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J Clin Pharm Ther 2003 Feb;28(1):53-9 Salvia officinalis extract in the

treatment

of patients with mild to moderate Alzheimer's disease: a double blind,

randomized and placebo-controlled trial. Akhondzadeh S, Noroozian M,

Mohammadi M, Ohadinia S, Jamshidi AH, Khani M. Roozbeh Psychiatric

Hospital, Tehran University of Medical Sciences, Tehran, Iran and Institute of

Medicinal Plants, Iranian Academic Centre for Education, Culture and

Research, Tehran, Iran. BACKGROUND: Alzheimer's disease is characterized

by a slow, progressive decline in cognitive function and behaviour.

Acetylcholine

esterase inhibitors are the only agents approved by the Food and Drug

Administration for the treatment of Alzheimer's disease. All other agents

prescribed for the treatment of Alzheimer's disease are used on an off-label

basis. Current research into new drugs is focused on agents that will prevent,

slow down and/or halt the progress of the disease process. Savia officinalis has

been used in herbal medicine for many centuries. It has been suggested, on

the basis of traditional medicine, its in vitro cholinergic binding properties

and

modulation of mood and cognitive performance in humans, that Salvia officinalis

might potentially provide a novel natural treatment for Alzheimer's disease. The

objective of this study was to assess the efficacy and safety of Salvia

officinalis

extract using a fixed dose (60 drops/day), in patients with mild to moderate

Alzheimer's disease, over a 4-month period. METHODS: This was a 4-month,

parallel group, placebo-controlled trial undertaken in three centres in Tehran,

Iran. Patients with mild to moderate Alzheimer's disease aged between 65 and

80 years (n = 42, 18 women) with a score of >/=12 on the cognitive subscale of

Alzheimer's Disease Assessment Scale (ADAS-cog) and </=2 on the Clinical

Dementia Rating (CDR) were randomized to placebo or fixed dose of S.

officinalis extract. Over the 16 weeks, the main efficacy measures were the

change in the ADAS-cog and CDR-Sum of Boxes scores compared with

baseline. In addition, side-effects were systematically recorded throughout the

study using a checklist. RESULTS: At 4 months, S. officinalis extract produced

a significant better outcome on cognitive functions than placebo (ADAS-cog: F

= 4.77, d.f. = 1, P = 0.03) (CDR-SB: F = 10.84, d.f. = 1, P < 0.003). There were

no significant differences in the two groups in terms of observed side-effects

except agitation that appears to be more frequent in the placebo group (P =

0.09). CONCLUSIONS: The results of this study indicate the efficacy of S.

officinalis extract in the management of mild to moderate Alzheimer's disease.

Moreover, S. officinalis may well reduce agitation of patients but this needs to

be confirmed. PMID: 12605619 [PubMed - in process]

 

Oncogene 2003 Feb 27;22(8):1261-72 Gene profiling and promoter reporter

assays: Novel tools for comparing the biological effects of botanical extracts

on

human prostate cancer cells and understanding their mechanisms of action.

Bigler D, Gulding KM, Dann R, Sheabar FZ, Conaway MR, Theodorescu D.

The use of botanical mixtures is commonplace in patients with prostate cancer,

yet the majority of these products have not been rigorously tested in clinical

trials. Here we use PC-SPES, a combination of eight herbs that has been

shown to be effective in clinical trials in patients with prostate cancer, as a

model system to demonstrate 'proof of principle' as to how gene expression

profiling coupled with promoter assays can evaluate the effect of herbal

cocktails on human prostate cancer. In addition, we demonstrate how such

approaches may be used for standardization of herbal extract activity by

comparing the gene profile of PC-SPES with that of PC-CARE, a product with a

similar herbal composition. Since prior studies have shown that PC-SPES

contains estrogenic organic compounds, and such compounds are known to

affect prostate cancer, an important issue is whether these are the primary

drivers of the gene profile. Our data suggest that gene expression profiles of

LNCaP human prostate cancer cells in response to PC-SPES are different from

those found when diethylstilbestrol (DES), a synthetic estrogen, is used,

suggesting that the estrogenic moieties within PC-SPES do not drive this

expression signature. In contrast, the expression profile of PC-CARE was

almost identical to that of DES, highlighting that mixtures containing similar

herbal compositions do not necessarily result in similar biological activities.

