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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5958_Библиотеки_им_академика_М_И_Перельмана
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leaves are 10 cm long, thick underneath and sparse above. There are
greenish or lurid-yellow flowers in axillary, umbellate cymes; berries are tiny,
globose, orange-red when ripe, encased in the persistent calyx; and it has
yellow seeds. The bright red fruit is gathered in the late fall and the seeds are
dried for spring sowing.
4
5.4 Composition
Using separation techniques such as thin-layer chromatography (TLC), col-
umn chromatography (CC), and high-performance liquid chromatography
(HPLC), several phytochemicals have been extracted from methanolic ex-
tracts of various plant components (leaves, twigs, etc.)ofW. somnifera.
Phytochemicals such as pubesenolide, jaborosalactone D, 4b,27-dihydroxy-
L-
oxo-22R-witha-2,5,24-trienolide, and 2,3-dihydrowithaferin A-3b-O-sulfate
are worthy of mention. Finally, the structures have been confirmed using
single-crystal X-ray diffraction (XRD) measurements. Based on anomalous
chlorine atom scattering in the crystal, the absolute configuration was de-
termined to be 6a-chloro-5b,17a-dihydroxy withaferin A. A nuclear magnetic
resonance (NMR) study has led to the discovery of other chlorinated
chemicals. Using a combination of gas chromatography-mass spectrometry
(GC–MS) and NMR on W. somnifera fruits extracted in n-hexane, aqueous
methanol, and water, chemically diverse metabolites such as aliphatic and
aromatic amino acids, phenolic acids, withanolides, organic acids, sugars,
tocopherols and sterols, fatty acids, and polyols have be en identified. Ac -
cording to some studies, more than 12 alkaloids, 40 withanolides, and many
sitoindosides have been discovered in various areas of WS using different
phytochemical assays. Only a few are important players in predicting
pharmacological qualities among this wide variety of pharmacologically
active principles. Withanolides are steroidal ergostane compounds with an
oxidized C-1 position and a lactone performance between C-22 and C-26
atoms. Withanolides are a marker compound found in plants belonging to
the Solanaceae family, particularly those belonging to the Withania genus.
Withanolide D and withaferin A are the two types of withanolides. The plant
extract has significant antioxidant properties and also neuroprotection
ability under in vitro circumstances. Withanolides A, VI and withanoside IV
have excellent anticancer and anti-inflammatory abilities. Withanolide A can
stimulate nominal networks also. Withanolides suppress acetylcholinester-
ase and promote dendritic growth in human neuroblastoma cells.
3
Figures 5.3 and 5.4 show the phytochemicals present in W. somnifera and
structural representations of some predominant phytochemicals.
Withasteroids, which are strong neurostimulants, were highly appreciated
in traditional Indian medicine, according to Maumita et al. Furthermore,
withaferine A and withanolide A, the two most important withanolides,
have C-28 steroidal lactones constructed on an intact or rearranged ergos-
tane framework. They can be found in the aerial and root parts of the plant.
Withanolides are typically found in leaves, ranging from 0.001 to 0.5% by
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weight. The production of withasteroid differs from plant to plant. According
to tests, the production of the main withasteroids is naturally controlled,
using hybrids of different chemotypes of W. somnifera. Asteroids with new
ring substitutions that aren’t found in the parent plants are produced by
these hybrids .
5
Apart from chemically active compounds like flavonoids, alkaloids (tro-
pine and anferine), terpenoids, steroidal lactones (anolides), and saponins
in extracts from different parts of the plant, bioactive compounds like ash-
wagandhine, cuscohygrine, anaferineisopelletierine, sitoindosides, anahy-
grine, withanamides, and tropine have been isolated and identified from
W. somnifera. Pure compounds are less efficient in some circumstances than
W. somnifera extracts containing a range of components. Antifungal and
antibacterial activities of W. somnifera extracts have been reported.
6
5.5 Therapeutical Potential
5.5.1 Neuroprotective Effects
W. somnifera has been shown to have neuroprotective properties. Leaf extract
of W. somnifera and its components reduced scopolamine-induced toxicity in
glial and neuronal cells. In neuronal cells, neurofilament-H (NF-H),
microtubule-associated protein-2 (MAP-2), postsynaptic density protein-95
(PSD-95), and growth-associated protein-43 (GAP-43) were all decreased. All
of these qualities were reduced after pretreatment with varying dosages of
withanone. Withanone may be useful as a neuroprotective agent, according
to these data.
