Antidiabetic effects of Panax ginseng berry extract and the identification of an effective component.

We evaluated antihyperglycemic and anti-obese effects of Panax ginseng berry extract and its major constituent, ginsenoside Re, in obese diabetic C57BL/6J ob/ ob mice and their lean littermates. Animals received daily intraperitoneal injections of Panax ginseng berry extract for 12 days. On day 12, 150 mg/kg extract-treated ob/ob mice became normoglycemic (137 +/- 6.7 mg/dl) and had significantly improved glucose tolerance. The overall glucose excursion during the 2-h intraperitoneal glucose tolerance test decreased by 46% (P < 0.01) compared with vehicle-treated ob/ob mice. The improvement in blood glucose levels in the extract-treated ob/ ob mice was associated with a significant reduction in serum insulin levels in fed and fasting mice. A hyperinsulinemic-euglycemic clamp study revealed a more than twofold increase in the rate of insulin-stimulated glucose disposal in treated ob/ ob mice (112 +/- 19.1 vs. 52 +/- 11.8 micromol x kg(-1) x min(-1) for the vehicle group, P < 0.01). In addition, the extract-treated ob/ob mice lost a significant amount of weight (from 51.7 +/- 1.9 g on day 0 to 45.7 +/- 1.2 on day 12, P < 0.01 vs. vehicle-treated ob/ob mice), associated with a significant reduction in food intake (P < 0.05) and a very significant increase in energy expenditure (P < 0.01) and body temperature (P < 0.01). Treatment with the extract also significantly reduced plasma cholesterol levels in ob/ob mice. Additional studies demonstrated that ginsenoside Re plays a significant role in antihyperglycemic action. This antidiabetic effect of ginsenoside Re was not associated with body weight changes, suggesting that other constituents in the extract have distinct pharmacological mechanisms on energy metabolism.

Brief communication: American ginseng reduces warfarin's effect in healthy patients: a randomized, controlled Trial.

BACKGROUND: People using prescription medication often concurrently take herbal supplements. In a case report, the anticoagulant effect of warfarin decreased after patients consumed ginseng. OBJECTIVE: To evaluate the interactions between American ginseng and warfarin. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: General Clinical Research Center, University of Chicago, Chicago, Illinois. PARTICIPANTS: 20 healthy patients. INTERVENTION: In this 4-week study, 20 patients received warfarin for 3 days during weeks 1 and 4. Beginning in week 2, patients were assigned to receive either American ginseng or placebo. MEASUREMENTS: International normalized ratio (INR) and plasma warfarin level. RESULTS: The peak INR statistically significantly decreased after 2 weeks of ginseng administration compared with placebo (difference between ginseng and placebo, -0.19 [95% CI, -0.36 to -0.07]; P = 0.0012). The INR area under the curve (AUC), peak plasma warfarin level, and warfarin AUC were also statistically significantly reduced in the ginseng group as compared with the placebo group. Peak INR and peak plasma warfarin level were positively correlated. LIMITATIONS: The study sample consisted of young, healthy volunteers in a research setting rather than patients taking therapeutic doses of warfarin. CONCLUSIONS: American ginseng reduces warfarin's anticoagulant effect. When prescribing warfarin, physicians should ask patients about ginseng use.

Transcutaneous electrical acupoint stimulation potentiates analgesic effect of morphine.

Pain is the major complaint of patients who choose acupuncture treatment. Transcutaneous electrical acupoint stimulation (TEAS) provides a safe, standardized technique without needle insertion. TEAS can be tested with the cold-pressor test, a simple, reliable, and widely used model in humansfor the induction of tonic pain. In this controlled study, the effects of TEAS on cold-pressor-induced pain were evaluated in 20 healthy human subjects. Electrical stimulation electrodes were applied to He-Gu (LI 4) and Nui-Guan (P 6) acupoints. The effects of saline plus no TEAS, 15-minute TEAS alone, 0.05 mg/kg morphine alone, and 15-minute TEAS plus morphine were assessed. Pain score ratings were evaluated at four time points from 30 to 170 seconds during the cold-pressor test. The authors observed analgesic effects in both TEAS-alone and morphine-alone sessions, and pain score rating reductions were statistically significant compared to unstimulated control (both p < 0.01). The degree of TEAS analgesia combined with 0.05 mg/kg morphine was significantly higher than TEAS alone (p < 0.01). The results support the efficacy of TEAS analgesia and suggest that combination of TEAS with low-dose morphine can achieve better pain control in a variety of clinical settings.

