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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5607_Библиотеки_им_академика_М_И_Перельмана
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Biomarkers as Targeted Herbal Drug Discovery
medicine is a valuable part of traditional medicine and modern medicine,
and it will be the same as in the future. There are now over 100 natural drug
products being clinically tested and at least 100 compounds or molecules at the
preclinical stage of development (Harvey Al, 2008). Most of these molecules
are derived from a lead from plant and microbial sources and are in the developmental stage. The cancer and infection medication discovery program are
based on natural products but a number of other therapeutic areas, such as
inflammation, cardiovascular, gastrointestinal, neurosciences, and metabolism, are also targeted. Among 108 different therapeutic projects, indicate that
46 are in pre-clinically active and 14 in phase-1, 41 in phase-2, 5 in phase-3,
and 2 are in the pre-registration phase (Harvey Al, 2008). There are generally
six categories for the NCEs class. However, botanical sources, fungi, bacteria,
and marine sources are the four major classes. In addition to these four classes
of substances, the modern pharmaceutical chemistry includes two different
classes of manufactured substances, synthetic chemistry, and combination
chemistry from these natural sources.
Bioactive lead compounds with structure may act as more potent compounds,
e.g., paclitaxel for Taxus species.
A new chromophore that can be transformed with/without chemical
analogs into a drug compound. Pure phytochemicals are used for standardization of crude plant extract or material as a marker for compounds. Pure
phytochemicals can be used as pharmacological tools.
Globally about 422,000 plant species have been identified, of which 12.5%
plant species have been used for medicinal purpose and 8% of the medicinal
plants are under the threatened’ category (Schippmann et al., 2002). Still the
biological activities of many plants are not explored, and few of the plants
are well recognized in official pharmacopeias, such as the Ayurvedic pharmacopeia of India and Japanese pharmacopeia. Indian Ayurvedic Pharmacopeia
contains 540 plant monographs and 976 compounds formulations (Joshi et al.,
th
2017). Japanese, 14
edition Pharmacopoeia lists 165 herbal and 16th edition
276 crude drugs such as herbal medicines and extracts that approved for use
in kampo remedies (Pan et al., 2014). The pharmacological actions and the
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concentration in plants depend on their phytoconstituents and on the plant
habits. The plant habit has a major impact on the concentration of phytoconstituent and this factor plays an important role in the medicinal importance of
any plant. Approximately, 90% of the medicinal herbs in the Indian medicinal
are collected from natural and wild sources. The unsuitable collection (stage
of maturity, dried haphazardly, and stored for a long time) is rapidly depleting
the resource and many species are under threat (Lalitha, 2013).
In 1906, German Physician Aloes Alzheimer, who first describe brain
disorder and named after its Alzheimer’s disease (AD). AD is a neurodegenerative and progressive disease that mainly affects an aged over 65, and
reported for 50%–60% of dementia cases (Francis et al., 1999). Alzheimer’s
condition is characterized by a decrease in speech function, increased apathy,
and deterioration of virtually all intellectual functions, progressive loss of
memory, disorientation, and gait irregularities.
The loss of memory is due to the scarcity of the neurotransmitter acetylcholine. Inhibiting the action of the enzyme acetylcholine esterase which
breaks up the neurotransmitter can improve the acetylcholine transmitter
concentration in the brain. Drugs that prevent messenger breakdown or
acetylcholine stop the disease’s growth (Jayaprakasam et al., 2010). Herbs
for antioxidant and anti-inammatory activities which could be used to treat
Alzheimer’s disease have been investigated. The herbal herbs that inhibit
AchE contain COX-2, which are used for the indication of AD as a herbal
medicine. Some Indian herbs used in the Ayurvedic preparations which are
excellent for slowing down the brain degeneration caused by Alzheimer’s
like Padma (Nelumbo nucifera), Kataj, Galo Satva, Musta Arjun, Guduchi,
Ashwagandha, Amalaki, Pancha-TiktaGhrutaGugguli, Vacha, etc.
