrine pathways. Elevated adiposity
provokes aromatase action, leading to augmented estrogen in postmenopausal women. Estrogens
generally elevate endometrial cell propagation and stimulating the production of IGF-binding protein
1 (IGF1)-cause endometrial cancer. Tumor development: Adipocyte normally synthesizes aromatase
and 17β-hydroxysteroid dehydrogenase (17β-HSD). In obese persons, there is elevated
transformation of the androgens Δ4-androstenedione (Δ4A) and testosterone (T) into the estrogens,
oestrone (E1) and oestradiol (E2), respectively, by an enzyme, aromatase. 17β-HSD catalyze the Δ4A
and E1 (less biologically active hormones) into the T and E2 (more active hormones), respectively.
The circulating levels of sex-hormone-binding globulin aids to elevate the amounts of E2 and T that
can readily diffuse across to target cells through binding with estrogen and androgen receptors.
Ultimately, they inhibit apoptosis and promote cellular proliferation in the breast epithelium and
endometrium. Diabetes: obesity leads to hyperinsulinemia and diabetes, which in turn produce AGE
cause pro-inflammatory state by NF-χB, protein kinase, and intracellular adhesion molecules. Based
on the reduction of NO and more leucocytes infiltration on the vessels cause endothelial and
microvascular dysfunction, which influenced by oxidative stress (ROS), eventually cause
atherosclerosis and hypertension. Carbohydrate and lipid metabolism: Excess glucose and fatty acid
oxidation leads to lipid peroxidation, which facilitates lipoprotein toxicity and enhances the rate of
hypertension in the blood vessels.
4.3. Dyslipidemia and Cardiac Alterations
Obesity is the most widespread cause of dyslipidemia, which produces metabolic syndrome
[34]. Overproduction of lipids due to obesity and insulin resistance results in elevated TG storage in
Figure 2.
Physiological disorders related to obesity and its impact on human health. Endometrial cancer:
Obesity elevates the threat of endometrial cancer via endocrine pathways. Elevated adiposity
provokes aromatase action, leading to augmented estrogen in postmenopausal women. Estrogens
generally elevate endometrial cell propagation and stimulating the production of IGF-binding protein
1 (IGF1)-cause endometrial cancer. Tumor development: Adipocyte normally synthesizes aromatase
and 17
β
-hydroxysteroid dehydrogenase (17
β
-HSD). In obese persons, there is elevated transformation
of the androgens
∆
4-androstenedione (
∆
4A) and testosterone (T) into the estrogens, oestrone (E1)
and oestradiol (E2), respectively, by an enzyme, aromatase. 17
β
-HSD catalyze the
∆
4A and E1 (less
biologically active hormones) into the T and E2 (more active hormones), respectively. The circulating
levels of sex-hormone-binding globulin aids to elevate the amounts of E2 and T that can readily diffuse
across to target cells through binding with estrogen and androgen receptors. Ultimately, they inhibit
apoptosis and promote cellular proliferation in the breast epithelium and endometrium. Diabetes:
obesity leads to hyperinsulinemia and diabetes, which in turn produce AGE cause pro-inflammatory
state by NF-
χ
B, protein kinase, and intracellular adhesion molecules. Based on the reduction of NO
and more leucocytes infiltration on the vessels cause endothelial and microvascular dysfunction, which
influenced by oxidative stress (ROS), eventually cause atherosclerosis and hypertension. Carbohydrate
and lipid metabolism: Excess glucose and fatty acid oxidation leads to lipid peroxidation, which facilitates
lipoprotein toxicity and enhances the rate of hypertension in the blood vessels.
4.3. Dyslipidemia and Cardiac Alterations
Obesity is the most widespread cause of dyslipidemia, which produces metabolic syndrome [
34
].
Overproduction of lipids due to obesity and insulin resistance results in elevated TG storage in
non-adipose tissues [
35
]. In addition, LDL rich in TG, partly degraded by a lipolytic enzyme (hepatic

Molecules 2018,23, 2880 7 of 26
lipase), are transformed into smaller LDL, causing atherosclerosis [
36
]. Moreover, obesity enhances
the threat of angina, cardiac arrest and death, and an unusual heartbeat. Elevated heartbeat in obese
individuals increases the frequency of ventricular dysrhythmias and cardiac arrhythmias. The annual
rate of cardiac deaths is almost 40 times higher in obese individuals than in non-obese persons [31].
4.4. Metabolic Syndrome
Obesity is the key danger factor for type 2 diabetes. In developed countries, obese individuals
are ten times more likely to be identified with diabetes than persons of a healthy weight. At present,
about 90% of individuals with diabetes are overweight or obese. Individuals with severe obesity are at
greater risk of type 2 diabetes than an obese person with a lower BMI [
34
]. Rizvi [
37
] confirmed that
the connection between obesity and diabetes, and impaired glucose intolerance. Generally, in obese
persons, there is massive adipose tissue, which produces a huge quantity of glycerol, free fatty acids,
pro-inflammatory cytokines, advanced glycation end products, intracellular adhesion molecules,
and hormones [
37
]. These substances are highly connected with insulin resistance, which develops
hyperinsulinemia with excess pancreatic islet stimuli and decreases or impairment of receptors leading
to type 2 diabetes. Ganesan and Gani [
38
] stated that obesity is the most important component of the
metabolic syndrome/disorder, described by the co-occurrence of impaired glucose tolerance, diabetes,
insulin resistance, abdominal obesity, hypertension, and the combination of increase TG and decrease
HDL cholesterol (Figure 2).
4.5. Cancer and Neurodegenerative Disorders
The World Cancer Research Fund and International Agency for Research on Cancer have
suggested that overweight or obese individuals are highly susceptible to get various cancers, namely
adenocarcinoma of the esophagus, colon, breast, endometrium, and kidney [
39
]. Epidemiological studies
have also indicated that malignancies of the liver, gallbladder, and pancreas are obesity-associated and
that obesity could enhance the danger for other malignancies including thyroid, prostate, leukemia,
non-Hodgkin’s lymphoma, multiple myeloma, and melanoma [
40
]. It has been appraised that about
20% of all cancer demises in the United States can be recognized as connected with overweight and
obesity [
41
,
42
]. The levels of circulating estrogens are strongly associated with adiposity. These
obesity-related malignancies are mostly ascribed to the elevated levels of estrogen in the adipose
tissue, inflammation, and infiltration of macrophages [
43
]. Overweight and obesity cause a mental
and emotional state in a person that reduces self-worth to mental depression. Certainly, the incidence
rates of anxiety and depression are 3–4 fold increased among obese people [
44
]. Obesity escalates
considerably the menace of neurodegenerative disorders such as Alzheimer’s, multiple sclerosis,
Parkinsonism, and amyotrophic lateral sclerosis. For incidence, a solid correlation occurs among BMI
and increase concentrations of amyloid. This protein normally accumulates in the Alzheimer’s patient
brain, eventually destroying nerve cells and creating mental and social problems [45].
4.6. Sex Hormone Imbalance
Obesity can influence reproductive functions causing problems such as hormonal imbalance,
impairment in ovulation, and infertility in malea and females [
43
]. Obesity has typically been linked
with impaired fecundity. Obese women are less likely to conceive per cycle. These women normally
suffer distresses to the hypothalamic-pituitary axis, menses disruption and are 3–4 times more likely
to get oligo-/anovulation [
46
]. Decreased levels of estrogen after menopause have also been linked
with excess adiposity and accumulation of visceral fat [
47
]. Besides that, obesity induced by hormonal
imbalances is connected to a range of adverse health complications as a result of cardiovascular
abnormalities and insulin resistance [
46
]. It is well known that testosterone is a primary hormone in
the pathophysiology of overweight and obesity. Decreased levels of testosterone are connected with
high-fat mass, particularly central adiposity and decreased thin mass in males. These characteristic
features are connected to metabolic syndrome and testosterone deficiency and are linked with energy

Molecules 2018,23, 2880 8 of 26
inequity, hyperglycemia, insulin resistance and dyslipidemia [
48
]. Testis dysplasia and alteration of
sex hormone levels exist in obese male adolescents. Obesity and accumulation of fat lead to elevated
estradiol and declined total and free testosterone that leads to erectile dysfunction [49].
5. Treatment of Obesity
Lifestyle (diet, exercise/physical exercise), pharmacotherapy (weight loss drugs and hormone
treatment), and behavioral therapy may cause modest weight reductions in severely obese individuals.
Lifestyle with pharmacotherapy has been shown to induce a 2–10% weight loss in obese individuals
per annum [50]. However, long-term treatment for obesity is medically a most challenging task.
5.1. Dietary Intervention and Diet Control
There is a great positive link between the quantity of total body fat and visceral adiposity. Hence,
any dietary intervention that will diminish total adiposity is likely to induce some loss of abdominal
fat. Lifestyle changes also promote weight loss, which can lead to reduced visceral and subcutaneous
adipose tissue. The nutritional recommendation with an emphasis on a low-calorie and low-fat diet,
with consumption of 800 to 1500 kcal of energy/day, persists. Reduced intake of calories (in the range
of 500–1000 kcal) is likely to reduce excess body weight [
26
]. Their will permit approximately 1 to
2 pounds of weight reduction in a week. Fasting or starvation are also indicated as causes of weight
loss in obesity [50]. Nutrition awareness is important for body weight management.
5.2. Physical Activity and Pharmacotherapy
Energy balance comprises the balance between intake of calories and the use of energy [
51
].
The main causes of obesity are due to the intake of easy and cheap readily available high-calorie
fat diets combined with an inactive lifestyle. Hence, negative energy balance (eating less food and
enhanced energy expenditure) is the only way to reduce obesity and overweight. Consistent physical
activity is a key element to dropping weight. A diversity of physical exercises are helpful and easy
to execute. Exercises not only help to reduce weight but also enhance cardio-respiratory fitness and
prevent CVD [
51
]. Exercise is the most effective therapy for obesity together with a low calorie regime.
Medication and weight loss surgery can help to reduce weight in obese persons. Medications regularly
require long administration periods as many individuals regain their lost weight when medication
is suspended. The suspension of medication use by individuals is typically due to their major side
effects, cost, and a potential lack of insurance coverage [52].
5.3. Surgical Treatment
Weight loss surgery (WLS)/metabolic surgery is an effective treatment for obesity [
53
].
The National Institute of Health consensus has recommended surgery only for those obese individuals
with high BMI (>35) and who have a serious clinical illness with sleep apnea.
5.4. Natural Products
Natural products that are possible medications for obesity are under investigation. According
to Ayurvedic medicine, this can be an outstanding, effective, and safe strategy [
54
]. Various natural
bioactive compounds can influence weight loss and avert diet-induced obesity. Hence, these products
have been extensively consumed for the treatment of abdominal obesity and overweight [
55
–
57
].
Various studies have shown the role of natural metabolites obtained from medicinal plants, which are
used in the prevention of obesity and obesity-related chronic disorders. This anti-obesity or weight loss
mechanism may be influenced by the medicinal plants, which modulate appetite suppression or the
restraint of lipid and carbohydrate metabolic enzymes or interfere with adipogenesis [
58
–
60
]. Recent
animal investigations that have also confirmed the role of various phytochemical-based strategies
encourages research into the prevention of obesity. These cellular studies support the notion that the

