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Chinese Scullcap (Baicalein)
General Features
Scutellaria baicalensis or Chinese scullcap is a member of the mint family and grows in China and Russia.1,2 The
plant root is a rich source of over 35 flavonoids, giving it a yellow color, and hence its traditional name of golden root or
Huang qin, the Chinese term for yellow gold (known as Ogon in Japanese).3,4 One of the major flavonoids contained
in the root of the plant is baicalin, a flavone glycoside (12-17% of all scullcap root flavonoids), which yields the
aglycone flavone baicalein, once hydrolyzed by gut bacteria.3 Baicalein is readily absorbed into the bloodstream
where it has been shown to exert a broad spectrum of important biological activities.5 Baicalein has been incorporated
into a number of herbal combinations in Traditional Chinese Medicine that treat a wide array of health conditions,
including the widely used Asian herbal remedy, “Sho-saiko-to”.6,7 Currently, baicalein is being studied for its anti-
cancer, anti-inflammatory, anti-viral, anti-bacterial and anti-allergy effects.8,9,10,11 As explained below, its ability to
halt the replication of various human cancer cell lines, via the inhibition of the 12 lipoxygenase enzyme system, is
attracting a great deal of attention from the scientific community as a premiere agent in cancer research.
Active Constituents
Primarily Flavonoids – The flavonoid Baicalein within Chinese scullcap is considered to be its most important active
constituent.3,5
Clinical Application and Mechanism of Action
1. Anti-Cancer Effects
Many experimental studies indicate that baicalein (5,6,7-trihydroxyflavone) prevents and inhibits cancer growth
via a number of direct and indirect physiological actions:
Inhibits 12-lipoxygenase enzyme and induces apoptosis of cancer cells - Baicalein has been shown to inhibit the
12-lipoxygenase enzyme, which converts arachidonic acid into a specific leukotriene (eicosanoid) that is required
for cancer cells to proliferate. Studies demonstrate that by inhibiting the 12-lipoxygenase enzyme baicalein has
been shown to inhibit cancer cell proliferation and induce apoptosis (programmed cell death) of human gastric
cancer cell lines.12 Further, activation of arachidonic acid by the 12-lipoxygenase enzyme has been shown to be
critical for metastasis of human prostate cancer cells. Experimental evidence demonstrates that after
intraprostatic injection of mice with human prostate cancer cells, the prostate cells pre-treated with baicalein failed
to metastasize to the lung and failed to express activity of the 12-lipoxygenase enzyme. This evidence suggests
that, in the presence of baicalein, various cancer cells can be prevented from multiplying and metastasizing to
other tissues and that a primary mechanism through which this occurs is via the inhibition of the 12-lipoxygenase
enzyme.13 The inhibition of cancer cell proliferation also lends itself to increased apoptosis and a better
opportunity for immune cells to destroy tumor cells.12,13 Other studies testing baicalein as an anti-tumor agent
have shown that it selectively induces apoptosis in human hepatoma cell lines (liver cancer cells) with minimal
influence on non-cancer cells.14,15,28,29 Its ability to induce apoptosis is under intensive investigation as many
studies provide evidence that baicalein exhibits an extraordinary ability to selectively encourage apoptosis of
many different human cancer cells. This is likely one of the primary ways in which it has been a useful addition to
herbal combinations that have been used in cancer treatment.16,17,18
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Anti-proliferative - Baicalein has also demonstrated anti-proliferative effects on human bladder cancer cell lines
and a murine bladder cancer cell line, in vitro. In an in vivo experiment, mice were injected with bladder cancer
cells with concurrent oral administration of a high baicalein-yielding supplement in one group, or with no baicalein
supplementation in the control group. All the control mice showed a progressive increase in tumor volume over