It is a source of an orange-yellow pigment called curcumin, (diferuloylmethane), compound of turmeric. Studies have shown that curcumin has
antioxidant and anti-inflammatory activity and that it aids in the fight against
AD (Jayaprakasam et al., 2010).
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Biomarkers as Targeted Herbal Drug Discovery
The herbal nutraceutical Bocopa monnieri (Brahmi), also recognized as
memory enhancement in patients with Alzheimer’s disease, is defined in the
Ayurveda system as memory improvement and concludes that it can be useful
in those patients but further research is required (Goswami et al., 2011).
Ginkgo biloba L. is the herb most renowned for its capacity to improve
circulation systematically. BP is reduced and the aggregation of platelets is
inhibited. Ginkgolides are the main chemical constituent of Ginkgo biloba
and are a relevant antioxidant, with neuro-protective, and cholinergic
activities in AD management. Scientific studies showed its promise on
cognition-enhancement, if used during the early stage of the Alzheimer’s
disease. Extract of Ginkgo biloba showed therapeutic benefits in similar, too
prescribed medicines like Donepezil or Tactrine with minimally unwanted
side effect in the controlled clinical trials of a control and placebo groups
(Elias et al., 2010).
Aqueous extract of licorice on A25-35 induces apoptosis in PC12 cells.
The result suggests that GWE exerts a protective effect against a fragmentinduced apoptotic neuronal cell death. Extract from the root of licorice is
reported to treat or even prevent the death of brain cells in disorders such as
Alzheimer’s and its related symptoms (Ji et al., 2011).
Lipidium meyenii Walp is also known as maca. Maca shows a profitable
improvement in learning and memory. Lipidium meyenii Walp improves
experimental memory impairment, induced by ovariectomy, due in part to
its AchE inhibitory and antioxidant activities. Results showed that Lipidium
meyenii Walp can improve learning and memory in ovariectomized (OVX)
mice and this impact may be linked to its capacity to reduce lipid peroxidation (LPO) and AchE in OVX mice (Kumari et al., 1995).
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The root of Ginseng has been used since ancient times in folk medicine
in countries such as Korea and China to boost Qi. The medicinal use of
Ginseng goes back to thousands of years. Panax Ginseng (Ren-Shen)
contains propanetriol, oleanolic acid (OA), and saponins protopanaxadiol,
reported having memory-enhancing action for learning impairment generated by scopolamine. The use of ginseng extract claims to attain and retain
both physical and mental well-being (Sheela et al., 1992).
L.
In the Ayurveda medicine system, Acorus calamus has been used for the
treatment of behavior changes, memory loss, and for learning performance. Acorus calamus L. inhibits the AChE. It contains a majority of
asarone (Karunanayaka et al., 1984). Acorus calamus also shows antiinflammatory, cardiovascular, immune-suppressive, antioxidant, antispasmodic, hypolipidemic, antimicrobial, antidiarrheal, anthelmintic, and
cytoprotective.
It is a chronic metabolic disorder of carbohydrate, protein, and fat, which is
a lifelong condition affecting the person’s blood glucose and insulin level
in the body. In diabetic condition, pancreases either do not produce enough
insulin or the body does not use it properly. It is estimated that the worldwide prevalence of diabetes will increase from 4% in 1995 to 5.4% by 2025.
According to WHO prediction, the major burden will occur in developing
countries?
A study in India over the last decade has shown that the prevalence of
diabetes is not only high, but also rapidly increasing in the urban population.
An estimated 33 million adult with diabetes is living in India. By 2025, the
number is expected to rise to 57.2 million.
Symptoms for diabetic conditions may include:
1. High level of blood sugar level;
2. Unusual thirst;
3. Frequent urination;
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Biomarkers as Targeted Herbal Drug Discovery
4. Loss of weight and extreme hunger;
5. Blurred vision;
6. Extreme weakness and tiredness;
7. Irritability, mood changes.
Many people use herbs and supplements to cure diabetes, but they are not
effective and stand-alone, but they may use herbs to relieve symptoms and
reduce the risk of complications.
Acacia is growing throughout India, particularly in the wild. The extract
of this plant acts as an anti-diabetic agent by acting as a secretagogue to
secrete insulin. In the experiment, it induces hypoglycemia in control rats.
