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Baikal Skullcap

Scientific Name(s): Scutellaria baicalensis Georgi.
Common Name(s): Baical skullcap, Chinese skullcap, Golden root, Huang chin, Huang lien, Huang-qin, Hwang-keum, Hwanggum, Koganebana, Senohgon, Whang-geum, Wogon

Clinical Overview

Use

Baikal skullcap has been used for anti-inflammatory, antioxidant, immunoprotective, anticancer, antimicrobial, antiviral, and circulatory conditions. However, limited quality clinical trials are available to support these uses.

Dosing

3 to 10 g/day, 3 to 9 g root/day, 2 to 6 g dry root/day, 4 to 12 mL fluid extract.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Few adverse reactions have been reported.

Toxicology

In a phase 1 study of healthy volunteers, baicalein 100 to 2,800 mg was not associated with hepatic or kidney toxicity.

Botany

Baikal skullcap is an herbaceous perennial with fleshy roots, growing to 0.3 to 1.2 m in height. It has lancet-shaped leaves, purple-blue flowers, and black-brown, egg-shaped nutlets. The plant is found in Japan, China, Korea, Mongolia, and Russia1 and thrives on sunny, grassy slopes and in dry, sandy soils. The dried root is used in traditional Chinese medicine. Baikal skullcap is related to skullcap (Scutellaria laterifolia), a North American species (see Scullcap monograph).2

History

Baikal skullcap is a Chinese medicinal herb that was used for over 2,000 years to treat fevers, hypertension, coughing, and other ailments, and is used today as a traditional remedy for dysentery and diarrhea. Baikal skullcap was included as an ingredient in several pharmaceutical combination preparations found in a second century AD tomb in northwestern China.2

Baikal skullcap is prescribed in China for fever, cough, GI, and urinary problems. These uses have been supported by clinical trials. Baikal skullcap is also used in Chinese herbal medicine for inflammation, allergies, dermatitis, hyperlipidemia, and atherosclerosis.2, 3

Chemistry

Major phytochemicals found in S. baicalensis include flavonoids, glycosides, and their glucoronides.1 Flavonoids present in S. baicalensis include baicalin, baicalein, wogonin, and wogonoside.2, 4 Reversed-phase high-performance liquid chromatography determination of flavonoids from S. baicalensis root has been reported.5 Flavone synthases Ι and ΙΙ, chrysin, wogonin, apigenin, salvigenin, scutellarein, and isoscutellarein were among flavonoid constituents also found in S. baicalensis leaf parts.6 Flavones baicalein, oroxylin, and skullcapflavone ΙΙ also were identified.7 Other reports confirmed similar flavonoid content.8, 9 One report described melatonin in certain plant samples.10 Other compounds include sterols and benzoic acid.2 The North American species, S. laterifolia differs in chemical constituents.

Uses and Pharmacology

Anti-inflammatory effects

Anti-inflammatory effects of Baikal skullcap are well documented. One study reported an effect similar to that of prednisolone with an methanolic extract of 3 flavonoids (wogonin, baicalein, and baicalin).11 Baicalein may be effective in yielding anti-inflammatory properties through inhibition of cyclooxygenase (COX), ultimately reducing the formation of prostaglandins.12

Animal/In vitro data

Another study reported that chloroform extract of Saxifraga rivularis exhibited greater inhibition than indomethacin against carrageenan-induced rat paw edema. Baicalin also demonstrated the most effective inhibition activity when compared with baicalein and wogonin.13 Wogonin, baicalein, and baicalin all have been found to influence some anti-inflammatory pathways via certain proteins, antigens, and enzymes.14, 15, 16

A standardized and purified extract of S. baicalensis containing baicalein, oroxylin A, and wogonin exerted anti-inflammatory effects in both in vitro and in vivo models of colitis. Specifically, the extract reduced tumor necrosis factor (TNF)-alpha-induced COX-2 expression by reducing the histopathological severity as well as the expression of COX-2, TNF-alpha, and interleukin-1beta.17 In a murine model, a Chinese formula containing S. baicalensis, Paeonia lactiflora, Glycyrrhiza uralensis, and Ziziphus jujube was similarly effective as compared with salicylazosulfapyridine in mice induced with colitis, resulting in improved colonic swelling and redness, and increased weight.18

In a study of 2,4-dinitrochlorobenzene-induced contact dermatitis in BALB/c mice, topical application of an aqueous extract of S. baicalensis suppressed dermatitis by reducing the production of inflammatory cytokines (ie, IL-4, IFN-gamma, TNF-alpha). Infiltration of leukocytes into the dermis and epidermal thickness were also reduced with S. baicalensis.19

