Search Results (8)

Natural plant products have been used for cancer treatment since ancient times and continue to play a vital role in modern anticancer drug development. However, only a small fraction of identified medicinal plants has been thoroughly investigated, particularly for their effects on cellular pathways in lung and colorectal cancers, two under-researched cancers with poor prognostic outcomes (lung cancers). This review focuses on the lung and colorectal cancer signaling pathways modulated by bioactive compounds from eleven traditional medicinal plants: Curcuma longa, Astragalus membranaceus, Glycyrrhiza glabra, Althaea officinalis, Echinacea purpurea, Sanguinaria canadensis, Codonopsis pilosula, Hydrastis canadensis, Lobelia inflata, Scutellaria baicalensis, and Zingiber officinale. These plants were selected based on their documented use in traditional medicine and modern clinical practice. Selection criteria involved cross-referencing herbs identified in a scoping review of traditional cancer treatments and findings from an international survey on herbal medicine currently used for lung and colorectal cancer management by our research group and the availability of existing literature on their anticancer properties. The review identifies several isolated phytoconstituents from these plants that exhibit anticancer properties by modulating key signaling pathways such as PI3K/Akt/mTOR, RAS/RAF/MAPK, Wnt/β-catenin, and TGF-β in vitro. Notable constituents include sanguinarine, berberine, hydrastine, lobeline, curcumin, gingerol, shogaol, caffeic acid, echinacoside, cichoric acid, glycyrrhizin, 18-β-glycyrrhetinic acid, astragaloside IV, lobetyolin, licochalcone A, baicalein, baicalin, wogonin, and glycyrol. Curcumin and baicalin show preclinical effectiveness but face bioavailability challenges, which may be overcome by combining them with piperine or using oral extracts to enhance gut microbiome conversion, integrating traditional knowledge with modern strategies for improved outcomes. Furthermore, herbal extracts from Echinacea, Glycyrrhiza, and Codonopsis, identified in traditional knowledge, are currently in clinical trials. Notably, curcumin and baicalin also modulate miRNA pathways, highlighting a promising intersection of modern science and traditional medicine. Thus, the development of anticancer therapeutics continues to benefit from the synergy of traditional knowledge, scientific innovation, and technological advancements. Full article

The search for new substances with cytotoxic activity against various cancer cells, especially cells that are very resistant to currently used chemotherapeutic agents, such as melanoma cells, is a very important scientific aspect. We investigated the cytotoxic effect of Chelidonium majus, Mahonia aquifolium and Sanguinaria canadensis extracts obtained from different parts of these plants collected at various vegetation stages on FaDu, SCC-25, MCF-7, and MDA-MB-231 cancer cells. Almost all the tested extracts showed higher cytotoxicity against these cancer cells than the anticancer drug etoposide. The highest cytotoxicity against the FaDu, SCC-25, MCF-7 and MDA-MB-231 cancer cell lines was obtained for the Sanguinaria candensis extract collected before flowering. The cytotoxicity of extracts obtained from different parts of Chelidonium majus collected at various vegetation stages was also evaluated on melanoma cells (A375, G361 and SK-MEL-3). The highest cytotoxic activity against melanoma A375 cells was observed for the Chelidonium majus root extract, with an IC50 of 12.65 μg/mL. The same extract was the most cytotoxic against SK-MEL-3 cells (IC50 = 1.93 μg/mL), while the highest cytotoxic activity against G361 cells was observed after exposure to the extract obtained from the herb of the plant. The cytotoxic activity of Chelidonium majus extracts against melanoma cells was compared with the cytotoxicity of the following anticancer drugs: etoposide, cisplatin and hydroxyurea. In most cases, the IC50 values obtained for the anticancer drugs were higher than those obtained for the Chelidonium majus extracts. The most cytotoxic extract obtained from the root of Chelidonium majus was selected for in vivo cytotoxic activity investigations using a Danio rerio larvae xenograft model. The model was applied for the first time in the in vivo investigations of the extract’s anticancer potential. The application of Danio rerio larvae xenografts in cancer research is advantageous because of the transparency and ease of compound administration, the small size and the short duration and low cost of the experiments. The results obtained in the xenograft model confirmed the great effect of the investigated extract on the number of cancer cells in a living organism. Our investigations show that the investigated plant extracts exhibit very high cytotoxic activity and can be recommended for further experiments in order to additionally confirm their potential use in the treatment of various human cancers. Full article

