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Fig 1.

Structure of betulin, lupeol and betulinic acid.

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Fig 2.

Extraction and purification process.

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Table 1.

Amount of betulin, betulinic acid, lupeol and other triterpenes in fractions.

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Table 1 Expand

Fig 3.

GC-MS chromatograms of four important fractions.

B0—original extract, A1—by-product enriched with betulinic acid, L2—by-product enriched with lupeol, B5—pure betulin; BA—betulinic acid; relative detector response (Y-axis) against retention time in minutes (X-axis).

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Fig 3 Expand

Fig 4.

Images of crystals of betulin, fraction B5.

A—microphotograph of crystalline fraction; B—large crystals obtained by slow cooling; C and D—macro- and microphotographs of crystals after free evaporation of ethanol.

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Fig 5.

Crystals of fraction B5 during heating.

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Fig 5 Expand

Fig 6.

Structure of outer bark.

A—bright-field microscopy, B—fluorescence microscopy of outer bark stained by nile red.

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Fig 6 Expand

Fig 7.

Antiproliferative/cytotoxic effect.

B0—original extract, B3—fraction 3 without betulinic acid and lupeol, B4—amorphous fraction of pure betulin, B5—crystalline fraction of pure betulin, B-S—pure betulin obtained from Sigma-Aldrich. The results are given as relative values to the untreated control in percent. Cells treated with topoisomerase II inhibitor doxorubicin at 1 and 2 μM were used as positive control for decreased cell survival. Bars indicate SD in three independent experiments. *Significantly different from control (P ≤ 0.001).

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