Guest guest Posted March 2, 2003 Report Share Posted March 2, 2003 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] Best regards, WORK : Teagasc Staff Development Unit, Sandymount Ave., Dublin 4, Ireland WWW : Email: < Tel : 353-; [in the Republic: 0] HOME : 1 Esker Lawns, Lucan, Dublin, Ireland WWW : http://homepage.eircom.net/~progers/searchap.htm Email: < Tel : 353-; [in the Republic: 0] Quote Link to comment Share on other sites More sharing options...
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