Interestingly, these three agents cause similar in vitro morphological changes

and growth effects on LNCaP. To validate the expression profiling data, we

evaluated the protein expression and promoter activity of prostate-specific

antigen (PSA), a gene induced by PC-SPES but repressed by DES. In order to

gain a mechanistic understanding of how PC-SPES and DES affect PSA

expression differently, LNCaP cells were transiently transfected with wild-type

and mutagenized PSA promoter, ARE concatemers and appropriate controls.

We provide evidence that androgen response elements (ARE) II and III within

the promoter region are responsible for the suppressive effects of DES and

stimulatory effects of PC-SPES. In addition, we show that the effects on PSA

transcription are ARE specific in the case of DES while PC-SPES affects this

promoter nonspecifically. In conclusion, expression profiling coupled with

mechanistic target validation yield valuable clues as to the mode of action of

complex botanical mixtures and provides a new way to compare objectively

mixtures with similar components either for effect or quality assurance prior to

their use in clinical trials.Oncogene (2003) 22, 1261-1272.

doi:10.1038/sj.onc.1206242 PMID: 12606954 [PubMed - in process]

 

J Pharmacol Exp Ther 2003 Jan 21; [epub ahead of print] Flavonoid Baicalein

Attenuates Activation-Induced Cell Death of Brain Microglia. Suk K, Lee H,

Kang SS, Cho GJ, Choi WS. Baicalein (5,6,7-trihydroxyflavone), a flavonoid

originated from the root of Chinese medicinal herb Scutellaria baicalensis, has

been shown to exert anti-inflammatory and anti-oxidant effects, and it is a

well-

known inhibitor of 12-lipoxygenase. We have previously reported that neuroglia

undergo nitric oxide (NO)-dependent and NO-independent apoptosis upon

inflammatory activation. In the current work, we asked how anti-inflammatory

baicalein influences auto-regulatory apoptosis of activated microglia and their

NO production. Baicalein attenuated NO production and apoptosis of

lipopolysaccharide (LPS)-activated, but not interferon (IFN)gamma-activated,

BV-2 mouse microglial cells as well as rat primary microglia cultures. The

inhibition of NO production by baicalein was due to the suppression of inducible

NO synthase (iNOS) induction. Moreover, baicalein inhibited LPS-induced NF-

kappaB activity in BV-2 cells without affecting caspase-11 activation, IRF-1

induction, or STAT1 phosphorylation. Transfection of BV-2 cells with a p65

subunit of NF-kappaB abolished the apoptosis-attenuating effects of baicalein,

indicating that the inhibition of NF-kappaB is a major mechanism of action.

Baicalein, however, did not significantly affect NO donor-mediated cytotoxicity,

and the apoptosis-attenuating effects of baicalein were independent of 12-

lipoxygenase inhibition. Based on our previous findings that activation-induced

cell death (AICD) of microglia occurs through two separate pathways (NO-

dependent pathway and caspase-11-dependent pathway), our current results

suggest that baicalein selectively inhibits the NO-dependent apoptotic pathway

of activated microglia by suppressing cytotoxic NO production. Also, the AICD-

inhibiting effects of baicalein were specific for the inflammatory stimulus that

activated microglia. PMID: 12606597 [PubMed - as supplied by publisher]

 

Ann Emerg Med 2003 Mar;41(3):396-399 Cardioactive steroid poisoning from an

herbal cleansing preparation. Barrueto F Jr, Jortani SA, Valdes R Jr, Hoffman

RS, Nelson LS. Department of Emergency Medicine, New York University

School of Medicine and the New York City Poison Control Center, New York,

NY (Barrueto, Hoffman, Nelson), and the Department of Pathology and

Laboratory Medicine, University of Louisville, Louisville, KY (Jortani, Valdes).