Scutellaria baicalensis extract decreases cisplatin-induced pica in rats.

PURPOSE: Nausea/vomiting are significant side effects associated with the use of chemotherapy in cancer patients. Treatment of nausea/vomiting caused by cisplatin, a potent chemotherapeutic agent and one of the most emetogenic stimuli, requires a combination of different antiemetic drugs. In this study, we investigated the effects of Scutellaria baicalensis, an antioxidant herbal medicine, on cisplatin-induced nausea using a rat model. METHODS: Rats react to emetic/nausea-producing stimuli, such as cisplatin, with altered feeding habits, manifested by pica or increased consumption of kaolin (a type of clay). We measured pica in rats to quantify cisplatin-induced nausea, and to evaluate the antinausea effect of pretreatment with S. baicalensis extract (SbE) given intraperitoneally. RESULTS: Cisplatin at 3 mg/kg induced significant pica accompanied by reduced food intake, suggesting the presence of nausea. Hence, this cisplatin dose was selected for testing the antinausea activity of SbE. Cisplatin-induced pica decreased significantly when animals were pretreated with SbE at doses of 1 mg/kg and 3 mg/kg ( P<0.01). At a higher SbE dose (10 mg/kg), kaolin consumption increased, rather than further decreased, and was significantly different from that in the groups treated with low SbE doses. CONCLUSIONS: SbE pretreatment decreased cisplatin-induced kaolin intake in the rat model of simulated nausea, suggesting that SbE and its active constituent(s) may play a therapeutic role in chemotherapy-induced emesis. Absence of therapeutic effect at the highest tested SbE dose could have been a result of prooxidant activity often associated with excess antioxidant concentration.

Alternative therapies for type 2 diabetes.

Type 2 diabetes is a chronic metabolic disease that has a significant impact on the health, quality of life, and life expectancy of patients, as well as on the health care system. Exercise, diet, and weight control continue to be essential and effective means of improving glucose homeostasis. However, lifestyle management measures may be insufficient or patient compliance difficult, rendering conventional drug therapies (i.e., oral glucose-lowering agents and insulin injection) necessary in many patients. In addition to adverse effects, drug treatments are not always satisfactory in maintaining euglycemia and avoiding late stage diabetic complications. As an alternative approach, medicinal herbs with antihyperglycemic activities are increasingly sought by diabetic patients and health care professionals. Commonly used herbs and other alternative therapies, less likely to have the side effects of conventional approaches for type 2 diabetes, are reviewed.

Alternative therapies for male and female sexual dysfunction.

Sexual dysfunction is prevalent in both men and women. Although new pharmaceutical agents have been identified for male erectile problems, sexual desire and orgasm disorders, individuals with sexual dysfunction often seek alternative therapies, including traditional Chinese medicine. This article reviews currently used alternative therapies, such as herbal medications, L-arginine, acupuncture, biofeedback and others. Potential herb-drug interactions are also presented.

Analgesic effects of different acupoint stimulation frequencies in humans.

Transcutaneous electrical acupoint stimulation (TEAS) provides a convenient and standardized technique for pain treatment. The cold-pressor test is a simple and reliable model in humans for the induction of tonic pain. In this controlled study, the effects of TEAS on cold pressor-induced pain were evaluated in 22 healthy human subjects. Electrical stimulation at 4 Hz and 32 Hz was applied to He-Gu (LI 4) and Nui-Guan (P 6) acupoints for 15 minutes. Pain score ratings were evaluated at four time points from 30-170 seconds during the cold-pressor test. We observed an analgesic effect at both 4 Hz and 32 Hz of stimulation, and pain score rating reductions were statistically significant compared to control (p < 0.01). Our data support the efficacy of TEAS analgesia. However, there was no significant difference between pain scores at 4 Hz and 32 Hz stimulation.

