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Herbal medicines for treatment of fungal infections: a systematic

review of controlled clinical trials. Martin, K. W.; Ernst, E.* (2004)

Mycoses 47 (3-4), pp. 87-92. Complementary Medicine, Peninsula

Medical School, Universities of Exeter and Plymouth, Exeter, UK;

E-mail: edzard.ernst Traditional medicine has made

use of many different plant extracts for treatment of fungal

infections and some of these have been tested for in vitro antifungal

activity. This systematic review evaluates antifungal herbal

preparations that have been tested in controlled clinical trials. Four

electronic databases were searched for controlled clinical trials of

antifungal herbal medicines. Data were extracted in a standardized

manner by two independent reviewers and are reviewed narratively.

Seven clinical trials met our inclusion criteria. Tea tree oil

preparations were tested in four randomized clinical trials and

some positive outcomes were attributed to the intervention in all

trials. Solanum species (two trials) and oil of bitter orange

preparations (one trial) were compared with conventional

treatments. In all cases encouraging results were reported. There

are few controlled clinical trials of herbal antifungal medicines. The

most thoroughly clinically tested is tea tree oil, which holds some

promise. All herbal remedies require further investigation in rigorous

clinical trials.

 

Ex vivo modulation of chemical-induced mutagenesis by subcellular

liver fractions of rats treated with rooibos (Aspalathus linearis) tea,

honeybush (Cyclopia intermedia) tea, as well as green and black

(Camellia sinensis) teas. (2004) Marnewick, J. L.*; Batenburg, W.;

Swart, P.; Joubert, E.; Swanevelder, S.; Gelderblom, W. C. A.

Mutation Research-Genetic Toxicology and Environmental

Mutagenesis 558 (1-2), pp. 145-154. PROMEC Unit, Medical

Research Council, P. O. Box 19070, Tygerberg 7505, South Africa;

E-mail: jeanine.marnewick Male Fischer rats were

given unprocessed (not oxidized) and processed (oxidized) rooibos

and honeybush teas as well as green and black teas as a sole

source of drinking fluid for 10 weeks, and sub cellular liver fractions

were prepared. Cytosolic fractions of rats consuming the

unprocessed herbal teas, green and black teas significantly

(P0.05) protected against 2-acetylaminofluorene (2-AAF)-induced

mutagenesis in the Salmonella mutagenicity test with strain TA 98,

using Aroclor 1254-induced microsomes. A marginal or no

protection was obtained with the processed herbal teas. The

mutagenic response of aflatoxin B1 (AFB1) against Salmonella

strain TA 100 was significantly (P<0.05) inhibited by cytosolic

fractions from rats treated with processed and unprocessed herbal

teas, while no effect was obtained with the green and black teas.

Microsomal fractions prepared from livers of rats treated with both

the processed and unprocessed rooibos teas and the unprocessed

honeybush tea, significantly (P<0.05) reduced the activation of

AFB1 while no protection was observed against 2-AAF-induced

mutagenesis. In contrast, microsomal fractions from rats treated

with the green, black and unprocessed honeybush teas

significantly (P<0.05) enhanced the mutagenic response of 2-AAF.

None of the tea treatments significantly affected the concentration

of the microsomal liver cytochrome P450.

 

 

Biological basis for the benefit of nutraceutical supplementation in

arthritis. Curtis, C. L.; Harwood, J. L.; Dent, C. M.; Caterson, B.

(2004) Drug Discovery Today 9 (4), pp. 165-172. Cardiff School of

Biosciences, Cardiff University, Cardiff, UK, CF10 3US. Arthritis is

a common disease in which the end-point results in joint

replacement surgery. This article reviews the use of nutraceuticals

as alternative treatments for pathological manifestations of arthritic

disease. The efficacy of fish oils (e.g. cod liver oil) in the diet has

been demonstrated in several clinical trials, animal feeding

experiments and in vitro models that mimic cartilage destruction in

arthritic disease. In addition, there is some evidence for beneficial

effects of other nutraceuticals, such as green tea, herbal extracts,

chondroitin sulphate and glucosamine. However, in most cases,

there is little scientific evidence at the cellular and molecular levels

to explain their mechanisms of action.

