Free-radical scavenging and mitochondrial antioxidant activities of Reishi-Ganoderma lucidum (Curt: Fr) P. Karst and Arogyapacha-Trichopus zeylanicus Gaertn extracts.

Endogenous damage to mitochondrial DNA by free radicals is believed to be a major contributory factor to aging. The current study examined the effects of the extracts of two important anti-fatigue and rejuvenating medicinal herbs Ganoderma lucidum and Trichopus zeylanicus for their free-radical scavenging property and for their effects on liver mitochondrial antioxidant activity in aged mice. Both extracts were administrated orally to aged BALB/c mice at doses of 50 and 250 mg/kg body weight for 15 days. Super oxide dismutase (SOD) and catalase (CAT) activity and levels of reduced glutathione (GSH) and lipid peroxidation as equivalents of malondialdehyde (MDA) formed were determined. Groups of young mice and aged mice (more than 15 months old) were taken as controls. Both G. lucidum and T. zeylanicus extracts increased antioxidant status in liver mitochondria of aged mice compared with the aged control. Higher levels of GSH, increased activity of SOD and CAT, and decreased level of MDA in both treated groups compared with the controls were evident. Both extracts possessed significant 2,2-diphenyl-1-picrylhydrazil (DPPH), 2, 2'-azinobis (3-ethylbenzothiazolin-6-sulphonic acid) (ABTS) radical scavenging activities and ferric reducing antioxidant power (FRAP). The DPPH, ABTS, and FRAP activities were higher in G. lucidum extract than in T. zeylanicus. G. lucidum extract also showed superoxide and hydroxyl radical scavenging activities. T. zeylanicus had significantly higher lipid peroxidation inhibiting activity than G. lucidum. Thus, we conclude that the antioxidative effect of the G. lucidum extract was higher than that of T. zeylanicus. Our findings suggest a potential therapeutic efficacy of G. lucidum extract to protect against aging and to a certain extent against age-related degenerative diseases.

A potent and selective tacrine analog--biomembrane permeation and physicochemical characterization.

Cholinesterase inhibitors have been used for years in treatment of Alzheimer's disease (AD). Tacrine is the first acetylcholinesterase inhibitor approved for treating AD by the regulatory agencies around the world. Unfortunately, a number of studies have shown tacrine to be associated with some severe side effects, including hepatotoxicity. These adverse effects may be attributed to its poor selectivity for acetylcholinesterase and have thus necessitated the research and development of more selective cholinesterase inhibitors with a greater specificity and higher potency. The heptylene-linked bis-tacrine analog (bis-THA) of Tacrine is a second-generation inhibitor of acetylcholinesterase, which has a potency that is 1000 times more potent than Tacrine in inhibition of the rat brain acetylcholinesterase and 10,000 times more selective for acetylcholinesterase over butyrylcholinesterase. A series of investigations have thus been initiated to characterize the physicochemical properties (e.g., pKa, partition coefficient, and stability) of this bis-THA analog as compared to its parent molecule (Tacrine). For AD treatment, the cholinesterase inhibitors need to be taken daily for long periods of time. Use of controlled-release dosage forms to deliver drugs for chronic administration, by taking advantage of their rate-controlling drug delivery features, has gained increasing popularity in recent years. On the other hand, the nasal route, which has been used to deliver drugs for achieving a direct delivery to the brain (via the olfactory pathway), could offer the benefits of brain targeting to the delivery of Tacrine and bis-THA. To investigate this feasibility, the permeation of Tacrine and bis-THA across the nasal mucosa was evaluated (in comparison with other absorptive mucosae). Studies of their permeation kinetics across the various absorptive mucosae, which were freshly excised from the domestic pig, indicated that the nasal mucosa could present a viable pathway for the systemic delivery of bis-THA. Delipidization studies suggested that the lipophilic components in the absorptive mucosae could play an important role in the permeation of bis-THA. The bis-THA has a pKa of approximately 8 and its partition coefficient showed a sigmoidal pattern with solution pHs. It was found to be relatively stable at acidic pHs but subjected to a base-catalyzed degradation at the alkaline pHs (> or = 8) and at higher temperatures (> or = 50 degrees C).