Feverfew (Tanacetum parthenium L.) belonging to the family Asteraceae (daisies) is a daisy-like perennial plant found commonly in gardens and along roadsides. The name stems from the Latin word febrifugia, “fever reducer.” The first-century Greek physician Dioscorides prescribed feverfew for “all hot inflammations.” Also known as “featherfew,” because of its feathery leaves. It is a short, bushy, aromatic perennial that grows 0.3–1 m in height. Its yellow-green leaves are usually less than 8 cm in length, almost hairless, and pinnate–bipinnate (chrysanthemum-like). Its yellow flowers, which bloom from July to October, are about 2 cm in diameter. They resemble those of chamomile (Matricaria chamomilla), for which they are sometimes confused, and have a single layer of white outer-ray florets. This aromatic plant gives off a strong and bitter odor. Its yellow-green leaves are alternate (in other words the leaves grow on both sides of the stem at alternating levels), and turn downward with short hairs. The small, daisy-like yellow flowers are arranged in a dense flat-topped cluster.

Feverfew (Tanacetum parthenium L.) is a medicinal plant traditionally used for the treatment of fevers, migraine headaches, rheumatoid arthritis, stomach aches, toothaches, insect bites, infertility, and problems with menstruation and labor during childbirth. The feverfew herb has a long history of use in traditional and folk medicine, especially among Greek and early European herbalists. Feverfew has also been used for psoriasis, allergies, asthma, tinnitus, dizziness, nausea, and vomiting. The plant contains a large number of natural substances, but the active principles probably include one or more of the sesquiterpene lactones known to be present, including parthenolide. Other potentially active constituents include flavonoid glycosides and pinenes. It has multiple pharmacologic properties, such as anticancer, anti-inflammatory, cardiotonic, antispasmodic, an emmenagogue, and as an enema for worms. The plant is widely cultivated to large regions of the world and its importance as a medicinal plant is growing substantially with increasing and stronger reports in support of its multifarious therapeutic uses. 1 Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3210009/

No serious side effects have been reported from feverfew use. Side effects can include nausea, digestive problems, and bloating; if the fresh leaves are chewed, sores and irritation of the mouth may occur.

People who are sensitive to ragweed and related plants may experience allergic reactions to feverfew.

Do not take feverfew while pregnant because it may affect uterine contractions. Little is known about whether it’s safe to use feverfew while breastfeeding.

Using feverfew topically may cause skin irritation. 1 Reference: https://www.nccih.nih.gov/health/feverfew

Feverfew (Tanacetum parthenium L.) is a well-known plant used in migraine prevention.

Feverfew is a medicinal herb possessing a range of healing properties and ability to alleviate headache that was recognised even in the Middle Ages. The healing properties of the feverfew in migraine pathophysiology is not entirely understood yet. Feverfew extract promotes secretion of serotonin (5-hydroxitriptamine) from platelets facilitated by several aggregation mediators. Physiologically, serotonin is involved in transmission of nerve impulses between neurons. It is also called a neurotransmitter. Serotonin is mainly found in the brain, gastrointestinal tract and platelets. Activity of serotonin in human body is specifically related to smooth muscle activity and impulse transmission between neurons, furthermore, serotonin triggers a sense of happiness and well-being.

Feverfew extracts and pure parthenolide inhibits synthesis of prostaglandins. Since prostaglandins are substances that trigger inflammation and pain, promote exudate (fluid that leaks from blood vessels during inflammation) and fever, the feverfew has beneficial impact on these aspects by preventing or mitigating them. Meanwhile parthenolide has a considerable impact on vasoconstriction and vasodilation mechanisms.

Several clinical studies have confirmed that benefits of feverfew in migraine prevention greatly exceed the risks. No evidence on serious side effects has been gathered from clinical studies and long-term users of this product regarding safety and tolerance of the feverfew. 1 Reference 1: Pfaffenrath, V., Diener, H., Fischer, M., Friede, M., & Henneicke-von Zepelin, H. (2002). The Efficacy and Safety of Tanacetum Parthenium (Feverfew) in Migraine Prophylaxis—a Double-Blind, Multicentre, Randomized Placebo-Controlled Dose-Response Study. Cephalalgia, 22(7), 523–532. doi:10.1046/j.1468-2982.2002.00396.x

Feverfew extracts inhibit 5-HT secretion in platelets by neutralising sulfhydryl groups both in cell and outside it. Sesquiterpenes found in the feverfew contain alpha-methylethylene butyric acetone units that can react with sulfhydryl groups

Feverfew seems to have more than one pathway mechanism of action. Plant extracts affect a number of physiological pathways. Some of these mechanisms were discussed above, for example, inhibition of prostaglandin synthesis, reducing of vessel's smooth muscle spasms and blocking of platelet granule secretion.

The feverfew is known worldwide, for example, Canadian Health Protection Department has granted the Drug Identification Number (DIN) to feverfew product allowing its producer to put a claim that this over-the-counter medication eliminates migraine headache. 2 Reference 2: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3210009/

Feverfew is well researched also in Europe and the European Medicines Agency in its evaluation report on feverfew (EMA/HMPC/48716/2019) has concluded that feverfew is being used for treating migraine and headache with a therapeutic dose of 100 mg of herbs per day.

1. The ancient Greeks called the herb “Parthenium,” supposedly because it was used medicinally to save the life of someone who had fallen from the Parthenon during its construction in the 5^th century BC.
2. Feverfew also was known as “medieval aspirin” or the “aspirin” of the 18^th century
3. In Central and South America, the plant has been used to treat a variety of disorders. The Kallaway Indians of the Andes mountains value its use for treating colic, kidney pain, morning sickness, and stomach ache. Costa Ricans use a decoction of the herb to aid digestion, as a cardiotonic, an emmenagogue, and as an enema for worms. In Mexico, it is used as an antispasmodic and as a tonic to regulate menstruation. In Venezuela, it is used for treating earaches
4. Feverfew also has been planted around houses to purify the air because of its strong, lasting odor, and a tincture of its blossoms is used as an insect repellant and balm for bites. It has been used as an antidote for overindulgence in opium.

Gotu Kola is a perennial plant native to India, Japan, China, Indonesia, South Africa, Sri Lanka, and the South Pacific. A member of the Apiaceae or carrot family, it has no taste or smell. It is also called pennywort, marsh penny, water pennywort, and sheep rot.

It thrives in and around water. It has small fan-shaped green leaves with white or light purple-to-pink flowers, and small oval fruit. The leaves and stems of the Gotu Kola plant are used as medicine. It can grow like a weed, but its description depends on its location. For example, in shallow water, the leaves float; but in dry areas, the plant develops many roots and thin, tiny leaves. The fan-shaped leaves may be smooth or lobed. Red flowers turn into fruit with a diameter of about 5 mm.

Gotu Kola's main active components are triterpenoids, although the Gotu Kola found in India, Sri Lanka, and Madagascar doesn't have the same properties. Gotu Kola's triterpenes can have a concentration from 1.1-8%, with most concentrations in the middle range.

The plant enhances brain and peripheral circulation, and is said to enhance memory. In the 1880s, the French began using Gotu Kola as part of regular pharmaceutical medicines. 1 References: https://www.mountsinai.org/health-library/herb/gotu-kola https://www.encyclopedia.com/medicine/encyclopedias-almanacs-transcripts-and-maps/gotu-kola

Gotu Kola is typically safe to consume. However, some reported side effects of the herb include: drowsiness, nausea, headaches, dizziness, diarrhea, skin irritation.

Although there is limited research on Gotu Kola’s effect on other medications, it’s possible that it can interfere with prescription or over-the-counter medications. Always consult your doctor before using Gotu Kola.  1 Reference:https://www.webmd.com/diet/health-benefits-gotu-kola#2

Stroke can cause cognitive decline. The frequency of cognitive impairment after an ischemic stroke ranges from 20 to 30%, with an increasing risk in the two years after stroke. In their research, Ballard et al. found that 25% of patients suffered from poststroke dementia, and the risk of poststroke patients developing dementia within the following five years is nine times higher than in the healthy population, especially for cognitive domains such as memory and attention. Management of cognitive impairment following cerebrovascular disease should be aimed at the prevention of secondary strokes and specific treatment for the improvement of cognitive function. Secondary stroke prevention includes control of risk factors such as blood pressure, cholesterol levels, and hyperhomocysteinemia.

