Abstract

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Come Back to Root – Therapeutic Activities of

Scutellaria baicalensis

Root in Aspect of Innate

Immunity Regulation – Part I

Wróć do korzenia – lecznicze działanie korzenia tarczycy bajkalskiej

w świetle regulacji wrodzonej odporności – część 1

1_{Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences,}

Wrocław, Poland

2_{Institute of Biology and Pharmaceutical Botany, Silesian Piasts University of Medicine in Wrocław, Poland}

Adv Clin Exp Med 2008, 17, 3, 337–345 ISSN 1230−025X

REVIEWS

© Copyright by Silesian Piasts University of Medicine in Wrocław

Abstract

Scutellaria baicalensis Georgi (Engl. skullcap or baical skullcap; Chin huang qin, Jap. ougon or ogon) is widely used in traditional and modern oriental medicine. This Asian plant is acclimated and cultivated in Central European condition (including Poland). Therapeutic activities of flavonoids of skullcap roots are known. Among the flavones: baicalein, baicalin, wogonin and wogonoside are the most important. In the review, several potential activities of the extracts and flavones of Scutellaria baicalensisroots are described. Anti−bacterial, anti−viral, anti− tumor, anti−inflammatory activities in aspect of innate immunity regulation seems very important. Moreover, pos− sible therapeutic activities in neurodegenerative diseases promise their therapeutic usefulness. Many diseases, i.e. tumor, neurodegenerative, include Alzheimer disease (AD), and inflammatory diseases (hepatitis, colitis, arthritis, dermatitis and others) are accompanied by inflammatory reactions. The inflammation of neurones is often the result of over−activation of immunity (i.e. by β−amyloid in AD). Some diseases are accompanied by deficiency of innate immunity reactions. The deficiency was described for infectious (bacterial and viral) and tumor diseases. In view of the wide activities of Scutellaria flavonoids in different inflammatory diseases, regulatory effect on the innate immunity is postulated (Adv Clin Exp Med 2008, 17, 3, 337–345).

Key words: Scutellaria baicalensis flavonoids, antiinflammatory activity, antimicrobial, antitumor, innate immunity.

Streszczenie

Tarczyca bajkalska (Scutellaria baicalensis Georgi) jest rośliną leczniczą, szeroko stosowaną w tradycyjnej i współczesnej medycynie orientalnej. Ta azjatycka roślina została zaaklimatyzowana i jest hodowana w środko− wej Europie (w tym w Polsce). Znane jest lecznicze działanie flawonoidów korzenia tarczycy, a wśród nich naj− ważniejszymi są: bajkaleina, bajkalina, wogonina i wogonozyd. W artykule opisano potencjalne działanie wycią− gów i flawonów uzyskanych z tej rośliny. Zdumiewająco szeroki zakres aktywności obejmuje: przeciwbakteryjne, przeciwwirusowe, przeciwzapalne, przeciwnowotworowe działanie. Przedstawiono działanie terapeutyczne w cho− robach neurodegeneracyjnych (np. chorobie Alzheimera) i zapalnych schorzeniach wątroby, skóry, okrężnicy i w artretyzmie. Wspólnym zaburzonym mechanizmem we wszystkich wymienionych chorobach jest wrodzona odporność, która ma nieswoisty charakter. W tym aspekcie regulacja wrodzonej odporności przez flawonowe pre− paraty uzyskane z tarczycy bajkalskiej budzi zainteresowanie (Adv Clin Exp Med 2008, 17, 3, 337–345).

The title of the review was inspired by Carl Nathan article [1]. According to Nathan’s, history of medicine (given by Anonymus) start in the ancient time.

– 2000 BC – Here, eat this root.

– AD 1000 – That root is heathen. Here, say this prayer.

– 1850 – That prayer is superstition. Here, drink this potion.

– 1920 – That potion is snake oil. Here, swal− low this pill.

– 1945 – That pill is ineffective. Here, take this penicillin.

– 1955 – Oops… bugs mutated. Here, take this tetracycline.

– 1960 –1999 – 39 more “oops”… Here, take this more powerful antibiotic.

– 2000 – The bugs have won! Here, eat this root.