Sanguinarine (SNG) is a benzophenanthridine alkaloid isolated mainly from Sanguinaria canadensis, Chelidonium majus, and Macleaya cordata. SNG is considered an antineoplastic agent based on its cytotoxic activity against various tumors. However, the exact molecular mechanism through which SNG mediates this activity has not been elucidated. Here, we report that SNG induces death in human cervical cancer (HeLa) cells through activation of two interdependent cell death pathways—apoptosis and ferroptosis. SNG-induced apoptosis was characterized by caspase activation and PARP cleavage, while ferroptosis involved solute carrier family 7 member 11 (SLC7A11) down-regulation, glutathione (GSH) depletion, iron accumulation, and lipid peroxidation (LPO). Interestingly, incubation with caspase inhibitor z-VAD-fmk not only inhibited the features of apoptosis, but also negated markers of SNG-induced ferroptosis. Similarly, pretreatment with ferroptosis inhibitor ferrostatin-1 (Fer-1), apart from rescuing cells from SNG-induced ferroptosis, also curbed the features of SNG-induced apoptosis. Our study implies that, together, apoptosis and ferroptosis act as partners in the context of SNG mediated tumor suppression in HeLa cells. Importantly, SNG increased the generation of reactive oxygen species (ROS), and ROS inhibition blocks the induction of both apoptosis and ferroptosis. These findings highlight the value of continued investigation into the potential use of SNG as an antineoplastic agent. Full article

Peroxisome proliferator-activated receptors (PPARs) play crucial roles in glucose and lipid metabolism and inflammation. Sanguinarine is a natural product that is isolated from Sanguinaria Canadensis, a potential therapeutic agent for intervention in chronic diseases. In this study, biochemical and cell-based promoter-reporter gene assays revealed that sanguinarine activated both PPARα and PPARγ, and enhanced their transcriptional activity; thus, sanguinarine was identified as a dual agonist of PPARα/γ. Similar to fenofibrate, sanguinarine upregulates the expression of PPARα-target genes in hepatocytes. Sanguinarine also modulates the expression of key PPARγ-target genes and promotes adipocyte differentiation, but with a lower adipogenic activity compared with rosiglitazone. We report the crystal structure of sanguinarine bound to PPARα, which reveals a unique ligand-binding mode of sanguinarine, dissimilar to the classic Y-shaped binding pocket, which may represent a new pharmacophore that can be optimized for selectively targeting PPARα. Further structural and functional studies uncover the molecular basis for the selectivity of sanguinarine toward PPARα/γ among all three PPARs. In summary, our study identifies a PPARα/γ dual agonist with a unique ligand-binding mode, and provides a promising and viable novel template for the design of dual-targeting PPARs ligands. Full article

Melanoma is an enormous global health burden, and should be effectively addressed with better therapeutic strategies. Therefore, new therapeutic agents are needed for the management of this disease. The aim of this study was the investigation of cytotoxic activity of some isoquinoline alkaloid standards and extracts obtained from Sanguinaria canadensis—collected before, during, and after flowering—against three different human melanoma cells (A375, G361, SK-MEL-3). The cytotoxicity of these extracts was not previously tested on these melanoma cell lines. Determination of alkaloid contents was performed by HPLC-DAD using Polar RP column and mobile phase containing acetonitrile, water, and 1-butyl-3-methylimidazolium tetrafluoroborate. The cytotoxicity of alkaloid standards was investigated by determination of cell viability and calculation of IC₅₀ values. Significant differences were observed in the alkaloids content and cytotoxic activity of the extracts, depending on the season of collection of the plant material. In the Sanguinaria canadensis extracts high contents of sanguinarine (from 4.8543 to 9.5899 mg/g of dry plant material) and chelerythrine (from 42.7224 to 6.8722 mg/g of dry plant material) were found. For both of these alkaloids, very high cytotoxic activity against the tested cell lines were observed. The IC₅₀ values were in the range of 0.11–0.54 µg/mL for sanguinarine and 0.14 to 0.46 µg/mL for chelerythrine. IC₅₀ values obtained for Sanguinaria canadensis extracts against all tested cell lines were also very low (from 0.88 to 10.96 µg/mL). Cytotoxic activity of alkaloid standards and Sanguinaria canadensis extracts were compared with the cytotoxicity of anticancer drugs—etoposide, cisplatin, and hydroxyurea. In all cases except the one obtained for cisplatin against A375, which was similar to that obtained for Sanguinaria canadensis after flowering against the same cell line, IC₅₀ values obtained for anticancer drugs were higher than the IC₅₀ values obtained for sanguinarine, chelerythrine, and Sanguinaria canadensis extracts. Our results showed that Sanguinaria canadensis extracts and isoquinoline alkaloids, especially sanguinarine and chelerythrine, could be recommended for further in vivo experiments in order to confirm the possibility of their application in the treatment of human melanomas. Full article

