Evaluation of potential antidiabetic and antibacterial activities of Bolivian nutraceutical plants

Type 2 diabetes mellitus is a health problem worldwide that requires the search for novel therapeutic strategies. Natural products are a source of potential therapies due to their acceptation and traditional use or consumption. This study aims to evaluate selected Bolivian traditionally consumed plants as potential antidiabetic products using animal models. Besides, focused on the urinary tract infection, as one common complication in diabetes, the antibacterial effect was evaluated in the uroepithelial in vitro infection. Initially, the screening of glycemia-reducing effect, performed in healthy Swiss albino mice, showed that the hydroethanolic extracts of Amaranthus caudatus, Chenopodium quinoa, Lupinus mutabilis, and Smallanthus sonchifolius reduced the postprandial glycemia and the glucose tolerance during the oral glucose tolerance test. Moreover, the in vitro insulin secretion in mice pancreatic islets was stimulated only by Amaranthus caudatus, Chenopodium quinoa and Lupinus mutabilis. Based on the results of the screening study, we continued evaluating the antidiabetic effect of Amaranthus caudatus and Lupinus mutabilis using the Goto-kakizaki (GK) type 2 diabetic rats and the respective healthy control the Wistar (W) rats. The oral administration of A. caudatus and L. mutabilis, separately, improved the glucose tolerance and augmented serum insulin levels in both GK and W rats, in a dose-dependent way. The daily oral administration of each extract (1000 mg/kg b.w.) during 21 days improved the glucose tolerance, increased the serum insulin and reduced the glycated hemoglobin. Additionally, the insulin secretion was stimulated in islets isolated from treated animals. Furthermore, both extracts stimulated the in vitro insulin secretion in a glucose-independent manner. In perifused islets, the insulin secretion was augmented in low glucose (3 mM), increased gradually in high glucose (16.7 mM), and was restored to basal levels when each extract was removed. The mechanism behind the stimulation of insulin secretion of A. caudatus mainly involved the protein kinases A and C activation, while the effect was partially dependent on the L-type calcium channel and the G protein-coupled exocytosis. L. mutabilis effect depended on L-type calcium channels, PKC and PKA systems, G protein-coupled exocytosis and K-ATP channels. The main constituents found in A. caudatus were amino acids, sugars, and polyphenols, while L. mutabilis extract has higher amounts of alkaloids. A caudatus is traditionally used to treat disorders in the urinary tract. L. mutabilis, on the other hand, is well known for its glycemic lowering effect. Since there is a globally increase of antibiotic resistance, we sought to investigate the possible role of these two medicinal plants in the treatment of urinary tract infections (UTI). We observed that the hydroethanolic extracts from A. caudatus and L. mutabilis prevented the uropathogenic E. coli (UPEC) in vitro infection. A. caudatus inhibited the first steps of infection, adhesion, and invasion of UPEC, including ESBL-producing E. coli and other uropathogenic bacteria, including multidrugresistant strains. The effect was attributed to the decrease of gene expression of uroplakin1a and caveolin-1. L. mutabilis inhibited UPEC adhesion and interfered in the adhesion process of other Gram-negative and positive uropathogenic bacteria, an effect observed in high glucose concentrations. This effect was explained by a downregulation of gene and protein expression of uroplakin-1a and an upregulation of the antimicrobial peptide RNase 7. Furthermore, the UPEC biofilm formation was inhibited only in low glucose conditions. In summary, this study provides information about the potential use of Amaranthus caudatus and Lupinus mutabilis, as a nutraceutical product, since they are part of the traditional Bolivian diet. The hydroethanolic extracts of Amaranthus caudatus and Lupinus mutabilis have pharmacological properties being promising candidates to treat type 2 diabetes mellitus and to prevent urinary tract infections

