Herbal Science Research - pharmaceutical

Media portrayal of herbal remedies versus pharmaceutical clinical trials: impacts on decision.

Site Editor — Sun, 30 Sep 2007 02:39:54 -0700

Media portrayal of herbal remedies versus pharmaceutical clinical trials: impacts on decision.: Med Law. 2007 Jun; 26(2): 363-73
Bubela T, Koper M, Boon H, Caulfield T

The use of Complementary and Alternative Medicines (CAM) in Europe and North America is increasing significantly with a concomitant growth in business interest. Users are educated and self-empowered and rely on information sources beyond mainstream medical practitioners. Not surprisingly, media coverage, much of dubious quality, has increased to meet demand for information. Here we present data from a study that explores how knowledge is translated in the socioeconomic-political context of CAM as compared to conventional pharmaceuticals. Specifically, we are interested in the nature of the information provided by clinical trials and the media and how this might impact decision-making regarding the use of CAM versus conventional pharmaceuticals and the reporting of conflicts of interest and industry funding of research. Our results suggest that, in the media, there were significant errors of omission in describing clinical trial quality and a serious under-reporting of risks of herbal remedies. Consumers, who often self-administer CAM are not being provided with information sufficient to make informed choices about treatment alternatives. The next step in the research is to determine whether these reporting dynamics in describing CAM clinical trials differ from those of reporting on pharmaceutical clinical trials.

[Effect of chinese herbs in enhancing prednisone for treatment of refractory rheumatoid arthritis]

Site Editor — Sat, 22 Sep 2007 18:15:33 -0700

[Effect of chinese herbs in enhancing prednisone for treatment of refractory rheumatoid arthritis]: Zhongguo Zhong Xi Yi Jie He Za Zhi. 2007 Aug; 27(8): 742-4 Liu W, Liu XY, Wang Y

OBJECTIVE: To investigate the Chinese herbal medicine in enhancing effect of prednisone for treatment of refractory rheumatoid arthritis (RA). METHODS: One hundred and twenty patients with refraetory RA were assigned to two groups, the treated group was orally administered with Qingbi Tablet, a patent Chinese herbal preparation formulated based on the clearing heat and removing toxic substances principle, and the control group was treated with intramuscular injection of amethopterin (MTX), oral intake of voltaren 75 mg and hydroxychloroquine 0.2 g once a day. Besides prednisone was given to all patients orally, the initiating dosage used in the treated group was lesser than that in the control group. The clinical index, dosage and adverse reaction of prednisone were recorded every 2 weeks. RESULTS: The curative effect evaluated by American College of Rheumatology (ACR) standard showed no statistical difference between the two groups (P > 0.05). Either clinical or laboratory indexes were improved significantly in both groups (P < 0.05), but the improvement in resting pain, patient's self-evaluation and doctor's evaluation in the treated group were better than those in the control group, showing statistical difference (P < 0.05). The 20-week total amount of prednisone used in the treated group was less than that in the control group (32,935 mg vs. 51,170 mg), while the dosage of prednisone used in various observation time points between the two groups was also significantly different respectively (P < 0.05), the former was less than the latter. CONCLUSION: Chinese herbal medicine can enhance the effect of prednisone in patients of refractory RA and alleviate the adverse reactions of prednisone.

Chasing molecules that were never there: misassigned natural products and the role of chemical synthesis...

Site Editor — Fri, 05 Jan 2007 19:47:05 -0800

Chasing molecules that were never there: misassigned natural products and the role of chemical synthesis in modern structure elucidation.: Angew Chem Int Ed Engl. 2005 Feb 4;44(7):1012-44 Authors: Nicolaou KC, Snyder SA

Over the course of the past half century, the structural elucidation of unknown natural products has undergone a tremendous revolution. Before World War II, a chemist would have relied almost exclusively on the art of chemical synthesis, primarily in the form of degradation and derivatization reactions, to develop and test structural hypotheses in a process that often took years to complete when grams of material were available. Today, a battery of advanced spectroscopic methods, such as multidimensional NMR spectroscopy and high-resolution mass spectrometry, not to mention X-ray crystallography, exist for the expeditious assignment of structures to highly complex molecules isolated from nature in milligram or sub-milligram quantities. In fact, it could be argued that the characterization of natural products has become a routine task, one which no longer even requires a reaction flask! This Review makes the case that imaginative detective work and chemical synthesis still have important roles to play in the process of solving nature's most intriguing molecular puzzles.