One medicinal herb commonly used is Gotu Kola (Centella asiatica). The main group of components in Gotu Kola is the triterpenes including asiaticoside, madecassoside, asiatic acid, and madecassic acid, which have antioxidant, anti-inflammatory, and antiapoptotic properties. This may explain why Gotu Kola has a positive influence on brain plasticity, as well as in increasing the length of dendrites and an enhancement of hippocampal CA3 neuronal dendritic arborization in mice inflicted with neurodegenerative diseases and memory disorders.

Study aimed to determine the improvement of cognitive function in patients with vascular cognitive impairment utilizing the Montreal Cognitive Assessment-Indonesian version (MoCA-Ina) after an intake of Gotu Kola (Centella asiatica) 750 mg/day and 1000 mg/day and of folic acid 3 mg/day for 6 weeks. 1 Reference: Kun Marisa Farhana, Rusdy Ghazali Malueka, Samekto Wibowo, and Abdul Gofir; Effectiveness of Gotu Kola Extract 750 mg and 1000 mg Compared with Folic Acid 3 mg in Improving Vascular Cognitive Impairment after Stroke;  Published online 2016 Jun 1. doi: 10.1155/2016/2795915 PMCID: PMC4908235

1. Historically, Gotu Kola has also been used to treat syphilis, hepatitis, stomach ulcers, mental fatigue, epilepsy, diarrhea, fever, and asthma.
2. The name sheep rot comes from the erroneous belief in Europe that Gotu Kola caused foot rot in sheep.
3. Gotu Kola is noted in India as a very powerful spiritual herb, and Ayurvedic medicine refers to it as Brahmi because it helps obtain knowledge of the spiritual being.
4. Chinese herbalist, Li Ching Yun, is supposed to have lived 256 years from drinking a herbal mixture containing Gotu Kola. An ancient Sinhalese saying, "Two leaves a day will keep old age away," also illustrates Gotu Kola's popularity as an agent for longevity.

Crocus, genus of about 75 low-growing cormose species of plants of the iris family (Iridaceae). Crocuses are native to the Alps, southern Europe, and the Mediterranean area and are widely grown for their cuplike blooms in early spring or fall. Spring-flowering plants have a long floral tube that allows the ovary to remain belowground, sheltered from climatic changes. The flowers close at night and in dull weather. Saffron, used for dye, seasoning, and medicine, is the dried feathery orange tip of the pistils of the lilac or white, autumn-flowering saffron crocus (Crocus sativus) of western Asia. Saffron crocus generally blooms with purple flowers in the autumn. The plant grows about 10 to 30 cm high.

Saffron is the dried elongated stigmas and styles of the blue-purple saffron crocus. Saffron stigmas contain four major bioactive compounds: crocins (family of six mono-glycosyl or di-glycosyl polyene esters), crocetin (a natural carotenoid dicarboxylic acid precursor of crocin), picrocrocin (monoterpene glycoside precursor of safranal and product of zeaxanthin degradation) and safranal. It appears that crocin and safranal inhibit reuptake of dopamine, norepinephrine, and serotonin. Saffron has the potential to enhance mental health through its antidepressant properties and, in a recent meta-analysis, was confirmed to be effective for the treatment of depression. 1 Atsauce: https://www.britannica.com/plant/Crocus#ref172302 2 Reference: Lopresti, A. L., & Drummond, P. D. (2014). Saffron (Crocus sativus) for depression: a systematic review of clinical studies and examination of underlying antidepressant mechanisms of action. Human Psychopharmacology: Clinical and Experimental, 29(6), 517–527. doi:10.1002/hup.2434   3 Mazidi, M., Shemshian, M., Mousavi, S. H., Norouzy, A., Kermani, T., Moghiman, T., … Ferns, G. A. A. (2016). A double-blind, randomized and placebo-controlled trial of Saffron (Crocus sativus L.) in the treatment of anxiety and depression. Journal of Complementary and Integrative Medicine, 13(2). doi:10.1515/jcim-2015-0043

When taken by mouth: Saffron is likely safe in food amounts and when taken as a medicine for up to 26 weeks. Some possible side effects include dry mouth, anxiety, agitation, drowsiness, low mood, sweating, nausea or vomiting, constipation or diarrhea, change in appetite, flushing, and headache. Allergic reactions can occur in some people.

Taking large amounts of saffron by mouth is possibly unsafe. High doses of 5 grams or more can cause poisoning. Doses of 12-20 grams can cause death.

Pregnancy and breast-feeding: Taking saffron by mouth in amounts larger than what is normally found in food is likely unsafe. Larger amounts of saffron can make the uterus contract and might cause a miscarriage.

There isn't enough reliable information to know if saffron is safe to use when pregnant or breast-feeding. Stay on the safe side and stick to food amounts.

Bipolar disorder: Saffron seems to be able to affect mood. There is a concern that it might trigger excitability and impulsive behavior (mania) in people with bipolar disorder. Don't use saffron if you have this condition.

Allergies to Lolium, Olea (includes olive), and Salsola plant species: People who are allergic to these plants might also be allergic to saffron.

Interactions. When used as a supplement, saffron may cause problems for people on blood pressure medicine or blood thinners. Check with your doctor before using it if you are taking medication. 1 Atsauce: www.webmd.com/vitamins/ai/ingredientmono-844/saffron

Depressive disorder is one of the most prevalent psychiatric diseases and has been estimated to affect up to 21% of the world’s population. Majority of patients are often reluctant to take synthetic antidepressant drugs in their appropriate doses because of the anticipated side effects such as the inability to drive a car, dry mouth, constipation, and libido. Hence, plant extracts are some of the most attractive sources of new drugs and have been shown to produce a better result with low side effects in the treatment of depression. 

The benefits of saffron as an antidepressant are well-documented. Almost 150 volatile and nonvolatile compounds are obtained from the chemical analysis of this plant. Fewer than 50 constituents elucidated and identified so far showed phytochemical characteristics.

Crocin and saffron extract had been revealed to prevent memory and spatial learning impairment because of chronic-induced stress. Prophylactic property of saffron against memory deficiency had been proposed to occur as the result of the correlation between the antioxidant activity of saffron and the impairment because of oxidative stress. Akhondzadeh et al., in 2004, had shown saffron extract to be equally efficient to imipramine during double-blind and randomized trial conducted over 6 weeks. The dried saffron petal also had been revealed to be effective in mild-to-moderate depression based on 6 weeks of double-blind randomized clinical trials. Crocin (30 mg/day), the main antioxidant constituent of saffron stigmas, was shown to amplify the effects of selective serotonin reuptake inhibitors in treating patients with mild-to-moderate depression with the absence of substantial side effects based on the observation of 4 weeks of randomized, double-blind, prospective, placebo-controlled pilot clinical trial with 40 patients of major depressive disorder.