Molecules 2018,23, 2880 9 of 26
consumption of dietary bioactive compounds decreases the proliferation of preadipocytes, reduces
the viability and differentiation of adipocytes, promotes lipolysis and fatty acid
β
-oxidation, and
minimizes triglyceride accumulation and inflammation [
7
,
9
]. Furthermore, animal studies have
strongly indicateed that the regular consumption of dietary bioactive compounds has a significant
influence on obesity, as demonstrated by the reduction of body weight and stored fat mass via
increasing energy and fat burning, and regulating glucose hemostasis [61].
5.5. Mushrooms
Mushrooms have been extensively used as foods, nutraceuticals, and medicines since time
immemorial [
61
]. They are recognized as one of the most important food supplements for their vital
roles in human health, nutrition, and various illnesses. They contain various bioactive compounds,
including primary metabolites that could avert oxidative stress [
62
]. Secondary metabolites such
as polysaccharides (mainly
β
-D-glucans), heteroglycans, chitinous substances, peptidoglycans,
proteoglycans, lectins, RNA components, lectins, lactones, alkaloids, terpenes, flavonoids, terpenoids,
steroids, phenols, glycoproteins, nucleotides, fatty acids, vitamins, proteins, amino acids, antibiotics
and minerals that have favorable impacts on the human body and protect it from the diseases [
62
].
These bioactive compounds are excellent antioxidants and anti-inflammatory agents beneficial to the
CNS, heart, kidney, and liver [
63
]. Furthermore, it has been proven that these bioactive compounds act
as chemopreventive agents and protect most serious diseases, including diabetes, obesity, CVD and
neurodegenerative diseases [1].
Several mushrooms have been widely consumed in most of the developed and developing
countries by different ethnicities, races and cultures and are proved to maintain normal health
and prevent or treat dreaded illnesses [
62
]. Nutritional analyses of mushrooms found that edible
mushrooms contain vital nutrients, taste, flavor and physiological functions [
64
]. They are rich
in high quality proteins, polyunsaturated fatty acids (with a relatively low content of total fat),
vitamins, minerals, and fiber. Mushrooms produce low energy which is favorable for weight loss;
the contain low glucose, and high mannitol, that is exactly appropriate for diabetics; and have no
cholesterol and low sodium, which is good for people suffering from hypertension [
63
,
64
]. Furthermore,
mushrooms have a high content of vitamin D and B-complex with a high content of minerals and a
significant quantity of many trace elements, especially of selenium, which is a potent antioxidant [
65
].
In addition to their nutritive value, edible mushrooms have exclusive features in terms of color, palate,
flavor, odor, and texture that make them more attractive for human ingestion. Several studies have
recommended regular ingestion of certain mushrooms are either as a regular food or as extracted
compound (nutraceuticals). Some of these compounds (polysaccharides) are active in both preventing
and treating various diseases [64].
Dietary and medicinal mushrooms are widely recognized for their immunomodulatory,
hepatoprotective, antiviral, antinociceptive, antitumor, anticancer, antidiabetic, and antimicrobial
properties [
66
,
67
]. Mushrooms constitute 22,000 well-known species, extensively present on Earth
and about 10% of them have been investigated [
27
]. The dietary mushrooms that have unique
functional and medicinal features include Lentinus,Auricularia,Hericium,Grifola,Flammulina,Pleurotus,
and Tremella species. Medicinal mushrooms recognized for their medicinal properties include
Ganoderma,Trametes, etc. [
65
]. The beneficial effects of edible mushrooms and their polysaccharides on
the gut microbiota [
68
,
69
] that is highly associated with obesity and diabetes is presently a dynamic
niche research area [
70
]. A study in mice showed that the extracts of G. lucidum decrease overweight
by modulating the microbiota, and hence mushrooms could be a novel prebiotic to control obesity [
68
].
The impact of a high-fat diet (HFD) on the microbiota in the gut is more complex than the impact
on energy equilibrium. Studies showed that HFD-induced alterations in gut microbiota provide a
reduction of Bacteroides and Firmicute elevation, which are linked to high energy harvest, fat storage
and eventually gut inflammation and permeability [
70
]. Mushrooms help to regulate dysbiosis and
augment antiobesity effects. Holmes [
71
], and Chang et al. [
69
] indicated that G. lucidum decreases

Molecules 2018,23, 2880 10 of 26
obesity in mice by regulating the composition of the microbiota. These considerations further suggest
that the likely functions of microbiota in the polysaccharide-induced reduction of obesity and diabetes.
Furthermore, modulating microbiota with the consumption of mushroom could also help maintain
glucose homeostasis and reduce insulin resistance linked to diabetes and obesity. Huang et al. [
72
]
demonstrated that the polysaccharides obtained from Pleurotus tuber-regium mushrooms showed
antihyperglycemic and antihyperlipidemic potential and reduced oxidative stress in obese diabetic rats.
6. Anti-Obesity Effects of Edible and Medicinal Mushrooms
Mushrooms have high nutritious value with numerous bioactive compounds that have
well-known impacts on various cardiac markers [
73
–
82
]. Mushrooms have been well documented
in traditional medicine as having hypocholesterolemic effects. These effects are connected to CVD
related lipid metabolism, anti-inflammatory properties, and the prevention of oxidative stress with
platelet agglutination [
74
]. Furthermore, the consumption of mushrooms diminishes CVD and
obesity due to their significant amounts of bioactive compounds [
8
]. Studies further showed that
the cholesterol-lowering effect might be due to a decrease in VLDL [
73
] and decrease in the catalytic
functions of HMG-CoA reductase and amplification of the rate of cholesterol catabolism [
75
]. A study
evidenced that mushrooms reduced TG, TC, plasma glucose and hypertension in diabetic rats [
73
].
These results further suggested that the intake of mushrooms provides health aids by acting on the
atherogenic profile under hyper- and normocholesterolemic circumstances in rats [73].
Obesity unfavorably affects systemic immunity via the inflammatory index, and platelet
markers [
76
]. Numerous investigations have examined the anti-obesity effect of polysaccharides
obtained from different mushrooms
in vitro
as well as
in vivo
. Polysaccharide obtained from
Coriolus versicolor triggered mice splenocytes via the MAPK-NF-
κ
B signaling pathway that induces
an immunomodulatory effect [
77
]. A polysaccharide obtained from Tremella fuciformis prevented
the variation of 3T3-L1 adipocytes by decreasing the expression of mRNA suggesting the possible
significance of the polysaccharide as an anti-obesity prebiotic [
63
]. Treatment of adipocytes with
G. lucidum reduced adipogenic transcription factor expression that stimulates transportation, storage of
glucose and lipids, and activates AMPK signaling pathways suggesting the potential significance of the
polysaccharide as an antiobesity and antidiabetic agent [
78
]. Long-term (1 year) and short-term (4-day)
clinical studies with obese or diabetic participants asked them to evaluate the impact of substituting 20%
of high-energy beef with 20% of low-energy white button mushrooms in the diet [
79
,
80
]. The results
showed that the mushroom regime consumers had lesser BMI, decreased belly circumference, and
increase satiety without diminishing palatability. The authors of the studies concluded that the
consumption of white button mushrooms (Agaricus bisporus) has potential as an antidiabetic and
antiobesity. Similarly this work has been extended to include other extremely health-promoting
mushroom varieties, like Hericium erinaceus (Lion’s mane) and Lentinus edodes (shiitake) species [
81
,
82
].
The
in vitro
and
in vivo
actions of edible and medicinal mushrooms and its anti-obesity potentials are
summarized in Table 1.
6.1. Actions on Hypertension
Hypertension is regulated by several mechanisms, one of the most significant of which is a
renin-angiotensin-aldosterone system (RAS). Normally RAS is regulated by the Zn-metallopeptidase
enzyme, angiotensin-converting enzyme (ACE). The main function of ACE is involvement in the
transformation of an Ang-I decapeptide into an Ang-II octapeptide. Typically Ang-II (a potent
vasoconstrictor), cooperates with the Ang-II type 1 receptor (AT1) provoking the synthesis of
aldosterone, which elevates sodium and water retention in the kidney and correspondingly raises
blood pressure by enhancing the volume of the intravascular fluid [83].
ACE inhibitors are used as an effective prescription for the inhibition and treatment of
hypertension-related diseases [
29
]. Commercially available ACE inhibitors are chemically synthesized
and clinically used as antihypertensive drugs [
84
]. The usage of these synthetic ACE inhibitors has

Molecules 2018,23, 2880 11 of 26
side effects such as a cough, dysgeusia and various hypersensitivity reactions. Therefore, it would
be useful to develop and use safe and comparatively low-cost ACE inhibitors of natural origin
(Figure 3). ACE inhibitors have been reported to diminish mortality in patients with hypertension [
85
].
Recently, investigators have described that Pleurotus ostreatus [
86
], P. cystidiosus [
85
], P. cornucopiae [
87
],
Auricularia auricula-judae [
88
], Ganoderma leucocontextum [
65
], Grifola frondosa [
89
], Agaricus bisporus [
30
]
and Leucopaxillus tricolor [
29
] are all ACE inhibitors that decrease hypertension. Wild mushrooms in
Nepal that also have ACE inhibitor activities were tested by Bang et al. [90].
Molecules 2018, 23, x FOR PEER REVIEW 11 of 26
natural origin (Figure 3). ACE inhibitors have been reported to diminish mortality in patients with
hypertension [85]. Recently, investigators have described that Pleurotus ostreatus [86], P. cystidiosus
[85], P. cornucopiae [87], Auricularia auricula-judae [88], Ganoderma leucocontextum [65], Grifola frondosa
[89], Agaricus bisporus [30] and Leucopaxillus tricolor [29] are all ACE inhibitors that decrease
hypertension. Wild mushrooms in Nepal that also have ACE inhibitor activities were tested by Bang
et al. [90].
Figure 3. Antihypertensive effect of mushrooms—Mushrooms are found to be Angiotensin
Converting Enzyme (ACE) inhibitors, which help to reduce hypertension by constraining ACE. This
enzyme is accountable for transforming the inactive protein Ang I into the active Ang II. The renin-
angiotensin system–angiotensin II has a multifaceted range of effects on the maintenance of blood
pressure and this impact elevates sodium and water retention through the release of aldosterone.
6.2. Actions on Dyslipidemia
Edible mushrooms are rich in dietary fiber, vitamins, proteins, microelements, and low in fat
that, making them the ultimate diet for treating atherosclerotic plaque [88]. Mushrooms prevented
weight gain in a rodent study suggesting a precious treatment for obesity and greater significance in
the prevention of hyperlipidemia and CVD [1]. Pleurotus ostreatus is an edible mushroom, which
decreases TC, TG, blood glucose and BP in diabetic individuals. These outcomes suggested that
ingestion of P. ostreatus offers greater health benefits by acting on the atherogenic lipid system [75].
Edible white button mushroom (Agaricus blazei), Kluyveromyces marxianus [91], P. ostreatus [92] and
Auricularia polytricha [93] are found to be well-known lipid-lowering agents by competitively
preventing HMG-CoA reductase activity, which plays a vital role in cholesterol biosynthesis [35]. The
results of P. ostreatus on serum TG levels could be enlightened due to increased lipoprotein lipase
activity by increasing lipase mRNA expression [75] and suppression of diacylglycerol acyl-
transferase, which catalyzes the final step in TG biosynthesis in rat liver microsomes [74]. The
mechanisms associated with cholesterol biosynthesis implicated in the hypocholesterolemic impact
Figure 3.
Antihypertensive effect of mushrooms—Mushrooms are found to be Angiotensin Converting
Enzyme (ACE) inhibitors, which help to reduce hypertension by constraining ACE. This enzyme is
accountable for transforming the inactive protein Ang I into the active Ang II. The renin-angiotensin
system–angiotensin II has a multifaceted range of effects on the maintenance of blood pressure and
this impact elevates sodium and water retention through the release of aldosterone.
6.2. Actions on Dyslipidemia
Edible mushrooms are rich in dietary fiber, vitamins, proteins, microelements, and low in fat
that, making them the ultimate diet for treating atherosclerotic plaque [
88
]. Mushrooms prevented
weight gain in a rodent study suggesting a precious treatment for obesity and greater significance
in the prevention of hyperlipidemia and CVD [
1
]. Pleurotus ostreatus is an edible mushroom, which
decreases TC, TG, blood glucose and BP in diabetic individuals. These outcomes suggested that
ingestion of P. ostreatus offers greater health benefits by acting on the atherogenic lipid system [
75
].
Edible white button mushroom (Agaricus blazei), Kluyveromyces marxianus [
91
], P. ostreatus [
92
]
and Auricularia polytricha [
93
] are found to be well-known lipid-lowering agents by competitively
preventing HMG-CoA reductase activity, which plays a vital role in cholesterol biosynthesis [
35
].
The results of P. ostreatus on serum TG levels could be enlightened due to increased lipoprotein lipase
activity by increasing lipase mRNA expression [
75
] and suppression of diacylglycerol acyl-transferase,