Scutellaria baicalensis

– History, Characteristics,

Therapeutic Activities

Scutellaria baicalensis Georgi (Engl. skullcap or Baikal skullcap, Chin. huang qin, jap. wogonor

ogon, Korean hwang−geum) is a perennial herb of

Lamiaceae family, cultivated in China, Japan, Korea and listed in the Chinese, Japanese and Korean Pharmacopoeias and others. The dried roots of this plant – Radix Scutellariae (Skullcap Root) has a particulary high flavonoid content (over 25%), which gives it a yellow colour and gives rise to its traditional name of Golden root or Golden skullcap. Multiple biological properties have been described for this herb, including anti− inflammatory, antiviral, anticarcinogenic, free−rad− ical−scavenging, antioxidant and immunostimula− tory effects. Radix Scutellariae baicalensisis wide− ly used in traditional and modern oriental medicine as remedies for fever, allergic diseases and inflam− mation, especially against bacterial and viral infec− tions of the respiratory and the gastrointestinal tract, i.e. chronic bronchitis, bacillary dysentery, viral hepatitis, and acute biliary tract infection, pancreatitis, colitis and others; also, in dermatolog− ical diseases, as atopic inflammation or psoriasis and in a stomatology, as periodontal disease, too. American Skullcap (Scutellaria laterifolia L.). In Chinese and Japanese herbal medicine, included TCM (Traditional Chinese Medicine) and Kampo medicine (Japanese) are used, too: Scutellaria amoena C.H. Wright (Engl. yunnan skullcap, TCM name – dian huang qin), Scutellaria indica L. (Engl. Indian Skullcap, TCM name – han xin cao),

and Scutellaria barbata D. Don. (Engl. Barbat Skullcap; TCM name – ban zhi lian). The Baikal Skullcap grows in northern China (is mainly pro− duced in the provinces of Habei, Inner Mongolia, Shandong and Shanxi), Siberia and Manchuria. The leaves are opposite, lanceolate and sessile with an acute apex. The flowers are blue, with a helmet− shaped upper lip (hence the name of genera Scutellaria). The root is used medicinally as the drug – Radix Scutellariae. In Chinese Pharmacopoeias are: Radix Scutellariae (Baikal Skullcap Root) and Herba Scutellariae barbatae (Barbated Skullcap herb). Scutellaria baicalensis

Georgi is acclimated and cultivated too in Central European conditions (Poland, Bohemia, Germany) and some investigation of pharmacological and immunological activities of flavones, esp. baicalein, baicalin and Antoksyd® _{– (commercial}

product of Herbapol – Wrocław, Poland) obtained from the roots Scutellariae baicalensis cultivated in Poland has been done. Radix Scutellariae con− tains flavonoids (above 20%) including baicalin up to 14%, baicalein (5,6,7−trihydroxyflavone), up to 5%, wogonin (5,7−dihydroxy−8−methoxyflavone), 0,7%, wogonoside, 4,0%, chrysin, oroxylin A., skullcapflavones I and II and others. Over 50 flavone derivatives has been isolated from the root of S. baicalensis. Baicalin (7−0−β−D−glucuronide – baicalein) and wogonoside (7−0−β−D−glucuronide – wogonin) are the two major compounds found in the root.

Antimicrobial Activity of

Scutellaria baicalensis

Root

Anti−Bacterial Activity

The root of S. baicalensis has a wide antibacte− rial activity in vitroagainst hemolytic streptococ− cus, pneumococcus, meningococcus, Staphylococ− cus aureus, Corynebacterium diphteriae, Shigella dysenteriae, Bacillus anthracis, Salmonella typhi, Salmonella paratyphi, Proteus, Esherichia coli, Pseudomonas aeruginosa, Bordetella pertussis and Vibrio comma. Baicalin and baicalein are the major antibacterial active component. In tests with selec− ted oral bacteria, including suspected periodonto− pathogens: Bacterioides melaminogenicus inter− medius was found to be most sensitive to a 2% decoction of S. baicalensis [2, 3]. A hot aqueous extract of the roots inhibited the growth of Alcali− genes calcoaceticus, Klebsiella pneumoniae, Pseu− domonas aeruginosaand Staphylococcus aureusat concentrations of 200.0–400.0 µg/ml [4].

