Preparati

PREPARATI CRNE ZOVE: Sambucus nigra Ø 

MATIČNA TINKTURA, CRNA ZOVA PLANINSKA TM,
hidroetanolni tečni ekstrakt svežihh delova biljke, DER 1:1 (Ph. Fra. 2007.),
hidroetanolni tečni ekstrakt svežihh delova biljke, DER 1:2 (Ph. Fra. 2007.).

Sambuci nigri floris recentis extractum ethanolicum liquidum
Sambuci nigri flos et folium recentis extractum ethanolicum liquidum
Sambuci nigri fructus recentis extractum ethanolicum liquidum
namenjeni kod tegoba respiratornog trakta, čistač krvi i celog organizma.

ATC: R05 – ekspektorans, R07AX – ostali preparati, A06A – laksativ, – dijaforetik, – diuretik.

U skladu sa:

1)  Based on Article 10a of Directive 2001/83/EC as amended (well-established use),

Based on Article 16d(1), Article 16f and Article 16h of Directive 2001/83/EC as amended (traditional use),

DIRECTIVE 2004/24/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 31 March 2004.

2) Eu. Ph. 2015 monografijom:
1217 Sambuci flos

3) 27 March 2018, EMA/HMPC/611512/2016, Committee on Herbal Medicinal Products (HMPC):
European Union herbal monograph on Sambucus nigra L., flos Final

4) 20 March 2018, EMA/HMPC/611504/2016, Committee on Herbal Medicinal Products (HMPC):
Assessment report on Sambucus nigra L., flos, Final

5) 28 January 2014, EMA/HMPC/32465/2013, Committee on Herbal Medicinal Products (HMPC):
Public statement on Sambucus nigra L., fructus, Final

6) 28 January 2014, EMA/HMPC/44208/2012, Committee on Herbal Medicinal Products (HMPC):
Assessment report on Sambucus nigra L., fructus

7) Fr. Ph. 2007 ANSM Sambucus nigra ad praeparationes homoeopathicas
ELDERBERRY FOR HOMOEOPATHIC PREPARATIONS

DEFINITION: Elderberry  mother  tincture  complies  with  the  requirements  of  the  general  technique  for  the preparation  of  mother  tinctures  (see  Homoeopathic  Preparations  (1038)  and  French Pharmacopoeia Authority Supplement).

The mother tincture is prepared with ethanol (45 per cent V/V), using the fresh, blooming flower head of Sambucus nigra L.

Content:  minimum  0.060  per  cent  m/m  of  total  flavonoids,  expressed  as  rutin  (C₂₇H₃₀O₁₆; Molecular Weight: 610.521 g/mol).

Biljni preparati u tečnom obliku (nerazblaženi ili razblaženi) za oralnu i lokalnu upotrebu.

a) Sambucus nigra L., fructus (Black elderberry fresh berry),
b) Sambucus nigra L., flores et inflorescentiae (Black elderberry fresh flower and inflorescence/ blooming flower heads).

Sastav:
a) tečni ekstrat (DER 1:2), ekstrakcioni rastvarač etanol 65% (v/v),
b) tečni ekstrat (DER 1:1), ekstrakcioni rastvarač etanol 51% (v/v).

Sambucus nigra L., sadrži 247 hemijskih jedinjenja koja ispoljavaju 694 istraženih dejstava (podaci ažurirani februara 2019.).

Sadržaj:
a) minimalno 0,06% m/m ukupnih flavonoida, izraženih kao rutin – rutin trihidrat (MF: C₂₇H₃₀O₁₆, MW: 610,6175 g/mol⁻¹; MF: C₂₇H₃₆O₁₉, MW: 664,56334 g/mol⁻¹),
b) u većoj koncentraciji sadrži alfa-amirenona, …
flower: CHLOROGENIC-ACID, RUTIN, OLEANOLIC-ACID, BETA-AMYRIN, PALMITIC-ACID, URSOLIC-ACID, BETA-SITOSTEROL, OLEIC-ACID, P-COUMARIC-ACID, PECTIN, LUPEOL, CHOLESTEROL, LINOLEIC-ACID, CAMPESTEROL, KAEMPFEROL, TRIDECANOIC-ACID, ASTRAGALIN, ISOQUERCITRIN, STIGMASTEROL, ALPHA-AMYRIN, …
fruit: FIBER, GLUCOSE, FRUCTOSE, DEXTROSE, LEVULOSE, POTASSIUM, MALIC-ACID, SUCROSE, CITRIC-ACID, PHOSPHORUS, TYROSINE, LACTIC-ACID, MAGNESIUM, ASCORBIC-ACID, CALCIUM, SODIUM, OXALIC-ACID, BETA-CAROTENE, IRON, ZINC …
c) više od svih biljaka sadrži alkana, kaprifolnu kiselinu, heneikosana, sambunigrina, sambucina, …
d) sadrži vode do 82,2% (plod), 

Indikacije: Biljni preparati su namenjeni poboljšanju opšteg stanja organizma kroz razna naučno dokazana dejstva. Upotreba kod respiratornih i kožnih tegoba.

Dr. Džems Djuk (Dr. James Duke) u Handbook of Medicinal Herbs, 2nd Ed. (2002). CRC Press, navodi sledeće: 

 – ima jako dejstvo kod: bronhitisa, nazeba, kašlja, groznice, gripa, ...

 – delotvoran kod: katara, konstipacije, dispneje, gripa, herpesa, inflamacija, influence, respiratornih infekcija, sinuzitisa, virusnih infekcija, zastoja tečnosti, prehlada, DM-a, …

 – u narodnoj medicini kod: pada imuniteta, artroza, astme, modrica, Ca.(dojke, jetre, kože, prepucijuma, slezine, želudca, materice), kondiloma, grčeva, hidropsije, ekcema, edema, epilepsije, erizipela, egzantema, gasova, gastritisa, gihta, glavobolje, hepatitisa, promuklosti, induracije, laringitisa i faringitisa, mialgije, neuralgije, neuroza, gojaznosti, otitisa, pneumonije, reumatizma, groznice, skleroza, škrofula, stomatitisa, zubobolje, sifilisa, psorijaze, uteritisa, … ekstrakt ploda ima umereno dejstvo na Candida albicans.

 – spoljašnja primena kod: ekcema,  šuge, bradavica, opekotina, dermatoza, …kozmetik, …

– upotrebljava se kao: antiinflamatik, antivirotik, diuretik, purgativ, ekspektorant, imunostimulator, laksativ, hemostatik, dijaforetik, mukolitik, sudorifik, … alternativ, antipiretik, karminativ, depurativ, analgetik, emetik, emolient, laktagog, stimulant fagocita, stomahik, emolient, laktagog, za ispiranje usta, oftalmik, …

 Monografija nemačke E komisije (Commission E Monographs), terapijski vodič za biljne lekove, preporučuje Sambucus nigra za kašalj, bronhitis, prehlade i groznicu.

Doziranje i način primene:
do 2 mL (80 kapi) podeljeno u 2 do 4 doze.
Biljni preparat CRNA ZOVA HSS i TM:
pojedinačna doza: 0,5-1 mL, preporučena dnevna doza (PDD): 2 mL.
Oralna (15 minuta pre obroka) i lokalna primena.
Upotreba na koži: aplicirati na obolelo mesto u tankom sloju ili obliku impregniranog zavoja.

Napraviti pauzu posle 4 nedelje neprekidne upotrebe.

Po preporukama, preparat postiže najbolje efekte pri upotrebi od 8 do 12 nedelja, duža upotreba je bezbedna uz pauze.

Kontraindikacije: preosetljivost na aktivne supstance, preosetljivost na biljke porodice (genus Sambucus, family Adoxaceae).

Čuvanje: na tamnom, suvom i hladnom mestu do 20˚C, van domašaja dece i izlaganja EM zračenju,  u dobro zatvorenoj originalnoj ambalaži.

 Rok upotrebe: 5 godina, posle prvog otvaranja 6 meseci. Uz odgovarajuće čuvanje, rok upotrebe je neograničen.

 Pakovanje: 50 mL i 100 mL, standarne farmaceutske braon bočice; 250 mL, 500 mL, 1L i 5 L na zahtev.

