Evaluation of in vivo and in vitro efficacy of solasonine/solamargine-loaded lipid-polymer hybrid nanoparticles against bladder cancer.

Solasonine (SS) and solamargine (SM) are alkaloids known for their antioxidant and anticancer properties, which can be further enhanced by encapsulating them in nanoparticles. This led to a study on the potential therapeutic benefits of SS and SM against bladder cancer when encapsulated in lipid-polymer hybrid nanoparticles (LPHNP). The LPHNP loaded with SS/SM were prepared using the emulsion and sonication method and their physical-chemical properties characterized. The biological effects of these nanoparticles were then tested in both 2D and 3D bladder cancer cell culture models, as well as in a syngeneic orthotopic mouse model based on the MB49 cell line and ethanol epithelial injury. The LPHNP-SS/SM had an average size of 130 nm, a polydispersity index of 0.22 and a positive zeta potential, indicating the presence of chitosan coating on the nanoparticle surface. The dispersion of LPHNP-SS/SM was found to be monodispersed with a span index of 0.539, as measured by nanoparticle tracking analysis (NTA). The recrystallization index, calculated from DSC data, was higher for the LPHNP-SS/SM compared to LPHNPs alone, confirming the presence of alkaloids within the lipid matrix. The encapsulation efficiency (EE%) was also high, with 91.08 % for SS and 88.35 % for SM. Morphological analysis by AFM and Cryo-TEM revealed that the nanoparticles had a spherical shape and core-shell structure. The study showed that the LPHNP-SS/SM exhibited mucoadhesive properties by physically interacting with mucin, suggesting a potential improvement in interaction with mucous membrane. Both the free and nanoencapsulated SS/SM demonstrated dose-dependent cytotoxicity against bladder cancer cell lines after 24 and 72 h of treatment. In 3D bladder cell culture, the nanoencapsulated SS/SM showed an IC50 two-fold lower than free SS/SM. In vivo studies, the LPHNP-SS/SM displayed an antitumoral effect at high doses, leading to a significant reduction in bladder volume compared to the positive control. However, there were observed instances of systemic toxicity and liver damage, indicated by elevated levels of transaminases (TGO and TGP). Overall, these results indicate that the LPHNPs effectively encapsulated SS/SM, showing high encapsulation efficiency and stability, along with promising in vitro and in vivo antitumoral effects against bladder cancer. Further evaluation of its systemic toxicity effects is necessary to ensure its safety and efficacy for potential clinical application.

Health Benefits of the Alkaloids from Lobeira (Solanum lycocarpum St. Hill): A Comprehensive Review.

Solanum is the largest genus within the Solanaceae family and has garnered considerable attention in chemical and biological investigations over the past 30 years. In this context, lobeira or "fruta-do-lobo" (Solanum lycocarpum St. Hill), a species predominantly found in the Brazilian Cerrado, stands out. Beyond the interesting nutritional composition of the fruits, various parts of the lobeira plant have been used in folk medicine as hypoglycemic, sedative, diuretic, antiepileptic, and antispasmodic agents. These health-beneficial effects have been correlated with various bioactive compounds found in the plant, particularly alkaloids. In this review, we summarize the alkaloid composition of the lobeira plant and its biological activities that have been reported in the scientific literature in the last decades. The compiled data showed that lobeira plants and fruits contain a wide range of alkaloids, with steroidal glycoalkaloid solamargine and solasonine being the major ones. These alkaloids, but not limited to them, contribute to different biological activities verified in alkaloid-rich extracts/fractions from the lobeira, including antioxidant, anti-inflammatory, anticancer, antigenotoxic, antidiabetic, antinociceptive, and antiparasitic effects. Despite the encouraging results, additional research, especially toxicological, pre-clinical, and clinical trials, is essential to validate these human health benefits and ensure consumers' safety and well-being.

In Vivo and in vitro antitumor activity of tomatine in hepatocellular carcinoma.

