There are no clinical trials of skullcap herb; skullcap root components have antimicrobial properties in vitro. Hepatotoxicity associated with skullcap is most likely due to adulteration with germander.

[LFODPKM ] Letter Key

Latin Name

Scutellaria laterifolia L.; Baikal skullcap, Scutellaria baicalensis Georgi

Family

Labiatae

Other Common Names

Huangqin (Scutellaria baicalensis, Scutellaria barbata, and other species of Scutellaria) (China), ogon, and wogon (Japan)

Description

• Skullcap is a perennial mint that grows 1 to 3 ft in height; it has a striated stem and violet-blue flowers with a typical hooded calyx. The plant favors rich woods and grows throughout much of eastern North America.

Part Used

Aerial part (United States and Western countries), root (Asia)

Known Active Constituents

• Root: Sterols and many different flavonoids, including the aglycone baicalein (scutellarein) (less than 0.1% to 5.2%), baicalin (0.1% to 20.6%), baicalein-7-O--D-glycopyranoside, wogonin (0.1% to 2.1%), wogonin-7-O-glucoronide (less than 0.1% to 5.4%), oroxylin A, oroxylin A 7-O-glucoronide (less than 0.1% to 4.1%), dihydrooroxylin A, scullcapflavone I, scullcapflavone II, and chrysin (1).
• Leaf: The flavonoids carthamidin, isocarthamidin, and isoscutellarein-8-O-glucoronide. Although neither flower nor leaf contain the major flavonoids found in the root, small amounts of baicalin and wogonin-7-O-glucoronide are found in the stem (higher amounts in the lower compared with the upper stem).
• S. baicalensis contains substantial amounts of melatonin (7.11 µg/g); S. laterifolia contains less (0.09 µg/g) (2).

Mechanism/Pharmacokinetics

• No information on pharmacokinetics identified in humans. In rats, after oral administration of baicalin, approximately half of metabolites were excreted in bile. The administration of baicalein results in recovery of the same metabolites, and it is thought that baicalin is hydrolyzed in the gastrointestinal tract to baicalein.
• Antimicrobial activity of Scutellaria may be due to stimulation of nitric oxide production from macrophages (3). Baicalein (5 to 25 mM) and wogonin (5 to 50 mM) inhibit lipopolysaccharide-induced nitric oxide generation, which may be involved in antiinflammatory effects (4).
• Several components of Scutellaria bind to the benzodiazepine site of the -aminobutyric acid _A (GABA _A) receptor; the order of affinity is wogonin > baicalein > scuttelarein > baicalin (5).
• Baicalein and baicalin were shown to have free radical scavenging and antioxidant effects (6).

[Outline]

• LLatin Name
• FFamily
• OOther Common Names
• DDescription
• PPart Used
• KKnown Active Constituents
• MMechanism/Pharmacokinetics

[CAO ] Letter Key

Clinical Trials

No clinical trials identified.

Animal/In Vitro

• No studies were identified with skullcap aerial parts; all studies identified used Scutellaria root extract or baicalein.
• Antimicrobial effects
  • Baicalin may be potentially useful as an adjunct to beta-lactam treatments against resistant microorganisms. Baicalin (16 µg/mL) decreases the minimum inhibitory concentration of benzyl penicillin against methicillin-resistant Staphylococcus aureus from 125 µg/mL to 4 µg/mL and against penicillin-resistant S. aureus from 250 µg/mL to 16 µg/mL (7). Baicalin inhibits HIV infection and replication in vitro (8) and also inhibits human T cell leukemia virus type 1 with no loss of cell viability (9).
  • Several flavones from S. baicalensis roots were found to inhibit Epstein-Barr virus early antigen activation (10). A lyophilized tea of Scutellaria was found to inhibit Klebsiella pneumoniae, Proteus vulgaris and Candida albicans at 200 µg/mL, and Mycobacterium smegmatis at less than 100 µg/mL (11).
  • A decoction of S. baicalensis was tested against oral bacteria; a concentration of 3.13% was required for bactericidal effect. Tetracycline, alexidine, and stannous fluoride were much more effective (12).
  • Antimicrobial activity may be due to stimulating nitric oxide production from macrophages; stimulation of recombinant interferon-gamma-primed mouse peritoneal macrophages with S. baicalensis resulted in increased nitric oxide production (Scutellaria on its own did not affect nitric oxide production) (3).
  • Sho-saiko-to, a seven-herb mixture, induced interleukin-10 production in mononuclear cells from patients with hepatitis B or hepatitis C; the effect was found to be due mainly to Scutellaria root and licorice root (13).
• Cardiovascular
  • An extract of S. baicalensis reduced cell death in a cardiomyocyte model of ischemia and reperfusion (14). In cultured human umbilical vein endothelial cells, baicalein prevents trypsin-induced thrombotic tendencies (15). Another experiment, also using cultured human umbilical vein endothelial cells, found that baicalein inhibited thrombin induced plasminogen activator inhibitor-1, possibly by reducing elevation of intracellular calcium (16). In rat mesenteric artery, baicalein had a contracting effect at low concentrations and relaxed arterial smooth muscle at higher concentrations (17).
• Anticancer
  • Several flavones from Scutellaria baicalensis roots were found to inhibit mouse skin tumor promotion in a two-stage carcinogenesis test (10).