7
Glycowithanolides from W. somnifera demonstrated signifi-
cant antioxidant activity in the cortex and striatum of the rat brain.
According to Satyan and Bhattacharya, the root powder of W. somnifera
preserved dying neurons in the Cornu Ammonis 2 (CA2) and Cornu Ammonis
3 (CA3) subareas of rats in the hippocampus region subjected to immobil-
ization stress and rescued mice from streptozotocin-induced oxidative stress.
In human neuroblastoma cell lines, W. somnifera root extract greatly boosted
neurite outgrowth. Withanolide A improved axonal and dendritic
Figure 5.3 Phytochemicals in W. somnifera.
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Figure 5.4 Structural representation of predominant phytochemicals.
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modification and synaptic repair in cortical neurons of rats treated with
amyloid beta-peptide (Ab).
8
W. somnifera extract decreased kainic acid toxicity
by decreasing the oxidative damage. Leaf extract of W. somnifera inhibited
glutamate-induced excitotoxicity in retinoic acid-differentiated C6 (rat glioma
cell line) and IMR-32 (human neuroblastoma cell line) cells.
9
Figure 5.5 shows
the overall therapeutic properties of phytochemical withaferin-A.
5.5.2 Anti-Parkinson Effects
In rat models of Parkinson’s disease, W. somnifera extracts were found to
protect against functional deficits and pathology caused by 6-hydroxydopamine
(6-OHDA). According to one study,
10
the antioxidant mechanisms in W. som-
nifera restored striatal dopamine and its metabolite levels.
W. somnifera root extract restored antioxidant balance, decreased oxidative
stress, stabilized catecholamine levels, and reversed functional deficits in the
midbrain in rats treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
W. somnifera extract treated oxidative stress, mitochondrial respiratory chain
enzymes, cholinergic dysfunction, and dopamine levels. There was an in-
crease in lethality as well as locomotory function. Due to its antioxidant and
antiinflammatory properties and its capacity to restore mitochondrial func-
tion, W. somnifera root powder reduced rotenone-induced toxicity in the ce-
rebellum and striatum of the rat brain striatal dopamine levels.
In a rat model of Parkinson’s disease, an ethanolic root extract of
W. somnifera reduced toxicity caused by Maneb and Paraquat. Tyrosine hy-
droxylase expression was preserved, nigral dopamine levels were normal-
ized, and locomotor activity was increased thanks to the antiinflammatory,
antiapoptotic, and antioxidant properties. Before glial fibrillary acidic
Figure 5.5 Important biological activities of withaferin-A.
Phytochemical, Botanical and Therapeutic Potential of Withania somnifera in Ayurveda 95
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protein (GFAP) levels declined, W. somnifera suppressed inducible nitric
oxide (NO) synthase expression, downregulated pro-apoptotic BCL2-associ-
ated X protein (Bax) and increased antiapoptotic B cell lymphoma (BCL-2)
protein expression.
11
5.5.3 Breast Cancer
According to one study, breast cancer is one of the most common malig-
nancies connected to Withaferin-A (WA) activity. Estrogen has a role in the
evolution and growth of breast tumors [through the nuclear estrogen re-
ceptor (ER)]. Steroid sex hormones influence breast cancer’s onset, course,
and prognosis. The significance of ER in breast cancer is widely understood
and targeted treatments are now being explored. ER-positive breast cancers
account for 75–80% of all breast cancers. Antiestrogens, such as tamoxifen,
have been demonstrated to reduce or eliminate tumors by lowering en-
dogenous estrogen levels (e.g., aromatase inhibitors) or interfering with ER
activation (antiestrogens, such as tamoxifen).
12
5.5.4 Cervical Cancer
Cervical cancer is the second most common cancer globally, and it is re-
garded as a significant worry in women’s health. Cervical cancer is caused by
chronic infection with particular types of human papillomavirus (HPV). The
primary cause of cervical cancer, WA, suppresses human papillomavirus
oncogenes and upregulates tumor suppressor proteins, resulting in
p53-dependent death of cancer cells in the human cervical region. Various
cervical cell lines, such as C33a, SiHa, CaSki, and HeLa, have displayed dose-
dependent anticancer activity when exposed to WA. Withaferin therapy re-
sulted in the downregulat ion of HPV E6 and E7 oncoproteins and increased
p53, resulting in the activation of different apoptotic markers. The elevated
level of p21 cip1/waf1 and its interaction with proliferating cell nuclear
antigen (PCNA) causes G2/M cell cycle arrest (which is connected with the
alteration of p34 cdc2, cyclin B1, and PCNA levels).