Molecules 2018,23, 2880 12 of 26
which catalyzes the final step in TG biosynthesis in rat liver microsomes [
74
]. The mechanisms
associated with cholesterol biosynthesis implicated in the hypocholesterolemic impact of mushrooms
are represented in Figure 4. An adequate level of PUFAs is found in edible mushrooms, which facilitates
the reduction of serum cholesterol [
91
]. As they lacking the trans-isomers of unsaturated fatty acids,
mushrooms can elevate the serum TC to HDL that reduces the cardiovascular menace [
74
]. Intake of
dietary fiber may also affect serum lipid levels, decrease TC, LDL concentrations and eventually reduce
CVD [
65
]. Mushrooms contain glucan-like viscous gels that prevent the TC and TG absorption. These
sticky consistencies are highly associated with augmentation of fecal bile acids and SCFA excretion,
which prevents acetate integration (a precursor of sterols and synthesis of fatty acids) to become serum
lipids. Auricularia auricula and Tremella fuciformis possess high fiber content, which produces a lowering
of LDL cholesterol levels and prevents CVD [
88
]. These findings might be the result of prevention
of TG synthesis by enhancing the SCFA production through the dietary fiber fermentation by gut
microbiota [72].
Molecules 2018, 23, x FOR PEER REVIEW 12 of 26
of mushrooms are represented in Figure 4. An adequate level of PUFAs is found in edible
mushrooms, which facilitates the reduction of serum cholesterol [91]. As they lacking the trans-
isomers of unsaturated fatty acids, mushrooms can elevate the serum TC to HDL that reduces the
cardiovascular menace [74]. Intake of dietary fiber may also affect serum lipid levels, decrease TC,
LDL concentrations and eventually reduce CVD [65]. Mushrooms contain glucan-like viscous gels
that prevent the TC and TG absorption. These sticky consistencies are highly associated with
augmentation of fecal bile acids and SCFA excretion, which prevents acetate integration (a precursor
of sterols and synthesis of fatty acids) to become serum lipids. Auricularia auricula and Tremella
fuciformis possess high fiber content, which produces a lowering of LDL cholesterol levels and
prevents CVD [88]. These findings might be the result of prevention of TG synthesis by enhancing
the SCFA production through the dietary fiber fermentation by gut microbiota [72].
Figure 4. Effect of edible and medicinal mushrooms on dyslipidemia.
Figure 4. Effect of edible and medicinal mushrooms on dyslipidemia.

Molecules 2018,23, 2880 13 of 26
Table 1. In vitro and in vivo actions of edible and medicinal mushrooms and their anti-obesity potential.
Edible/Medicinal
Mushroom Botanical Name Study Model/Methods Bioactive Compounds References
Edible Agaricus campestris Hypercholesterolemic diet and STZ induced rats-plasma glucose,
TG, TC, ALT, AST and LDL
Vitamin C, D, B12, folates, and
polyphenols [63]
Edible Agaricus bisporus High-fat diet in rats-serum cholesterol and hepatic LDL receptor mRNA Fibers [32]
Hypertensive rats-Angiotensin I-Converting Enzyme assay Oligopeptide [30]
Edible Agaricus brasiliensis
STZ-induced diabetic rats-plasma glucose, TG, TC, glycated hemoglobin, TBARS
Polyphenols and flavonoids [94,95]
Hypertensive rats-Angiotensin I-Converting Enzyme assay Oligopeptide [27]
Edible Boletus bicolor Hypertensive rats-Angiotensin I-Converting Enzyme assay Oligopeptide [96]
Edible Leucopaxillus tricolor Hypertensive rats-Angiotensin I-Converting Enzyme assay Oligopeptide [29]
Edible Catathelasma ventricosum STZ induced diabetic rats-plasma glucose, total TC, TG Heteropolysaccharide [97]
Edible Pleurotus geesteranus STZ induced diabetic rats-plasma glucose, total TC, TG Polysaccharides [98]
Edible Flammulina velutipes
STZ-induced diabetic rats-SOD, GSH-Px, CAT, MDA, ALT, AST, BUN,
CRE, TC, LDL-C and HDL-C Polysaccharides [99]
In vitro-DPPH free radical & Hydroxy radical scavenging, in vitro
α-glycosidase, aldose reductase inhibitory assays Polysaccharides [100]
Edible G. lucidum Hypertensive rats-ACE assay Oligopeptide [101]
Edible Gloeostereum incarnatum Hypertensive rats-ACE assay Oligopeptide [29]
Edible Grifola frondosa Hypertensive rats-ACE assay Oligopeptide [29]
Hypertensive rats-ACE assay Oligopeptide [102]
Edible Hericium erinaceus
C57BL/6J mice model-serum and hepatic TG levels Flavonoids [103]
Hyperlipidemic rats-plasma total cholesterol, LDL, HDL, cholesterol,
triglyceride, phospholipid, atherogenic index, and hepatic HMG-CoA reductase
Exo-polymer [104]
Edible Hypsizygus marmoreus Hypertensive rats-ACE assay Oligopeptide [84]
Edible Lactarius deterrimus STZ-induced diabetic rats-plasma glucose, TG, glycated hemoglobin,
glycated serum protein, and AGE, SOD, CAT, GSH levels Polyphenols and flavonoids [105]

Molecules 2018,23, 2880 14 of 26
Table 1. Cont.
Edible/Medicinal
Mushroom Botanical Name Study Model/Methods Bioactive Compounds References
Edible Lentinula edodes
High-fat diet in rats-TG, TC, LDL, cholesterol 7-α-hydroxylase 1 Lentinan KS-2 [106]
High-fat diet in rats-TG, TC, LDL, total lipids, phospholipids, LDL/HDL ratio,
BIL, CRE, Urea, BUN, Uric acid, Total protein, Na, Ca, Cl, K, albumin, P, Mg Lentinan KS-2 [107]
High-fat diet in rabbits-TC, histological, immunohistochemical and
morphometrically analysis Lentinan KS-2 [8]
High-fat diet in rats-TG, TC, ALT, AST, Urea, glucose, malondialdehyde Lentinan KS-2 [108]
Edible Lentinus lepideus High-fat diet in rats-TG, TC, LDL, total lipids, phospholipids, LDL/HDL ratio,
BIL, CRE, Urea, BUN, Uric acid, Total protein, Na, Ca, Cl, K, albumin, P, Mg Lentinan KS-2, flavonoids [109]
Edible Lenzites elegans in vitro enzymatic starch digestion assay Polyphenols and flavonoids [110]
Edible Morchella vulgaris Hypertensive rats-ACE assay Oligopeptide [29]
Edible Oudemansiella radicata Hypertensive rats-ACE assay Oligopeptide [29]
Edible Pholiota adipose Hypertensive rats-ACE assay Oligopeptide [111]
Edible Pholiota nameko SW-02
mice hyperlipidemic models-blood lipid levels (TC, TG, HDL-C, LDL-C,
and VLDL-C), liver lipid levels (TC and TG) and antioxidant status
(SOD, T-AOC, MDA, and LPO)
Mycelia zinc polysaccharide [112]
Edible Pleurotus abalonus
Diabetic mice-Inhibition of the proliferation of hepatoma HepG2 cells
and breast cancer MCF7 cells, antioxidant activity in erythrocyte hemolysis,
blood glucose and TG
Polysaccharide-peptide
complex LB-1b [113]
Edible Pleurotus cornucopiae Hypertensive rats-Angiotensin I-Converting Enzyme assay Oligopeptide [87]
Edible Pleurotus cystidiosus O.K. Miller Hypertensive rats-Angiotensin I-Converting Enzyme assay Oligopeptide [85]
Edible Pleurotus djamor STZ-induced diabetic rats-SOD, GSH-Px, CAT, MDA, ALT, AST, BUN,
CRE, TC, LDL-C and HDL-C Mycelium zinc polysaccharides [114]
Edible Pleurotus eryngii High-fat diet in rats-TG, TC, LDL, total lipids, phospholipids, LDL/HDL ratio,
BIL, CRE, Urea, BUN, Uric acid, Total protein, Na, Ca, Cl, K, albumin, P, Mg Polysaccharides [115]
Edible Pleurotus ferulae High-fat diet in rats-TG, TC, LDL, total lipids, phospholipids, LDL/HDL ratio,
BIL, CRE, Urea, BUN, Uric acid, Total protein, Na, Ca, Cl, K, albumin, P, Mg Polysaccharides [116]
Edible Pleurotus ostreatus High-fat diet in rats-TG, TC, LDL, total lipids, phospholipids, LDL/HDL ratio,
BIL, CRE, Urea, BUN, Uric acid, Total protein, Na, Ca, Cl, K, albumin, P, Mg Polysaccharides [86]

