Immunomodulation-mediated anticancer activity of a novel compound from Brugmansia suaveolens leaves.

Immunomodulation activity-guided fractionation of ethanol extract of Brugmansia suaveolens leaves was carried out to isolate a novel compound SUPH036-022A (1) by co-culturing the test fraction/compound activated PBMC with MCF7 and A549 cancer cell lines. Assessment of immune markers in PBMC, and analysis of apoptosis markers and cell cycle was carried out for cancer cells. The structure of the isolated compound was elucidated by spectral analysis. Compound 1 enhanced the secretion of immune markers, IL-2 and IFN-γ, from PBMC. Further, compound 1 treated PBMC increased cell death in MCF7 and A549 cell lines and induced ROS production and mitochondrial membrane perturbation, leading to apoptosis. Flow cytometry analysis revealed; compound 1 stimulated PBMC to cause a five-fold increase in cell cycle perturbations in the sub-G1 stage of cancer cells as compared to the negative control. The compound, in the absence of PBMC, only had a weak cytotoxic activity against these cell lines. Thus, compound 1 is a novel lead for immunomodulation-mediated anticancer activity.

Review on the genus Brugmansia: Traditional usage, phytochemistry, pharmacology, and toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Brugmansia belongs to the Solanaceae family and contains approximately 7-8 species distributed in America, Europe, Africa, and Asia. The genus Brugmansia plants are used in the traditional medicine of different parts of the world for the treatment of inflammations, rheumatic arthritis, wounds, skin infections, headache, asthma, colic, aches, and so on. AIM OF THE REVIEW: To the best of our knowledge, this is the first review study that focuses on the phytochemistry, pharmacology, toxicity, and traditional uses of Brugmansia species in order to understand the link between the traditional uses, phytochemistry, and modern therapeutic uses, and provide a scientific fundamental for further research in the phytochemical and pharmacological activities of their species. MATERIALS AND METHODS: The information reported in this study was retrieved from the scientific database such as ScienceDirect, PubMed, Springer, CNKI, Wiley, Google Scholar, and Baidu Scholar, up until May 2020. The key search word was "Brugmansia." Additionally, information was derived by search on the reference lists of included articles and Ph.D. dissertations. RESULTS: As traditional uses, Brugmansia species are used against a wide range of diseases such as body pain, inflammatory conditions, skin infection, wound, and other diseases. Also, these species are used as a hallucinogen, protection from evil, and magical rituals. Phytochemical investigations have led to reporting approximately 189 chemical compounds in this genus. Among these components, tropane alkaloids, terpenes, and flavonoids are the most representative components of Brugmansia species. The plant extracts and chemical constituents of Brugmansia species exhibit a broad spectrum of biological and pharmacological activities, including anti-inflammatory, cytotoxic, antioxidant, antibacterial, antispasmodic, anti-asthmatic, antinociceptive, antiprotozoal activities, and so on. CONCLUSION: This review summarized and analyzed the information of traditional uses, phytochemical, pharmacological activities, and toxicity of the genus Brugmansia plants, which show their species have interesting chemical constituents with different biological activities. The traditional uses of some species from this genus have been estimated by pharmacological activities, such as the anti-inflammatory, antispasmodic, antiasthma, antinociceptive, anti-addictive, and antiprotozoal activity. However, the traditional uses of many species have not been confirmed, also the secondary metabolites of the many species have not yet been determined and have never been pharmacologically estimated. Considerably more research is needed to assert the ethnopharmacological uses, determine the chemical constituents, toxicity, and pharmacological activities of the genus Brugmansia species. The present review will be helpful for further research in the phytochemistry and pharmacology of Brugmansia species.

Anti-Inflammatory Effect of Flavonoids from Brugmansia arborea L. Flowers.

Brugmansia arborea L. (Solanaceae), commonly known as "angel's trumpet," is widely grown in North America, Africa, Australia, and Asia. It has been mainly used for ornamental purposes as well as analgesic, anti-rheumatic, vulnerary, decongestant, and anti-spasmodic materials. B. arborea is also reported to show anti-cholinergic activity, for which many alkaloids were reported to be principally responsible. However, to the best of our knowledge, a phytochemical study of B. arborea flowers has not yet been performed. Four flavonol glycosides (1-4) and one dihydroflavanol (5) were for the first time isolated from B. arborea flowers in this study. The flavonoids showed significant antioxidant capacities, suppressed nitric oxide production in lipopolysaccharide (LPS)-treated RAW 264.7 cells, and reduced inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) protein production increased by LPS treatment. The contents of compounds 1-4 in n-BuOH fraction were determined to be 3.8 ± 0.9%, 2.2 ± 0.5%, 20.3 ± 1.1%, and 2.3 ± 0.4%, respectively, and that of compound 5 in EtOAc fraction was determined to be 12.7 ± 0.7%, by HPLC experiment. These results suggest that flavonol glycosides (1-4) and dihydroflavanol (5) can serve as index components of B. arborea flowers in standardizing anti-inflammatory materials.