the case of bacterial resistance to antibiotics. The resistance is a serious global problem and includes strains of beta−lactam−resistant Staphylococcus aureus. Baicalin for example, showed synergy with beta−lactam antibiotics against methicillin− resistant Staphylococcus aureus (MRSA). Japanese and Chinese authors [5, 6] noted also the remarkable synergies between baicalein and tetra− cycline, and baicalein and β−lactams against methicillin−resistant Staphylococcus aureus. Mini− mum inhibitory concentrations (MICs) of ben− zylpenicillin against MRSA was reduced when 10 µg mL(−1) baicalein was added. The obtained reduction was from 125 and 250 µg mL(−1) to 4 and 15 µg mL(−1), respectively. This activity of baicalein or baicalin was dose−dependent. From the other authors constated, that the killing of MRSA and beta−lactam−resistant S. aureuscells by 10 to 50 µg mL(−1) ampicillin, amoxycillin, ben− sylpenicillin, methicillin and cefotaxime was potentiated by 25 µg mL (−1) baicalin. They con− cluded that baicalin has the potential to restore the effectiveness of β−lactam antibiotics against MRSA and other strains of β−lactam−resistant

S. aureus. In view of this activity, plant comple− mentary medicine for treatment bacterial and viral diseases is an alternative.

Anti−Fungal Activity

The aqueous extract was shown in vitro to be active against Candida albicans and Rhodotorula rubra and against 10 kinds of skin fungi including

Trichophyton violaceum, Microsporum audouini

and Microsporum canis [3, 7]. The extracts of

Scutellaria baicalensis rootsobtained by the suc− cessive exhaustion in chloroform and in ethyl acetate present clear fungistatic activities in vitro

against to some cutaneous and ungual pathogenic fungi, and particularly upon strains of Candida albicans, Cryptococcus neoformans and

Pityrosporum ovale. The ethyl acetate extract appears the most interesting because of its effi− ciency and of its stability. An antifungal substance is found out as the baicalein which possessed potent specific activity against the pathogenic yeasts with MIC of 70–100 µg/ml The good inhibitory activity of baicalein could be linked to the group hydroxyl (−OH) in position seven of the molecule (ring A).

Anti−Viral Activity

Complementary medicines might be useful in therapy of such theratening viral diseases as AIDS, hepatitis C and B, or even influenza and herpes, especially herpes genitalis. Studies in vitro

show inhibition effect of Scutellaria baicalensis

flavones on human immunodeficiency virus (HIV) replication [8, 9, 10]. Positive effects were obtained after treatment HIV−infected patients with the herbal decoction, or isolated flavones. Inhibition of viral replication was found for infec− tions with hepatitis type C virus (HCV) [11], hepatitis type B virus (HBV) [12], influenza A and B viruses[13], herpesviruses type 1 and 2 (HSV−1, HSV−2) and Epstein−Barr virus (EBV) [14]. All the viruses differ in their virions structure (RNA and DNA, with or without envelope), taxonomic affiliation, and replication process. HIV for exam− ple, has RNA containing genome, surface enve− lope and belongs to Retroviridaefamily, influenza viruses (Orthomyxoviridae) have genomic RNA and envelope, HCV (Flaviviridae) is RNA con− taining virus without envelope, HBV (Hepadnaviridae) and HSV−1, HSV−2, EBV belonging toHerpesviridae contain genomic DNA and envelope. The process of replication is differ− ent for each of the viruses. There are several liter− ature data concerning inhibitory activity of Scutellaria flavones on HIV replication. The data are, however, insufficient and usually unrepeat− able. According to the data, baicalin may inhibit HIV−1 replication at the level of viral entry to cell, or on the level synthesis of viral enzymes: reverse transcriptase, or protease [8–10]. It must be stressed that extracts of Scutellaria baicalensis

roots might exert beneficial effect on anti−HIV HAART therapy. Protease inhibitors used in the therapy causes significant gastrointestinal distur− bances such as nausea. According to Aung et al [15] Scutellaria baicalensis decreases ritonavir induced nausea. Extremely large number of differ− ent viruses inhibited by skullcap flavones is astounding and suggest more universal mechanism engaged in the antiviral effect.