the ensuing days of the study, whereas the mice treated with baicalein (scutellaria) showed a significant inhibition
of tumor growth.19 In other experiments, baicalein has demonstrated anti-proliferative effects on human
pancreatic cancer cell lines and T lymphoid leukemia cells. The mechanism of action was shown to be through
the reduction of protein tyrosine kinase activity and protein kinase C activity. Both of these enzyme activities are
required for normal cellular proliferation to occur. Thus, in addition to inhibiting the 12 lipoxygenase enzyme
pathway and inducing apoptosis of cancer cells, baicalein is also known to reduce cancer cell proliferation by
directly or indirectly inhibiting specific enzymes (protein tyrosine kinase and protein kinase C) required for cellular
division and proliferation.28
Antioxidant - Baicalein is also a strong antioxidant, and has been shown to protect DNA from undergoing
cancerous mutations in challenge studies using potent carcinogens such as benzo{a}pyrene, and toxins such as
aflatoxin (AF) B.1,20,21
Stimulates DNA repair enzymes - In vitro evidence indicates baicalein stimulates recombination and repair of
damaged DNA, supporting its traditional inclusion in cancer formulas, and suggesting possible use after sunburn
and radiation damage.22
Inhibits the 5alpha-reductase enzyme - Baicalein has been shown to inhibit the 5alpha-reductase enzyme,
which converts testosterone to dihydrotestosterone (DHT). DHT is strongly associated with the development of
prostate enlargement (benign prostatic hyperplasia) and prostate cancer. As such, baicalein is reported to be
potentially useful for the prevention and/or treatment of androgen-dependent (testosterone-driven) disorders,
including prostate enlargement and prostate cancer.23
Human Studies Involving Prostate Cancer Patients
Studies on humans have primarily involved patients with advanced prostate cancer, who were shown to be
unresponsive to traditional medical drugs and other interventions. In a study performed by researchers from the
University of California at San Francisco and Memorial Sloan-Kettering Cancer Center in New York, the oral
administration of a herbal combination containing baicalein to patients with metastatic prostate cancer (previously
unresponsive to standard treatments) demonstrated reversal and/or stabilization of their condition with
significantly improved survival, quality of life scores and other positive outcomes in almost all patients receiving
the supplement. After a median treatment period of 57 weeks, 100% of patients with androgen-dependent cancer
had a decline of 80% or more in their prostate-specific antigen (PSA) levels, and these levels were undetectable
in 81% of the patients. In 31 of 32 patients, the testosterone level declined to that seen in castrated men. Of nine
men with elevated prostatic acid phosphatase levels (a marker for cancer progression), all had declines of more
than 50%. Of two patients with positive bone scans, one had a complete disappearance of cancerous bone
lesions, and the other showed improvement. One patient had a complete disappearance of a bladder mass,
demonstrated by CT scan.
Of 35 patients with androgen-independent prostate cancer 54% showed a drop in their PSA levels by 50% or
more, and of 25 patients with metastasis to bone, 2 showed marked improvement, 7 remained stable, 11
progressed, and 5 had no further bone scan follow up due to an increasing trend in their PSA levels.24 Other
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studies involving men with known prostate cancer, taking this herbal combination, have demonstrated similar
results. In one study PSA levels dropped from 100ng/mL to 24 and from 386ng/mL to 114 within 16 months of
supplementation in a two case report of hormone-refractory prostate cancer.25 Studies following larger groups of
men with prostate cancer for up to four years have also shown this herbal formula to significantly reduce PSA
levels and improve survival and quality of life scores.26,27
Researchers attribute much of the anti-tumor effects of this herbal combination to the presence of baicalein.