Nutritivne informacije:
CRNA ZOVA HSS i TM:
a) energetska vrednost u 100 mL: 1504 kJ/ 360 kcal,
u preporučenoj dnevnoj dozi (PDD) 2 mL: 30kJ/ 7,17 kcal,
suve materije(DR)više od 1,7% (HAB 2000).
b) energetska vrednost u 100 mL: 1172 kJ/ 280kcal,
u preporučenoj dnevnoj dozi (PDD) 2 mL: 23,45kJ/ 5,6kcal;
suve materije (DR) više od 2,2% (Fr. Ph.).

Bez konzervanasa, proteina, masti i ugljenih hidrata. CRNA ZOVA TM su rukom rađeni proizvodi. 

 Analizu na teške metale, pesticide i mikrobiološku ispravnost preparata broj 4603120601 od 29.03.2016. godine

izvršila ANAHEM LABORATORIJA BEOGRAD, u sklopu preparata RESPIRO 30.

CENOVNIK

MATIČNA TINKTURA, CRNA ZOVA TM, hidroetanolni tečni ekstrakt svežih cvetova biljke, DER 1:1 (Ph. Fr.).

50 mL – 600,00 RSD (5 evra); 100 mL – 1200,00 RSD (10 evra).

NAPOMENA: Deca preko 2 godine starosti mogu da koriste matične tinkture u količini 1 kap po godini života, 3 puta dnevno, maksimalno 30 kapi dnevno. Poželjna konsultacija zdravstvenog profesionalca.

Poželjno pogledati sve informacije na: http://www.biljni-preparati.com/preparati/crna-zova/

Podaci objavljeni prvi put 30. maja 2015. godine. Podaci ažurirani oktobra 2020.godine.

Upotreba crne zove (Sambucus nigra L.) sa referencama.

Sambucus nigra (Caprifoliaceae) Common names Sauco; Zovika;  Murver Agaci; Elder Rind; European Elder; Khaman Kabir; Elderberry

Data by National Agricultural Library

Sambucus nigra (Adoxaceae)

Common names: Elder; European Alder; Black Elder; European Elderberry; European Elder

Activities: 694    Chemicals w/Activities: 129   All Chemicals: 247

Activity (dejstva po broju aktivnih biojedinjenja) ukupno 694

VAŽNA NAPOMENA: SVE DEJSTVA SU POTKREPLJENA REFERENCAMA.

pesticide, antioxidant, antibacterial, Cancer-preventive, antiinflammatory, antitumor, antiseptic, antiviral, antimutagenic, antispasmodic, antiulcer, hepatoprotective, hypocholesterolemic, analgesic, hypotensive, antihepatotoxic, FLavor, perfumery, aldose-reductase-Inhibitor, fungicide, antidiabetic, allergenic, anticancer, antiradicular, insectifuge, antiedemic, Irritant, antihistaminic, sedative, antileukemic, antiallergic, cytotoxic, Nematicide, antinociceptive, antiarthritic, antitumor-promoter, choleretic, hypoglycemic, vasodilator, choleretic, antiperoxidant, candidicide, antifeedant, antiherpetic, immunomodulator, chemopreventive, antiaggregant, antitumor (colon), lipoxygenase-inhibitor, cardioprotective, antihypertensive, carcinogenic, anticariogenic, antirheumatic, ornithine-decarboxylase-inhibitor, antialzheimeran, COX-2-Inhibitor, antidepressant, vulnerary, apoptotic, anticonvulsant, antiflu, antitumor (breast), antinitrosaminic, prostaglandin-synthesis-inhibitor, insecticide, antiacne, antiarrhythmic, antiobesity, antiosteoporotic, antimalarial, antidementia, antitumor (lung), laxative, tyrosinase-inhibitor, antiaging, sweetener, myorelaxant, anxiolytic, antilithic, anticarcinomic, antimetastatic, antialcoholic, antiPMS, estrogenic, antiLyme, antialopecic, antihangover, antiplaque, antilymphomic, antidermatitic, calcium-antagonist, ACE-inhibitor, cyclooxygenase-inhibitor, antistaphylococcic activity, anticarcinomic, antimetastatic, antiophidic, expectorant, cosmetic, antinephritic, allelochemic, CNS-depressant, antiandrogenic, antimigraine, anticoronary, antineuralgic, hemostat, antisyndrome-X, propecic, xanthine-oxidase-Inhibitor, sunscreen, hypercholesterolemic, antiacetylcholinesterase, …

Elderberry Fruit, whole (Sambucus nigra)

Elderberry Fruit Tinctures-Liquid Herbal Extracts

Sambucus nigra fruit has been used for centuries in North America, Western Asia, Europe and North Africa.

Medicinal benefits of Sambucus nigra fruit extracts have been used to stimulate the immune system and protect against free radicals that attack healthy cells. In fact, certain studies have proven its effectiveness in helping in the fight against viruses such as herpes, AIDS, and HIV, or human immunodeficiency virus. Its antioxidant activity is found to be useful in lowering cholesterol, improving vision, heart health and for coughs, colds and other viral and bacterial infections and tonsillitis. People who have taken Sambucus nigra fruit have reported less severe symptoms and have felt much better, much faster than those who did not. It was used in 1995, in Peru to stop a flu epidemic! So, at the first sign of a cold or virus, treat yourself to Sambucus nigra. Some have stated that it has helped considerably to alleviate the symptoms, and within 72 hours. This herbal extract has also been used to help with weight loss, and as a treatment for headaches and migraines, rheumatism, gout, edema, hepatic disease, syphilis, epilepsy, toothache, asthma and to help wounds heal faster. As a revitalizing stimulant and rejuvenating tonic, it is said to promote circulation, kidney function and good lymphatic system health. Since eating the berries doesn’t give you the same concentrated benefits it is more beneficial as an Sambucus nigra fruit tincture.
Sambucus nigra enhances the immune system function by focusing on the nutritional needs of the immune system. Flavonoids, including quercetin and anthocyanins, may account for the therapeutic actions of the flowers and berries. These are powerful antioxidants that protect cells against damage. Further research has indicated that the anthocyanins found in the berries possess more antioxidant capacity than either vitamin E or vitamin C. As a matter of fact, certain studies have proven its effectiveness in fighting viruses such as herpes, genital warts, and HIV, or human immunodeficiency virus. The wide range of medical benefits, from colds to debilitating asthma, diabetes, and weight loss, is probably due to the enhancement of each individual’s immune system.
Sambucus nigra is said to reduce the course of the infection for cold or other viral infections and is a potent remedy and preventative herb. Ingesting a generous amount of dosage of Sambucus nigra liquid extract every day will secure the body against the straining effects of the common cold. And it has been as a remedy for those diagnosed with type B influenza and has been found to be equally effective on type A influenza. Several studies have shown that an extract of Sambucus nigra demonstrated efficacy in the treatment of both adults and children with either type A or B influenza, reducing both the severity and duration of flu symptoms in otherwise healthy subjects. This should not be considered a substitute for influenza vaccination in high-risk individuals. An in vitro study also showed Elderberry’s potential effectiveness against the H5N1 avian influenza virus.

Sambucus nigra is antiviral, antibiotic and antibacterial and has been used for centuries for soothing upper respiratory infections. It is an excellent remedy for asthma, bronchial infections, furunculosis, and sinusitis.

Sambucus nigra has long been used to treat coughs, common colds, sore throat and runny nose. As an expectorant, it reduces excessive mucus and expels phlegm. Taking Sambucus nigra will also usually promote heavy perspiration and sweating; and following a soothing sleep, a fever may be lowered.
The flavonoids in Sambucus nigra extracts are effective in decreasing inflammation and preventing and repairing the destruction of joint tissue. Acute symptoms of gout are often caused by urate crystals, the uric acid that builds up and settles into hard lumps under the skin around the joints, leading to joint deformity and decreased the range of motion. These hard lumps, called tophi, may also develop in the kidneys and other internal organs, under the skin of the ear, or at the elbow. People with gout usually face a higher risk of developing kidney stones and kidney disease.

