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The prevalence and predictors of herbal medicine use in surgical patients.

BACKGROUND: Despite the rapid rise in herbal medicine consumption, explicitly eliciting and documenting herbal medicine usage among surgical patients is poor. STUDY DESIGN: A survey by means of a self-administered questionnaire was conducted among patients undergoing elective surgery inquiring into the self-health perceptions, herbal medicine use, and communication of such usage to surgical health-care staff. RESULTS: Sixty-five percent (n =2,186) of all the patients undergoing elective surgery completed the survey during a 10-week period. Fifty-seven percent of respondents admitted to using herbal medicine at some point in their life, 38% in the past 2 years (eg, echinacea [48%], aloe vera [30%], ginseng [28%], garlic [27%], and ginkgo biloba [22%] were the most common). One in six respondents continued the use of herbal medicine during the month of surgery. Herbal medicine usage was significantly higher among patients undergoing a gynecologic procedure (odds ratio [OR] 1.68; 95% confidence interval [CI] 1.29 to 2.18) and patients with a self-perception of good health (OR 1.32; 95% CI 1.04 to 1.69); it was lower among patients with a history of pulmonary symptoms (OR 0.77; 95% CI 0.62 to 0.94), African Americans (OR 0.69; 95% CI 0.51 to 0.95), in patients having a primary care physician (OR 0.71; 95% CI 0.52 to 0.98), in patients with a history of diabetes mellitus (OR 0.46; 95% CI 0.32 to 0.68), and in patients undergoing vascular surgery (OR 0.19; 95% CI 0.07 to 0.48). CONCLUSIONS: Herbal medicine use is common among surgical patients and is consistent with the substantial increase in the use of alternative medical therapies. Awareness of this rising herbal medicine usage and documentation of the use of herbal medicines by surgical health-care staff is important to prevent, recognize, and treat potential problems that may arise from herbal medications taken alone or in conjunction with conventional medications during the perioperative period.

Adult↗

Structural analysis of saponins from medicinal herbs using electrospray ionization tandem mass spectrometry.

The underivatized saponins from Tribulus terrestris and Panax ginseng have been investigated by electrospray ionization multi-stage tandem mass spectrometry (ESI-MS(n)). In ESI-MS spectra, a predominant [M + Na](+) ion in positive mode and [M - H](-) ion in negative mode were observed for molecular mass information. Multi-stage tandem mass spectrometry of the molecular ions was used for detailed structural analysis. Fragment ions from glycoside cleavage can provide information on the mass of aglycone and the primary sequence and branching of oligosaccharide chains in terms of classes of monosaccharides. Fragment ions from cross-ring cleavages of sugar residues can give some information about the linkages between sugar residues. It was found that different alkali metal-cationized adducts with saponins have different degrees of fragmentation, which may originate from the different affinity of a saponin with each alkali metal in the gas phase. ESI-MS(n) has been proven to be an effective tool for rapid determination of native saponins in extract mixtures, thus avoiding tedious derivatization and separation steps.

Carbohydrate Sequence↗

In vivo rat metabolism and pharmacokinetic studies of ginsenoside Rg3.

Metabolism of an anti-tumor active component of Panax ginseng, ginsenoside (20R)-Rg(3), was studied for better understanding its pharmacokinetics in rat. LC-MS was used to determine Rg(3) and its metabolites in rat plasma, urine and feces samples. An average half-life of 18.5 min was obtained after the ginsenoside was intravenously dosed at 5 mg/kg. However, Rg(3) was not detected in rat plasma collected after oral administration at 100 mg/kg. Only 0.97-1.15% Rg(3) of the dosed amount was determined in feces. Hydrolysis and oxygenated metabolites were detected and identified in feces collected after oral administration by using LC-MS and MS-MS.

Administration, Oral↗

Effect of medicinal plant extracts on forced swimming capacity in mice.

