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SCIENTIFIC STUDIES ON INGREDIENTS

1. Jatamansi (Nardostachya jatamansi)

 

Sleep disorders have a comparatively high prevalence worldwide and create a burden on the health system. Pharmacological agents used for insomnia are asso-ciated with considerable side effects. Therefore, searching for safe and effective agents from plant-based natural sources is a worthy effort.Jatamansi(Nardostachys jatamansi DC.) rhizome has been recommended for insomnia and mental conditions in the Indian system of medicine.

Data suggested that Jatamansi did not produce a significant effect on the behavior of animals. It reduced the horizontal activity significantly (P < 0.001) in the open-field apparatus. The test drug did not show a significant decrease in latency of fall-off time in rota-rod performance in mice. Still, it exerted a significant effect by a reduction in latency of onset of sleep (P < 0.01) and also extended the total duration of sleep (P < 0.05) in al-bino mice in comparison to the control group.

This study shows that Jatamansi rhizome powder possesses CNS depressant activity without affecting gross behavior and muscle coordination in rats.

Nardostachys jatamansi DC. belonging to the family Valerianaceae is used for the treatment of depressive illness, convulse- ive affections, palpitation of the heart, intestinal colic, high blood pressure, and dysmenorrhea.  The Ayurvedic Pharmacopeia of India recommends its rhizomes in skin diseases, cellulitis, disturbed mental state, and insomnia. It is used as a substitute for valerian and as an ingredient of many Ayurvedic drugs for mulations such as Mamsyadi Kwatha used for sleep disorders.  Sesquiterpenes and coumarins are major active principles in the herb. Major sesquit- erpenes from oil are d-nardostachone, valeranone and jatamansone.  The active principle, jatamansone is reported to have tranquilizing, antiemetic, sleep-regulating, and anticonvulsant activities. Reported activities in essential oil are antimicrobial, antifungal, hypotensive, anti-arrhythmic, and anticonvulsant.  An alkaloidal fraction from rhizome possesses hypotensive action.

Most experimental studies have been conducted on various extracts, essential oils, or isolated components from Jatamansi. However, in Ayurveda, the drug is used clinically as a whole in crude form, not in an isolated component. Crude drugs and their isolated fraction do not behave similarly in a biological system and therefore may not have similar activity. Hence, a crude form of the herb is required to be investigated for the presence of activities re-ported in isolated components or fractions. Keeping this in view, the central nervous system (CNS) depressant activity of the whole powder of Jatamansi rhizome was evaluated on experimental models.

Reduction in locomotor activity may lead to soothing and sedation as a result of reduced excitability of the CNS. The test drug did not produce significant muscle relaxant activity on Rotarod performance in albino mice, indicating the absence of muscle relaxant activity in the rhizome of Jatamansi.

Jatamansi potentiated the effect of pentobarbital by shortening sleep latency and prolonging total sleeping time in Swiss albino mice, though not as remarkable as that of diazepam. Earlier reports suggest that the increase and decrease of pentobarbitone-induced sleep time can be a useful tool for examining the stimulatory or inhibitory effects on CNS, especially for investigating influences on gamma-aminobutyric acid (GABAA) ergic systems in CNS.

The previous report suggested that ethanolic extract of Jatamansi significantly altered locomotor activity. Jataman- sone exerted a tranquilizing effect in mice and monkeys and a significant reduction in hyperactivity and improvement in restlessness and aggressiveness in hyperkinetic children similar to amphetamine. Alcoholic extract of Jatamansi root increased the level of GABA on acute administration and increased the levels of most of the central biogenic amines and inhibitory neuro-transmitters on chronic administration. Thus, earlier studies indicate isolated compounds or extracts exert highly significant sedative activity while data from this study indicates a crude form of drug administered at the recommended dose produced comparatively mild CNS depressant activity.

This study shows that Jatamansi rhizome powder possesses CNS depressant activity without affecting gross behavior and muscle relaxation in animals. It can be helpful in the treatment of insomnia, as claimed in Ayurveda by clinical trials.