Isoquinoline alkaloids may have a wide range of pharmacological activities. Some of them have acetylcholinesterase activity inhibition. Nowadays, neurodegenerative disorders such as Alzheimer’s disease have become a serious public health problem. Searching for new effective compounds with inhibited acetylcholinesterase activity is one of the most significant challenges of modern scientific research. The aim of this study was the in vitro investigation of acetylcholinesterase activity inhibition of extracts obtained from Sanguinaria canadensis collected before, during and after flowering. The acetylcholinesterase activity inhibition of these extracts has not been previously tested. The aim was also to quantify selected alkaloids in the investigated extracts by high performance liquid chromatography (HPLC). The analyses of alkaloid content were performed using HPLC in reversed phase (RP) mode using Polar RP column and mobile phase containing acetonitrile, water and ionic liquid (IL). The acetylcholinesterase activity inhibition of the tested plant extracts and respective alkaloid standards were examined using high performance liquid chromatography with diode-array detector (HPLC-DAD) for the quantification of 5-thio-2-nitro-benzoic acid, which is the product of the reaction between the thiocholine (product of the hydrolysis of acetylthiocholine reaction) with Ellman reagent. The application of the HPLC method allowed for elimination of absorption of interfering components, for example, alkaloids such as sanguinarine and berberine. It is revealed that the HPLC method can be successfully used for the evaluation of the acetylcholinesterase inhibitory activity in samples such as plant extracts, especially those containing colored components adsorbing at wavelength in the range 405–412 nm. The acetylcholinesterase inhibition activity synergy of pairs of alkaloid standards and mixture of all investigated alkaloids was also determined. Most investigated alkaloids and all Sanguinaria canadensis extracts exhibited very high acetylcholinesterase activity inhibition. IC₅₀ values obtained for alkaloid standards were from 0.36 for berberine to 23.13 µg/mL for protopine and from 61.24 to 89.14 µg/mL for Sanguinaria canadensis extracts. Our investigations demonstrated that these plant extracts can be recommended for further in vivo experiments to confirm their acetylcholinesterase activity inhibition. Full article

Invasive glossy buckthorn could reduce restoration potential for understory native forest herbs by compromising their growth and biodiversity. Few studies of glossy buckthorn’s effects on forest herbs exist, and none were done in early-successional, partially open hardwood forests. This study was conducted in a mature hybrid poplar plantation invaded by buckthorn, located in southeastern Québec. We tested the effect of buckthorn removal on the growth of three forest herb species, whether this effect varied among species, and if canopy type (two poplar clones) influenced this effect. Forest herbs were planted in herbicide (buckthorn removed) and control treatments in the plantation understory, an environment similar to that of early-successional hardwood forests. Over the first two growing seasons, species showed specific reactions to buckthorn cover. Mean relative growth rate (RGR) for Asarum canadense and Polygonatum pubescens was increased in the herbicide treatment (48% and 33%, respectively) and decreased in the control treatment (−35% and −33%, respectively). Sanguinaria canadensis growth was the highest among species, with no difference between treatments. No effects of canopy type were detected. Results suggest that planting forest herbs for restoration purposes may be unsuccessful if buckthorn is present. Important changes in understory flora biodiversity are likely to occur over the long term in forests invaded by buckthorn. Full article

Sanguinaria canadensis, also known as bloodroot, is a traditional medicine used by Native Americans to treat a diverse range of clinical conditions. The plants rhizome contains several alkaloids that individually target multiple molecular processes. These bioactive compounds, mechanistically correlate with the plant’s history of ethnobotanical use. Despite their identification over 50 years ago, the alkaloids of S. canadensis have not been developed into successful therapeutic agents. Instead, they have been associated with clinical toxicities ranging from mouthwash induced leukoplakia to cancer salve necrosis and treatment failure. This review explores the historical use of S. canadensis, the molecular actions of the benzophenanthridine and protopin alkaloids it contains, and explores natural alkaloid variation as a possible rationale for the inconsistent efficacy and toxicities encountered by S. canadensis therapies. Current veterinary and medicinal uses of the plant are studied with an assessment of obstacles to the pharmaceutical development of S. canadensis alkaloid based therapeutics. Full article