Ashwagandha medicinal properties. What are the benefits of ashwagandha, how is it used and what are the contraindications. Why is ashwagandha banned in Russia?

They say that everything new is well forgotten old. Indian traditional medicine is the clearest illustration of this simple truth. But one of the most frequently used remedies is ashwagandha, it is banned in Russia, which is why the incredible properties of this product are not available to Russian consumers.

Withania somnifera: brief description of the plant

In the nightshade family, withania somnifera, or ashwagandha, stands out, which is widely used as a means of Ayurvedic medicine.

Externally, the plant looks quite remarkable:

• This is a perennial shrub of relatively small height (only 35-75 centimeters);
• The branches extend radially from the main trunk in all possible directions;
• The leaves are matte green in color and shaped like an ellipse (oval). They are large in size compared to the shrub itself (up to 12 cm in length);
• The flowers are small, green, bell-shaped;
• Ripe fruits are orange-red in color.

The plant is cultivated mainly in India, in the states of Madhya Pradesh, Punjab, Sindh, Gujarat, Kerala and Rajasthan. Because of this, ashwagandha is also known as Indian ginseng.

The biochemical properties of culture deserve a separate discussion. Its main chemical components are alkaloids and steroidal lactones. Cuscohygrin, an intoxicating oily substance chemically “related” to atropine and cocaine, can be obtained from the plant.

Ashwagandha: medicinal properties and contraindications

As noted above, ashwagandha is known primarily within the framework of traditional Indian medicine, or Ayurveda. In the East, it is considered almost a panacea that cures the following health problems:

1. Metabolic disorders;
2. Weakening of the body's defense system;
3. Depression and chronic stress;
4. The rehabilitation period after major operations or illnesses;
5. Restoration of vital energy for people of older age groups;
6. Exhaustion of the body;
7. Stimulation of the development of the body of adolescents. It concerns not only growth, but also mental abilities;
8. Problems with memory and mental sphere;
9. General calming effect on the nervous system. Thanks to this, Indian ginseng is an ideal sleeping pill, as the Latin name Withania somnifera clearly indicates.

However, some better to abstain from taking this natural medicine:

• Women during the period of bearing or feeding a child;
• Children under seven years old;
• Suffering from severe damage to the excretory system or dysfunction of the thyroid gland.

Medications based on sleeping pills

In order to experience the full power of the healing properties of ashwagandha, you should not rush to get a visa to India. In pharmacies around the world you can see drugs with the label " Ashwagandha» from such companies:

1. "Now Foods";
2. Jarrow Formulas;
3. Himalaya Herbal Healthcare;
4. Organic India;
5. "Life Extension".

As a rule, such drugs are dispensed in the form of capsules with an amount of active substance of several milligrams. Only Starwest Botanicals decided to produce the extract of the legendary plant in powder form.

Cost of drugs varies greatly: from 500 rubles per jar from Now Foods to an impressive 1,500 rubles for Organic India products. Considering that, on average, such a package is only enough for a month of stable use, dietary supplements turn out to be quite an expensive pleasure for the average Russian family.

However, this is not the only obstacle that residents of our country who wish to join the thousand-year achievements of Ayurveda will have to face.

Reasons for the ban on the sale of plants in the territory of the Russian Federation

Herbal medicines with ashwagandha extract have never been included in the register of the State Pharmacopoeia - the main regulatory document concerning medicines dispensed in our country. Moreover, a number of them are directly prohibited due to very rational reasons:

• Such drugs are only biologically active food supplements (BAA). The health benefits of them are highly questionable, although manufacturers actually position their products as medicine. What already falls under the law on advertising;
• Cases of serious side effects of such drugs have been recorded. Thus, a case of two women suffering from kidney failure after taking this dietary supplement received wide publicity;
• The vast majority of herbal medicines are very difficult to license and standardize. This means that checking them for quality and safety is very difficult. It is not known whether Ayurvedic remedies undergo any clinical trials.

These arguments are quite enough to understand why official authoritiesdon't like it“medicines” based on ashwagandha. However, especially purposeful Russians manage to purchase the treasured product on foreign online platforms or, at their own peril and risk, smuggle them from abroad.

Ashwagandha: how to take a man?

The importance of ashwagandha for men's health is difficult to overestimate. Hindus have long used it as the right remedy for restoring potency at an older age. When making tinctures, Ayurvedic healers used the tuberous brown roots of the shrub.

But today you can strengthen your men’s health only by taking tablets with a natural extract:

• The intensity of intake depends on many factors. Since the extract has a strong sedative and hypnotic effect, it should be taken with great caution by men who experience severe physical activity throughout the day. Only 1 capsule is allowed once a day;
• For those who do not need to strain their muscles, the dose can be doubled, to a couple of capsules per day;
• The dosage may be different: it all depends on the concentration of the active substance in the capsule. For example, Himalaya Herbal Healthcare is taken no more than once a day, Now Foods - up to three times;
• This dietary supplement is taken on an empty stomach;
• To achieve a therapeutic effect, it is necessary to take a course of treatment for two weeks. If potency remains at the same level, this is a serious reason to contact a qualified specialist.

The roots and leaves of this shrub are an indispensable medicine for treating insomnia, stress and impotence. But the presence of a large number of contraindications and the lack of clinical trials have led to the fact that almost all products with the name “Ashwagandha” on the label are banned in Russia. Why you should be careful when ordering dietary supplements from abroad.

Video: Ashwagandha and testosterone levels in men

In this video, nutritionist Anton Valuev will tell you how to use ashwagandha correctly and what this substance can affect:

Ashwagandha is an herb and a popular dietary supplement. It has neuroprotective, anticancer effects, increases potency, and can also prevent anxiety.

general information

Withania somnifera, commonly known as Ashwagandha, is an herb used in Ayurveda. Ashwagandha means “Horse Smell,” which is based on the horse-like odor of the fresh root. Popular beliefs say that the use of this herb gives strength and power to the horse. Ashwagandha is an adaptogen. Primarily, this plant is consumed for its ability to prevent anxiety. The calming effects of ashwagandha are also synergistic with alcohol. The herb can relieve symptoms of insomnia, stress due to depression. Ashwagandha can significantly reduce cortisol concentrations and stress-induced immunosuppressive reactions. In addition to reducing stress levels, ashwagandha may improve physical performance in both sedentary people and athletes by lowering levels of “bad” cholesterol. Ashwagandha may improve memory formation and may contribute to improvements in Alzheimer's disease, but more research is needed to more accurately identify the effects of ashwagandha on Alzheimer's disease. More research is needed to determine the mechanism of action of ashwagandha. Ashwagandha is traditionally recommended for cancer patients. It's important to note that there is no concrete evidence that ashwagandha can treat cancer in humans. However, this plant is an excellent remedy for reducing immunosuppression. It may also relieve chemotherapy pain while reducing stress and fatigue. Ashwagandha should not be used to treat cancer, but may be prescribed as part of adjuvant therapy, that is, used as an aid.

Other names: Withania Somnifera, Indian ginseng, horse scent, winter cherry, Solanaceae

Not to be confused with Withania coagulans (another plant)

Interesting to note:

While ashwagandha root extract appears to be virtually non-toxic at this time, high dosages of isolated Withaferin A (an anti-cancer molecule) are toxic; in the worst case, toxic doses are 4 times higher than the therapeutic dosage, which is difficult to achieve using the root extract

There is insufficient evidence of drug interactions with ashwagandha and P450 enzymes.

Represents

Adaptogen

Stress reliever

Remedy from Ayurveda

Productivity Enhancer

Pairs well with:

Terminalia arjuna to increase physical performance

Nrf2/ARE inducers (curcumin or silymarin from milk thistle) to induce HO-1 activity and antioxidant effect

ERK/p38 inhibitors (chemotherapeutic effect)

Notch2/4 inhibitors (chemotherapeutic effect)

SSRI-type drugs (to reduce obsession)

Especially useful:

For anxiety

To increase fertility (male)

Doesn't go well with:

JNK inhibitors (blocks the chemotherapeutic properties of ashwagandha)

MAO inhibitors (can inhibit MAOI-induced inhibition)

Ashwagandha: instructions for use

The lowest effective dosage for a single dose of ashwagandha is 300-500 mg. The optimal dosage is 6000 mg per day, divided into three doses (2000 mg each). While a dosage of 300-500 mg is effective in most cases, a lower dosage of 50-100 mg may be effective only in some cases, for example, to reduce immunosuppression caused by stress and increased anxiety. Ashwagandha root extract is the preferred form of ashwagandha for use as a supplement. Ashwagandha should be taken with food. When used once daily, take it with breakfast.