Molecules 2018,23, 2880 15 of 26
Table 1. Cont.
Edible/Medicinal
Mushroom Botanical Name Study Model/Methods Bioactive Compounds References
Edible Pleurotus pulmonarius Hypertensive rats-Angiotensin I-Converting Enzyme assay Oligopeptide [117]
Edible Pleurotus salmoneostramineus L. Vass High-fat diet in rats-TG, TC, LDL, total lipids, phospholipids, LDL/HDL ratio,
BIL, CRE, Urea, BUN, Uric acid, Total protein, Na, Ca, Cl, K, albumin, P, Mg Polysaccharides [118]
Edible Pleurotus tuber-regium Ob diabetic rats-TC, TG, LDL, HDL, and PPAR-αmRNA expression Polysaccharides [72]
Edible Ramaria botrytoides Hypertensive rats-ACE assay Oligopeptide [29]
Edible Russula aeruginea Hypertensive rats-ACE assay Oligopeptide [29]
Edible Tremella fuciformis in vitro α-glycosidase, aldose reductase inhibitory assays,
DPPH free radical scavenging Polyphenols and flavonoids [119]
Edible Tricholoma giganteum Hypertensive rats-ACE assay Oligopeptide [120]
Edible Tricholoma matsutake Hypertensive rats-ACE assay Oligopeptide [96]
Edible Tuber micheli Hypertensive rats-ACE assay Oligopeptide [29]
Edible Pleurotus ostreatus
TC content in serum, lipoproteins in the liver,
and HMG-CoA reductase in liver microsomes Polysaccharides [121]
Inhibition of HMG CoA reductase-lovastatin Polysaccharides [92]
Edible Adiantum capillus-veneris L. High cholesterol diet fed Wistar rats-Pancreatic triacylglycerol lipase and
α-amylase/α-glucosidase, OGTT, TC, TG Polyphenols [9]
Edible Aster spathulifolius Maxim
High-fat diet fed Wistar rats-body weight gain, visceral fat pad weights, serum
lipid levels, as well as hepatic lipid levels, numbers of lipid droplets, expression
of fat intake-related gene ACC2 and lipogenesis-related genes (e.g., SREBP-1c,
ACC1, FAS, SCD1, GPATR, AGPAT, and DGAT), fatty acid oxidation and
thermogenesis-related genes (e.g., PPAR-α, ACO, CPT1, UCP2, and UCP3),
phosphorylated AMPKα, phosphorylated ACC
Polysaccharides [3]
Edible Kluyveromyces marxianus The high-fat diet fed Wistar rats-TC, TG, HDL-C, LDL-C,
levels in the serum and liver, atherogenic index Polysaccharides [91]
Edible and
Medicinal
Collybia peronata,Ganoderma australe,
Ganoderma lingzhi,Heterobasidion
linzhiense,Heterobasidion linzhiense,
Inocybe sp., Inonotus andersonii,
Lactarius hatsudake, Lenzites betulina,
Panellus sp., Phellinus conchatus,
Phellinus gilvus,Phlebia tremellosa,
Postia stiptica, Rigidoporus sp., Trametes
versicolor,Tricholoma caligatum
ACE Inhibitory Assay Polyphenol [90]

Molecules 2018,23, 2880 16 of 26
Table 1. Cont.
Edible/Medicinal
Mushroom Botanical Name Study Model/Methods Bioactive Compounds References
Medicinal Armillariella mellea STZ-induced diabetic rats-plasma glucose, TG, TC, ALT, AST exo-biopolymers [122]
Medicinal Auricularia auricula-judae High-fat diet in mice-phospholipids, liver enzymes, TG, glycerol,
glycerol-3-phosphate dehydrogenase Phenolic compound [88]
Medicinal Collybia confluens STZ induced animal model-plasma glucose, total TC, TG, ALT, AST Exo-polymer [123]
Medicinal Cordyceps militaris
In vitro-Superoxide anion, DPPH free radical & Hydroxy radical scavenging,
In vitro-HMG-CoA reductase and α-glucosidase Polysaccharides [124]
mice hyperlipidemic models-blood lipid levels (TC, TG, HDL-C, LDL-C,
and VLDL-C), liver lipid levels (TC and TG) and antioxidant status
(SOD, T-AOC, MDA, and LPO)
Polysaccharides [73]
Medicinal Cordyceps sinensis STZ-induced diabetic rats-plasma glucose, TG, TC, ALT, AST exo-biopolymers [122]
Medicinal Coriolus versicolor STZ-induced diabetic rats-plasma glucose, TG, TC, ALT, AST exo-biopolymers [122]
Medicinal Flammulina velutipes
High-fat diet in rats-TC, LDL, body weight, food intake, liver weight, cecum
weight, cecum pH, Cecal acetic acid, butyric acid, and total SCFA Fibers [89]
High-fat diet in male hamsters-TG, TC, LDL, total lipids, phospholipids,
LDL/HDL ratio
Dietary fiber, polysaccharide,
and mycosterol, [125]
Medicinal Fomes fomentarius STZ-induced diabetic rats-plasma glucose, TG, TC, ALT, AST Exo-biopolymers [89]
Medicinal Ganoderma leucocontextum In vitro-HMG-CoA reductase and α-glucosidase Lanostane (Triterpenes) [65]
Medicinal Ganoderma lucidum
STZ-induced diabetic rats-plasma glucose, TC, TG, glycated hemoglobin, TBARS
Polysaccharides [94,95]
STZ-induced diabetic rats-plasma glucose, TG, TC, NO, SOD, CAT, GPx Polysaccharides [126–128]
in vitro α-glycosidase, aldose reductase inhibitory assays,
DPPH free radical scavenging Polyphenols and flavonoids [119]
Medicinal Ganoderma philippii in vitro enzymatic starch digestion assay Appanoxidic acid A [110]
Medicinal Grifola frondosa High-fat diet in rats-TC, LDL, body weight, food intake, liver weight, cecum
weight, cecum pH, Cecal acetic acid, butyric acid, and total short-chain fatty acid
Fiber [89]
Medicinal Lentinus edodes
STZ induced animal model-plasma glucose, total cholesterol, and triglyceride Exo-polymer [129]
High-fat diet in rats-TC, LDL, body weight, food intake, liver weight, cecum
weight, cecum pH, Cecal acetic acid, butyric acid, and total short-chain fatty acid
Fibers [89]
Medicinal Paecilomyces japonica STZ-induced diabetic rats-plasma glucose, TG, TC, ALT, AST exo-biopolymers [122]

Molecules 2018,23, 2880 17 of 26
Table 1. Cont.
Edible/Medicinal
Mushroom Botanical Name Study Model/Methods Bioactive Compounds References
Medicinal Phellinus baumii STZ induced diabetic rats-plasma glucose, TG, TC, ALT, AST Heteropolysaccharides and
two proteoglycans [130]
Medicinal Phellinus rimosus
Alloxan-induced diabetic rats-plasma glucose,
OGTT, TC, TG, SOD, CAT, GPx, and GSH Polysaccharides [131]
STZ-induced diabetic rats-plasma glucose, lipid profile, ALT, AST,
serum insulin, liver glycogen Polysaccharides [132]
Medicinal Rigidoporus ulmarius in vitro enzymatic starch digestion assay Polysaccharides [110]
Medicinal Tremella fuciformis
ob/ob mice-Plasma glucose, OGTT, TG Exopolysaccarides [133]
In vitro-ABTS radical scavenging activity, DPPH radical scavenging activity,
LDL oxidation; NO synthase expression in RAW 264.7 cells Polyphenols and flavonoids [134]
Medicinal Ganoderma applanatum and Collybia
confluens STZ-induced diabetic rats-Plasma glucose, TC, TG Exo-polymer [135]
Medicinal Auricularia polytricha Serum total lipids and TC Polysaccharides [93]
Medicinal Pleurotus sajor-caju (Fr.) Singer
C57BL/6J mice fed on a high-fat diet-body weight, serum lipid, and liver
enzymes, protein carbonyl and lipid hydroperoxide levels, enzymic antioxidants
(SOD, CAT, and GPx) activities, Expression of hormone-sensitive lipase,
adipose triglyceride lipase, peroxisome proliferator-activated receptor gamma,
sterol regulatory binding protein-1c, and lipoprotein lipase
β-glucan [1]
Abbreviations: 17
β
-HSD: 17
β
-hydroxysteroid dehydrogenase; ACC1: acetyl-CoA carboxylase 1; ACE: angiotensin converting enzyme; ACO: 1-aminocyclopropane-1-carboxylate
oxidase; AGE: advanced glycation end products; AGPAT: 1-acylglycerol-3-phosphate O-acyltransferase 1; AgRP: agouti-related peptide; ALT: alanine transaminase; AMPK: 5
0
adenosine
monophosphate-activated protein kinase; Ang-I: angiotensin I; Ang-II: angiotensin II; AST: aspartate transaminase; AT-1: angiotensin II type 1 receptor; BMI: body mass index; BMR:
basal metabolic rate; BUN: blood urea nitrogen; Ca: calcium; CAT: catalase; Cl: chloride; CNS: central nervous system; CPT1: carnitine Palmitoyltransferase 1A; CRE: creatinine; CRP:
c-reactive protein; CVD: cardiovascular diseases; DGAT: diacylglycerol O-Acyltransferase 1; DPPH: 2,2-diphenyl-1-picrylhydrazyl; E1: estrone; E2: estradiol; FFA: free fatty acids; GPATR:
glycerol-3-phosphate acyltransferase; GSH: glutathione; GSH-Px: glutathione peroxidase; HDL: high density lipoprotein; HFD: high fat diet; HMG-CoA:
β
-hydroxy,
β
methyl glutaryl
COA; ICAM: Intercellular Adhesion Molecule; IGF1: IGF binding protein 1; IL-1: interleukin 1; IL-6: interleukin 6; K: potassium; LDL: low density lipoprotein; LPO: lipid peroxidation;
MAPK: mitogen-activated protein kinases; MCH: melanin concentrating hormone; MDA: melondialdehyde; Mg: magnesium; mRNA: messenger ribonucleic acids; Na: sodium; NF-χB:
nuclear factor kappa B; NO: nitric oxide; NPY: neuropeptide Y; OGTT: oral glucose tolerance test; P: phosphorus; POMC: pro-opiomelanocortin; PPAR-
α
: peroxisome proliferator-activated
receptor alpha; PUFA: poly unsaturated fatty acids; RAS: renin-angiotensin-aldosterone system; ROS: reactive oxygen species; SCD1: stearoyl-CoA desaturase 1; SCFA: short chain fatty
acids; SCFA: short chain fatty acids; SOD: superoxide dismutase; SREBP-1c: sterol regulatory element-binding transcription factor 1; STZ: streptozotocin; T-AOC: total antioxidant capacity;
TBARS: thiobarbituric acid reactive substances; TC: total cholesterol; TG: triglycerides; TNF-
α
: tumour necrosis factor-
α
; UCP2: mitochondrial uncoupling proteins 2; UCP3: mitochondrial
uncoupling proteins 3; VCAM: vascular cell adhesion molecule; VLDL: very low density lipoprotein; ∆4A: ∆4-androstenedione.

Molecules 2018,23, 2880 18 of 26
7. Conclusions and Future Perspectives
Obesity is a dreaded disease that affects a great proportion of the global population and
contributes to extensive morbidity and death. Weight management is a lifelong progression as
enduring weight decline is very hard to attain. The main cause of obesity is a disproportion
between calorie intake and energy outlay resulting from multifaceted relations between hereditary
and environmental influences. Effective weight control programs are urgently required to stabilize
calorie intake with energy expenditure. Diet and physical activity can usually regulate weight control.
Mushrooms are highly nutritive species containing enormous amounts of bioactive compounds
(polysaccharides, fibers, terpenes, polyphenols, sterols, flavonoids, and alkaloids) that are potentially
antioxidant-rich constituents with effects on numerous cardiac biomarkers to treat obesity-related
cardiovascular system illnesses. Various animal studies have demonstrated that regular consumption
of mushrooms significantly reduces hypertension, atherosclerosis, dyslipidemia, inflammation, and
obesity. Nevertheless, this practice ought to be combined with regular physical exercise, as well as
dietary and lifestyle alterations. The practice of regular consumption of mushroom might however
result in synergistic and improved effects.
Author Contributions:
K.G. and B.X. conceived and designed the manuscript. K.G. wrote the review; B.X.
critically revised and improved the manuscript.
Funding:
The work was jointly supported by a grant UIC201714 from Beijing Normal University-Hong
Kong Baptist University United International College and one research grant from Zhuhai Higher Education
Construction Project (Zhuhai Key Laboratory of Agricultural Product Quality and Food Safety).
Conflicts of Interest: The authors declare no conflict of interest.
Abbreviations
17β-HSD 17β-hydroxysteroid dehydrogenase
ACC1 acetyl-CoA carboxylase 1
ACE angiotensin converting enzyme
ACO 1-aminocyclopropane-1-carboxylate oxidase
AGE advanced glycation end products
AGPAT 1-acylglycerol-3-phosphate O-acyltransferase 1
AgRP agouti-related peptide
ALT alanine transaminase
AMPK 50adenosine monophosphate-activated protein kinase
Ang-I angiotensin I
Ang-II angiotensin II
AST aspartate transaminase
AT-1 angiotensin II type 1 receptor
BMI body mass index
BMR basal metabolic rate
BUN blood urea nitrogen
Ca calcium
CAT catalase
Cl chloride
CNS central nervous system
CPT1 carnitine Palmitoyltransferase 1A
CRE creatinine
CRP c-reactive protein
CVD cardiovascular diseases
DGAT diacylglycerol O-Acyltransferase 1
DPPH 2,2-diphenyl-1-picrylhydrazyl