Another study (in this double-blind, placebo-controlled and randomized trial, patients were randomly assigned to receive capsule of petal of C. sativus 30 mg/day (BD) (Group 1) and capsule of placebo (BD) (Group 2) for a 6-week study) showed that patients with mild-to-moderate depression receiving petal of C. sativus experienced statistically significant benefits in their mood after 6 weeks treatment. The clinical relevance of these findings was emphasized by the improvements seen in the Hamilton Depression Rating Scale measures in the saffron group. Moreover, there were no significant differences in the two groups in terms of observed side effects. It has been reported that stigma of C. sativus has antidepressant effect by at least three clinical trials (Akhondzadeh et al., 2004, 2005; Noorbala et al., 2005). 1 Reference: Mohammad J. Siddiqui, Mohammed S. M. Saleh, Siti N. B. Binti Basharuddin, Siti H. Binti Zamri, Mohd H. bin Mohd Najib, Muhammad Z. bin Che Ibrahim, Nur A. binti Mohd Noor, Hanin N. Binti Mazha, Norazian Mohd Hassan, and Alfi Khatib; Saffron (Crocus sativus L.): As an Antidepressant; J Pharm Bioallied Sci. 2018 Oct-Dec; 10(4): 173–180. doi: 10.4103/JPBS.JPBS_83_18 2 Reference: Akhondzadeh S, Fallah-Pour H, Afkham K, Jamshidi AH, Khalighi-Cigaroudi F. Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial [ISRCTN45683816] BMC Complement Altern Med. 2004;4:12. 3 Reference: Esmail Moshiria, Afshin Akhondzadeh Bastib, Ahamad-Ali Noorbalac, Amir-Hossein Jamshidid, Seyed Hesameddin Abbasie, Shahin Akhondzadeh; Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: A double-blind, randomized and placebo-controlled trial; Phytomedicine 13 (2006) 607–611

1. Saffron crocus smells a little like vanilla and spice, and the dried stigmas add a distinct flavor to foods like Spanish paella, rice dishes, and bouillabaisse. 
2. The origin of the word saffron is the French term “Safran,” which was derived from the Latin word “safranum” and yellowish in color, phytochemical analysis have revealed that the color is mainly because of the degraded carotenoid compounds, crocin and crocetin.
3. The stigma of saffron has been used as a medicine over 3600 years ago. Saffron was used in various opioid preparations for pain relief (sixteenth to nineteenth centuries). Also, saffron has been used in coloring tunics in the region of Spain and by the Babylonian culture around 2400 BC.
4. At a retail price of up to $11 000 per kg, it is the world’s most expensive spice, reflected by the labour intensiveness associated with its production. Each of the flowers has three red-colored stigma, and one stigma of saffron weighs approximately 2 mg. 150 000 crocus blossoms or 450 000 hand-picked stigmas to produce just 1 kg of this unique spice.
5. Quantities of 10 g or more can cause an abortion and the lethal dose in human is 20 g
6. Saffron is used for depression in Persian traditional medicine. Indeed, it is a Persian herb with a history as long as the Persian Empire itself.

Passiflora (Passiflora incarnata L.) or the passion flower is cultivated to obtain raw materials for pharmaceutical needs.Passiflora incarnata is one of the best-documented species of the Passiflora genus with medicinal properties. Both the plant as a whole, and blossoms and fruits are used for medicinal purposes.

The valuable properties and side effects of passiflora have long been studied in various medicinal preparations. Considering the fact that this plant has unique pharmacological properties, it is becoming increasingly popular lately.

Passiflora is a source of alkaloids, phenolic compounds, flavonoids and cyanogenic glycosides. The primary phytochemicals of passiflora are flavonoids (apigenin, luteolin, quercetin, and kaempferol) and flavonoid glycosides (vitexin, isovitexin, orientin, and isoorientin).1

The C-glycosylated flavonoids and isovitexin found in passiflora modulate GABAA receptors through their benzodiazepine binding sites and simultaneously create effects characteristic for anxiolytic means and the effect of cognitive improvement.2

On 25 March 2014, the European Medicines Agency published aherbal monograph on Passiflora incarnata, thereby recognising its status as a medicinal product.3

Passiflora incarnata is important in the plant-based medicinal treatment of anxiety or nervousness, generalised anxiety disorder, opiate withdrawal symptoms, insomnia, neuralgia, convulsions, spasmodic asthma, UDHS, palpitations, heart rhythm abnormalities, hypertension, sexual dysfunction, and menopause.

Despite the shortcomings of our understanding of neurophysiological processes, it is being increasingly recognisedthat neuropsychiatric conditions connected with depression and anxiety in the central nervous system relate to the balance between chemical excitation and inhibition. One mechanism involves the γ-aminobutyric acid (GABA) system.4 Therefore, the effects of Passiflora incarnata dry extract on the GABA system in vitro were investigated. Studies have shown that many of the pharmacological effects of Passiflora incarnata are related to modulation of the GABA system, including affinity (the ability of a substance to form a compound with another substance) for GABAA and GABABreceptors and effects on GABA uptake. The anxiolytic activities of polyphenols and flavones in passiflora can be partially attributed to their anti-irritant and antioxidant effects due to their specific structures. In addition, a significant number of these compounds have been proven to have anxiolytic properties through the activation of GABAA receptors.5 1 Atsauce: 1) Janda, K., Wojtkowska, K., Jakubczyk, K., Antoniewicz, J., & Skonieczna-Żydecka, K. (2020). Passiflora incarnata in Neuropsychiatric Disorders—A Systematic Review. Nutrients, 12(12), 3894. doi:10.3390/nu12123894 2) Oliveira, D. R. de, Todo, A. H., Rêgo, G. M., Cerutti, J. M., Cavalheiro, A. J., Rando, D. G. G., & Cerutti, S. M. (2018). Flavones-bound in benzodiazepine site on GABA A receptor: Concomitant anxiolytic-like and cognitive-enhancing effects produced by Isovitexin and 6-C-glycoside-Diosmetin. European Journal of Pharmacology, 831, 77–86. doi:10.1016/j.ejphar.2018.05.004 3) https://www.ema.europa.eu/en/medicines/herbal/passiflorae-herba 4) Fonseca, L. R. da, Rodrigues, R. de A., Ramos, A. de S., da Cruz, J. D., Ferreira, J. L. P., Silva, J. R. de A., & Amaral, A. C. F. (2020). Herbal Medicinal Products from Passiflora for Anxiety: An Unexploited Potential. The Scientific World Journal, 2020, 1–18. doi:10.1155/2020/6598434 5) Sita Sharan Patel, Neelesh Kumar Verma, Karunakaran Gauthaman; Passiflora Incarnata Linn: A Review on Morphology, Phytochemistry and Pharmacological Aspects; Phcog Rev. Vol, 3, Issue 5, 186-192, 2009

Side effects are sometimes observed when using products containing passiflora . The most common side effects are:

• • dizziness;
• • drowsiness;
• • confusion;
• • nausea;
• • vomiting;
• • low blood pressure;
• • abnormal heartbeat and rhythm.

Passiflora should be used with caution if you are already taking any sedative medications, such as alprazolam (Xanax), lorazepam (Ativan), temazepam (Restoril), and zolpidem (Ambien), because using them concurrently with passiflora increases the risk of excessive drowsiness and sedation.

Passiflora should be used cautiously together with blood pressure medications such as enalapril (Vasotec), losartan (Cozaar), atenolol (Tenormin), amlodipine (Norvasc), and furosemide (Lasix). Passiflora has a blood pressure-lowering effect, and taking blood pressure medications in combination with passiflora can lower your blood pressure more than necessary.

If you are taking any medications and have questions about the compatibility of these medications with passiflora, consult your doctor before using this product.

Passiflora is not recommended for women during pregnancy and breast-feeding.

Stress is a natural body reaction. It can be caused by factors of a physical (hunger, thirst, infection) and/or psychological nature (perceived threats, anxiety or concern), i.e., stress factors. Stress is associated with cell irritation. Physiologically, the body's response to stress causes an immediate activation of the adrenergic system and the sympathetic-adrenomedullary axis (SAM axis), followed by the hypothalamic-pituitary-adrenal axis (HPA axis). Chronic, long-term stress is a pathological condition that can impair concentration and memory, and lead to affective disorders such as depression, schizophrenia, and post-traumatic stress disorder. Passiflora incarnata is one of the plant-based remedies used to reduce the effects of stress. A study in rats demonstrated that a long-term use of passiflora was associated with reduced stress levels and, consequently, increased motivation to act and improved motor activity. The beneficial effects of passiflora on memory function have also been confirmed.

Stress can affect the quality of sleep and cause insomnia. The use of passiflora in people with chronic insomnia can have a therapeutic effect in the case of sleep disorders, memory loss and degenerative brain disease. Passiflora, due to its calming effect, can also be useful in anxiety, restlessness, insomnia and depressive conditions.1

The most commonly used drugs for anxiety include the anxiolytics benzodiazepine and buspirone, as well as various antidepressants, which can cause side effects and tolerability problems.

