PeruNPDB: the Peruvian Natural Products Database for in silico drug screening.

Since the number of drugs based on natural products (NPs) represents a large source of novel pharmacological entities, NPs have acquired significance in drug discovery. Peru is considered a megadiverse country with many endemic species of plants, terrestrial, and marine animals, and microorganisms. NPs databases have a major impact on drug discovery development. For this reason, several countries such as Mexico, Brazil, India, and China have initiatives to assemble and maintain NPs databases that are representative of their diversity and ethnopharmacological usage. We describe the assembly, curation, and chemoinformatic evaluation of the content and coverage in chemical space, as well as the physicochemical attributes and chemical diversity of the initial version of the Peruvian Natural Products Database (PeruNPDB), which contains 280 natural products. Access to PeruNPDB is available for free ( https://perunpdb.com.pe/ ). The PeruNPDB's collection is intended to be used in a variety of tasks, such as virtual screening campaigns against various disease targets or biological endpoints. This emphasizes the significance of biodiversity protection both directly and indirectly on human health.

Integrated metabolite analysis and health-relevant in vitro functionality of white, red, and orange maize (Zea mays L.) from the Peruvian Andean race Cabanita at different maturity stages.

The high maize (Zea mays L.) diversity in Peru has been recognized worldwide, but the investigation focused on its integral health-relevant and bioactive characterization is limited. Therefore, this research aimed at studying the variability of the primary and the secondary (free and dietary fiber-bound phenolic, and carotenoid compounds) metabolites of three maize types (white, red, and orange) from the Peruvian Andean race Cabanita at different maturity stages (milk-S1, dough-S2, and mature-S3) using targeted and untargeted methods. In addition, their antioxidant potential, and α-amylase and α-glucosidase inhibitory activities relevant for hyperglycemia management were investigated using in vitro models. Results revealed a high effect of the maize type and the maturity stage. All maize types had hydroxybenzoic and hydroxycinnamic acids in their free phenolic fractions, whereas major bound phenolic compounds were ferulic acid, ferulic acid derivatives, and p-coumaric acid. Flavonoids such as luteolin derivatives and anthocyanins were specific in the orange and red maize, respectively. The orange and red groups showed higher phenolic ranges (free + bound) (223.9-274.4 mg/100 g DW, 193.4- 229.8 mg/100 g DW for the orange and red maize, respectively) than the white maize (162.2-225.0 mg/100 g DW). Xanthophylls (lutein, zeaxanthin, neoxanthin, and a lutein isomer) were detected in all maize types. However, the orange maize showed the highest total carotenoid contents (3.19-5.87 µg/g DW). Most phenolic and carotenoid compounds decreased with kernel maturity in all cases. In relation to the primary metabolites, all maize types had similar fatty acid contents (linoleic acid > oleic acid > palmitic acid > α-linolenic acid > stearic acid) which increased with kernel development. Simple sugars, alcohols, amino acids, free fatty acids, organic acids, amines, and phytosterols declined along with grain maturity and were overall more abundant in white maize at S1. The in vitro functionality was similar among Cabanita maize types, but it decreased with the grain development, and showed a high correlation with the hydrophilic free phenolic fraction. Current results suggest that the nutraceutical characteristics of orange and white Cabanita maize are better at S1 and S2 stages while the red maize would be more beneficial at S3.

Diversity of the Peruvian Andean maize (Zea mays L.) race Cabanita: Polyphenols, carotenoids, in vitro antioxidant capacity, and physical characteristics.

The high diversity of the Peruvian Andean maize (Zea mays L.) represents a biological and genetic heritage relevant for food security, but few studies are targeted toward its characterization and consequent valorization and preservation. The objective of this study was to evaluate the potential of the Peruvian Andean maize race Cabanita with respect to its bioactive profiles (free and bound phenolic and carotenoid composition), physical characteristics, and in vitro antioxidant properties. Maize landraces with variable kernel pigmentation were collected from two provinces (Caylloma and Castilla) within the Arequipa region (among ten Andean sites) and the phytochemical profile was evaluated by Ultra High-Performance Liquid Chromatography with diode array detector (UHPLC-DAD). All maize samples were important sources of phenolic compounds mainly soluble p-coumaric and ferulic acid derivatives whereas anthocyanins were only detected in maize with partially red pigmented kernels. Major phenolic compounds in the bound phenolic fractions were ferulic acid and its derivatives along with p-coumaric acid. Carotenoid compounds including xanthophylls such as lutein, lutein isomers, and zeaxanthin were only detected in orange and white-yellow pigmented maize and are reported for the first time in Peruvian landraces. The multivariate analysis using Principal Components Analysis (PCA) revealed low variability of all data which may indicate a level of similarity among maize samples based on evaluated variables. However, maize grown in Caylloma province showed more homogeneous physical characteristics and higher yield, whereas higher phenolic contents and antioxidant capacity were observed in maize from Castilla. Samples CAY (yellow-pigmented kernel, Castilla) and COM (orange-pigmented kernel, Caylloma) had the highest total phenolic (246.7 mg/100 g dried weight basis, DW) and carotenoid (1.95 µg/g DW) contents among all samples. The variable Andean environmental conditions along with differences in farming practices may play a role and should be confirmed with further studies. Current results provide the metabolomic basis for future research using integrated omics platforms targeted toward the complete characterization of the ethnic-relevant maize race Cabanita.