We describe a case of unintentional poisoning from a cardioactive steroid and

the subsequent analytic investigation. A 36-year-old woman with no past

medical history and taking no conventional medications ingested an herbal

preparation marketed for " internal cleansing. " Its ingredients were neither

known

to the patient nor listed on the accompanying literature. The next morning,

nausea, vomiting, and weakness developed. In the emergency department, her

blood pressure was 110/60 mm Hg, and her pulse rate was 30 beats/min. Her

ECG revealed a junctional rhythm at a rate of 30 beats/min and a digitalis

effect

on the ST segments. After empiric therapy with 10 vials of digoxin-specific Fab

(Digibind), her symptoms resolved, and she reverted to a sinus rhythm at a rate

of 68 beats/min. Her serum digoxin concentration measured by means of the

fluorescence polarization immunoassay (Abbott TDx) was 1.7 ng/mL. Further

serum analysis with the Tina Quant digoxin assay, a more digoxin-specific

immunoassay, found a concentration of 0.34 ng/mL, and an enzyme

immunoassay for digitoxin revealed a concentration of 20 ng/mL (therapeutic

range 10 to 30 ng/mL). Serum analysis by means of high-performance liquid

chromatography revealed the presence of active digitoxin metabolites; the

parent compound was not present. When the diagnosis of cardioactive steroid

poisoning is suspected clinically, laboratory analysis can confirm the presence

of cardioactive steroids by using immunoassays of varying specificity. An

empiric dose of 10 vials of digoxin-specific Fab might be beneficial in patients

poisoned with an unknown cardioactive steroid. PMID: 12605208 [PubMed - as

supplied by publisher]

 

Alcohol Clin Exp Res 2003 Feb;27(2):177-85 Herbal remedies for alcoholism:

promises and possible pitfalls. Overstreet DH, Keung WM, Rezvani AH, Massi

And M, Lee DY. This review summarizes the findings of the effects on alcohol

intake in alcohol-preferring rats of extracts or purified compounds from two of

the most promising herbs: kudzu ( ) and St. John's Wort ( ). It is a summary of

a symposium presented at the 2002 RSA meeting in San Francisco. The

meeting organizers/co-chairs were David Overstreet and Wing-Ming Keung. The

presentations were (1) Introduction to the symposium, by David Y. W. Lee and

David H. Overstreet; (2) Effects of daidzin on alcohol intake-search for

mechanisms of action, by Wing-Ming Keung; (3) Long-term suppressive effects

of puerarin on alcohol drinking in rats, by David Overstreet and David Y. W.

Lee;

(4) St. John's Wort extract reduces alcohol intake in FH and P rats, by Amir

Rezvani and David Overstreet; and (5) extracts reduce alcohol intake in

Marchigian Sardinian alcohol-preferring rats, by Maurizio Massi. PMID:

12605067 [PubMed - in process]

 

J Pharmacol Exp Ther 2003 Mar;304(3):1258-67 Effects of the flavonoids

biochanin a, morin, phloretin, and silymarin on p-glycoprotein-mediated

transport. Zhang S, Morris ME. Department of Pharmaceutical Sciences,

School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State

University of New York, Amherst, New York. Flavonoids are constituents of

fruits, vegetables, and plant-derived beverages, as well as components in

herbal-

containing dietary supplements. The objective of this investigation was to

characterize the effect of flavonoids on P-glycoprotein (P-gp)-mediated cellular

efflux and to determine the molecular mechanism(s) of the flavonoid-drug

interaction. Studies were conducted in the sensitive and multidrug resistant

human breast cancer cell lines MCF-7 and MDA435/LCC6 and examined the

effects of the flavonoids biochanin A, morin, phloretin, and silymarin on

daunomycin (DNM) accumulation and doxorubicin cytotoxicity. The potential

mechanism(s) involved in the interaction was evaluated by determining flavonoid

effects on 1) P-gp ATPase activity, 2) [(3)H]azidopine photoaffinity labeling of

P-

gp, and 3) cellular P-gp levels. The flavonoids increased [(3)H]DNM

accumulation in P-gp positive cells, but not P-gp negative cells, and these

effects were both flavonoid concentration- and P-gp expression level-dependent.

Biochanin A and silymarin potentiated doxorubicin cytotoxicity in P-gp positive

cells. Biochanin A and phloretin stimulated, whereas morin and silymarin

inhibited P-gp ATPase activity, confirming that these flavonoids interact with

P-

gp. Morin and silymarin significantly inhibited [(3)H]azidopine photoaffinity

labeling of P-gp, suggesting a direct interaction with P-gp substrate binding. A

24-h preincubation with all flavonoids, followed by flavonoid removal, did not

alter

cellular P-gp level in P-gp positive cells. In conclusion, biochanin A, morin,

phloretin, and silymarin all inhibited P-gp-mediated cellular efflux and the

mechanism of the interaction involved, at least in part, a direct interaction.

The

findings of this study indicate a potential for significant flavonoid-drug

interactions with P-gp substrates. PMID: 12604704 [PubMed - in process]

 

Clin Exp Pharmacol Physiol 2003 Mar;30(3):157-63 Modulatory effect of

Coccinia indica on aortic collagen in streptozotocin-induced diabetic rats.