Background: There is abundant ethnopharmacological evidence the uses of regarding Solanum species as antitumor and anticancer agents. Glycoalkaloids are among the molecules with antiproliferative activity reported in these species. Purpose: To evaluate the anticancer effect of the Solanum glycoalkaloid tomatine in hepatocellular carcinoma (HCC) in vitro (HepG2 cells) and in vivo models. Methods: The resazurin reduction assay was performed to detect the effect of tomatine on cell viability in human HepG2 cell lines. Programmed cell death was investigated by means of cellular apoptosis assays using Annexin V. The expression of cancer related proteins was detected by Western blotting (WB). Reactive oxygen species (ROS) and calcium were determined by 2,7-dichlorodihydrofluorescein diacetate and Fluo-4, respectively. Intrahepatic HepG2 xenograft mouse model was used to elucidate the effect of tomatine on tumor growth in vivo. Results and Discussion: Tomatine reduced HepG2 cell viability and induced the early apoptosis phase of cell death, consistently with caspase-3, -7, Bcl-2 family, and P53 proteins activation. Furthermore, tomatine increased intracellular ROS and cytosolic Ca+2 levels. Moreover, the NSG mouse xenograft model showed that treating mice with tomatine inhibited HepG2 tumor growth. Conclusion: Tomatine inhibits in vitro and in vivo HCC tumorigenesis in part via modulation of p53, Ca+2, and ROS signalling. Thus, the results suggest the potential cancer therapeutic use of tomatine in HCC patients.

Extracción de glicoalcaloides de papa nativa (Solanumphureja) variedad ratona morada con líquidos presurizados / Extraction of glycoalkaloids of native potato (Solanum phureja) ratona morada variety with pressurized liquids

RESUMEN La cáscara de papa es un residuo originado por su procesamiento agroindustrial, que genera un gran impacto ambiental debido a su inadecuado manejo o eliminación. No obstante, la cáscara de papa es una buena fuente de ingredientes funcionales como los glicoalcaloides (GA). Este estudio investigó la extracción de dos GA (α-solanina y α-chaconina) de cáscara de papa nativa (Solanum phureja) variedad ratona morada del departamento de Nariño-Colombia, utilizando la tecnología de extracción con líquidos presurizados (ELP), mediante un diseño experimental central compuesto, con el fin de determinar el efecto de la presión (P) y la temperatura (T), sobre el rendimiento y la composición de GA. Los extractos se analizaron por cromatografía líquida HPLC. Los resultados obtenidos permitieron establecer que la temperatura ejerció un efecto significativo (p <0,05) sobre el rendimiento, α-solanina y α-chaconina. El rendimiento óptimo fue de 5,62 % p/p. Los GA, α-solanina y α-chaconina, aumentaron su concentración al disminuir la temperatura. La extracción con líquidos presu-rizados promete ser una buena alternativa al uso de solventes orgánicos para obtener compuestos bioactivos de cáscara de papa.

SUMMARY Potato peel is a waste originated by its agro-industrial processing, generating an environmental impact due to its inadequate handling or elimination. However, potato peel is a good source of functional ingredients such as glycoalkaloids (GA). This study investigated the extraction of two GA (α-solanine and α-chaconine) from native potato rind (Solanum phureja) ratona morada variety from the department of Nariño-Colombia, using the technology of extraction with pressurized liquids (PLE), through a experimental central composite design, in order to determine the effect of pressure (P) and temperature (T), on the performance and composition of GA. The extracts were analyzed by liquid chromatography HPLC. The results obtained allowed us to establish that the temperature exerted a significant effect (p <0.05) on the yield, α-solanine and α-chaconine. For the yield an optimum value of 5.62 % w/w was reached. α-solanine and α-chaconine increased their concentration as the temperature decreased. The extraction with pressurized liquids promises to be a good alternative in the use of organic solvents to obtain bioactive compounds of potato husk.

Extending compound identification for molecular network using the LipidXplorer database independent method: A proof of concept using glycoalkaloids from Solanum pseudoquina A. St.-Hil.

INTRODUCTION: Molecular networks are now established as the method of choice for tandem mass spectrometry dereplication and similarity-based structure elucidation. Node identification can be used to start the propagation of the structure elucidation of unknown compounds progressively. OBJECTIVE: To demonstrate the capabilities of using the LipidXplorer data results along with molecular networking to identify nodes and aid sequential structure elucidation of unknown compounds. MATERIAL AND METHODS: Molecular fragmentation query language (MFQL) files were written to identify glycoalkaloids based on known structures described for Solanum species. A dataset generated from liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis of Solanum pseudoquina sample were submitted to dereplication on both LipidXplorer software and Global Natural Products Social Molecular Network (GNPS) online system. The resulting attribute table from GNPS calculations was merged with the LipidXplorer results and this merged file was used for network visualisation in Cytoscape. Nodes in the molecular network were labelled using the LipidXplorer identifiers, thus assisting the structure elucidation of unidentified compounds. RESULTS: The combination of the LipidXplorer glycoalkaloids list and GNPS analysis was used in Cytoscape to label nodes in the molecular network. The analysis of the network using these labelled starting points triggered the structure elucidation of closely related nodes leading to the identification of 30 compounds using the LipidXplorer output and four purified and structure elucidated compounds, including a new glycoalkaloids identified as 3-O-(ß-d-xylopyranosyl)-(20R,25S)-22,26-epimino-16-acetyl-cholesta-5,22(N)-diene. CONCLUSION: A significant compound identification completely based on molecular formula and fragmentation queries was achieved. This new and effective approach could help researches to expand the identification rate of compounds in dereplication studies using molecular networks.