13
5.5.5 Ovarian Cancer
Ovarian cancer is the sixth most common malignancy in women and the
seventh leading cause of death worldwide.
14
WA has shown exceptional
success in treating ovarian cancer, mainly when combined with other can-
cers. It has been revealed that the anticancer medication doxorubicin (DOX)
has improved therapeutic activity in ovarian cancer when coupled with WA
via reactive oxygen species (ROS)-induced necroptosis. The combination
treatment of doxorubicin and withaferin increases cell death and inhibits
the proliferation of various epithelial cells such as CaOV3, A2780, and A2780/
CP70 in a concentration- and time-dependent manner. Doxorubicin in
combination with W. somifera increases ROS production, necroptosis
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induction, and LC3B levels. In in vivo xenograft models of ovarian cancer and
in vitro 3D tumors, tumor cell proliferation was reduced by 70–80%. As a
result, the study shows that combining WA with DOX can minimiz e treat-
ment side effects and dosage.
15
In the case of ovarian cancer, Kakar et al.
demonstrated that WA inhibits tumor cell formation and spread by in-
hibiting potential cancer stem cells. The researchers found that in athymic
mice, orthotopic ovarian tumors injected with cisplatin and WA in a human
ovarian epithelial cancer cell line (A2780) showed a 70–80% reduction in
tumor formation and complete suppression of metastasis to other organs as
compared to untreated controls. By injecting human ovarian epithelial
cancer cell lines (A2780) with WA and cisplatin, the authors demonstrated
that in nude mice with orthotopic ovarian tumors, WA alone or combined
with cisplatin resulted in a 70–80% reduction in tumor development, as well
as complete inhibition of metastases to other organs, as compared to un-
treated mice.
16
5.5.6 Role of W. somnifera in Anxiety
In the laboratory, many recent investigations have looked into the anti-
anxiety qualities of W. somnifera. In rats and humans, the plant has been
shown to reduce anxiety. The aqueous concentration of roots of W. somnifera
has demonstrated anxiety effects after extraction with chloroform and spray
drying in a dose-dependent manner. The antianxiety effect of W. somnifera
was comparable to that of lorazepam, a benzodiazepine medicine used to
treat anxiety disorders. The gamma-aminobutyric acid (GABA) mimic effe ct
of glycowithanolides of the plant, known as withaferin by HPLC, has been
attributed to enabling the antianxiety eff ect of this extract.
17
In a recent study, W. somnifera root extract, that is commercially available
containing 2.8% (w/w) withanolides, was found to be sufficient in decreasing
stress generated by electric foot shock in rats. Other phytochemicals found
in W. somnifera, such as withalongolide-A, an analog of WA and with-
anamides, are thought to be responsible for this effect. Figure 5.6 shows root
and leaf extracts of W. somnifera possess anxiolytic properties, which has
been validated under different paradigms. In another chronic stress study,
rats were subjected to a mild and unexpected foot shock, monitored once a
day for 21 days. The roots of W. somnifera were extracted with aqueous :
ethanol (1 :1) aqueous : chloroform (1: 1) to study, the dry powder was
combined with 0.3% carboxymethyl cellulose. W. somnifera was given once a
day for 21 days, 1 hour before footshock. Porsolt’s swim stress-induced be-
havioral despair test revealed that rats given W. somnifera had lower levels of
behavioral depression. In the stress-induced behavioral despair test, chronic
stress resulted in a significant increase in the immobility period and several
escape failures, as well as a decrease in the number of avoidance responses,
but W. somnifera’s adaptogenic properties signi ficantly altered these effects
in a dose-dependent manner.