Other Claimed Benefits/Actions

• Leaf
  • Tonic
  • Sedative
  • Antispasmodic
  • Anticonvulsant
• Root
  • Diuretic
  • Sedative
  • Antihypertensive
  • Antiviral
  • Antibacterial
  • Anticancer
  • Antiinflammatory

[Outline]

• CClinical Trials
• AAnimal/In Vitro
  • Antimicrobial effects
  • Cardiovascular
  • Anticancer
• OOther Claimed Benefits/Actions
  • Leaf
  • Root

[ADT ] Letter Key

Adverse Reactions

• Hepatotoxicity
  • Hepatotoxicity has been attributed to skullcap, but all of these cases are likely due to mistaken identity; skullcap is commonly adulterated with common germander (Teucrium chamaedrys), which is known to be hepatotoxic. The common names can be confusing; material known as "pink skullcap" is actually wild germander (Teucrium canadense) (18). In all cases of hepato-toxicity, combination herbal products were used, and none of the reports include analyses of the herbs, so the actual identity of the plant material was never established.
  • Four cases of acute hepatitis in the United Kingdom were attributed to the use of stress-reducing tablets (three used the preparation called Kalms, which purportedly contains valerian, asafetida, hops, and gentian), and one used a preparation called Neurelax (other ingredients are not listed in the case report) (19). Although skullcap and valerian were common to both preparations, numerous other herbs were present in these tablets.
  • Another case of hepatitis occurred in a 49-year-old woman taking herbal tablets that contained mistletoe, motherwort, kelp, wild lettuce, and skullcap (20); as the authors point out, mistletoe has known hepatotoxic effects.
  • A 56-year-old woman in Australia developed hepatitis after taking a variety of herbal products that included mistletoe, celery fruit, guaiacum, burdock root, sarsaparilla, valerian, skullcap, and passion flower (1).
  • In a fatal case, a 28-year-old man presented with jaundice after treating mild multiple sclerosis with zinc, skullcap (six tablets daily, no other information given), and p’au d’arco (21). The patient tested negative for HIV and hepatitis virus A, B, and C; toxicology screens were negative, and antinuclear antibodies were positive. On autopsy, hepatic venoocclusive disease with associated hepatic necrosis was noted. The herbal compounds were not analyzed, but the authors conjecture that the mixture was adulterated with an herb containing pyrrolizidine alkaloids.
• Scutellaria is commonly used in traditional Chinese medicine, and normally neither administration of root preparations nor injection of baicalin or baicalein have been associated with adverse effects beyond rare gastrointestinal symptoms (1). However, an unreferenced statement in a pharmacology text states that 150 mg baicalin given by intramuscular injection can cause fever and muscle aches; 27 mg baicalin administered intravenously can cause fever and decreased leukocytes (22).

Drug Interactions

• None reported. In rats, S. baicalensis root decoction administered for 5 days had no effect on cytochrome P450 levels or bilirubin metabolizing enzymes (23).

Animal Toxicity

• Baicalin administered intraperitoneally was reported to have an LD₅₀ of 3 g/kg in mice.
• Chinese studies of Scutellaria root have found low toxicity when administered orally (1).
• Female mice treated subcutaneously with an aqueous extract of S. baicalensis for 5 days did not experience decreased fertility. Rats treated with aqueous extract concentrates of Scutellaria root in oral doses up to 25 g/kg/day from day 7 to day 17 of pregnancy were observed to have offspring with an increased incidence of lumbar rib and abnormalities of the urinary system (1).

[Outline]

• AAdverse Reactions
  • Hepatotoxicity
• DDrug Interactions
• TAnimal Toxicity

Common Dosage Forms

• Dried herb: 1 to 2 g t.i.d.
• Infusion: 1 to 2 g t.i.d.
• Liquid extract: (1:1, 25% ethanol) 2 to 4 mL t.i.d.
• Tincture: (1:5, 45% ethanol) 1 to 2 mL t.i.d.

Q: Wasn’t skullcap once used to treat rabies?

A: Yes, which explains its 18th century name of mad-dog skullcap. Popular in the late 18th and early 19th centuries, skullcap was considered a quack remedy by the 1820s (18).