Sources and composition

Sources and uses

Withania somnifera (from the family solanaceae) is a highly valued medicinal plant in Ayurveda, also called ashwagandha, although it is also called the king of Ayurveda, Indian ginseng (not related to regular ginseng), and also winter cherry. The herb is classified as rasayana in Ayurvedic medicine due to its tonic effect, in modern terms this effect can be called adaptogenic, the herb can also be classified as bhalya (increases strength) and vajikara (is an aphrodisiac). The name Ashwagandha literally translates to “the smell of a horse,” which is believed to be due to two main reasons: the root itself resembles the smell of a horse, and in addition, the root, in its effects, “endows the strength and power of a horse.” In addition to the listed purposes, the herb is traditionally used as an analgesic, astringent, antispasmodic and immunostimulant; In addition, it is used in the treatment of inflammation, cancer, stress, fatigue, diabetes, cardiovascular diseases, while its adaptogenic effect appears in an enhanced form in persons with stress caused by insomnia, weakness, and nervous exhaustion. Ashwagandha also has an immunostimulating effect with properties of suppressing factors that cause a decrease in immunity due to stress. Ashwagandha is a highly valuable medicinal plant; in Indian folk medicine it is used to treat a wide range of diseases, usually primarily associated with stress, impaired immunity (as a result of stress, anxiety and depression (as a result of stress), in the treatment of cancer and inflammation ; this plant does not exhibit toxicity when its root extract is consumed in food.

Compound

Ashwagandha (root unless otherwise noted) typically includes:

Steroid lactones withanone (dry weight of roots - 5.54+/-0.4 mg per g and 18.42+/-0.8 mg per g of leaves), 27-deoxywithanone (1.63+/-0.2 mg per g in leaves and 3.94+/-0.4 mg per g in roots), 27-hydroxywithanone (0.50+/-0.1 mg per g dry weight of leaves and roots)

5,6-epoxy steroid lactones withaferin A (22.31+/-1 mg per g dry weight of leaves and 0.92+/-0.4 mg per g in roots) and 17-hydroxy-27-deoxy-withaferin A (3.61+/-0.5mg/g leaf dry weight and 0.66+/-0.2mg/g root)

Withanolide-type 6,7-epoxy steroid lactones predominantly in the form of withanolide A (root at 3.88+/-0.7 mg per g, leaves at 2.11+/-0.5 mg per g), as well as B-D; There are also options like 27-hydroxy-withanolide B (0.55+/-0.2 mg per g root and 2.78+/-0.5 mg per g leaf dry weight)

Withanoside-type steroidal lactones, usually withanoside IV (0.44+/-0.1 mg per g dry weight of root and 1.60+/-0.2 in leaves) and VI (1.90+/-0.2 mg per g in leaves and 3.74+/-0.2 mg per g in roots), although there are up to 19

Diepoxide variants of withanolides, e.g. 5β,6β,14α,15α-diepoxy-4β,27-dihydroxy-1-oxovitol-2,24-dienolide

Chlorinated variant of withanolide, such as 27-acetoxy-4β,6α-dihydroxy-5β-chloro-1-oxovitol-2,24-dienolide and withanolide Z

12-deoxyvitastromonolide at 2.15+/-0.5mg/g in leaves and 1.90+/-0.5mg/g in roots

Fizagulin (3.46+/-0.4 mg/g in leaves; not found in root) with variants (4,16-dihydroxy-5β,6β-epoxyphysagulin D) and glycosides (27-O-β-d-glucopyranosiphysagulin D)

Ashwagandanolide (dimer of withaferin A, bound to sulfur compounds, which is destroyed by epoxy molecules or "thiowithanolide"), the same molecule, only with a sulfoxide (withanolide sulfoxide)

Other sulfated steroid lactones

Naringenin at 0.50 mg per g dry weight of fruit (not found in roots or leaves)

Catechins at 12.82 mg per g (roots), 19.48 mg per g (fruit), 28.38 mg per g dry weight (leaves)

Gallic acid at 0.18 mg per g leaf dry weight (not found in roots or fruits)

Phenolic acids e.g. syringic acid (0.30 mg per g in leaves), p-coumaric acid (0.80 mg per g in leaves), vanillic acid (0.15 mg per g dry weight of leaves), benzoic acid ( 0.80 mg per g in leaves)

Trigonelline (1.33+/-0.3mg/g in leaves)

Palmitic acid in leaves (3.55+/-0.5 mg per g dry weight) and root (1.18+/-0.2 mg per g dry weight)

Oleic acid in leaves (0.71+/-0.1 mg per g dry weight) and root (0.39+/-0.1 mg per g dry weight)

Linoleic acid in leaves (1.52+/-0.2 mg per g dry weight) and roots (1.31+/-0.2 mg per g dry weight)

Linolenic acid in leaves (4.38+/-0.5 mg per g dry weight) and root (0.15+/-0.1 mg per g dry weight)

The content of polysaccharides in the roots is also noted (196 mg per 20 g of dry root), which consist of 65% sugars (52% arabinose, 22% galactose, 18% glucose, 6% rhamnose and 2% fucose), 22% proteins and 9% from uronic acid. The 28kDa acidic glycoprotein is also present in Ashwagandha roots, which has an inhibitory effect on hyaluronidase. Ashwagandha is a source of withanolide structures, which are either steroidal lactones (four basic ring steroidal structures with five carbon lactone groups at the top right) or their glycosides. These are perhaps the main components (and also special for this plant), while they may be bioactive polysaccharides. Withanolides are present in all plants of the nightshade family, of which Withania Somnifera (ashwagandha) has the highest concentration. Ashwagandha is also characterized by the presence of phenolic compounds, reaching 17.8-32.6 mg per g of dry weight, which is comparable to the content of flavonoids: 15.49-31.58 mg per g of dry weight; in both cases, the highest concentration is observed in the leaves, and the lowest in the roots (medium in the fruits). In an 80% ethanolic extract, the flavonoid content in the roots is approximately 530+/-80 mg per 100 g (quercetin equivalent) and 520+/-60 mg per 100 mg in the leaves. High variability in the amount of active withanolides in nutritional supplements has also been reported due to the lack of a standard for root powder content. Although there is no standard, the amount of active withanolide A (as the main ingredient) and withaferin A is 1% of the leaf dry weight (with minor amounts in the roots) of Withania Somnifera. The 50% ethanolic extract of the roots has been noted to contain Withaferin A (17+/-4 mg per 100 g), Withanoside VI (24+/-3 mg per 100 g), Withanoside IV (79+/-5 mg per 100 g). d), fisagulin (103+/-3 mg per 100 g), 27-hydroxywithanone (22+/-2 mg per 100 g), withanolide A (1340+/-6 mg per 100 g), withanone (315+/- -5), 12-deoxyvitastramonolide (23+/-3 mg per 100 g), vitastramonolide (17+/-2 mg per 100 g), withanolide D is not detected.

Physicochemical characteristics

Withaferin A appears to be more soluble in ethanol than in water; When stored under standard conditions, 90% alcoholic Withaferin A is 90% stable after 6 months and 80% stable after a year.

Options and drugs

There is a preparation called Mamsyadi Kwatha, which includes ashwagandha along with jatamansi (Nardostachys jatamansi) and Parasika Yanavi (Hyocymus niger) in a ratio of 4:8:1; it is used to treat mental disorders.

Molecular targets

Vimentin

While it was initially noted that withaferin A could irreversibly degrade the 56kDa protein in HUVEC cells, it was later discovered that the protein was vimentin, an intermediate substance; thus, it is a protein involved in wound healing, cancer suppression and metastasis. Withaferin A docks to the amino acids Gln324, Cys328 and Asp331 (binding to Cys328 was initially thought to be necessary, but this was found to be unnecessary); and although this bond does not per se block the aggregation of vimethine in the tetramer (involved in its mechanism of action), it contributes to a change in its binding, causing fragmentation and depolymerization. Withaferin A can also participate in the phosphorylation of serine 56 on vimentin (at a concentration of 250-500 nM), which is phosphorylated before half-decomposition, and the C3 carbon on the A-ring of withaferin (two carbon atoms between the epoxy and ketone groups) is critical for such phosphorylation; This phosphorylation was detected in vivo with injections of 4 mg per kg body weight of mice with mammary tumors. Decreased vimentin is not associated with decreased cellular protein levels until chronic incubation; it can occur at low nanomolar concentrations, reducing vimentin content in a concentration- and time-dependent manner, suggesting selectivity. Withaferin A may also reduce the TGF-β-induced increase in vimentin (in the range of 500-1000 nM), although TGF-β has not been shown to prevent increases in vimentin mRNA levels, nor does it reduce overall vimentin mRNA levels. Withaferin A appears to directly bind to vimentin, causing its degradation. Reduction of vimentin levels is considered one of the main mechanisms of action of withaferin A, since it underlies proteasome inhibition (which, in itself, is the basis for many prothyroid cancer mechanisms); it is also a fundamental element in the suppression of metastasis and angiogenesis. It is noted that the binding of vimentin is not unique, as many intermediate filament proteins also undergo similar interactions with withaferin A, although they are less sensitive (requires 4 µm keratin heteropolymer IF or KIF to induce degradation; 1 µm peripherin (PF) and neurofilament triplet protein (NIF)); the inhibitory effects of vimentin (despite being irreversible during co-aging) are reversible three hours after removal of withaferin A from the medium. Due to exposure of all four intermediate filament proteins (KIF, PF, NIF and VIF), there is disruption of microtubules and formation of microfilaments in the cell cytoskeleton, as well as an increase in actin stress fibers at 2 µM withaferin A. All intermediate filament proteins appear to be affected in a similar manner with vimentin exposure (although vimentin is more sensitive), high levels of withaferin A negatively affect cellular structure and integrity; this fact suggests that it is reasonable not to exceed nanomolar concentrations of withaferin A, since low concentrations (100-500 nM) are selective for vimentin, but not for other IFPs.

