Eurycoma longifolia Jack (known as tongkat ali), a popular traditional herbal medicine, is a flowering plant of the family Simaroubaceae, native to Indonesia, Malaysia, Vietnam and also Cambodia, Myanmar, Laos and Thailand. E. longifolia, is one of the well-known folk medicines for aphrodisiac effects as well as intermittent fever (malaria) in Asia. Decoctions of E. longifolia leaves are used for washing itches, while its fruits are used in curing dysentery. Its bark is mostly used as a vermifuge, while the taproots are used to treat high blood pressure, and the root bark is used for the treatment of diarrhea and fever. Mostly, the roots extract of E. longifolia are used as folk medicine for sexual dysfunction, aging, malaria, cancer, diabetes, anxiety, aches, constipation, exercise recovery, fever, increased energy, increased strength, leukemia, osteoporosis, stress, syphilis and glandular swelling. The roots are also used as an aphrodisiac, antibiotic, appetite stimulant and health supplement. The plant is reported to be rich in various classes of bioactive compounds such as quassinoids, canthin-6-one alkaloids, β-carboline alkaloids, triterpene tirucallane type, squalene derivatives and biphenyl neolignan, eurycolactone, laurycolactone, and eurycomalactone, and bioactive steroids. Among these phytoconstituents, quassinoids account for a major portion of the E. longifolia root phytochemicals. An acute toxicity study has found that the oral Lethal Dose 50 (LD 50 ) of the alcoholic extract of E. longifolia in mice is between 1500-2000 mg/kg, while the oral LD 50 of the aqueous extract form is more than 3000 mg/kg. Liver and renal function tests showed no adverse changes at normal daily dose and chronic use of E. longifolia. Based on established literature on health benefits of E. longifolia, it is important to focus attention on its more active constituents and the constituents' identification, determination, further development and most importantly, the standardization. Besides the available data, more evidence is required regarding its therapeutic efficacy and safety, so it can be considered a rich herbal source of new drug candidates. It is very important to conserve this valuable medicinal plant for the health benefit of future generations.

Orally administered drugs may be metabolized by intestinal microbial enzymes before absorption into the blood. Accordingly, coadministration of drugs affecting the metabolic activities of gut microbes (e.g., antibiotics) may lead to drug-drug interactions (DDI). In this study, gut microbiota-mediated DDI were investigated by studying the pharmacokinetics of lovastatin in antibiotic-treated rats. Incubation of lovastatin with human and rat fecalase preparations produced four metabolites, M1 (demethylbutyryl metabolite), M4 (hydroxylated metabolite), M8 (the active hydroxy acid metabolite), and M9 (hydroxylated M8), indicating involvement of the gut microbiota in lovastatin metabolism. The plasma concentrationtime profiles of M8 were compared after oral administration of lovastatin to control rats or those treated with either ampicillin (100 mg/kg) or an antibiotic mixture consisting of cefadroxil (150 mg/kg), oxytetracycline (300 mg/kg), and erythromycin (300 mg/kg). Pharmacokinetic analyses indicated that systemic exposure to M8 was significantly lower in antibiotic-treated rats compared with controls. In addition, fecal M8 formation decreased by 58.3 and 59.9% in the ampicillin-and antibiotic mixture-treated rats, respectively. These results suggested that antibiotic intake may reduce the biotransformation of orally administered drugs by gut microbiota and that the subsequent impact on microbiota metabolism could result in altered systemic concentrations of either the intact drug and/or its metabolite(s).

These results showed that antibiotic intake might increase the bioavailability of amlodipine by suppressing gut microbial metabolic activities, which could be followed by changes in therapeutic potency. Therefore, coadministration of amlodipine with antibiotics requires caution and clinical monitoring.

