H3Co Och Hydrastine

Aconitum fischeri Reichb., or fischer's monkshood, American aconite, bao ye wu tou, or wu tou (Chinese), is an herb that grows to a height of 1.6 m tall in China, Korea,

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Fig. 77. Aconitum fischeri Reichb.

Russia, and the Rocky Mountain region of the United States. The stem is erect and pubescent at apex. The leaves are orbicular 8-12 X 12-15 cm and deeply three- to five-lobed. The flowers are arranged in racemes, deep blue color, 8 mm long, with a spur that is slightly circinate. The fruits are 1.4 cm long follicles (Fig. 77). The drug consists of the dried rhizome. In China, the rhizome is used to treat cold, cause abortion, and as a treatment for lumbago, pox, and ulcers.

The pharmacological potential of this herb is currently unexplored. One might set the hypothesis that the plant contains aconitine and other diterpene alkaloids, such as songorine, which is common in the Aconitum species. Interestingly, songorine, is a non competitive antagonist at the GABAa receptor, which inhibits the specific binding of [3H]muscimol to GABAergic receptors with an IC50 value of 7.06 mM (116). Using electrophysiological methods, Ameri showed that songorine (1-100 ^M) enhances the excitatory synaptic transmission by agonistic action at D2 receptors (117). This effect is completely abolished by the selective dopamine D2 receptor antagonists sulpiride (0.1 (iM) and haloperidol (10 (iM) and mimicked by amantadine (100 (iM).

Coptis teeta Wall. (Coptis chinensis Franch, Coptis teeta Wall. var. chinensis Franch.), or Indian goldthread, yun nan huang lian, wang lien, or chih lien (Chinese), grows wild in China and is cultivated in Szechuan. It is an herb that grows to a height of 50 cm from a rhizome. The petioles are up to 19 cm glabrous and the blade is ovate-triangular, 6-13 cm X 6-9 cm, and membranaceous. The fruits are papery follicles of about 1 cm long (Fig. 78). The drug consists of the roots, which are said to have a bird's claw appearance. It is bitter, yellow within, and aromatic. In China, the plant is used to soothe inflamed eyes, reduce fever, treat dysentery and diabetes, promote digestion, and counteract poisoning. The root is given to newborns to prevent syphilitic poisoning and mouth sores. In Cambodia, Laos, and Vietnam, the root is used to treat leucorrhea, promote menses, heal mouth sores and ulcers, and treat conjunctivis. The root abounds with berberine and coptisine, which impart to the plant most of its medicinal properties.

The plant is regarded as a sort of panacea by Chinese doctors, and has attracted a great deal of interest for its cytotoxic and antibacterial properties. The plant was a source of berberine sulphate (British Pharmacopoeia, 1949) that was given orally as bitter and in India parenterally for the treatment of oriental sore. Berberine inhibits the enzymatic activity of sortase, with an IC50 value of 8.7 (ig/mL, and exhibits antibacterial activity against Gram-positive bacteria and could be of value as a source of clinical antiperiod-ontobacterial agent (118).

Coptis chinensis abrogates the survival of a broad spectrum of cancerous cell-lines—SK-Hep1, HepG2, and Hep3B—and berberine and coptisine inhibit the proliferation of both hepatoma and leukemia cell lines, with IC50 values ranging from 1.4 to 15.2 (ig/mL and from 0.6 to 14.1 (ig/mL, respectively. However, icariin showed no inhibition of either the hepatoma or leukemia cell lines. An extract of Coptis chinensis is cytotoxic against a broad spectrum of cancerous cell-lines—SK-Hep1, HepG2, and Hep3B—and berberine and coptisine have potent antineoplastic properties (119). Note that the anti-inflammatory property of the plant is confirmed, as an extract of the plant exhibited free radical scavenging activity (120). Both the cytotoxic and antibacterial properties are known, but much less work has been done however on the dopaminergic potentials of this herb and the genus Coptis in general.

Lee et al. made the first observation that protoberberine alkaloids from Coptis japonica Makino, such as berberine and palmatine, induced 77% inhibition on dopamine content in PC12 cells with IC50 value of 19.5 (ig/mL, and inhibited the biosynthesis catalyzed by tyrosine hydroxylase in PC12 cells with IC50 values of berberine and palmatine of 9.5 and 7.7 (ig/mL, respectively, indicating that the Coptis species—and possibly other protoberberines—and sensu lato isoquinoline-containing plants might play some role in the etiology of Parkinsonism (121). It is again interesting to note that both dopaminergic and anti-dopaminergic principles coexist in the same taxonomic group.

Fig. 79. Cimicifuga foetida L.

Surprisingly, C. chinensis attenuated the scopolamine-induced amnesia in rats when given orally for 1 week (122).

What is the role of dopamine on memory? The dopamine D3 receptor has been extensively studied in animal models of drug abuse and psychosis; however, less is known of its possible role in cognitive functions. Laszy et al. investigated the effects of different D3 antagonists and a partial agonist on spatial learning performance in a water labyrinth test, and clearly demonstrated that D3 antagonists, such as SB-277011 (24 mg/kg orally) attenuated the memory impairments caused by FG-7142, suggesting that dopamine D3 receptor antagonists have potentials in improving cognition associated with several psychiatric disorders (123).

Cimicifuga foetida L., or sheng ma (Chinese), is an herb that grows from a rhizome to a height of 2 m in China, Bhutan, India, Kazakhstan, Mongolia, Burma, and Siberia. The leaves are pinnate; the petiole grows up to 15 cm long; and the leaf blade is lobed and serrate. The flowers are 4 mm in diameter and the petals are broadly elliptic. The fruits are 8-14-cm X 2.5-5-mm follicles (Fig. 79). The drug consists of the rhizome, which is used to treat headhaches, sore throat, dysentery, measles, smallpox, ulcers, antidotal, and calming in China. The pharmacological potential of this plant is, to date, unveiled. Note that the plant elaborates a series of triterpenoid saponins and original cycloartane triterpenes, such as neocimicidine of the cycloartane (124,125).

Neocimicidine

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