The tonic effect of Cordyceps militaris (CM), Paecilomyces japonia (PJ), Phellinus linteus (PL), Ganoderma lucidum (GL), Grifola frondosa (GF), and Panax ginseng (PG) was examined based on the forced swimming capacity and the change of biochemical parameters in ICR mice. The treatment groups were orally administered medicinal plant extracts (500 mg/kg per day), while the control group received distilled water for 4 weeks. The swimming times to exhaustion were longer in the CM, PJ, and GF groups than in the control group (P < 0.05). Plasma TG levels were lower in the treatment groups than in the control group. Plasma glucose levels were not significantly different between the control group and each treatment group except the PG group. Plasma lactate and ammonia levels of the PJ and GF groups were lower than those of the control group (P < 0.05). There were no significant differences in the content of liver and gastrocnemius muscle glycogen between the control group and each treatment group. In conclusion, PJ and GF extracts enhanced the forced swimming capacity of mice by increasing fat utilization and by delaying the accumulation of plasma lactate and ammonia.

Animals↗

Application of modified in vitro screening procedure for identifying herbals possessing sulfonylurea-like activity.

We describe here the application of a modified in vitro procedure for identifying herbs potentially possessing sulfonylurea-like activity. The procedure consists of the combination of an SUR1 receptor binding assay and an insulin secretion assay in cultures of HIT-T15 cells. This procedure could be used as an initial step in identifying new safe and efficacious agents for the management of Type II diabetes. The application of this screening procedure to a set of selected herbs produced results that were consistent with the previously reported properties of those herbs. The collected data suggest that the hypoglycemic properties of bitter melon (Momordica charantia, Linn. Family, Cucurbitacea), cerasse (Momordica charantia, Linn. wild variety, Family, Cucurbitacea) and American ginseng (Panax quinquefolius, Linn., Family Araliacea) are at least partially due to their sulfonylurea-like activity.

ATP-Binding Cassette Transporters↗

Trends in ethnopharmocology.

The use of plants, plant extracts or plant-derived pure chemicals to treat disease is a therapeutic modality, which has stood the test of time. Indeed today many pharmacological classes of drugs include a natural product prototype. Aspirin, atropine, ephedrine, digoxin, morphine, quinine, reserpine and tubocurarine are a few examples of drugs, which were originally discovered through the study of traditional cures and folk knowledge of indigenous people. There is a revival of interest in herbal products (botanicals) at a global level and the conventional medicine is now beginning to accept the use of botanicals once they are scientifically validated. Ispaghula, Garlic, Ginseng, Ginger, Ginkgo, St. John's Wort, and Saw palmetto are a few examples of botanicals which are gaining popularity amongst modern physicians and this trend is likely to continue partly due to high cost involved in the development of patentable chemical drugs. There is growing evidence to show that medicinal plants contain synergistic and/or side-effects neutralizing combinations. Ethnopharmacology has already played important role in the development of conventional medicine and is likely to play more significant role in the years to come. A team work amongst ethnobotanists, ethnopharmacologists, physicians and phytochemists is essential for the fruitful outcome on medicinal plants research. While the ethnopharmacologists have a greater role to play in the rationalization of combination of activities, the phytochemist's role will slightly shift towards standardization of botanicals.

Ethnopharmacology↗

Inhibitory effect of the Korean herbal medicine, Dae-Jo-Whan, on platelet-activating factor-induced platelet aggregation.

The anti-thrombic properties of the Korean herbal medicine, Dae-Jo-Hwan (DJW) were investigated. Water extracts, a 70% methanol (MeOH) extract and an ethyl acetate (EtOAc) soluble fraction (III) from DJW inhibited platelet-activating factor (PAF)-induced platelet aggregation in vitro and in vivo assays. The extracts of DJW and eleven herbs from which it is derived, except for Panax ginseng Meyer, Angelica sinensis (OLIV.) DIELS and Schisandra chinensis Baill., inhibited AA-induced blood platelet aggregation to various extents. The effects observed with total DJW was synergistic over-additive rather that additive since the sum of single contributions was lower than the effect of the total extract. Fraction III was specially protected against the lethality of PAF, while verapamil did not afford any protection. Exogenously applied arachidonic acid (AA) (100 microM) led to a 89% platelet aggregation, the release of 14 pmol of ATP, and the formation of either 225 pg of thromboxane A2 (TXA2) or 45 pg of prostaglandin E2 (PGE2), each parameter being related to 10(6) platelets. An application of DJW 5 min before AA, dose-dependently diminished aggregation, ATP-re lease, and the synthesis of TXA2 and PGE2, with IC(50) values of 70, 87, 65 and 72 microg/ml, respectively. The similarity of the IC(50) values suggests the inhibition of cyclooxygenase (COX) by DJW as the primary target, thus suppressing the generation of TXA2, which induces platelet aggregation and the exocytosis of ATP by its binding on TXA2-receptors. These results indicate that DJW shows anti-thrombotic action on human platelets and inhibits the action of PAF in vivo by an antagonistic effect on PAF. Therefore, it may be useful in treating disorders caused by PAF.