In powdery seeds of Acacia administered to normal rabbits at a weight of 2,
3, and 4 g/kg, the hypoglycemic effect is caused by insulin-releasing in the
pancreas cells (Wadood et al., 1989).
Blood glucose and serum cholesterol and urea are reduced by aqueous leaf
extract and reduced relative to controlled alloxanized rats. The hypoglycemic activity also occurs through the injection and avoided a maximum
blood sugar growth at a 1-hour oral tolerance test (Karunanayake et al.,
1984).
Dried onion powder fraction either soluble or insoluble compound show
anti-hypoglycemic activity in diabetic rabbits. Onion also has hypolipidemic
and antioxidant activity. Administration of the amino acid sulfur S-methyl
cysteine (SMCS) in alloxan-driven diabetic rats for 45 days has significantly
controlled blood glucose, serum, and tissues lipids and normalizes liver
glucose activities 6-phosphatase, hexokinase, and HMG Co-A reductase
activity (Roman-Ramos et al., 1995; Kumari et al., 1995). When a single
oral dose of allium cepa juice was given to diabetic patients, the level of
postprandial glucose was significantly controlled.
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Garlic is a herb grown throughout India. It has allicin, a compound that
contains sulfate that gives a smooth odor and has significant hypoglycemic
activity (Sheela et al., 1992). The hypoglycemic impact is supposed to be
attributed to enhanced hepatic metabolism, enhanced beta-cell glucose
discharge, or insulin-sparing (Zacharias et al., 1980). Garlic aqueous homogenate (10 ml/kg/day) orally administered to rabbits for 2 months 10 g/kg/
day in the water, hepatics glycogen and amino acid, rapid sugar, and serum
triglycerides decrease, as opposed to sucrose controls (Augusti et al., 1996).
S-allyl cysteine is oxidant-controlled sulfur that contains the amino acid, a
precursor of garlic oil and allicin, rather than insulin and glibenclamide that
controls the lipid by oxidation (Al-Awadi et al., 1987). Garlic also exhibits
anticancer, antimicrobial, and cardioprotective activities.
Aloe vera is a popular house decorative plant and a multipurpose folk remedy.
Aloe has two basic products: latex and gel. Aloe gel is commonly known pulp
or mucilage as aloe juice, and aloe latex is a bitter yellow exudate of per cycle
tube below the outer skin of the leaves. Aloe gum extract effectively increases
glucose tolerance in common rats as well as in diabetic ones (Aiabnoor et al.,
1990). Treatment of chronic have no single dose of Aloe barbadenis exudates
in alloxan diabetic rats indicates a hypoglycemic impact. The hypoglycemic
action was also demonstrated in the diabetic rat, together with a chronic amount
of the bitter principle of the same plant. This action of Aloe vera is through
stimulation of synthesis and/or insulin release from pancreatic beta cells (Devis
et al., 1989). This plant has anti-inflammatory activities that depend on the doses
and improves the wound healing in diabetic mice (Chattopadhyay et al., 1987).
Hydro-alcoholic extract from this plant reported anti-hyperglycemic effects
in treated streptozotocin rats and this effect is due to increased absorption of
glucose in isolated rats and glycogen deposition (Chattopadhyay et al., 1987;
Biswas et al., 2002). Apart from this neem having anti-diabetic activity,
antimaterial, anti-bacterial, hepatoprotective, and antioxidant effects (Chattopadhyay et al., 2003).
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Biomarkers as Targeted Herbal Drug Discovery
This is commonly found in arid regions throughout India. In alloxanized
rats, the hypoglycemic effect occurs when 30% extract from Capparis
decidua (C. decidua) fruit powder was given to rats for three decades. In
erythrocytes, kidney, liver, this extract also reduces alloxan-induced lipid
peroxidation significantly. C. decidua has also been found to change superoxide dismutase (SOD) and enzyme catalase (CAT) concentration in order
to decrease oxidative stress (Agarwal et al., 1988). Additionally, decidua
demonstrated hypolipidemic activity (Kamble et al., 1998).