Antioxidant effects

Flavonoids from S. baicalensis have been studied for antioxidant effects. Four major flavonoids (baicalein, baicalin, wogonin, and wogonoside) have been studied in various systems, confirming antioxidant activity.20

Animal/In vitro data

One study found that baicalein exhibited the most consistent antioxidant effects, with baicalin and wogonin also displaying some antioxidant effects. Wogonoside was found to be inactive.21 An extract of the plant also demonstrated protective action against oxidation induced by ultraviolet light, suggesting potential use against certain skin diseases.22 Another study found that flavonoid baicalein inhibited lipid peroxidation in rat liver microsomes.23 Studies also found that baicalein and baicalin scavenged hydroxyl radical, superoxide anion, and other free radicals in a dose-dependent manner,4 and that baicalein directly scavenged superoxide, hydrogen peroxide, and hydroxyl radicals in cardiomyocytes.24 Flavonoids wogonin and wogonoside demonstrated subtle effects on these radicals, but did inhibit nitric oxide production, along with water extract of the plant.4, 25, 26 Results also showed that ganhuangenin isolated from S. baicalensis had greater antioxidant potency than alpha-tocopherol.27

Clinical data

There is no clinical data regarding the use of Baikal skullcap as an antioxidant.

Immunoprotective/Anticancer effects

Because of its potential effects as an antioxidant, Baikal skullcap also has been studied in immunology and cancer research.

Animal/In vitro data

In rats with Pliss lymphosarcoma associated with disorders in platelet-mediated hemostasis, S. baicalensis administration produced a normalizing effect that may be responsible for its antitumor and metastasis-preventing effect.28 In other reports, a 14-flavone combination from S. baicalensis had marked inhibitory effects on mouse skin tumor promotion29 and also demonstrated anticancer activity in laboratory mice with head and neck squamous cell carcinoma.30 S. baicalensis, in an herbal preparation with 8 other herbs, was evaluated for treating prostate cancer. PC-SPES therapy reduced prostate-specific antigen by 50% in patients with hormone-resistant prostate cancer. Enzyme prostate acid phosphatase, commonly elevated in prostate cancer, was also decreased by the preparation.31, 32 However, PC-SPES was recalled and withdrawn from the market in February 2002 because certain batches were contaminated with US Food and Drug Administration–controlled prescription drugs. The manufacturer is no longer in operation, and PC-SPES is no longer being made. PC-SPES is not legally available in the United States.33

One study found that the administration of skullcap 25 mg/kg orally once daily in mice sensitized with ovalbumin in order to induce a food allergy response was associated with reduced anaphylactic response as well as reduction in cytokine production, concluding that skullcap may be a preventive moiety for food allergies.34

In a murine model of adenocarcinoma, baicalin ameliorated anorexia by reducing cytokine (ie, TNF-alpha, IL-6) levels and preventing muscle atrophy. Food intake was greater in mice receiving baicalin compared with those receiving a placebo.35

Baicalein inhibited the migration, adhesion, and invasion caused by 17-beta-estradiol in a line of breast cancer cells by interfering with the activation of the GPR30 signaling pathway.36

Wogonin inhibited cell viability in both a time- and dose-dependent manner in HL-60 leukemia cells and also increased the activation of caspases 3, 8, and 9.37

In human colorectal cancer HCT116 cells, baicalein reduced cell viability in a concentration-dependent fashion. After 24 hours of treatment with baicalein, the cells were more rounded and dispersed with aggregation. Baicalein induced apoptosis of these colorectal cancer cells. Suppression of migration occurred with baicalein treated through its ability to inhibit matrix metalloproteinases 2 and 9. Baicalein also reduced the formation of tumors associated with inflammation.38

Cell viability of peripheral blood leukocytes obtained from children with acute lymphocytic leukemia was reduced with the use of a S. baicalensis extract.39

Clinical data

S. baicalensis administered to lung cancer patients improved certain immunoglobulins.40 Another report investigated the effects of the components of a Japanese herbal medicine Sho-saiko-to (TJ-9) on IL-12 production in the adherent cell (monocyte/macrophage) fraction and in the nonadhered cell (lymphocyte) fraction of peripheral blood mononuclear cells obtained from liver cirrhosis patients and healthy subjects. IL-12 is an important cytokine that maintains systemic defense and bioregulation.41 Dry extract of baical skullcap given to 88 lung cancer patients increased hematopoiesis stimulation and improved other anticancer parameters.42 Baicalin and baicalein inhibited cell proliferation in certain cell lines,43 induced quinone reductase,44 and induced apoptosis in prostate cancer cells.45 Other in vitro effects included antigenotoxic actions of baicalein.46