Potential Uses of Jatamansi Due to Antioxidant & Stress-relieving Activity:

The hydro-ethanolic extract of jatamansi was evaluated for its anti-stress effect due to its antioxidant properties in a rat model. This may indicate the potential anti-stress property of jatamansi. However, more studies would be needed to understand to what extent it may be helpful for humans.

Potential Uses of Jatamansi Due to Anti Cataleptic Activity:

The hydro-ethanolic extract from the root of jatamansi was evaluated for its antioxidant and anti-cataleptic (i.e. against a state of marked loss of voluntary motion in which the limbs remain in whatever position they are placed) activity in a rat model.

Potential Uses of Jatamansi Due to Nootropic Activity:

The ethanolic extract of jatamansi was studied in a mice model for its potential to enhance memory and learning and reverse amnesia. This may indicate that, jatamansi might have some effect on restoring memory and that it may help with dementia. However, the studies are insufficient to indicate the exact effect of jatamansi on humans.

Potential Uses of Jatamansi Due to Antioxidant & Stress-relieving Activity:

The hydro-ethanolic extract of jatamansi was evaluated for its anti-stress effect due to its antioxidant properties in a rat model. This may indicate the potential anti-stress properties of jatamansi.

Potential Uses of Jatamansi as an Antidepressant:

The extract of jatamansi was studied and it was found to have antidepressant activity, which was determined in the mice model. This suggests that it might be beneficial for people suffering from depression because of sleep disturbances.

 

2. Ashwagandha (Withania somnifera)

 

The botanical Withania somnifera (L.) Dunal, family Solanaceae, is widely known as “Ashwagandha”, a Sanskrit name deriving from its use in traditional medicine in India. Withania somnifera (WS) enjoys a formidable reputation in Ayurvedic medicine as a Rasayana herb, i.e., one that can rejuvenate the body and promote the health of all tissues. WS is, therefore, also classified as an adaptogen: an agent that promotes homeostasis of the whole body not only by one specific pharmacological mechanism but by eliciting complex responses as well. The reputed properties of WS include the ability to improve concentration, memory, and mood, as well as providing resilience against pathogens and disease.

Anti-anxiety effects were observed for root extracts, leaf extracts, and isolated compounds from WS, in cluding with aferin A  and a mixture of sitoindosides VIl. WS ex-tracts produced from leaf or root and with various solvents (water, ethanol, methanol, hydroalcoholic), solvent ratios, and extraction methods all produced anti-anxiety effects, suggesting the possibility of multiple bioactive compounds. In addition, WS extracts potentiated the effects of well-known anti-anxiety drugs. A subtherapeutic dose of a WS root extract potentiated the anti-anxi- ety effect of a subtherapeutic dose of diazepam in a rat model of social isolation.

The elevated plus maze test has been validated to assess pharmaceutical agents for anti-anxiety activity in rodents.

The marble burying test, in which increased marble burying is said to indicate anxiety-like behavior, was another commonly used test. However, the validity of this test as a measure of anxiety is questionable. Other measures used to evaluate anxiety-like behavior in rodent studies included the open field test, social interaction test, novelty-suppressed feeding latency test, and pentylenetetrazol-induced defecation and urination. A zebrafish model of benzo[a]pyrene-in- reduced neurotoxicity used the light/dark preference test and the novel tank diving test to assess anxiety-like behavior WS root and leaf extracts exhibited noteworthy anti-stress and anti-anxiety activity in animal and human studies. WS also improved symptoms of depression and insomnia, though fewer studies investigated these applications. WS may alleviate these conditions predominantly through modulation of the hypothalamic-pituitary-adrenal and sympathetic-adrenal medullary axes, as well as through GABAergic and serotonergic pathways. While some studies link specific withanolide components to its neuropsychiatric benefits, there is evidence for the presence of additional yet unidentified active compounds in WS.

While benefits were seen in the reviewed studies, significant variability in the WS extracts examined prevents a consensus on the optimum WS preparation or dosage for treating neuropsychiatric conditions. WS generally appears safe for human use;

WS has seen an increase in worldwide usage due to its reputation as an adaptogen. This popularity has elicited increased scientific study of its biological effects, including a potential application for neuropsychiatric and neurodegenerative disorders.