Molecules 2018,23, 2880 19 of 26
E1 estrone
E2 estradiol
FFA free fatty acids
GPATR glycerol-3-phosphate acyltransferase
GSH glutathione
GSH-Px glutathione peroxidase
HDL high density lipoprotein
HFD high fat diet
HMG-CoA β-hydroxy, βmethyl glutaryl COA
ICAM Intercellular Adhesion Molecule
IGF1 IGF binding protein 1
IL-1 interleukin 1
IL-6 interleukin 6
K potassium
LDL low density lipoprotein
LPO lipid peroxidation
MAPK mitogen-activated protein kinases
MCH melanin concentrating hormone
MDA melondialdehyde
Mg magnesium
mRNA messenger ribonucleic acids
Na sodium
NF-χB nuclear factor kappa B
NO nitric oxide
NPY neuropeptide Y
OGTT oral glucose tolerance test
P phosphorus
POMC pro-opiomelanocortin
PPAR-αperoxisome proliferator-activated receptor alpha
PUFA poly unsaturated fatty acids
RAS renin-angiotensin-aldosterone system
ROS reactive oxygen species
SCD1 stearoyl-CoA desaturase 1
SCFA short chain fatty acids
SCFA short chain fatty acids
SOD superoxide dismutase
SREBP-1c sterol regulatory element-binding transcription factor 1
STZ streptozotocin
T-AOC total antioxidant capacity
TBARS thiobarbituric acid reactive substances
TC total cholesterol
TG triglycerides
TNF-αtumour necrosis factor-α
UCP2 mitochondrial uncoupling proteins 2
UCP3 mitochondrial uncoupling proteins 3
VCAM vascular cell adhesion molecule
VLDL very low density lipoprotein
WHO world health organization
WLS weight loss surgery
∆4A ∆4-androstenedione

Molecules 2018,23, 2880 20 of 26
References
1.
Kanagasabapathy, G.; Malek, S.N.A.; Mahmood, A.A.; Chua, K.H.; Vikineswary, S.; Kuppusamy, U.R.
Beta-glucan-rich extract from Pleurotus sajor-caju (Fr.) Singer prevents obesity and oxidative stress in
C57BL/6J Mice fed on a high-fat diet. Evid. Based Complement. Altern. Med.
2013
,2013, 185259. [CrossRef]
[PubMed]
2.
Kim, J.Y.; Tfayli, H.; Michaliszyn, S.F.; Arslanian, S. Impaired lipolysis diminished fat oxidation and metabolic
inflexibility in obese girls with polycystic ovary syndrome. J. Clin. Endocrinol. MeTable.
2018
,103, 546–554.
[CrossRef] [PubMed]
3.
Kim, S.J.; Bang, C.Y.; Guo, Y.R.; Choung, S.Y. Anti-obesity effects of Aster spathulifolius extract in
high-fat-diet-induced obese rats. J. Med. Food 2016,19, 353–364. [CrossRef] [PubMed]
4.
Kennett, G.A.; Clifton, P.G. New approaches to the pharmacological treatment of obesity: Can they break
through the efficacy barrier? Pharmacol. Biochem. Behav. 2010,97, 63–83. [CrossRef] [PubMed]
5.
Bardou, M.; Barkun, A.N.; Martel, M. Obesity and colorectal cancer. Gut
2013
,62, 933–947. [CrossRef]
[PubMed]
6.
Kuwabara, W.M.T.; Panveloski-Costa, A.C.; Yokota, C.N.F.; Pereira, J.N.B.; Filho, J.M.; Torres, R.P.;
Hirabara, S.M.; Curi, R.; Alba-Loureiro, T.C. Comparison of Goto-Kakizaki rats and high fat diet-induced
obese rats: Are they reliable models to study Type 2 Diabetes mellitus? PLoS ONE
2017
,12, e0189622.
[CrossRef] [PubMed]
7.
Gooda Sahib Jambocus, N.; Saari, N.; Ismail, A.; Khatib, A.; Mahomoodally, M.F.; Abdul Hamid, A.
An investigation into the antiobesity effects of Morinda citrifolia L. leaf extract in high-fat diet-induced obese rats
using a (1)H NMR metabolomics approach. J. Diabetes Res. 2016,2016, 2391592. [PubMed]
8.
Yamada, T.; Oinuma, T.; Niihashi, M.; Mitsumata, M.; Fujioka, T.; Hasegawa, K.; Nagaoka, H.; Itakura, H.
Effects of Lentinus edodes mycelia on dietary-induced atherosclerotic involvement in rabbit aorta. J. Atheroscler.
Thromb. 2002,9, 149–156. [CrossRef] [PubMed]
9.
Kasabri, V.; Al-Hallaq, E.K.; Bustanji, Y.K.; Abdul-Razzak, K.K.; Abaza, I.F.; Afifi, F.U. Antiobesity and
antihyperglycaemic effects of Adiantum capillus-veneris extracts:
In vitro
and
in vivo
evaluations. Pharm. Biol.
2017,55, 164–172. [CrossRef] [PubMed]
10.
World Health Organization. Obesity and Overweight. Fact Sheet. Updated in June 2016. Available online:
http://www.who.int/mediacentre/factsheets/fs311/en/ (accessed on 28 June 2016).
11.
Rodríguez-Rodero, S.; Menéndez-Torre, E.; Fernández-Bayón, G.; Morales-Sánchez, P.; Sanz, L.; Turienzo, E.;
González, J.J.; Martinez-Faedo, C.; Suarez-Gutiérrez, L.; Ares, J.; et al. Altered intragenic DNA methylation
of HOOK2 gene in adipose tissue from individuals with obesity and type 2 diabetes. PLoS ONE
2017
,
12, e0189153. [CrossRef] [PubMed]
12.
Flegal, K.M.; Carroll, M.D.; Ogden, C.L.; Curtin, L.R. Prevalence and trends in obesity among United States
adults, 1999–2008. J. Am. Med. Assoc. 2010,303, 235–241. [CrossRef] [PubMed]
13.
Gooding, H.C.; Ning, H.; Gillman, M.W.; Shay, C.; Allen, N.; Goff, D.C., Jr.; Lloyd-Jones, D.; Chiuve, S.
Application of a lifestyle-based tool to estimate premature cardiovascular disease events in young adults: The
coronary artery risk development in young adults (CARDIA) Study. JAMA Int. Med.
2017
,177, 1354–1360.
[CrossRef] [PubMed]
14.
Elffers, T.W.; de Mutsert, R.; Lamb, H.J.; de Roos, A.; Willems van Dijk, K.; Rosendaal, F.R.; Jukema, J.W.;
Trompet, S. Body fat distribution, in particular, visceral fat, is associated with cardiometabolic risk factors in
obese women. PLoS ONE 2017,12, e0185403. [CrossRef] [PubMed]
15.
Reales, G.; Rovaris, D.L.; Jacovas, V.C.; Hünemeier, T.; Sandoval, J.R.; Salazar-Granara, A.; Demarchi, D.A.;
Tarazona-Santos, E.; Felkl, A.B.; Serafini, M.A.; et al. A tale of agriculturalists and hunter-gatherers: Exploring
the thrifty genotype hypothesis in native South Americans. Am. J. Physiol. Anthropol.
2017
,163, 591–601.
[CrossRef] [PubMed]
16.
Provencher, M.D.; Bélanger, M.È.; Shriqui, C.; Lachance, I.; Bonneville, S. Psychoeducation for overweight
patients with psychiatric disorders: The Wellness program developed in Quebec. Encephale
2016
,42, 201–207.
[CrossRef] [PubMed]
17.
Vandyk, A.D.; Baker, C. Qualitative descriptive study exploring schizophrenia and the everyday effect of
medication-induced weight gain. Int. J. Ment. Health Nurs. 2012,21, 349–357. [CrossRef] [PubMed]