Effect of

Scutellaria

baicalensis

Flavones on

Inflammatory Reactions

nitric oxide (NO). In production most of them and their activity transcription factor NFκB is involved. After activation, NFκB translocate to nucleus and bind to promoters of cytokine and other proteins genes and activate production or action. Tang et al [16] studied effect of wogonin, flavonoid of Scutellaria baicalensis, on the NK cells activity, macrophage phagocytosis, release of cytokines: IL−1α, TNFα, and NFκB activation in leukocytes from rats. They found that wogonin promoted the activity NK cells and macrophages and induced cytotoxicity. Wogonin stimulated also IL−1α and TNFα level in dose−dependent way. Kim et al [17] studied the effect of baicalin on age− related NFκB activation in kidney tissue from old rats feeded with baicalin. Increased expression of NFκB targeting genes (hemoxygenase−1, inducible nitric oxide synthase (iNOS) and COX−2 in old rats was reduced by baicalin. Furthermore, baicalin pretreatment decreased tissue myeloper− oxidase activity and lipid peroxidation, but increased the superoxide dismutase level. In vitro

studies indicated that the beneficial effect of baicalin was associated with reduced cytokine pro− duction from lymphocytes and reduced TNF−α− −induced hepatocyte apoptosis. These results sug− gest that baicalin has therapeutical potential for T−cell−mediated liver injury [18].

Interleukin−12 (IL−12) is an important cytokine for maintenance of normal systemic defense and bioregulation. The Japanese herbal medicine Sho−saiko−to (TJ−9) containing Radix Scutellariae and Radix Glycyrrhizae uralensishas been administered to 1.5 million Japanese patients with chronic liver diseases. TJ−9 is known to sig− nificantly suppress cancer development in the liver and has macrobiotic effects. Effects of the Japanese herbal medicine “Sho−saiko−to” (TJ−9) on interleukin−12 production in patients with HCV−positive liver cirrhosis was studied.The lev− els of IL−12 produced by the patients were signifi− cantly lower than those produced by healthy sub− jects (p < 0.01, p < 0.05). However, when TJ−9 was added to the cultures, the IL−12 production levels in both cell fractions increased approxi− mately three fold, and the levels from the mono− cyte/macrophage fraction were almost the same as those from healthy subjects. This effect of TJ−9 was attributable to two of its seven herb compo− nents, that is Scutellariaroot and Glycyrrhizaroot. One possible mechanism for the macrobiotic effects of TJ−9 on liver−cirrhosis patients may be the improvement in IL−12 production.

Chemokines belong to a large family of inflammatory cytokines responsible for migration and accumulation of leukocytes at inflammatory sites. Baicalin possess anti−inflammatory activity

through its ability to complex with chemokine IL−8 and thus reduces their capacity to bind and activate their receptors. Woo et al. [19] found that balcalein has capacity to inhibit cyclooxygenase (COX−2) gene expression in macrophage cell line Raw 264. In view of the effect of scutellaria flavones on inflammatory reactions the therapeutic activity in cardiatic, dermatologic, hepatitis and pancreatitis is possible. The further experiments seem to con− firm the idea. Since oxidants play also roles in inflammatory diseases, the effect of extract from

Scutellaria baicalensis (SbE) on cultured car− diomyocyte death caused by oxidant stress in the context of explanation the mechanism of lethal cell damage in ischemia was studied by Chang et al [20]. They found that SbE attenuate oxidant stress and protect the myocytes from lethal oxi− dant. In vivo study on therapeutic efficacy of baicalin in experimantal severe acute pancreatitis (SAP) of rats was performed by group of Chinese scientists Zhang et al. [21]. The contents of amy− lase, TNFα, IL−6, malondialdehyde and PLA(2) were significant lower in the treated than in con− trol group, what indicate significant therapeutic effect of baicalin on SAP rats. Next the pathologi− cal changes in multiple organs pancreas, liver, kid− ney, and lung in SAP rats were studied. Zhang et al found them milder than those in control group. The experimental works performed on rats indi− cate possible therapeutic effect in pancreatitis.

A new “medical food” recently hit the American pharmaceutical market as a treatment for osteoarthrtis (OA). LIMBRE (flavocoxid) con− sists of a proprietary blend of the two types of flavonoids: baicalin from Scutellaria baicalensis

root and catechine from Acacia catechu bark. These ingredients are Generally Recognized AS Safe (GRAS) by U.S. Food and Drug Administration (FDA), and are listed as such by regulation in Volume 21 Code of Federal Regulations (CFR), Section 182, 184, and 186. LIMBREL®_{– named flavocoxid (flavonoids hav−}

ing antiinflammatory activities), its capsulles (U.S. pending) by oral administration, for the clin− ical dietary management of the metabolic process− es of osteoarthritis (OA). According to FDA instruction the preparation must be administered under physician supervision.