Eugenia jambolana in India is used to treat diabetes in households. This
is also an important component of many herbal medicines for diabetes
formulations. Aqueous, alcoholic, and lyophilized powder extracts have
anti-hyperglycemic effects and a drop in blood glucose levels. It depends on
the level of diabetes. It indicates 73.51% decrease in mild arthritis (plasma
sugar >180 mg/dl), compared to 55.6% and 17.62% reduced in moderate
(plasma glucose >280 mg/dl) and severe diabetes (plasma sugar >400 mg/
dl). In streptozotocin-induced mice, the extract of Jamun pulp exhibited
hypoglycemic activity within 30 minutes, whereas seeds of the fruit needed
24 hours. The oral administration of extract has led to an increased serum
insulin level in diabetic rats. The incubation of plant extract with the isolated
islet of Langerhans from both normal and diabetic animals stimulated insulin
secretion. These extracts also inhibited liver and kidney insulins activity
(Aderibigbe et al., 1999).
Momordica charantia is used as an antidiabetic and antihyperglycemic agent in
both India and other Asian countries. Extract of the pulp of fruits, seed, leaves,
and entire plants were shown in various animal models as having a hypoglycemic activity. Polypeptide p, isolated from fruits and tissue of M. charantia, has
a significant hypoglycemic impact on langurs and humans when administered
subcutaneously (Shibib et al., 1993). Ethanolic extract of M. charantia (200 mg/
kg) had an anti-hypoglycemic and hypoglycemic impact in ordinary diabetic
rats and STZ rats. This can be due to inhibition of glucose-6-phosphatase in the
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liver and stimulation of hepatic glucose-6-phosphate dehydrogenase activities
in addition to fructose-1,6-biphosphatase (Vats et al., 2002).
Milk thistle may have anti-inflammatory characteristics that may be helpful
to people with diabetes. People have been using thistle as a tonic for the liver
and many different ailments since ancient times. Silymarin is a compound
that has been given the greatest attention by scientists with antioxidant and
anti-inflammatory properties. These are the properties which can make milk
thistle a useful herb for diabetes patients. Many of the silymarin studies are
promising but, according to one review published in 2016, the research is not
strong enough to recommend the herb or extract alone for diabetes. No side
effect report appears and as a supplement, many people take milk thistle.
However, it is best to talk to a doctor first before using any supplement.
New stearoyl glucose of ursolic acid, urs-12-en-3-ol-28-oic acid 3-D-glucopyranosyl-4’-octadecanoate, and other compound were isolated from Latana
camera L leaf. By the standard spectroscopic method, the structure of this
new glycoside was elucidated and established. It showed a reduction in
blood glucose levels in streptozotocin-induced diabetic rats.
Cancer is mainly responsible for the abnormal and uncontrolled division of
cells. Cancer with abnormal cell growth that invades or spreads to other parts
of the body. Signs and symptoms include an abnormal bleeding, unexpected
weight loss, prolonged cough, lump, and a change in bowl movement. These
symptoms may indicate cancer or may be due to other causes. Many plant
species are already used for cancer treatment or prevention. Researchers
have identified new plant species that have proven anti-cancer properties
with a high emphasis on herbal medicines used in developing countries. The
th
most common cause of death in carcinoma is primary liver cancer in
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the world and the 3
rd
leading cause of mortality. Hepatocellular carcinoma
(HCC) cause for 85% to 90% of main liver cancer. The HCC has several
Biomarkers as Targeted Herbal Drug Discovery
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interesting epidemiological characteristics, including dynamic temporal
trends; considerable differences between geographical regions, racial, ethnic,
and male and female; and several well-documented environmental variables
that could possibly be avoided. In addition, there is an increasing knowledge
of the molecular mechanism that causes hepatocarcinogenesis that almost
rises significantly in reaction to chronic liver injury at the cirrhosis stage.
