Scutellaria baicalensis

Baikal skullcap

Baikal skullcap (Scutellaria baicalensis Georgi), also known as Chinese skullcap or Huang-qin in Pinyin, is a perennial plant with pretty violet flowers of the mint (Lamiaceae) family. It is related to the mad-dog skullcap (Scutellaria lateriflora) but with an entirely different range of indications (see table 1). The root of the Baikal skullcap is used in traditional Chinese medicine to clear 'Heat and dry Dampness'. Diseases with 'Heat' are associated with symptoms such as fever, irritability, thirst, cough and expectoration of thick, yellow sputum. Damp diseases may be associated with diarrhoea, a feeling of heaviness of the chest and painful urination (Bensky & Gamble 1986). From a modern perspective this suggests that Baikal may be useful for infection and inflammation of the respiratory, digestive and urinary systems and scientific investigations have indeed shown that Baikal skullcap and its constituents have antibacterial, antiviral, anti-inflammatory, hepatoprotective and diuretic actions (Zhang, Li, & Liu 2001). Baikal is also an ingredient in the very popular traditional Chinese/Japanese formulation, Minor Bupleurum Combination known as Xiao Chai Hu Tang (Chinese) and Sho-saiko-to (Japanese) described in Table 2. Minor Bupleurum Combination has been used in China for about 3000 years for the treatment of pyretic diseases. In Japan, Sho-saiko-to is now a prescription drug approved by the Ministry of Health and Welfare and widely used in the treatment of chronic viral liver diseases. Since 1999, Sho-saiko-to has been administered to 1.5 million patients with chronic liver diseases due to its ability to significantly suppress cancer development in the liver. (Yamashiki et al. 1999a) Saiboku-to is also used for the treatment of bronchial asthma in Japan (Nakajima et al. 2001a).

Phytochemistry

Baikal skullcap contains numerous flavonoids and their glycosides. The main flavonoids are baicalin and its aglycone, baicalein and wogonin. Baicalin itself is poorly absorbed from the gut, but is hydrolysed to its aglycone, baicalein, by intestinal bacteria and then restored to its original form from the absorbed baicalein in the body (Akao et al. 2000). Resin and tannins are also present. The root also contains melatonin. It has been shown that dietary melatonin directly contributes to the circulating level of the hormone. The clinical effects of plant-derived melatonin remains to be investigated (Hardeland & Poeggeler 2003)

Anti-inflammatory activity

The anti-inflammatory activity of Baikal skullcap has been well documented by in vitro and in vivo studies. The main constituents responsible are baicalein and wogonin (Chang et al. 2001a;Chi, Cheon, & Kim 2001b;Chung, Park, & Bae 1995b;Krakauer, Li, & Young 2001a;Li et al. 2000b;Park et al. 2001b;Wakabayashi 1999a). In a study using mice, baicalein 50 mg/kg has been shown to ameliorate the inflammatory symptoms of induced colitis including body weight loss, blood haemoglobin content, rectal bleeding and other histological and biochemical parameters (Hong et al. 2002). The methanolic extract of the baikal skullcap root and its flavonoids wogonin, baicalein and baicalin have been shown to inhibit lipo-polysaccharide induced inflammation of the gingivae (gums) in vivo. The three flavonoids exerted an anti-inflammatory effect similar to prednisolone. In addition, the flavonoids exerted a moderate inhibition (33-36%) of collagenolytic activity, comparable to 40% inhibition by tetracycline. Meanwhile, the cellular activity of fibroblasts was augmented remarkably (40%) by baicalein and slightly by baicalin and wogonin. Consistent with the cellular activation, the flavonoids enhanced the synthesis of both collagen and total protein in fibroblasts in vitro (Chung, Park, & Bae 1995a). The anti-inflammatory mechanisms are varied and summarised in table 3.