Sambucus nigra are an excellent herb for gout as they are low in purine and high in cyanidin. Sambucus nigra is a diuretic, this herb increases urine flow and promotes all fluid secretions, helping to cleanse the system. By promoting heavy sweating,

Sambucus nigra also opens the pores, and it aids the further elimination of toxic material and impurities from the body through the skin.

Sambucus nigra extract is also good for circulation of the blood and may help to dispel rheumatism, as well as treat fractures and injuries from falls.Sambucus nigra is a mild laxative and has been used as a natural intestinal cleanser for centuries. It has been said to work like very quickly to evacuate the bowels and relieve constipation.

Sambucus nigra tinctures can help to alleviate problems associated with the intestinal tract. It is soothing to the stomach and helps aid in digestion. At the same time, the herbal product is understood to help to kill bacterial infections, and other forms of infection within the body, including the intestinal tract. They also have a mild tonic action that may help to stop diarrhea. Many herbalists believe that there is a very strong connection between bowel problems and respiratory congestion. There also appears to be a strong connection between bowel obstruction and fevers in children.
Sambucus nigra may have a direct effect on the spread and growth of cancerous tissues. In one study it was shown to inhibit the ability of tumors to grow their own blood vessels. Research (2009) suggests that berries may be among the most potent cancer-fighting fruits, with a particular emphasis on Elderberry, Blackberry, Red Raspberry, Strawberry, and Blueberry.
Sambucus nigra fruit contains a number of healthful compounds including vitamins, selenium, calcium, polyphenols and, perhaps most notably, anthocyanins, which give berries their color and have, in laboratory tests, produced slower tumor growth and fewer esophageal tumors.
Sambucus nigra extract is beneficial to the heart, by improving blood flow throughout the body. A rise in bad cholesterol levels has proven to be harmful to the heart and arterial system. Studies have proven that Sambucus nigra fruit extract with its cyanidin glucoside content prevents the oxidation of LDL-the low-density lipids or bad cholesterol, preventing the onset of cardiovascular diseases, especially heart attacks and strokes. Sambucus nigra was also found to have an extraordinary effect on reducing stress and helps to significantly shorten recovery time after physical exertion.
Several animal studies show that the polyphenols present in Sambucus nigra extracts help to lower blood sugar and fat levels. They also possess significant antioxidant activity and may help to protect individuals with diabetes from the harmful effects of unstable free radicals that are formed as result of metabolic processes in the body. Sambucus nigras have shown to possess insulin-like activity and may promote increased secretion of insulin from the pancreas. Sambucus nigra may also help with other complications of diabetes, such as immune deficiencies.
Sambucus nigra delivers benefits to the skin by providing antioxidants to sensitive, aging skin, while providing instant antioxidant hydration. The anthocyanins, provided by the extract of elderberries, are known for their high-performance anti-aging effects. Although skin lightening effects have been studied, it is the Elderberry flower that is known to gently stimulate the epidermis and is high in astringent tannins that make it useful for firming the skin, wound healing and toning. Eczema, psoriasis, scleroderma, rash and other skin problems resistant to conventional treatments are said to be no match for Elderberry’s powerful properties. Acne-ridden skin is said to especially benefit from Sambucus nigra extract. Other traditional uses for Sambucus nigra have included the treatment of burns, bruises and wound healing.

Ingredients: Sambucus nigra Flower (Whole), Structured Water, 96% Alcohol.
Non-Alcohol: Sambucus nigra Flower (Whole), Structured Water, Organic Vegetable Glycerin
Ingredients: Sambucus nigra Fruit (Whole), Structured Water, 96% Alcohol.
Non-Alcohol: Sambucus nigra Fruit (Whole), Structured Water, Organic Vegetable Glycerin.
All of our ingredients are Certified Organic, Kosher, or Responsibly Wildcrafted. No genetically modified organisms (GMO’s) are involved. All other products that are distributed by us meet our high-quality standards.
Instructions: Use 10-20 drops in juice or water, under the tongue or as desired. May be taken 3 times daily. Shake well. Store in cool dark place. Keep out of reach of children.
Disclaimer: The information presented herein by Herbal Alchemy is intended for educational purposes only. These statements have not been evaluated by the FDA and are not intended to diagnose, cure, treat or prevent disease. Individual results may vary, and before using any supplements, it is always advisable to consult with your own healthcare provider.

HOMOEOPATHIC MATERIA MEDICA
by William BOERICKE, M.D.
Presented by Médi-T

  
SAMBUCUS NIGRA
Elder

Acts especially on the respiratory organs. Dry coryza of infants, snuffles, śdematous swellings. Profuse sweat accompanies many affections.

Mind.–Sees images when shutting eyes. Constant fretfulness. Very easily frightened. Fright followed by suffocative attacks.

Face.–Turns blue with cough. Red, burning spots on cheeks. Heat and perspiration of face.

Abdomen.–Colic, with nausea and flatulence; frequent watery, slimy stools.

Urine.–Profuse urine with dry heat of skin. Frequent micturition, with scanty urine. Acute nephritis; dropsical symptoms, with vomiting.

Respiratory.–Chest oppressed with pressure in stomach, and nausea Hoarseness with tenacious mucus in larynx. Paroxysmal, suffocative cough, coming on about midnight, with crying and dyspnśa. Spasmodic croup. Dry coryza. Sniffles of infants; nose dry and obstructed. Loose choking cough. When nursing child must let go of nipple, nose blocked up, cannot breathe. Child awakes suddenly, nearly suffocating, sits up, turns blue. Cannot expire (Meph). Millar’s asthma.

Extremities.–Hands turn blue. Śdematous swelling in legs, insteps, and feet. Feet icy cold. Debilitating night-sweats (Salvia; Acet ac).

Fever.–Dry heat while sleeping. Dreads uncovering. Profuse sweat over entire body during waking hours. Dry, deep cough precedes the fever paroxysm.

Skin.–Dry heat of skin during sleep. Bloated and swollen; general dropsy; profuse sweat on waking.

Modalities.–Worse, sleep, during rest, after eating fruit. Better, sitting up in bed, motion.

Relationship.–Compare: Ipec; Meph; Opium; Sambucus Canadensis (great value in dropsies; large doses required-fluid extract, 1/4 to 1 teaspoonful three times daily).

Antidotes: Ars; Camph.

Dose.–Tincture, to sixth potency.

Copyright © Médi-T 1999

SAMBUCUS NIGRA Urtinktur DHU

CERES Sambucus nigra Urtinktur 20 ml Tropfen von CERES

Elderberry (Sambucus nigra) Mother Tincture

Medicinal uses

Uses supported by clinical data

None.

Uses described in pharmacopoeias and in traditional systems of medicine

As a diaphoretic for treatment of fever and chills, and as an expectorant for treatment of mild inflammation of the upper respiratory tract. Also for symptomatic treatment of the common cold (1, 7, 14).

Uses described in folk medicine, not supported by experimental or clinical data

Treatment of conjunctivitis, constipation, diabetes, diarrhoea, dry skin, headaches and rheumatism (5, 13, 15).

Pharmacology

Experimental pharmacology

Anti-inflammatory activity

An 80% ethanol extract of Flos Sambuci had moderate anti-inflammatory activity in rats: it inhibited carrageenan-induced footpad oedema by 27%. The extract was administered intragastrically (100 mg/kg body weight) 1 hour prior to administration of carrageenan. The control drug, indometacin (5mg/kg body weight) inhibited carrageenan-induced footpad oedema by 45% (16). Intraperitoneal administration of an unsaponifiable fraction of the flowers to mice moderately enhanced phagocytosis at a dose of 0.5 ml/animal (17). A 100% methanol extract of the flowers inhibited the biosynthesis of the inflammatory cytokines interleukin-1α, interleukin-1β and tumour necrosis factor-α at a concentration of 30 µg/ml in human peripheral mononuclear cells in vitro (18).

Diuretic activity

Intragastric administration of an infusion of the flowers (20 ml/kg body weight) or of a potassium- and flavonoid-rich extract of the flowers had a diuretic effect in rats which was greater than that observed with theophylline (5mg/kg body weight) (19).