Molecules 2018,23, 2880 21 of 26
18.
Charlotte, M.; Schwartz, E.; Slade, E.; Medoff, D.; Li, L.; Dixon, L.; Kilbourne, A.M.; Kreyenbuhl, J. Gender
differences in mood stabilizer medications prescribed to Veterans with serious mental illness. J. Affect. Disord.
2015,188, 112–117. [CrossRef] [PubMed]
19.
Nihalani, N.; Schwartz, T.L.; Siddiqui, U.A.; Megna, J.L. Weight gain, obesity, and psychotropic prescribing.
J. Obes. 2011,2011, 893629. [CrossRef] [PubMed]
20.
Wierucka-Rybak, M.; Bojanowska, E. Bacteria, viruses, and hypothalamic inflammation: Potential new
players in obesity. Postepy Hig. Med. Dosw. 2014,68, 271–279. [CrossRef]
21.
Karlsson, E.A.; Beck, M.A. The burden of obesity on infectious disease. Exp. Biol. Med.
2010
,235, 1412–1424.
[CrossRef] [PubMed]
22.
Kirchner, H.; Heppner, K.M.; Holland, J.; Kabra, D.; Tschöp, M.H.; Pfluger, P.T. Ablation of ghrelin
O-acyltransferase does not improve glucose intolerance or body adiposity in mice on a leptin-deficient
ob/ob background. PLoS ONE 2013,8, e61822. [CrossRef] [PubMed]
23.
Palou, M.; Sanchez, J.; Rodriguez, A.M.; Priego, T.; Pico, C. Induction of NPY/AgRP orexigenic peptide
expression in rat hypothalamus is an early event in fasting: Relationship with circulating leptin, insulin, and
glucose. Cell Physiol. Biochem. 2009,23, 115–124. [CrossRef] [PubMed]
24.
Yamamoto, J.; Imai, J.; Izumi, T.; Takahashi, H.; Kawana, Y.; Takahashi, K.; Kodama, S.; Kaneko, K.;
Gao, J.; Uno, K.; et al. Neuronal signals regulate obesity-induced
β
-cell proliferation by FoxM1 dependent
mechanism. Nat. Commun. 2017,8, 1930. [CrossRef] [PubMed]
25.
Das Graças Coelho de Souza, M.; Kraemer-Aguiar, L.G.; Bouskela, E. Inflammation-induced microvascular
dysfunction in obesity—A translational approach. Clin. Hemorheol. Microcirc.
2016
,64, 645–654. [CrossRef]
[PubMed]
26.
Ganesan, K.; Sukalingam, K.; Xu, B. Impact of consumption and cooking manners of vegetable oils on
cardiovascular diseases—A critical review. Trends Food Sci. Technol. 2018,71, 132–154. [CrossRef]
27.
Tsubone, H.; Makimura, Y.; Hanafusa, M.; Yamamoto, Y.; Tsuru, Y.; Motoi, M.; Amano, S. Agaricus brasiliensis
KA21 improves circulatory functions in spontaneously hypertensive rats. J. Med. Food
2014
,17, 295–301.
[CrossRef] [PubMed]
28.
Sukalingam, K.; Ganesan, K. Rhesus blood groups associated with risk to obesity and diabetes mellitus:
A report on Punjabi population in Selangor, Malaysia. Int. J. Integr. Med. Sci. 2015,2, 105–109.
29.
Geng, X.; Tian, G.; Zhang, W.; Zhao, Y.; Zhao, L.; Ryu, M.; Wang, H.; Ng, T.B. Isolation of an Angiotensin
I-Converting Enzyme inhibitory protein with antihypertensive effect in spontaneously hypertensive rats
from the edible wild mushroom Leucopaxillus tricolor.Molecules
2015
,20, 10141–10153. [CrossRef] [PubMed]
30.
Lau, C.C.; Abdullah, N.; Shuib, A.S.; Aminudin, N. Novel angiotensin I-converting enzyme inhibitory
peptides derived from edible mushroom Agaricus bisporus (J.E. Lange) Imbach identified by LC-MS/MS.
Food Chem. 2014,148, 396–401. [CrossRef] [PubMed]
31. Sowers, J.R. Diabetes mellitus and vascular disease. Hypertension 2013,61, 943–947. [CrossRef] [PubMed]
32.
Fukushima, M.; Nakano, M.; Morii, Y.; Ohashi, T.; Fujiwara, Y.; Sonoyama, K. Hepatic LDL receptor mRNA
in rats is increased by dietary mushroom (Agaricus bisporus) fiber and sugar beet fiber. J. Nutr.
2000
,
130, 2151–2156. [CrossRef] [PubMed]
33.
Kurukulasuriya, L.R.; Stas, S.; Lastra, G.; Manrique, C.; Sowers, J.R. Hypertension in obesity. Med. Clin.
N. Am. 2011,95, 903–917. [CrossRef] [PubMed]
34.
Ece, I.; Yilmaz, H.; Alptekin, H.; Yormaz, S.; Colak, B.; Yilmaz, F.; Sahin, M. Comparative effectiveness of
laparoscopic sleeve gastrectomy on morbidly obese, super-obese, and super-super obese patients for the
treatment of morbid obesity. Obes. Surg. 2017,28, 1484–1491. [CrossRef] [PubMed]
35.
Jeong, S.C.; Jeong, Y.T.; Yang, B.K.; Islam, R.; Koyyalamudi, S.R.; Pang, G.; Cho, K.Y.; Song, C.H.
White button mushroom (Agaricus bisporus) lowers blood glucose and cholesterol levels in diabetic and
hypercholesterolemic rats. Nutr. Res. 2010,30, 49–56. [CrossRef] [PubMed]
36.
Ganesan, K.; Gani, S.B. Attenuation of curcumin on isoproterenol-induced alterations in cardiac marker
enzymes in Wistar albino rats. Int. J. Appl. Biosci. 2014,2, 78–83.
37.
Rizvi, A.A. Addressing hypertension in the patient with type 2 diabetes mellitus: Pathogenesis, goals, and
therapeutic approach. Eur. Med. J. Diabetes 2017,5, 84–92. [PubMed]
38.
Ganesan, K.; Gani, S.B. Relationship between ABO, Rh Blood Groups, and Diabetes Mellitus, obesity in
Namakkal town, Tamilnadu. Int. J. Adv. Pharm. Biol. Chem. 2014,3, 995–998.

Molecules 2018,23, 2880 22 of 26
39. De Pergola, G.; Silvestris, F. Obesity as a major risk factor for cancer. J. Obes. 2013,2013, 291546. [CrossRef]
[PubMed]
40.
Allott, E.H.; Masko, E.M.; Freedland, S.J. Obesity and prostate cancer: Weighing the evidence. Eur. Urol.
2013,63, 800–809. [CrossRef] [PubMed]
41.
Ganesan, K.; Sukalingam, K.; Xu, B. Impact of consumption of repeatedly heated cooking oils on the
incidence of various cancers—A critical review. Crit. Rev. Food Sci. Nutr.
2017
,58, 1–18. [CrossRef] [PubMed]
42.
Ganesan, K.; Xu, B. Molecular targets of vitexin and isovitexin in cancer therapy: A critical review. Ann. N. Y.
Acad. Sci. 2017,1401, 102–113. [CrossRef] [PubMed]
43.
Bao, B.; Wang, Z.; Li, Y.; Kong, D.; Ali, S. The complexities of obesity and diabetes with the development and
progression of pancreatic cancer. Biochim. Biophys. Acta 2011,1815, 135–146. [CrossRef] [PubMed]
44.
Xu, Q.; Anderson, D.; Lurie-Beck, J. The relationship between abdominal obesity and depression in the
general population: A systematic review and meta-analysis. Obes. Res. Clin. Pract.
2011
,5, e267–e278.
[CrossRef] [PubMed]
45.
Hagan, K.A.; Munger, K.L.; Ascherio, A.; Grodstein, F. Epidemiology of Major Neurodegenerative Diseases
in Women: Contribution of the Nurses’ Health Study. Am. J. Public Health
2016
,26, 1650–1655. [CrossRef]
[PubMed]
46.
Brewer, C.J.; Balen, A.H. The adverse effects of obesity on conception and implantation. Reproduction
2010
,
140, 347–364. [CrossRef] [PubMed]
47.
Tchernof, A.; Després, J.-P. Pathophysiology of Human Visceral Obesity: An Update. Physiol. Rev.
2013
,
93, 359–404. [CrossRef] [PubMed]
48. Kelly, D.M.; Jones, T.H. Testosterone and obesity. Obes. Rev. 2015,16, 581–606. [CrossRef] [PubMed]
49.
Zhang, L.D.; Li, H.C.; Gao, M.; Wang, L.; Deng, Q.; Shi, T.; He, J.L.; Chong, T.; Wang, Z.M. Sexual development
characteristics and sex hormone levels in obese male adolescents. Zhonghua Nan Ke Xue
2013
,19, 434–438.
[PubMed]
50.
Steenackers, N.; Gesquiere, I.; Matthys, C. The relevance of dietary protein after bariatric surgery: What do
we know? Curr. Opin. Clin. Nutr. Metab. Care 2018,21, 58–63. [CrossRef] [PubMed]
51.
Frith, E.; Loprinzi, P.D. The protective effects of a novel fitness-fatness index on all-cause mortality among
adults with cardiovascular disease. Clin. Cardiol. 2017,40, 469–473. [CrossRef] [PubMed]
52.
Gontarev, S.; Kalac, R.; Zivkovic, V.; Velickovska, L.A.; Telai, B. The association between high blood pressure,
physical fitness and fatness in adolescents. Nutr. Hosp. 2017,34, 35–40. [CrossRef] [PubMed]
53.
Kissane, N.A.; Pratt, J.S.A. Medical and surgical treatment of obesity. Best Pract. Res. Clin. Anaesthesiol.
2011
,
25, 11–25. [CrossRef] [PubMed]
54.
Bessesen, D.H.; Van Gaal, L.F. Progress and challenges in anti-obesity pharmacotherapy. Lancet Diabetes Endocrinol.
2018,6, 237–248. [CrossRef]
55.
Banu, G.S.; Kumar, G.; Pandian, M.R. Cholesterol lowering activity of the aqueous fruit extract of Trichosanthes
dioica Roxb. in normal and streptozotocin diabetic rats. J. Clin. Diagn. Res. 2007,1, 561–569.
56.
Kumar, G.; Murugesan, A.G. Hypolipidaemic activity of Helicteres isora L. bark extracts in streptozotocin
induced diabetic rats. J. Ethnopharmacol. 2008,116, 161–166. [CrossRef] [PubMed]
57.
Ganesan, K.; Ramasamy, M.; Gani, S.B. Antihyperlipideamic effect of Solanum trilobatum L. leaves extract on
streptozotocin induced diabetic rats. Asian J. Biomed. Pharm. Sci. 2013,3, 51–56.
58.
Kumar, G.; Banu, G.S.; Murugesan, A.G. Attenuation of Helicteres isora L. bark extracts on
streptozotocin-induced alterations in glycogen and carbohydrate metabolism in albino rats. Hum. Exp. Toxicol.
2009,28, 689–696. [CrossRef] [PubMed]
59.
Kumar, G.; Banu, G.S.; Murugesan, A.G. Effect of Helicteres isora bark extracts on heart antioxidant status
and lipid peroxidation in streptozotocin diabetic rats. J. Appl. Biomed. 2008,6, 89–95.
60.
Jayachandran, M.; Zhang, T.; Ganesan, K.; Xu, B.; Chung, S.S.M. Isoquercetin ameliorates hyperglycemia
and regulates key enzymes of glucose metabolism via insulin signaling pathway in streptozotocin-induced
diabetic rats. Eur. J. Pharmacol. 2018,829, 112–120. [CrossRef] [PubMed]
61.
Friedman, M. Mushroom polysaccharides: Chemistry and antiobesity, antidiabetes, anticancer, and antibiotic
properties in cells, rodents, and humans. Foods 2016,5, 80. [CrossRef] [PubMed]
62.
Chang, S.T.; Wasser, S.P. The Role of Culinary-Medicinal Mushrooms on Human Welfare with a Pyramid
Model for Human Heath. Int. J. Med. Mushrooms 2012,14, 95–134. [CrossRef] [PubMed]