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Alcoholism is a significant health concern that has a significant negative
impact on one’s health and general quality of life. An addict’s abstinence
from alcohol usually results in anxiety and despair. The effect of W. somnifera
root extract on ethanol suspended in 0.5% (w/v) carboxymethylcellulose was
investigated in a rat model of ethanol withdrawal in which the rats were given
free access to ethanol for 16 days via a liquid diet (4.6% v/v on day 1, 7.5% v/v
on day 2, and 9% v/v from the third day onwards for 16 days). Animals were
provided an ethanol-free liquid diet starting on day 16. The treatment of
W. somnifera ethanolic root 3 days after withdrawal lowered anxiety in the
mice. The extract’s antianxiety impact has been shown to be related to the
plant’s gamma-aminobutyric acid (GABA) mimic and adaptogenic capabil-
ities, which help to downregulate gamma-aminobutyric acid type (GABA
A
)
receptors. Figure 5.7 shows a graphical abstract depicting pleiotropic roles of
Ashwagandha in neuroplasticity mediated by modulation of multiple path-
ways such as synaptic plasticity, cell survival, and senescence/apoptotic cell
death. Obsessive-compulsive disorder (OCD), characterized by irrational
thoughts and concerns that lead to compulsive activity, is an anxiety-related
mental diseases. Fear of germs or the urge to organize objects precisely are
common symptoms in OCD. Antidepressants that block serotonin (5-hydro-
xytryptamine or 5-HT) reuptake are used to treat OCD. The effect of
Figure 5.6 Root and leaf extracts of W. somnifera possess anxiolytic properties,
which have been validated under different paradigms.
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W. somnifera methanolic aqueous root extract on mice’s marble-burying be-
havior, which is a familiar model for OCD, has been examined. The results of
both parts are comparable to fluoxetine, a common anti-OCD medication that
blocks 5-HT uptake. Both aqueous and methanolic extracts are thought to
have a similar mechanism of action as fluoxetine. At the level of postsynaptic
5-HT receptors, both sections have been shown to promote serotonergic
transmission.
18
When patients have Katigraha (lumbago), they have muscle pain, usually in
the lower back. Due to poor postural habits and psychological variables, ap-
proximately 60% of the general public and 80% of the working population will
experience lower back pain at some point in their lives. One combination to
ease Katigraha is Madhur Dravya (Ashwagandha Taila). Madhur Dravya is one
of the most effective methods for reducing pain and stiffness.
19
5.5.7 Antivenom
Venom hyaluronidases aid in the rapid spread of toxins in humans by dam-
aging the integrity of the tissue’s cellular matrix. From W. somnifera, a hya-
luronidase resister has been isolated. This glycoprotein inhibits the
hyaluronidase activity of viper (Daboia russelii) and cobra (Naja naja) venoms,
as evidenced by a zymogram assay and differential activity staining of skin
tissues. At a concentration of 1 : 1 w/w toxin, it entirely blocked the enzyme’s
training. External application of the plant extract as an antidote to a snakebite
has been provided to victims in some rural parts of India, and appears to have
a scientific basis. Antitoxin–phospholipase A2 (PLA2) glycoprotein obtained
from W. somnifera inhibited the PLA2 activity of cobra venom. The relevance
of these new PLA2 toxin inhibitor groups in snake biology and the creation of
novel therapeutic reagents for snake envenomation has been studied.
20
Figure 5.7 A graphical abstract depicting pleiotropic roles of Ashwagandha in
neuroplasticity mediated by modulation of multiple pathways such as
synaptic plasticity, cell survival, senescence/apoptotic cell death.
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5.5.8 Immunity
In normal and cyclophosphamide-treated mice, the roots of W. somnifera
show cytoprotective and immune-potentiating effects by increasing the le-
vels of interferon (IFN), interleukin (IL)-2, and granulocyte-macrophage
colony-stimulating factor. Iron is abundant in the root, which helps to in-
crease the red blood cell count. W. somnifera has a more subtle influence on
the immune system than merely decreasing the immunological/inflamma-
tory response. The active compound (withanolide A) found in the roots of
W. somnifera enhances T-helper 1 (Th1) cytokine expression and CD4 and
CD8 counts. It also improves natural killer cell activity in immune-
suppressed animals, resulting in a faster recovery of CD4þ T cells. Apart
from the features listed above, stimulated macrophage function, as seen by
increased production of nitrile, IL-2 and TNF-2, reduced IL-4 substantially
while having little effect on IL-10, implying that it only influenced the Th1
cytokine profile . The root powder of this plant stimulates cell-mediated
immunity, immunoglobulin M (IgM) and immunoglobulin G (IgG) pro-
duction, and lymphocyte proliferation and differentiation.