In a study2 setting a hypothesis that the oral use of Passiflora incarnata would be an effective anxiolytic agent with limited effects on anaesthesia and recovery, the effect of passiflora (500 mg) on anxiety in preoperative patients was demonstrated. Conclusion: In outpatient surgery, peroral administration ofPassiflora incarnata as premedication reduces anxiety without inducing sedation (drowsiness).

Passiflora incarnata at 500 mg/day provides a safe and effective anxiolytic effect without impairing psychomotor functions. 1 Atsauce: 1) Janda, K., Wojtkowska, K., Jakubczyk, K., Antoniewicz, J., & Skonieczna-Żydecka, K. (2020). Passiflora incarnata in Neuropsychiatric Disorders—A Systematic Review. Nutrients, 12(12), 3894. doi:10.3390/nu12123894; 2) Movafegh, A., Alizadeh, R., Hajimohamadi, F., Esfehani, F., & Nejatfar, M. (2008). Preoperative Oral Passiflora Incarnata Reduces Anxiety in Ambulatory Surgery Patients: A Double-Blind, Placebo-Controlled Study. Anesthesia & Analgesia, 106(6), 1728–1732. doi:10.1213/ane.0b013e318172c3f9

Among the 66 species of kelp, Fucus vesiculosus is one of the most prominent in the shallow waters of the Arctic region - the Atlantic Ocean, the North Pacific Ocean, the Barents, White, Norwegian, Baltic and Irminger seas. These algae dominate shallow water macroalgal populations at depths of 0.5-4 m in marine waters. They are used not only in food, but also in cosmetics, biological fertilisers, animal feed and the pharmaceutical industry.1

Fucus vesiculosus contains a range of health-promoting compounds such as fucoidans, polyphenols, fucoxanthin and a source of essential minerals, including iodine, which is highly bioavailable, and selenium, which plays a key role in regulating thyroid gland function. Bladderwrack is particularly rich in iodine and is used as a natural source of iodine, which is organically incorporated into cellular metabolism.

Alginic acid found in kelp (up to 35% of dry mass) is known in the food industry. It serves as an ingredient in soups and soup mixes as an emulsifier, thickener and stabiliser. On the other hand, preparations based on alginates (salts of alginic acid) are used to treat heartburn and gastric acid reflux.2 Alginic acid stimulates phagocytosis, thereby increasing the antimicrobial, antiviral and antifungal activity of cells; binds the excess amount of immunoglobulin E, due to which allergy develops; promotes the synthesis of immunoglobulin A (antibodies), which increases the body's resistance to microbes. Likewise, thanks to alginic acid, Fucus vesiculosus lowers blood pressure, removes harmful radionuclides and heavy metals and weakens body intoxication.

Another important component of Fucus vesiculosus is fucoidans. Fucoidans are polysaccharides from the Fucus family, compounds unique to brown algae (kelp). Various pharmacological effects of fucoidans have been reported, including antioxidant, anti-obesity, antidiabetic, antiageing, antimicrobial, anticancer (by modulating the host immune system and inhibiting tumour angiogenesis), anticoagulant, and anti-inflammatory effects.1

Fucus vesiculosus reduces the activity of trans-sialidase in the blood, an enzyme associated with cholesterol accumulation, by as much as 36%.3 This may be useful in patients with hypothyroidism, as slow metabolism is associated with the excessive accumulation of lipids and glucose.

Summing up the valuable qualities of Fucus vesiculosus, it should be mentioned that it effectively cleanses the body of slags and toxins, as well as maintains the health of the endocrine system. Recommended for hypothyroidism, blood circulation disorders, poisoning with heavy metal salts. Fucus vesiculosus slows down the development of atherosclerosis, and reduces the level of cholesterol in the blood. Bladderwrack polysaccharides swell, increase their volume and irritate the intestinal mucosa, thereby stimulating peristalsis, promoting intestinal cleansing, which is used to reduce weight in obese people. Polysaccharides bind toxins, remove them from the body. Bladderwrack alginates remove heavy metals and radionuclides from the body. Bladderwrack contains more trace elements than land plants. 1 Atsauces: 1) Ekaterina D. Obluchinskaya, Olga N. Pozharitskaya, Denis V. Zakharov, Elena V. Flisyuk, Inna I. Terninko, Yulia E. Generalova, Irina E. Smekhova, and Alexander N. Shikov; The Biochemical Composition and Antioxidant Properties of Fucus vesiculosus from the Arctic Region; Mar Drugs. 2022 Mar; 20(3): 193.; doi: 10.3390/md20030193 2) Mandel, Daggy, Brodie, & Jacoby. (2000). Review article: alginate-raft formulations in the treatment of heartburn and acid reflux. Alimentary Pharmacology and Therapeutics, 14(6), 669–690. doi:10.1046/j.1365-2036.2000.00759.x 3) Aksenov, D. V., Kaplun, V. V., Tertov, V. V., Sobenin, I. A., & Orekhov, A. N. (2007). Effect of plant extracts on trans-sialidase activity in human blood plasma. Bulletin of Experimental Biology and Medicine, 143(1), 46–50. doi:10.1007/s10517-007-0013-2

There are no clinical studies supporting the safety of Fucus vesiculosus, but based on the use of Fucus as a traditional food, moderate consumption of the seaweed is generally considered safe. Seaweed can be exposed to chemical contamination present in the water in which it is harvested, so its origin and manufacturer's quality requirements are of particular importance. Cases of Fucusnephrotoxicity, possibly due to arsenic contamination, have been reported. Therefore, pay attention if products containing algae are unusually cheap or are not registered with food safety authorities.

Due to the limited number of studies, there are no well-defined recommendations for daily doses of bladderwrack; however, mostly, it is recommended not to exceed 500 mg daily.

Pregnancy and breastfeeding period: Fucus vesiculosus is probably not safe to use during pregnancy or breastfeeding unless prescribed by a doctor.

Allergy to iodine: Fucus vesiculosus can contain large amounts of iodine, which can cause an allergic reaction in sensitive people. Do not use them as a food product in excessive amounts, but it can be used as a dietary supplement in controlled amounts.

Surgery: Fucus vesiculosus can slow down blood clotting. This can cause additional bleeding during and after surgery. Tell your doctor how much algae you are taking and, if necessary, stop taking Fucus vesiculosus at least 2 weeks before surgery if your doctor tells you to.

Drug interactions:

Be careful if you use:

Taking Fucus vesiculosus together with lithium may increase the risk of changes in thyroid gland function.

Taking Fucus vesiculosus with medicines for a hyperactive thyroid gland can change the effects of these medicines.

Fucus vesiculosus can slow down blood clotting. Taking them with medicines that also slow down blood clotting can increase the risk of bruising and bleeding.1 1 Atsauce: 1) https://medlineplus.gov/druginfo/natural/726.html

In our latitudes, a common phenomenon is a reduced thyroid function, or hypothyroidism. Almost every third or fourth woman has it. Women are more affected by this problem, because the function of the thyroid gland and its activity is influenced by the psycho-emotional state. The thyroid gland is very sensitive to adrenaline and the stress hormone cortisol. Typical signs of hypothyroidism are freezing (intolerance to cold), fluid retention, and it is especially evident in premenopausal age.1

The body of a healthy adult contains 15 to 20 mg of iodine, of which 70 to 80% is located in the thyroid gland. In the case of a chronic iodine deficiency, the iodine content in the thyroid gland may fall below 20 µg. If a sufficient amount of iodine is available to the body, then the thyroid gland “uses” about 60 µg of iodine per day to balance its loss and maintain the synthesis of thyroid hormones; accordingly, iodine is an essential component of the hormones produced by the thyroid gland.2