Efectos reductores de la glucemia de las plantas nutracéuticas bolivianas

Introduction: The prevalence of diabetes type 2 is increasing worldwide, thus the search of novel alternative therapies is needed. According to their traditional use, we selected five Bolivian plants Chenopodium quinoa (CQ) Amaranthus caudatus (AC), Chenopodium pallidicaule (CP), Lupinus mutabilis (LM) and Smallanthus sonchifolius (SS) that are traditionally used to control glycemia. Methods: The effect of a single oral administration of Ethanolic (EtOH), hydro-ethanolic (EtOH70) and aqueous (Aq) extracts from all plant species were tested for their effect on blood glucose in non-fasted mice and during the oral glucose tolerance test (OGTT). The effect on insulin secretion was evaluated in mice pancreatic islets. Results: EtOH70 extracts of all the plants showed glucose-reducing effect at the highest dose evaluated (2000 mg/ kg b.w.). EtOH70 extracts improved the glucose tolerance evaluated by the OGTT in mice fasted for 12 hours. The extracts have different effects on glucose homeostasis since just extracts of AC, LM and CQ but not CP and SS increased insulin secretion as shown on mice pancreatic islets. The phytochemical qualitative characterization of EtOH70 extracts detected phenolic acids and flavonoids in AC, CP and CQ; alkaloids in LM and anthocyanidins in SS. None of EtOH70 extracts tested showed in vitro or in vivo acute toxicity at concentrations where they exhibit glucose lowering effects. Conclusions: We report here that extracts from AC, CQ, CP, LM and SS exhibit glucose lowering effect while just AC, CQ and LM stimulate directly the insulin secretion.Introducción: La prevalencia de diabetes tipo 2 está aumentando en todo el mundo, por lo que se necesita la búsqueda de nuevas terapias alternativas. Según su uso tradicional, seleccionamos cinco plantas bolivianas Chenopodium quinoa (CQ) Amaranthus caudatus (AC), Chenopodium pallidicaule (CP), Lupinus mutabilis (LM) y Smallanthus sonchifolius (SS) que se usan tradicionalmente para controlar la glucemia. Métodos: Se evaluó el efecto de la administración oral única de extractos etanólicos (EtOH), hidroetanólicos (EtOH70) y acuosos (Aq) de las plantas mencionadas para determinar su efecto sobre la glucosa en sangre en ratones en o sin ayunas y durante la prueba de tolerancia a la glucosa oral (PTGO). El efecto sobre la secreción de insulina se evaluó en islotes pancreáticos de ratones. Resultados: Los extractos de EtOH70 de todas las plantas disminuyeron la glucemia a la dosis más alta evaluada (2000 mg / kg b.w.). Los extractos de EtOH70 mejoraron la tolerancia a la glucosa evaluada mediante la PTGO en ratones con ayuno de 12 horas. Los extractos tienen diferentes efectos sobre la homeostasis de la glucosa, ya que solo los extractos de AC, LM y CQ pero no CP y SS aumentaron la secreción de insulina como se muestra en los islotes pancreáticos de los murinos. La caracterización cualitativa fitoquímica de extractos de EtOH70 detectó ácidos fenólicos y flavonoides en AC, CP y CQ, alcaloides en LM y antocianidinas en SS. Ninguno de los extractos de EtOH70 probados mostró toxicidad aguda in vitro o in vivo a concentraciones en las que exhiben efectos reductores de glucosa. Conclusión: Los extractos de AC, CQ, CP, LM y SS exhiben un efecto reductor de la glucosa, mientras que solo AC, CQ y LM estimulan directamente la secreción de insulina.Swedish International Development Cooperation Agency, SID

Potential of NIRS Technology for the Determination of Cannabinoid Content in Industrial Hemp (<i>Cannabis sativa</i> L.)

Industrial hemp (Cannabis sativa L.) is a plant native to Asia, and is considered to be a primary source of food, textile fiber, and medicines. It is characterized by containing minimal concentrations of delta-9 tetrahydrocannabidol (THC), which is the main psychoactive chemical component, and cannabidiol (CBD), a non-psychoactive substance. In most European countries, the maximum concentration legally allowed for cultivation is 0.2% of THC, and it is currently under debate whether to increase this level to 0.3%. Moreover, in many countries its production is being regularized and legalized, increasing the need for a rapid analysis method. The present work evaluated the cannabinoid content in hemp (Cannabis sativa L.) using near infrared spectroscopy (NIRS) technology in combination with chemometric techniques. For this, several samples of the Kompolti variety were analyzed. Samples were dried and ground, and the content of total THC (%) and total CBD (%) was determined by high performance liquid chromatography (HPLC) with a diode array detector as reference measurements, and then the spectra were collected by NIRS. Principal component analysis and partial least square regression models were developed. Good coefficients of determination of cross-validation of 0.77 for THC and CBD, and a ratio of prediction to deviation >2 for total THC and CBD, were achieved. The results obtained show that NIRS technology has potential for the quantitative determination of cannabinoids. Therefore, this analytical method would allow a simpler, more robust, precise, and sustainable estimation than the current HPLC approach

