Berberis berberine from

Figures 3 and 4. Structures of hyperforin from Hypericum perforatum L. and berberine from Berberis vulgaris...

Its earliest isolation under the name xanthopicrit by Chevalier and Pelletan (177) from Zanthoxylum caribaeum is of historical interest only. The subsequent isolation under the name of berberine from Berberis vvlgaris (180) and its further examination by Fleitmann (181) served only to facilitate the work of Perrins (167), who not only determined the correct formula, C20H19O6N, but showed that the products from the two sources were identical. 

The reaction of oxyberberine (58) and berberine (15) with dichlorocarbene has been previously reviewed (11). An interesting product was the keto lactam 189, which was obtained from 58 via the adduct 188 (Scheme 34) (105). This product was later isolated from Berberis darwinii and named magallanesine (106) however, this alkaloid has since been shown to be an artifact (107). 

STEFFENS, P., NAGAKURA, N., ZENK, M.H., Purification and characterization of the berberine bridge enzyme from Berberis beaniana cell cultures, Phytochemistry, 1985, 24, 2577-2583. 

Berberine was isolated for the first time from Berberis vulgaris L. (472). The pharmacological properties of berberine resemble those of... 

The extract from Berberis vulgaris as well as that of the alkaloids berberine, oxyacanthine, berbamine, jatrorrhizine, and columbamine stimulate secretion of the bile (480, 481). The strongest effect was produced by berberine, followed by berbamine and oxyacanthine. The choleretic effect of berberine was also studied by Vartazaryan (482). Turova et al. (483) examined the effect of berberine on 225 patients with chronic cholecystitis. Peroral doses of 5-20 mg three times daily before meals over a period of 24-48 hours caused disappearance of the clinical symptoms, decrease in the level of bilirubin, and increase in the bile volume in the gall bladder. Berberine also had a favorable effect in patients with toxic hepatitis induced by intoxication. No side effects were observed on the liver functions or the blood composition. The effect of berberine on the stimulation of bile secretion was also studied by Samaj et al. (484). 

S)-Reticuline is a branch-point intermediate in the biosynthesis of most BAs. Most work has focused on branch pathways leading to the benzophenanthridine (e.g., sanguinarine), protoberberine (e.g., berberine), and morphinan (e.g., morphine and codeine) alkaloids.19 Most enzymes involved have been isolated, many have been purified, and four corresponding cDNAs have been cloned.19 The first committed step in benzophenanthridine and protoberberine alkaloid biosynthesis involves the conversion of (S)-reticuline to (5)-scoulerine by the berberine bridge enzyme (BBE) (Fig.7.2). BBE was purified from Berberis beaniana,20 corresponding cDNAs were cloned from E. californica and B. stolonifera,21 22 and BBE genes have been isolated from P. somniferum and E. californica.23,24... 

Protoberberines Berberine (umbellatine) (MD—Phe C5N C5N Phe) (DNA-binding cytotoxic, adrenergic receptor antagonist and AChE inhibitor from Berberis vulgaris (Berberidaceae) and other plants). 

Figure 2.6 Biosynthesis of berberine from (5)-reticuline in Berberis species and Coptis japonica. BBE, berberine bridge enzyme SCMT, (5)-scoulerine-9-0-methyltransferase CAS, (5)-canadine synthase STOX, tetrahydroberberine oxidase COX, enzyme found in Coptis japonica.

S)-canadine can act as a substrate for the tetrahydroberberine oxidase (STOX) enzyme isolated from Berberis and may be converted by this enzyme to berberine (Zenk, 1995) however, the oxidase found in Coptis japonica (COX)... 

The formation of the methylenedioxy bridge in Berberis has been found to be caused by the demethylating activity of a peroxidase (POD) found within the vesicle. It was also found that the cytochrome P450-requiring enzyme (canadine synthase) from microsomes of Berberis, Thalictrum and Coptis species formed the methylene bridge in (S)-tetrahydrocolumbamine (Ikezawa et al, 2003), but not in the quaternary alkaloid columbamine (Galneder et al, 1988 Zenk, 1995). Because of the substrate specificity of canadine s)mthase, the berberine pathway is considered to be that presented in Fig. 2.5 (Rueffer and Zenk, 1994). Columbamine, once proposed as an alternative route to berberine, is however converted to palmatine by a specific methyltransferase first isolated from Berberis wilsoniae cell cultures (Rueffer and Zenk, 1985 Ikezawa et al, 2003). 

Figure 10. The structure of 5 -methoxyhydnocarpin-D, an MDR inhibitor isolated from Berberis species that enhances the antibacterial activity of berberine.

A new method of bioactivity-directed fractionation, based on multidrug resistant pump (MDR) inhibition in Staphylococcus aureus, was reported for medicinal plants. This work resulted in the isolation, from berberine-containing Berberis species, two compounds that are themselves devoid of antibacterial activity, but that form potent synergistic couples with a sub-inhibitory concentration of berberine. The bacterial MDR pump inhibitors were identified as the flavonolignan 2 and the porphyrin 3 [98]. The isoflavones not only enhanced the antibacterial activity of the natural product, berberine. Fig. 4, but also the activity of synthetic... 