1. DeSmet PAGM. Scutellaria species. In: DeSmet PAGM, Keller K, Hänsel R, Chandler RF, eds. Adverse effects of herbal drugs, vol 2. Berlin: Springer-Verlag, 1992:289–296.
2. Murch SJ, Simmons CB, Saxena PK. Melatonin in feverfew and other medicinal plants. Lancet 1997;350:1598–1599.
3. Kim HM, Moon EJ, Li E et al. The nitric oxide-producing activities of Scutellaria baicalensis. Toxicology 1999;135:109–115.
4. Wakabayashi I. Inhibitory effects of baicalein and wogonin on lipopolysaccharide-induced nitric oxide production in macrophages. Pharmacol Toxicol 1999;84:288–291.
5. Hui KM, Wang XH, Xue H. Interaction of flavones from the roots of Scutellaria baicalensis with the benzodiazepine site [Letter]. Planta Med 2000;66:91–93.
6. Gao Z, Huang K, Yang X et al. Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. Biochim Biophys Acta 1999;1472:643–650.
7. Liu IX, Durham DG, Richards RM. Baicalin synergy with beta-lactam antibiotics against methicillin-resistant Staphylococcus aureus and other beta-lactam-resistant strains of S. aureus. J Pharm Pharmacol 2000;52:361–366.
8. Li BQ, Fu T, Yan YD et al. Inhibition of HIV infection by baicalin—a flavonoid compound purified from Chinese herbal medicine. Cell Mol Biol Res 1993;39:119–124.
9. Baylor NW, Fu T, Yan YD, Ruscetti FW. Inhibition of human T cell leukemia virus by the plant flavonoid baicalin (7-glucuronic acid, 5,6-dihydroxyflavone). J Infect Dis 1992;165:433–437.
10. Konoshima T, Kokumai M, Kozuka M et al. Studies on inhibitors of skin tumor promotion. XI. Inhibitory effects of flavonoids from Scutellaria baicalensis on Epstein-Barr virus activation and their anti-tumor-promoting activities. Chem Pharm Bull 1992;40:531–533.
11. Franzblau SG, Cross C. Comparative in vitro antimicrobial activity of Chinese medicinal herbs. J Ethnopharmacol 1986;15:279–288.
12. Tsao TF, Newman MG, Kwok YY et al. Effect of Chinese and western antimicrobial agents on selected oral bacteria. J Dent Res 1982;61:1103–1106.
13. Yamashiki M, Nishimura A, Suzuki H et al. Effects of the Japanese herbal medicine "Sho-saiko-to" (TJ-9) on in vitro interleukin-10 production by peripheral blood mononuclear cells of patients with chronic hepatitis C. Hepatology 1997;25:1390–1397.
14. Shao ZH, Li CQ, Vanden Hoek TL et al. Extract from Scutellaria baicalensis Georgi attenuates oxidant stress in cardiomyocytes. J Mol Cell Cardiol 1999;31:1885–1895.
15. Kimura Y, Okuda H, Ogita Z. Effects of flavonoids isolated from scutellariae radix on fibrinolytic system induced by trypsin in human umbilical vein endothelial cells. J Nat Prod 1997;60:598–601.
16. Kimura Y, Yokoi K, Matsushita N et al. Effects of flavonoids isolated from scutellariae radix on the production of tissue-type plasminogen activator and plasminogen activator inhibitor-1 induced by thrombin and thrombin receptor agonist peptide in cultured human umbilical vein endothelial cells. J Pharm Pharmacol 1997;49:816–822.
17. Chen ZY, Su YL, Lau CW et al. Endothelium-dependent contraction and direct relaxation induced by baicalein in rat mesenteric artery. Eur J Pharmacol 1999;374:41–47.
18. Foster S. Scullcap: an herbal enigma. Business Herbs 1996;May–June:14–16.
19. MacGregor FB, Abernethy VE, Dahabra S et al. Hepatotoxicity of herbal remedies. BMJ 1989;299:1156–1157.
20. Harvey J, Colin-Jones DG. Mistletoe hepatitis. BMJ Clin Res Ed 1981;282:186–187.
21. Hullar TE, Sapers BL, Ridker PM et al. Herbal toxicity and fatal hepatic failure [Letter]. Am J Med 1999;106:267–268.
22. Huang KC. Pharmacology of Chinese herbs, 2nd ed. Boca Raton, FL: CRC Press, 1999:385–386.
23. Yin J, Wennberg RP, Miller M. Induction of hepatic bilirubin and drug metabolizing enzymes by individual herbs present in the traditional Chinese medicine, yin zhi huang. Dev Pharmacol Ther 1993;20:186–194.