 

3. Valerian wallichi (Tagar)

 

Valerian is one of the medicinal plants used to reduce anxiety and sleep disorders. Valerian contains 150 to 200 different substances including volatile oils, ketones, phenols, iridoid esters such as valepotriates, alkaloids, valeric acid, amino acids like aminobutyric acid, arginine, tyrosine, glutamine, and noncyclic, monocyclic, and bicyclic hydrocarbons.¹ Valerian/cascade mixture significantly decreased the latency time for sleeping and increased total sleeping time. The mixture significantly increased the non-rapid eye movement sleep time, while rapid eye movement sleeping time was decreased. Electroencephalography investigation indicated decreased awakening and increased total sleep time.  It has also been administered as a sedative-hypnotic herb for many years. Valepotriates and valerenic acid found in valerian root are responsible for the plant’s sedative and anxiolytic effects.” Assisting sleep effect of valerian/cascade mixture was shown to be due to the upregulation of gamma-aminobutyric acid A (GABA) receptor. The valerenic acid contained in valerian inhibits the enzyme system responsible for the catabolism of GABA.17 Valerian and its constituents (e.g., valerenic acid) serve as GABA agonists, and the effect of the plant on GABA receptors is similar to the effect of benzodiazepines.¹ The mechanism of action of valerian has been explained by several theories. The constituents of valerian may increase GABA concentrations and decrease central nervous system activity by inhibiting the enzyme system responsible for the central catabolism of GABA. Valerian may also stimulate the release and reuptake of GABA and bind directly to GABA receptors. According to the available evidence, valerian may be the most promising agent for assisting sleep’ that is also considered a parrial Agonist of the 5-hydroxy terpyridine 2A receptor that boosts melatonin release. Antidepressant and mood-stabilising effects have also been proposed for valerian, which could be due to the plant’s ability to interfere with noradrenergic and dopaminergic neurotransmitters, especially serotonin and GABA.” Over the past few decades, the root extract of valerian has been widely used as a flowering plant to treat sleeping disorders in Europe. Ziegler et al.

compared the effects of a six-week treatment with valerian extract (600 mg/day) and oxazepam (10 mg/ day) in 202 patients. They found that both groups enjoyed an enhanced sleep quality, while valerian was at least equally effective as oxazepam. The effects of valerian and oxazepam were perceived to be very good by 83% and 73% of the patients, respectively.

The US Food and Drug Administration lists valerian as a food supplement with no contraindications for its use.  Valerian is a perennial herb native to North America, Asia, and Europe whose root is believed to possess sedative and hypnotic properties.

Today, valerian root extract is an accepted over-the-counter medicine for treating stress and nervous tension, disturbed sleep patterns, and anxiety in Germany, Switzerland, Belgium, Italy, and France. Valerian can also affect sleep quality in patients with multiple sclerosis. Studies have indicated that valerian is effective in treating anxiety and depression in menopausal women. Valerian is a safe herbal remedy in HD. Valerian has also shown efficacy with few or no adverse effects when used correctly and following expert recommendations.

It is thought valerian might be a safe herbal medicine for use in HD, considering the high prevalence of sleep disorders, depression, and state anxiety and their related complications in HD patients. To date, there are contradictory results on the effectiveness of valerian on these issues in this group. Previous studies have examined the effect of valerian on sleep disorders or depression and state anxiety in non-HD patients. In the present study, the effect of valerian on sleep quality, depression, and state anxiety was explored in HD patients.

Tagara group In this group, 16 patients were registered, and the study was completed with 15 patients. Tagara Churna (powder of V. wallichii rhizome) in the dose of 4 gm with milk was administered 3 times a day after food for 1 month.

Tagara group provided a significant improvement in the duration of sleep by 55.17%, in the initiation of sleep by 76.00%, in disturbed sleep by 69.58%, and in disturbances in routine work by 73.95%. This difference was statistically highly significant (P < 0.001)

Tagara provided significant relief in An- gamarda (78.33%), Shirogourav (72.60%), Shirashoola (55.83%), Jrumbha (26.41%), Glani (36.79%), Bhrama (86.02%), Shrama (80.45%), and Klama (83.33%)

It is obvious from the foregoing study that Tagara  provided significant relief in signs and symptoms of the patients of Anidra. It can be stated that Tagara provided better relief to the patients of Anidra. Thus, it can be concluded that Tagara which has the property of Nidrajanana (sedative and hypnotic) was found to be more effective in Anidra.

