Solasodine targets NF-κB signaling to overcome P-glycoprotein mediated multidrug resistance in cancer.

P-glycoprotein (P-gp) mediated multidrug resistance (MDR) is the leading cause of chemotherapy failure since it causes the efflux of chemotherapeutic drugs from the cancer cells. Solasodine, a steroidal alkaloid and oxaspiro compound, present in the Solanaceae family showed significant cytotoxic effects on various cancer cells. However, the effect of solasodine on reversing P-gp mediated drug resistance is still unknown. Primarily in this study, the integrative network pharmacology analysis found 71 common targets between solasodine and cancer MDR, among them NF-κB was found as a potential target. The results of immunofluorescence analysis showed that solasodine significantly inhibits NF-κB-p65 nuclear translocation which caused downregulated P-gp expression in KBChR-8-5 cells. Further, solasodine binds to the active sites of the TMD region of P-gp and inhibits P-gp transport activity. Moreover, solasodine significantly promotes doxorubicin intracellular accumulation in the drug resistant cells. Solasodine reduced the fold resistance and synergistically sensitized doxorubicin's therapeutic effects in KBChR-8-5 cells. Additionally, the solasodine and doxorubicin combination treatment increased the apoptotic cell populations and G2/M phase cell cycle arrest in KBChR-8-5 cells. The MDR tumor bearing xenograft mice showed tumor-suppressing characteristics and P-gp downregulation during the combination treatment of solasodine and doxorubicin. These results indicate that solasodine targets NF-κB signaling to downregulate P-gp overexpression, inhibit P-gp transport activity, and enhance chemosensitization in MDR cancer cells. Considering its multifaceted impact, solasodine represents a potent natural fourth-generation P-gp modulator for reversing MDR in cancer.

A Review on the Chemical Properties, Plant Sources, Anti-shock Effects, Pharmacokinetics, Toxicity, and Clinical Applications of Anisodamine.

Alkaloids are natural products that occur widely in many herbal plants. Anisodamine, widely present in the Solanaceae family, is an alkaloid extracted from the roots of the Anisodus tanguticus Maxim. It is an antagonist to M-choline receptors and exhibits diverse pharmacological effects, such as cholinolytic effect, calcium antagonist effect, anti-oxygenation effect. Anisodamine, a prominent constituent of the tropine alkaloid family, exhibits a range of pharmacological effects akin to those of atropine and scopolamine. owing to its low toxicity and moderate efficacy in clinical to wide applications, especially for varieties of shock treatment. However, there remains a dearth of research regarding the in vivo pharmacokinetics, mechanism of action, and toxicity of anisodamine. Consequently, this paper provides a comprehensive review of the anti-shock effects, toxicity, and pharmacokinetic characteristics of anisodamine to increase the understanding of its medicinal value, and provide reference and inspiration for the clinical application and further in-depth research of anisodamine.

New Solasodine-Type Glycoalkaloids Isolated from Solanum nigrum and Their Cytotoxic Activity.

Three undescribed solalodine-type glycoalkaloids, named solanigrinoside A-C (1-3), and six known compounds (4-9) were isolated from the whole plants of Solanum nigrum. Their structures were elucidated based on analysis of HR-ESI-MS, 1D- and 2D-NMR spectral data, and comparison with those reported in literatures. The solanigrinoside A-C (1-3), solasodine (4), and 3-acetoxysolasodine (5) exhibited cytotoxic effects against LU-1, Hep-G2, and MCF-7 cells with IC50 values in range from 4.6 µM to 56.2 µM. Compound 2 showed the significant cytotoxic activity with corresponding IC50 values of 5.7 µM, 7.9 µM, and 4.6 µM, respectively.

Anticancer effects of solasonine: Evidence and possible mechanisms.

The effectiveness and safety of traditional Chinese medicine's active ingredients in anti-tumor effects have attracted widespread attention worldwide. Solasonine is the main anti-tumor component of the traditional Chinese medicine Solanum nigrum L, which can inhibit tumor cell proliferation, induce apoptosis, induce ferroptosis in tumor cells, and inhibit of tumor cell metastasis, thereby inhibiting tumor progression. Therefore, we summarized anti-tumor mechanisms and targets of solasonine to provide new ideas and theoretical basis for its further development and application.

Bioactive solanidane steroidal alkaloids from Solanum lyratum.