Animals↗

Effects of homocysteine and ginsenoside Rb1 on endothelial proliferation and superoxide anion production.

BACKGROUND: Homocysteine (Hcy) is an independent risk factor for cardiovascular disease by its multiple effects on vascular cells and throbmosis factors, which may be involved in oxidative stress mechansims. Ginsenoside Rb1, a constituent of ginseng, bears various beneficial effects on the cardiovascular system. In the present study, we investigated the effect of Hcy on endothelial proliferation and a protective effect of ginsenoside Rb1 on the action of Hcy. METHODS: We initially incubated a mouse lymph node endothelial cell line (SVEC4-10) with increasing concentrations of Hcy or for different time periods and then assessed cell proliferation by using [(3)H]-thymidine incorporation. We then incubated SVEC4-10 cells with Hcy (50 microM) for 24 h with or without Rb1 (10 microM) to examine its inhibitory effect on the proliferation. These experiments were repeated in human umbilical vein endothelial cells (HUVECs). To explore the underlying molecular mechanisms, we measured superoxide anion, a reactive oxygen species (ROS), by using dihydroethidium (DHE) staining. RESULTS: SVEC4-10 cells treated with Hcy (50, 100, and 200 microM) for 24 h significantly reduced cell proliferation by 43%, 42%, and 40%, respectively, as compared with control cells (P < 0.01). SVEC4-10 cells treated with Hcy (50 microM) for 12 and 24 h showed a significant reduction of cell proliferation (P < 0.05). In HUVECs, Hcy (50 microM) significantly reduced cell proliferation by 55% as compared with control cells (P < 0.05). In the presence of Rb1, Hcy-induced inhibition of cell proliferation was effectively blocked in both SVEC4-10 and HUVECs. Furthermore, Hcy (50 microM) significantly increased superoxide anion production by 23% in SVEC4-10 as compared with control cells (P < 0.05). However, in the presence of Rb1, Hcy increased superoxide anion production by only 8%, showing that RB1 almost completely blocked the effect of Hcy. CONCLUSION: Hcy significantly inhibits endothelial proliferation with increased production of superoxide anion, which is effectively blocked by ginsenoside Rb1. This study provides some new aspects of Hcy-induced endothelial dysfunction, and suggests a potential role of Rb1 to block Hcy action, which may have clinical applications.

Animals↗

Ginsenosides compound (shen-fu) attenuates gastrointestinal injury and inhibits inflammatory response after cardiopulmonary bypass in patients with congenital heart disease.

OBJECTIVE: This study was undertaken to demonstrate that gastrointestinal mucosal injury occurs during cardiopulmonary bypass in children, increasing systemic inflammatory responses, and to determine whether shen-fu injection (the major components of which are ginsenosides compound, extract of Panax ginseng shown to have antioxidant properties) could attenuate gastrointestinal mucosal injury and subsequent inflammatory responses. METHODS: Twenty-four children undergoing heart surgery for congenital heart defects were randomly assigned to groups C (placebo control, n = 12) and G (1.35 mg/kg ginsenosides compound intravenously before and throughout the course of cardiopulmonary bypass, n = 12). Central venous blood samples were taken before cardiopulmonary bypass and at 60 and 120 minutes after aortic declamping (reperfusion). Gastric intramucosal pH was measured by perioperative tonometry. Plasma lipid peroxidation product malondialdehyde, myocardium-specific creatine kinase isoenzyme MB activity, diamine oxidase, lipopolysaccharide, and interleukin 6 were all measured. RESULTS: Significant decrease in gastric intramucosal pH and increase in plasma diamine oxidase were seen during reperfusion in group C, accompanied by increases in plasma levels of malondialdehyde, lipopolysaccharide, interleukin 6, and creatine kinase isoenzyme MB (P < .01 vs before cardiopulmonary bypass). Shen-fu injection significantly attenuated these changes (P < .05). Consequently, fewer patients in group G (2/12) than in group C (7/12) needed postoperative inotropic support. Postoperative intensive care unit stay was shorter in group G than in group C. A tight positive correlation was seen between diamine oxidase and interleukin 6 at 60 minutes after aortic declamping and between diamine oxidase and lipopolysaccharide at 120 minutes after aortic declamping (r = 0.79, P < .0001). CONCLUSION: Ginsenosides compound may attenuate gastrointestinal injury and inhibit inflammatory response after cardiopulmonary bypass in patients with congenital heart disease.

