In traditional Chinese medicine, different medicinal herbs are used in combination to increase therapeutic benefits and reduce side effects often through antagonisms and synergisms. A combination composed of Radix Bupleurum Chinese DC (“B”), Rhizoma Corydalis yanhusuo WT Wang (“Y”), Caulis Polygonum multiflorum Thunb (“P”) and Flos Albizia julibrissin Durazz (“A”) was previously found by us to be effective in anxiolysis. In this study, the anti-oxidant and anti-neuroinflammation effects of various combinations of these four herbs were examined in a D-galactose induced murine accelerated-aging model. Oral administration of some of the herbal combinations brought about significant improvement in spatial memory in the Y-maze test, reduction of brain levels of the pro-inflammatory cy...[ Read more ]

In traditional Chinese medicine, different medicinal herbs are used in combination to increase therapeutic benefits and reduce side effects often through antagonisms and synergisms. A combination composed of Radix Bupleurum Chinese DC (“B”), Rhizoma Corydalis yanhusuo WT Wang (“Y”), Caulis Polygonum multiflorum Thunb (“P”) and Flos Albizia julibrissin Durazz (“A”) was previously found by us to be effective in anxiolysis. In this study, the anti-oxidant and anti-neuroinflammation effects of various combinations of these four herbs were examined in a D-galactose induced murine accelerated-aging model. Oral administration of some of the herbal combinations brought about significant improvement in spatial memory in the Y-maze test, reduction of brain levels of the pro-inflammatory cytokines tumor necrosis factor-alpha and interleukin-6 and the oxidative stress marker malondialdehyde, as well as prevention of loss of whiskers, suggesting their potential utility for the prevention and/or treatment of physiological changes incurred by normal aging or age-related neurodegenerative diseases. Some of the herbal combinations also induced anxiolysis and/or sedative effects applicable to the treatment of sleep disorders. Notably, synergisms and antagonisms between the component herbs of some combinations were observed with respect to their anxiolytic and sedative effects. Such removal of sedative effects through antagonisms from the BYP, BY, BP, YP, and BYPA formulas will facilitate their usage as anti-oxidant and anti-neurodegenerative agents on a chronic basis. Over the range of dosages examined, all the herbal combinations were devoid of significant side effects in the form of altered locomotor activity, decreased muscle coordination and anterograde amnesia.

The racemate dl-tetrahydropalmatine (dl-THP), one of the major active constituent of Rhizoma Corydalis yanhusuo WT Wang, is known for its analgesic and sedative effects and has been shown to be a potential agent for the treatment of anxiety. In the present study, dl-THP, l-THP, and d-THP were compared regarding their anxiolytic and antidepressant properties in ICR mouse behavioral models. Low-dose l-THP exhibited much greater anxiolytic potencies in the elevated plus-maze (0.1-2.5 mg/kg) and antidepressant potencies in the tail suspension test (0.5-5.0 mg/kg) than dl-THP, whereas d-THP was inactive in either of these tests. Moreover, l-THP enhanced the sociability and preference for social novelty at 0.1-0.5 mg/kg and inhibited amphetamine-induced manic-like hyperactivity at 0.05-0.2 mg/kg. These effects of l-THP were unaccompanied by locomotor and myorelaxant side-effects and pointed to the potential of l-THP as a potential therapeutic agent for anxiety, depression and bipolar disorders. While the anxiolytic and antidepressant effects of low-dose l-THP were inhibited by co-administration of flumazenil, a GABA_A receptor benzodiazepine site antagonist, the binding affinity of l-THP was high for D2-like receptors but low for GABA_A receptors, suggesting that the observed anxiolytic and antidepressant activities of l-THP at dosages more than 20 times lower than those reported for analgesic, antinociceptive and anti-posttraumatic stress disorder activities could be mediated by dopaminergic-GABAergic circuits with downstream GABAceptive neurons. Since its effective dosage range employed herein is much lower than the dosage range for its approved clinical usage as an analgesic, l-THP represents a promising drug candidate for a spectrum of neuropsychiatric disorders with a wide safety window.