Thorns of Gleditsia sinensis have historically been used in Chinese medicine
and were considered one of the most important herbs for treatment. There is
currently an investigation of the effect of Gleditsia sinensis on cancer. New
drug development still necessary for the therapy of HCC, the most prevalent
form of main liver cancer, with greater effectiveness. The beneficial impact
of Gleditsia sinensis extract (GSE) and its regulatory effects on the miRNAs
were determined by the use of the rat HCC model implanted with cancerous
Walker-256 cells. GSE improves liver morphology significantly and dramatically induced HCC rat cell apoptosis. Furthermore, miR-21/181b/183 was
up-regulated in HCC liver and both sorafenib and GSE reduced the elevation
of these miRNAs. Down-Regulation PTEN/TIMP3/PDCD4 was consistent
with the HCC liver target of miR3621/181b/183 and both GSE and Sorafenib
altered the target genes. Also determined were the impacts of TIMP3 on
MMP-2/9’ expression. The results show the potential of GSE in HCC treatment and increase the understanding of miRNA-related mechanisms in GSE
cancer (Lopez-Lazaro, 2008).
Curcumin (diferuloylmethane), obtained from Curcuma aromatica widely
used as coloring and spice agent in food, possesses potent anti-inflammatory,
antioxidant, and anticarcinogenic properties. The anti-carcinogenic property of curcumin has been reported different cancer (Chuang et al., 2000).
Three important curcumin properties were studied with respect to HCC:
Anti-HCC; anti-metastatic; and anti-angiogenesis activity. Chuang et al.
checked the effect of curcumin on HCC mice model; cancer induced by
N-diethylnitrosamine (DEN) and reported that curcumin inhibits effectively
DEN-induced HCC in the C3H/HeN mice. Mice treated with DEN show a
remarkable increase in the level of p21 (ras), expression of proliferating cell
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nuclear antigen (PCNA) and CDC2 protein, while curcumin inverted the
level of all these biological markers. The effect of curcumin and tetrahydrocurcumin on tumor angiogenesis of HCC mice is also found in a study
conducted by Joysungnoen et al. Human HCC cell line (HepG2) was inoculated with tetrahydro-curcumin orally injected into a dorsal peeling chamber
of male BALB/v nude mice at 300 and 300 mg/Kg–1 per day. A fluorescence
video microscopy and capillary vascularity (CV) were observed to measure
tumor microvasculature. They found a substantial reduction in the curcumin
and tetrahydrocurcumin (THC) in the CV. THC and curcumin have a dosedependent anti-angiogenic effect and represent a common mechanism for
their action against cancer (Yoysungnoen et al., 2005, 2006).
Resveratrol has been shown to have a strong growth inhibitory effect on
various human cells, including HCC, as a compound of polyphenol found in
peanuts, grape skins, red vine, and berries.
It rapidly absorbed by the liver and accumulates in it. Lancon et al.
studied the resveratrol absorption and efux in HepG2 cells. Resveratrol
has been rapidly combined and fully metabolized to form two major resveratrol metabolites in eight hours: disulfate and monosulfate. In order to
assess the inhibitory effect of hepatocarcinogenesis resveratrol, the HCC
rat model is used by Bishayee et al. A single intraperitoneal (I.P) injection
of diethylnitrosamine (DENA) produced the HCC, followed by promotion
in drinking water with phenol barbital. Resveratrol has been discovered
to have an important chemoprotective impact on hepatocarcinogenesis
initiated by DENA through inhibition of apoptosis and cell proliferation.
They found that a feasible mechanism could be that the apoptogenic
signal induced by resveratrol is mediated through Bcl-2 down-regulation
and Bax up-regulation (Bishayee et al., 2008). The inhibitory impact of
resveratrol on apoptosis and cell proliferation in HepG 2 cells also were
demonstrated by an in vitro study by Stervbo et al. resveratrol has been
found to inhibit the synthesis of DNA and to increase the nuclear scale
and granularity of HepG 2 cells in G1 and S phases. Resveratrol also
activated apoptosis in HepG 2 cells, which was concentration-dependent.
Resveratrol has been found that it interferes with distinct phase of cycle
inhibiting cell proliferation and triggers apoptosis stimulation. The
HepG2 cells were also used by Notas et al. to examine the effects of
resveratrol on cell growth. They show that stilbene resveratrol inhibits
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