According to researchers, baicalein has demonstrated impressive anti-cancer effects against androgen-
dependent and androgen-independent human prostate cancer cells lines, and many of its anti-cancer
mechanisms have been uncovered in recent years, in vitro and in vivo experiments.16,17,18,24,25,26,27,28 It
appears to be of particular benefit in prostate cancer treatment and in combination with other phytonutrients
(plant-based nutrients) and micronutrients (vitamins and minerals) may help to prevent the development of
clinically important prostate cancer, reducing prostate cancer incidence.26 Animal studies indicate that baicalein
may be effective in the treatment of other cancers as well, with experimental evidence supporting its potential use
in stomach, pancreatic, bladder, liver12, 14, 15,19, 28 and breast cancer. 29, 30, 31
Hepatoma and Leukemia Patients
Based on its traditional use, and the documentation of its anti-tumor effects against various human cancer cell
lines, Baicalein has been used recently by doctors in Asia as a complementary supplemental agent in the
treatment of hepatomas and leukemia in human subjects.29
2. Anti-viral/Anti-HIV
Baicalein has been shown in experimental studies to inhibit the activity of HIV-1 integrase enzyme, which is an
essential enzyme in the life cycle of the HIV-virus. This enzyme is responsible for catalyzing the insertion of the
viral genome into the host cell chromosome. It is an attractive target for the design of a HIV antiviral drug
because the integrase enzyme has no human counterpart.32 In a review of all herbal medicines frequently used
as an alternative medical therapy by HIV positive patients and AIDS patients, JA Wu et al, emphasized that
experimental data suggest that the flavonoid, Baicalein inhibits infectivity and replication of HIV, and shows great
promise as an important component to be included in herbal remedies used for HIV treatment.33
3. Asthma and Allergies
Baicalein inhibits type I and II hypersensitivity reactions, confirming its traditional use in asthma34,35 and allergic
dermatitis.3
4. Anti-inflammatory
Baicalein has shown impressive anti-inflammatory effects that appear to be mediated via repression of leukotriene
B4 (inhibition of the 5-lipoxygenase enzyme), inhibition of interleukin-1B, and prostaglandin E2. Studies reveal it
may be of benefit in the treatment of gingivitis (gum inflammation).29, 36, 37
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5. Alzheimer’s and Dementia
In a rat model Baicalein has been shown to prevent the build up of amyloid beta peptide (Abeta), which is known
to generate free radical damage to brain cells and participate to a significant degree in the development and
progression of Alzheimer’s disease. Additionally, chronic inflammation occurs in Alzheimer’s pathogenesis and
Baicalein was shown to inhibit the 12- lipoxygenase enzyme responsible for brain inflammation, to a large degree.
When tested against other known 12-lipoxygenase inhibitor agents, only Baicalein was able to attenuate both
nerve cell death (apoptosis) and over-expression of Abeta production. As such, Baicalein may help to prevent or
forestall the development of Alzheimer’s disease by reducing the build up of the toxic brain protein, Abeta and
inflammatory mediators, and preventing brain cell death, which has been shown to be triggered by the
accumulation of Abeta in affected brain cells. 38 In studies using human neuroblastoma cells, the antioxidant
properties of Baicalein were shown to inhibit free radical damage to these nerve cells induced by treatment with
hydrogen peroxide (a powerful free radical generating agent). The researchers argue that oxidative (free radical)
stress plays an important role in the development of neurodegenerative diseases (e.g. Alzheimer’s disease,
Multiple Sclerosis, Parkinson’s disease) and that antioxidants such as Baicalein and Quercetin (also a flavonoid)
may be useful bioactive agents in the prevention and/or management of these conditions, pending further studies.
Both of these flavonoids have shown impressive protective effects under experimental conditions.39
6. Inhibition of Xanthine Oxidase (Gout Treatment)
Baicalein is one of few bioactive agents that has been shown to inhibit the enzyme xanthine oxidase, which is
responsible for the conversion of hypoxanthine to xanthine, and xanthine to uric acid, in the pathway for
degradation of purines in the body. High levels of uric acid is a hallmark feature of gout and thus, Baicalein
supplementation may be an effective complementary intervention in the long-term management of this
condition.40 The drug Allopurinol is a Xanthine Oxidase inhibitor and is a primary medication prescribed for the
treatment of gout.
Dosage
Therapeutic Purposes: The usual doses for therapeutic purposes ranges from 150 to 200 mg per day of Baicalein.6
General wellness: Consider 50-100mg per day.
Toxicity and Adverse Side Effects
Baicalein supplementation at therapeutic doses appears to be safe with no reports of significant side effects or toxicity.