Antifibrotic and hepatoprotective activity

Minor Bupleurum Combination (Sho-saiko-to) has been shown to play a chemopreventive role in the development of hepatocellular carcinoma in cirrhotic patients in a prospective study and several studies have demonstrated the preventive and therapeutic effects of Sho-saiko-to on experimental hepatic fibrosis. Sho-saiko-to has been shown to inhibit the activation of hepatic stellate cells, the major collagen-producing cells. Sho-saiko-to has potent antifibrotic effect by inhibiting oxidative stress in hepatocytes and hepatic stellate cells. It is proposed that the active components are baicalin and baicalein. Baicalin and baicalein has chemical structures very similar to silybinin, the active compound in Silybum marianum (St Mary's thistle) that exhibits anti-fibrotic activities.

In addition, Sho-saiko-to has been shown to inhibit chemical hepatocarcinogenesis in animals, acts as a biological response modifier and suppresses the proliferation of hepatoma cells by inducing apoptosis and arrests the cell cycle. These effects may be due to baicalin, baicalein and saikosaponins (from Bupleurum falcatum), which have the ability to inhibit cell proliferation (Shimizu 2000).

A methanolic extract of Baikal skullcap has been shown to inhibit fibrosis and lipid peroxidation in rat liver induced by bile duct ligation or carbon tetrachloride. Bile duct ligation in rodents is an experimental model for extrahepatic cholestasis caused by e.g. cholelithiasis (gall stones). Liver fibrosis was assessed by histological observations and by measuring levels of liver hydroxyproline, lipid peroxidation based on malondialdehyde production, and serum enzyme activities. Treatment with Baikal skullcap significantly reduced the levels of liver hydroxyproline and malondialdehyde, with improved histological findings (Nan et al. 2002).

Baicalein, baicalin and wogonin have been shown to have hepatoprotective effects in vivo. The flavonoids decreased the toxicity produced by a variety of chemicals. Significant protective effects were seen by comparing the serum glutamate oxaloacetate transaminase (sGOT), serum glutamate pyruvate transaminase (sGPT) and histopathologic examination (Lin & Shieh 1996).

Baikal flavonoids inhibit hepatic CYP1A2, suggesting that Baikal extract may be hepatoprotective via prevention of CYP1A2-induced metabolic activation of toxins (Kim et al. 2002).

Antioxidant activity

Several studies have shown Baikal skullcap constituents to be antioxidant in vitro and in vivo. Flavones produced a concentration-dependent protection of liposome membrane against UV-induced oxidation. The ability to scavenge free radicals and protect against the effects of lipid peroxidation (here caused by sunlight irradiation) may in part account for the herb's underlying mechanism of action (Gabrielska et al. 1997)

Fourteen flavonoids and flavone glycosides have been demonstrated to possess good free radical scavenging properties in vitro (Gao et al. 1999;Lin & Shieh 1996). Baicalin has been found to have the most potent antioxidant effect (Bochorakova et al. 2003).

Baicalin's antioxidant effect has been found to mainly be based on scavenging superoxide radicals whilst baicalein was a good xanthine oxidase inhibitor. Xanthine oxidase inhibitors are known to be therapeutically useful for the treatment of hepatitis and brain tumour (Shieh, Liu, & Lin 2000).

Oxidative stress plays an important role in the pathological process of neurodegenerative diseases including Alzheimer's disease. The protective effects of Baikal flavonoids on the oxidative injury of neuronal cells has been demonstrated in vitro (Choi et al. 2002;Gao, Huang, & Xu 2001a;Gao, Huang, & Xu 2001b).

Antiallergic activity

Flavonoids have anti-allergic activities and are known to inhibit histamine release from basophils and mast cells. Luteolin and baicalein have been shown to inhibit IgE antibody-mediated immediate and late phase allergic reactions in mice. In an in vitro study, luteolin and baicalein inhibited IgE-mediated histamine release from mast cells. The compounds also inhibited IgE-mediated TNF-alpha and IL-6 production from mast cells. However, the compounds did not affect the histamine, serotonin or platelet activating factor-induced cutaneous reactions in rats (Kimata, Inagaki, & Nagai 2000).