The body does not produce iodine, so it is essential to consume foods that contain iodine or to take iodine with food additives or nutritional supplements. Iodine is found in a variety of foods, however seafood has a higher iodine content because marine plants and animals are able to concentrate iodine from seawater. Iodine is found in large quantities in organic form in algae, incl. Fucus vesiculosus . If the body does not have enough iodine, it cannot produce enough thyroid gland hormones. Thus, iodine deficiency can cause thyroid gland enlargement, hypothyroidism, and intellectual disability in infants and children whose mothers were iodine deficient during pregnancy.3 Strict vegans are especially at risk because their daily food intake is limited.4

Fucus vesiculosus contains the flavonoid fucoxanthin and is reported to have the highest antioxidant activity among edible seaweeds. Fucus vesiculosus, rich in minerals and halides including iodine, has shown beneficial effects in the treatment of thyroid gland dysfunction such as Hashimoto's disease and sub-clinically

hypothyroidism. Fucus also has the ability to reduce the activity of trans-sialidase in the blood, which is associated with the accumulation of cholesterol. This may be important in hypothyroid patients whose metabolism is associated with hyperlipidemia.5 1 Atsauce: 1) https://nra.lv/veseliba/181158-veseliba-vairogdziedzera-disfunkcija-21-gadsimta-pandemija.htm 2) Zimmermann, M. B. (2009). Iodine Deficiency. Endocrine Reviews, 30(4), 376–408. doi:10.1210/er.2009-0011 10.1210/er.2009-0011 3) https://www.thyroid.org/iodine-deficiency/ 4) Lightowler HJ, Davies GJ. Iodine intake and iodine deficiency in vegans as assessed by the duplicate-portion technique and urinary iodine excretion. Br J Nutr 1998;80(6):529-535. 5) Jill Stansbury,Paul Saunders, David Winston; Promoting Healthy Thyroid Function with Iodine, Bladderwrack, Guggul and Iris; ©2012, Jill Stansbury, ND Journal Compilation ©2012, AARM; DOI 10.14200/jrm.2012.1.1008

Lavender is a perennial plant of the Labiatae family with thousands of years of history. It is a small, fragrant shrub that reaches a maximum height of 80 centimetres and is both a nectar plant and an essential oil plant. Lavender has oppositely arranged, grey-green, lanceolate leaves with a curled edge. The flowers are double-lipped, blue or violet-blue, arranged in false spikes, which in turn form a spike at the end of the inflorescence.

The lavender genus includes up to 47 species. Under natural conditions, lavender grows in North and East Africa, Australia, the Arabian Peninsula, India, the Canary Islands and Southern Europe. However, as a crop it is found all over the world.

Looking at the great variety of species, three main types can be distinguished: English, Spanish and French lavender. Although they share many similarities, French and English varieties can be distinguished by appearance, growth habit, flowering time, fragrance and use.

English or “true” lavender (Lavandula officinalis angustifolia) is more dense, with a fuller flower, and it is this lavender species that is mostly used for medicinal purposes.

Its flowers contain 3% essential substances, anthocyanins, phytosterols, sugars, minerals and tannins. The qualitative and quantitative composition of lavender essential oil is variable and depends on the genotype, place of growth, climatic conditions, propagation and morphological features. Lavender essential oil contains more than 300 different chemical compositions, the main of which is linalool (the amount varies from 9.3% to 68.8% and has the following medicinal properties: anti-inflammatory, anticonvulsant, relaxant, analgesic, sedative, antidepressant, anti-stress agent and anxiolytic agent), linalyl acetate (amount varies from 1.2% to 59.4%), lavandulyl acetate, ocimene, cineole and terpinen-4-ol. 1 Atsauces: Prusinowska, R., & Śmigielski, K. B. (2014). Composition, biological properties and therapeutic effects of lavender (Lavandula angustifolia L). A review. Herba Polonica, 60(2), 56–66. doi:10.2478/hepo-2014-0010

Lavender essential oil has good antioxidant and antimicrobial activities when applied to the skin, as well as significant positive effects on the digestive and nervous systems when taken orally.

Linalool and linalyl acetate are thought to be the main components of lavender oil, which could be related to sleep-promoting effects by modulating the effects of glutamate and GABA. 2 Atsauces: Kim, J., Lee, S. L., Kang, I., Song, Y. A., Ma, J., Hong, Y. S., … Kim, J. E. (2018). Natural Products from Single Plants as Sleep Aids: A Systematic Review. Journal of Medicinal Food, 21(5), 433–444. doi:10.1089/jmf.2017.4064

Lavender has been shown to act as an anxiolytic aid (anxiety reliever) and as a sedative aid to increase body relaxation and resting, thereby promoting sleep.

Lavender interacts with the neurotransmitter GABA (a chemical naturally produced in the nervous system that allows nerve cells to communicate with each other and a lack or excess of which can cause a variety of mood disorders) to help calm the brain and nervous system, reducing agitation, anger, aggression and anxiety. Lavender also works as a pain reliever.

The toxicity of lavender oil is not a concern. Components such as linalool and linalyl acetate are not mutagenic. 1 Atsauce: https://www.ema.europa.eu/en/documents/herbal-report/draft-assessment-report-lavandula-angustifolia-mill-aetheroleum-lavandula-angustifolia-mill-flos_en.pdf]] Given that lavender is also used in food, it is also safe when used as medicine. Side effects may include constipation, diarrhoea and headache.

Be careful when using sedative medications (central nervous system depressants) with lavender because they interact.

Lavender can cause drowsiness and slow breathing. Sedatives (medications) can also cause drowsiness and decelerated breathing. Taking lavender with sedative medications can cause breathing problems and/or excessive drowsiness.

Insomnia is one of the most common sleep disorders among the population. This disorder is also among the most frequent complaints in primary health care centres. Lavender is called a “brain broom” in various Eastern traditional medicines, because it is able to “clean” the head in the same way that a broom sweeps a room of debris. It is one of the most commonly used herbs for patients with sleep disorders.

According to the European Medicines Agency assessment report 1 Atsauce:  2" https://www.ema.europa.eu/en/documents/herbal-report/draft-assessment-report-lavandula-angustifolia-mill-aetheroleum-lavandula-angustifolia-mill-flos_en.pdf]]

EMA/HMPC/143183/2010, lavender oil acts as a sedative aid and promotes sleep. Separate studies have shown that individuals reported greater alertness and vigour the morning after exposure to lavender, as well as an increase in non-REM, or slow, light sleep, and a decrease in rapid eye movement (REM) sleep, and its duration.

At the same time, the time before waking up after first falling asleep (waking up after the beginning of sleep) increased. 2 Atsauce: Goel, N., Kim, H., & Lao, R. P. (2005). An Olfactory Stimulus Modifies Nighttime Sleep in Young Men and Women. Chronobiology International, 22(5), 889–904. doi:10.1080/07420520500263276

Plants and herbal medicines for the treatment of various sleep disorders have been used for medicinal purposes for centuries - including lavender. Various, complex biochemical processes in the brain provide us with sleep, incl. interaction with GABAergic signals.

As the main inhibitory neurotransmitter, GABA helps maintain the overall balance of neuronal excitation and inhibition in the central nervous system and plays one of the key roles in brain development and function. More than 20% of all neurons in the brain are thought to be GABAergic. Three different GABA receptors: GABAA, GABAB and GABAC are involved in the regulation of sleep and arousal (although to varying degrees). The most commonly used sleeping pills act directly on the GABA systems, ​especially benzodiazepine. 3 Atsauce: Bruni, O., Ferini-Strambi, L., Giacomoni, E., & Pellegrino, P. (2021). Herbal Remedies and Their Possible Effect on the GABAergic System and Sleep. Nutrients, 13(2), 530. doi:10.3390/nu13020530

Lavender's active ingredients can bind glutamate N-methyl-D-aspartate receptors (NMDA) and serotonin transporters. The NMDA receptor is believed to be crucial for the control of synaptic plasticity and to mediate memory function. Sleep-promoting GABAergic neurons are a major target for the pharmacological treatment of insomnia.