Multivariate analysis of integrated and full-resolution 1H-NMR spectral data from [...] : St. John's Wort.

Site Editor — Wed, 04 Oct 2006 18:50:35 -0700

Multivariate analysis of integrated and full-resolution 1H-NMR spectral data from complex pharmaceutical preparations: St. John's wort.: Planta Med. 2006 May; 72(6): 556-63 Rasmussen B, Cloarec O, Tang H, Staerk D, Jaroszewski JW

Commercial herbal preparations are typically very complex mixtures and the relationship between content of various constituents and pharmacological action of the formulation is usually unclear. Such formulations are nevertheless standardized using a single marker constituent or a group of closely related constituents, which provides no information about other abundant constituents present in the extract. In this study, principal component analysis of 600 MHz 1H-NMR spectra of extracts of commercial formulations of St. John's wort (Hypericum perforatum), acquired in methanol-d4 and DMSO-d6, was shown to be able to discriminate between various preparations according to their global composition, including differentiation between various batches from the same supplier, while no clustering into classes of tablets and capsules was observed. This suggests that the plant extract variability rather than the manufacturing process accounts for the data clustering. Major variations in the content of flavonoids, recently linked to the antidepressant activity of St. John's wort extracts, were detected. Use of two NMR solvents provided complementary data sets, allowing assessment of various aspects of sample composition from separate PCA models. Both integrated (about 200 variables) and full-resolution NMR data (about 30,000 variables) have been used. The latter approach, applied for the first time in analysis of a herbal preparation, provided via loading plots more precise information about constituents responsible for data clustering, and may be generally preferable for PCA analysis of NMR data of plant extracts and herbal medicines.

A Preadipocyte Differentiation Assay as a Method for Screening Potential Anti-Type II Diabetes Drugs from Herbal Extracts.

Site Editor — Fri, 09 Jun 2006 07:14:26 -0700

A Preadipocyte Differentiation Assay as a Method for Screening Potential Anti-Type II Diabetes Drugs from Herbal Extracts.: Planta Med. 2006 Jan;72(1):14-9 Authors: Xu ME, Xiao SZ, Sun YH, Ou-Yang Y, Guan C, Zheng XX

A cell-based method for screening drug candidates from herbal extracts that have possible anti-type II diabetic effects was established. The differentiation of preadipocytes into adipocytes was used as a sensitive primary indicator of a drug's potential effect on type II diabetes. We established a quantitative method by using a computer image analysis system for assessing the morphological alterations. The assay was validated by screening compounds extracted from Chinese herbs and the known drug rosiglitazone for their capability of modulating PPARgamma gene expression and glucose uptake by adipocytes. Two drug candidates having possible anti-type II diabetic effects were identified. Abbreviations. DMEM:Dulbecco's modified Eagle's medium FCS:fetal calf serum RT-PCR:reverse transcriptase-polymerase chain reaction WST:water-soluble tetrazolium PPARgamma:peroxisome proliferator-activated receptor FITC:fluorescein isothiocyanate PI:propidium iodide PS:phosphatidyl serine.

Assessment of the antioxidant activities of Brazilian extracts of propolis alone and in topical pharmaceutical formulations.

Site Editor — Fri, 09 Jun 2006 04:06:36 -0700

Assessment of the antioxidant activities of Brazilian extracts of propolis alone and in topical pharmaceutical formulations.: J Pharm Biomed Anal. 2005 Sep 15;39(3-4):455-62 Authors: Marquele FD, Di Mambro VM, Georgetti SR, Casagrande R, Valim YM, Fonseca MJ

The antioxidant activity of extracts of propolis and of formulations added with these extracts were measured by scavenging different radicals in different systems. For the ethanolic extract of propolis (EEP) and the glycolic extract of propolis (GEP) the IC50 observed were respectively of 0.024 and 0.035 microL/mL in scavenging hydroxyl radical, 0.016 and 0.012 microL/mL in inhibiting lipid peroxidation, 0.22 and 0.24 microL/mL in inhibiting chemiluminescence produced in the H2O2/luminol/horseradish peroxide (HRP) system and about 0.005 microL/mL for both extracts in inhibiting chemiluminescence produced in the xanthine/luminol/xanthine oxidase (XOD) system. The antioxidant activity of extracts of propolis in the formulations was not able to be assessed neither using the deoxyribose assay, since the formulation components interfered in the assay measurements, nor using chemiluminescence in the H2O2/luminol/HRP system, since this method did not show to be sensitive for the extract of propolis evaluation. However, the antioxidant activity of extracts of propolis could be successfully evaluated in the formulations using both lipid peroxidation and chemiluminescence generated in the xanthine/luminol/XOD system inhibitions.