This process is both enzymatic as well as oxida− tive, and occurs at a cellular level the essential fatty acid – arachidonic acid (AA) is converted into various inflammatory products. In addition, AA is converted via an oxidative mechanism mediated by ROS to F2−isoprostane, malondialdehyde, and 4−hydroxynonenal, oxidized lipids which directly degrade cartilage and induce other inflammatory proteins. With age, elevated levels of AA accumu− late both from the diet, and from the increased conversion of phospholipids produced by further damage to cells in the joint. Though the initial damage that causes OA is mainly due to overuse, injury, or genetics, the cartilage degradation which occurs over time is characterized by the chronic, heightened metabolism of the accumulated AA to excess inflammatory metabolites. Therefore, OA is sustained by imbalaced AA metabolism. Managing AA metabolism benefits OA patients by decreasing the damaging, metabolic inflammatory processes in the joint to improve functional mobil− ity, reduce stiffness and decrease joint discomfort.

In treatment of OA, a mixed extract containing two naturally occurring flavonoids: baicalin from

Scutellaria baicalensis and catechin (derived of fla− vanes) from Accacia catechuwas tested for COX−1 and COX−2, and 5−LOX inhibition, via enzyme, cel− lular, and in vivo models [22]. The 50% inhibitory concentration for inhibition of both ovine COX−1 and COX−2 peroxidase enzyme activities was 15 mi− crog/ml, while the mixed extract showed a value for potato 5−LOX enzyme activity of 25 microg/ml. Prostaglandin E2 generation was inhibited by the mixed extract in human osteosarcoma cells express− ing COX−2, while leukotriene production was inhib− ited in both human cell lines, immortalizes THP−1 monocyte and HT−29 colorectal adenocarcinoma. In an arachidonic acid−induced mouse ear swelling model, the extract decreased edema in a dose−depen− dent manner. When arachidonic acid was injected directly into the intra−articular space of mouse ankle joints, the mixed extract abated the swelling and restored function in a rotary drum walking model. These results suggest that this natural, flavonoid mixture baicalin with catechin acts via “duals inhi− bition” of COX and LOX enzymes to reduce pro− duction of pro−inflammatory eicosanoids and atten− uate edema in an in vivomodel of inflammation.

Antitumor Effect of

Scutellaria baicalensis

Flavonoids

Traditional Chinese herbal medicines (TMC) that for centuries have been used in disease pre− vention and treatment are finding use as alterna−

tives to Western cancer therapies. PC−SPES is herbal mixture used by prostate cancer patients as an alternative form of treatment. Scutellaria baicalensis and two other herbs (Glycyrrhiza uralensis and Serenoa repens)were found to lower intracellular and secreted prostate−specific antigen (PSA). From a panel of the herbals, the purified plant flavonoids from Scutellaria roots were examined for anticancer activity. Cancer is hyper− proliferative disorder that involves morphological cellular transformation, dysregulation of apopto− sis, uncontrolled cellular proliferation, invasion, angiogenesis and metastasis. In vitro mechanism of PS−SPES according to Chen [23] include the following: induction of apoptosis and cell cycle modulation, inhibition of cell proliferation, down− regulation of bcl−2, bcl−6, effect on cell nuclear antigen and prostate−specific, antigen proteins, downregulation of androgen receptor and upregu− lation of p53, bax and p21 proteins.

Antiproliferative effect on various cancer cell lines was shown by different groups of scientist. Chen et al. [23] demonstrated significant suppres− sion of prostate cancer cell growth by restriction of cell cycle progression at G(1)/S and drastic reduc− tion in expression of androgen receptor and PSA. The antiproliferative effect was obtained in human hepatocellular carcinoma cell lines and in lung cancer cell line by some authors [24–26]. It must be stressed that the growth inhibitory effect of flavonoids was observed among human cancer cells but not in normal diploid cells [24]. Inhibition cell proliferation is not the only anti− cancer mechanism of flavones.

the gene transcription and expression of cyclin may play an important role. Anticancer, antiradical and antioxidative actions of novel Antoksyd S®

and its major components, baicalin and baicalein was found by Ciesielska et al. [28, 29]. Antiproliferative and apoptic activity against acute lymphocytic leukemia, lymphoma and myeloma cell lines by Scutellaria baicalensis flavonoids was found by Kumagai et al [29]. Additionally antimutagenic and antiradical properties of flavones from the roots of Scutellaria baicalensis

(Antoksyd®_{) was found by Woźniak et al [30].}

Effect of

Scutellaria

baicalensis

Flavonoids in

Neurodegenerative Diseases

Beneficial effect of Scutellaria baicalensis

root was observed in neurodegenerative diseases such as Alzheimer disease, ischemia, spinal cord injury, multiple sclerosis, prion diseases, Parkinson disease, and epilepsy [32–39}. These diseases are caused by neuro−immunomech− anisms, which contribute actively to the neurode− structive process. Besides them, the most of the lit− erature data concern mechanism of explanation neuroprotection by flavones of Scutellariae radix

and its antioxidative activities.

