Inhibition of monoamine oxidase B (MAO-B) by Chinese herbal medicines.

Monoamine oxidase (MAO) catalyzes the oxidative deamination of biogenic amines accompaned by the release of H2O2. Two subtypes, MAO-A and MAO-B, exist on the basis of their specificities to substrates and inhibitors. The regulation of MAO-B activity is important in the treatment of neurodegenerative diseases. Twenty-seven species of plants used in traditional Chinese medicines, selected from an enthnobotanical survey, were used in an investigation of their inhibitory effect on MAO-B in rat brain homogenates. The 50% aqueous methanol extracts of four active extracts, Arisaema amurense, Lilium brownii var. colchesteri, Lycium chinense, and Uncaria rhynchophylla, exhibited the best activity and selectivity towards MAO-B with IC50 values of 0.44, 0.29, 0.40, and 0.03 mg/ml, respectively. A kinetic study of MAO-B inhibition by the four extracts using the Lineweaver-Burk plot for each active extract revealed the IC50 concentrations, and results show that: Ki = 0.59 mg/ml for A. amurense for the mixed-type mode, Ki = 0.58 mg/ml for L. brownii var. colchesteri for the mixed-type mode, Ki = 5.01 mg/ml for L. chinense for the uncompetitive mode, and Ki = 0.02 mg/ml for U. rhynchophylla for the uncompetitive mode. These may therefore be candidates for use in delaying the progressive degeneration caused by neurological diseases.

Free radical-scavenging activity of Taiwanese native plants.

The 70% aqueous acetone extracts of ten Taiwanese native plants were evaluated by various antioxidant assays, including 1, 1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl (.OH) radicals, and reducing power assay. In the present study, extracts of Acer buerferianum var. formosanum, Cleyera japonica var. morii, Cyclobalanopsis stenophylla var. stenophylloides, and Machilus zuihoensis exhibited stronger activity against DPPH radicals, and their IC50 values ranged from 5.4 to 8.3 microg/ml. The ten selected extracts effectively inhibited the formation of .OH generated in the Fenton reaction system. Among the extracts whose reducing power activities were determined, A. buerferianum var. formosanum, C. japonica var. morii, C. stenophylla var. stenophylloides, Eriobotrya deflex, and M. zuihoensis showed high activity. The results indicate the 70% aqueous acetone extracts of A. buerferianum var. formosanum, C. japonica var. morii, C. stenophylla var. stenophylloides, and M. zuihoensis with great potency in these assay systems and may be candidates for the development of natural antioxidants.

Monoamine oxidase B and free radical scavenging activities of natural flavonoids in Melastoma candidum D. Don.

Monoamine oxidase type B (MAO-B) activity and free radicals are elevated in certain neurological diseases. Four natural flavonoids, quercitrin, isoquercitrin, rutin, and quercetin, were isolated for the first time from the leaves of Melastoma candidum D. Don. They exhibited an inhibitory effect on MAO-B. These potent flavonoids were purified using bioassay-guided fractionation and were separated by Diaion, Sephadex LH-20, and MCI CHP20P columns. The IC(50) values of the four potent flavonoids, quercitrin, isoquercitrin, rutin, and quercetin on monoamine oxidase were 19.06, 11.64, 3.89, and 10.89 microM and enzyme kinetics analysis revealed apparent inhibition constants (K(i)) of 21.01, 2.72, 1.83, and 7.95 microM, respectively, on the substrate, benzylamine. The four potent compounds also exhibited hydroxyl radical scavenging activity as determined using a spin trapping electron spin resonance method. This suggests that the four flavonoids from M. candidum possess both MAO-B inhibitory and free radical scavenging activities. These important properties may be used for preventing some neurodegenerative diseases in the future.

Capnocytophaga bacteremia: clinical features of patients and antimicrobial susceptibility of isolates.

Capnocytophaga has been recognized as an opportunistic pathogen causing systemic infections in immunocompromised individuals with granulocytopenia and oral ulceration. Treatment of Capnocytophaga infection is often empiric. We retrospectively analyzed the clinical features of all patients with Capnocytophaga bacteremia seen at the National Taiwan University Hospital between January 1981 and December 1996 and the antimicrobial susceptibility of the isolates recovered from these patients. All the patients had underlying diseases, namely neoplastic disease (9 patients), hyperthyroidism (1), and bronchiectasis and tetralogy of Fallot (1). The clinical features of these patients were primary bacteremia (10) and pneumonia (1). Nine patients had nosocomial bacteremia and 10 patients had monomicrobial bacteremia. None had septic shock. All the patients responded well to appropriate antimicrobial therapy and survived. All isolates were susceptible to amoxicillin-clavulanate, imipenem, ciprofloxacin, erythromycin, clindamycin, tetracycline, and chloramphenicol but resistant to aminoglycosides and sulfamethoxazole-trimethoprim. The susceptibilities to penicillin, ampicillin, piperacillin, cephalosporins, and aztreonam were variable. Capnocytophaga bacteremia should be included in the differential diagnosis of febrile neutropenia in immunocompromised patients, especially in the presence of oral mucositis and ulceration.

Bacteremia due to Klebsiella oxytoca: clinical features of patients and antimicrobial susceptibilities of the isolates.

Forty-three patients with Klebsiella oxytoca bacteremia were seen between July 1980 and June 1996 at National Taiwan University Hospital (Taipei, Taiwan). We retrospectively analyzed the clinical features of these patients and the antimicrobial susceptibilities of the 43 isolates recovered from them. Twenty-seven patients (63%) had community-acquired bacteremia, and 16 patients (37%) had polymicrobial bacteremia. The clinical syndromes included hepatobiliary infections (58% of patients), primary bacteremia (23%), intravascular device-associated infections (7%), urinary tract infections (5%), skin and soft-tissue infections (5%), and peritonitis (2%). Most of these patients (93%) had underlying diseases including hepatobiliary diseases (53%), neoplastic diseases (42%), and diabetes mellitus (16%). Eight patients (19%) had septic shock, and two (5%) had disseminated intravascular coagulation. Four patients (9%) died of K. oxytoca bacteremia. All isolates were susceptible to ampicillin/sulbactam, cefmetazole, imipenem, aminoglycosides, and quinolones, and 86% of the isolates were susceptible to cefazolin.

Flavimonas oryzihabitans bacteremia: clinical features and microbiological characteristics of isolates.

Flavimonas oryzihabitans is rarely reported as a pathogen in humans. Twelve cases of F. oryzihabitans bacteremia were diagnosed at National Taiwan University Hospital over a 3-year period. The clinical features of these patients were analyzed, and antimicrobial susceptibilities and random amplified polymorphic DNA (RAPD) patterns of the 12 isolates were studied. Among these 12 patients, eight (67%) had underlying neoplastic diseases and all acquired F. oryzihabitans bacteremia while hospitalized. The clinical syndromes included primary bacteremia in 5 patients (42%), biliary tract infection in 3 (25%), and peritonitis, subdural empyema, infusion-related bacteremia, and pneumonia in 1 each. Polymicrobial bacteremia or concomitant fungemia was seen in three patients (25%). All the patients survived after antibiotic treatment. All isolates were susceptible to piperacillin, third-generation cephalosporins, aminoglycosides, and quinolones but resistant to cephalothin, cefuroxime, and trimethoprim. Susceptibility to aztreonam was variable (25%). The RAPD patterns differed among the isolates, indicating the epidemiological unrelatedness of these infections. F. oryzihabitans should be included as an etiology of severe nosocomial infection in patients with underlying debilitating diseases.