Chinese herbs for dementia diseases.

In the last twenty years a considerable body of information has accumulated on the chemical constituents of Chinese herbs and their therapeutic potential. Our evaluation/systematic review [1, 2] of well-designed, randomized double blind controlled trials on Chinese herbal medicines beneficial for the improvement of cognitive function revealed a range of either single herbs or herbal mixtures that provided neuroprotective benefits. Oxidative stress may directly initiate neurodegeneration and herbal antioxidant neuroprotection is considered as a preventative and therapeutic approach. We encountered Acoris gramineus rhizome (AGR), Panax ginseng, Polygala tenuifolia and Poria cocos as the four most frequently used herbs as single/herbal mixtures that were associated with positive cognitive enhancing outcomes. This review focuses on the evidence of their medicinal effects attributed to those constituents present in relatively high concentration.

Redox chemistry of green tea polyphenols: therapeutic benefits in neurodegenerative diseases.

Evidence for the medicinal and health benefits of polyphenols in green tea for the prevention of chronic diseases such as heart disease, various types of cancer and neurodegenerative diseases is advancing. Their in vivo effectiveness and molecular mechanisms are difficult to elucidate and remain a challenging task. We review the redox responsiveness and amyloid protein perturbation biophysical properties of the major green tea polyphenol constituent (-)- epigallocatechin-3-gallate [EGCG].

Efficacy, chemistry and pharmacology of chinese herbal medicine for allergic rhinitis.

An extensive literature search identified six randomized controlled clinical trials in which the efficacy of Chinese herbal medicine had been investigated for the treatment of allergic rhinitis. Although four of these trials had methodological flaws, the therapeutic outcomes of all six have been reviewed. One of two trials considered to be of high quality was concerned with the treatment of seasonal allergic rhinitis and the other with perennial allergic rhinitis. It is considered that all six studies demonstrated various degrees of alleviation of the symptoms of allergic rhinitis. No serious side effects were reported in any of the trials. A number of the herbs in the Chinese herbal formulae used in the trials, and/or their constituent compounds have been reported to possess anti-allergic, anti-inflammatory or immune modulation activity. Such actions include inhibition of the release or action of mast cell mediators such as histamine, inhibition of inflammation induced by chemical agents, and modulation of serum IgE levels or of lymphocyte and/or macrophage activity. An aqueous, unresolved extract of the herbal formula used in one of the six trials has been reported to exhibit a range of pharmacological actions relevant to the treatment of allergic rhinitis. Essential oils, lignans, flavonoids and saponins are chemical classes that are frequently represented in individual herbs of the six Chinese herbal formulae used in the trials. The chemical structures characterising these classes of compound and the pharmacological actions of these and other constituents of the herbs, relevant to allergic rhinitis, have been reviewed.

Panax ginseng and Eleutherococcus senticosus may exaggerate an already existing biphasic response to stress via inhibition of enzymes which limit the binding of stress hormones to their receptors.

A mechanism of action for Panax ginseng (PG) and Eleutherococcus senticosus (ES) is proposed which explains how they could produce the paradoxical effect of sometimes increasing and sometimes decreasing the stress response. The mechanism suggests that this biphasic effect results from increased occupancy of positive and negative feedback stress hormone receptors by their natural ligands due to inhibition of specific enzymes which function to limit receptor occupancy. Specifically, it is suggested that PG inhibits 11-beta hydroxysteroid dehydrogenase one and ES inhibits catechol- O -methyl transferase, both of which reside in close proximity to stress hormone receptors and catalyse the degradation of stress hormones into inactive compounds. In addition, it is suggested that the increased energy said to result from PG and ES may be a consequence of their increasing the occupancy of stress hormone receptors which function to redistribute the body's energy reserves from regeneration to activity.

The effects of Eleutherococcus senticosus and Panax ginseng on steroidal hormone indices of stress and lymphocyte subset numbers in endurance athletes.

A clinical trial was undertaken to investigate the effects of Eleutherococcus senticosus (ES) and Panax ginseng (PG) on competitive club-level endurance athletes engaged in their normal in-season training. Participants were matched for training stress and received a 33% ethanolic extract (8 mL/day) containing either ES, PG (equivalent to 4 g and 2 g/day of dried root, respectively), or a placebo. A pre-test and post-test were used to evaluate the effects of six weeks of supplementation on cortisol, testosterone, and testosterone to cortisol ratio (TCR) as well as circulating numbers of total T-cells, T-helper cells (CD4), T-suppressor cells (CD8), CD4 to CD8 ratio, natural killer cells, and B lymphocytes. None of the immune system variables changed significantly nor showed any clear trend from pre to post test in any of the treatment groups. No significant change in testosterone, cortisol or TCR was observed in the PG group. In the ES group, however, TCR decreased by 28.7% from 0.0464 to 0.0331 (P=0.03). The main contribution to this decrease appeared to be a non-significant (P= 0.07) 31% trend towards increased cortisol rather than a very small non-significant (P = 0.36) 7% decrease in the calculated mean for testosterone. This result suggested that contrary to initial expectation, ES increased rather than decreased hormonal indices of stress, which may be consistent with animal research suggesting a threshold of stress below which ES increases the stress response and above which ES decreases the stress response.

