# Remedy/Alkaloids

Historically, Zanthoxylum (Prickly ash) bark was used in traditional medicine.
Def. any "of many organic (often heterocyclic) bases that occur in nature and often have medicinal properties" is called an alkaloid.
Species identified in Nigeria contains several types of alkaloids including benzophenanthridines (nitidine, dihydronitidine, oxynitidine, fagaronine, dihydroavicine, chelerythrine, dihydrochelerythrine, methoxychelerythrine, norchelerythrine, oxychelerythrine, decarine and fagaridine), furoquinolines (dictamine, 8-methoxydictamine, skimmianine, 3-dimethylallyl-4-methoxy-2-quinolone), carbazoles (3-methoxycarbazole, glycozoline), aporphines (berberine, tembetarine, magnoflorine, M-methyl-corydine), canthinones (6-canthinone), acridones (1-hydroxy-3-methoxy-10-methylacridon-9-one, 1-hydroxy-10-methylacridon-9-one, zanthozolin), and aromatic and aliphatic amides. Hydroxy-alpha sanshool is a bioactive component of plants from the genus Zanthoxylum, including the Sichuan pepper.

## Aporphines

Aporphines include berberine and tembetarine found in Prickly ash bark.

## Benzophenanthridines

Benzophenanthridines incude nitidine, dihydronitidine, oxynitidine, fagaronine, dihydroavicine, chelerythrine, dihydrochelerythrine, methoxychelerythrine, norchelerythrine, oxychelerythrine, decarine and fagaridine found in Prickly ash bark.

## Berberine

Berberine is a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids found in such plants as Berberis, such as Berberis vulgaris (barberry), Berberis aristata (tree turmeric), Mahonia aquifolium (Oregon grape), Hydrastis canadensis (goldenseal), Xanthorhiza simplicissima (yellowroot), Phellodendron amurense (Amur cork tree), Coptis chinensis (Chinese goldthread), Tinospora cordifolia, Argemone mexicana (prickly poppy), and Eschscholzia californica (Californian poppy).
Berberine is usually found in the roots, rhizomes, stems, and bark.
The safety of using berberine for any condition is not adequately defined by evidence-based medicine, high-quality clinical research.
Its potential for causing adverse effects is high, including untoward interactions with prescription drugs, reducing the intended effect of established therapies. Berberine inhibits the CYP2D6 and CYP3A4 enzymes which are involved in metabolism of endogenous substances and xenobiotics, including many prescription drugs.
It is particularly unsafe for use in children. On the other hand, in May 2021, a comprehensive review article was published that highlighted the efficacy of berberine as a promising anti-oncogenic herpesvirus drug.
Reticuline is known as the immediate precursor of protoberberine alkaloids in plants. Berberine is an alkaloid derived from tyrosine. L-DOPA and 4-hydroxypyruvic acid both come from L-tyrosine. Although two tyrosine molecules are used in the biosynthetic pathway, only the phenethylamine fragment of the tetrahydroisoquinoline ring system is formed via DOPA, the remaining carbon atoms come from tyrosine via 4-hydroxyphenylacetaldehyde. L-DOPA loses carbon dioxide to form dopamine 1. Likewise, 4-hydroxypyruvic acid also loses carbon dioxide to form 4-hydroxyphenylacetaldehyde 2. Dopamine 1 then reacts with 4-hydroxy-phenylacetaldehyde 2 to form (S)-norcolaurine 3 in a reaction similar to the Mannich reaction. After oxidation and methylation by S-Adenosyl methionine (SAM), (S)-reticuline 4 is formed. (S)-reticuline serves as a pivotal intermediate to other alkaloids. Oxidation of the tertiary amine then occurs and an iminium ion is formed 5. In a Mannich-like reaction the ortho position to the phenol is nucleophilic, and electrons are pushed to form 6. Product 6 then undergoes keto–enol tautomerism to form (S)-scoulerine, which is then methylated by SAM to form (S)-tetrahydrocolumbamine 7. Product 7 is then oxidized to form the methylenedioxy ring from the ortho-methoxyphenol, via an O$_2$-, NADPH- and cytochrome P450-dependent enzyme, giving (S)-canadine 8. (S)-canadine is then oxidized to give the quaternary isoquinolinium system of berberine. This happens in two separate oxidation steps, both requiring molecular oxygen, with H$_2$O$_2$ and H$_2$O produced in the successive processes.

## Carbazoles

Carbazoles include 3-methoxycarbazole and glycozoline found in Prickly ash bark.

## Furoquinolines

Furoquinolines include dictamine, 8-methoxydictamine, skimmianine, and 3-dimethylallyl-4-methoxy-2-quinolone found in Prickly ash bark.

## Valerian alkaloids

Actinidine, chatinine, shyanthine, valerianine, and valerine