It must be said that despite the availability of several sleep medications, side effects are still a problem and there is still a demand for safer insomnia treatment options. Studies show that several substances of plant origin, incl. found in lavender, can act as sleep inducers by modulating GABAergic signalling in the brain. The safety and wide acceptance (absence of side effects) of herbal products among patients is a strong argument for preferring herbs over industrially produced drugs.

California poppies are plants of the Eschscholzia genus of the poppy family (Papaveraceae). Depending on the place of growth, they are divided into two large subspecies E.californica subsp. californica and E. californica subsp. Mexican.

The natural range of the California poppy is the United States (states: California, Oregon, Washington, Nevada, Arizona, New Mexico) and Mexico (States: Sonora and Baja California), but as an ornamental plant it is distributed throughout the world.

The California poppy is an annual (in places where it does not grow naturally) or a perennial 130-152 cm tall plant. The flowers are yellow to orange in colour. It blooms from February to September (in the natural distribution areas) and the flowers have a specific aroma.

Californian poppy leaves are said to have been used by the Indians as a medicine, and the pollen - in cosmetics. The seeds, on the other hand, can be used in cooking.

California poppies are known for their calming, anti-anxiety and sleep-inducing effects. This effect is associated with protopine and allocryptopine. Both alkaloids act as weak stimulants - GABA receptor initiators (agonists) and as acetylcholinesterase inhibitors preventing the breakdown of acetylcholine (ACh) and increasing the duration of action and the level of ACh at the nerve endings, called synapses.[[1:: Atsauces: Fedurco, M., Gregorová, J., Šebrlová, K., Kantorová, J., Peš, O., Baur, R., … Táborská, E. (2015). Modulatory Effects of Eschscholzia californica Alkaloids on Recombinant GABAA Receptors. Biochemistry Research International, 2015, 1–9. doi:10.1155/2015/617620]] Another aporphine alkaloid isolated from this plant, namely N-methyllaurotetanine (NMT), acts as a serotonin 5HT 1A R receptor blocker (antagonist). 2 Atsauces: S. Gafner, B. M. Dietz, K. L. McPhail et al., “Alkaloids from Eschscholzia californica and their capacity to inhibit binding of [3H]8-hydroxy-2-(di-N-propylamino) tetralin to 5-HT1A receptors in vitro” Journal of Natural Products, vol. 69, no. 3, pp. 432–435, 2006 .Protopine and allocryptopine have been found to block the human serotonin and noradrenaline transporters (hSERT and NERT) and have antidepressant-like effects. 1 Atsauces: Fedurco, M., Gregorová, J., Šebrlová, K., Kantorová, J., Peš, O., Baur, R., … Táborská, E. (2015). Modulatory Effects of Eschscholzia californica Alkaloids on Recombinant GABAA Receptors. Biochemistry Research International, 2015, 1–9. doi:10.1155/2015/617620

In addition to the mentioned alkaloids, California poppies also contain other active components: alkaloids - cryptopine and chelidonine, as well as flavonoids and glycosides.

California poppies have no narcotic effects and are completely safe to use. It is not an opiate family plant. If the opium poppy has a disorientating effect, the California poppy has a normalising effect on human physiology and psychology. Alkaloids have a calming and relaxing effect on the body and mind, but they work gently.

California poppy is safe for most people when taken correctly perorally for up to three months. There is not enough research on the safety of long-term use of the California poppy.

If surgical intervention is planned: California poppies act on the central nervous system, causing drowsiness and other symptoms. There is a possibility that the California poppy may excessively slow down the central nervous system when used with anaesthesia and/or other drugs used during and after surgery. Stop using California poppy preparations at least 2 weeks before the scheduled surgery.

INTERACTION

Sedative medications (benzodiazepines and CNS depressants)

Interaction assessment: Moderate. Be careful when using this combination. Talk to your health care professional.

California poppies can cause drowsiness. Taking California poppy along with sedative medications can cause excessive drowsiness.

Some of these sedative medications include clonazepam (Klonopin), diazepam (Valium), lorazepam (Ativan), phenobarbital (Donnatal), zolpidem (Ambien), and others.

California poppy is not recommended for:

Insomnia is defined as difficulty falling asleep or staying asleep that is caused by the effects of the day's events and is not related to environmental conditions or insufficient duration of sleep. In the international classification of sleep disorders, insomnia is considered chronic if it persists for a long time - at least three months with a frequency of at least three times a week. In other cases, insomnia is defined as temporary and can be considered corrective, acute, or anxiety-related insomnia.

The Committee on Herbal Medicinal Products (HMPC) and the European Medicines Agency (EMA) have concluded that California poppy can be used to relieve mild symptoms of mental stress and as a sleeping aid. 1 Atsauce: https://www.ema.europa.eu/en/medicines/herbal/eschscholziae-herba]]

The sedative and anxiolytic properties of California poppy have been demonstrated in several preclinical studies. With the use of this herb, an increase in sleep time and a decrease in motor activity during sleep were observed. 2 Atsauce:  Abdellah, S. A., Berlin, A., Blondeau, C., Guinobert, I., Guilbot, A., Beck, M., & Duforez, F. (2019). A combination of Eschscholtzia californica Cham. and Valeriana officinalis L. extracts for adjustment insomnia: A prospective observational study. Journal of Traditional and Complementary Medicine. doi:10.1016/j.jtcme.2019.02.003

The chemical composition of California poppy, like all other representatives of the poppy family, is rich in alkaloids, ​especially protopine, berberine, allocryptopine, escholtzine, and californidine. Flavonoids, especially rutose, have been found in the plant. California poppy contains various carotenoids, such as zeaxanthin, which determine the colour of the plant.

The medicinal properties are related to the alkaloids contained in its chemical composition. Thanks to the alkaloids, California poppy has a calming, antispasmodic and even analgesic effect on the human body.

With the help of California poppy, you can normalise sleep, get rid of insomnia, and the slightly antispasmodic and sedative effect of alkaloids allows the use of the plant extract for the treatment of psychological and physical problems and nervous disorders.

Β-glucan is a water-soluble dietary fibre obtained from oats, barley, bacteria, yeast, algae, and mushrooms. Cell wall of baker’s yeast, that is, Saccharomyces cerevisiae is most abundant in β-glucan. β-glucan is a water-soluble polysaccharide consisting of glucose units. Glucose monomers are linked via β-(1→3) glycosidic bonds in bacteria and algae whereas glucose monomers are linked via β-(1→3) and β-(1→6) glycosidic bonds in yeast and mushrooms. In oats and barley, glucose monomers are linked via β-(1→4) and β-(1→3) glycosidic bonds. Β-glucan obtained from bacteria and algae shows a linear structure whereas β-glucan extracted from yeast, mushrooms, oats, and barley exhibits a branched structure. Β-glucan synthesis in the cell wall is a complex process because of the identification of a large number of different classes of glucans. Several classes of enzymes are involved in the synthesis of β-glucan. No sharp distinction lies between the insoluble and soluble fractions of β-glucan; however, the water solubility of β-glucan is dependent on its structure.¹

Thus, mushrooms, bacteria and plants produce different glucans with large differences in the proportions and arrangements of their 1→3, 1→4 and 1→6 β-glycosidic bonds; respectively, they are different types of β-glucans. These three types not only differ at the molecular level but also have different effects on the body. Although each of these types of β-glucans can have positive health effects, the benefits vary depending on the type of β-glucan.²

Oat-based β-glucans are notable for promoting heart health and helping manage LDL (bad) cholesterol. They improve metabolic parameters such as dyslipidaemia and insulin resistance.

Although mushroom β-glucans have been shown to have immune health benefits, research indicates that their potency is lower than that of certain well-studied baker’s yeast β-glucans.

Yeast-derived β-glucans act as immune-modulators, particularly by stimulating the innate immune response.³ They usually originate in either baker’s yeast or brewer’s yeast. Even though both are β-(1→3) and β-(1→6) from Saccharomyces cerevisiae, the source matters – the beta-glucans extracted from the cell walls of baker’s yeast have a different molecular pattern from that of brewer’s yeast, which can influence the immune-modulating abilities.