Clinical pharmacology

Diaphoretic activity

Flos Sambuci is reported to increase the response of the sweat glands to heat stimuli (7, 20, 21), and increase diaphoresis in healthy subjects (7, 21).

Contraindications

No information available.

Warnings

No information available.

Precautions

No information available on general precautions or precautions concerning drug interactions; drug and laboratory test interactions; carcinogenesis, mutagenesis, impairment of fertility; teratogenic and non-teratogenic effects in pregnancy; nursing mothers; or paediatric use. Therefore, Flos Sambuci should not be administered during pregnancy or lactation or to children without medical supervision.

Adverse reactions

No information available.

Dosage forms

Crude drug for decoctions and infusions (crude drug also available in tea bags); as a component of multi-ingredient products (7). Store in a well-closed container, protected from light (2).

Posology

(Unless otherwise indicated)
Daily dosage: crude drug 3-5 g as an infusion (preferably taken hot) three times daily; 25% ethanol extract 3-5 ml; tincture (1:5 in 25% ethanol) 10-25 ml (22).

Izvor: WHO

X X X

Mechanism of Action

Pharmacology:

– Constituents: There are multiple chemical and biochemical studies of chemical constituents in S. nigra. The bark contains α-amyrenone, α-amyrin, betulin, oleanolic acid, beta-sitosterol¹², as well as nigrin b, a lectin similar to ricin, and other type 2 ribosome inactivating proteins (RIPs) that are less toxic to cells and animals ¹³. The flowers/leaves contain flavonoids including quercetin (up to 3%), rutin, hyperoside¹⁴, and anthocyanins ¹¹, as well as essential oils (responsible for the muscat aroma characteristic of elder flowers)¹⁵, mucilage, tannins (3%), organic acids, glycoside (0.042% by weight), plastocyanin ¹⁶, and sambunigrin (0.042% by weight). High amounts of N-phenylpropenoyl-L-amino acid amides were found in the flowers of Sambucus nigra.¹⁷

– The fruit contains the protein Sambucus nigra agglutinin Ivf or SNAIVf, which is homologous to type 2 ribosome inactivating protein (RIP)¹⁸, while the bark contains a novel type 2 RIP (SNLRP), consisting of an A-chain with N-glycosidase activity and a B-chain devoid of carbohydrate binding activity normally present^19,20. Two additional RIPs were further identified in bark (SNAI and SNAI’)¹⁹, demonstrating the complexity of Type 2 RIP/lectins in S. nigra. The lectin isolated from bark is tetrameric with two distinct subunits and is rich in glutamine/glutamic acid, valine, and leucine.²¹ The fruit type 2 RIP lectin is 10 amino acids longer than the bark lectin.²² Elder RIPs with N-glycosidase activity are reported to inhibit protein synthesis in rabbits but not in plants.⁵

– Quercetin is also present in elder and has been shown to be a potent inhibitor of xanthine oxidase.²³ S. nigra has been shown to bind heavy metals.²⁴

– Experimental assays: The lectin of S. nigra has been used in multiple experimental clinical assays, due to its carbohydrate binding properties and its ability to precipitate highly sialylated glycoproteins²⁵, including the use of S. nigra agglutinin binding to identify pregnant women at risk for pre-term delivery (by detecting fibronectin in cervicovaginal secretions using a glycoprotein lectin immunoabsorbent assay)²⁶; distinguishing normal from stone-forming kidneys (using N-acetylneuraminic acid-calcium binding ratios)²⁷; examining colorectal carcinoma by examining rates of colonic mucin sialylation (by comparing alpha 2,6-linked sialic acid versus sialyl-Tn antigen)²⁸; evaluating ulcerative colitis by monitoring differences in sialylation in Asian versus European colitis patients²⁹; examining increased beta-galactoside alpha 2,6-sialyltransferase activity (by detection of dioxigenin-conjugated S. nigra agglutinin)³⁰; evaluating SNA levels in women with breast and ovarian cancer³¹; glycohistochemically identifying microglial cells from Alzheimer’s disease samples³²; measuring decreased sialylation of glycoproteins in nasal glands of patients with sinusitis³³; monitoring elevated serum sialic acids associated with increased cardiovascular mortality³⁴; and enriching stem cell samples/depleting T-cells in bone marrow harvests³⁵.

– Anti-inflammatory effects: S. nigra is reported to modulate the inflammatory cytokines IL-1 and TNF-alpha^3,36; increase human basophil secretion of IL-4, IL-13, and histamine⁹; alter function of human neutrophils³⁷, and inhibit macrophage release of proinflammatory cytokines and nuclear transcription factor kB and phosphatidylinositol 3-kinase⁴.

– Antioxidant effects: Elderberries contain flavonoids (flavone, flavonone, isoflavone derivatives and anthocyanins), which are reported to possess antioxidant activity and to protect against oxidative stressors, such as hydrogen peroxide, 2-amidinopropane, dihydrochloride (AAPH), ferrous sulfate, and ascorbic acid.^38,39,40,41

– Antiproliferative effects: S. nigra agglutinin has been reported to inhibit nuclear protein transport in neuroblastoma cells, suggesting a functional significance of sialation.⁴²

– Antiviral effects: Based on laboratory and animal study, S. nigra may possess antiviral effects by inhibiting influenza virus types A and B and herpes simplex virus-1⁴³, reducing hemagglutination of red blood cells, and inhibiting replication of several strains of influenza A and B⁶. A case report exists of an HIV positive women, taking no HIV drugs, who experienced a viral load drop from 17,000 to 4,000 after ingestion of Sambucol^® with olive leaf extract.⁸ The report also included a placebo controlled, double-blind study of Sambucol associated with a rapid recovery from influenza and inhibited replications of nine other strains of the flu virus by elderberry. The mechanism is believed to be rendering viruses nonfunctional by staining and coating them.

– Diuretic effects: In a rat study, diuretic effects and sodium excretion were associated with an extract of S. nigra flowers.⁷

– Glucose/insulin metabolism: In vitro research¹⁰ refutes earlier study⁴⁴, and reports stimulation of glucose metabolism and promotion of insulin secretion from beta cells.

– Respiratory effects: The combination herbal product Sinupret^®, which contains elder, has been studied for its effects on bronchitis. There is a lack of reliable human evidence evaluating elder monotherapy as a treatment for bronchitis, however, and a mechanism of action is unclear.

– Vascular effects: The multi-ingredient product OptiBerry IH141 has been shown to possess antiangiogenic properties via inhibition of H₂O₂ and TNF-alpha-induced Vascular Endothelial Growth Factor.¹ In another study, elderberry extracts were associated with significantly impaired angiogenesis in human dermal microvascular endothelial cells.²

Pharmacodynamics/Kinetics:

– Absorption: Anthocyanins, which are potent flavonoid antioxidants found in elder, are not absorbed in their unchanged glycosylated forms in humans.⁴⁵ The maximum concentration of anthocyanins found in blood after injection of a highly concentrated solution was 35mg/mL at one hour, followed by a quick decay.³⁹

– Elimination: The elimination of plasma anthocyanins appears to follow first-order kinetics, and most anthocyanin compounds are excreted in urine within four hours after ingestion.⁴⁵ After ingestion of about 30mL of elderberry extract (147.3mg total anthocyanins), the t_½ was 1.74 hours.⁴⁶ The urinary excretion rate of intact anthocyanins was fast, and appeared to be monoexponetial with high variability.

– At a dose of 3g/kg, S. nigra extract did not modify the growth rate of rats.³

– Flowers are believed to be safe for use in food, provided HCN levels are below 25ppm.