NF-kB

NF-kB is a locus reflecting inflammation and cell survival, which is inactive due to the IkB inhibitor (directly preventing NF-kB from activation). IkB can be phosphorylated by IKK (IkB kinase), releasing NF-kB, suggesting a positive effect of IKK on NF-kB activity. IKK itself is a complex of two subunits, namely IKK-alpha and IKK-beta, and a regulatory subunit known as NEMO (NF-kB master modulator), which is sometimes called IKKc. IKK-beta has sufficient intrinsic resources to stimulate IkB phosphorylation, inhibiting the formation of IKK-beta and NEMO; this mechanism is considered to be quite novel for NF-κB suppression. Withanolide A showed direct docking with NEMO in the so-called “binding pocket”; energy was -9.44 kcal per mole, primarily due to Glu 89, which is critical for the binding of NEMO to Ser 733 of IKK-beta, and withanolide A is also associated with Glu 99, being involved in binding with Phe 92, Leu 93, Phe 97 and Ala 100 (all of which are involved in NEMO binding to IKK-beta, Arg 101 alone is involved, unaffected by withanolide A), although they are quite unstable in MD-type stimulation. Withanolide A, as already noted, directly binds to NEMO, interfering with the interaction of NEMO with IKK-beta; all of this can lead to decreased NF-kB activation. Subsequently, weaker NF-κB activation will lead to decreased cellular survival of tumor cells and increased other apoptosis-inducing agents. Withaferin A may also inhibit NF-kB activation secondary to inhibition of IkB-alpha degradation (an inhibitor whose degradation is required for the release of active NF-kB), which by blocking IKK-beta (acts to degrade IkB-alpha by phosphorylation) is secondary to MEK1/ERK with an IC50 value of 250 nm, achieving 95% inhibition. This potent inhibition by MEK1/ERK is prevented by special reducing agents, which are thought to act via a thioalkylation reaction between the lactone and cysteine ​​groups on proteins (theoretically, this could also happen with steroidal lactones, since this process is also active on to lactone groups). However, at least one study has shown that NF-kB inhibition (as well as Akt suppression) is partially prevented when vimentin is removed from the cell. Withaferin A suppresses NF-kB through a different mechanism (increasing the effect of MEK1/ERK, which suppresses IKK-beta and prevents IKK-beta from releasing NF-kB from its inhibitor (IkB-alpha); this is thought to be due to protein modification MEK1/ERK due to direct thioalkylation, which also involves vimentin).

20S proteasome

Vitaferin A has been found to inhibit chymotrypsin-like activity in the rabbit 20S proteasome (IC50 4.5 µm) and isolated cancer cells in the prostate (5-10 µm). The ketone structure of Withaferin A appears to be necessarily (90% inhibition at 10 μM was reduced to 30% at the time of the ketone structure decrease) similar to how Celastrol is involved in proteasome inhibition; it was noted that inhibition at maximum concentrations (10 μm) is rather weak when direct inhibition of catalytic activity occurs (catalytic inhibition was measured at 340+/-80 at 0.5-10 μm for withaferin A; for comparison, a direct proteasome inhibitor epoxomicin reached 44510+/-7000 at 10-75 nm). Vitaferin A is known as a link to the specific catalytic beta subunit of the 20S proteasome at Thr1, which leads to its inhibition within three hours of incubation, with a maximum inhibition of 30-60% occurring after 6 hours; the concentration of withaferin A induced by this process was set at 10 nm and was comparable to that of bortezomib. Regarding the manifestation of proteasome inhibition, it did not occur at 0.1 to 1 μm, these doses were found to be ineffective. Withaferin A is known to inhibit proteasome activity in vitro, showing direct binding to the 20S proteasome, typically; however, direct binding of withaferin A does not lead to a strong inhibitory effect on the activity of the proteasome in total activity (occurs even at low concentrations), being minimal. Intermediate aggregation of filament proteins affects the functioning of the proteasome, the ability of withaferin A to inhibit the proteasome is significantly reduced in cells that do not express vimentin; this suggests a biologically relevant mechanism for proteasome inhibition secondary to vimentin degradation. Vimentin degradation is thought to explain the inhibitory proteasome actions of withaferin A. Inhibition of proteasome activity is known to cause accumulation of target proteins (normally degrade), including Bax, IkB-alpha, p27 Kip1. One study (using malignant pleural mesothelioma or MPM cells) showed that inhibition of the proteasome from 10 µM of Withaferin A was accompanied by (expectedly) downregulation of a vast number of anti-apoptotic proteins; there is also an increase in thioredoxin redutase 1 (3.46 times), TFG-beta induced protein 68kDa (2.37 times), TIMP2 (2.2 times) and CARP-1; CARP-1 is a protein involved in cell growth suppression that is critical for the growth prevention properties of Withaferin A. Proteasome inhibition was confirmed in vivo when 4-8 mg/kg withaferin A was administered intraperitoneally to mice (associated with 54-70% inhibition of tumor growth). Proteasome inhibition suppresses the levels of many proteins, but appears to increase the levels of a number of proteins; one such protein, CARP-1, is associated with the growth-inhibitory properties of withaferin A in cancer cells. This proteasome inhibition was confirmed to be relevant in vivo after injections of withaferin A.

Anti-apoptotic proteins

Withanone is noted to have strong (-19.1088 kJ per mole) similarity to a protein known as survinin, particularly in the BIR5 region; survinin is an anti-apoptotic protein in cancer cells; its inhibition will enhance the process of apoptosis in cancer cells. There is also another related protein called mortalin (heat shock protein of the Hsp70 family, which regulates proliferation and stress response, is found in excess in cancer cells), which in complex with p53 sequesters it in the nucleus, increasing its activity in normal cells, but may cause cancer cells to become resistant to chemotherapy. Withanone can also bind to mortalin, as is the case with survinin; binding occurs to segments of mortalin that MKT-077 (known as mortalin ligands) binds to Phe 272 and Asn 139 (withanone lactone ring); bonds can also be made with Asp277 and Arg284 with binding energies ranging from -5.99 to -6.60 kcal per mole. Withanone can be a direct inhibitor of both survinin and mortalin by directly binding to them; and since cancer cells become more resistant when exposed to these proteins, inhibiting these proteins will allow cancer cells to die more easily.

Aurora A

TPX2-Aurora A is a complex formed between the Aurora A protein and the spindle protein TPX2 (after TPX2 is released from importins alpha and beta by GTPase RAN); since this complex prevents PP1 from negatively regulating the genomic effects of Aurora A; Aurora A is an oncogenic agent that is typically overactive in cervical, breast, and pancreatic cancers, so inhibition of Aurora A (or inhibition of TPX2 activity causing indirect inhibition of Aurora A) may be considered therapeutic in various cancers. Ashwagandha exhibits apoptotic properties to weaken cancer cells when TPX2 is not active due to siRNA; With all this, withanone showed direct semi-flexible docking (energy binding index equal to 7.18 kcal per mole) due to hydrogen bonds of His 280 in Aurora A, which is the residue that binds to TPX2, the other part of the withanone molecule binds to Arg 180 and Thr 288 for Aurora A; ultimately, this (and some possible interactions directly with TPX2 at Phe 35 and Lys 83) inhibit the complex formation and downregulation of TPX2-Aurora, this was confirmed in vitro with withanone (15 μg per ml) due to less activation of histone H3 ( target Aurora A) and complex formation due to immunoprecipitation. Withanon prevents the Aurora A and TPX2 complex from forming by physically blocking their interaction, and since the two proteins cannot join, they do not affect the genome together; in the end, this leads to a decrease in their activity; Considering the fact that Aurora A is a substance that promotes the development of tumors, reducing its activity is a therapeutic property for cancer.

Protein kinase C

Protein kinase C is noted to dock with both withanone (energy docking index is -22.57 kcal per mole) and withaferin A (energetic docking index is -28.47 kcal per mole), which leads to its inhibition; two substances attached to protein kinase C undergo a catalytic reaction, and inhibition affects skin cells.