Gastric effects of galanin and its interaction with leptin on brainstem neuronal activity.

Galanin is a 29-amino acid peptide that is widely distributed throughout the central nervous system, peripheral nervous system, and gastrointestinal and genitourinary tracts. Leptin is a hormone secreted from adipose tissue and the gut and other tissues. In this study, using an in vitro neonatal rat preparation, we investigated the gastric effects of galanin and its interaction with leptin on nucleus tractus solitarius (NTS) neurons receiving gastric vagal inputs. We showed that peripheral gastric galanin (300 nM) produced a mean inhibition response of 53.2 +/- 2.1% compared with the control level of 100% (P < 0.01) in 27 of 58 neurons tested. A concentration-dependent effect of galanin on NTS neuronal activity was observed. The galanin receptor antagonist [galanin-(1-12)-Pro3-(Ala-Leu)2-Ala amide], or M40, significantly reversed the galanin-induced inhibition effect (P < 0.01). In contrast, we showed that the peripheral gastric effect of leptin (10 nM) produced a mean activation response of 167.4 +/- 8.2% compared with the control level. The NTS neurons that we recorded could respond to both galanin and leptin or respond to only one of them. Subsequently, we evaluated gastric interactions between galanin and leptin on NTS unitary activity when galanin (100 nM) and leptin (10 nM) were applied together in the gastric compartment. We observed that the effect of leptin when applied alone (168.8 +/- 7.7%) was reduced to 146.2 +/- 4.7% after coapplication of both compounds (P < 0.05 compared with leptin alone; P < 0.01 compared with galanin alone, 55.1 +/- 3.2%). Our data suggest that galanin modulates the leptin signals, which regulate the ingestive process in neonates.

Kavalactones and dihydrokavain modulate GABAergic activity in a rat gastric-brainstem preparation.

Using an in vitro neonatal rat gastric-brainstem preparation, the activity of majority neurons recorded in the nucleus tractus solitarius (NTS) of the brainstem were significantly inhibited by GABA A receptor agonist, muscimol (30 microM), and this inhibition was reversed by selective GABA A receptor antagonist, bicuculline (10 microM). Application of kavalactones (300 microg/ml) and dihydrokavain (300 microM) into the brainstem compartment of the preparation also significantly reduced the discharge rate of these NTS neurons (39 % and 32 %, respectively, compared to the control level), and this reduction was partially reversed by bicuculline (10 microM). Kavalactones or dihydrokavain induced inhibitory effects were not reduced after co-application of saclofen (10 microM; a selective GABA B receptor antagonist) or naloxone (100 nM; an opioid receptor antagonist). Pretreatment with kavalactones (300 microg/ml) or dihydrokavain (300 microM) significantly decreased the NTS inhibitory effects induced by muscimol (30 microM), approximately from 51 % to 36 %. Our results demonstrated modulation of brainstem GABAergic mechanism by kavalactones and dihydrokavain, and suggested that these compounds may play an important role in regulation of GABAergic neurotransmission.

Anti-diabetic effects of Gymnema yunnanense extract.