 

4. Hyoscyamus niger (Khurasani ajwain)

 

Hyoscyamus niger belongs to the family Solanaceae. It is also known as “henbane”. The roots, leaves, fruits, and seeds of the plant contain atropine, scopolamine, and hyoscine. In ancient times, the plant was used to treat pain and insomnia and as a local anesthetic. In the Middle Ages, the use of Hyoscyamus was associated with witchcraft and later was used as an anesthetic (Lee,2006a,b; Orbak, Tan, Karakelle Oglou, Alp, Akdag, 1998; Sands & Sands, 1976). Currently, the inflammatory, analgesic, antipyretic, and antiparkinsonian properties of the plant are under investigation (Begum etal., 2010; Mateus,

The plant is usually consumed by mistake because of its similarity with other edible plants or by children, especially in areas of low socioeconomic level (Doneray, Orbak, & Karavelioglu, 2007). The plant can also be used intentionally by users of these substances, causing illusions (Spoerke etal.),

Henbane is used in traditional herbal medicine for ailments of the bones, rheumatism, toothache, asthma, cough, nervous diseases, and stomach pain. It might also be used as an analgesic, sedative, and narcotic in some cultures.  Adhesive bandages with henbane extract behind the ear are reported to prevent discomfort in travel-sick people [medical citation needed] Henbane oil is used for medicinal massage.

Hyoscyamine, scopolamine, and other tropane alkaloids have been found in the foliage and seeds of the plant.  The standard alkaloid content has been reported to be 0.03% to 0.28%.

Its psychoactive and pharmacological effects are a result of these alkaloids exerting an anticholinergic mechanism of action which blocks the function of acetylcholine in the brain and antagonizes the muscarinic receptors.  This results in an altered state of consciousness, hallucinogenic experiences, and typically, delirium. This mechanism of action is not only linked to dangerous effects and accidents, but dementia as well.  Since toxicity/lethality is such a major concern with plants like henbane; many traditional preparations of henbane or other similar scopolamine-containing plants were designed to be applied transdermally, often in “magical ointments” by herbalists.

 

5. Lactuca serriola (Tukh-ME-Kahu)

L. serriola has a conventional use in the treatment of headache, insomnia, nervousness, hypertension, palpitation, fever, etc. It has been found in a recent finding that L. serriola contains active components that have biological functions in disease control. They display diverse pharmacological activities, including sedative, hypnotic, diuretic, antioxidant, anesthetic, antispasmodic, anticancer, antibacterial, bronchodilator, and vasorelaxant.

The L. serriola plant has traditional medicinal uses, like a sedative, hypnotic, expectorant, cough suppressant, purgative, demulcent, diuretic, antiseptic, vasorelaxant, and antispasmodic. Thus, it is used to manage bronchitis, asthma, pertussis, gastrointestinal, and various other ailments.

The whole plant is rich in a milky sap that flows freely from any cut on the plant. The milky sap becomes hard and dries upon coming in contact with air. The sap contains “Lactucarium,” used in medicine for its medicinal properties. such as anodyne, antispasmodic, digestive, diuretic, hypnotic, narcotic, and sedative properties. Lactucarium neither has the effect of a feeble opium, but without its tendency to cause digestive upsets, nor is it addictive. It is taken internally in the treatment of insomnia, anxiety, neuroses, hyperactivity in children, dry coughs, whooping cough, rheumatic pain, etc. Concentrations of Lactucarium are low in young plants and most concentrated when the plant comes into flower. It is commercially collected by cutting the plants’ heads and scraping the juice into China vessels several times a day until the plant is exhausted. An infusion of the fresh or dried flowering plant can also be used.  The fixed oil from the seeds is said to possess antipyretic and hypnotic properties

Analgesic and Sedative Activities

L. serriola exhibited dose-dependent potent analgesic activity. Fayyaz et al. reported that the methanolic extract of L. serriola could produce significant analgesic activity.