Antimicrobial effects

Animal/In vitro data

Several studies evaluating the antimicrobial effects of Baikal skullcap have been conducted. In vitro testing of an S. baicalensis preparation on selected oral bacteria demonstrated bacteriostatic and bactericidal effects at specified concentrations.47 The flavone isolate baicalin was found to be synergistic with beta-lactam antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) and other beta-lactam-resistant strains of S. aureus.48 One study found that baicalein was effective against penicillinase-producing S. aureus and MRSA by inhibiting penicillinase in a dose-dependent manner.49 Antiviral effects of the plant also have been reported. A flavonoid compound from S. baicalensis inhibited T-cell leukemia virus type Ι (HTLV-Ι). Constituent baicalin inhibited reverse transcriptase activity in HTLV-Ι-infected cells, as well as the activity of purified reverse transcriptase from Moloney murine leukemia virus and Rous-associated virus type 2.50 Other flavones, such as isoscutellarein from S. baicalensis leaves, also showed anti-influenza virus activity in vitro.51 Isoscutellarein-8-methylether from S. baicalensis roots had effects against influenza A and B viruses, with results suggesting inhibition of the replication of A/Guizhou and B/Ibaraki viruses by inhibiting the fusion of viral envelopes with the endosome/lysosome membrane that occur in the early stage of the virus infection cycle.52

Another in vitro study found baicalein exerted antimicrobial effects against 11 different oral bacterial species. Baicalein also exerted synergistic and sometimes additive effects when administered in combination with ampicillin and/or gentamicin in these bacterial strains.53

Clinical data

A Scutelleria compound injection versus intravenous piperacillin was studied in 60 patients with pulmonary infection. Results were comparable in certain parameters, such as effective rates, leucocyte count, and low adverse reaction incidence. However, in the piperacillin group, 4 of the 30 patients had subsequent fungal infections; whereas, in the Scutelleria group, no fungal infections were found after treatment.54 High antifungal activity was found against Candida albicans caused by S. baicalensis in an herbal screening study.55 Antifungal effect was due to baicalein in another report in which S. baicalensis was found to be active against Cryptococcus neoformans and Pityrosporum.56

Cardiovascular effects

Animal/In vitro data

Baikal skullcap has been used to alleviate circulatory problems (eg, high blood pressure, arteriosclerosis, varicose veins, bruising).2 Flavone baicalein inhibited thrombin and thrombin-induced calcium and plasminogen activators in cultured human umbilical vein endothelial cells, suggesting potential benefits in arteriosclerosis and thrombosis.57

S. baicalensis roots have been suggested to reduce blood pressure, particularly in renin-dependent hypertension; however, in a murine model, baicalein increased sensitivity to vasoconstriction. Inhibition of lipoxygenase may also explain baicalein’s hypotensive effects.12

Baicalein reduced thrombin-mediated fibrin polymerization, prolonged activated partial thromboplastin time and prothrombin time, reduced platelet aggregation, decreased FeCl3-induced thrombus formation, and inhibited activated factor X and thrombin activity. Additionally, bleeding time measured in mice tails was prolonged. However, baicalein exerted weaker anticoagulant activities when compared with warfarin and heparin.58

Clinical data

Research reveals no clinical data regarding the use of Baikal skullcap for cardiovascular effects.

Neuroprotective effects

Baikal skullcap may exert a protective effect in neurodegenerative diseases due to anti-inflammatory, antioxidant, and antiapoptotic effects.1

Animal/In vitro data

Baikal skullcap may be useful for the treatment of Alzheimer disease. Flavonoids from Baikal skullcap exerted a protective effect on hippocampal neurons by reducing lipid peroxidation build up and glial cell proliferation.59 In a murine model of okadaic acid-induced neuronal damage, S. baicalensis reduced neuronal injuries in the hippocampus and cerebral cortex. Additionally, S. baicalensis reversed the reduction in neuron count.60

In an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced murine model of Parkinson disease, baicalein 140 or 280 mg/kg improved behavioral deficits caused by the MPTP similar to those of the positive control of madopar. Baicalein was also associated with improvements in neurogenesis, neuroblast proliferation, neurotrophin signaling pathway, walking and locomotor behaviors, and regulation of gene expression.61

Clinical data

There is no clinical data regarding the use of Baikal skullcap for neuroprotective effects.