Characterization of the chicken brain melatonin-binding protein using iodinated and tritiated ligands.

The melatonin-binding protein in chicken brain membranes was characterized using both [125I]-2-iodomelatonin and [3H]-melatonin as radioligands. Saturation studies conducted at 25 degrees C revealed a single class of binding site with dissociation constants of 24 +/- 4.8 pM (n = 7) and 125 +/- 21 pM (n = 6) for the iodinated and tritiated ligands, respectively. Calculation of the affinity constant using data from kinetic experiments gave values of 2.2 +/- 0.4 pM and 135 +/- 15 pM for the iodinated and tritiated ligands, respectively. Competition studies showed that the rank order of inhibition of binding by melatonin analogues was similar for both radioligands (2-iodomelatonin > melatonin > 2,3-dihydromelatonin > N-acetyl-5-methoxykynurenamine > N-acetylserotonin > 5-methoxytryptamine). The calculation of Ki, which depends upon the affinity constant, was 22 +/- 4.9 pM and 129 +/- 21 pM for 2-iodomelatonin and melatonin, respectively, when the affinity constant derived from the [125I]-2-iodomelatonin saturation experiments was used, but 4.9 +/- 1.5 pM and 33 +/- 5.5 pM when the kinetically derived constant was used. When [3H]-melatonin was used, the Ki for melatonin was 72 +/- 8 pM and 20 +/- 4.6 pM for 2-iodomelatonin and melatonin. Binding of [125I]-2-iodomelatonin to the membranes was partially reversible at 25 degrees C in contrast to the complete reversibility of [3H]-melatonin. Examination of the effects of temperature on binding indicated that at 37 degrees C both association and dissociation of both ligands were accelerated. Closer examination showed that at 37 degrees C there was a loss of approximately 40% of the [125I]-2-iodomelatonin binding sites and little influence upon the affinity of binding with time. By contrast, when [3H]-melatonin was used, the affinity decreased fourfold, with only a slight change in the number of sites. If membranes were incubated at 37 degrees C and then switched 25 degrees C, binding increased, emphasizing the fact that the binding sites were not destroyed. Whereas there appears to be little doubt that 2-iodomelatonin is a biologically active melatonin agonist, the binding of the radioactive form of this agonist to the putative melatonin receptor binding site is quite different from that of the endogenous ligand. This may have serious consequences in studies where receptor content is determined following physiological or pharmacological interventions.

Structure-activity studies of melatonin analogues in prepubertal male rats.

Comparison has been made between the activity of the pineal hormone melatonin, and several analogues and metabolites in inhibiting sexual development in a protein-restricted prepubertal rat model. Eleven melatonin analogues or metabolites were tested with the aim of evaluating the model as a test of the hypothesis that melatonin acts as a prohormone and that the ring schism metabolites (kynurenamines) mediate many of the effects attributable to melatonin. Although the hypothesis could not be confirmed, modification of the melatonin structure by lengthening the acrylamide side chain or by replacing the 5 methoxy function with fluorine resulted in loss of biological potency. Modification of the melatonin structure to block the two known points of metabolism resulted in no significant alteration in biological activity. Thus 6-chloromelatonin (blocking 6-hydroxylation) and 2,3-dihydromelatonin (blocking oxidative cleavage of the C2-C3 bond) and 6-chloro-2,3-dihydromelatonin remained biologically active. The metabolic products of brain indoleamine-2,3-dioxygenase, N-acetyl-N2-formyl-5-methoxy kynurenamine (aFoMK) and N-acetyl-5-methoxy kynurenamine (aMK), paradoxically were also biologically active.

Prolactin response in Border-Leicester x merino ewes to administration of melatonin, melatonin analogues, a melatonin metabolite and 6-methoxybenzoxazolinone.

The effect of structural modifications of the melatonin molecule on plasma half-life of the analogues and basal prolactin secretion was studied in Border-Leicester x Merino ewes. Halogenation at position 6 and/or unsaturation of the 2,3-double bond of the melatonin molecule slightly lengthened the half-life of the analogues. Melatonin, 6-chloromelatonin, 2,3-dihydromelatonin and 6-chloro-2,3-dihydromelatonin decreased plasma prolactin to 31, 45, 54 and 48% of control levels respectively when administered daily (100 micrograms at 1600 h) for 21 days. The brain metabolite of melatonin, N-acetyl-N'-formyl-5-methoxykynurenamine, and the putative natural melatonin analogue, 6-methoxybenzoxazolinone, failed to affect prolactin levels when administered in a similar manner. These results indicate that certain structural modifications to the melatonin molecule can be tolerated biologically; however, the modifications reported here still did not prevent rapid clearance from the circulation.