Lupinus mutabilis Edible Beans Protect against Bacterial Infection in Uroepithelial Cells

Lupinus mutabilis is a South American herb with edible beans, known to reduce serum glucose levels in diabetic patients. Furthermore, L. mutabilis contains phytochemicals known to decrease bacterial load. Based on the increased urinary tract infections experienced among patients with diabetes, we investigated the effect of L. mutabilis on bladder epithelial cells in the protection of E. coli infection during normal and high glucose concentrations. We did not observe any direct antibacterial effect by L. mutabilis extract. Instead we observed an influence on the host cells, with indirect impact on bacteria and their possibility of causing infection. L. mutabilis extract decreased adhesion to bladder epithelial cells of uropathogenic bacteria, including drug-resistant strains. Moreover, uroplakin1a, involved in adhesion, was downregulated while the antimicrobial peptide RNase 7 was upregulated in L. mutabilis treated cells irrespectively of glucose concentration. This supports an early effect fighting bacteria. Additionally, L. mutabilis prevented bacterial biofilm formation, which is used by bacteria to evade the immune system and antibiotics. In summary, L. mutabilis protects against bacterial infection in uroepithelial cells by preventing adhesion through alteration of the cell surface, increasing antimicrobial peptide expression, and reducing biofilm formation. Together, this promotes bacterial clearance, suggesting that L. mutabilis as extract or as a dietary item can contribute to the prevention of urinary tract infections, which is of importance in an era of increasing antibiotic resistance

Amaranthus caudatus Stimulates Insulin Secretion in Goto-Kakizaki Rats, a Model of Diabetes Mellitus Type 2

Diabetes Mellitus Type 2 prevalence is increasing worldwide; thus efforts to develop novel therapeutic strategies are required. Amaranthus caudatus (AC) is a pseudo-cereal with reported anti-diabetic effects that is usually consumed in food preparations in Bolivia. This study evaluated the anti-diabetic nutraceutical property of an AC hydroethanolic extract that contains mainly sugars and traces of polyphenols and amino acids (as shown by nalysis with liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR)), in type 2 diabetic Goto-Kakizaki (GK) rats and healthy Wistar (W) rats. A single oral administration of AC extract (2000 mg/kg body weight) improved glucose tolerance during Oral Glucose Tolerance Tests (OGTT) in both GK rats and in W rats. Long-term treatment (21 days) with AC (1000 mg/kg b.w.) improved the glucose tolerance evaluated by the area under the curve (AUC) of glucose levels during the OGTT, in both GK and W rats. The HbA1c levels were reduced in both GK (19.83%) and W rats (10.7%). This effect was secondary to an increase in serum insulin levels in both GK and W rats and confirmed in pancreatic islets, isolated from treated animals, where the chronic AC exposure increased the insulin production 4.1-fold in GK and 3.7-fold in W rat islets. Furthermore, the effect of AC on in vitro glucose-dependent insulin secretion (16.7 mM glucose) was concentration-dependent up to 50 mg/mL, with 8.5-fold increase in GK and 5.7-fold in W rat islets, and the insulin secretion in perifused GK and W rat islets increased 31 and nine times, respectively. The mechanism of action of AC on insulin secretion was shown to involve calcium, PKA and PKC activation, and G-protein coupled-exocytosis since the AC effect was reduced 38% by nifedipine (L-type channel inhibitor), 77% by H89 (PKA inhibitor), 79% by Calphostine-C (PKC inhibitor) and 20% by pertussis toxin (G-protein suppressor)

Lupinus mutabilis Extract Exerts an Anti-Diabetic Effect by Improving Insulin Release in Type 2 Diabetic Goto-Kakizaki Rats