Six previously unreported solanidane steroidal alkaloids, namely lyrasolanosides A-F, were isolated from Solanum lyratum. In addition, five known steroidal alkaloids were also identified. The structures of these compounds were determined through the use of NMR, HRESIMS,UV, IR and ECD analysis. To assess their bioactivities, the cytotoxic effects of the six previously unreported compounds were evaluated on A549 cells. The results revealed that lyrasolanoside B (2) exhibited the highest potency among them. Lyrasolanoside B (2) exhibited significant inhibition of cell migration, invasion, and adhesion dramatically. Mechanistically, it was found to suppress the activity of JAK2/STAT3 signaling pathway by downregulating the expression of phosphorylated JAK2/STAT3 in an exosome-dependent manner. In addition, lyrasolanoside B (2) was found to significantly upregulate the expression of E-cadherin and downregulate the expression of N-cadherin and vimentin. These findings indicate that lyrasolanoside B (2) inhibits the metastasis of A549 cells by suppressing exosome-mediated EMT. These findings suggest that lyrasolanoside B (2) may inhibit the metastasis of lung cancer by regulating A549-derived exosomes.

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.

Protective role of pretreatment with Anisodamine against sepsis-induced diaphragm atrophy via inhibiting JAK2/STAT3 pathway.

There is an increasing tendency for sepsis patients to suffer from diaphragm atrophy as well as mortality. Therefore, reducing diaphragm atrophy could benefit sepsis patients' prognoses. Studies have shown that Anisodamine (Anis) can exert antioxidant effects when blows occur. However, the role of Anisodamine in diaphragm atrophy in sepsis patients has not been reported. Therefore, this study investigated the antioxidant effect of Anisodamine in sepsis-induced diaphragm atrophy and its mechanism. We used cecal ligation aspiration (CLP) to establish a mouse septic mode and stimulated the C2C12 myotube model with lipopolysaccharide (LPS). After treatment with Anisodamine, we measured the mice's bodyweight, diaphragm weight, fiber cross-sectional area and the diameter of C2C12 myotubes. The malondialdehyde (MDA) levels in the diaphragm were detected using the oxidative stress kit. The expression of MuRF1, Atrogin1 and JAK2/STAT3 signaling pathway components in the diaphragm and C2C12 myotubes was measured by RT-qPCR and Western blot. The mean fluorescence intensity of ROS in C2C12 myotubes was measured by flow cytometry. Meanwhile, we also measured the levels of Drp1 and Cytochrome C (Cyt-C) in vivo and in vitro by Western blot. Our study revealed that Anisodamine alleviated the reduction in diaphragmatic mass and the loss of diaphragmatic fiber cross-sectional area and attenuated the atrophy of the C2C12 myotubes by inhibiting the expression of E3 ubiquitin ligases. In addition, we observed that Anisodamine inhibited the JAK2/STAT3 signaling pathway and protects mitochondrial function. In conclusion, Anisodamine alleviates sepsis-induced diaphragm atrophy, and the mechanism may be related to inhibiting the JAK2/STAT3 signaling pathway.

[Solasonine promotes apoptosis of non-small cell lung cancer cells by regulating the Bcl-2/Bax/caspase-3 pathway].

OBJECTIVE: To investigate the effect of solasonine, an active component of Solanum nigrum, on proliferation and apoptosis of non-small cell lung cancer PC9 cells. METHODS: PC9 cells were treated with 2, 5, 10, 15, 20, or 25 µmol/L solasonine, and the changes in cell proliferation were examined using CCK-8 assay. Tetramethyl rhodamine ethyl ester (TMRE) was used to detect the changes in mitochondrial membrane potential, and caspase-3/7 detection kit and GreenNucTM caspase-3/Annexin V-mCherry kit for live cell were used to analyze the changes in caspase-3 of the cells. Annexin V-FITC/PI double staining was employed to analyze the apoptosis rate of the cells. The effect of PTEN inhibitors on solasonine-induced cell apoptosis was examined by detecting apoptosis-related protein expressions using Western blotting. RESULTS: Solasonine treatment for 24, 48, and 72 h significantly lowered the viability of PC9 cells. The cells treated with solasonine for 24 h showed significantly decreased mitochondrial membrane potential and increased cell apoptosis with enhanced caspase-3/7 and caspase-3 activities and expression of cleaved caspase-3. Solasonine treatment significantly decreased phosphorylation levels of PI3K and Akt, increased the protein expressions of PTEN and Bax, and lowered the expression of Bcl-2 protein in the cells. CONCLUSION: Solasonine inhibits proliferation and induces apoptosis of PC9 cells by regulating the Bcl-2/Bax/caspase-3 pathway and its upstream proteins.