Venkateswaran S, Pari L, Suguna L, Chandrakasan G. Department of

Biochemistry, Faculty of Science, Annamalai University, Annamalai Nagar and

Department of Biochemistry, Central Leather Research Institute, Adyar,

Chennai, Tamil Nadu, India. 1. The effects of Coccinia indica, an indigenous

plant used in Ayurvedic medicine in India, on aortic collagen content and its

characteristics were assessed in streptozotocin (STZ) diabetic rats. 2. Rats

were made diabetic with a single intraperitoneal injection of STZ (45 mg/kg).

Blood glucose, hydroxyproline, collagen, extent of glycation, collagen-linked

fluorescence, soluble pattern of pepsin-soluble collagen, shrinkage

temperature, alpha/beta ratio of type I collagen and type I/type III collagen

ratio

were determined in rats treated with C. indica leaf extract (CLEt; 200 mg/kg for

45 days using an oral intragastric tube). 3. In diabetic rats, the collagen

content, as well as the degree of cross-linking, was increased, as evidenced by

increased shrinkage temperature and decreased pepsin solubility. The

alpha/beta ratio of type I collagen and the type I/type III collagen ratio of

pepsin-

soluble collagen were significantly decreased in STZ diabetic rats. 4. In

conclusion, administration of CLEt for 45 days to STZ diabetic rats

significantly

reduced the accumulation and cross-linking of collagen. The effects of C. indica

(collagen content 23.87 +/- 1.52 mg/100 mg tissue (t value = 6.80), extent of

cross-linking 0.893 +/- 0.072 mg hydroxyproline/100 mg tissue (t value = 9.0))

were comparable with those of glibenclamide (collagen content 26.18 +/- 1.65

mg/100 mg tissue (t value = 4.58), extent of cross-linking 0.787 +/- 0.057 mg

hydroxyproline/100 mg tissue (t value = 7.1)), a reference drug. PMID:

12603344 [PubMed - in process]

 

Zhejiang Da Xue Xue Bao Yi Xue Ban 2002 Aug;31(5):367-368 [Treatment of

partial thickness burn wound with herb plaster Tangshangxiaobogao] [Article in

Chinese] Hu XQ, Tao YJ, Xu J, Chen GX, Pu SS. The Second Affiliated

Hospital, College of Medical Sciences, Zhejiang University, Hangzhou 310009,

China. OBJECTIVE: To evaluate the therapeutic effect of the herbal plaster

Tangshangxiaobagao on partial thickness burn wound. METHODS: A

randomized controlled trial was conducted with two herbal plasters: Tangshang-

xiaobagao and Jingwanhong in 57 hospitalized burn patients. Both the effect

and safety of two herbal plasters were noted in patients with partial thickness

burns. RESTULTS: In superficial second degree burns, the 7 d healing rate of

both groups was (61.35+/-36.26)%and (51.21+/-37.24)% and the healing time

(10.56+/-3.43)d and (11.98+/-4.13)d P<0.05 respectively. While in deep second

degree burns, the 14 d healing rate of both groups was (62.9+/-36.0) % and

(53.9+/-32.2) % and the healing time (19.4+/-4.9)d and (21.5+/-5.5)d,

respectively. Study group had lower VAS(visual analogue scale)score than

control group. No obvious side effects were observed in study group.

CONCLUSION: Tangshangxiaobagao is safe and may be an effective adjunct

for treatment of partial thickness burn wounds. PMID: 12601888 [PubMed - as

supplied by publisher]

 

Indian J Exp Biol 2002 Jul;40(7):831-4 Synergistic effect of ayurvedic pearl

preparation on enhancing effectiveness of antibiotics. Kulkarni M, Deopujari

JY,

Purohit HJ. National Environmental Engineering Research Institute, Nehru

Marg, Nagpur 440 020, India. Studies were carried out with ayurvedic

preparations derived from pearl, which include preparations bhasma and pishti.

The synergistic effect to reduce the dose of antibiotic was tested against E.

coli

the test bacterium with ampicillin antibiotic by bore well and disks diffusion

methods. It was observed that pearl preparations do not show any antibacterial

activity but when used at 200 microg/ml concentration with antibiotics, then

even at sub-lethal dose, the antibiotic has effectively shown the results with

reduced contact time. The protocol was also tested with the other bacteria like,

Pseudomonas aeruginosa. Vibrio cholarae, Salmonella typhi, and

Staphylococcus aureus and has shown similar results. The pearl bhasma

synergistic effect was also tested with other antibiotics such as erythromycin,

kanamycin, and ampicillin. PMID: 12597554 [PubMed - in process]

 

 

 

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