 

Biologically Active Compounds from Aphyllophorales (Polypore)

Fungi. Zjawiony, J. K. (2004) Journal of Natural Products 67, (2),

pp. 300-310. Department of Pharmacognosy and National Center

for Natural Product Research, Research Institute of Pharmaceutical

Sciences, School of Pharmacy, The University of Mississippi,

University, Mississippi 38677-1848. This review describes

biologically active natural products isolated from Aphyllophorales,

many of which are known as polypores. Polypores are a large

group of terrestrial fungi of the phylum Basdiomycota

(basidiomycetes), and they along with certain Ascomycota are a

major source of pharmacologically active substances. There are

about 25 000 species of basidiomycetes, of which about 500 are

members of the Aphyllophorales, a polyphyletic group that

contains the polypores. Many of these fungi have circumboreal

distributions in North America, Europe, and Asia and broad

distributions on all inhabited continents and Africa; only a small

number of the most common species with the most obvious fruiting

bodies (basidiocarps) have been evaluated for biological activity. An

estimated 75% of polypore fungi that have been tested show strong

antimicrobial activity, and these may constitute a good source for

developing new antibiotics. Numerous compounds from these fungi

also display antiviral, cytotoxic, and/or antineoplastic activities.

Additional important components of this vast arsenal of compounds

are polysaccharides derived from the fungal cell walls. These

compounds have attracted significant attention in recent years

because of their immunomodulatory activities, resulting in

antitumor effects These high molecular weight compounds, often

called biological response modifiers (BRM), or immunopotentiators,

prevent carcinogenesis, show direct anticancer effects , and

prevent tumor metastasis. Some of the protein-bound

polysaccharides from polypores and other basidiomycetes have

found their way to the market in Japan as anticancer drugs. Finally,

numerous compounds with cardiovascular, phytotoxic ,

immunomodulatory, analgesic, antidiabetic, antioxidant,

insecticidal, and nematocidal activities, isolated from polypores,

are also presented. In fact many of the fungi mentioned in this

paper have long been used in herbal medicine, including polypores

such as Ganoderma lucidum (Reishi or Lingzhi), Laetiporus

sulphureus (—°?‘½E‹Û Liuhuangjun, Liuhuangduokongjun,

Chicken-of-the-Woods), Trametes versicolor (Yunzhi), Grifola

umbellata (Zhuling), Inonotus obliquus (Baihuarong, Chaga), and

Wolfiporia cocos (Fuling, Hoelen).

 

 

Concomitant administration of an isopropanolic extract of black

cohosh and tamoxifen in the in vivo tumor model of implanted

RUCA-I rat endometrial adenocarcinoma cells. Nisslein, T.;

Freudenstein, J. (2004) Toxicology Letters 150 (3), pp. 271-275.

Schaper & Bruemmer Co. R & D-Department of Veterinary

Medicine, Bahnhofstr. 35, 38259, Salzgitter, Germany; E-mail:

thomas.nisslein Black cohosh is a well

known herbal remedy of long traditional use against menopausal

complaints. Recently published studies on postmenopausal

hormone replacement with synthetic substances associated severe

negative side effects with an increase in duration of administration.

The subsequent popularity of alternative treatments , often herbal

drugs, made investigations into the safety of these preparations

more pressing. Until now, black cohosh demonstrated no estrogen-

agonistic activity in mammary cells, neither in animal model nor in

cell culture, i.e. no gene transcription or cell proliferation was

induced. Here we tested for the influence of a standardized

isopropanolic extract of black cohosh on an animal model of

endometrial cancer. Ectopic growth of the primary tumor as well as

the incidence and localization of metastases were examined, partly

in the setting of a combination treatment with tamoxifen. In

contrast to the endometrial estrogen agonist tamoxifen, black

cohosh did not further growth or metastasizing potential of the

primary tumor. Absence of detectable supportive or antagonistic

effects between both treatments most probable come from the

relatively high tamoxifen dose.