Hsp90

Heat shock proteins (HSPs) are small intracellular signaling proteins that are known as chaperones and are involved in helping to fold and establish other protein structures. Of these, Hsp90 is one of the most important and abundant heat shock proteins (1-2% of the total proteins in the cell under non-stress conditions); beyond it, it can maintain a structure of client proteins with those that are clients of Hsp90, including the androgen receptor, p53, Raf-1, Akt among more than 100 others. Many Hsp90 clients are commonly overexpressed during cancer, so inhibition of Hsp90 activity is considered therapeutic in cancer settings. It can be inhibited by blocking co-chaperones (other chaperone proteins are required to form the active Hsp90 "super-chaperone" complex), and the main co-chaperone is cell division cycle protein 37 (Cdc37). Withaferin A has been noted to inhibit the effects of Hsp90 in pancreatic cancer cells. Withaferin A also binds to Hsp90 (coupling energy of -9.10 kcal per mole and inhibitory constant of 214.73 nm), which is associated with hydrogen bonds, primarily Asp102 and partially Asp54, with van der Waals forces between different amines (Leu48, Asn51, Asp54, Ala55, Leu107, Ala111, Val136 and Phe138), which are not binding units for Cdc37. It appears that withaferin A binding structurally disrupts the process by which Cdc37 binds to Hsp90, which causes inhibition of complex formation. Hsp90 is a heat shock protein that is induced in response to stress, helping in the formation and maintenance of other proteins in the cell; requires a co-chaperone for effective functioning; is hyperactive in cancer cells; Withaferin A appears to slightly inhibit the binding of Hsp90 to co-chaperones that inhibit its functions.

Pharmacology

Blood serum

In mice given 10 mg/kg Withaferin A alone, a Cmax of 8.41+/-1.4 μg/mL was achieved after 3 hours with a half-life of 7.1+/-1.2 hours and total AUC of 55.01+/-8.4 mcg per hour per ml. An aqueous extract of Ashwagandha (0.046% Withaferin A and 0.048% Withanolide A) administered orally to mice at a dosage of 1000 mg/kg body weight rapidly achieved Cmax values ​​of 16.69+/-4.02 ng a ml (withaferin A ) and 26.59+/-4.47 ng per ml (withanolide A) with Tmax of 20 and 10 minutes, respectively. Their respective half-lives were 60 and 45 minutes with AUC values ​​of 1673.10+/-54.53 ng per hour per ml and 2516.41+/-212.10 ng per hour per ml. There are very limited pharmacokinetic data on ashwagandha supplementation, but it appears that oral administration of an aqueous extract of ashwagandha results in changes in blood concentrations of key bioactives in the low nanomolar range; no data available for alcoholic extract.

Distribution

The volume of distribution of Withaferin A was noted to be 0.043 L, and the average residence time was 6.52 hours.

Mineral bioaccumulation

Ashwagandha was noted to be able to reduce the bioaccumulation of cadmium in the body when cadmium was 0.1% of the total chicken diet for 28 days; consuming ashwagandha helped reduce the bioaccumulation of cadmium by 81% (in the liver) and by 55% (in the kidneys) after just two weeks; Ashwagandha's potency is comparable to ocimum sanctum (holy basil), slightly superior to other adaptogens; These two substances are also capable of normalizing changes during oxidative stress to a degree that correlates with the removal of cadmium from the body. Ashwagandha has shown protective properties against lead nitrate (where 80% methane extract was taken at a dosage of 200-500 mg per kg along with lead; a decrease in hematological and liver toxicity was observed). Ashwagandha has the ability to reduce mineral bioaccumulation in the body when taken orally, and the potency (among adaptogens) is comparable to holy basil.

Phase II enzyme interaction

Heme oxygenase 1 (HO-1) is a redox-sensitive antioxidant protein that works by releasing the gas transmitter carbon monoxide. In liver tissues, it was noted that 100 mg of ashwagandha (root extract) per kg body weight failed to change the concentration of GO-1, although the increase in GO-1 expression in response to gamma irradiation was found to be 45.6% higher than in controls measurements; This increased reactivity is accompanied by a complete abolition of oxidative changes such as MDA, glutanion, SOD, catalase and a significant reduction in DNA damage. In addition, it is noted that ashwagandha (as well as brahmi along with green tea catechins) did not show induction in isolated cells (neuroblastoma and pancreas); increased HO-1 induction has been noted with the use of curcumin and/or silymarin (from milk thistle). Ashwagandha appears to enhance the ability of pro-oxidants (including hormetic supplements that cause oxidative damage to the environment) in causing HO-1 induction via Nrf2/Are, but, by itself, it does not interfere with this mechanism. In practical situations, due to oxidative damage to the environment, it will have an effect similar to HO-1 induction.

Lifespan

Rationale

Withanon is able to suppress P21WAF1 in normal fibroblast cells (TIG-1, MRC5, WI38) due to the suppression of P53, despite the increase in p53 levels in cancer cells; due to the positive effect of P21WAF1 on the rate of aging in normal cells, 2.5 μg per kg of body weight withanon, which induced a decrease in P21WAF1, caused an increase of 10-12-fold increase, correlating with an increase in cell lifespan by 20%, not only a relative decrease is noted accumulated molecular damage, which is associated with the fact that withanon increases P21WAF1, it also stands out that withanon cancels the effect of withaferin-A. Withanone appears to downregulate P21WAF1 in cells and upregulates it in cancer cells; this appears to delay the rate of cellular senescence at sufficiently low concentrations.

Neurology

Mechanisms

One study in rats using pentylenetetrazole increased inhibition of MAO-A (109.1%) and MAO-B (70.6%) activity; Ashwagandha glycovitanolides (1.13% root extract) at a dosage of 20-50 mg/kg were able to prevent this inhibitory activity; this has also been noted with the drug lorazepam (500 mcg/kg), suggesting a link to GABA exposure. The possibility of MAO enzyme inhibition is being explored, which may be beneficial in preventing excessive MAO inhibition when combined with different supplements (high levels of MAO inhibition suggest various side effects); Despite the limited confirmation of this fact, it has so far been confirmed in vivo.

Cholinergic neurotransmission

Regarding the acetylcholinesterase enzyme, withanolide has a direct inhibitory effect on acetylcholinesterase (molecular docking at Thr78, Trp81, Ser120 and His442), which is observed in vitro with an IC50 value of 84.0+/-1.5 µM (stronger than 5β,6β -epoxy-4β,17α,27-trihydroxy-1-oxovit-2,24-dienolide and 5β,6β-epoxy-4β-hydroxy-1-oxovit-2,14,24-trienolide at 161.5 μm and 124, 0 µM respectively, but weaker than 6α,7α-epoxy-5α,20β-dihydroxy-1-oxovitol-2,24-dienolide at 50 µM). Injection of 40 mg per kg of a mixture of alkaloids (half withanolide A and half sitoinsides) has been noted to affect acetylcholinesterase with a slight increase in activity in the lateral septum and globus pallidus of the brain, a decrease in activity (indicative of inhibition) noted in the basal ganglia forebrain. When mice consumed 100 mg of aqueous extract per kg of body weight, a slight decrease in acetylcholinesterase activity was observed compared to the control measurement (approximately 10%). Withanolide A directly molecularly docks with acetylcholinesterase, where it can inhibit its functions, but the enzyme activity required for inhibition is very high and cannot be replenished by oral ingestion of these molecules; despite this, a basic aqueous extract of the root showed moderate inhibitory activity in rodents. Consumption of 100 mg of aqueous extract of ashwagandha root per kg of body weight for a month along with a neurological oxidative toxin (propoxur, a pesticide) led to a significant attenuation of memory impairment, but this was not associated with practical changes in acetylcholinesterase levels (propoxur is known to reduce its activity ). Injections of ashwagandha (40 mg alkaloids per kg body weight; half of which was withanolide A) increased M1 receptor binding in some brain regions (lateral and medial septum), while increasing M2 receptor binding in other brain regions (cingulate, piriformis, parietal and retrosplenial cortex); in the case of the frontal cortex, there is improvement in both cases. There may also be positive modulation of cholinergic effects at the level of receptors associated with bioactive substances in ashwagandha, but the practical value of this information when taken orally is not yet known.

Glutamine Neutrotransmission

A relatively small concentration of ethanol extract of ashwagandha (400 ng per ml) is capable of causing neuronal depolarization secondary to increased effects of NMDA receptors, in particular through glycine-binding NMDA receptors, which is partially inhibited by blocking these receptors. Glutamate receptors NMDA and AMPA, which do not appear to be altered by systemic administration of ashwagandha bioactives (withaferin A and sitoindosides), although in epileptic rats both ashwagandha (100 mg per kg body weight) and withanolide A alone (100 μg per kg body weight) kg body weight) may reduce abnormal increases in glutamate (similar in potency to carbamazepine), acting in part to normalize adverse changes in AMPA receptors. The protective effect extends to NMDA receptors. Ethanol extract appears to enhance the effects of NDA by interacting with glycine, although this does not alter glutamine receptors, it may also have a maintenance effect secondary to general neuroprotection. Glioma and neuronal cell models (RA, C6 and IMR-32 differentiated) with 0.01% ashwagandha aqueous extract culture and glutamate excitotoxicity lead to protective effects of ashwagandha on cell morphology and cell death biomarkers, which may be associated with previously noted increase in glutanione concentrations in cells exposed to ashwagandha, or by preventing oxidation-induced changes in NMDA receptors (which predispose cells to glutamate-induced oxidative stress), although preventing oxidative-induced changes in Hsp70 is vital. Ashwagandha appears to exhibit neuroprotective properties against glutamate-induced neurotoxicity, although it is unclear what mechanisms contribute to this and which ashwagandha molecules are involved in this process.