References

1. Bagchi, D., Sen, C. K., Bagchi, M., and Atalay, M. Anti-angiogenic, antioxidant, and anti-carcinogenic properties of a novel anthocyanin-rich berry extract formula. Biochemistry (Mosc)2004;69(1):75-80, 1. 14972022
2. Roy, S., Khanna, S., Alessio, H. M., Vider, J., Bagchi, D., Bagchi, M., and Sen, C. K. Anti-angiogenic property of edible berries. Free Radic Res2002;36(9):1023-1031. 12448828
3. Mascolo N, Autore G, Capasso F, and et al. Biological screening of Italian medicinal plants for anti-inflammatory activity. Phytotherapy Research 1987;1(1):28-31.
4. Harokopakis, E., Albzreh, M. H., Haase, E. M., Scannapieco, F. A., and Hajishengallis, G. Inhibition of proinflammatory activities of major periodontal pathogens by aqueous extracts from elder flower (Sambucus nigra). J Periodontol2006;77(2):271-279. 16460254
5. de Benito, F. M., Iglesias, R., Ferreras, J. M., Citores, L., Camafeita, E., Mendez, E., and Girbes, T. Constitutive and inducible type 1 ribosome-inactivating proteins (RIPs) in elderberry (Sambucus nigra L.). FEBS Lett5-22-1998;428(1-2):75-79. 9645479
6. Zakay-Rones, Z., Varsano, N., Zlotnik, M., Manor, O., Regev, L., Schlesinger, M., and Mumcuoglu, M. Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama. J Altern Complement Med1995;1(4):361-369. 9395631
7. Beaux, D., Fleurentin, J., and Mortier, F. Effect of extracts of Orthosiphon stamineus Benth, Hieracium pilosella L., Sambucus nigra L. and Arctostaphylos uva-ursi (L.) Spreng. in rats. Phytother Res1999;13(3):222-225. 10353162
8. Konlee, M. A new triple combination therapy. Posit Health News1998;(No 17):12-14. 11366542
9. Haas, H., Falcone, F. H., Schramm, G., Haisch, K., Gibbs, B. F., Klaucke, J., Poppelmann, M., Becker, W. M., Gabius, H. J., and Schlaak, M. Dietary lectins can induce in vitro release of IL-4 and IL-13 from human basophils. Eur J Immunol1999;29(3):918-927. 10092096
10. Gray, A. M., Abdel-Wahab, Y. H., and Flatt, P. R. The traditional plant treatment, Sambucus nigra (elder), exhibits insulin-like and insulin-releasing actions in vitro. J Nutr2000;130(1):15-20. 10613759
11. Mulleder, U., Murkovic, M., and Pfannhauser, W. Urinary excretion of cyanidin glycosides.J Biochem Biophys Methods 2002;53(1-3):61-66. 12406587
12. Lawrie W, McLean J, and Paton AC. Triterpenoids in the bark of elder (Sambucus nigra). Phytochemistry1964;3:267-268.
13. Battelli, M. G., Citores, L., Buonamici, L., Ferreras, J. M., de Benito, F. M., Stirpe, F., and Girbes, T. Toxicity and cytotoxicity of nigrin b, a two-chain ribosome- inactivating protein from Sambucus nigra: comparison with ricin. Arch Toxicol1997;71(6):360-364. 9195017
14. Davidek J. Isolation of chromatographically pure rutin from flowers of elder. Nature1961;189(4763):487-488.
15. Toulemonde B and Richard HM. Volatile constituents of dry elder (Sambucus nigra L.) flowers.J Agric Food Chem 1983;31(2):365-370.
16. Scawen, M. D., Ramshaw, J. A., Brown, R. H., and Boulter, D. The amino-acid sequence of plastocyanin from Sambucus nigra L. (Elder). Eur J Biochem5-2-1974;44(1):299-303. 4854645
17. Hensel, A., Deters, A. M., Muller, G., Stark, T., Wittschier, N., and Hofmann, T. Occurrence of N-phenylpropenoyl-L-amino acid amides in different herbal drugs and their influence on human keratinocytes, on human liver cells and on adhesion of Helicobacter pylori to the human stomach. Planta Med2007;73(2):142-150. 17295182
18. van Damme, E. J., Roy, S., Barre, A., Rouge, P., van Leuven, F., and Peumans, W. J. The major elderberry (Sambucus nigra) fruit protein is a lectin derived from a truncated type 2 ribosome-inactivating protein. Plant J1997;12(6):1251-1260. 9450339
19. van Damme, E. J., Roy, S., Barre, A., Citores, L., Mostafapous, K., Rouge, P., van Leuven, F., Girbes, T., Goldstein, I. J., and Peumans, W. J. Elderberry (Sambucus nigra) bark contains two structurally different Neu5Ac(alpha2,6)Gal/GalNAc-binding type 2 ribosome-inactivating proteins. Eur J Biochem5-1-1997;245(3):648-655. 9183001
20. van Damme, E. J., Barre, A., Rouge, P., van Leuven, F., and Peumans, W. J. Isolation and molecular cloning of a novel type 2 ribosome-inactivating protein with an inactive B chain from elderberry (Sambucus nigra) bark. J Biol Chem3-28-1997;272(13):8353-8360. 9079659
21. Broekaert, W. F., Nsimba-Lubaki, M., Peeters, B., and Peumans, W. J. A lectin from elder (Sambucus nigra L.) bark. Biochem J7-1-1984;221(1):163-169. 6466312
22. Peumans, W. J., Roy, S., Barre, A., Rouge, P., van Leuven, F., and van Damme, E. J. Elderberry (Sambucus nigra) contains truncated Neu5Ac(alpha- 2,6)Gal/GalNAc-binding type 2 ribosome-inactivating proteins. FEBS Lett3-20-1998;425(1):35-39. 9541002
23. Chang, W. S., Lee, Y. J., Lu, F. J., and Chiang, H. C. Inhibitory effects of flavonoids on xanthine oxidase. Anticancer Res1993;13:2165-2170. 8297130
24. Coupe, S. A., Taylor, J. E., and Roberts, J. A. Characterisation of an mRNA encoding a metallothionein-like protein that accumulates during ethylene-promoted abscission of Sambucus nigra L. leaflets. Planta1995;197(3):442-447. 8580758
25. Shibuya, N., Goldstein, I. J., Broekaert, W. F., Nsimba-Lubaki, M., Peeters, B., and Peumans, W. J. The elderberry (Sambucus nigra L.) bark lectin recognizes the Neu5Ac(alpha 2-6)Gal/GalNAc sequence. J Biol Chem2-5-1987;262(4):1596-1601. 3805045
26. Hampel, D. J., Kottgen, B., Dudenhausen, J. W., and Kottgen, E. Fetal fibronectin as a marker for an imminent (preterm) delivery. A new technique using the glycoprotein lectin immunosorbent assay.J Immunol Methods 4-22-1999;224(1-2):31-42. 10357204
27. Hofbauer, J., Fang-Kircher, S., Steiner, G., Wiener, H., Susani, M., Simak, R., Ghoneim, M. A., and Marberger, M. N-acetylneuraminic acids (nana): a potential key in renal calculogenesis. Urol Res1998;26(1):49-56. 9537697
28. Murayama, T., Zuber, C., Seelentag, W. K., Li, W. P., Kemmner, W., Heitz, P. U., and Roth, J. Colon carcinoma glycoproteins carrying alpha 2,6-linked sialic acid reactive with Sambucus nigra agglutinin are not constitutively expressed in normal human colon mucosa and are distinct from sialyl-Tn antigen. Int J Cancer3-4-1997;70(5):575-581. 9052758
29. McMahon, R. F., Warren, B. F., Jones, C. J., Mayberry, J. F., Probert, C. S., Corfield, A. P., and Stoddart, R. W. South Asians with ulcerative colitis exhibit altered lectin binding compared with matched European cases. Histochem J1997;29(6):469-477. 9248854
30. Dall’Olio, F. and Trere, D. Expression of alpha 2,6-sialylated sugar chains in normal and neoplastic colon tissues. Detection by digoxigenin-conjugated Sambucus nigra agglutinin. Eur J Histochem1993;37(3):257-265. 7693064
31. Goodarzi, M. T. and Turner, G. A. Decreased branching, increased fucosylation and changed sialylation of alpha-1-proteinase inhibitor in breast and ovarian cancer. Clin Chim Acta 5-15-1995;236(2):161-171. 7554283
32. Zambenedetti, P., Giordano, R., and Zatta, P. Histochemical localization of glycoconjugates on microglial cells in Alzheimer’s disease brain samples by using Abrus precatorius, Maackia amurensis, Momordica charantia, and Sambucus nigra lectins. Exp Neurol 1998;153(1):167-171. 9743580
33. Ueno, K., Wang, Z. H., Hanamure, Y., Yoshitsugu, M., Fukuda, K., Furuta, S., Uehara, F., and Ohyama, M. Reduced sialylation of glycoproteins in nasal glands of patients with chronic sinusitis.Acta Otolaryngol 1997;117(3):420-423. 9199529
34. Crook, J. R., Goldman, J. H., Dalziel, M., Madden, B., and McKenna, W. J. Increased ventricular sialylation in patients with heart failure secondary to ischemic heart disease. Clin Cardiol1997;20(5):455-458. 9134277
35. Mumcuoglu, M., Manor, D., and Slavin, S. Enrichment for GM-CFU from human bone marrow using Sambucus nigra agglutinin: potential application to bone marrow transplantation. Exp Hematol1986;14(10):946-950. 3533587
36. Yesilada, E., Ustun, O., Sezik, E., Takaishi, Y., Ono, Y., and Honda, G. Inhibitory effects of Turkish folk remedies on inflammatory cytokines: interleukin-1alpha, interleukin-1beta and tumor necrosis factor alpha. J Ethnopharmacol1997;58(1):59-73. 9324006
37. Timoshenko, A. V. and Cherenkevich, S. N. [H2O2 generation and human neutrophil aggregation as affected by lectins]. Gematol Transfuziol1995;40(4):32-35. 7557235
38. Abuja PM, Murkovic M, and Pfannhauser W. Antioxidant and prooxidant activities of elderberry (Sambucus nigra) extract in low density lipoprotein oxidation.J Agric Food Chem 1998;46:4091-4096.
39. Murkovic, M., Adam, U., and Pfannhauser, W. Analysis of anthocyane glycosides in human serum. Fresenius. J Anal.Chem2000;366(4):379-381. 11220323
40. Youdim, K. A., Martin, A., and Joseph, J. A. Incorporation of the elderberry anthocyanins by endothelial cells increases protection against oxidative stress. Free Radic Biol Med7-1-2000;29(1):51-60. 10962205
41. Middleton E Jr and Kandaswami, C. Effects of flavonoids on immune and inflammatory cell functions. Biochem Pharmacol3-17-1992;43(6):1167-1179. 1562270
42. Emig, S., Schmalz, D., Shakibaei, M., and Buchner, K. The nuclear pore complex protein p62 is one of several sialic acid- containing proteins of the nuclear envelope. J Biol Chem6-9-1995;270(23):13787-13793. 7775435
43. Serkedjieva J, Manolova N, Zgorniak-Nowosielska I, and et al. Antiviral activity of the infusion (SHS-174) from flowers of Sambucus nigra L., aerial parts of Hypericum perforatum L., and roots of Saponaria officinalis L. against influenza and herpes simplex viruses. Phytotherapy Research1990;4(3):97-100.
44. Swanston-Flatt, S. K., Day, C., Flatt, P. R., Gould, B. J., and Bailey, C. J. Glycaemic effects of traditional European plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice. Diabetes Res1989;10(2):69-73. 2743711
45. Milbury, P. E., Cao, G., Prior, R. L., and Blumberg, J. Bioavailablility of elderberry anthocyanins. Mech Ageing Dev4-30-2002;123(8):997-1006. 12044949
46. Bitsch, I., Janssen, M., Netzel, M., Strass, G., and Frank, T. Bioavailability of anthocyanidin-3-glycosides following consumption of elderberry extract and blackcurrant juice. Int J Clin Pharmacol Ther2004;42(5):293-300. 15176653