Adolescent↗

Mesothelium regeneration on acellular bovine pericardia loaded with an angiogenic agent (ginsenoside Rg1) successfully reduces postsurgical pericardial adhesions.

OBJECTIVE: Our objective was to reduce postsurgical pericardial adhesions with porous acellular bovine pericardia loaded with ginsenoside Rg1, an angiogenic agent isolated from Panax ginseng (the Acellular/Rg1 patch). METHODS: The acellular/Rg1 patch was used as a substitute to repair a defect created in the pericardium of a rabbit model. A commercially available expanded polytetrafluoroethylene patch, the cellular pericardium (the cellular patch), and the acellular pericardium without loading Rg1 (the acellular patch) were used as controls. The implanted samples were retrieved at 1 and 3 months after surgery (n = 5 per group at each time point). RESULTS: It was found that each side of the implanted patch could be remesothelialized provided that regeneration of neo-tissue fibrils occurred initially on its surfaces. Because remesothelialization did not take place on the surfaces of the expanded polytetrafluoroethylene and cellular patches, moderate to severe adhesions to the lung and epicardium were clearly observed. As compared with the cellular patch, the acellular patch significantly reduced postsurgical pericardial adhesions, especially on its lung side, as a result of remesothelialization. In the presence of Rg1, a faster remesothelialization was observed on each side of the acellular/Rg1 patch. Therefore, the acellular/Rg1 patch was free of any adhesions to the lung; however, there was still a filmy adhesion to the epicardium observed in 3 of the 5 studied animals at 3 months after surgery, due to incomplete remesothelialization. CONCLUSIONS: The acellular/Rg1 patch effectively repaired pericardial defects in rabbits and successfully reduced the formation of pericardial adhesions.

Animals↗

Calcium-independent CaMKII activity is involved in ginsenoside Rb1-mediated neuronal recovery after hypoxic damage.

Recent studies have indicated that Ginsenoside Rb1, one of the major components of ginseng root, may play an important role in protecting cells from damage. Here, we investigated the neuroprotective activity of Rb1 after hypoxic injury in young rats. About 50% animals were dead by exposing hypoxic condition three times in three consecutive days. Then, the pretreatment with Rb1 prior to hypoxic stimulation reduced animal death to 12%, and also significantly reduced the recovery time from hypoxia-related, compromised symptoms in survived animals. Rb1 also significantly reduced levels of lactate dehydrogenase (LDH) release from primary hippocampal neurons which were maintained at low oxygen concentration, indicating increased neuronal survival by Rb1. Ca(2+)/calmodulin-dependent kinase II (CaMKII) activity in the hippocampal tissues of hypoxia-induced rats was decreased to about 50% of the control animal. Then Rb1-treatment prior to hypoxic stimulation significantly elevated Ca(2+)-independent kinase II activity when measured 48 hr after hypoxic stimulation. Thus, the present data suggest that calcium independent CaMKII activity may be involved in the process of ginsenoside Rb1-mediated recovery of neuronal cells after hypoxic damage.

Animals↗

Proteomic analysis effects of ginsenoside Rg1 on human umbilical vein endothelial cells stimulated by tumor necrosis factor-alpha.