GABA neutrotransmission

GABAA receptors are a subclass of GABA receptors that cause an influx of chloride into the neuron, similar to glycinergic effects (via glycine receptors), which act to suppress the ability of neurons to produce further responses. GABAB receptors are G protein-coupled receptors. Ashwagandha appears to be involved in signaling through GABAA receptors, which has a beneficial effect on sleep; the effect can be prevented by the activation of GABAA antagonists and enhanced by GABAA agonists, the ability of ashwagandha to enhance GABAA effects due to diazepam was noted already at 5 μg of its methanol extract and 100-200 mg per kg body weight when ashwagandha was taken orally in mice. Action through GABAA receptors substantiates the ability of 400 ng per ml of methanol extract to release GnRH. This increase in GABA effects coincides with that of the Scutellaria baicalensis plant, and where it was noted that ashwagandha interfered with the binding of GABA to the receptor (5 mcg caused 20% inhibition, 1 mg caused 100% inhibition), which increased the binding of flunitrazepam (while simultaneously binding the benzodiazepine). Ashwagandha can enhance its effects through GABAA receptors in a manner similar to Scutellaria Baikal, having a beneficial effect on enhancing sleep, as well as having a possible anxiolytic effect.

Dopaminergic Neutrotransmission

Despite the presence of partial remnants of dopaminergic neuroamines in the brain of rats after ingestion of a dopaminergic toxin (6-OHDA) at a concentration of 25-60%, 100-300 mg per kg body weight of oral administration of ashwagandha root extract daily for three weeks did not affect the levels of these neurotransmitters. With respect to spiperone binding to D2 receptors, which are increased following 6-OHDA ingestion, 100-300 mg/kg body weight of ashwagandha may attenuate the increased binding noted with toxicity without altering the binding abilities of these receptors.

Adrenergic neurotransmission

The antidepressant effect of ashwagandha appears to be blocked by pre-administration of prazosin (a general alpha-adrenergic receptor blocker), while depressive symptoms induced by clonidine (an alpha2 and imidazoline agonist) and reserpine (a catecholamine depleter) were prevented by pre-consumption of ashwagandha. at an antidepressant dosage, while haloperidol (a dopamine antagonist) was not affected. These effects are similar to yohimbine, which may block the depressant effects of clonidine to the same extent as ashwagandha; Yohimbine enhances the effects of SSRIs. Andrenergic effects appear to be involved in the antidepressant effects of ashwagandha, and there is also a parallel in the effects exhibited by yohimbine. However, it is not yet clear how ashwagandha exerts these effects.

Serotonin neurotransmission

Supplementation of 100 mg/kg ashwagandha root to normal rats for eight weeks reduces serotonin 5-HT1A exposure in response to agonists while increasing 5-HT2 exposure. A study using ashwagandha notes an increase in plasma serotonin in rats under stress, along with an antidepressant effect; this effect is repeated with other herbs (clitoria trifoliate, brahmi and asparagus racemosus). However, another study on stressed mice notes that ashwagandha root, by itself, is effective in preventing the loss of serotonin (though not completely) due to the reduction in corticosterone. Ashwagandha may reportedly increase 5-HT2 receptor exposure while decreasing 5-HT1A receptor exposure; all this happens against the background of redistribution and changes in the effects of serotonin. 5-HT2 receptors may be involved in the suppression of nNOS activity in neurons (nNOS colocalizes with glutamine NMDA receptors, being involved in NMDA and excitotoxicity), so inhibition of 5-HT2 enhances nNOS activity, ashwagandha may also enhance the effects of these receptors, reducing nNOS immunostaining after stress. It is possible that enhanced effects through 5-HT2 receptors carry some of the neuroprotective effects caused by ashwagandha.

Neuroprotection

Withanolides and sitoindosides VII-X can enhance glutanion peroxidase, superoxide dismutase and catalase in the frontal cortex and striatum of rats after oral administration; a dosage of 10-20 mg per kg has the same effectiveness as 2 mg deprenyl per kg body weight. They also appear to be able to induce antioxidant enzymes in the brain after oral consumption, which may underlie the neuprotective properties of ashwagandha. There is a chain of events that occurs after the serotonergic effect switches from 5-HT1A to 5-HT2; this change inhibits nNOS (reduced nitric oxide formation), this enzyme is the substance that provokes an increase in corticosterone and subsequent memory loss, from which the body protects ashwagandha, contributing to an additional blocking of nitric oxide release. Regardless of the source that caused the increase in serotonergic effects due to 5-HT2 recipes, it prevents an excessive increase in nNOS and nitric oxide, which then leads to the prevention of the formation of excessively high levels of corticosterone, having a neuroprotective and adaptogenic effect. Ashwagandha has been shown to reduce symptoms (orofacial) of tardive dyskinesia in a dose-dependent manner after reserpine-induced toxicity causing tardive dyskinesia in mice. This reversal of symptoms has also been observed in the case of haloperidol-induced dyskinesia, in both cases there are positive symptoms secondary to increased expression of antioxidant enzymes. Dopaminergic neurons are also protected by ashwagandha during morphine withdrawal; this period is characterized by significant localized atrophy of dopaminergic neurons. It is possible that these inductions of antioxidant enzymes are secondary to the induction of heme-oxygenase 1, which, via ashwagandha, acts on KEAP-1 to induce Nrf2 activation; however, one in vitro study using industry funding and PLoS registration found that ashwagandha (particularly isolated withanone) could inhibit premature oxidation-induced cell senescence through an Nrf2-induced and antioxidant response, keeping antioxidant enzyme levels stable near baseline. value equal to 10 µm. This induction was stronger than with genistein, a soy isoflavone. The underlying mechanism associated with antioxidant enzymes may mediate protection against various cognitive diseases associated with oxidative stress. This may be Nrf2 induction, where its effects are thought to be similar to those of many other polyphenolic compounds.

neurogenesis

One aspect of ashwagandha's neuroprotective effects is its ability to induce neurogenesis, which is thought to play a rehabilitative role in cognitive decline. Several isolated molecules have shown such properties, including withanolide A at concentrations as low as 1 μM, withanoside IV and VI, and the aglycone of withanoside IV known as sominon. Withanoside IV (and its cominone aglycone) has been noted to enhance neurogenesis and axonal length of neurons in the presence of Alzheimer's fibrils (Aβ25-35), which is partly due to its protective effects against these fibrils. When incubated in glial cells, ashwagandha leaf extract (800 ng per ml) and withanone (5 μg per ml), but not withaepherin A (200 ng per ml), can promote astrocyte differentiation. At the cellular level, components of ashwagandha can induce neurogenesis and prevent the suppression of neurogenesis by neurotoxins (Aβ25-35). The concentration that is sufficient to produce this effect is small and can be achieved by oral administration. Sominon can induce axonal (maximum potency at 100 nm) and dendritic extension (maximum potency at 1 µM), which is thought to be due to direct phosphorylation of the RET receptor (up to 124.4% of control measurements at 1 µM Sominon) , being a molecular target for the glial neurotrophic factor GDNF; this was confirmed using intraperitoneal injections of sominon (10 µM per kg body weight; maximum effective dosage) in mice in which RET phosphorylation occurred within an hour. Expression of the receptor is not significantly altered, only its phosphorylation, and sominon does not induce GDNF secretion. When studying BDNF (neurological growth factor), ashwagandha leaf extract at 200 mg per kg body weight appears to activate BDNF to 130% of control levels in mice when consumed for a week. Studying the mechanisms of ashwagandha-induced neurogenesis, sominon is a direct agonist for the RET receptor and other components; Ashwagandha can stimulate the production of BDNF (another brain-derived neurotrophic factor that acts through various receptors). In mice given ashwagandha (100-300 mg/kg body weight) orally prior to scolopamine-induced amnesia, the decline in BDNF and GFAP in amnesia was halved, fully recovering at 200-300 mg/kg body weight, and BDNF increased by half compared to control measurements, despite the presence of scolopamine, GFAP only returned to normal. Oral intake of 200 mg/kg of ashwagandha (leaf extract; has higher levels of steroidal lactones than root extract) can completely reverse the effects of scolopamine, which induces a decrease in BDNF.

Stroke and oxygenation

In rats that were pre-administered ashwagandha (aqueous-alcoholic extracts at 1000 mg per kg body weight orally) for 15-30 days before stroke, the supplement was able to preserve post-stroke motor function to a degree dependent on the duration of use, as assessed by foot closure test (40-68%), handle test (50% reduction with 33% recovery), rotarod test (54-70%) with statistical significance after 30 days, in addition to improvements in physical function, lower oxidation was noted lipids and neurological damage.