Primary and Phenolic Metabolites Analyses, In Vitro Health-Relevant Bioactivity and Physical Characteristics of Purple Corn (Zea mays L.) Grown at Two Andean Geographical Locations.

Purple corn (Zea mays L.) is native to the Andean region, but limited research has been performed about the potential metabolic variability when grown under Andean environmental conditions. This study was aimed at evaluating the phenolic and primary polar metabolites composition of purple corn (kernels and cobs) grown at two Peruvian Andean locations (lowland and highland) using targeted UHPLC (ultra-high-performance liquid chromatography) and untargeted GC-MS (gas chromatography mass spectrometry) metabolomic platforms, respectively. Changes in the physical characteristics and the in vitro bioactivity were also determined. Purple corn from the highland zone showed higher contents of ash, crude fiber, total phenolic contents, DPPH (2,2-diphenyl-1-picrylhydrazyl) antioxidant capacity, and α-amylase inhibitory activity in kernels, whereas increased levels of flavonoids (anthocyanins and quercetin derivatives) and ABTS [2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)] antioxidant capacity were observed in cobs in comparison to lowland samples. No effect of the Andean location was found on the α-glucosidase inhibitory activity relevant for hyperglycemia management, while yield-linked physical characteristics were high in purple corn grown at the lowland zone. Polar primary metabolites related to the carbohydrate (monosaccharides, sucrose, and d-sorbitol), amino acid (valine and alanine), and tricarboxylic acid cycle (succinic, fumaric, and aconitic acid) metabolism were higher in highland purple corn (cob and kernel) likely due to abiotic stress factors from the highland environment. This study provides the foundation for further breeding improvements at Andean locations.

Evaluation of phenolic antioxidant-linked in vitro bioactivity of Peruvian corn (Zea mays L.) diversity targeting for potential management of hyperglycemia and obesity.

Peruvian corn biodiversity is one of the highest in the world and may represent an important natural source of health relevant phenolic bioactive compounds whose potential needs to be investigated. This study investigated twenty-two Peruvian corn samples corresponding to five corn races (Arequipeño, Cabanita, Kculli, Granada and Coruca) in relation to their total phenolic contents (TPC), anthocyanin contents, Ultra-Performance Liquid Chromatography (UPLC) phenolic profiles and antioxidant capacity (ABTS and ORAC methods). Subsequently using both free and cell-wall bound phenolic fractions their health relevance targeting hyperglycemia (α-glucosidase and α-amylase inhibition) and obesity (lipase inhibition) potentials was evaluated using in vitro assay models. Antioxidant capacity and TPC were high in bound fractions from yellow-colored races in contrast to the purple-colored race (Kculli) which had high TPC (mainly anthocyanins) and antioxidant capacity in the free form. The major phenolic acids detected by UPLC were ferulic and p-coumaric acids. High α-glucosidase (32.5-76.1%, 25 mg sample dose) and moderate α-amylase inhibitory activities (13.6-29.0%, 250 mg sample dose) were found in all free fractions, but only samples from the Kculli race had lipase inhibitory activity (58.45-92.16%, 12.5 mg sample dose). Principal component analysis revealed that the variability of data was affected by the race and the α-glucosidase and lipase inhibitory activities positively correlated with anthocyanins and antioxidant capacity. Some accessions of Kculli, Granada and Cabanita races are promising for future breeding strategies focused on the development of improved corn varieties targeted for the design of functional foods relevant for hyperglycemia and obesity prevention.

Antimicrobial activity of an Amazon medicinal plant (Chancapiedra) (Phyllanthus niruri L.) against Helicobacter pylori and lactic acid bacteria.