In vitro activities of glycoalkaloids from the Solanum lycocarpum against Leishmania infantum

ABSTRACT Leishmania infantum is an etiologic agent of visceral leishmaniasis. This disease is a neglected disease that can be fatal if not treated and additionally, the few therapeutic option present several drawbacks, including difficult route of administration and toxicity, which turn the search for new therapeutic alternatives necessary. Herein, we evaluated the leishmanicidal in vitro activity of the solanum extract from Solanum lycocarpum A. St.-Hil., Solanaceae, and the isolated alkaloids solasodine, solamargine and solasonine against promastigotes and intracellular amastigotes of L. infantum. Solasodine (IC50-pro = 4.7 µg/ml; IC50-ama = 10.8 µg/ml) and solamargine (IC50-pro = 8.1 µg/ml; IC50-ama = 3.0 µg/ml) exhibited interesting leishmanicidal ativity. Solasonine was approximately four-times (Selective Index 3.7) more selective to the parasite than to the host cells. This data suggest that solasonine might be considered as a potential drug candidate for leishmaniasis treatment.

Ecofriendly Synthesis of Silver Nanoparticles Using Potato Steroidal Alkaloids and Their Activity Against Phytopathogenic Fungi

ABSTRACT In order to reduce the excessive reliance on the toxic chemical fungicides, the present study aimed to isolate the total potato glycoalkaloids (TPAs), and the two steroidal alkaloids α-chaconine and α-solanine from potatoes, Solanum tuberosum L. Their structures were characterized using physical and spectroscopic methods including (UV, IR, 1H, 13C--NMR, 2D 1H-1H COSY, HMBC and NOESY). Silver nanoparticles (AgNPs) were prepared from potato alkaloids through a green synthesis approach. Potato alkaloids and their nanoparticles inhibited mycelial growth of the phytopathogenic fungi Alternaria alternate, Rhizoctonia solani, Botrytis cinerea and Fusarium oxysporum f. sp. lycopersici with low minimal inhibitory and minimal fungicidal concentrations. R. solani was the most susceptible, while F. oxysporum was the most resistant. TPAs was the most fungitoxic (EC50's were 19.8, 22.5, 26.5 and 32.3 µg/ml against R. solani, A. alternate, B. cinerea and F. oxysporum respectively). A mixture of α-solanine and α-chaconine (1:1) showed a marked antifungal activity. AgNPs (size 39.5-80.3 diameter) from alkaloids showed improved fungitoxic activity (EC50's of TPAs nanoparticles ranged between 10.9 and 16.1 µg/ml). Alkaloids exhibited no or a slight phytotoxicity against wheat and radish. Results recommend the potential of using potato alkaloids and their nanoparticles as biorational alternatives to conventional fungicides.

In vitro and in vivo evaluation of the delivery of topical formulations containing glycoalkaloids of Solanum lycocarpum fruits.

The glycoalkaloids solasonine (SN) and solamargine (SM) have been studied for their antiparasitic, antifungal, and anticancer properties, especially in vitro and in vivo against non-melanoma skin cancer. Thus, the alkaloidic extract of Solanum lycocarpum, which contains approximately 45% each of SN and SM, was used to define the best experimental conditions for in vitro and in vivo assays. The in vitro assays were performed with the Franz cell diffusion porcine skin model to evaluate the effects of different pHs and the presence of monoolein, ethoxydiglycol or ethanol penetration enhancers on the skin penetration and retention of SN and SM after 3, 6, 9 and 12h of exposure. The in vivo assay was performed on hairless mice with the formulation selected in the in vitro assays. The results showed that pH 6.5 was optimal for SM penetration. The formulation containing 5% alkaloidic extract, 5% propylene glycol, 5% monoolein and a hydroxyethyl cellulose gel base (Natrosol) (pH 6.5) was optimal for the delivery of SN and SM into the skin, and this formulation is potentially useful for the topical therapy of several skin disorders.