In this study, we evaluated anti-hyperglycemic effect and body weight reduction activity of Gymnema yunnanense extract in obese ob/ob and diabetic db/db mice. Animals received daily intraperitoneal injections of the extract 100 mg/kg for 12 days. On Day 5, the extract-treated ob/ob mice had significantly lower fasting blood glucose levels compared to vehicle-treated mice (161+/-14.5mg/dl versus 238+/-21.5mg/dl, P<0.01). On Day 12, the extract-treated ob/ob mice had normal fasting blood glucose levels, compared with vehicle-treated mice (119+/-3.3mg/dl versus 240+/-12.9 mg/dl, P<0.01). Glucose tolerance improved significantly. This was demonstrated by overall glucose excursion calculated as area under the curve (AUC) during the 2h intraperitoneal glucose tolerance test (IPGTT), which decreased by approximately 22% (P<0.01) compared to vehicle-treated ob/ob mice. In addition, extract-treated ob/ob mice lost weight significantly from 51.7+/-1.9 g on Day 0 to 45.7+/-1.2g on Day 12 (P<0.05 compared to vehicle-treated mice). In db/db mice, after treatment with same dose of the extract, fasting blood glucose levels also decreased significantly from Day 0 of 247+/-13.9 mg/dl to Day 5 of 172+/-7.5mg/dl and to Day 12 of 190+/-2.7 mg/dl (both P<0.01 compared to vehicle-treated group from Day 0 of 239+/-12.1mg/dl to Day 5 of 230+/-8.5mg/dl and Day 12 of 247+/-18.9 mg/dl, respectively). After 12 days of extract treatment, body weight in db/db mice reduced from 61.8+/-1.4 g on Day 0 to 59.8+/-1.1g on Day 12 (P<0.05). Our results support an in vivo anti-hyperglycemic and body weight reduction activity of G. yunnanense extract that may prove to be of clinical importance in improving the management of type 2 diabetes.

Baicalein attenuates oxidant stress in cardiomyocytes.

Flavonoids within Scutellaria baicalensis may be potent antioxidants on the basis of our studies of S. baicalensis extract. To further this work, we studied the antioxidative effects of baicalein, a flavonoid component of S. baicalensis, in a chick cardiomyocyte model of reactive oxygen species (ROS) generation during hypoxia, simulated ischemia-reperfusion, or mitochondrial complex III inhibition with antimycin A. Oxidant stress was measured by oxidation of the intracellular probes 2',7'-dichlorofluorescin diacetate and dihydroethidium. Viability was assessed by propidium iodide uptake. Baicalein attenuated oxidant stress during all conditions studied and acted within minutes of treatment. For example, baicalein given only at reperfusion dose dependently attenuated the ROS burst at 5 min after 1 h of simulated ischemia. It also decreased subsequent cell death at 3 h of reperfusion from 52.3 +/- 2.5% in untreated cells to 29.4 +/- 3.0% (with return of contractions; P < 0.001). In vitro studies using electron paramagnetic resonance spectroscopy with the spin trap 5-methoxycarbonyl-5-methyl-1-pyrroline-N-oxide revealed that baicalein scavenges superoxide but does not mimic the effects of superoxide dismutase. We conclude that baicalein can scavenge ROS generation in cardiomyocytes and that it protects against cell death in an ischemia-reperfusion model when given only at reperfusion.

Grape seed proanthocyanidin extract attenuates oxidant injury in cardiomyocytes.

This study sought to test whether grape seed proanthocyanidin extract (GSPE) attenuates exogenous and endogenous oxidant stress induced in chick cardiomyocytes and whether this cytoprotection is mediated by PKC activation, mito K(ATP) channel opening, NO production, oxidant scavenging, or iron chelating effects. Cells were exposed to hydrogen peroxide (H(2)O(2)) (exogenous oxidant stress, 0.5mM) or antimycin A (endogenous oxidant stress, 100 micro M) for 2h following pretreatment with GSPE at various concentrations for 2h. Cells were also pretreated with GSPE or with inhibitors of PKC (chelerytherine), mito K(ATP) channel (5-hydroxydecanoate), nitric oxide synthase (nitro-L-arginine methyl ester) for 2h. Oxidant stress was measured by 2',7'-dichlorofluorescin diacetate and cell viability was assessed using propidium iodide. Free radical scavenging and iron chelating ability was tested in vitro. GSPE dose-dependently attenuated oxidant formation and significantly improved cell survival and contractile function. However, inhibitors of PKC, mito K(ATP) channel or NO synthase failed to abolish the protective action of GSPE during H(2)O(2) or antimycin A exposure. In vitro studies suggested that GSPE scavenges H(2)O(2), hydroxyl radical and superoxide, and may chelate iron. These results indicate that GSPE confers cardioprotection against exogenous H(2)O(2)- or antimycin A-induced oxidant injury. Its effect does not require PKC, mito K(ATP) channel, or NO synthase, presumably because it acts by reactive oxygen species scavenging and iron chelating directly.