Baicalein has been found to be 5-10 times more potent than the antiallergic drug, azelastine. Baicalein significantly suppressed leucotriene C4 release by polymorphonuclear leukocytes obtained from asthmatic patients compared to healthy subjects (Niitsuma et al. 2001).

Neuroprotective activity

Cerebral ischaemia can cause a significant elevation in the concentrations of amino acid neurotransmitters in the cerebral cortex. Baicalin administration can attenuate the elevations of glutamic acid and aspartic acid induced by cerebral ischaemia. This research demonstrates that baicalin may act as a neuroprotectant during cerebral ischaemia (Li et al. 2003). Wogonin has been shown to exert neuroprotective effect by inhibiting microglial activation, which is a critical component of pathogenic inflammatory responses in neurodegenerative diseases. Wogonin inhibited inflammatory activation of cultured brain microglia by diminishing lipopolysaccharide-induced tumour necrosis factor-alpha (TNF-alpha), interleukin-1β and nitric oxide (NO) production. Wogonin inhibited NO production by suppressing inducible NO synthase (iNOS) induction and NF-kappaB activation in microglia. The neuroprotective effect of wogonin has also been shown in vivo using two experimental brain injury models (Lee et al. 2003).

Baikal skullcap is used in traditional Chinese medicine for the treatment of stroke. Methanol extracts from the dried roots (0.1-10 mg/kg) administered intra-peritoneally significantly protected neurons against 10 minute transient forebrain ischaemia. The extract inhibited microglial tumour necrosis factor-alpha and nitric oxide production, and protected cells from hydrogen peroxide-induced toxicity in vitro (Kim et al. 2001).

Vascular activity

Treatment with baicalein also lowered the blood pressure in hypertensive but not in normotensive rats (Takizawa, DelliPizzi, & Nasjletti 1998). Baikal extract and baicalein have been shown to lower blood pressure in rats and cats (Kaye et al. 1997;Takizawa, DelliPizzi, & Nasjletti 1998). The exact mechanisms underlying the hypotensive action are unclear. Monocyte chemotactic protein-1 (MCP-1), a potent chemoattractant for monocytes, plays a crucial role in case of early inflammatory responses including atherosclerosis. Wogonin has been shown to inhibit MCP-1 induction by endothelial cells in a dose dependent manner. Wogonin and baikal skullcap may be potentially beneficial in inflammatory and vascular disorders (Chang et al. 2001b).

Baikal flavonoids have been shown to inhibit platelet aggregation in vitro (Kubo, Matsuda, & Tani 1985) and baicalein and baicalin inhibited the conversion of fibrinogen to fibrin induced by thrombin. Baicalein inhibited the elevation of Ca2+ induced by thrombin and thrombin receptor agonist peptide. These findings suggest a potential benefit of baicalein in the treatment of arteriosclerosis and thrombosis (Kimura et al. 1997). One in vivo study has shown that Scutellaria baicalensis extract produces peripheral vasodilatation (Lin et al. 1980a).

Cholesterol reduction

Flavonoids are known to reduce cholesterol. A 30-day study of induced hyperlipidaemia in rats found that baicalein, quercetin, rutin and naringin reduced cholesterol with baicalein being the most potent. Baicalein was also the most effective flavonoid in reducing triglyceride levels (De Oliveira et al. 2002).

Anxiolytic activity

Wogonin, baicalein, scutellarein and baicalin (in reducing order of potency), which all contain a certain flavonoid phenylbenzopyrone nucleus, have been shown in vitro to bind with the benzodiazepine site of the GABA-A receptor (Hui, Wang, & Xue 2000).

Oral administration of wogonin (7.5-30 mg/kg) has been shown to interact with GABA-A receptors and produce an anxiolytic response that was similar to diazepam in the elevated plus-maze. Unlike benzodiazepines, wogonin was able to reduce anxiety without causing sedation or myorelaxation (Hui et al. 2002;Kwok et al. 2002).