Furthermore, Wesołowska and colleagues evaluated the analgesic and sedative properties of Lactucin and its derivatives. lactucopicrin and 1 beta, 13-dihydrolactucin in mice, the results revealed that Lactucopicrin is the most potent analgesic of the three tested compounds. Lactucin and lactucopicrin, but not 11-beta, 13-dihydro-lactucin, also showed sedative properties in the spontaneous locomotor activity test.

Antioxidant Activities

Kim manifested the antioxidant activity of L. serriola by measuring the radical scavenging effect on DPPH (1, 1-diphenyl-2-picrylhydrazyl) radical and found that the methanolic extract of the aerial parts of L. serriola showed intense radical scavenging activity. Besides, El-Esawi et al. showed the effects of genetic transformation and hairy root induction in enhancing the antioxidant activities of L. serriola L.

Anticancer Activities

Elsharkawy E and Alshathly M found that the methanol extracts prepared from leaves and stems of L. serriola showed cytotoxic activity against A549, HePG, MCF7, and HCT116.26

Anxiolytic and Antidepressant Activities

A randomized placebo-controlled double-blind trial of L. serriola Linn seeds on mixed anxiety depressive disorder has shown a significant effect in reducing anxiety and depressive symptoms.

Lactuca sativa, a member of the Compositae family, is the most popular herb used in salads in Korea. In addition, lettuce seed oil has been used as a sleeping aid and for pain and inflammation relief in folk medicine for a long time. The extracts of L. sativa seeds with crude methanol and petroleum ether have been reported to have a time- and dose-dependent analgesic effect in the formalin test in addition to a dose-dependent anti-inflammatory activity in a carrageenan model of inflammation.

Therefore, in the current study, the hydro-alcoholic was prepared from varieties of commercial lettuces, and its sleep-prolonging effect was examined with the analysis of the content of lactucin and lacucopicrin.

Therefore, in the current study, the hydro-alcoholic was prepared from varieties of commercial lettuces, and its sleep-prolonging effect was examined with the analysis of the content of lactucin and lacucopicrin, which were known to be sleep-inducing compounds. Moreover, romaine lettuce extracts, which showed a shorter sleep latency time than other lettuce, were assessed for their sleep latency and sleep duration in a pentobarbital-induced sleep model, and for their radical-scavenging activity against oxidative stress.

Pentobarbital-induced sleep test

The experiments were performed from 1:00 to 5:00 pm; the mice were not fed for 24 hours. A 0.9% solution of physiological saline was used to suspend all the samples. The lettuce extract was orally administered in both groups (80 mg and 160 mg/kg), such that the observers were blind to the individual treatment. The mice were injected with the pentobarbital (hypnotic dose: 42 mg/kg) 40 min later. Finally, the mice were housed individually and the sleep latency and duration were measured using the method described by Yang et al. [13]. Mice that did not sleep 15 min after the injection were excluded from the experiment.

Traditionally, lettuce has been suggested to have a sedative-hypnotic property. Lactucopicrin and lactucin are the major active compounds of lactucarium and were reported to have analgesic activity equal to or greater than that of ibuprofen in mice. They also showed a sedative activity as revealed by measuring the spontaneous movement in mice. Lactucin, a sesquiterpene lactone of the Lactuca species, was reported to have a sedative property in the spontaneous locomotor activity test. The lettuce opium is known to have these analgesic antitussive, and sedative properties because of the lactucin; its ester lactucopicrin has been used in Europe for centuries. However, no analgesic and sedative effect has been reported for lactucopicrin in the other report. Unlike lactucopicrin, lactucin is presumed to be the predominant substance exhibiting sedative properties including sleep-promoting effects.

The seed extract had a significant effect on the sleep duration at a dose of 80 mg/kg compared to control, but not at 160 mg/kg. The leaf extract had a significant effect on the sleep duration at 160 mg/kg compared to the control. The effect of the seed extract at 80 mg/kg and the leaf extract at 160 mg/kg on the sleep duration did not show a significant difference. Thus, the seed and leaf ex- tracts derived from romaine lettuce induced an increase in sleep duration at low and high doses respectively. In addition, both low and high doses of the seed and leaf extracts derived from romaine lettuce caused a significant reduction in sleep latency (p < 0.05).