By activating and enhancing immune cells, β-glucans help the body fight off viruses, bacteria, and other pathogens.⁴

However, it is important to choose high-quality β-glucans as they provide biological activity, and the desired mechanism for action in the body. The manufacturing or processing methods used to extract the β-glucans can impact their structure. If the β-glucan’s structure is damaged or altered during the manufacturing process, the result could be a loss of measurable immune health benefits in the finished product.

There is no information on beta-glucan deficiency. Also, there is no specific Recommended Dietary Allowance (RDA) for beta-glucans. However, given that beta-glucans are a fibre, there are recommendations for total fibre intake, and, unfortunately, many people do not get enough fibre in their diet.

The adequate intake of fibre is at least 14 grams of fibre/1000 calories of intake. The recommended amount of fibre varies between women and men – it ranges from 21 to 26 grams of fibre daily for women and 30 to 38 grams daily for men, depending on age.

Beta-glucans are naturally present in various foods. Good sources are oats, barley, sorghum, rye, corn, wheat, rice, mushrooms, seaweed (algae).

The highest concentrations of beta-glucans are found in grains such as barley and oats. Furthermore, this fibre is found in some types of bacteria and mushrooms, including Saccharomyces cerevisiae, which is used to make nutritional yeast, wine, beer and some bakery products. However, this does not mean that alcoholic beverages are a good source of beta-glucans.

No side effects have been reported when beta-glucans are taken orally.

When applied on skin: beta-glucans are safe when used temporarily. For some people they may cause skin irritation and/or rashes.

If taking medication, in some cases there may be a moderate interaction between the medication and beta-glucans.

1. Medications that decrease the immune system (Immune-suppressants) interact with beta-glucans.

Beta-glucans can increase the activity of the immune system. Some medications, such as those used after a transplant, decrease the activity of the immune system. Taking beta-glucans along with these medications might decrease the effects of these medications.

2. Medications for high blood pressure (Antihypertensive drugs) interact with beta-glucans.

Oat-based beta-glucans might lower blood pressure. Taking beta-glucans along with medications that lower blood pressure might cause blood pressure to go too low. Monitor your blood pressure closely.

Biologically active, safe and mainly natural immune stimulants have been sought throughout human history. Some of them, such as beta-glucans, are being intensively studied. To date, there are more than 15 000 publications, but the search continues.

Beta-glucan, a natural plant-derived molecule, “modulates” (alters) the immune system by activating every immune cell in the body: macrophages, neutrophils, basophils, NK (natural killer) cells, etc. Specifically, macrophages trigger a range of immune functions that allow the body to produce the most complete, effective and appropriate immune response possible. The activity of the immune cells of the body determines how well the immune system captures and defeats “invaders” that are foreign to the body. Beta-glucan triggers immune cells to be ready to “fight back”.

Basically, beta-glucan is a catalyst that makes the immune system smarter by increasing our body’s defences. When first confronted with a pathogen, the immune system initially reacts quickly and non-specifically, using its innate immune function. Symptoms associated with this response, such as pain and swelling, are the result of the body’s inflammatory response.

This is followed by a slower, specific response to the pathogen by the adaptive side of the immune system. Adaptive immunity involves the part of the immune system that has long-term memory and prevents many pathogens from infecting us more than once.

Immune-modulating molecules, some of which can be ingested, can help the body defend itself against pathogens by adapting the normal immune response so that it responds more effectively when a pathogen is detected.

In particular, beta-glucans derived from yeast affect the inflammatory and antimicrobial activities of neutrophils and macrophages, cells that are part of the innate immune system. There is emerging evidence that yeast beta-glucans may “train” the body’s immune cells to react more effectively when a pathogen is detected.

Training the body’s immune system refers to a newly recognised phenomenon that occurs when innate immune cells encounter specific pieces of microbes (living or non-living), causing the cells to adopt a more effective response to a future threat. In essence, this means that innate immune cells, after experiencing one of these training stimuli, retain a “memory” of the experience that allows them to respond more quickly and effectively when they encounter another pathogen.

A key difference between innate immune training and the traditional immune memory is how broad the trained response is. In traditional immune memory, the immune system encounters a pathogen (for example, measles) through illness or vaccination and the adaptive immune system creates several types of specific molecules to recognise that pathogen (measles) in the future and block the body from becoming infected.

By contrast, in trained immunity, the innate immune system’s encounter with living or non-living microbes (the “trainer” stimuli) adjusts the innate immune response to allow for a more efficient reaction toward pathogens that are not related to the “trainer.” This more general effect is essential for immune defence because it is helpful to have some level of protection from pathogens you have never encountered before.

Trained immunity, induced by an initial encounter with a training stimulus such as yeast beta-glucan, results in an enhanced response to subsequent infections. Several different functions of immune cells are primed for quicker activation from this process including the production of antimicrobial molecules.

The emerging evidence shows that yeast beta-glucan could be a training stimulus for the immune system 1 Ref.: De Marco Castro, E., Calder, P. C., & Roche, H. M. (2020). β‐1,3/1,6‐Glucans and Immunity: State of the Art and Future Directions. Molecular Nutrition & Food Research, 65(1), 1901071. doi:10.1002/mnfr.201901071 . Additionally, some observations from previously published studies investigating the mechanism of action of Wellmune^® are consistent with how an innate immune trainer acts.

To summarise the benefits, beta-glucans may interact positively with the immune system. The potential benefits of beta-glucan for the immune system are:

1) increasing the immune response against colds and influenza (improving protection against colds, influenza and other respiratory infections);

2) reducing seasonal allergy symptoms in some cases (reduced sneezing and nasal stuffiness);

3) reducing inflammation due to intense exercise: several studies show that beta-glucans reduce exercise-related inflammation.

1. Beta-glucans are a polysaccharide sugar derived from yeast, mushrooms or oats. They have antioxidant properties and are skin soothing agents.
2. Investigations into beta-glucans started in the 1960s and 1970s on different continents at the same time. Mainly in the USA and Europe, but also in Asia, mainly in Japan. Research on beta-glucans in Europe and America was based on knowledge of immunomodulatory effects of zymosan, a mixture of polysaccharides isolated from the cell walls of Saccharomyces cerevisiae.
3. In Asian medicine, the consumption of different medicinal mushrooms (e.g., shiitake, maitake, reishi, etc.) has a long tradition. In detailed studies of the biological effects of these mushrooms, especially anti-cancer actions, beta-glucans were found to be a main cause of non-specific immune-modulation.
4. Goro Chihara from Teikyo University in Kawasaki, isolated beta-glucan from mushroom shiitake (Lentinula edodes) and named them lentinan.
5. All sufficiently purified polysaccharide immunomodulators distinguish themselves by very low toxicity.
6. Unlike most other natural products, purified beta-glucans retain their bioactivity, which permits the characterisation of how beta-glucans work on a cellular and molecular level.

Black elder (Sambucus nigra L.) is one of many species of elderberry. The black elder is an up to 6 m tall tree or shrub. It has creamy-white flowers in shield-like clusters and black-purple stone fruits with three stones. The flowers bloom in June and July. The oppositely arranged leaves are pinnate with 3, 5 or 7 leaflets. The natural range is southern Europe, North Africa and the Middle East. 1 Ref.: https://en.wikipedia.org/wiki/Sambucus_nigra

Elderberries contain many active chemicals with pharmacological activity, including anthocyanins (mainly cyanidin 3-glucoside and cyanidin 3-sambubioside), which have been shown to strengthen the immune system and show antiviral activity. 2 Ref.: Hawkins, J., Baker, C., Cherry, L., & Dunne, E. (2019). Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: A meta-analysis of randomized, controlled clinical trials. Complementary Therapies in Medicine, 42, 361–365. doi:10.1016/j.ctim.2018.12.004  Oral use of elderberry has resulted in plasma levels of these anthocyanins.

Other components include vitamins and minerals in small amounts and carbohydrates such as pectin and up to 7.5% glucose and fructose.