Lupinus mutabilis (LM) is a legume part of Bolivian traditional diet that has a nutraceutical property reducing blood glucose levels. The prevalence of type 2 diabetes is increasing worldwide thus; the search for novel anti-diabetic drugs is needed. Based on its traditional use, we evaluated the anti-diabetic effect of LM in the spontaneously diabetic Goto-Kakizaki (GK) rat, a model of type 2 diabetes and in Wistar (W) rats as healthy control. LM seeds hydroethanolic extract, analyzed by gas chromatography-mass spectrometry and high-performance liquid chromatography-high resolution mass spectrometry, is a complex mixture of volatile and non-volatile components. A single oral administration of LM extract (2000 mg/kg b.w.) improved glucose tolerance during the oral glucose tolerance test (OGTT) (30&ndash;120 min) in GK and W rats (p &lt; 0.0001). The long-term treatment with LM (1000 mg/kg b.w.), for 21 days, improved the area under the curve (AUC) of glucose during OGTT at day 20, in both GK (p &lt; 0.01) and W rats (p &lt; 0.01). The HbA1c (GK rats, p &lt; 0.05 and W rats, p &lt; 0.0001) and the non-fasting glucose (GK rats, p &lt; 0.05) were also reduced. LM increased both serum insulin levels (2.4-fold in GK rats and 2.5-fold W rats), and the glucose-induced (16.7 mM glucose) insulin release in isolated islets from treated animals (6.7-fold in GK rats, and 6.6-fold in W rats). Moreover, LM (10 mg/mL) stimulated in vitro glucose induced (16.7 mM glucose) insulin release in batch incubated GK and W rat islets (p &lt; 0.0001). In perifused GK rat islets, insulin release in 16.7 mM glucose was increased 95.3-fold compared to untreated islets (p &lt; 0.0001), while no significant differences were found in perifused W rat islets. The LM mechanism of action, evaluated using inhibitory compounds of the insulin secretion pathway, showed that LM-dependent insulin secretion was reduced 42% by diazoxide (p &lt; 0.001), 70% by nifedipine (p &lt; 0.001), 86.7% by H89 (p &lt; 0.0001), 70.8% by calphostine-C (p &lt; 0.0001) and 93% by pertussis toxin (p &lt; 0.0001). A similar effect was observed in W rats islets. Our findings provide evidence that LM has an anti-diabetic effect through stimulation of insulin release. The effect is-dependent on L-type calcium channel, protein kinase A and C systems, and G protein-coupled exocytosis and is partially mediated by K-ATP channels

A Research Roadmap: Connected Health as an Enabler of Cancer Patient Support

The evidence that quality of life is a positive variable for the survival of cancer patients has prompted the interest of the health and pharmaceutical industry in considering that variable as a final clinical outcome. Sustained improvements in cancer care in recent years have resulted in increased numbers of people living with and beyond cancer, with increased attention being placed on improving quality of life for those individuals. Connected Health provides the foundations for the transformation of cancer care into a patient-centric model, focused on providing fully connected, personalized support and therapy for the unique needs of each patient. Connected Health creates an opportunity to overcome barriers to health care support among patients diagnosed with chronic conditions. This paper provides an overview of important areas for the foundations of the creation of a new Connected Health paradigm in cancer care. Here we discuss the capabilities of mobile and wearable technologies; we also discuss pervasive and persuasive strategies and device systems to provide multidisciplinary and inclusive approaches for cancer patients for mental well-being, physical activity promotion, and rehabilitation. Several examples already show that there is enthusiasm in strengthening the possibilities offered by Connected Health in persuasive and pervasive technology in cancer care. Developments harnessing the Internet of Things, personalization, patient-centered design, and artificial intelligence help to monitor and assess the health status of cancer patients. Furthermore, this paper analyses the data infrastructure ecosystem for Connected Health and its semantic interoperability with the Connected Health economy ecosystem and its associated barriers. Interoperability is essential when developing Connected Health solutions that integrate with health systems and electronic health records. Given the exponential business growth of the Connected Health economy, there is an urgent need to develop mHealth (mobile health) exponentially, making it both an attractive and challenging market. In conclusion, there is a need for user-centered and multidisciplinary standards of practice to the design, development, evaluation, and implementation of Connected Health interventions in cancer care to ensure their acceptability, practicality, feasibility, effectiveness, affordability, safety, and equity.European Cooperation in Science and Technology (COST) ENJECT TD 1405European Union's Horizon 2020 grant number: 722012Tatra banka Foundation (2018vs108)Research Agency in Slovakia (ITMS: 26240120038)Fundação para a Ciência e a Tecnologia (FCT) SFRH/BSAB/142983/2018Fundação para a Ciência e a Tecnologia (FCT) UID/DTP/00617/201