Izvor: www.sigmaaldrich.com

German Commission E Monographs (Phytotherapy) flos

German Commission D Monographs (Phytotherapy) preparationes

European Elder
by Gayle Engels, Josef Brinckmann
HerbalGram. 2013; American Botanical Council

European Elder

Sambucus nigra, L.

Family: Caprifoliaceae

INTRODUCTION

European elder (Sambucus nigra, Caprifoliaceae), also known as black elder¹ and elderberry, is a deciduous tree that grows to 30 feet and is native to Europe, northern Africa, and western Asia.² It has flat-topped clusters of small, creamy-white flowers in early summer, followed by large, drooping bunches of purplish-black, juicy drupes (commonly referred to as berries) in late summer or early fall.^2,3

Both the elder flower and berry are used medicinally. Most of the elder flower in commerce is collected from the wild, mainly from Albania,⁴ Bosnia-Herzegovina, Bulgaria, Croatia, Romania,⁵ Hungary, Macedonia,⁶ Poland,⁷ Russia,⁸ Serbia, and Montenegro.⁹ Elderberries also are wild-collected in the aforementioned countries, but there are several distinct cultivars grown in commercial orchards, particularly in Austria (e.g., mainly the “Haschberg,” “Rubin,” and “Tattin” varieties), Denmark (e.g., “Sambu,” “Sampo,” “Samdal,” “Samyl,” “Allesoe,” and “Korsör”), and Germany (e.g., “Haschberg,” “Sambu,” “Sampo,” “Samyl,” and “Haidegg 13”). Due to successful auto-vegetative propagation, regular yields, and high coloring matter content, “Haschberg” is the chief variety cultivated in both Austria and Germany.¹⁰

For the sake of convenience, European elder will be referred to as elder in this article, and the plant part under discussion will be specified.

HISTORY AND CULTURAL SIGNIFICANCE

The genus Sambucus contains more than 20 species, many with similar chemical constituents to S. nigra. One such species, American elder (S. canadensis), is a fast-growing, deciduous North American shrub that can reach up to 12 feet with flowers and berries similar to S. nigra.^1,3 While this species was used by Native American tribes and as a folk remedy in some of the same ways as S. nigra, it will not be discussed in this article for reasons set forth below in the Modern Research section.

The use of elder as a medicine dates back to antiquity, according to the writings of Hippocrates (ca. 470-410 BCE), Pliny the Elder (ca. 23-79 CE), and Dioscorides (ca. 40-90 CE).¹¹ The word elder is derived from the Anglo-Saxon word æld,meaning “fire,” because one could start a fire by blowing through its young, hollow branches.¹² Historically, medicinal uses for European elder could be found in Italian, Dutch, Portuguese, Croat-Slovak, German, Austrian, Swiss, and Hungarian pharmacopeias.¹³

Of interesting historical note, in Anatomi Sambuci: The Anatomy of the Elder, written in 1677, the physician Martin Blochwich described medicines made from the various parts of elder, including a berry tincture, extract (or essence), wine, spirits (fermentation), syrup, tragea (powdered elderberry kernels), and rob (a thickened juice made from the berries, either with or without sugar), as well as seed oil.¹⁴ He also noted elder flower-derived preserves, syrup or honey, water and spirits, vinegar and oxymel (vinegar and honey), wine, and oil. Additionally, Blochwich elaborated upon powder, preserves, and syrup that could be made from the buds or sprouts of the plant, and also medicines that could be made with the leaves, middle bark, roots, pith, and fungus, including those in the form of water, syrup, oils, and liniments. Lastly, he chronicled making a “salt and its spirit” by reducing the entire plant to ashes over an open fire, pouring boiling water over it, and again reducing it over a low fire. This process produced the salt from which the spirit was then made. Blochwich then addressed the many ways in which these elder preparations were used alone (some of which might seem quite strange to the modern reader) and in combination with other “medicines” that are now known to be toxic. Common ailments these elder preparations were used to treat include headache, toothache, eye conditions, facial blemishes, mouth and throat conditions, cough, asthma, hoarseness, fever, smallpox, measles, stomach and intestinal conditions, stones, arthritis, menstrual complaints, inflammation, edema, and burns. Some of the more unusual conditions treated include deliria and affections (in combination with lily water, rose water, and opium); melancholy (by provoking vomiting); epilepsy (using an elder amulet worn over the heart); apoplexy and palsy (by vigorous rubbing of the extremities with elder spirit); protection from plague (by carrying and smelling an elder vinegar-soaked sponge in a hollow juniper-wood globe); and wound healing (by drinking wine that had elder leaves pounded into it, followed by a poultice of elder kernel oil, Venice turpentine, and verdigris [a poisonous green pigment caused by the action of acetic acid on copper]).