Elderberry contains diversely bioactive ingredients, such as (poly)phenolic compounds and terpenoid compounds. Polyphenols, known for their free radical scavenging activity, together with anthocyanins are the most important groups of bioactive compounds present in elderberry in relatively high concentrations.

Recent studies 3 Ref.: Liu D, He XQ, Wu DT, Li HB, Feng YB, Zou L, Gan RY. Elderberry (Sambucus nigra L.): Bioactive Compounds, Health Functions, and Applications. J Agric Food Chem. 2022 Apr 13;70(14):4202-4220. doi: 10.1021/acs.jafc.2c00010. Epub 2022 Mar 29. PMID: 35348337 report that some food processing methods can affect the content of bioactive compounds in elderberry, and that the chemical composition depends on various factors such as location, stage of ripening and climatic conditions. 4 Ref.: Młynarczyk K, Walkowiak-Tomczak D, Łysiak GP. Bioactive properties of Sambucus nigra L. as a functional ingredient for food and pharmaceutical industry. J Funct Foods. 2018 Jan;40:377-390. doi: 10.1016/j.jff.2017.11.025. Epub 2017 Dec 22. PMID: 32362939; PMCID: PMC7185606 For instance, the method of production of the juice, which is widely used in both food supplements and syrups, influences the content of bioactive compounds. Elderberry juices processed using enzymatic treatment (pectinolysis) demonstrated a lower average content of most investigated phenolic compounds compared to the juices produced without enzymatic treatment. Therefore, when choosing supplements with elderberry juice or extract, consider the standardisation of the active substances (polyphenols and anthocyanins). Elderberry exhibits various health functions in vitro and in vivo, including antioxidant, anti-inflammatory, anticancer, anti-influenza, antimicrobial, antidiabetic, cardiovascular protective, and neuroprotective activities. 3 Ref.: Liu D, He XQ, Wu DT, Li HB, Feng YB, Zou L, Gan RY. Elderberry (Sambucus nigra L.): Bioactive Compounds, Health Functions, and Applications. J Agric Food Chem. 2022 Apr 13;70(14):4202-4220. doi: 10.1021/acs.jafc.2c00010. Epub 2022 Mar 29. PMID: 35348337 However, elderberry is mainly used to treat common cold symptoms: fever, cough, stuffy nose, runny nose and flu, as well as preventively to strengthen the immune system. 4 Ref.: Młynarczyk K, Walkowiak-Tomczak D, Łysiak GP. Bioactive properties of Sambucus nigra L. as a functional ingredient for food and pharmaceutical industry. J Funct Foods. 2018 Jan;40:377-390. doi: 10.1016/j.jff.2017.11.025. Epub 2017 Dec 22. PMID: 32362939; PMCID: PMC7185606

Elderberry bark, unripe berries, and seeds contain small amounts of substances known as lectins, which can cause stomach problems if consumed excessively. 1 Ref.: https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-sambucus-nigra-l-fructus_en.pdf In addition, the elderberry plant contains substances called cyanogenic glycosides that can release cyanide in some circumstances. This is a toxin also found in apricot seeds and almonds 2 Ref.: Ulbricht C, Basch E, Cheung L, Goldberg H, Hammerness P, Isaac R, Khalsa KP, Romm A, Rychlik I, Varghese M, Weissner W, Windsor RC, Wortley J. An evidence-based systematic review of elderberry and elderflower (Sambucus nigra) by the Natural Standard Research Collaboration. J Diet Suppl. 2014 Mar;11(1):80-120. doi: 10.3109/19390211.2013.859852. Epub 2014 Jan 10. PMID: 24409980 . However, its content is not high – 3% of the estimated lethal dose for a person weighing 60 kg, or more precisely 3 mg per 100 grams of fresh berries and 3–17 mg per 100 grams of fresh leaves.

However, it is important to know that commercial preparations and cooked berries do not contain cyanide. Symptoms of eating uncooked berries, leaves, bark or elderberry roots include nausea, vomiting and diarrhoea.

Elder is not known to have severe, serious or moderate drug interactions. Do not use preparations containing elder if an allergic reaction has been observed.

Elderberry extract is shown to be effective in mitigating the duration and severity of flu symptoms in several strains of influenza viruses. 1 Ref.: Porter RS, Bode RF. A Review of the Antiviral Properties of Black Elder (Sambucus nigra L.) Products. Phytother Res. 2017 Apr;31(4):533-554. doi: 10.1002/ptr.5782. Epub 2017 Feb 15. PMID: 28198157  A study of 312 air travellers taking capsules containing 300 mg of elderberry extract three times per day found that those who got sick experienced a shorter duration of illness and less severe symptoms. 2 Ref.: Tiralongo E, Wee SS, Lea RA. Elderberry Supplementation Reduces Cold Duration and Symptoms in Air-Travellers: A Randomized, Double-Blind Placebo-Controlled Clinical Trial. Nutrients. 2016 Mar 24;8(4):182. doi: 10.3390/nu8040182. PMID: 27023596; PMCID: PMC4848651

Studies 3 Ref.: Chatterjee A, Yasmin T, Bagchi D, Stohs SJ. Inhibition of Helicobacter pylori in vitro by various berry extracts, with enhanced susceptibility to clarithromycin. Mol Cell Biochem. 2004 Oct;265(1-2):19-26. doi: 10.1023/b:mcbi.0000044310.92444.ec. PMID: 15543930 4 Ref.: Krawitz C, Mraheil MA, Stein M, Imirzalioglu C, Domann E, Pleschka S, Hain T. Inhibitory activity of a standardized elderberry liquid extract against clinically-relevant human respiratory bacterial pathogens and influenza A and B viruses. BMC Complement Altern Med. 2011 Feb 25;11:16. doi: 10.1186/1472-6882-11-16. PMID: 21352539; PMCID: PMC3056848 have shown that elderberry is effective against a variety of pathogens, such as Helicobacter pylori (can cause stomach ulcers, abdominal pain, nausea), Streptococcus pyogenes (the most common bacterial cause of pharyngitis), Streptococci group C and G, Branhamella catarrhalis (can cause infections of the human respiratory system, middle ear, eyes, central nervous system and joints) and Haemophilus influenza (can cause pneumonia, otitis, sinusitis, laryngotracheitis, bronchitis).

The immune-modulatory effect of standardised elderberry extract against leishmaniasis and malaria infections was found to delay disease progression. 5 Ref.: Waknine-Grinberg, J., El-On, J., Barak, V., Barenholz, Y., & Golenser, J. (2009). The Immunomodulatory Effect of Sambucol on Leishmanial and Malarial Infections. Planta Medica, 75(06), 581–586. doi:10.1055/s-0029-1185357

Black elder has many bioactive constituents beneficial for general health and associated with the alleviation of a wide range of health disorders; accordingly, elder is promising for the treatment of low-risk influenza and other viruses and non-viral pathogens – and possibly also as a prophylactic agent for acute viral infections. 1 Ref.: Porter RS, Bode RF. A Review of the Antiviral Properties of Black Elder (Sambucus nigra L.) Products. Phytother Res. 2017 Apr;31(4):533-554. doi: 10.1002/ptr.5782. Epub 2017 Feb 15. PMID: 28198157

1. The elder tree was once considered sacred because it protected against many dangers and misfortunes – fires, evil people, even robbers and, of course, many diseases and illnesses.
2. Elder is considered mature after 3–4 years. Elderberries are not suitable for mechanical harvesting because they are difficult to separate from the stems, but in some countries, they are harvested using machinery designed for other berry crops and adapted to the elderberry.
3. The history of Elderberry dates all the way back to 400 BC, when Hippocrates, the “Father of Medicine”, called the elder tree his “medicine chest”.
4. Elder flowers, berries and leaves are excellent sources of antioxidants. For example, one of the anthocyanins found in the berries has 3.5 times the antioxidant power of vitamin E.
5. Elderberries may reduce levels of uric acid in the blood. Elevated uric acid is linked to increased blood pressure and negative effects on heart health.