 

St. John's Wort (Hypericum perforatum) induces overexpression of

multidrug resistance protein 2 (MRP2) in rats: a 30-day ingestion

study. Shibayama, Y.; Ikeda, R.; Motoya, T.; Yamada, K. (2004)

Food and Chemical Toxicology 42, (6), pp. 995-1002. Department

of Clinical Pharmacy and Pharmacology, Graduate School of

Medical and Dental Sciences, Kagoshima University, 8-35-1

Sakuragaoka, Kagoshima, 890- 8520, Japan; E-mail:

yamada St. John's Wort (Hypericum

perforatum, SJW) has been used as a herbal medicine for the

treatment of depression in oral doses of 900-1050 mg/day in

humans. However, the ingestion of SJW was reported to cause

interactions with drugs. In the present study, we examined the

effects of SJW treatment on the induction of drug transporters and

enzymes in rats. An immunoblot analysis was performed to

quantify the expression of the transporters and enzymes. SJW was

given at a dose of 400 mg/kg/day, since it was reported that 400

mg/kg/day is antidepressant effective dose in rats. When SJW was

administered for 10 days, the amounts of multidrug resistance

protein 2 (MRP2), glutathione S- transferase-P (GST-P) and

cytochrome P450 1A2 (CYP1A2) in the liver were increased to

304%, 252% and 357% of controls, respectively, although the

amounts of P-glycoprotein

and multidrug resistance protein 1 were not changed. Under the

same conditions, an increase of MRP2 in the kidney was not

observed. The increase in the levels of each protein was maximal

at 10 days after SJW treatment and lasted for at least 30

consecutive days. These results suggest that SJW induces

hepatic MRP2, GST-P and CYP1A2 overexpressions, and

thus, it could affect drug metabolism, conjugation and

disposition.

 

Induction and recovery of hepatic drug metabolizing enzymes in

rats treated with Ginkgo biloba extract. Sugiyama, T.; Kubota,

Y.; Shinozuka, K.; Yamada, S.; Yamada, K.; Umegaki, K.

(2004) Food and Chemical Toxicology 42, (6), pp. 953-957.

National Institute of Health and Nutrition, 1-23-1 Toyama,

Shinjuku-ku, Tokyo 162-8636, Japan; E-mail:

umegaki Herb-drug interactions, especially

cytochrome P450 (CYP)-mediated interactions, cause an

enhancement or attenuation in efficacy of co-administered drugs.

In a previous study, we reported that repeated oral ingestion of

Ginkgo biloba extract (GBE) markedly induced hepatic drug

metabolizing enzymes in rats (Jpn. J. Pharmacol. 90, 345-351,

2002). In this study, we focused on the recovery of GBE-

induced hepatic drug metabolizing enzymes after the

discontinuation of GBE in rats. Feeding of a 0.5% GBE diet to

rats for 1 week markedly increased liver weight, content of total

CYP, activities of 6 CYP subtypes and glutathione S-transferase

(GST). The content and activities of CYP enzymes were

recovered to almost basal levels within 1 week after the

discontinuation of GBE, while the activity of GST gradually

decreased and recovered to the control level after 3 weeks.

These results indicated that GBE- induced hepatic drug

metabolizing enzymes in rats, especially CYPs, were rapidly

recovered by discontinuation of GBE in rats even after excess

treatment , and suggested that interactions of GBE with drugs

could be avoided by discontinuation of GBE.

 

Effect of kami-untan-to on the impairment of learning and

memory induced by thiamine-deficient feeding in mice.