Baicalin (10 mg/kg i.p.) and baicalin (20 mg/kg i.p.) have also been shown in vivo to produce an anxiolytic effect, mediated through activation of the benzodiazepine binding sites of GABA-A receptors (Liao, Hung, & Chen 2003)

A water extract of Baikal skullcap has been shown in vivo to have anticonvulsant activity against electroshock-induced tonic seizures. Interestingly, the authors suggest that anticonvulsant effect might not be via the activation of the benzodiazepine binding site of GABA-A receptors, but probably via the prevention of seizure spread (Liao, Hung, & Chen 2003;Wang, Liao, & Chen 2000).

Antiviral and antimicrobial activity

Baikal extract and flavonoids have been shown in numerous studies to be antibacterial, antiviral and antifungal. The antimicrobial effect of baikal extract is mild and the clinical efficacy of baikal in infectious diseases may be more associated with its anti-inflammatory rather than its antimicrobial activities. (Hahm et al. 2001). (Tang, Peng, & Zhan 2003) (Blaszczyk, Krzyzanowska, & Lamer-Zarawska 2000). Antiviral effects have been demonstrated for Baikal in numerous in vitro and in vivo tests. The in vitro studies are summarised in table 4.

Antidiabetic activity

5-alpha-reductase inhibition

Diabetics may accumulate intracellular quantities of the sugars sorbitol and dulcitol, due to an increase of the polyol pathway involving the enzyme 5-alpha-reductase. Oral baicalin and liquid extract of liquorice (also rich in flavonoids) reduce sorbitol levels in the red blood cells of diabetic rats (Lin et al. 1980b;Zhou & Zhang 1989).

Alpha-glucosidase inhibition

Alpha-glucosidase inhibitors (e.g. Glucobay [Acarbose]) is a class of oral medicine for type 2 diabetes, which blocks enzymes that digest starches in food. The result is a slower and lower rise in blood glucose throughout the day, especially right after meals. Methanol extracts of Scutellaria baicalensis, Rheum officinale and Paeonia suffruticosa showed potent inhibitory activity against rat intestinal sucrase. The active principles were identified as baicalein and methyl gallate (from the later two plants). In addition to its activity against the rat enzyme, baicalein also inhibited human intestinal sucrase in vitro (Nishioka, Kawabata, & Aoyama 1998).

Renal-protective activity

Baicalein inhibited angiotension II-induced increases in the cellular protein content of aortic smooth muscle cells in vitro (Natarajan et al. 1994). In another in vitro study, baicalein prevented the angiotension II-induced increase in renal vascular resistance by 50% and promoted the glomerular filtration rate (Bell-Quilley et al. 1993). Pretreatment with baicalein significantly inhibited a decrease in nephrotoxin-induced glomerular filtration rate and renal blood flow in vivo (Wu, Bresnahan, & Lianos 1993). Oral intake of baikal flavonoids and extract has been shown to produce a diuretic effect. The effect is mediated via regulation of the prostaglandin metabolism.

Antineoplastic activity

Immunostimulation

Sho-saiko-to has been shown to stimulate granulocyte colony-stimulating factor (G-CSF) which may explain its use in infectious diseases and cancer (Yamashiki et al. 1992). G-CFS is, like growth hormone, interleukins 2 and 4 and interferon, a signalling ligand which stimulates immune function. G-CSF, a glycoprotein, produce mainly by macrophages, induces proliferation of neutrophil colonies and differentiation of precursor cells to neutrophils. It also stimulates the activity of mature neutrophils (Hill, Osslund, & Eisenberg 1993).

Sho-saiko-to is known to significantly suppress cancer development in the liver. Moderate regulation of the cytokine production system in patients with hepatitis C by using TJ-9 may be useful in the prevention of disease progression (Yamashiki et al. 1997). One possible mechanism for the beneficial effects of TJ-9 on patients with liver cirrhosis may be the improvement in IL-12 production. Interleukin-12 is an important cytokine for maintenance of normal systemic defence and bioregulation. This effect of TJ-9 is attributed to two of its seven herb components, Baikal and liquorice roots (Yamashiki et al. 1999b).