Psoriasis

Animal/In vitro data

In a murine model, topical application of baicalin cream inhibited a 2,4-dinitrofluorobenzene-induced contact hypersensitivity reaction. The anti-inflammatory effect was not the same magnitude as that seen with tacrolimus. The effects were stronger at higher concentrations as well as at 48 hours as compared with 24 hours. Additionally, baicalin cream produced differentiation in the epidermis of mouse tails with psoriasis, with the 5% cream having the greatest effect compared with baicalin 1% and 3% creams.62

Clinical data

One case report described the successful treatment of psoriasis with a topical ointment containing S. baicalensis as well as Indigo naturalis and Cortex phellodendri. An 8-year-old male with a 2-year history of psoriasis was originally responsive to traditional therapies; however, his symptoms worsened with continued therapy. After receiving the combination ointment twice daily for 2 months, his previous 80% body surface coverage improved to 0%. He remained in remission for 1 year, and for occasional small flare-ups, reapplication to the ointment was beneficial.63 However, no clinical evidence exists.

Other effects

Baicalin exhibited hepatoprotective actions in rats as well.64 Other uses of Baikal skullcap preparations include treatment of neonatal jaundice,65 marked antiulcerogenic actions,66 sores, swelling, boils, and diabetic problems.2

An in vitro study reported weak estrogenic activity associated with S. baicalensis.67

Five flavonoids derived from S. baicalensis were found to inhibit alpha-glucosidase activity in vitro. Specifically, the strongest inhibitor was baicalein followed by wogonin, baicalin, chrysin, and oroxylin A.68 Additionally, baicalein inhibited the activity of rat intestinal sucrose as well as human intestinal sucrose expression in Caco-2 cells. Therefore, the compound might be useful in lowering postprandial blood glucose levels.69

Dosing

3 to 10 g/day, 3 to 9 g root/day, 2 to 6 g dry root/day, 4 to 12 mL fluid extract.70

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. In a study of mice, administration of an aqueous extract of S. baicalensis root up to 32 g/kg/day did not result in fetal malformation. However, the maximum dose 32 g/kg/day resulted in maternal elevations in liver and kidney weights.71, 72, 73, 74

Interactions

Alpha glucosidase inhibitors

Because baicalein may have a mechanism of action similar to that of alpha-glucosidase inhibitors,69 use caution in patients receiving alpha glucosidase inhibitors should be monitored for hypoglycemia if taken with baicalein.

Antiplatelets/Anticoagulants

Due to potential antiplatelet, anticoagulant, and profibronolytic effects of baicalein,58 it should be used with caution in patients taking any medications or supplements that can prolong bleeding time.

Garlic supplementation

In a murine model, the addition of garlic to S. baicalensis was associated with a reduced area under the curve and time to maximum plasma concentration.75

Adverse Reactions

Few adverse reactions have been reported. Because flavones of Baikal skullcap have been shown to interact with the benzodiazepine site of the gamma-aminobutyric acid A receptor, sedation may occur with coadministration.76 No adverse reactions were reported in liver, kidney, or medulla regions in a 60-patient study of IV Scutellaria compound.54 Isolate isoscutellarein from S. baicalensis leaves produced negligible toxic effects in mice.48 Limbrel (flavocoxid), a prescription medical food product containing baicalin and catechins, has been associated with hepatic injury. A case series reported 4 cases of liver injury due to flavocoxid (250 to 500 mg twice per day) for the treatment of osteoarthritis in women between 57 and 68 years of age. The appearance of symptoms (ie, jaundice, pruritus, abdominal pain, fever, rash) occurred within 1 to 3 months of initiation and resolved within a few days of discontinuation. Because Limbrel contains a proprietary blend of compounds from both S. baicalensis and A. catechu, discerning which may be responsible for liver injury may not be possible.77 Hyperactive bowel sounds, abdominal distention, constipation, dizziness, somnolence, blurred vision, reduction in plasma fibrinogen, and reduction in blood leukocyte were reported in healthy volunteers taking baicalein 100 to 2,800 mg in a phase 1 study.78

Toxicology

In a phase 1 study of healthy volunteers, baicalein 100 to 2,800 mg was not associated with hepatic or kidney toxicity.78

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