Stress and anxiety

Ashwagandha is known as an adaptogen due to the presence of withanolide adaptogens (for example, this is influenced by withanoside IV to a greater extent than withaferin A). Adaptogens may reduce the perception of stress, while their mechanisms are not well understood; in the case of ashwagandha, this may be due to preventing stress-induced increases in NADPH diaphosphorase (e.g., nNOS), which may be associated with maintaining a decrease in its negative regulators (serotonin), while preventing positive regulators (corticosterone, glutamate) from increasing during stress. Ashwagandha has significant anti-stress effects, this anti-stress effect may be due to the effects of corticosterone and the suppression of neuronal excitation (nNOS and glutamate) in response to stress. There is also a decrease in the anxiety effect, secondary to the anti-stress effect, but other factors may also be involved (serotonergic and GABA effects). Studying Ashwagandha roots, a 70% ethanol extract of the roots (9.23% yield), which is divided into aqueous fractions (1.43% yield), contains the main bioactive substances; a dosage of 12.5-100 mg per kg is able to increase endurance during swimming (by 35.03-93.68%), reduce tension assessed in stomach ulcers (12-58% protection against swimming and stationary stress). Oxidation in organs such as the liver is significantly reduced, and when compared with ginseng (100 mg per kg body weight), it is noted that under chronic stress conditions, 25-50 mg of ashwagandha extract (withanolide glycoside) per kg body weight was marginally more effective with a decrease in stress biomarkers. The basic aqueous extract of the root also shows effectiveness when administered once at a dosage of 360 mg per kg body weight. There was also a significant fatigue-reducing effect using the rotarod test (strength balance tested immediately after a stress load in a swimming test), where 100 mg of extract per kg of body weight immediately relieved stress fatigue, while after 30 minutes any dosage from 25 to 100 mg per kg body weight was effective. Ashwagandha includes an anti-stress component, which underlies its adaptogenic properties; This fact is associated with a decrease in the circulation of cortisol (see the section on corticosteroid hormones) and an improvement in physical functioning under conditions of psychological stress. 20-50 mg of withanolide glycosides per kg body weight (1.13% yield from root) for five days was able to increase social interaction in rats; this dosage had no effect on locomotion. Standard dosages of basic root extract (100-500 mg/kg body weight) are also effective in socially isolated rats, with lower near-effective dosages increasing the effects. In people under stress, 300 mg of ashwagandha daily for 60 days resulted in improvements in social functioning as assessed by the General Health Questionnaire-28, which noted a 68.1% reduction in “social dysfunction” (with placebo an increase of 3. 7%). Interestingly, the use of ashwagandha as an adjuvant (2000 mg three times daily) in cancer patients led to improvements in social and romantic functioning and well-being. Regarding social interaction (a mechanism associated with serotonin neurotransmission and anxiety), Ashwagandha may promote social interaction, mitigating the negative effects on social function. In rats treated with 20-50 mg of withanolide glycoside (1.13% dry weight of the root; taken daily for five days before the plus-maze test) orally per kg of body weight, comparable to 500 μg of lorazepam (a benzodiazepine) per kg of body weight in reducing anxiety. A similar potency of diazepam can be seen in the case of low dosages of ashwagandha, and is also noted in the case of joint use to enhance the calming effect of alcohol, which acts due to the effects of GABA. Standard dosages of ashwagandha are known to have anxiolytic effects secondary to the effects of GABA; low dosages of ashwagandha enhance the anxiolytic properties of GABA; This includes drinking alcohol. In people with chronic mental stress, 300 mg of ashwagandha showed significant reductions in stress and anxiety; on the stress scale by 44% (placebo - by 5.5%); The General Health Questionnaire-28 showed a 58-59% improvement compared to placebo. However, in people with stress taking 125-250 mg of ashwagandha (11.90% withanolide glycosides; 1.05% withaferin A; 40.25% oligosaccharides and 3.44% polysaccharides) as two divided dosages in one and same period, there was a significant reduction in anxiety and its comorbidities (forgetfulness, lack of sleep, etc.) 300 mg twice daily (1.5% withanolide) along with counseling and breathing techniques was associated with a 56.5 improvement in symptoms % (in the case of placebo – by 30.5%); 250 mg of an ethanol extract of the root twice daily for six weeks in people with increased anxiety (mainly generalized anxiety disorder) was superior to placebo in reducing symptoms on the HAMA rating scale. Ashwagandha's anxiety-reducing properties are particularly strong in humans, although the effectiveness of ashwagandha as an anxiolytic drug is low when used alone (when used alone to treat anxiety); effectiveness is increased if the subject experiences anxiety secondary to stress.

Depression

In animals, ashwagandha exhibits antidepressant effects over a course of several weeks; 20-50 mg of withanolide glycosides (1.13% dry weight of roots) per kg of body weight was slightly less effective compared to 10 mg of imipramine per kg of body weight in reducing the effects of depression. , while reducing immobility in forced swimming testing by 30.4-44.7% in comparison with the control measurement. One study notes that while haloperidol failed to block the antidepressant effect of ashwagandha (suggesting the absence of a dopaminergic mechanism), pravozin was able to prevent the antidepressant effect, suggesting an adrenergic effect. 50-150 mg/kg of total ashwagandha root extract for 14 days prior to testing was able to produce dose-dependent antidepressant effects in rats with a potency statistically comparable to 32-64 mg/kg of imipramine (indicating lesser efficacy), in while a combination of low dosages, namely 50 mg of ashwagandha per kg of body weight and 16 mg of imipramine per kg of body weight, proved to be more effective than monotherapy; The data are based on the helplessness test and the swimming test. This study also notes that brachy acts synergistically with imipramine, but is less effective in isolated forms and less effective when ashwagandha is used instead of brachy; It also turned out that when using dosages of ashwagandha close to effective (50 mg per kg of body weight), together with diazepam, an antidepressant effect is detected; a synergistic effect is also observed with imipramine (replication) and the SSRI fluoxetine. Ashwagandha exhibits antidepressant effects on its own with a potency comparable to imipramine (although a slightly higher dosage is required); is extremely synergistic with other antidepressants, for example, imipramine and fluoxetine. This power has so far been discovered in animals. In individuals with chronic stress, symptoms of depression (assessed by the GHQ-28 and DASS scales) were reduced by 77-79.2% when consuming 300 mg of ashwagandha daily over a 60-day course. One study that measured depressive symptoms while taking ashwagandha in individuals with elevated stress levels found a significant reduction in depressive symptoms along with improvements in stress scores; To date, there are no studies based on depressed individuals who are not under stress.

Memory and learning

In a study of ashwagandha's anti-amnesia properties, ashwagandha was consumed by relatively healthy individuals; there was no increase in memory formation with 100 mg of aqueous extract of the root per kg body weight for one month.] Limited data from relatively healthy rodents suggests that ashwagandha has no relatively nootropic effect on memory formation. In rats treated with scopolamine to induce amnesia, administration of a 50% ethanol leaf extract (high in withanone and withaferin A) may reduce amnesia associated with decreased Arc protein expression in the hippocampus in the frontal cortex. The amnesic effect of beta-amyloid proteins appeared to be effectively prevented by oral administration of 10 mol of withanolide A per kg body weight over a 13-day course; a basic root extract may reduce the amnesic effects of hypoxia by preventing excess nitric oxide production (via nNOS, which increases corticosterone levels and neuronal cell loss). Anti-amnesia effects have also been observed with streptozotocin, injections of which into the blood vessels of the brain are also an example of Alzheimer's disease. The anti-amnesia effect is manifested in neurological toxins that are activated during the induction of Alzheimer's disease; The anti-amnesia effect is due to withanolide A and withanone (although other steroidal lactones may also be active). Hippocampal damage observed during immobilization stress in mice can be partially attenuated by 20 mg hydroalcoholic extract of ashwagandha root per kg body weight for a month immediately prior to stress in the CA2 and CA3 region.

Sedation and sleep

Ashwagandha (100-200 mg/kg body weight) may be as potent as 500 mcg diazeapam in reducing sleep latency while improving sleep quality in mice; GABAA receptors are implicated in this process, as the effects of ashwagandha are inhibited by GABAA antagonists (picrotoxin) and enhanced by GABAA agonists (muscimol). Oxidative stress found in sleep disorders in mice was reversed by consuming 100-200 mg of ashwagandha root per kg body weight for five days. Ashwagandha is believed to improve sleep by having a signaling effect through GABAA receptors, and since this can be enhanced by direct GABAA agonists, this would be a reinforcing effect. In a rat study that did not examine sleep quality, 3000 ashwagandha per kg body weight (above normal dosage) could induce sedation in rats, although lower dosages improved libido, the same effect was observed with 100 mg ashwagandha per kg. bodies of mice in obsessive-compulsive disorder (decreased symptoms, indicating the manifestation of sedation). Studies in rats using high single doses of ashwagandha result in sedation as a side effect of treatment. Human studies include two control groups: 1) Ayurveda group using multiple herbs (10 g total, of which 2000 mg is ashwagandha root; other important components: 1000 mg phyllanthus emblica, 250 mg sida and 250 mg cucubha) ; 2) a group of yogis. It turned out that the consumption of herbs did not have a significant effect on improving sleep quality, but definitive conclusions cannot be formulated due to the large number of herbs. One study using 750-1250 mg of aqueous root extract (equivalent to 6-10 g of root) in relatively healthy subjects showed improved sleep in 6 out of 17 cases; the study was not anonymous. Human studies where ashwagandha is used throughout the day (even if not for stress) are sporadic in improving sleep quality.