Baicalein or Chinese scullcap are not known to be contraindicated for any health conditions.41,42
Drug-Nutrient Interaction
There are no known drug-nutrient interactions for Baicalein or Chinese skullcap.42
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Pregnancy and Lactation
During pregnancy and lactation, the only supplements that are considered safe include standard prenatal vitamin and
mineral supplements. All other supplements or dose alterations may pose a threat to the developing fetus and there is
generally insufficient evidence at this time to determine an absolute level of safety for most dietary supplements other
than a prenatal supplement. Any supplementation practices beyond a prenatal supplement should involve the
cooperation of the attending physician (eg., magnesium and the treatment of preeclampsia.)
References: Pregnancy and Lactation
1.
Encyclopedia of Nutritional Supplements. Murray M. Prima Publishing 1998.
2.
Reavley NM. The New Encyclopedia of Vitamins, Minerals, Supplements, and Herbs. Evans and Company Inc. 1998.
3.
The Healing Power of Herbs (2nd edition). Murray M. Prima Publishing 1995.
4.
Boon H and Smith M. Health Care Professional Training Program in Complementary Medicine. Institute of Applied Complementary
Medicine Inc. 1997.
Bone K. Clinical Applications of Ayurvedic and Chinese herbs: Monographs for the Western herbal practitioner. Warwick, Australia
1996;p.75-9
2.
Newall CA, Anderson LA, Phillipson JD. Herbal Medicines: A Guide For Health-Care Professionals. London; Pharmaceutical Press
1996;p.239-40
3.
Tang W, Eisenbrand G. Chinese Drugs of Plant origin: Chemistry, Pharmacology, and Use in Traditional and Modern Medicine. New
York; Springer-Verlag 1992.
4.
Hsu HY. Oriental Materia Medica: a concise guide. Long Beach CA; Oriental Healing Arts Institute 1986.
5.
Nishioka Y, Kyotani S, Miyamura M, Kusunose M. Influence of time of administration of Shosaiko-To extract granule on blood
concentration of its active constituents. Chem Pharm Bull 1992; 40:p.1335-7.
6.
Chen S, Ruan Q, Bedner E, Deptala A, Wang X, Hsieh TC et al. Effects of the flavonoid baicalin and its metabolite baicalein on
androgen receptor expression, cell cycle progression and apoptosis of prostate cancer cell lines. Cell Prolif 2001 Oct; vol
34(5):p.293-304.
7.
Rossi M, Meyer R, Constantinou P, Caruso F, Castelbuono D, O’Brien M, et al. Molecular structure and activity toward DNA of
baicalein, a flavone constituent of the Asian herbal medicine ‘Sho-saiko-to’. J Nat Prod 2001 Jan; vol 64(1):p.26-31.
8.
Kubo M, Kimura Y, Odani T, et al. Studies on Scutellariae radix. Part II: The antibacterial substance. Planta Medica 1981; 43:p.194-
201.
9.
Mahmood N, Pizza C, Aquino R, et al. Inhibition of HIV infection by flavonoids. Antivir Res 1993; 22:p.189-99.
10.
Ono K, Nakane H, Fukushima M, et al. Differential inhibitory effects of various flavonoids on the activities of reverse transcriptase
and cellular DNA and RNA polymerases. Eur J Biochem 1990; 190:p.469-79.
11.
Razina TG, Udintsev SN, Tiutrin II, et al. The role of thrombocyte aggregation function in the mechanism of the antimetastatic action
of an extract of Baikal scullcap. Vopr Onkologii 1989; 35:p.331-5.
12.
Wong, BC, Wang WP, Cho CH, Fan XM Lin MC, Kung HF, et al. 12-Lipoxygenase inhibition induced apoptosis in human gastric
cancer cells. Carcinogenesis 2001 Sep; vol 22(9):p.1349-54.