Reactive oxygen species (ROS), nitric oxide (NO) and product of arachidonic acid metabolism prostaglandin E2 (PGE2) are important mediators in a number of neurodegenerative diseases. Effects flavones of skullcap on release of these mediators is frequently studied.

In Alzheimer disease, amyloid β(Aβ) protein is known to increase free radical production and lipid peroxidation leading to apoptosis neurons. Heo et al. [37] found that baicalein and baicalin reduced cytotoxicity of Aβprotein in PC12 nerve cells. Li et al. [38] showed that baicalein by anti− inflammatory and antioxidant properties protect primary midbrain rat neuron−glia cultures from degeneration. Effect of amelioration of total flavonoids from stem and leaves of Scutellaria baicalensis Georgi on cognitive deficits, neural damage and free radicals disorder induced by cere− bral ischemia in rats was found by Shang et al. [39]. Potent inhibitory effect of flavonoids in

Scutellaria baicalensis amyloid beta protein− induced neurotoxicity was found by Heo et al. [37]. The capacity of the S. baicalensis extract and baicalin for reducing the effect of psychoemotion− al stress on the blood system is apparently related to their influence on the adrenergic structures and confirm the adaptogenic activities of drugs.

Effects of

Scutellaria

baicalensis

on Innate

Immune Reactions

Beneficial effects of Scutellaria baicalensis

extracts was observed in astounding wide spec− trum of illnesses as: infectious, tumor, inflamma− tory, autoimmune, neurodegenerative, asthmatic and others. The wide spectrum of activities prompted authors to search for common mecha− nism engaged in development of all the diseases. Such common reaction attending all the diseases is inflammation. Inflammatory reaction results from overstimulation cells of immune system especially innate system, and defective natural regulation based on adenosine, SOCS and Tyro−3 molecules or cytokines IL−10, TGFβ[40]. Among different ideas, the regulation of innate immunity by

sider IFNs type I and type II as the most patho− genic effectors in autoimmunity. A higher produc− tion of cytokines, oxidative stress and high pro− duction of NO accompany autoimmunity and neu− rodegeneration. In central nervous system (CNS) microglia cells presenting TLRs, play a role of innate immunity cells, which protect neurons from neurotoxic effects. However, when they are over− stimulated (i.e. by Aβ in Alzheimer disease) instead protect, they kill neurons.

In the context of the antiviral activity of

Scutellaria baicalensis, against broad spectrum viruses, the effect of baicalein− and wogonin− enriched preparations on three mechanisms of innate immunity: natural resistance of human leukocytes to viral infection, production of cytokines and killing virally infected leukocytes were studied.

The obtained results indicate that extracts con− taining baicalein and wogonin express antiviral activity by augmentation of the resistance/innate

antiviral immunity of PBLs sensitive to infection, by stimulation of killing the virally infected leuko− cytes and by modulation of cytokines production i.e. inhibition IFNα, IFNγ an stimulation TNFα, IL−12 and IL−10 (46).

Strengthen of antiviral resistance of leuko− cytes, stimulation of IL−12 production, killing virally infected cells by flavones from Scutellariae baicalensis radixmay be the mechanisms of their antiviral and perhaps an antitumor activity.

Several biotechnology and pharmaceutical companies have programmes to develop new drugs that are either: agonists of TLRs to enhance immune responses against tumors and infectious diseases or to correct allergic responses; or antag− onist designed to reduce inflammation due infec− tion or autoimmune and neurodegenerative dis− eases. Flavones from Scutellaria baicalensis root with regulatory effect on innate immunity, have opportunity to join the new drugs list.

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Address for correspondence:

Zofia Błach−Olszewska

Ludwik Hirszfeld Institute of Immunology and Experimental Therapy Polish Academy of Sciences

Rudolfa Weigla 12 53−114 Wrocław Poland

Tel.: +48 71 337 11 72

E−mail: [email protected]

Conflict of interest: None declared