Symptom → Plant Sources
Birch (Betula pendula) as a tool for helping with Cancer (anticancer research)
inferred from anticancer action
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Flavonoids are bioactive secondary metabolites of plants, which exert anti-cancer effects. However, metabolism in enterocytes and the liver can influence the biological activity of flavonoids contained in the diet. Therefore, results from in vitro studies on cancer cells from the digestive tract and liver may reflect the real effects in the human body. Previously, we have found that the extract from birch buds exerts antiproliferative activity in a panel of cancer cells. In the present study, the anti-cancer activity of ten flavonoids isolated from the buds of Betula pubescens and Betula pendula was characterized. Among them, santin and cirsimaritin significantly reduced viability, proliferation and clonogenicity of gastric (AGS), colon (DLD-1) and liver (HepG2) cancer cells. Both flavonoids induced apoptosis, accompanied by activation of caspase-3, caspase-7, caspase-8 and caspase-9. Moreover, upregulation of p53 was detected only in wild-type p53 harbouring cells. Together, our results suggest that santin and cirsimaritin exhibit promising anti-cancer activity in cultures of digestive system cancer cells.
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Mechanistic basis
This use is associated with the plant's anticancer (preclinical) action. Further evidence for that pharmacology:
Ethnopharmacological relevance Betula pendula subsp. Mandshurica (Regel) Ashburner & McAll. Cortex (birch bark) is a globally traditional medicine for treating multiple inflammatory diseases. Its records are included in the Compendium of Materia Medica and other ancient medical literatures. However, uncovering its chemical profile and exploring novel biologically active compounds from birch bark remains a significant challenge. Aim of the study To uncover the anti-inflammatory, -oxidative, and -proliferative mechanisms and potentially effective compounds of birch bark extract by combing chemical profiling, isolation, identification, together with in vivo, in vitro, and silico evaluation. Materials and methods Ultra-performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) was used to obtain the chemical profile of birch bark extract. The new compounds were obtained via column chromatography and analyzed using X-ray diffraction and electronic circular dichroism for absolute configuration confirmation. The zebrafish caudal fin inflammation-induced model, qPCR, and Western blot analysis were used to explore the effects and underlying mechanisms of birch bark extract. In vitro cytotoxicity assays and kinases screening conducted to gain preliminary insight into the anti-proliferative effects of birch bark extract and its isolated compounds. In addition, in-silico molecular docking was performed to investigate the putative mechanism. Results UPLC-QTOF-MS/MS chemical profiles revealed 105 compounds in birch bark extract, with 80 of these were first reported in B. pendula subsp. Mandshurica cortex. We selected five compounds speculated as novel and isolated three ones (one triterpenoid derivative and two lupine series triterpenoids) for further analysis. Birch bark extract exerted antioxidative and anti-inflammatory effects on zebrafish, as shown by the downregulated reactive oxygen species levels and COX-2α, IL-1β, and TNF-α expression, which occurred through NF-ĸB signaling pathway activation. The in vitro anti-proliferative effects of birch bark extract and compound 44 were also unveiled. Moreover, the putative anti-tumor mechanism of compound 44 was revealed using kinase screening and in-silico molecular docking. Conclusions This study provided a predictable chemical profile and demonstrated the pharmacological effects of birch bark extract, elucidated the mechanism of this traditional Chinese medicine and suggested it as a novel anti-cancer candidate.
Birch buds (Gemmae Betulae) are widely used in Russian and Chinese traditional medicine mainly as a diuretic and diaphoretic agent but also as an antiseptic, anti-inflammatory and analgesic. Despite the long history of therapeutic use of birch buds in folk medicine, the existing information on their chemical composition and pharmacological effects is insufficient. This circumstance warrants further study of the chemistry and pharmacology of birch buds. The present study was designed to investigate (a) the chemical composition of buds from two species of white birch and (b) the in vitro cytotoxic effect of extracts from these sources on selected tumour cells. Extracts from Betula pubescens Ehrh. and Betula pendula Roth. buds were obtained using three different methods: carbon dioxide supercritical fluid extraction (SFE), washing of exudate covering whole buds, and extraction of milled buds with diethyl ether. The chemical composition of extracts was investigated by GC-MS. Cytotoxicity was determined by MTT assay, and cell proliferation was determined by [3H]thymidine uptake in cancer cells and normal skin fibroblasts. The GC-MS investigation identified a total of 150 substances of different classes. The chemical composition of B. pubescens and B. pendula buds differed, with bud extracts from the former containing a relatively high quantity of sesquiterpenoids and flavonoids, while the main components of extracts from the latter were triterpenoids. The results of the biological assay indicated that birch bud extracts demonstrated time- and concentration-dependent and differential cytotoxicity. The highest cytotoxic activity demonstrated bud exudates and SFE extracts obtained from both Betula species. The rich chemical composition of birch buds suggests the possibility of a wider spectrum of biological activity than previously thought. Birch bud extracts could be a promising source of compounds with cytotoxic activity against various cancers.