Nakagawasai, O.; Yamadera, F.; Iwasaki, K.; Arai, H.;

Taniguchi, R.; Tan-No, K.; Sasaki, H.; Tadano, T. (2004)

Neuroscience

125, (1), pp. 233-241. Department of Pharmacology, Tohoku

Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku,

Sendai 981-8558, Japan; E-mail: osamun

We have recently reported that thiamine deficient (TD) mice

show an impairment of learning and memory on the 20th day

after start of TD feeding. Interestingly, it has been reported that

the kampo medicine, 'kami-untan-to' (KUT) may be useful as a

potential therapeutic agent in diseases associated with

cholinergic deficit such as Alzheimer's disease. In the present

study, we investigated the effects of KUT on the impairment of

memory-related behavior concomitant with psychoneuronal

symptoms after TD feeding in mice. Oral administration of KUT

had no effect on the food intake, body weight or locomotor

activity in TD mice, but the mortality rate in the KUT-treated TD

group was significantly lower compared with that in the non-

treated TD group. Daily administration of KUT from the 1st day

of TD feeding protected against the impairment of memory-

related behavior induced by TD. The intensity of the choline

acetyltransferase fluorescence decreased in the field of CA1 and

dentate gyrus in the hippocampus in TD mice compared with

pair-fed mice as the control group, and KUT treatment inhibited

this decrease. These results suggest that the effect of KUT on

the impairment of memory-related behavior induced by TD

feeding may be closely related to the activation of cholinergic

neurons in the hippocampus.

 

 

Butterbur, a herbal remedy, confers complementary anti-

inflammatory activity in asthmatic patients receiving inhaled

corticosteroids. Lee, D. K. C.; Haggart, K.; Robb, F. M.;

Lipworth, B. J. (2004) Clinical and Experimental Allergy 34,

(1), pp. 110-114. Asthma & Allergy Research Group,

Ninewells Hospital & Medical School, University of Dundee,

Dundee DD1 9SY, UK; E-mail: b.j.lipworth

Background The effects of butterbur (BB), a herbal remedy, as

add-on therapy to inhaled corticosteroids in patients with atopic

asthma is currently unknown. Objective We evaluated the

effects of BB, given as add-on therapy to asthmatic patients

maintained on inhaled corticosteroids, assessing adenosine

monophosphate (AMP) bronchoprovocation (primary outcome

variable) along with other surrogate inflammatory markers such

as exhaled nitric oxide, serum eosinophil cationic protein and

peripheral blood eosinophil count. Methods Sixteen atopic

asthmatic patients with mean (standard error of mean) forced

expiratory volume in 1 s (FEV sub(1)) of 78 (4)% predicted,

maintained on their constant dose of inhaled corticosteroids

throughout the study, received twice daily for 1 week either BB

25 mg or placebo (PL), in a double-blind, cross-over fashion,

with a 1-week washout period prior to each randomized

treatment Measurements were made at baselines prior to each

randomized treatment and following the randomized treatment

period. Results Baseline values for the primary and secondary

outcomes were not significantly different prior to BB and PL.

AMP provocative concentration causing a 20% reduction from

baseline FEV sub(1) (PC sub(20)) as doubling dilution change

from baseline, significantly improved (P<0.05) with BB, 0.6

(0.2), compared with PL, -0.1 (0.3); a 0.7 doubling dilution

difference. Exhaled nitric oxide as change from baseline was

significantly reduced (P<0.05) with BB, -1.2 (0.8) p.p.b.,

compared with PL, 0.5 (0.4) p.p.b. Both serum eosinophil

cationic protein and peripheral blood eosinophil count as change

from baseline were also significantly suppressed (P<0.05) with

BB, -3.9 (3.3) mu g/L, -31 (28)x10 super(6)/L compared with

PL, 3.3 (2.5) mu g/L, 38 (16)x10 super(6)/L, respectively.

Conclusion Chronic dosing with BB conferred complementary

anti-inflammatory activity in atopic asthmatic patients maintained

on inhaled corticosteroids. Further studies are now required to

assess the potential role for BB as either monotherapy in milder

patients or add-on therapy in more severe asthmatics.