Miers), Menivpemwceacs Breslau, Arch. Pharm. 245, 586 (1908) Spatb, Burger, Ber. 59, 1486 (1926) Reed, Diss. Abslr. 23, 3638 (1963) from Berberis lambertii R. N. Parker, Berberidaceae Chatterjee, Banerjee, J. Indian Chem, Soc. 30, 705 (1953). Synthesis from berberine Cava, Reed, J. Org. Chem. 32, 1640 (1967). 

Scoulerine (145 R = H), the main constituent of Argemone albiflora, had not been previously obtained from Argemone species.The previously named alkaloid HF 1 isolated from Hunnemannia fumariaefolia was found to be identical with ( —)-scoulerine. The co-occurrence of (— )-tetrahydropalmatine (145 R = Me) and (-f )-armepavine in Argemone turnerae has been established for the first time.The isolation and characterization of two artefact alkaloids, berberine chloroform (146 R + R = CH2 R = H,CCl3) and palmatine chloroform (146 R = R = Me, R = H,CCl3), from Berberis lycium have... 

The biosynthesis of protoberberine alkaloids, including berberine, has been extensively studied, and all the enzymes of the biosynthetic pathway have been characterized (11,121,391,508). Interestingly the pathway leading to berberine in Berberis was found to be different from that in Coptis and Thalictrum (509). In the former species berberine is formed from columbamine, in the latter plant species from tetrahydroberberine (121). The production of isoquinoline alkaloids, including the protoberberine alkaloids, by plant cell cultures have been reviewed by Riiffer (390) and Ikuta (510). Table XXVI summarizes patents concerning the production of berberine by means of plant cell cultures. In Table XXVII a summary is given of the occurrence of berberine in some plant cell cultures. 

Nevertheless in 1985 an oxidase was reported from crude extracts of Coptis japonica cell cultures with different properties as compared to the enzyme from Berberis. This led to a systematic comparison of the two cell cultures concerning the last steps of the berberine biosynthesis. The purified oxidase from... 

Freile ML, Giannini F, Pucci G, Sturniolo A, Rodero L, Pucci O, Balzareti V, Enriz RD (2003) Antimicrobial activity of aqueous extracts and of berberine isolated from Berberis heterophylla. Fitoterapia 74(7-8) 702-705... 

Soffar SA, Metwali DM, Abdel-Aziz SS, el-Wakil HS, Saad GA (2001) Evaluation of the effect of a plant alkaloid (berberine derived from Berberis aristata) on Trichomonas vaginalis in vitro. J Egypt Soc Parasitol 31 893-904... 

Berberine was first isolated from Berberis vulgaris, a shrub of Berberidaceae (21). Since then this alkaloid has been isolated from many plants, namely Annonaceae, Ranunculaceae (mostly herbaceous), Berberidaceae, Menispermaceae, and Papaveraceae (Fumariaceae) (mostly herbaceous). 

Seen together, the transport of berberine in roots and rhizomes of Coptis and Thalictrum is dominated by the activities of transporters at the plasm membrane and the tonoplast. These mechanisms are in contrasting with observations from Berberis, where the transfer of the alkaloid to the vacuole most probably occurs in ER derived vesicles that contain the final enzyme of berberine biosynthesis (Bock et al., 2002). It appears that vesicular transfer is employed in plants that synthesize and store berberine in the same cells, whereas the above berberine carriers serve the intercellular transfer of this alkaloid in plants that established a spatial separation of alkaloid formation and storage (Shitan and Yazaki, 2007). 

Employing labeled A-norlaudanosolines it has been shown that it is the precursor of papaverine, the hydrophenanthrene alkaloids (IIB), and reticuline (203) in Papaver somniferum. Laudanosoline itself was found to be incorporated into berberine in Berberis japonica, the carbon atom 8 of the latter base originating from the A-methyl group of the former (198). 

Although some alkaloids of this type show pharmacological activity, very few of them have been used then ieutically. Berberine, isolated from Berberis vulgaris, has antimicrobial and protozoodde activity. The biogenesis of scoulerine, a tetrahydroprotoberbmine alkaloid, is shown in Scheme 11. This type of alkaloid has been reviewed (48-50). 

Berberine, 162, 169, 170, 171, 287, 328, 329, 331, 344, 345, 631 Berberine, quaternary ammonium bases from tetrahydro-derivative, 337 Berberine and related bases, pharmacological action, 345 syntheses, 334 Berberineacetone, 333 cptBerberine, 297 profoBerberine, 336 4-Berberines, 335 Berberinium hydroxide, 333 Berberinol, 333 Berberis spp., 328, 331, 346 Berberoline, 332 Berberonic acid, 507 Berberrubine, 329, 343 Berbine, 336 Betaine, 518 Bicucine, 170, 209... 

Chandra, P. and Purohit, A. N. 1980. Berberine contents and alkaloid profile of Berberis species from different altitudes. Biochem. Syst. Ecol. 8 379-380. 

Barberry root is a yellow-red dye that has been used since prehistoric times it is extracted with hot water from the stems, bark, and roots of Berberis vulgaris, a bush that grows indigenously in Europe as well as in North America. The coloring matter in the dye is the organic compound berberine. Silk and wool can be dyed directly with barberry root, yielding a yellow color however, for dyeing cotton, a mordant is required to attach the dye to the substrate fibers. 

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