Obsession and addiction

At least one study suggests that ashwagandha may help with obsessive-compulsive disorder. Based on the assumption that ashwagandha is used to treat "mood swings", the study was conducted on mice with unstable behavior (establishing a special research model of OCD); found that 10-100 mg of ashwagandha ethanol extract per kg of body weight can reduce OCD-like symptoms; 25 and 50 mg per kg of body weight are considered the most effective; 10 mg per kg body weight did not show any effectiveness; 100 mg/kg body weight is associated with sedation (anti-OCD still persists). Ashwagandha at 10mg/kg bw was as effective as fluoxetine 5mg/kg (both not particularly effective at these doses); however, the simultaneous combination of these two substances prevented OCD-like effects; ashwagandha together with ritanserin (a serotonergic antagonist) negates the effectiveness of each of the substances separately; Ashwagandha consumption acts on OCD through serotonergic mechanisms. Ashwagandha may reduce compulsive behavior by being synergistic when tested with fluoxetine. Animals with alcoholism who then took ashwagandha root (200-500mg/kg bw) showed an increase in resistance to convulsions; in rats undergoing alcohol withdrawal at high doses of ashwagandha (200mg/kg were not found to be effective), 500mg/kg bw showed antidepressant and anxiolytic effects, comparable to diazepam 1mg/kg bw.

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List of used literature:

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Baliga MS, et al. Rasayana Drugs From the Ayurvedic System of Medicine as Possible Radioprotective Agents in Cancer Treatment. Integr Cancer Ther. (2013

Deocaris CC, et al. Merger of ayurveda and tissue culture-based functional genomics: inspirations from systems biology. J Transl Med. (2008)

Chatterjee S, et al. Comprehensive metabolic fingerprinting of Withania somnifera leaf and root extracts. Phytochemistry. (2010)

Namdeo AG, et al. Metabolic characterization of Withania somnifera from different regions of India using NMR spectroscopy. Planta Med. (2011)

Zhao J, et al. Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities. Chem Pharm Bull (Tokyo). (2002)

Choudhary MI, et al. Chlorinated and diepoxy withanolides from Withania somnifera and their cytotoxic effects against human lung cancer cell line. Phytochemistry. (2010)

Pramanick S, et al. Withanolide Z, a new chlorinated withanolide from Withania somnifera. Planta Med. (2008)

Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. Altern Med Rev. (2000)

Ganzera M, Choudhary MI, Khan IA. Quantitative HPLC analysis of withanolides in Withania somnifera. Fitoterapia. (2003)

Mulabagal V, et al. Withanolide sulfoxide from Aswagandha roots inhibits nuclear transcription factor-kappa-B, cyclooxygenase and tumor cell proliferation. Phytother Res. (2009)

Misra L, et al. Unusually sulfated and oxygenated steroids from Withania somnifera. Phytochemistry. (2005)

Alam N, et al. High catechin concentrations detected in Withania somnifera (ashwagandha) by high performance liquid chromatography analysis. BMC Complement Altern Med. (2011)

Misra L, et al. 1,4-Dioxane and ergosterol derivatives from Withania somnifera roots. J Asian Nat Prod Res. (2012)

Girish KS, et al. Antimicrobial properties of a non-toxic glycoprotein (WSG) from Withania somnifera (Ashwagandha). J Basic Microbiol. (2006)

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Hello, dear readers! Have you ever heard of the ashwagandha plant? In Asia, everyone knows about winter cherries! There, the natural gift enjoys about the same reputation as chamomile or milk thistle in our country. Berries are incredibly effective: they help improve your intimate life, cope with depression and improve joint health. And that's not all! Meet: ashwagandha medicinal properties and contraindications.

Cherry antidepressant

Of all the "powers" of the plant, I was most interested in its effect on the nervous system. This is worth talking about separately. The tool perfectly fights anxiety, relieves panic attacks and eliminates anxiety. The natural gift rejuvenates from the inside, therefore treats stress. Fewer destructive oxidative processes occur in the body. Winter cherries are a strong adaptogen. After regular intake, it becomes easier for a person to adapt to new conditions.

Amukkira improves sleep quality, but does not have a motion sickness effect. Drinks and capsules activate the brain, increase concentration and strengthen memory. In addition, the plant protects cells and even promotes their restoration. In the future, scientists plan to use ashwagandha for the treatment of Parkinson's disease.

Calmness and attentiveness double your productivity. How does amukkira affect other systems?

1. Immunity

In India, decoctions are drunk after serious illnesses and operations. The plant “triggers” internal defense mechanisms. These are not just words: as a result of research, it turned out that after taking winter cherries, leukocytes are actively produced.

2. Reproductive system

Amukkira is traditionally considered a male plant, as it contains a plant analogue of testosterone. The fruits help the stronger sex get rid of infertility and impotence. Women often doubt whether they can use ashwagandha. Fears are in vain! Research has been conducted in the United States to confirm or refute the myth. The experimental group, consisting of girls, regularly received drugs based on a natural gift. Six months later, the menstrual cycle improved in women, and the menstruation itself began to flow more comfortably, without pain. Later it turned out that the fruits also help with female infertility.

3. Heart

Indian ginseng slightly lowers blood pressure by removing cholesterol plaques from the walls of blood vessels and slightly thinning the blood. The load on the heart and the risk of blood clots are reduced. Glucose levels drop. By the way, in addition, the product discourages cravings for sweets, so it can be included in the diet in moderation.

4. Joints

Sun-leaved physalis relieves inflammation and eliminates pain. At best, the drug “reanimates” joints and cartilage; at worst, it will slow down the course of the disease. It makes sense to combine it with taking traditional medications.

5. Prevention of cancer and infections

The product contains a huge amount of antioxidant compounds. This helps prevent the formation of tumors and the development of many other diseases. If a person is already sick, decoctions will restore immunity undermined by chemotherapy. Scientists have found that amukkira suppresses the proliferation of cancer cells. This is a huge breakthrough in the fight against cancer.

The roots destroy fungus and infectious agents. Winter cherries are especially effective for lesions of the stomach and genitourinary system. Douching is used for candidiasis. The plant provides immunity to a number of dangerous bacteria (for example, salmonella) and relieves intoxication.

6. Skin

The powerful anti-aging effect also affects the appearance. Drinks prolong youth. A paste made from crushed roots accelerates wound healing. Taking the drug improves the condition of the skin from the inside. The epidermis stops peeling and inflammation goes away. Hormonal metabolism is improved and collagen production is activated.

7. Hair

Lowering cortisol (stress hormone) levels reduces hair loss. Dandruff disappears, psoriasis symptoms soften. Curls grow faster. Removing toxins and stimulating the bulbs restores health and shine. Sun-leaved physalis enhances melanin production and minimizes its loss. This prevents graying.

Winter cherries have a lot of beneficial properties! How to implement them?

How to take Ashwagandha

The drug is usually produced in the form of capsules, powder or liquid extract. Be sure to read the summary! The standard daily dose is 1-2 capsules. Doctors do not recommend consuming more than 5 g of Indian ginseng per day.

If you manage to find the root, you can make an infusion yourself. Pour 2 g of raw material into a glass of boiling water and place on the stove. When it boils, simmer for 15 minutes. After another 10 minutes, you can remove the sediment. Drink no more than 2 glasses a day.

I make a rejuvenating facial toner from the roots. I mix dry lemon zest, ginger rhizomes and amukkira (1:1:2). For 4 tsp. I take a glass of water from the mixture, put it on the fire, let it boil and strain. The skin becomes firm and elastic, but the composition dries out.

Contraindications

Alas, not everyone can accept this natural gift. In pregnant women, Indian ginseng can cause miscarriage. In some cases, the diuretic effect can harm the kidneys. If you have autoimmune diseases, you should stop taking Physalis. Winter cherry does not combine well with a number of medications: sedatives, respiratory, sedatives, etc.

In case of an overdose, side effects may occur: diarrhea, weight gain, fever, chest pain. Be sure to consult your doctor first!

Ashwagandha is an incredibly powerful herbal medicine! It is for this reason that it must be handled with care. If you follow the rules of administration and dosage, you will get mild sedative and stimulating effects.

Friends, hello everyone!

Today I want to tell you about what Ashwagandha is or why its root is called Indian ginseng or the root of life.

This is one of my relatively recent discoveries for myself in the field of Health and Beauty.

You know, I really liked this tool because it is, I would say, multi-purpose, just with a huge range of useful properties, as well as areas of application!

And I love such multifunctional products, it’s very practical when you don’t need to use a bunch of narrowly focused things, but have a couple of tools in your arsenal for health, as they say “all in one bottle”, right? ☺

From this article you will learn:

Ashwagandha - beneficial properties and recipes for use

What is Ashwagandha?

Ashwagandha is a perennial shrub with branched leaves, about a meter high, which grows in some parts of India, in the eastern regions of Asia, as well as in northern Africa, in the Mediterranean region.