The potential of water extracts of the Amazon medicinal plant Chancapiedra (Phyllanthus niruri L.) from Ecuador and Peru for antimicrobial activity against Helicobacter pylori and different strains of lactic acid bacteria such as Lactobacillus acidophilus, Lactobacillus casei and Lactobacillus plantarum was investigated. H. pylori was inhibited by both water extracts in a dose dependent manner, whereas lactic acid bacterial growth was not affected. Both extracts contained ellagic acid and hydroxycinnamic acid derivatives and exhibited high free radical scavenging linked-antioxidant activities (89%). However, gallic acid was detected only in the Ecuadorian extract. Preliminary studies on the mode of action of Chancapiedra against H. pylori revealed that inhibition may not involve proline dehydrogenase-based oxidative phosphorylation inhibition associated with simple mono-phenolics and could involve ellagitannins or other non-phenolic compounds through a yet unknown mechanism. This study provides evidence about the potential of Chancapiedra for H. pylori inhibition without affecting beneficial lactic acid bacteria.

Phenolic compounds, antioxidant activity and in vitro inhibitory potential against key enzymes relevant for hyperglycemia and hypertension of commonly used medicinal plants, herbs and spices in Latin America.

Traditionally used medicinal plants, herbs and spices in Latin America were investigated to determine their phenolic profiles, antioxidant activity and in vitro inhibitory potential against key enzymes relevant for hyperglycemia and hypertension. High phenolic and antioxidant activity-containing medicinal plants and spices such as Chancapiedra (Phyllantus niruri L.), Zarzaparrilla (Smilax officinalis), Yerba Mate (Ilex paraguayensis St-Hil), and Huacatay (Tagetes minuta) had the highest anti-hyperglycemia relevant in vitro alpha-glucosidase inhibitory activities with no effect on alpha-amylase. Molle (Schinus molle), Maca (Lepidium meyenii Walp), Caigua (Cyclanthera pedata) and ginger (Zingiber officinale) inhibited significantly the hypertension relevant angiotensin I-converting enzyme (ACE). All evaluated pepper (Capsicum) genus exhibited both anti-hyperglycemia and anti-hypertension potential. Major phenolic compounds in Matico (Piper angustifolium R.), Guascas (Galinsoga parviflora) and Huacatay were chlorogenic acid and hydroxycinnamic acid derivatives. Therefore, specific medicinal plants, herbs and spices from Latin America have potential for hyperglycemia and hypertension prevention associated with Type 2 diabetes.

Evaluation of indigenous grains from the Peruvian Andean region for antidiabetes and antihypertension potential using in vitro methods.

The health-relevant functionality of 10 thermally processed Peruvian Andean grains (five cereals, three pseudocereals, and two legumes) was evaluated for potential type 2 diabetes-relevant antihyperglycemia and antihypertension activity using in vitro enzyme assays. Inhibition of enzymes relevant for managing early stages of type 2 diabetes such as hyperglycemia-relevant alpha-glucosidase and alpha-amylase and hypertension-relevant angiotensin I-converting enzyme (ACE) were assayed along with the total phenolic content, phenolic profiles, and antioxidant activity based on the 1,1-diphenyl-2-picrylhydrazyl radical assay. Purple corn (Zea mays L.) (cereal) exhibited high free radical scavenging-linked antioxidant activity (77%) and had the highest total phenolic content (8 +/- 1 mg of gallic acid equivalents/g of sample weight) and alpha-glucosidase inhibitory activity (51% at 5 mg of sample weight). The major phenolic compound in this cereal was protocatechuic acid (287 +/- 15 microg/g of sample weight). Pseudocereals such as Quinoa (Chenopodium quinoa Willd) and Kañiwa (Chenopodium pallidicaule Aellen) were rich in quercetin derivatives (1,131 +/- 56 and 943 +/- 35 microg [expressed as quercetin aglycone]/g of sample weight, respectively) and had the highest antioxidant activity (86% and 75%, respectively). Andean legumes (Lupinus mutabilis cultivars SLP-1 and H-6) inhibited significantly the hypertension-relevant ACE (52% at 5 mg of sample weight). No alpha-amylase inhibitory activity was found in any of the evaluated Andean grains. This in vitro study indicates the potential of combination of Andean whole grain cereals, pseudocereals, and legumes to develop effective dietary strategies for managing type 2 diabetes and associated hypertension and provides the rationale for animal and clinical studies.

Effect of different cooking conditions on phenolic compounds and antioxidant capacity of some selected Brazilian bean (Phaseolus vulgaris L.) cultivars.