Idosos vítimas de trauma: doenças preexistentes, medicamentos em uso no domicílio e índices de trauma / Elderly victims of trauma: preexisting conditions, medications taken at home and indexes of trauma / Ancianos víctimas de trauma: condiciones preexistentes, medicamentos tomados en el hogar e índices de trauma

Objetivou-se identificar o perfil sociodemográfico de idosos vítimas de trauma, caracterizar doenças preexistentes e medicamentos utilizados no domicílio; calcular índices de trauma e desfecho clínico. Estudo retrospectivo e exploratório, com a análise de dados secundários de um banco de dados de um hospital geral terciário, entre 2008 e 2010. Foram estudados 131 idosos, média de idade 69,9 anos, 73,3% homens, 55,1% casados, 54,7% aposentados; 65,6% possuíam doenças preexistentes e 48,9% usavam medicamentos no domicílio. Houve representatividade de quedas (31,3%), seguidas por atropelamento (28,2%), com cabeça/pescoço sendo a região mais acometida (59,5%). Prevaleceu o trauma moderado (44,3%), com condições de sobrevida após o evento (80,2%). Houve associação entre mecanismo do trauma e doença preexistente (p=0,01) e entre mecanismo do trauma e sexo (p=0,03). O conhecimento das variáveis envolvidas com idosos vítimas de trauma possibilita aos profissionais de saúde o planejamento de medidas preventivas, visando aprimorar sua assistência.

The objective was to identify the sociodemographic profile of the elderly victims of trauma, to characterize preexisting conditions and medications taken at home, and to calculate indices of trauma and clinical outcomes. This is a retrospective and exploratory analysis from a database of a general hospital between 2008 and 2010. There were studied 131 elderly, mean age 69.9 years, 73.3% male, 55.1% married, 54.7% retired, 65.6% had preexisting conditions and 48.9% used drugs at home. There was a representative number of falls (31.3%), followed by running over (28.2%), with the head/neck region being the most affected (59.5%). Moderate trauma prevailed (44.3%), with conditions of survival after the event (80.2%). There was an association between mechanism of trauma and preexisting disease (p=0.01) and between mechanism of trauma and sex (p=0.03). The knowledge of the variables involved with the elderly victims of trauma enables healthcare professionals to plan preventive measures aimed at improving the assistance. Key words: Aged; Wounds and Injuries; Disease; Drug Utilization.

Se objetivó identificar el perfil sociodemográfico de ancianos víctimas de trauma, caracterizar condiciones preexistentes y medicamentos tomados en casa, y calcular índices de trauma y evolución clínica. Se realizó un análisis retrospectivo y exploratorio de una base de datos de un hospital general terciario entre 2008 y 2010. Se estudiaron 131 ancianos, media of 69,9 años, 73,3% hombres, 55,1% casados, 54,7% jubilados, 65,6% tienen condiciones preexistentes y 48,9% estaban tomando medicación en casa. Hubo representación de las caídas (31,3%), seguido de atropello (28,2%). La región cabeza/cuello fue el más afectado (59,5%). Prevaleció trauma moderado (44,3%), con condiciones de supervivencia después del evento (80,2%). Se observó una asociación entre mecanismo de lo trauma y enfermedad previa (p=0,01) y entre mecanismo de lo trauma y sexo (p=0,03). El conocimiento de las variables que intervienen con ancianos víctimas de trauma permite a los profesionales de la salud planificar medidas preventivas para mejorar su asistencia.

Chemical and pharmacological investigation of Solanum species of Brazil: a search for solasodine and other potentially useful therapeutic agents

A systematic search for solasodine, an important staring material for the partial synthesis of steroidal hormones as well as other potentially bioactive constituents of various Solanum species of Brazil has been undertaken. Thus, the fruits of S. paludosum, S. asperum, S. sessiliforum and Solanum sp. were found to contain significant amounts of solasodine. The root bark of S. paludosum which showe durare like activity yelded tomatidenol and another yet unidentified alkaloid responsible for the biological activity. The fruits of S. asperum yelded a new spirosolane alkaloid, solaparnaine. The stem bark of S. pseudo-quina showed convulsive and exitatory activity from which (25S)-isosolafloridine was identified as the active principle. In addition, the latter alkaloid was also found to show antimicrobial activity.

Uso do amido dos frutos da lobeira (Solanum lycocarpum St Hill) por indivíduos diabéticos: relato de caso / The use of starch obtained from lobeira (Solanum lycocarpum ST Hill) by diabetes mellitus patientes: case reports

Para avaliar o efeito do amido obtido dos frutos da lobeira (Solanum lycocarpum St. Hill) no controle da diabetes, entrevistamos sete pacientes hiperglicêmicos que deliberadamente usaram o produto para controle da doença. Os pacientes relataram reduçäo da glicemia quando consumiam o amido como parte da dieta.(au)