Herbal medications are becoming increasingly popular worldwide as they
have fewer adverse effects than synthetic drugs. Ayurveda asserts that certain
plants have healing properties. A great deal of work continues to be invested
into developing this multipurpose drug-producing plant. However, the data
are disjointed. As a result, this review has attempted to synthesize all ac-
cessible materials. This plant has been the subject of much research for the
past three decades. However, further research into this traditional medi-
cation’s biological activities, efficacies, and mechanisms is still required.
W. somnifera, W. ashwagandha, and W. coagulans are the three species of
Withania discovered in India. The main chemicals discovered in these three
species are withanolides, with some withanolides being unique to each of
them. W. somnifera and W. ashwagandha include withaferin A as the main
component, but W. coagulans has multiple levels of coagulin L. W. somnifera
has a unique thio-dimer of withanolide called Ashwagandhanolide. This
plant has been used for centuries as an antioxidant, adaptogen, aphrodisiac,
liver tonic, antiinflammatory agent, anticancer agent, central nervous system
depressant, hepatoprotective, and astringent, and more recently as an
antibacterial, antihyperglycemic, hypolipidemic , and antitumoral, as well as
to treat ulcers, senile dementia, Parkinson’s disease, and Alzheimer’s dis-
ease. In general, it has increased its therapeutic value. The broad activity
described for the extracts, fractions, and withanolides obtained from this
important medicinal plant bodes well for future studies. Withanolides could
become a significant player in the current pharmaceutical industry. The
active compounds’ pharmacological value will be enhanced through large-
scale isolation, chemical transformations, and synthesis. The pharmaco-
phores of withanolides that are pharmacologically active have yet to be
discovered. All of these benefits demonstrate W. somnifera’s importance in
natural product re search. Despite their vast therapeutic potential,
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Ashwagandha variations require a multifaceted strategy to become more
competitive. It is necessary to improve the pharmacological effects of with-
anolide by selecting and improving chemotypes that produce large amounts
of the desired withanolide.
21
5.5.9 Antiaging
Ashwagandha Rasayana is a well-known Ayurvedic medicine that people of
all ages can use. Nerves, bone marrow. and reproductive organs are all
revitalized by it. Regular consumption is thought to delay aging, correct
sense organ defects and muscular hypotrophy, regenerate reproductive
organs, and boost fertility. Stress, weakness, nervous tiredness, sexual de-
bility, geriatric difficulties, memory loss, muscle weakness, sleeplessness,
and cough can all benefit from it. It is also said to slow down the aging
process and speed up the body’s anabolic processes. Ashwagandha Rasayana
has been found in preclinical tests to have radioprotective properties,
reducing radiation-induced emaciation, decreasing organ weight, and low-
ering serum alanine amino transaminase levels and lipid peroxidation.
Numerous research works have demonstrated that W. somnifera promotes
physical and mental health and rejuvenates the body in weakened situ-
ations, increasing longevity. Ashwagandha also aids in treating epilepsy,
stress, and neurodegenerative diseases (such as Parkinson’s and Alzheimer’s
disease, tardive dyskinesia, and cerebral ischemia) and general well-being.
22
5.5.10 Antidiabetic Effect
The leaf and root extracts of W. somnifera, when administered to diabetic rats
induced with streptozotocin, decreased the blood glucose level and restored
the biochemical parameters. This study showed that the leaf and root extract
of W. somnifera has significant antidiabetic activity. The methanolic root
extract of W. somnifera is evident to resist DPP-4 (dipeptidyl peptidase-4),
a salient target for antidiabetic activity. Catechin is a crucial compound
that is responsible for providing this effect. The root and leaf extracts of
W. somnifera showed hypoglycemic activity on diabetic rats induced by
alloxan, which is similar to the standard glibenclamide. The root extracts of
W. somnifera made into capsules were given to seven patients with non-
insulin-dependent diabetes mellitus. This study revealed this preparation is
comparable with the standa rd oral hypoglycemic drug.
23
5.6 Ethnomedicinal Practice
In India, W. somnifera is widely distributed in the drier parts of the country,
especially in Punjab, Gujarat, Uttar Pradesh, Maharashtra, West Bengal, and
Rajasthan. The various ethnomedical use s of W. somnifera are presented in
Table 5.1
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