Mechanisms involved in the anti-inflammatory effect of a standardized willow bark extract.

Site Editor — Fri, 09 Jun 2006 04:03:49 -0700

Mechanisms involved in the anti-inflammatory effect of a standardized willow bark extract.: Arzneimittelforschung. 2005;55(11):677-87 Authors: Khayyal MT, El-Ghazaly MA, Abdallah DM, Okpanyi SN, Kelber O, Weiser D

A standardized willow bark extract (STW 33-I) has been examined to clarify its possible mechanism of action as an anti-inflammatory agent. Various facets have been investigated in two inflammation models: the 6-day air pouch model in rats, representing the acute state and the adjuvant induced arthritis representing the chronic one. Parameters included leukocytic infiltration, levels of cytokines and prostanoids in blood, and effects on cyclo-oxygenase (COX)-1 and/or COX-2 enzymes as well as effects involving free radical production. The effect of the extract was compared at two dose levels with comparable anti-inflammatory doses of acetylsalicylic acid (CAS 50-78-2, ASA) as a non-selective COX inhibitor, and celecoxib (CAS 169590-42-5) as a selective COX-2 inhibitor. On a mg/kg basis, the extract was at least as effective as ASA in reducing inflammatory exudates and in inhibiting leukocytic infiltration as well as in preventing the rise in cytokines, and was more effective than ASA in suppressing leukotrienes, but equally effective in suppressing prostaglandins. On COX-2, STW 33-I was more effective than ASA. The present findings show that STW 33-I significantly raises GSH (reduced glutathione) levels, an effect which helps to limit lipid peroxidation. The extract was more potent than either ASA or celecoxib. Higher doses of the extract also reduced malondialdehyde levels and raised shows definite superiority to either ASA or celecoxib in protecting the body against oxidative stress. It is therefore evident that STW 33-I is at least as active as ASA on all the parameters of inflammatory mediators measured, when both are given on a similar mg/kg dose. Considering, however, that the extract contains only 24% salicin (molecular weight 286.2), while ASA has a molecular weight of 180.3, it follows that on a molar basis of salicin vs salicylate, the extract contains less than a sixth of the amount of salicin as the amount of salicylate in ASA. Thus it appears that STW 33-I with its lower "salicin" content than an equivalent dose of ASA, is at least as active as ASA on the measured parameters, a fact that leads one to speculate that other constituents of the extract contribute to its overall activity. The presence of polyphenols in STW 33-I probably plays a significant role in enhancing its free radical scavenging properties. The fact that STW 33-I was superior to ASA in this respect would suggest that the extract may have a better anti-inflammatory effect than ASA on a weight to weight basis, with possibly less side effects.

Reduction of catechin astringency by the complexation of gallate-type catechins with pectin.

Site Editor — Fri, 09 Jun 2006 03:43:50 -0700

Reduction of catechin astringency by the complexation of gallate-type catechins with pectin.: Biosci Biotechnol Biochem. 2005 Jul;69(7):1306-10 Authors: Hayashi N, Ujihara T, Kohata K

The reductive effect of pectin on tea catechin astringency was investigated by using a taste sensor system and (1)H-NMR spectroscopy. The sensor analysis revealed that the astringency of gallate-type catechins (EGCg and ECg) was reduced by the addition of pectin, whereas that of non-gallate-type catechins (EGC and EC) hardly changed. Changes in the (1)H-NMR chemical shifts of the catechins and pectin in mixed solutions showed that the gallate-type catechins formed complexes with pectin more closely than the non-gallate-type catechins. These results demonstrate that complexation between the gallate-type catechins and pectin is a factor for reducing catechin astringency.