Patients who were given Baikal skullcap showed a tendency towards increase in the relative number of T-lymphocytes and their

theophylline-resistant population during antitumour chemotherapy. The immunoregulation index in this case was approximately twice the background values during the whole period of investigation. The inclusion of Baikal skullcap in the therapeutic complex promoted an increase in the number of immunoglobulins A at a stable level of immunoglobulins G (Smol'ianinov et al. 1997).

Apoptosis induction

Baicalein, baicalin and wogonin have been shown to induce apoptosis, disrupt the mitochondria and inhibit proliferation in various human hepatoma cell lines (Chang, Chen, & Lu 2002b; Chen et al. 2000). Platelet-type 12-Lipoxygenase (12-LOX ) pathway is a critical regulator of prostate cancer progression and apoptosis by affecting various proteins regulating these processes. Baicalein inhibits 12-LOX and may be a potential therapeutic agent in the treatment of prostate cancer (Pidgeon et al. 2002) as well as breast cancer (Tong, Ding, & Adrian 2002).

Antiproliferative effects

Baicalein, baicalin and wogonin has been shown to induce apoptosis and inhibit proliferation in various human hepatoma cell lines (Chang, Chen, & Lu 2002a).

Baicalin has been shown to inhibit the proliferation of prostate cancer cells in vitro. However, the responses to baicalin was different among different cell lines (Chan et al. 2000).

Cyclooxygenase-2 (COX-2), which converts arachidonic acid to prostaglandin E2 (PGE2), is highly expressed in head and neck squamous cell carcinoma (HNSCC). Scutellaria baicalensis, but not baicalein, suppressed proliferation cell nuclear antigen expression and PGE2 synthesis. A 66% reduction in tumour mass was observed in the mice with HNSCC. Baikal selectively and effectively inhibits cancer cell growth in vitro and in vivo and can be an effective chemotherapeutic agent for HNSCC.

Inhibition of PGE2 synthesis via suppression of COX-2 expression may be responsible for its anticancer activity. Differences in biological effects of Baikal compared with baicalein suggest the synergistic effects among components in Baikal(Zhang et al. 2003). Baicalein, baicalin and wogonin have been shown to reduce proliferation of human bladder cancer cell lines in a dose-dependent manner, but baicalin exhibited the greatest antiproliferative activity. In an in vivo study Baikal skullcap extract had a significant inhibition of tumour growth (P<0.05)(Ikemoto et al. 2000).

Amelioration of chemotherapy

In experiments with murine and rat transplantable tumours, Baikal skullcap extract treatment was shown to ameliorate cyclophosphamide and 5-fluorouracil-induced myelotoxicity and to decrease tumour cell viability (Razina et al. 1987).

Prevention of metastases

The advancement of Pliss' lymphosarcoma in rats was shown to be associated with disorders of platelet-mediated haemostasis, presenting with either lowered or increased aggregation activity of platelets. Extract of Baikal was shown to produce a normalising effect on platelet-mediated haemostasis whatever the pattern of alteration. This activity is thought to be responsible for the drug's antitumour and, particularly, metastasis-preventing effect (Razina et al. 1989).

Experiments on mice inoculated with metastasing Lewis lung carcinoma showed that the antitumour and antimetastatic effects of cyclophosphamide are potentiated by Baikal, Rose root (Rhodiola rosea), Liquorice (Glycyrrhiza glabra), and their principal acting components, baicalin, paratyrosol and glycyrrhizin (Razina et al. 2000).

Chemoprevention

Baicalein has been shown to prevent chemically induced DNA damage in a cell culture model (Chan et al. 2002).