Molecules 2018,23, 2880 23 of 26
63.
Jeong, H.J.; Yoon, S.J.; Pyun, Y.R. Polysaccharides from edible mushroom Hinmogi (Tremella fuciformis)
inhibit differentiation of 3T3-L1 adipocytes by reducing mRNA expression of PPAR
γ
, C/EBP
α
, and leptin.
Food Sci. Biotechnol. 2008,17, 267–273.
64.
Nyam, K.L.; Chow, C.F.; Tan, C.S.; Ng, S.T. Antidiabetic Properties of the Tiger’s milk medicinal mushroom,
Lignosus rhinocerotis (Agaricomycetes), in streptozotocin-induced diabetic rats. Int. J. Med. Mushrooms
2017
,
19, 607–617. [CrossRef] [PubMed]
65.
Wang, K.; Bao, L.; Xiong, W.; Ma, K.; Han, J.; Wang, W.; Yin, W.; Liu, H. Lanostane triterpenes from the tibetan
medicinal mushroom Ganoderma leucocontextum and their inhibitory effects on HMG-CoA reductase and
α-glucosidase. J. Nat. Prod. 2015,78, 1977–1989. [CrossRef] [PubMed]
66.
Zhang, J.J.; Li, Y.; Zhou, T.; Xu, D.P.; Zhang, P.; Li, S.; Li, H.B. Bioactivities and health benefits of mushrooms
mainly from China. Molecules 2016,21, 938. [CrossRef] [PubMed]
67.
Ng, T.B.; Cheung, R.C.; Wong, J.H.; Chan, Y.S.; Dan, X.; Pan, W.; Wang, H.; Guan, S.; Chan, K.; Ye, X.; et al.
Fungal proteinaceous compounds with multiple biological activities. Appl. Microbiol. Biotechnol.
2016
,
100, 6601–6617. [CrossRef] [PubMed]
68.
Delzenne, N.M.; Bindels, L.B. Gut microbiota: Ganoderma lucidum, a new prebiotic agent to treat obesity?
Nat. Rev. Gastroenterol. Hepatol. 2015,12, 553–554. [CrossRef] [PubMed]
69.
Chang, C.J.; Lin, C.S.; Lu, C.C.; Martel, J.; Ko, Y.F.; Ojcius, D.M.; Tseng, S.F.; Wu, T.R.; Chen, Y.Y.; Young, J.D.;
et al. Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota.
Nat. Commun. 2015,6, 7489. [CrossRef] [PubMed]
70.
Murphy, E.A.; Velazquez, K.T.; Herbert, K.M. Influence of high-fat diet on gut microbiota: A driving force
for chronic disease risk. Curr. Opin. Clin. Nutr. Metab. Care 2015,18, 515–520. [CrossRef] [PubMed]
71.
Holmes, D. Obesity: Medicinal mushroom reduces obesity by modulating microbiota. Nat. Rev. Endocrinol.
2015,11, 504. [CrossRef] [PubMed]
72.
Huang, H.Y.; Korivi, M.; Yang, H.T.; Huang, C.C.; Chaing, Y.Y.; Tsai, Y.C. Effect of Pleurotus tuber-regium
polysaccharides supplementation on the progression of diabetes complications in obese-diabetic rats.
Chin. J. Physiol. 2014,57, 198–208. [CrossRef] [PubMed]
73.
Wang, L.; Xu, N.; Zhang, J.; Zhao, H.; Lin, L.; Jia, S.; Jia, L. Antihyperlipidemic and hepatoprotective activities
of residue polysaccharide from Cordyceps militaris SU-12. Carbohydr. Polym.
2015
,131, 355–362. [CrossRef]
[PubMed]
74.
Sun, Q.; Ma, J.; Campos, H.; Hankinson, S.E.; Manson, J.E.; Stampfer, M.J.; Rexrode, K.M.; Willett, W.C.;
Hu, F.B. A prospective study of trans fatty acids in erythrocytes and risk of coronary heart disease. Circulation
2007,115, 1858–1865. [CrossRef] [PubMed]
75.
Bobek, P.; Hromadová, M.; Ozdín, L. Oyster mushroom (Pleurotus ostreatus) reduces the activity of
3-hydroxy-3-methylglutaryl CoA reductase in rat liver microsomes. Experientia
1995
,51, 589–591. [CrossRef]
[PubMed]
76.
Furuncuo˘glu, Y.; Tulgar, S.; Dogan, A.N.; Cakar, S.; Tulgar, Y.K.; Cakiroglu, B. How obesity affects the
neutrophil/lymphocyte and platelet/lymphocyte ratio, systemic immune-inflammatory index and platelet
indices: A retrospective study. Eur. Rev. Med. Pharmacol. Sci. 2016,20, 1300–1306. [PubMed]
77. Mao, G.H.; Ren, Y.; Feng, W.W.; Li, Q.; Wu, H.Y.; Jin, D.; Zhao, T.; Xu, C.Q.; Yang, L.Q.; Wu, X.Y. Antitumor
and immunomodulatory activity of a water-soluble polysaccharide from Grifola frondosa.Carbohydr. Polym.
2015,134, 406–412. [CrossRef] [PubMed]
78.
Thyagarajan-Sahu, A.; Lane, B.; Sliva, D. ReishiMax, mushroom-based dietary supplement, inhibits adipocyte
differentiation, stimulates glucose uptake and activates AMPK. BMC Complement. Altern. Med.
2011
,11, 74.
[CrossRef] [PubMed]
79.
Cheskin, L.J.; Davis, L.M.; Lipsky, L.M.; Mitola, A.H.; Lycan, T.; Mitchell, V.; Mickle, B.; Adkins, E. Lack of
energy compensation over 4 days when white button mushrooms are substituted for beef. Appetite
2008
,
51, 50–57. [CrossRef] [PubMed]
80.
Poddar, K.H.; Ames, M.; Hsin-Jen, C.; Feeney, M.J.; Wang, Y.; Cheskin, L.J. Positive effect of mushrooms
substituted for meat on body weight, body composition, and health parameters. A 1-year randomized
clinical trial. Appetite 2013,71, 379–387. [CrossRef] [PubMed]
81.
Kim, S.P.; Park, S.O.; Lee, S.J.; Nam, S.H.; Friedman, M. A polysaccharide isolated from the liquid culture of
Lentinus edodes (Shiitake) mushroom mycelia containing black rice bran protects mice against a Salmonella
lipopolysaccharide-induced endotoxemia. J. Agric. Food Chem.
2013
,61, 10987–10994. [CrossRef] [PubMed]

Molecules 2018,23, 2880 24 of 26
82.
Friedman, M. Chemistry, Nutrition, and Health-Promoting Properties of Hericium erinaceus (Lion’s Mane)
Mushroom Fruiting Bodies and Mycelia and Their Bioactive Compounds. J. Agric. Food Chem.
2015
,
63, 7108–7123. [CrossRef] [PubMed]
83.
Lafarga, T.; Hayes, M. Bioactive peptides from meat muscle and by-products: Generation, functionality, and
application as functional ingredients. Meat Sci. 2014,98, 227–239. [CrossRef] [PubMed]
84.
Kang, M.G.; Kim, Y.H.; Bolormaa, Z.; Kim, M.K.; Seo, G.S.; Lee, J.S. Characterization of an antihypertensive
angiotensin I-converting enzyme inhibitory peptide from the edible mushroom Hypsizygus marmoreus.
BioMed Res. Int. 2013,2013, 283964. [CrossRef] [PubMed]
85.
Lau, C.C.; Abdullah, N.; Shuib, A.S. Novel angiotensin I-converting enzyme inhibitory peptides derived
from an edible mushroom, Pleurotus cystidiosus O.K. Miller identified by LC-MS/MS. BMC Complement.
Altern. Med. 2013,13, 313. [CrossRef] [PubMed]
86.
Alam, N.; Yoon, K.N.; Lee, T.S.; Lee, U.Y. Hypolipidemic activities of dietary Pleurotus ostreatus in
hypercholesterolemic rats. Mycobiology 2011,39, 45–51. [CrossRef] [PubMed]
87.
Jang, J.H.; Jeong, S.C.; Kim, J.H.; Lee, Y.H.; Ju, Y.C.; Lee, J.S. Characterization of a new antihypertensive
angiotensin I-converting enzyme inhibitory peptide from Pleurotus cornucopiae.Food Chem.
2011
,127, 412–418.
[CrossRef] [PubMed]
88.
Reza, M.A.; Hossain, M.A.; Damte, D.; Jo, W.S.; Hsu, W.H.; Park, S.C. Hypolipidemic and hepatic steatosis
preventing activities of the wood ear medicinal mushroom Auricularia auricula-judae (Higher Basidiomycetes)
ethanol extract in vivo and in vitro. Int. J. Med. Mushrooms 2015,17, 723–734. [CrossRef] [PubMed]
89.
Fukushima, M.; Ohashi, T.; Fujiwara, Y.; Sonoyama, K.; Nakano, M. Cholesterol-lowering effects of maitake
(Grifola frondosa) fiber, shiitake (Lentinus edodes) fiber, and enokitake (Flammulina velutipes) fiber in rats.
Exp. Biol. Med. 2001,226, 758–765. [CrossRef]
90.
Bang, T.H.; Suhara, H.; Doi, K.; Ishikawa, H.; Fukami, K.; Parajuli, G.P.; Katakura, Y.; Yamashita, S.;
Watanabe, K.; Adhikari, M.K. Wild mushrooms in Nepal: Some potential candidates as antioxidant and
ACE-inhibition sources. J. Evid. Based Complement. Altern. Med. 2014,2014, 195305.
91.
Xie, Y.; Zhang, H.; Liu, H.; Xiong, L.; Gao, X.; Jia, H.; Lian, Z.; Tong, N.; Han, T. Hypocholesterolemic effects
of Kluyveromyces marxianus M3 isolated from Tibetan mushrooms on diet-induced hypercholesterolemia in
rat. Braz. J. Microbiol. 2015,46, 389–395. [CrossRef] [PubMed]
92.
Cimerman, N.G.; Cimerman, A. Pleurotus fruiting bodies contain the inhibitor of 3-hydroxy-3-
methylglutaryl-coenzyme A reductase—lovastatin. Exp. Mycol. 1995,19, 1–6. [CrossRef]
93.
Zhao, S.; Rong, C.; Liu, Y.; Xu, F.; Wang, S.; Duan, C.; Chen, J.; Wu, X. Extraction of a soluble polysaccharide
from Auricularia polytricha and evaluation of its anti-hypercholesterolemic effect in rats. Carbohydr. Polym.
2015,122, 39–45. [CrossRef] [PubMed]
94.
Vitak, T.Y.; Wasser, S.P.; Nevo, E.; Sybirna, N.O. The effect of the medicinal mushrooms Agaricus
brasiliensis and Ganoderma lucidum (Higher Basidiomycetes) on the erythron system in normal and
streptozotocin-induced diabetic rats. Int. J. Med. Mushrooms 2015,17, 277–286. [CrossRef] [PubMed]
95.
Yurkiv, B.; Wasser, S.P.; Nevo, E.; Sybirna, N.O. Antioxidant Effects of Medicinal Mushrooms Agaricus
brasiliensis and Ganoderma lucidum (Higher Basidiomycetes): Evidence from Animal Studies. Int. J.
Med. Mushrooms 2015,17, 943–955. [CrossRef] [PubMed]
96.
Geng, X.; Tian, G.; Zhang, W.; Zhao, Y.; Zhao, L.; Wang, H.; Ng, T.B. A Tricholoma matsutake peptide with
Angiotensin Converting Enzyme inhibitory and antioxidative activities and antihypertensive effects in
spontaneously hypertensive rats. Sci. Rep. 2016,6, 24130. [CrossRef] [PubMed]
97.
Liu, Y.; Chen, D.; You, Y.; Zeng, S.; Hu, Y.; Duan, X.; Liu, A.; Chen, H.; Hu, X.; Chen, S.; et al. Structural
characterization and antidiabetic activity of a glucopyranose-rich heteropolysaccharide from Catathelasma
ventricosum.Carbohydr. Polym. 2016,149, 399–407. [CrossRef] [PubMed]
98.
Mao, D.; Ma, Y.; Geng, L.; Zhao, A.; Zheng, J.; Xu, C. Fermentation characteristics in stirred-tank reactor of
exopolysaccharides with hypolipidemic activity produced by Pleurotus geesteranus 5#. An. Acad. Bras. Cienc.
2013,85, 1473–1481.
99.
Lin, L.; Cui, F.; Zhang, J.; Gao, X.; Zhou, M.; Xu, N.; Zhao, H.; Liu, M.; Zhang, C.; Jia, L. Antioxidative
and renoprotective effects of residue polysaccharides from Flammulina velutipes.Carbohydr. Polym.
2016
,
146, 388–395. [CrossRef] [PubMed]