Association between frequent use of nonsteroidal anti-inflammatory drugs and breast cancer.

Site Editor — Fri, 09 Jun 2006 03:30:32 -0700

Association between frequent use of nonsteroidal anti-inflammatory drugs and breast cancer: BMC Cancer. Authors: Elham Rahme, Joumana Ghosn, Kaberi Dasgupta, Raghu Rajan and Marie Hudson.

Background: Eighty percent of all breast cancers and almost 90% of breast cancer deaths occur among post-menopausal women. We used a nested case control design to examine the association between nonsteroidal anti-inflammatory drug (NSAID) use and breast cancer occurrence among women over 65 years of age. The cyclooxygenase (COX)-2 enzyme is expressed more in breast cancers than in normal breast tissue. COX-2 inhibition may have a role in breast cancer prevention. Methods: In the Canadian province of Quebec, physician services are covered through a governmental insurance plan. Medication costs are covered for those [greater than or equal to] 65 years of age and a publicly funded screening program for breast cancer targets all women 50 years of age or older. We obtained encrypted data from these insurance databases on all women [greater than or equal to] 65 years of age who filled a prescription for COX-2 inhibitors, non-selective NSAIDs (ns-NSAIDs), aspirin, or acetaminophen between January 1998 and December 2002. Cases were defined as those women who have undergone mammography between April 2001 and June 2002 and had a diagnosis of breast cancer within six months following mammography. Controls included those who have undergone mammography between April 2001 and June 2002 without a diagnosis of any cancer during the six months following mammography. The exposure of interest, frequent NSAID use, was defined as use of ns-NSAIDs and/or COX-2 inhibitors for [greater than or equal to] 90 days during the year prior to mammography. Frequent use served as a convenient proxy for long term chronic use. Results: We identified 1,090 cases and 44,990 controls. Cases were older and more likely to have breast cancer risk factors. Logistic regression models adjusting for potential confounders showed that frequent use of ns-NSAIDs and/or COX-2 inhibitors was associated with a lower risk of breast cancer (OR: 0.75, 95% confidence interval 0.64-0.89). Results were similar for COX-2 inhibitors (0.81, 0.68-0.97) and ns-NSAIDs (0.65, 0.43-0.99), when assessed separately. Frequent use of aspirin at doses > 100mg/day in the year prior to mammography was also associated with a lower risk of breast cancer (0.75, 0.64-0.89). However, use of aspirin at doses [less than or equal to] 100mg/day did not have any association with breast cancer (0.91, 0.71-1.16). Conclusion: Women who use NSAIDs or doses of ASA > 100 mg frequently may have a lower risk of breast cancer.

Uncommon trajectories: steroid hormones, Mexican peasants, and the search for a wild yam.

Site Editor — Fri, 09 Jun 2006 03:29:20 -0700

Uncommon trajectories: steroid hormones, Mexican peasants, and the search for a wild yam.: Stud Hist Philos Biol Biomed Sci. 2005 Dec;36(4):743-760 Authors: Soto Laveaga G

This article analyzes how evolving pharmaceutical technology, chemical advances, and world politics created the need for an abundant and cheap supply of steroids, and how decisions made in faraway laboratories ultimately determined that a Mexican yam, barbasco, was the best possible raw material. Following this discovery, this article explores how barbasco's exploitation impacted on the Mexican countryside and specifically the men and women hired to gather wild yams. In analyzing, for example, the peasant organizations that emerged, the use of chemical terms by barely literate peasants, and the Mexican government's political strategy to control rural unrest by controlling barbasco production one begins to understand the unexpected consequences of the global search for medicinal plants. In this particular case, the merging of science and peasant life reshuffled social hierarchies in the countryside, granted monetary value to an erstwhile 'weed', and gave a novel reinterpretation to laboratory knowledge and its (social) uses.

Valerian-hops combination and diphenhydramine for treating insomnia: a randomized placebo-controlled clinical trial.