Anti-angiogenesis

Baicalein and baicalin have demonstrated in vitro anticancer activity against several cancers. The flavonoids have also been shown to be potent inhibitors of angiogenesis in vitro and in vivo. Baicalein was found to be more potent than baicalin (Liu et al. 2003).

Antiemetic activity

Pre-treatment with baikal root extract has been shown to decrease cisplatin-induced pica in rats (animal models use the level of kaolin (a type of clay) intake as a measure of the intensity of nausea). This suggests that Baikal may help to reduce cisplatin-induced nausea and emesis during cancer therapy (Aung et al. 2003;Wu, Akatsu, & Okada 1995)

Clinical uses

There are no clinical studies utilising an extract of baikal skullcap in isolation. Chinese studies have been based on either injection of isolated constituents or the oral administration of traditional formulations containing baikal skullcap.

Respiratory infection

Sixty patients with respiratory infection (mainly nosocomial pneumonia) were treated either by injection of an unidentified baikal compound or IV piperacillin sodium. The total efficacy was evaluated after treatment for one week. Total effective treatment rates were 73.3% for Baikal compared to 76.7% in the antibiotic treatment group. Body temperature was decreased similarly and symptoms disappeared or were relieved in 11.67 +/- 6.75 days with the herb and 11.53 +/- 7.30 days with the antibiotic. Additionally, leucocyte decreased to normal and roentgenographic shadows disappeared or became smaller in both groups. In the piperacillin sodium group, fungal infections were found in 4 of 30 patients, but there was none in the Baikal treatment group (Lu 1990)

Bone marrow stimulation during chemotherapy

Haemopoiesis was studied in 88 patients with lung cancer during combination treatment with chemotherapy and a Scutellaria baicalensis extract. Administration of the plant preparation was accompanied with haemopoiesis stimulation, intensification of bone-marrow erythrocytopoiesis and granulocytopoiesis and increase in the content of circulating precursors of the type of erythroid and granulomonocytic colony-forming units (Gol'dberg et al. 1997).

Epilepsy

Saiko-keishi-to, a spray dried decoction of bupleurum, cinnamon, peony, ginger, liquorice, ginseng, pinellia, zizyphus and baikal) was applied to 24 epileptics, who had frequent uncontrollable seizures (3-5 seizures per day in the most severe case and 5 seizures per month in the mildest case) of various types, in spite of sufficient combined therapy with ordinary medical anticonvulsants. Six patients were definitively controlled well with Saiko-keishi-to. Thirteen showed improvement and three showed no effect. No patients experienced worsening of their condition. Two patients dropped out during treatment (Narita et al. 1982).

Chronic active hepatitis

Sho-saiko-to was found in a double-blind multicentre clinical study of 222 patients with chronic active hepatitis to significantly decrease AST and ALT values compared with placebo. The difference of the mean value between the treatment and placebo group was significant after 12 weeks. In patients with chronic active type B hepatitis, a tendency towards a decrease of HBeAg and an increase of Anti-HBe antibodies was also observed. No remarkable side effects were noticed (Hirayama et al. 1989).

Safety

There have been several case reports of Sho-saiko-to induced interstitial pneumonia (Liu et al. 2002). One case of Sho-saiko-to induced pneumonia in a patient with autoimmune hepatitis was reported (Katou & Mori 1999), however, direct toxicity is very low. Toxicity studies of three different traditional Chinese/Japanese formulations containing baikal suggests a very low acute or subchronic toxicity for the herbs in them. The studies found no herb-related abnormalities such as changes in body weight or food consumption; abnormalities on ophthalmological and haematological examination, urinalysis and gross pathological examination; changes in organ weights or optical microscopic examination (Iijima et al. 1995; Kanitani et al. 1995; Kobayashi et al. 1995; Minematsu et al. 1992; Minematsu et al. 1995). The acute lethal activity of wogonin is low, with an LD50 of 3.9 g/kg (Kwok, Huen, Hong, Zheng, Sigel, Baur, Ren, Zhi, Wong, & Xue 2002).