Traditional herbal medicines have been processed to enhance their therapeutic effects, remove or reduce toxicity and side effects, and facilitate preparation and storage. In addition, the increased biological activities have been thought to be closely related to the compounds which are modified through processing.1-3) Therefore, there has been a growing interest in the bioactive constituents of herbal drugs modified by processing. [4][5][6] The root of ginseng, Panax ginseng C.A. MEYER (Araliaceae), has been heat processed to make white ginseng (WG, roots dried after peeling) and red ginseng (RG, steamed at 98-100°C and dried ginseng roots without peeling) for consumption. Especially, RG is more common as a functional food than WG in Asian countries, because steaming induces a change in the chemical constituents and enhances the biological activities of ginseng. [7][8][9][10] Recently, a method to increase the RG-specific ginsenosides by steaming WG at a higher temperature than RG was developed.2,11) This heat processed ginseng is termed sun ginseng (SG), and we have been investigating its enhanced free radical scavenging activity compared to conventional ginsengs and its active constituents.Phenolic compounds and maltol were responsible for the increased free radical scavenging activities of SG. In addition, Maillard reaction products (MRPs) were also thought to be related to the increased antioxidant activity of ginseng by heat processing, 5,6) because the Maillard reaction has been thought to be the major source correlated with increased efficacy by heat processing in various crude drugs or foods. 12,13) On the other hand, ginsenoside is one of the easily changeable components of ginseng by heat processing, 2,14) but heat processing-induced chemical and activity changes of ginsenosides considering the Maillard reaction have not yet been fully elucidated. In addition, the contents of less-polar ginsenosides Rg 3 , Rk 1 , Rg 5 , and maltol are known to increase by heat processing, and these compounds are supposed to be produced by the deglycosylation of diol-type ginsenosides and the Maillard reaction in ginseng by steaming. 6,14) Therefore, there is a need to investigate the structure and activity changes of isolated ginsenosides by heat processing with amino acids.In this study, we investigated the hydroxyl radical (· OH) scavenging activity changes of ginsengs and ginsenoside-Rb 2 (Rb 2 ) by heat processing using an electron spin resonance spectrometer (ESR). No report has compared the · OH scavenging activities of WG, RG, and SG using ESR, and ESR is thought as a versatile tool to detect free radicals even with slightly insoluble ginsenosides in suspension. In addition, Rb 2 , a well known diol-type triterpene glycoside that exists abundantly in Panax ginseng, was steamed with glycine, a frequently used amino acid in the Maillard reaction model system, 15) and the chemical and · OH scavenging activity changes were analyzed and compared. Shillim-Dong, Kwanak-gu, Seoul 151-742, Korea. Received October 7, 20...

Hesperidin is a biologically active flavanone glycoside occurring abundantly in citrus fruits. In the present study, effects of intestinal microflora on pharmacokinetics of hesperidin were investigated using a pseudo-germ-free rat model treated with antibiotics. After administration of hesperidin to rats, hesperetin, hesperetin glucuronides, and metabolites postulated to be eriodictyol, hemoeriodictyol, and their glucuronides were detected in urine while hesperetin glucuronide was predominantly found in plasma. The plasma concentration-time profile of hesperetin was compared between non-antibiotic-exposed and pseudo-germ-free rats administered this compound. The maximal concentration (C(max)) values of hesperetin in non-antibiotic-exposed and pseudo-germ-free rats were 0.58 and 0.20 μg/ml, respectively, and area under the curve (AUC) values were 6.3 and 2.8 μg-h/ml, respectively. Thus, systemic exposure as evidenced by AUC and C(max) was significantly higher in normal compared to pseudo-germ-free rats. Fecal β-glucosidase activities of non-antibiotic-exposed and pseudo-germ-free rats were 0.21 and 0.11 nmol/min/mg, while fecal α-rhamnosidase activities were 0.37 and 0.12 nmol/min/mg, respectively. The rate of hesperidin transformation to hesperetin was 6.9 and 2.9 nmol/min/g in fecal samples in non-antibiotic-exposed and pseudo-germ-free rats, respectively. Taken together, these results showed that pharmacokinetic differences between non-antibiotic-exposed and pseudo-germ-free rats may be attributed to differing hesperidin uptake, as well as alterations in metabolic activities of intestinal flora.

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