Ginsenoside Rg1 (derived from ginseng root) has been found to have many vasoprotective activities. The present study was undertaken to examine effect of ginsenoside Rg1 on the secretion of nitric oxide (NO) in human umbilical vein endothelial cells (HUVECs) stimulated with or without tumor necrosis factor-alpha (TNF-alpha). We showed here that ginsenoside Rg1 can increase the basal and TNF-alpha-attenuated NO production in a dose-dependent manner. As little is known regarding the vascular molecular mechanism of ginsenoside Rg1 on HUVECs and proteomic technique has more advantages in molecular identification, we attempted to use proteomic analysis to explain vascular molecular mechanism of ginsenoside Rg1 on HUVECs. Proteomic analytical result showed that 21 protein spots were changed in TNF-alpha stimulated HUVECs, including 9 up-regulated spots, 11 down-regulated spots, and 1 spot detected in TNF-alpha stimulated group only. The expression level of proteins such as MEKK3, phosphoglycerate mutase was increased, and nitric-oxide synthase, mineralocorticoid receptor were decreased in TNF-alpha stimulated HUVECs, while ginsenoside Rg1 could prevent this change or reverse to some degree. This study suggested that NO production increased via ginsenoside Rg1 played an important role in the protective effect on TNF-alpha stimulated HUVECs and was helpful to deeply understand the active mechanism of ginsenoside Rg1 to HUVECs at the molecular level.

Blotting, Western↗

The Herbal Alternatives for Menopause (HALT) Study: background and study design.

We designed a randomized double-blind randomized trial to examine the short and long-term effects of alternative approaches commonly used to manage menopause symptoms. Women were randomly assigned to: (1) black cohosh 160 mg daily; (2) multibotanical (50 mg black cohosh, alfalfa, chaste tree, dong quai, false unicorn, licorice, oats, pomegranate, Siberian ginseng, boron) four capsules daily; (3) multibotanical plus telephone counseling to increase dietary soy; (4) conjugated equine estrogen 0.625 mg +/- 2.5 mg medroxyprogesterone acetate; or (5) placebo. Working with a skilled CAM provider helped us choose interventions that reflected naturopathic practices worthy of study. Mass mailing, with careful tracking and rapid responses to recruitment rates, was an effective and cost-effective recruitment strategy. Creativity was necessary to construct methods for blinding capsules and the dietary soy intervention. Independent testing of herbal products was vital to confirming their constituents. The Data and Safety and Monitoring Committee, and project officers at the funding agency, were critical partners in designing responses to unanticipated Women's Health Initiative findings published during the HALT trial. Careful monitoring of adverse events may provide much needed information about side effects of herbal products and supplements. Despite inherent challenges, the study of alternative therapies for menopause symptoms is a rewarding and important area deserving of further inquiry.

Cimicifuga↗

Neuroprotective effects of ginsenoside-Rg1 in primary nigral neurons against rotenone toxicity.

Ginsenoside-Rg1, the pharmacologically active component isolated from ginseng, demonstrated neuroprotective effects on primary cultured rat nigral neurons against rotenone toxicity. Rotenone, a common household pesticide known for its specific and irreversible mitochondria complex I inhibition, has been suggested to be the causal agent of Parkinson's disease (PD) by inducing degeneration of cells in the substantial nigra. The present study demonstrated that co-treatment of rotenone and Rg1 could reduce rotenone-induced cell death by 58% (SEM=+/-5.60; N=3). Rotenone-induced mitochondria membrane potential (MMP, DeltaPsim) depletion was restored and elevated by at least 38% (SEM=+/-2.15; N=3) by Rg1. In addition, Rg1 prevented cytochrome c release from the mitochrondrial membrane and increased the phosphorylation inhibition of the pro-apoptotic protein Bad through activation of the PI3K/Akt pathway. The protective effects of Rg1 was blocked by glucocorticoid receptor antagonist RU486, indicating that the action of Rg1 is mediated through glucocorticoid receptor (GR). In conclusion, Rg1 inhibits the mitochondrial apoptotic pathway and increases the survival chance of the primary cultured nigral neurons against rotenone toxicity. Thus, Rg1 and its related compounds may be developed as protective agents against neurodegenerative diseases induced by mitochondrial toxins.

