Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions.

Herbal medicinals are being used by an increasing number of patients who typically do not advise their clinicians of concomitant use. Known or potential drug-herb interactions exist and should be screened for. If used beyond 8 weeks, Echinacea could cause hepatotoxicity and therefore should not be used with other known hepatoxic drugs, such as anabolic steroids, amiodarone, methotrexate, and ketoconazole.

However, Echinacea lacks the 1,2 saturated necrine ring associated with hepatoxicity of pyrrolizidine alkaloids. Nonsteroidal anti-inflammatory drugs may negate the usefulness of feverfew in the treatment of migraine headaches. Feverfew, garlic, Ginkgo, ginger, and ginseng may alter bleeding time and should not be used concomitantly with warfarin sodium. Additionally, ginseng may cause headache, tremulousness, and manic episodes in patients treated with phenelzine sulfate. Ginseng should also not be used with estrogens or corticosteroids because of possible additive effects. Since the mechanism of action of St John wort is uncertain, concomitant use with monoamine oxidase inhibitors and selective serotonin reuptake inhibitors is ill advised. Valerian should not be used concomitantly with barbiturates because excessive sedation may occur. Kyushin, licorice, plantain, uzara root, hawthorn, and ginseng may interfere with either digoxin pharmacodynamically or with digoxin monitoring. Evening primrose oil and borage should not be used with anticonvulsants because they may lower the seizure threshold. Shankapulshpi, an Ayurvedic preparation, may decrease phenytoin levels as well as diminish drug efficacy. Kava when used with alprazolam has resulted in coma. Immunostimulants (eg, Echinacea and zinc) should not be given with immunosuppressants (eg, corticosteroids and cyclosporine). Tannic acids present in some herbs (eg, St John wort and saw palmetto) may inhibit the absorption of iron. Kelp as a source of iodine may interfere with thyroid replacement therapies. Licorice can offset the pharmacological effect of spironolactone. Numerous herbs (eg, karela and ginseng) may affect blood glucose levels and should not be used in patients with diabetes mellitus.
Miller LG
Department of Pharmacy Practice, Texas Tech University Health Sciences Center, Amarillo 79121, USA.

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Benfotiamine Prevents Postprandial Symptoms in Diabetes

NEW YORK (Reuters Health) Sept 22 - Benfotiamine prevents the endothelial dysfunction and oxidative stress that follow a meal rich in advanced glycation end (AGE) products in type 2 diabetics, according to a report in the September issue of Diabetes Care.

"Benfotiamine was used for decades as a treatment of diabetic neuropathy, without any exact knowledge of the beneficial mechanism," Dr. Alin Stirban from Ruhr-University, Bochum, Germany told Reuters Health. "Our data bring benzoctamine from the relatively restricted field of diabetic neuropathy into the much larger field of vascular function and prove in humans effects previously postulated."

Dr. Stirban and colleagues investigated the effects of a real-life, cooked, AGE-rich meal on endothelial function and oxidative stress with or without benfotiamine pretreatment in 13 adults with type 2 diabetes.

The high-AGE meal significantly impaired endothelium-dependent vasodilatation, the authors report, but this impairment was completely prevented by benfotiamine.

The high-AGE meal, with or without benfotiamine pretreatment, did not affect endothelium-independent vasodilatation, the results indicate.

Benfotiamine pretreatment also prevented the decrease in reactive hyperemia and the increase in circulating markers of endothelial dysfunction, inflammation, and oxidative stress seen after a high-AGE meal, the researchers note. The beneficial effects of benfotiamine treatment were accompanied by lower serum levels of AGEs and dicarbonyls, the report indicates.

"Our study does not completely elucidate the mechanisms through which benfotiamine prevents postprandial vascular dysfunction but raises some hypotheses," the authors conclude. "Further studies are warranted to bring light into these subtle mechanisms."

"We intend to investigate in a placebo-controlled manner medium-term effects of benfotiamine on endothelial function," Dr. Stirban said. "But we will extend our observation also on other cell types of critical importance for people with diabetes, such as adipocytes."

Diabetes Care 2006;29:2064-2071.
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Effect of Diabecon on sugar-induced lens opacity in organ culture: mechanism of action.

Cataract is the leading cause of blindness worldwide. Apart from ageing, diabetes has been considered to be one of the major risk factors of cataract. The high sugar levels in diabetes may cause tissue disruption and intumescences by osmotic changes induced via aldose reductase (AR) mediated polyol pathway.

Therefore, agents that can inhibit AR and prevent sorbitol accumulation may be helpful to combat sugar-induced cataract. In the present study, AR inhibitory activity of Diabecon (an herbal drug used for diabetes) was studied together with its effect against sugar-induced lens opacity in organ culture. Diabecon aqueous extract (DAE) showed potential inhibitory activity with an IC50 value of 10 microg/ml against rat lens AR. Incubation of goat lens with supraphysiological concentrations of glucose (100 mM) led to the loss of lens transparency associated with increased AR activity, decreased soluble protein and increased protein carbonyls and glycation. Addition of DAE (0.3 mg/ml) to the medium preserved transparency and ameliorated the decrease in lens soluble protein due to hyperglycemia and also prevented the formation of glycated protein. Interestingly DAE inhibited aldose reductase activity in lens incubated with 100 mM glucose. DAE decreased protein carbonyls, prevented the loss of beta(L)-crystallin against 100 mM of glucose. We have also demonstrated here that most of these effects are mainly due to Gymnema sylvestre, one of the constituent herbs of Diabecon. These results suggest that Diabecon protect the lens against sugar-induced cataract by multiple mechanisms.
Moghaddam MS ; Kumar PA ; Reddy GB ; Ghole VS
Biochemistry Division, Department of Chemistry, University of Pune, Pune 411007, India

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