Traditionally, numerous ailments have been treated by elderberry including dysentery and diarrhea. It also was used to induce perspiration in order to remove toxins and increase resistance to illness.¹³ Currently, elderberries are used to treat symptoms associated with colds, flu, and in feverish conditions as a diaphoretic (an agent that increases perspiration).^12,15,16 The expressed juice of the berries, as well as extracts and dried juice concentrates, are used as components of oral ingestion products like medicated syrups and tablets, as well as topical application products like lozenges and skincare products.¹⁰ The fresh ripe berries are used in juices, jams, marmalades, liqueurs and dessert wines, and also as a coloring agent in beverages, foods, and textiles.¹⁰

Elder flowers are used as a diuretic, laxative, and diaphoretic.^12,17 Additionally, they are used as an astringent for the skin and in treating rheumatism, usually as an infusion (tea) or in a poultice.¹⁸ The dried flowers of elder are used in European traditional herbal medicinal products mainly in the form of herbal teas, liquid extracts, and tinctures.¹⁹ The German Commission E approved elder flower — administered as fluid extract, herbal tea, or tincture — for common cold symptoms in 1986.²⁰ In 1992, the British Herbal Medicine Association published an elder flower monograph in its British Herbal Compendium, specifying the forms of herbal tea infusion (drunk hot), liquid extract (1:1, 25% ethanol), and tincture (1:5, 25% ethanol) for treating feverish common cold conditions.²¹ Elder flower water also has been used in eye and skin moisturizers, and flower extracts are used in perfumery.¹⁸

Both elderberry and elder flower extracts are used as flavorings in food products, alcoholic  (bitters and vermouth) and nonalcoholic beverages, and confectionary items.¹⁸

CURRENT AUTHORIZED USES IN COSMETICS, FOODS, AND MEDICINES

In 2008, the European Medicines Agency (EMA) published a final labeling standards monograph on elder flower (as herbal tea for oral use, liquid extract [1:1, 25% V/V ethanol], or tincture [1:5, 25% V/V ethanol]), which superseded existing monographs of EU national authorities for the registration and marketing authorization of traditional herbal medicinal products that contain elder. The authorized therapeutic indication is “for the relief of early symptoms of common cold.”²²

One prerequisite of registration is that the quality of the herbal material complies with the corresponding quality standards monograph of the European Pharmacopoeia (Sambuci flos PhEur), which, for example, requires the dried flowers to contain a minimum of 0.80% flavonoids, expressed as isoquercitroside.²³ In European countries, elder flower also is found as an active ingredient of clinically tested polypreparations such as Sinupret^® (Bionorica SE, Neumarkt, Germany), a licensed herbal medicinal product sold only in pharmacies and indicated for acute and chronic inflammation of the paranasal sinuses. (Sinupret also contains primrose [Primula veris, Primulaceae] flowers with calyx, common sorrel [Rumex acetosa, Polygonaceae] herb, European vervain [Verbena officinalis, Verbenaceae] herb, and gentian [Gentiana lutea, Gentianaceae] root.²⁴) In the United Kingdom, aqueous liquid extract (1:1) of elder flower is an active ingredient of Cold and Flu Relief by Potter’s Herbals (Wigan, UK; founded by Henry Potter in 1812), a registered traditional herbal medicinal product available without prescription from pharmacies and other retail outlets with the authorized therapeutic indication “used to relieve the symptoms of colds and flu, chills and sore throats.”²⁵ (Potter’s Cold and Flu Relief also contains ethanolic liquid extracts [1:1] of hemlock spruce [Pinus canadensis, Pinaceae] needle and bayberry [Myrica cerifera, Myricaceae] bark.)

In 2011, the EMA called for scientific data to be used by its Committee on Herbal Medicinal Products for assessment work toward the establishment of a community herbal monograph and/or community list entry for elderberries (Sambuci fructus).²⁶ Presently, there are also some elderberry-containing food supplement products in the European market, such as Wellion Diabasic^® tablets (MED TRUST; Lichtenwörth, Austria), a dietetic food supplement labeled for special medical needs of diabetic patients with disease-related nutrient deficiencies.²⁷ Another example is the enzyme complex and herbal preparation Snorin^® tablets (VitaBasix^®; Maastricht, the Netherlands), labeled for chronic snoring whose cause is not determined to be anatomic after other causes (obesity, alcoholism, chronic tonsillitis, or sinusitis) have been excluded.²⁸

Concerning use of elder in cosmetic products, the European Commission Health and Consumers Directorate lists “Sambucus Nigra Fruit Extract” for astringent (contracts the skin) function and “Sambucus Nigra Fruit Juice” for both astringent and skin-conditioning functions. “Sambucus Nigra Flower,” “Sambucus Nigra Flower Juice” (juice expressed from the flower), and “Sambucus Nigra Flower Water” (aqueous solution of the steam distillate obtained from the flowers) are approved for use as skin-conditioning ingredients, while “Sambucus Nigra Flower Extract” is listed for refreshing (imparts a pleasant freshness to the skin), skin-conditioning, soothing (helps lightening discomfort of the skin or of the scalp), and tonic (produces an invigorating sensation on skin and hair) functions.²⁹

In the United States, elder tree leaf is classified as a Generally Recognized as Safe (GRAS) natural flavoring substance, although its use is limited to only alcoholic beverages and not to exceed 25 ppm (parts per million) prussic acid in the natural flavor ingredient.³⁰ The essential oil or natural extractives (including distillates) of elder flower are GRAS flavoring agents in food products.³¹ Elderberry and elder flower also are permitted as dietary supplement components in the United States, requiring Food and Drug Administration notification within 30 days of marketing a product (if a “structure-function” claim is made). In Canada, they are regulated as active ingredients of licensed natural health products (NHPs) requiring pre-market authorization from the Natural Health Products Directorate. As one example, Sambucol^®* Original Lozenges (Healthcare Brands International Ltd., Surrey, UK), an elderberry preparation, is a licensed NHP indicated for reducing severity of flu symptoms (aches and pains, cough, congestion) and shortening duration of influenza A and B viruses.³²Elder flower preparations, such as Gaia Garden Herbals Elder Flowers Tincture (Flora Manufacturing & Distributing Ltd.; Burnaby, Canada), are licensed NHPs with the authorized therapeutic indication “as a diaphoretic in conditions requiring fever management, including the common cold and influenza and for sinusitis and chronic nasal catarrh [inflammation of mucus membranes] with deafness.”³³

MODERN RESEARCH

Numerous in vivo and in vitro laboratory studies have assessed elder flowers and berries for antibacterial, anticancer, anti-inflammatory, antimicrobial, antiproliferative, antiviral, antioxidant, and immunomodulating activity, as well as chemopreventive and cytotoxic potential, cellular uptake, burn healing, insulin-simulating and insulin-releasing actions, anti-angiogenic (inhibiting the growth of blood vessels) activity, cardioprotective activity, and antihypertensive properties. Human clinical studies support the traditional use of and laboratory findings on elderberry and flower.

During the 2009 flu season, a short-term, randomized, double-blind, placebo-controlled pilot study was conducted on 64 volunteers suffering from three or more flu-like symptoms (coughing, fever, headache, muscle aches, and/or nasal congestion and mucosal discharge) for less than 24 hours.³⁴ The patients were randomized into two groups of 32 and administered four doses of 175 mg proprietary elderberry extract (HerbalScience Singapore Pte. Ltd.; standardized and enriched in phenolic acids, polyphenolics, and a broad diversity of other flavonoids)³⁵ or placebo daily for two days. After 48 hours, the elderberry group reported a significant reduction in symptoms with 28% of volunteers being symptom free. The symptoms of the patients in the placebo group were either unchanged or worse.

In 2004, a randomized, double-blind, placebo-controlled study (n=60) demonstrated the safety and efficacy of Sambucol in the treatment of influenza.³⁶ Patients with influenza type A or B received 15 ml Sambucol or placebo four times per day. Flu symptoms decreased significantly in the elder group by the third or fourth day versus seven-to-eight days in the placebo group. Treatment was initiated within 48 hours of symptom onset and the authors suggested that the elder preparation might have been even more effective with earlier intervention.