Its other names are: sunny-leaved physalis, winter cherry, Ethiopian agol, Indian ginseng.

The medicinal raw material is the root, which in this plant is quite large, fleshy, having a length of up to forty centimeters, and a thickness of about two centimeters.

It is he who has the list of hyper-useful means, which will be discussed later in this article.

How are raw materials prepared?

You know, friends, when I studied the properties of ashwagandha, I really liked the fact that only experienced, competent herbalists are engaged in the preparation of raw materials for this remedy !!!

At the same time, they quite strictly observe all Ayurvedic traditions in order to preserve the maximum amount of useful healing substances of this root!

For me, this information became important when choosing when I made the decision whether to use such a remedy or not.

How about you, friends? Is this important? Write in the comments, I’m very interested!

Chemical composition and main components of ashwagandha root

This healing root contains a large number of powerful biologically active substances.

Among them there are many phytosterols and alkaloids (such as isopelletierine, anaferine, somniferine).

Contains natural plant antibiotics that can kill pathological microorganisms, even such as streptococci, gonococci, staphylococci!!!

What are the benefits of ashwagandha?

Ashwagandha is the main plant in the practice of eastern medicine - Ayurveda - the Vedic healing tradition of India.

There this plant is also called the “queen of sleep”, as it helps treat insomnia.

Ashwagandha (winter cherry) is one of the world's most powerful herbal remedies, traditionally used in Ayurvedic herbal medicine to help the body adapt to physiological and psychological stress.

What else does Ayurveda say about the beneficial properties of ashwagandha:

• This is an excellent tonic for the entire body, a strong adaptogen, and a powerful stress reliever.
• If you use it regularly, you can completely cure chronic fatigue, accumulated nervous tension, relieve stress, remove depression, and get rid of insomnia, since taking it quite significantly increases the level of vital energy, otherwise called ojas in the Eastern Indian tradition.
• After all, Ayurveda claims that dangerous diseases, degenerative processes in the body, difficult-to-treat infections, difficult-to-treat inflammations, and so on, begin precisely when the level of ojas (Life Energy) drops! And ashwagandha root helps prevent all this!

Ayurveda specialists recommend its use for:

• General metabolic disorders.
• With weakened, nervous fatigue.
• For sexual weakness, as it is recognized by experts as an excellent aphrodisiac.
• During periods of recovery after illness, after operations, after injuries.
• Its use is especially recommended for elderly people to activate all life processes in the body.
• When the body is exhausted.
• Promotes faster growth and development of the child's body. This is especially true for children who are lagging behind in their development.
• When there is poor blood circulation, which causes oxygen starvation (hypoxia) of all cells of the body, including brain cells.
• For multiple sclerosis, paralysis, rheumatism, problems with the respiratory tract, colds, coughs, as well as infertility problems.
• Ashwagandha enhances stamina (especially male sexual stamina) and supports adrenal health.
• Calms the nervous system and promotes good sleep.

Ayurvedic healers call this plant rasayana, which means "a plant with a strong rejuvenating effect on the human body."

In European medical practice this is called an antioxidant.

Interesting facts about the plant:

• Conducted studies prove the extraordinary effectiveness of ashwagandha in the treatment of diseases of the male genital area, in particular, impotence, spermatorrhea, insufficient amount of sperm, its poor quality (low active spermatozoa), inflammation in the prostate gland.
• And for women, taking this drug will bring relief from menstrual pain, menstrual irregularities, and infertility. Long-term use (with a course of up to five months) normalizes the level of hormones in the female body, heals fibromyoma, mastopathy, and also restores women's health after childbirth.
• For men, it will be important that taking the root of this plant helps to increase muscle strength, increase endurance, raise the body's energy to a qualitatively new level, and improve performance.
• For schoolchildren, students, the elderly, it will be interesting to know that this drug improves brain function, increasing the level of information memorization, the ability to concentrate, and think logically.
• It has excellent efficacy in the treatment of tumors, including the presence of malignant tumors.
• The drug has proven itself perfectly in the treatment of problems of internal organs, disorders in the gastrointestinal tract, with hemorrhoids, dysbacteriosis, bloating, diarrhea.

In what form should I take and where to buy ashwagandha root?

Most often, ashwagandha preparations are available in the dosage form of capsules with a powder inside.

Take 1 - 2 pieces per day with meals.

When it comes to the root, a typical traditional dose of ashwagandha is 1 to 2 grams of the root (boiled in milk or water for 15-20 minutes), taken 3 times a day.

Contraindications for use

Ashwagandha is considered a safe herb, but the root is not recommended for pregnant or breastfeeding women, young children, or anyone with severe kidney or liver disease.

According to one animal study, ashwagandha can increase thyroid hormone levels. For this reason, it should not be used by people with hyperthyroidism.

This is the healthy ashwagandha root.

I hope, friends, this information will be useful to you and serve you well ☺

Good health to everyone and bye bye!

Cover photo @marilina https://depositphotos.com/

Ashwagandha (Withania somnifera) is also known by the names: Indian Winter Cherry and Indian Ginseng. It is one of the most important herbs in the world and has been used for thousands of years.

She is a component Rasayana- a set of formulas that prolong youth and health on a physical and mental level, and also make a person more satisfied in life. In Ayurveda it is called Sattvika Kapha Rasayana- formula , which is an adaptogen, and helps to overcome.

Most commonly, Ashwagandha is used as a powder (Churna) that can be mixed with water, ghee or honey. It improves the functioning of the brain and nervous system, and also strengthens memory. The reproductive system benefits, immunity increases, and cells are protected from damage by free radicals.

The name “Ashwagandha” itself is translated from Sanskrit as “the smell of a horse” - perhaps it reflects, on the one hand, the characteristic aroma of the herb, and on the other, the vitality and reproductive power of the horse (or horse), which implies support for the health of the male reproductive system.

According to Paul Sebastian’s work “Ayurvedic Medicine: The Principles of Traditional Practice” (Pole, Sebastian. Ayurvedic Medicine: The Principles of Traditional Practice), the main beneficial properties of the plant are to stimulate, support and rejuvenate the body’s functions. Ashwagandha has been praised for its “dual” effects: simultaneous stimulation and calming.

Stress can lead to fatigue, accompanied by agitation and poor sleep. Ashwagandha supports the health of the nervous system by nourishing it and stimulating its activity. As a result, stress has less impact on the nerves, and side effects such as poor sleep and anxiety go away naturally. This effect of the plant makes it an important part of the body's rejuvenation process.

In addition to the stimulating and calming effect, Ashwagandha is also useful in the following ways:

• Supports overall immune system health
• Relieves mental tension
• Improves sleep quality
• Ensures reproductive system health in men and women
• Increases tone, overall energy level, strength, endurance, vitality and overall physical activity
• Helps keep your back and body healthy.

Traditional use in Ayurveda

In Ayurveda it is used to eliminate and. Ashwagandha has a warming, oily and accumulative nature, so in high dosages, it can lead to and also cause a buildup of toxins in the body.

At the same time, if the correct doses are taken, Ashwagandha is useful in that it strengthens and nourishes, balances vata dosha, and ensures healthy muscles and reproductive organs.

Ashwagandha: application

Of course, specific instructions for use will depend on the form of release. Usually, this remedy is available in the form of a powder (Churna) and capsules (tablets). There is also a liquid extract.

A common use is as a powder mixed with warm milk and honey. It is taken before bed - this method balances, promotes sound, healthy sleep, and increases vitality.

Usual dose: a quarter to half a teaspoon 1-2 times a day.

Another option: with ghee and honey in equal quantities (in this case, honey and ghee are anupanas; anupana is a "carrier" that enhances the effects of a drug or food). If you add sugar, you get a cooling effect - it can be used instead of honey during the hot season.

Also, ghee and sugar as a carrier are suitable for supporting the female reproductive system and joints. In general, Ashwagandha is just as beneficial for women as it is for men.

Capsules or tablets are in some ways more convenient to take, especially if you're on the go or don't like the taste of the powder. The liquid form is also quite convenient to take and is easy to digest. However, it is worth noting that the powder may be a little more effective (by analogy with).

Side effects

Large doses of Ashwagandha can lead to abdominal discomfort and diarrhea (data from the work of Paul Sebastian mentioned above).

Ashwagandha: contraindications

In India, the plant is traditionally used during pregnancy, but in the West this is not recommended. The fact is that it can cause antispasmodic activity in the uterus, and experiments with animals have shown that at high doses, miscarriages occurred in animals (experiments on animals are a harsh thing, but in this case here are simply facts from the works of Paul Sebastian and Deepak Chopra ).

If Ashwagandha is used along with respiratory depressants, it can cause problems (according to naturalmedicines.therapeuticresearch.com).

From the point of view of Ayurveda, if you have elevated or a lot of toxins in your body, you need to use this remedy with caution.

You can buy Ashwagandha in Ayurvedic stores. Price: from 300 rub. for powder and capsules, and more than 1000 rubles. for liquid extract.