The effects of different cooking conditions such as soaking, atmospheric (100 degrees C) or pressure boiling (121 degrees C), and draining of cooking water following thermal treatment on phenolic compounds and the DPPH radical scavenging capacity from two selected Brazilian bean cultivars (black and yellow-brown seed coat color) were investigated using a factorial design (2(3)). Factors that significantly reduced the total phenolic contents and antioxidant capacity in both cultivars were the soaking and draining stage. Independent of cooking temperature, total phenolics and antioxidant capacities were enhanced in treatments without soaking and where cooking water was not discarded, and this was likely linked to an increase of specific phenolic compounds detected by high performance liquid chromatography such as flavonols and free phenolic acids in both cultivars. Cooking of beans either at 100 or 121 degrees C, without a soaking stage and keeping the cooking water, would be recommendable for retaining antioxidant phenolic compounds.

Evaluation of antihyperglycemia and antihypertension potential of native Peruvian fruits using in vitro models.

Local food diversity and traditional crops are essential for cost-effective management of the global epidemic of type 2 diabetes and associated complications of hypertension. Water and 12% ethanol extracts of native Peruvian fruits such as Lucuma (Pouteria lucuma), Pacae (Inga feuille), Papayita arequipeña (Carica pubescens), Capuli (Prunus capuli), Aguaymanto (Physalis peruviana), and Algarrobo (Prosopis pallida) were evaluated for total phenolics, antioxidant activity based on 2, 2-diphenyl-1-picrylhydrazyl radical scavenging assay, and functionality such as in vitro inhibition of alpha-amylase, alpha-glucosidase, and angiotensin I-converting enzyme (ACE) relevant for potential management of hyperglycemia and hypertension linked to type 2 diabetes. The total phenolic content ranged from 3.2 (Aguaymanto) to 11.4 (Lucuma fruit) mg/g of sample dry weight. A significant positive correlation was found between total phenolic content and antioxidant activity for the ethanolic extracts. No phenolic compound was detected in Lucuma (fruit and powder) and Pacae. Aqueous extracts from Lucuma and Algarrobo had the highest alpha-glucosidase inhibitory activities. Papayita arequipeña and Algarrobo had significant ACE inhibitory activities reflecting antihypertensive potential. These in vitro results point to the excellent potential of Peruvian fruits for food-based strategies for complementing effective antidiabetes and antihypertension solutions based on further animal and clinical studies.

Antidiabetes and antihypertension potential of commonly consumed carbohydrate sweeteners using in vitro models.

Commonly consumed carbohydrate sweeteners derived from sugar cane, palm, and corn (syrups) were investigated to determine their potential to inhibit key enzymes relevant to Type 2 diabetes and hypertension based on the total phenolic content and antioxidant activity using in vitro models. Among sugar cane derivatives, brown sugars showed higher antidiabetes potential than white sugars; nevertheless, no angiotensin I-converting enzyme (ACE) inhibition was detected in both sugar classes. Brown sugar from Peru and Mauritius (dark muscovado) had the highest total phenolic content and 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity, which correlated with a moderate inhibition of yeast alpha-glucosidase without showing a significant effect on porcine pancreatic alpha-amylase activity. In addition, chlorogenic acid quantified by high-performance liquid chromatography was detected in these sugars (128 +/- 6 and 144 +/- 2 microg/g of sample weight, respectively). Date sugar exhibited high alpha-glucosidase, alpha-amylase, and ACE inhibitory activities that correlated with high total phenolic content and antioxidant activity. Neither phenolic compounds or antioxidant activity was detected in corn syrups, indicating that nonphenolic factors may be involved in their significant ability to inhibit alpha-glucosidase, alpha-amylase, and ACE. This study provides a strong biochemical rationale for further in vivo studies and useful information to make better dietary sweetener choices for Type 2 diabetes and hypertension management.

Polyphenols and antioxidant capacity of seed coat and cotyledon from Brazilian and Peruvian bean cultivars (Phaseolus vulgaris L.).

Seed coats and cotyledons from 25 Brazilian and 3 Peruvian bean cultivars were investigated in relation to their phenolic profiles and antioxidant capacity. Condensed tannins, anthocyanins, and flavonols such as kaempferol and quercetin glycosides were mostly found in seed coats. Cotyledons were rich in phenolic acids, such as ferulic, sinapic, chlorogenic, and other hydroxycinnamic acids. In general, the seed coat color pattern and the type of cultivar showed an important influence on the variability of phenolic profiles and levels, respectively. Total phenolics and antioxidant capacity assessed by the DPPH method were higher in seed coats than in cotyledons. The antioxidant capacity had a significant correlation with condensed tannins for all samples and with total anthocyanins in black and red seed coats, whereas in cotyledons, it was more related to the total phenolic content.