Site Editor — Fri, 09 Jun 2006 03:28:12 -0700

Valerian-hops combination and diphenhydramine for treating insomnia: a randomized placebo-controlled clinical trial.: Sleep. 2005 Nov 1;28(11):1465-71 Authors: Morin CM, Koetter U, Bastien C, Ware JC, Wooten V

CONTEXT: Insomnia is a prevalent health complaint associated with daytime impairments, reduced quality of life, and increased health-care costs. Although it is often self-treated with herbal and dietary supplements or with over-the-counter sleep aids, there is still little evidence on the efficacy and safety of those products. OBJECTIVE: To evaluate the efficacy and safety of a valerian-hops combination and diphenhydramine for the treatment of mild insomnia. DESIGN AND SETTING: Multicenter, randomized, placebo-controlled, parallel-group study conducted in 9 sleep disorders centers throughout the United States. PATIENTS: A total of 184 adults (110 women, 74 men; mean age of 44.3 years) with mild insomnia. INTERVENTIONS: (1) Two nightly tablets of standardized extracts of a valerian (187-mg native extracts; 5-8:1, methanol 45% m/m) and hops (41.9-mg native extracts; 7-10:1, methanol 45% m/m) combination for 28 days (n = 59), (2) placebo for 28 days (n = 65), or (3) 2 tablets of diphenhydramine (25 mg) for 14 days followed by placebo for 14 days (n = 60). OUTCOME MEASURES: Sleep parameters measured by daily diaries and polysomnography, clinical outcome ratings from patients and physicians, and quality of life measures. RESULTS: Modest improvements of subjective sleep parameters were obtained with both the valerian-hops combination and diphenhydramine, but few group comparisons with placebo reached statistical significance. Valerian produced slightly greater, though nonsignificant, reductions of sleep latency relative to placebo and diphenhydramine at the end of 14 days of treatment and greater reductions than placebo at the end of 28 days of treatment. Diphenhydramine produced significantly greater increases in sleep efficiency and a trend for increased total sleep time relative to placebo during the first 14 days of treatment. There was no significant group difference on any of the sleep continuity variables measured by polysomnography. In addition, there was no alteration of sleep stages 3-4 and rapid eye movement sleep with any of the treatments. Patients in the valerian and diphenhydramine groups rated their insomnia severity lower relative to placebo at the end of 14 days of treatment. Quality of life (Physical component) was significantly more improved in the valerian-hops group relative to the placebo group at the end of 28 days. There were no significant residual effects and no serious adverse events with either valerian or diphenhydramine and no rebound insomnia following their discontinuation. CONCLUSIONS: The findings show a modest hypnotic effect for a valerian-hops combination and diphenhydramine relative to placebo. Sleep improvements with a valerian-hops combination are associated with improved quality of life. Both treatments appear safe and did not produce rebound insomnia upon discontinuation during this study. Overall, these findings indicate that a valerian-hops combination and diphenhydramine might be useful adjuncts in the treatment of mild insomnia.

'Safe' painkiller is leading cause of liver failure

Site Editor — Fri, 09 Jun 2006 03:25:32 -0700

Safe painkiller is leading cause of liver failure - Accidental overdoses of a popular painkiller - known as acetaminophen in the US and paracetamol in the UK - cause many cases of acute liver failure in the US.

HPLC-MS/MS analysis of willow bark extracts contained in pharmaceutical preparations.

Site Editor — Fri, 09 Jun 2006 03:12:31 -0700

HPLC-MS/MS analysis of willow bark extracts contained in pharmaceutical preparations. - Phytochem Anal. 2005 Nov-Dec;16(6):470-8 Authors: Kammerer B, Kahlich R, Biegert C, Gleiter CH, Heide L

Preparations containing willow bark extract are popular herbal remedies, but they are mostly standardised with respect to only one compound (usually salicin). RP-HPLC using a C18-column eluted with water:methanol:tetrahydrofuran and coupled to electrospray triple-quadrupole MS and MS/MS was used for the characterisation of dried extracts of Salix spp. and for the identification of their constituents. Comparison with reference substances led to the identification of 13 compounds (saligenin, salicylic acid, salicin, isosalicin, picein, salidroside, triandrin, salicoylsalicin, salicortin, isosalipurposide, salipurposide, naringenin-7-O-glucoside and tremulacin). Two pharmaceutical preparations containing willow bark extract, used in clinical trials and labelled Salix daphnoides and S. purpurea x daphnoides extracts, were compared using the described method and exhibited several clear differences, the most prominent of which was the possible presence of picein in the former preparation. The described method may be utilised for the characterisation of herbal medicines in order to ensure comparability of medication in further clinical trials.