 

 

Effects of Ginkgo biloba on corticosterone stress responses after

inescapable shock exposure in the rat. Markus, C. R.;

Lammers, J. H. C. M. (2003) Pharmacology Biochemistry and

Behavior 76, (3-4), pp. 487-492. Department of Experimental

Psychology, University of Maastricht, Maastricht, The

Netherlands; E-mail: R. Markus

Extracts from the leaves of the Ginkgo biloba tree (GBE) are

found to be clinically effective in neuroprotection, cerebral and

cardiovascular function and cognitive processing. Recent animal

findings suggest that GBE also may improve stress adaptation and prevent

learned helplessness, as evidenced by its reduction of behavioral acquisition

deficits of active avoidance after inescapable shock exposure. In the present

report, the effects of two doses of GBE were studied on corticosterone stress

responses and acquisition of active avoidance after inescapable shock exposure.

Forty-eight rats were divided into three groups: either receiving a daily dose

of 50 mg/kg or 150 mg/kg of GBE (containing 24% flavonoid and 6% terpenoid) or

vehicle for 2 weeks. After 2 weeks of administration, animals were trained for

active-avoidance acquisition following inescapable shock exposure (stress

induction) or nonshock exposure (nonstress). Administration of 150 mg/kg but

not of 50 mg/kg of GBE significantly prevented a corticosterone stress response

after inescapable shock exposure (P<.0001) without any beneficial behavioral

effect on active avoidance. Repeated administration of GBE particularly

improves biological adaptation to noxious stimuli without beneficial behavioral

consequences. Present findings do not support previous claims about the

benefits of G. biloba on improving behavioral stress adaptation and acquisition

of active avoidance and on reducing behavioral deficits indicative of 'learned

helplessness.'

 

 

45. Repair of amyloid beta (25-35)-induced memory impairment and synaptic loss

by a Kampo formula, Zokumei-to. Tohda, C.; Tamura, T.; Komatsu, K.* (2003)

Brain Research 990, (1-2), pp. 141-147. Research Center for Ethnomedicines,

Institute of Natural Medicine, Toyama Medical and Pharmaceutical University,

2630 Sugitani, Toyama 930-0194, Japan; E-mail: katsukok

Although Zokumei-to (ZMT), a Kampo formula, has been used for postapopletic

sequelae such as paralysis and logopathy, only few studies of this drug have

been carried out. We hypothesized that ZMT may affect neuronal plasticity and

investigated whether or not this drug is capable of improving learning

impairment and synaptic loss observed in patients with Alzheimer's disease

(AD). Amyloid beta (25-35) ÝA beta (25-35)¨ (4.7 nmol) was

intracerebroventricularly injected into ddY mice (male, 6 weeks old). Fourteen

days after the injection, mice were given ZMT extract (500 mg/kg/day) per os

for 15 days. In a memory acquisition test, the A beta (25-35)-injected mice

required more time to master this task than did mice in the saline- or reverse

peptide A beta (35-25)-treated groups. ZMT-treated mice shortened escape

latencies during trial days 3-5, but not significantly. Three days after the

last drug treatment , a retention test was performed. Following ZMT, the number

of crossings over a platform was significantly decreased in A beta

(25-35)-injected mice compared with those in the control groups. However,

ZMT-treated mice showed complete recovery of this number.

Although A beta (25-35) injection decreased synaptophysin

expression in the cerebral cortex and the hippocampus, ZMT

treatment significantly increased the level of expression of

synaptophysin up to the control level. Donepezil hydrochloride

(DNP, 0.5 mg/kg/day, po) clinically used for AD had no effect

on memory retention and synaptophysin levels. A beta (25-35)-

induced neuronal loss was not observed in any region of the

brain. The present results suggest that memory impairment and

synaptic loss in AD patients may be improved by treatment with

ZMT, even after such impairment has already progressed.

 

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