There are reports of baikal flavonoids interacting with P-450 enzymes. Baikal flavonoids inhibit hepatic CYP1A2, suggesting that Baikal extract may be hepatoprotective via prevention of CYP1A2-induced metabolic activation of toxins (Kim, Soo, Kim, Kim, Park, & Byung 2002). Theoretically, inhibition of CYP1A2 may affect certain medical drugs metabolised by this P-450 enzyme. There are, however, no clinical reports of such herb-drug interaction.

Sho-saiko-to during interferon therapy

Sho-saiko-to as well as interferon is used for the treatment of chronic hepatitis. There have been reports of acute pneumonitis due to a possible interferon-herb interaction. Pneumonitis, also called extrinsic allergic alveolitis, is a complex syndrome caused by sensitisation to an allergen. The mechanism of the Sho-saikoto-interferon interaction seems to be due to an allergic-immunological mechanism rather than direct toxicity (Ishizaki et al. 1996).

Baikal and the formulation sho-saiko-to (Minor Bupleurum Combination, Xiao Chai Hu Tang) are contraindicated during interferon therapy. Baikal is contraindicated in Cold conditions in traditional Chinese medicine.

Baikal is used in traditional Chinese medicine for restless fetus (threaten abortion) and toxaemia of pregnancy. A recent animal study found that Baikal combined with Atractylodes macrocephala had an anti-abortive effect through inhibition of maternal-fetal interface immunity. The herbs prevented lipo-polysaccharide-induced abortion by reducing natural killer cells and interleukin-2 activity (Zhong et al. 2002).

Dosage

The traditional dosage of Baikal skullcap is given as 6-15 g daily by decoction (Bensky & Gamble 1986).

Conclusion

Baikal is traditionally used for infectious diseases with fever, irritability, thirst, cough, tight chest and expectoration of thick, yellow mucus. Baikal is also used for diarrhoea, abdominal distension, jaundice and painful urinary disorders (Bensky & Gamble 1986). Extrapolating from in clinical studies on formulations containing Baikal, in vitro and in vivo studies, it may be deducted that Baikal skullcap may be useful as an adjunctive therapy during cancer treatment. Baikal may reduce chemotherapy-induced nausea, increase apoptosis and stimulate recovery of the haemopoietic system. The anti-inflammatory and antiallergic activities may be beneficial in the treatment of allergic conditions including allergic rhinitis, asthma, eczema and urticaria. The antiviral, antibacterial and anti-inflammatory activities may be beneficial in the treatment of respiratory tract infections in combination with other antimicrobial and immune stimulant herbs. The hepatoprotective, antifibrotic and antioxidant activities may be beneficial in the treatment of liver disorders and reduce the risk of the development of malignancies.

Table 1: Mad-dog skullcap

Scutellaria lateriflora (Skullcap)
Native Americans used Skullcap for fever, heart disorders, nerve and breast pain, diarrhoea, to help expel afterbirth and to prevent smallpox (Moerman DE 1998) The Eclectic physicians in America used Skullcap in chorea, convulsions, tremors, intermittent fever, neuralgia and many nervous afflictions. Skullcap was used for restlessness and wakefulness during or after acute and chronic ailments, and in cardiac disorders of a purely nervous type. The Eclectics preferred Scutellaria lateriflora but did use other species (Felter HW & Lloyd JU 21983). The British Herbal Pharmacopoeia considers Skullcap to be anticonvulsive and a sedative, indicated for epilepsy, chorea, hysteria and nervous tension states (BHMA Scientiffic Committee 1983). No WHO or German Commission E monograph has been published for either S. scutellaria or S. baicalensis.

Table 2: Minor Bupleurum Combination approved by the Ministry of Health and Welfare of Japan and widely used in the treatment of chronic viral liver diseases.