In a previous placebo-controlled, double-blind study conducted in 1995 on 27 patients with influenza symptoms for 24 hours or less, patients received either Sambucol or placebo daily for three days (two tablespoons per day for children five-to-11 years of age and four tablespoons per day for adults 12 years and older).³⁷ Within two days, 93.3% of the elderberry group experienced a significant improvement in symptoms, and complete resolution was achieved by 90% of the group within two to three days. The placebo group did not experience similar improvement or resolution until day six.

A 2004 randomized, double-blind, placebo-controlled study investigated the effect of elderberry juice on cholesterol, triglyceride concentrations, and antioxidant status in young volunteers.³⁸ In the first arm of the study, 34 participants took three daily doses of 400 mg encapsulated spray-dried elderberry juice (Iprona; Lana, Italy; 10% anthocyanins, equal to 5 ml elderberry juice, processed first by ultra filtration after which the liquid extract is spray dried to a powder using maltodextrin as the carrier), or placebo for two weeks. A subgroup continued for another week to test for resistance to oxidation of low-density lipoprotein (LDL) cholesterol. There was a small, statistically insignificant change in cholesterol in the elderberry group (from 199 to 190 mg/dl) compared to placebo (from 192 to 196 mg/dl). Resistance to copper-induced oxidation of LDL did not change within the three weeks. In the second arm of the study, six participants took a single dose of 50 ml elderberry juice with a high-fat breakfast, and no significant post-meal triglyceride concentrations were observed. The authors stated that low-dose, spray-dried elderberry extract has a minor effect on serum lipids and antioxidative capacity, but that further studies employing higher, nutritionally relevant doses might affect significant postprandial serum lipids.

Based on evidence supporting the cardioprotective role of anthocyanins, a 2009 parallel-designed, randomized, placebo-controlled study was conducted to examine the effect of chronic anthocyanin consumption on biomarkers of cardiovascular disease (CVD) risk and kidney function.³⁹ Healthy postmenopausal volunteers (n=52) consumed 500 mg per day elderberry anthocyanins (Artemis International; Fort Wayne, IN; 125 mg cyanidin-3-glucoside, extraction method not stated) or placebo for 12 weeks. No significant change in biomarkers of CVD risk was observed and liver and kidney function remained within clinically acceptable ranges. The authors stated that while their findings are consistent with two previous studies that are not directly comparable (elderberry and cranberry [Vaccinium macrocarpon, Ericaceae] juices), their findings are inconsistent with two previous studies that showed reduction in CVD biomarkers (using Bing cherry [Prunus avium, Rosaceae] anthocyanins) and inflammatory markers (bilberries [Vaccinium myrtillus, Ericaceae] and blackcurrants [Ribes nigrum, Grossulariaceae]). They explained that differences in study design may explain the inconsistent results because the participants in their trial had lower levels of CVD risk than participants in the other study populations. They also suggested that the difference in inflammatory markers could be a result of this study’s examination of high levels of anthocyanin intake over a short period of time rather than long-term intake of anthocyanin-rich foods.

Studies have been conducted on elder in combination with other plant materials investigating their usefulness in a variety of conditions. A 2009 monograph by the American Botanical Council on Sinupret concluded that the “scientific and clinical literature supported [its] pharmacological mechanisms of mucolytic, secretolytic, anti-inflammatory, antibacterial, antiviral, and immunological activity, some of which has been documented in open-label and randomized, controlled human clinical trials.”²⁴

A small, randomized, crossover, placebo-controlled, single-blinded study performed in 2010 evaluated the laxative efficacy of a combination product that has been available in Brazil since 1926.⁴⁰ The product contains fruits of anise (Pimpenella anisum, Apiaceae) and fennel (Foeniculum vulgare, Apiaceae), as well as flowers of elder and senna (Cassia angustifolia, Fabaceae) (Laboratórios Klein; Porto Alegre, Brazil; described only as a “homogeneous mixture of dried botanicals”). Each of the 20 patients with chronic constipation who participated in the study received the compound as a tea (15 g infused for five minutes in 1,500 ml boiling water) or placebo for five days. Following a washout period of nine days during which the patients were free to use other laxatives, the treatment was reversed in the two groups. The number of evacuations in the group receiving the combination tea increased during the use of the tea and significant differences were observed as of the second day of treatment. No adverse effects were observed.

In 2008, authors of an observational study sought to obtain information on the compounds in a food supplement sold as a weight reduction aid to determine its short-term effectiveness and safety as an initiator of lifestyle change.⁴¹ While the name of the supplement was not stated, it consisted of elderberry juice supplemented with elder flower juice (concentrate based on 120 g fresh berries and extract of 3.9 g dried flowers), elder tablets (225 mg berry powder and 600 mg flower extract) three times per day, psyllium (Plantago arenaria, Plantaginaceae) two to three teaspoons each morning, and a dose of asparagus (Asparagus officinalis, Asparagaceae) tablets equivalent to 40.5 g dried asparagus per day. Participants (n=80) followed a 13-to-15 day protocol after which time their mean body mass index (BMI), weight, blood pressure, physical and emotional wellbeing, and quality of life had improved significantly. The authors stated that it remained to be established if any of the chemical constituents in the supplements contributed to the efficacy of the diet.

FUTURE OUTLOOK

For generations, European elder flower and elderberry preparations have been labeled and marketed as non-prescription herbal medicinal products available at most pharmacies and drugstores throughout Europe, as well as in countries where traditional European herbal medicines are licensed, listed, or registered (in particular, Australia, Canada, and New Zealand). In the United States, elder preparations are offered mainly as dietary supplements, although some, such as Sambucol Cold & Flu Relief, are listed homeopathic drug products. In recent years, new demand for elder is being driven, in part, by several alcoholic beverage brands offering certified organic elder flower and elderberry liqueurs, schnapps, spirits, and wines that have become trendy in both Europe and America. Moreover, non-alcoholic drinks — including the certified organic BIONADE^® (Peter Bier, Ostheim vor der Rhön) Elderberry flavor (entered EU market in 1996) — are sold in conventional, natural, and organic grocery stores throughout Europe and are popular on the menus of cafes, clubs, and bars. The elderberries used in BIONADE products are organically grown in Germany’s Rhön region (State of Hesse) and in Lower Franconia (State of Bavaria).

Elder (as elderberry) was the 18^th top-selling herbal dietary supplement in the Food, Drug, and Mass Market channel in the United States for 2011.⁴² A reported total of $797,915.00 in elderberry products was sold in that channel of trade, down almost 15 percent from 2010.

In a 2003 report, the estimated annual quantity of dried elder flowers wild-collected in Bosnia-Herzegovina was about 44 tons (five percent used domestically and 95 percent exported), and in Romania about 150 tons of elder flowers and 40 tons of elder fruits are wild-harvested annually.⁵ A 2010 report by the European Herb Growers Association (Europam) states that elder flowers and fruits remain among the highest volume wild-collected medicinal plants in both Bulgaria and Romania for export trade as well as for domestic herbal tea and phyto-pharmaceutical production.⁴³ An International Trade Centre study on certified organic wild-collected plants estimated that, in 2005, about 472 tons of elderberries, 19 tons of elder flowers, and six tons of elder leaves were collected according to an organic wild-crop harvesting practice standard.⁴⁴Demand for European elder flower and fruit with sustainability certifications (e.g., Organic Wild and FairWild) appears to be increasing as evidenced by the fact that wild-collection firms are implementing ecological and social standards for elder harvesting in a number of countries, including Albania, Bosnia-Herzegovina, Hungary, Macedonia,⁶ Croatia, and the Ukraine.⁴⁵ In Croatia, about 75 percent of the wild-harvested elder flowers are traded in the local and national markets, and about 25 percent are exported.⁵

* Sambucol was the initial trade name for the elderberry extract made by Razei Bar Industries in Jerusalem, Israel. Razei Bar was purchased by Health Brands International Ltd. (a private equity company based in the United Kingdom) in 2007. Health Brands International sold the Sambucol rights to PharmaCare Labortories, a Sydney, Australia company, which now markets the brand in the United States.

—Gayle Engels and Josef Brinckmann

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