Pyrrolizidine Alkaloids of Boraginaceae Family and Safety Assessment of Acute Toxicity

INTRODUCTION. Plants of Boraginaceae family (Pulmonaria mollis, Nonea rossica, Onosma simplicissima, and Cynoglossum officinale) are widespread over the Russian Federation and are promising sources of phytomedicines with important pharmacological properties, such as antimicrobial, antianaemic, anticoagulant etc. Currently, Boraginaceae are not classified as officinal plants, presumably due to pyrrolizidine alkaloids (PA) that can cause hepatotoxic effect.

AIM. This study aimed to assess safety using Boraginaceae plants based on acute toxicity and content of pyrrolizidine alkaloids.

MATERIALS AND METHODS. The research objects were dried herbs of Pulmonaria mollis, Nonea rossica, Onosma simplicissima, and Cynoglossum officinale, collected from flowering plants in Novosibirsk region over 2023–2024. The composition and amount of alkaloids in alcohol extracts were determined by high-performance liq­uid chromatography with diode array and mass-spectrometry detection with electrospray ionisation. Acute toxicity was tested in vivo in 102 mature male and female CD-1 mice weighing 24.0±2.0 g, aged 12 weeks, taken from Conventional Animal Vivarium of Scientific Center of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences. The animals received a single dose of dried study extracts diluted in distilled water at 5 g/kg.

RESULTS. The absence of PA in P. mollis herb was established, alongside with its trace amounts (0.01 μg/g) in P. mollis leaves. In other studied plant species, PA, such as enantiomers of intermedine, lycopsamine and their deriva­tives were found: O. simplicissima herb — 1.07±0.03 μg/g, N. rossica herb — 8.25±0.08 μg/g; in C. officinale herb — 676.3±7.4 μg/g. Assessed acute toxicity made it possible to classify dry extracts from P. mollis herbs and leaves, N. rossica herb and O. simplicissima herb as toxicity class 5, and C. officinale herb as toxicity class 4.

CONCLUSIONS. Study doses of extracts taken from herbs and leaves of P. mollis are non-toxic. For extracts from O. simplicissima and N. rossica herb, further research is relevant to determine toxicity in prolonged use. Extracts from C. officinale herb are toxic and cannot be used per os.

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