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Coleus Forskohlii (Forskolin)
General Features
Coleus Forskohlii is a small perennial member of the mint family, which has been extensively used for many
applications in Aryuredic medicine. Its unique active ingredient, the diterpene, forskolin, has been shown to activate
the enzyme adenylate cyclase in various tissues, which in turn, increases cellular levels of cyclic AMP (Cyclic
Adenosine Monophosphate). Cyclic AMP is nicknamed “the second messenger” as its synthesis triggers the action of
various hormones, enzymes and other biological activities that have profound effects on local cells, as well as systemic
effects, in some instances, on the entire body. It is primarily via the increased synthesis of cyclic AMP that Coleus
Forskohlii may exert its medicinal influences on a significant number of common health conditions.1,11
Principle Active Constituents
The primary active constituent in coleus forkohlii is a diterpene compound (saponin) that is unique to this herb, known
as Forskolin.1,11 Other diterpene compounds have also been isolated from coleus forskohlii, which may provide
synergistic physiological effects. 12
Clinical Application and Mechanism of Action
Cardiovascular Conditions
6. Congestive Heart Failure – as a therapeutic intervention in congestive heart failure forskolin has been shown to
activate the enzyme adenylate cyclase, which increases production of cyclic adenosine monophosphate (cAMP)
in heart muscle cells (cardiac muscle). Epinephrine has a similar effect on increasing cAMP. Increased levels of
cAMP in turn, increases the ability of the heart muscle to produce ATP, which is the energy required for heart
muscle contraction and optimal force of muscle contraction with each beat (increased stroke volume). Forskolin
also relaxes the artery wall, decreasing blood pressure and thus, pre-load stress on the heart muscle. All of these
effects appear to be mediated via increased cAMP synthesis, which acts as a secondary messenger on various
cellular processes that manifest the stated outcomes.
7. Hypertension - as mentioned, forskolin relaxes blood vessel smooth muscles via increased cAMP synthesis,
helping to reduce high blood pressure, by reducing resistance to blood flow.
8. Platelet Function - forskolin antagonizes the action of platelet-activating factor (PAF) by interfering with the
binding of PAF to receptor sites on cells. In turn, this reduces platelet stickiness as well as smooth muscle
contraction of blood vessels and bronchiole air passageways. Once again, these effects are mediated through
increased synthesis of cAMP.1,2,3,4,5
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Asthma and Skin Conditions
Asthma and Eczema – both of these conditions are associated with a relative decrease in cAMP in bronchial smooth
muscle and skin cells, respectively. In turn, this results in degranulation of mast cells and increased contraction of
smooth muscle in the bronchiole passageways. Increased PAF also contributes to this problem. Pharmaceutical
drugs for allergic conditions, asthma, and eczema are often aimed at increasing cAMP levels (corticosteroids,
methylxanthines).6 Corticosteroid drugs stimulate adenylate cyclase enzyme, increasing the synthesis of cAMP
whereas, methylxanthine-containing drugs inhibit phosphodiesterase enzyme, which breaks down cAMP. Forskolin
may be utilized alone or in conjunction with these drugs in the complementary management of these conditions.1,7,11
Psoriasis - low levels of cAMP appears to disrupt the balance of cAMP with cGMP (Cyclic Guanine Monophosphate).
In turn, this has been shown to cause rapid cellular proliferation (a rate that is 1,000 times faster than normal cells),
which is a main feature of the psoriatic condition. In experimental studies Coleus Forskohlii administration has been
shown to slow the proliferation rate of skin cells by improving the relative balance of cAMP to cGMP.7
Author’s Note: In general, the above noted physiological effects associated with Coleus Forskohlii explain its
historical use for the treatment of cardiovascular conditions, asthma, skin conditions, and as an antispasmodic in the
management of irritable bowel syndrome and uterine cramps. Unfortunately, no well-designed, large, clinical studies
have been performed to establish its true therapeutic efficacy for any of these conditions and as such, recommending
this herb for these conditions is primarily based upon historical use and animal experimental evidence supporting its
role as an adenylate cyclase enzyme activator.11,13
Lipolysis and Body Fat Reduction
Recent evidence suggests that supplementation with Coleus Forskohliimay help to reduce body fat in overweight
adults. As with other substances that increase cAMP (caffeine, adrenaline, ephedrine, epinephrine), forskolin
enhances the breakdown and release of fat from fat cells. The synthesis of cAMP in fat cells initiates a chain