Analysis of Variance↗

The anti-gastric ulcer effect of Gynostemma pentaphyllum Makino.

Gynostemma pentaphyllum is an oriental medicinal herb reputed to have broad-spectrum activities. The plant's principal saponin components are structurally similar to those found in ginseng plants and this similarity is assumed to be responsible for the claimed activities. The present study was undertaken to evaluate a G. pentaphyllum butanol fraction (GPB) for its anti-gastric ulcer activity using experimental models. Oral administration of the GPB at 200 and 400 mg/kg body wt. significantly inhibited gastric ulcer formation induced by indomethacin, HCl/EtOH and water-immersion restraint stress in rats. In pylorus-ligated rats, pretreatment with the GPB had no effect on gastric volume, pH or acidity output, thus indicating a lack of anti-secretory effect. In ethanol-induced ulcerated rats, gastric wall mucus and hexosamine content were markedly preserved by GPB pretreatment. The findings indicate that the butanol fraction of G. pentaphyllum possesses gastroprotective potential related to the preservation of gastric mucus synthesis and secretion.

Administration, Oral↗

Overexpression of squalene synthase in Eleutherococcus senticosus increases phytosterol and triterpene accumulation.

Squalene synthase (SS) catalyzes the first committed step in sterol and triterpenoid biosynthesis. Transgenic Eleutherococcus senticosus Rupr. and Maxim. plants were generated by introducing an SS-encoding gene derived from Panax ginseng (PgSS1) together with genes expressing hygromycin phosphotransferase and green fluorescent protein (GFP) through Agrobacterium-mediated transformation. Early globular embryo clusters developing from the embryogenic callus were used for Agrobacterium-mediated transformation. Transformants were selected on Murashige Skoog medium containing 25 mg/L hygromycin. Hygromycin-resistant somatic embryos developed into plants after the cotyledonary embryos were treated with 14.4 microM gibberellic acid. Transformation was confirmed by polymerase chain reaction, Southern, and GFP analyses. The SS enzyme activity of the transgenic plants was up to 3-fold higher than that of wild-type plants. In addition, GC-MS and HPLC analysis revealed that phytosterols (beta-sitosterol and stigmasterol) as well as triterpene saponins (ciwujianosides B (1), C(1) (2), C(2) (3), C(3) (4), C(4) (5), D(1) (6) and D(2) (7)) levels in transgenic E. senticosus were increased by 2- to 2.5-fold. These results suggest that the metabolic engineering of E. senticosus to enhance production of phytosterols and triterpenoids by introducing the PgSS1 gene was successfully achieved by Agrobacterium-mediated genetic transformation.

Eleutherococcus↗

Cloning and characterization of a cDNA encoding beta-amyrin synthase from petroleum plant Euphorbia tirucalli L.

Euphorbia tirucalli L., known as the petroleum plant, produces a large amount of triterpenes, such as beta-amyrin. Degenerate RT-PCR based on the sequences conserved among known beta-amyrin synthases led to cloning of a putative triterpene synthase cDNA, EtAS, from leaves of E. tirucalli. The deduced amino acid sequence of the EtAS cDNA showed the highest identity of 82% to the Panax ginseng beta-amyrin synthase. Heterologous expression of the EtAS ORF in the methylotrophic yeast, Pichia pastoris, resulted in production of beta-amyrin, revealing that the EtAS cDNA codes for a beta-amyrin synthase. This is the first report of a gene involved in the triterpene synthetic pathway from Euphorbiaceae plants.

Amino Acid Sequence↗

Discrimination of herbal medicines by molecular spectroscopy and chemical pattern recognition.

The molecular spectroscopy (including near infrared diffuse reflection spectroscopy, Raman spectroscopy and infrared spectroscopy) with OPUS/Ident software was applied to clustering ginsengs according to species and processing methods. The results demonstrate that molecular spectroscopic analysis could provide a rapid, nondestructive and reliable method for identification of Chinese traditional medicine. It's found that the result of Raman spectroscopic analysis was the best one among these three methods. Comparing with traditional methods, which are laborious and time consuming, the molecular spectroscopic analysis is more effective.

Cluster Analysis↗