Minor Bupleurum Combination (Sho-saiko-to, Xiao Chai Hu Tang)
Bupleurum falcatum (Bupleurum)
Scutellaria baicalensis (Baikal skullcap)
Pinellia ternate (Pinellia)
Panax ginseng (Korean ginseng)
Zizyphus jujube (Zizyphus)
Glycyrrhiza uralensis (Chinese liquorice)
Zingiber officinale (Ginger)

Table 3

Anti-inflammatory activity Mechanism
Cytokine inhibition It has been proposed that the anti-inflammatory activity is partly caused by limiting the biological function of chemokines. This may be associated with a reduced capacity of the chemokines to induce cell migration. such as the recruitment of eosinophils to sites of allergic inflammation. (Nakajima et al. 2001b) (Krakauer, Li, & Young 2001c) (Li et al. 2000c) Various flavonoids, including wogonin and baicalein, have been shown to inhibit chemically induced histamine release from rat mast cells in vitro. (Kubo, Matsuda, & Kimura 1984).
Cox-2 inhibition

Wogonin is a direct COX-2 inhibitor. Wogonin inhibits both inducible nitric oxide synthase and cyclooxygenase-2 induction (Chi, Cheon, & Kim 2001a). Wogonin has been shown to inhibit inducible prostaglandin E2 production in macrophages by inhibiting COX-2 (Wakabayashi and Yasui 2000).

Wogonin may be beneficial for cyclooxygenase-2-related skin disorders. When applied topically to the dorsal skin of mice, it inhibited cyclooxygenase-2 expression and prostaglandin E2 production (Byoung et al. 2001;Park et al. 2001a).

Lipoxygenase inhibition The inhibition of the 5-lipoxygenase pathway of arachidonic acid metabolism may be one of the mechanisms of baicalein's anti-inflammatory activity according to an in vivo study (Butenko, Gladtchenko, & Galushko 1993).
Nitric oxide synthase inhibition Baicalein and wogonin attenuate lipo-polysaccharide-stimulated nitric oxide synthase induction in macrophages, which helps to explain the anti-inflammatory action of these flavonoid compounds (Wakabayashi 1999b).
Antioxidant activity The anti-inflammatory activity of baicalein may be associated with inhibition of leukocyte adhesion by the scavenging of reactive oxygen intermediates (Shen et al. 2003).

Table 4: The in vitro antiviral effects of Baikal skullcap and its constituents

Baikal extract Baikal extract was bactericidal against periodontal pathogens isolated from patients with periodontal disease in vitro (Tsao et al. 1982). Aqueous extract inhibits human immunodeficiency virus type-1 protease (Lam et al. 2000).
Baikal flavonoids Intraperitoneal and intranasal administration of baikal flavonoids significantly inhibits influenza virus in vivo and in vitro (Nagai et al. 1992;Nagai et al. 1995c;Nagai et al. 1995b;Nagai, Yamada, & Otsuka 1989).
Wogonin Wogonin suppresses Hepatitis B virus surface antigen production without evidence of cytotoxicity (Huang et al. 2000). 5,7,4'-trihydroxy-8-methoxyflavone inhibits the fusion of influenza virus with endosome/lysosome membrane (Nagai et al. 1995a).
Bacalin Bacalin inhibits human T-cell leukaemia virus type I (HTLV-I) (Baylor et al. 1992). Baicalin inhibits HIV-1 infection and replication (Li et al. 1993). Baikal flavonoids inhibit Epstein Barr virus early antigen activation (Konoshima et al. 1992). Baicalin reduces the pathogenic effects of superantigenic staphylococcal exotoxins by inhibiting the signalling pathways activated by superantigens (Krakauer, Li, & Young 2001b). Baicalin may selectively induce apoptosis of HIV-infected human T-leukaemia (CEM-HIV) cells which have a high virus-releasing capacity, and stimulate proliferation of CEM-HIV which have a relatively lower capacity of HIV-production (Wu, Akatsu, & Okada 1995).
Baicalein Baicalein inhibits HIV-1 infection at the level of viral entry (a process known to involve interaction between HIV-1 envelope proteins and the cellular CD4 and chemokine receptors) (Li et al. 2000a).

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