Molecules 2018,23, 2880 25 of 26
100.
Zhang, Z.; Lv, G.; He, W.; Shi, L.; Pan, H.; Fan, L. Effects of extraction methods on the antioxidant activities
of polysaccharides obtained from Flammulina velutipes.Carbohydr. Polym.
2013
,98, 1524–1531. [CrossRef]
[PubMed]
101.
Mohamad Ansor, N.; Abdullah, N.; Aminudin, N. Anti-angiotensin converting enzyme (ACE) proteins from
mycelia of Ganoderma lucidum (Curtis) P. Karst. BMC Complement. Altern. Med.
2013
,13, 256. [CrossRef]
[PubMed]
102.
Choi, H.S.; Cho, H.Y.; Yang, H.C.; Ra, K.S.; Suh, H.J. Angiotensin I-converting enzyme inhibitor from Grifola
frondosa.Food Res. Int. 2001,34, 177–182. [CrossRef]
103.
Hiwatashi, K.; Kosaka, Y.; Suzuki, N.; Hata, K.; Mukaiyama, T.; Sakamoto, K.; Shirakawa, H.; Komai, M.
Yamabushitake mushroom (Hericium erinaceus) improved lipid metabolism in mice fed a high-fat diet.
Biosci. Biotechnol. Biochem. 2010,74, 1447–1451. [CrossRef] [PubMed]
104.
Yang, B.K.; Park, J.B.; Song, C.H. Hypolipidemic effect of an Exo-biopolymer produced from a submerged
mycelial culture of Hericium erinaceus.Biosci. Biotechnol. Biochem.
2003
,67, 1292–1298. [CrossRef] [PubMed]
105.
Grdovi´c, N.; Dini´c, S.; Arambaši´c, J.; Mihailovi´c, M.; Uskokovi´c, A.; Markovi´c, J.; Poznanovi´c, G.; Vidovi´c, S.;
Zekovi´c, Z.; Muji´c, A.; et al. The protective effect of a mix of Lactarius deterrimus and Castanea sativa extracts
on streptozotocin-induced oxidative stress and pancreatic
β
-cell death. Br. J. Nutr.
2012
,108, 1163–1176.
[CrossRef] [PubMed]
106.
Yang, H.; Hwang, I.; Kim, S.; Hong, E.J.; Jeung, E.B. Lentinus edodes promotes fat removal in hypercholesterolemic
mice. Exp. Ther. Med. 2013,6, 1409–1413. [CrossRef] [PubMed]
107.
Yoon, K.N.; Lee, J.S.; Kim, H.Y.; Lee, K.R.; Shin, P.G.; Cheong, J.C.; Yoo, Y.B.; Alam, N.; Ha, T.M.; Lee, T.S.
Appraisal of Antihyperlipidemic Activities of Lentinus lepideus in Hypercholesterolemic Rats. Mycobiology
2011,39, 283–289. [CrossRef] [PubMed]
108.
Spim, S.R.; de Oliveira, B.G.; Leite, F.G.; Gerenutti, M.; Grotto, D. Effects of Lentinula edodes consumption on
biochemical, hematologic and oxidative stress parameters in rats receiving high-fat diet. Eur. J. Nutr.
2017
,
56, 2255–2264. [CrossRef] [PubMed]
109.
Yoon, K.N.; Alam, N.; Lee, J.S.; Cho, H.J.; Kim, H.Y.; Shim, M.J.; Lee, M.W.; Lee, T.S. Antihyperlipidemic effect
of dietary Lentinus edodes on plasma, feces and hepatic tissues in hypercholesterolemic rats. Mycobiology
2011,39, 96–102. [CrossRef] [PubMed]
110.
Kaur, A.; Dhingra, G.S.; Shri, R. Evaluation of carbohydrate metabolism inhibition by some species of
medicinal mushrooms from India. Int. J. Med. Mushrooms 2015,17, 351–360. [CrossRef] [PubMed]
111.
Koo, K.C.; Lee, D.H.; Kim, J.H.; Yu, H.E.; Park, J.S.; Lee, J.S. Production and characterization of
antihypertensive angiotensin I-converting enzyme inhibitor from Pholiota adiposa.J. Microbiol. Biotechnol.
2006,16, 757–763.
112.
Zheng, L.; Zhai, G.; Zhang, J.; Wang, L.; Ma, Z.; Jia, M.; Jia, L. Antihyperlipidemic and hepatoprotective
activities of mycelia zinc polysaccharide from Pholiota nameko SW-02. Int. J. Biol. Macromol.
2014
,70, 523–529.
[CrossRef] [PubMed]
113.
Li, N.; Li, L.; Fang, J.C.; Wong, J.H.; Ng, T.B.; Jiang, Y.; Wang, C.R.; Zhang, N.Y.; Wen, T.Y.; Qu, L.Y.
Isolation and identification of a novel polysaccharide-peptide complex with antioxidant, antiproliferative
and hypoglycaemic activities from the abalone mushroom. Biosci. Rep.
2012
,32, 221–228. [CrossRef]
[PubMed]
114.
Zhang, J.; Meng, G.; Zhang, C.; Lin, L.; Xu, N.; Liu, M.; Cui, F.; Jia, L. The antioxidative effects of acidic-,
alkalic-, and enzymatic-extractable mycelium zinc polysaccharides by Pleurotus djamor on liver and kidney
of streptozocin-induced diabetic mice. BMC Complement. Altern. Med. 2015,15, 440. [CrossRef] [PubMed]
115.
Alam, N.; Yoon, K.N.; Lee, J.S.; Cho, H.J.; Shim, M.J.; Lee, T.S. Dietary effect of Pleurotus eryngii on biochemical
function and histology in hypercholesterolemic rats. Saudi J. Biol. Sci.
2011
,18, 403–409. [CrossRef] [PubMed]
116.
Alam, N.; Yoon, K.N.; Lee, T.S. Antihyperlipidemic activities of Pleurotus ferulae on biochemical and
histological function in hypercholesterolemic rats. J. Res. Med. Sci. 2011,16, 776–786. [PubMed]
117.
Ibadallah, B.X.; Abdullah, N.; Shuib, A.S. Identification of angiotensin-converting enzyme inhibitory proteins
from mycelium of Pleurotus pulmonarius (oyster mushroom). Planta Med.
2015
,81, 123–129. [CrossRef]
[PubMed]
118.
Yoon, K.N.; Alam, N.; Shim, M.J.; Lee, T.S. Hypolipidemic and antiatherogenesis effect of
culinary-medicinal pink oyster mushroom, Pleurotus salmoneostramineus L. Vass. (higher Basidiomycetes),
in hypercholesterolemic rats. Int. J. Med. Mushrooms 2012,14, 27–36. [CrossRef] [PubMed]

Molecules 2018,23, 2880 26 of 26
119.
Wu, T.; Xu, B. Antidiabetic and antioxidant activities of eight medicinal mushroom species from China. Int. J.
Med. Mushrooms 2015,17, 129–140. [CrossRef] [PubMed]
120.
Hyoung Lee, D.; Ho Kim, J.; Sik Park, J.; Jun Choi, Y.; Soo Lee, J. Isolation and characterization of a novel
angiotensin I-converting enzyme inhibitory peptide derived from the edible mushroom Tricholoma giganteum.
Peptides 2004,25, 621–627. [CrossRef] [PubMed]
121.
Bobek, P.; Ozdín, L.; Kuniak, L.; Hromadová, M. Regulation of cholesterol metabolism with dietary addition
of oyster mushrooms (Pleurotus ostreatus) in rats with hypercholesterolemia. Cas Lek Cesk
1997
,136, 186–190.
[PubMed]
122.
Yang, B.K.; Kim, G.N.; Jeong, Y.T.; Jeong, H.; Mehta, P.; Song, C.H. Hypoglycemic effects of exo-biopolymers
produced by five different medicinal mushrooms in STZ-induced diabetic rats. Mycobiology
2008
,36, 45–49.
[CrossRef] [PubMed]
123. Yang, U.K.; Jeong, S.C.; Lee, H.J.; Sohn, D.H.; Song, C.H. Antidiabetic and hypolipidemic effects of Collybia
confluens mycelia produced by submerged culture in streptozotocin—Diabetic rats. Arch. Pharmacol. Res.
2006,29, 73–79. [CrossRef]
124.
Chen, X.; Wu, G.; Huang, Z. Structural analysis and antioxidant activities of polysaccharides from cultured
Cordyceps militaris.Int. J. Biol. Macromol. 2013,58, 18–22. [CrossRef] [PubMed]
125.
Yeh, M.Y.; Ko, W.C.; Lin, L.Y. Hypolipidemic and antioxidant activity of enoki mushrooms (Flammulina
velutipes). BioMed Res. Int. 2014,2014, 352385. [CrossRef] [PubMed]
126.
Zhang, H.N.; Lin, Z.B. Hypoglycemic effect of Ganoderma lucidum polysaccharides. Acta Pharmacol. Sin.
2004
,
25, 191–195. [PubMed]
127.
Li, F.; Zhang, Y.; Zhong, Z. Antihyperglycemic effect of Ganoderma lucidum polysaccharides on
streptozotocin-induced diabetic mice. Int. J. Mol. Sci. 2011,12, 6135–6145. [CrossRef] [PubMed]
128.
Zheng, J.; Yang, B.; Yu, Y.; Chen, Q.; Huang, T.; Li, D. Ganoderma lucidum polysaccharides exert
anti-hyperglycemic effect on streptozotocin-induced diabetic rats through affecting
β
-cells. Comb. Chem.
High Throughput Screen 2012,15, 542–550. [CrossRef] [PubMed]
129.
Yang, B.K.; Kim, D.H.; Jeong, S.C.; Das, S.; Choi, Y.S.; Shin, J.S.; Lee, S.C.; Song, C.H. Hypoglycemic effect of
aLentinus edodes exo-polymer produced from a submerged mycelial culture. Biosci. Biotechnol. Biochem.
2002
,
66, 937–942. [CrossRef] [PubMed]
130. Hwang, H.J.; Kim, S.W.; Lim, J.M.; Joo, J.H.; Kim, H.O.; Kim, H.M.; Yun, J.W. Hypoglycemic effect of crude
exopolysaccharides produced by a medicinal mushroom Phellinus baumii in streptozotocin-induced diabetic
rats. Life Sci. 2005,76, 3069–3080. [CrossRef] [PubMed]
131.
Rony, K.A.; Ajith, T.A.; Mathew, J.; Janardhanan, K.K. The medicinal cracked-cap polypore mushroom
Phellinus rimosus (higher Basidiomycetes) attenuates alloxan-induced hyperglycemia and oxidative stress in
rats. Int. J. Med. Mushrooms 2013,15, 287–300. [CrossRef] [PubMed]
132.
Rony, K.A.; Ajith, T.A.; Janardhanan, K.K. Hypoglycemic and hypolipidemic effects of the cracked-cap
medicinal mushroom Phellinus rimosus (Higher Basidiomycetes) in streptozotocin-induced diabetic rats.
Int. J. Med. Mushrooms 2015,17, 521–531. [CrossRef] [PubMed]
133.
Cho, E.J.; Hwang, H.J.; Kim, S.W.; Oh, J.Y.; Baek, Y.M.; Choi, J.W.; Bae, S.H.; Yun, J.W. Hypoglycemic effects
of exopolysaccharides produced by mycelial cultures of two different mushrooms Tremella fuciformis and
Phellinus baumii in ob/ob mice. Appl. Microbiol. Biotechnol. 2007,75, 1257–1265. [CrossRef] [PubMed]
134.
Li, H.; Lee, H.S.; Kim, S.H.; Moon, B.; Lee, C. Antioxidant and anti-inflammatory activities of methanol
extracts of Tremella fuciformis and its major phenolic acids. J. Food Sci.
2014
,79, C460–C468. [CrossRef]
[PubMed]
135.
Yang, B.K.; Jung, Y.S.; Song, C.H. Hypoglycemic effects of Ganoderma applanatum and Collybia confluens
exo-polymers in streptozotocin-induced diabetic rats. Phytother. Res.
2007
,21, 1066–1069. [CrossRef]
[PubMed]
©
2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).