Biological Activities of Miracle Berry Supercritical Extracts as Metabolic Regulators in Chronic Diseases.

Synsepalum dulcificum (Richardella dulcifica) is a berry fruit from West Africa with the ability to convert the sour taste into a sweet taste, and for this reason, the fruit is also known as the "miracle berry" (MB). The red and bright berry is rich in terpenoids. The fruit's pulp and skin contain mainly phenolic compounds and flavonoids, which correlate with their antioxidant activity. Different polar extracts have been described to inhibit cell proliferation and transformation of cancer cell lines in vitro. In addition, MB has been shown to ameliorate insulin resistance in a preclinical model of diabetes induced by a chow diet enriched in fructose. Herein, we have compared the biological activities of three supercritical extracts obtained from the seed-a subproduct of the fruit-and one supercritical extract obtained from the pulp and the skin of MB. The four extracts have been characterized in terms of total polyphenols content. Moreover, the antioxidant, anti-inflammatory, hypo-lipidemic, and inhibition of colorectal cancer cell bioenergetics have been compared. Non-polar supercritical extracts from the seed are the ones with the highest effects on the inhibition of bioenergetic of colorectal (CRC) cancer cells. At the molecular level, the effects on cell bioenergetics seems to be related to the inhibition of main drivers of the de novo lipogenesis, such as the sterol regulatory element binding transcription factor (SREBF1) and downstream molecular targets fatty acid synthase (FASN) and stearoyl coenzyme desaturase 1 (SCD1). As metabolic reprograming is considered as one of the hallmarks of cancer, natural extracts from plants may provide complementary approaches in the treatment of cancer. Herein, for the first time, supercritical extracts from MB have been obtained, where the seed, a by-product of the fruit, seems to be rich in antitumor bioactive compounds. Based on these results, supercritical extracts from the seed merit further research to be proposed as co-adjuvants in the treatment of cancer.

GC-MS Metabolomics profiling and HR-APCI-MS characterization of potential anticancer compounds and antimicrobial activities of extracts from Picrorhiza kurroa roots.

The present study explores pharmacological potential and phytochemicals profiling of Picrorhiza kurroa extracts against mammalian cancer cell lines and pathogenic microbes. Bioactive extracts from roots of Picrorhiza kurroa were recovered in the methanol, 50% aqueous dichloromethane (50 : 50 v/v) and n-hexane. Antimicrobial activity of the bioactive extracts was assessed against selected strains of bacteria and pathogenic fungi. Aqueous dichloromethane extract showed highest zone of growth inhibition (39.06 ± 1.0 mm) towards Staphylococcus aureus bacteria while methanolic extract showed the lowest inhibition (6.3 ± 4.1 mm) to Escherichia coli bacteria. The tested extracts such as methanol and aqueous dichloromethane exhibited higher inhibition antifungal activity against Aspergillus flavus compared to Fusarium oxysporum. As far as cytotoxicity (MTT assay) of the tested extracts is concerned, n-hexane and aqueous dichloromethane extracts were found to be very active against all cancer cell lines (breast cancer MCF7, MDA-MB-231, SKBR3 and ovarian cancer SKOV3). A preliminary phytochemicals profiling was performed in extracts using GC-MS. Several fractions of active extract were separated with HPLC and analyzed using High Resolution Atmospheric Pressure Chemical Ionization Mass Spectrometry (HR-APCI-MS). Two purified compounds (Dihydromikanolide and 1,3-Dicyclohexyl-4-(cyclohexylimino)-2-(cyclohexylethylamino)-3,4-dihydro-1,3-diazetium) were further evaluated for their anticancer activity against ovarian cancer cell line. Our findings depict that all the tested extracts showed considerable anticancer potential through cell viability assays. The purified compound 1 - Dihydromikanolide from methanolic extract was found to be active against ovarian cancer cells and can be explored as a promising nutra-pharmaceutical candidate against ovarian cancer. However, further studies exploring the molecular pathways and in vivo testing are required.

In vitro activity of bioactive extracts from rare actinomycetes against multi-drug resistant Streptococcus pneumoniae.

AIMS: In this study, we investigated the in vitro potential of the bioactive extracts from five putatively novel species of actinomycetes isolated from the Indian hot desert against multi-drug resistant (MDR) Streptococcus pneumoniae. METHODS AND RESULTS: The antimicrobial activity of 10 different extracts was evaluated against S. pneumoniae strains with, erm(B) and mef(E) genes as well as fluoroquinolone-resistant (FQ(R) ) strains using the micro-broth dilution method. Of these 10 extracts, four exhibited good to excellent anti-S. pneumoniae activity with minimum inhibitory concentrations (MICs) ranging from 0·125 to 8 µg ml(-1) . The time-kill kinetics study showed that these extracts killed the pathogens in 2-8 h. In vitro cell-free transcription/translation of luciferase gene using S30 bacterial extract and TNT mammalian ribosome indicated that they inhibited bacterial ribosomes at much lower concentrations than those required to inhibit the mammalian ribosomes. CONCLUSIONS: This study demonstrates that these are potent concentration-dependent bactericidal metabolites with 16-fold higher in vitro activity than levofloxacin against MDR S. pneumoniae. SIGNIFICANCE AND IMPACT OF THE STUDY: Metabolites from actinomycetes can be excellent inhibitors of MDR S. pneumoniae. Considering the in vitro efficacy of these crude extracts against S. pneumoniae MDR spp., once purified these can be used against streptococcal pathogens causing community-acquired pneumonia.

Biological capacities of seven Chilean ferns.

Sticherus squamulosus, Hymenophyllum dentatum, Blechnum microphyllum, Polypodium Feuillei, Blechnum chilense, Lophosoria quadripinnata, and Lissopimpla excelsa are native fern species found in southern Chile and are often used in traditional medicine. However, their bioactive properties have not been confirmed. In this study, ethanolic extracts of ferns exhibited significant antibacterial capacity against human pathogens. H. dentatum and S. squamulosus were selected for further analysis owing to their antimicrobial and antioxidant capacities. The entire H. dentatum extract exhibited fungistatic and fungicidal capacity on Botrytis cinerea and Penicillium digitatum, with minimum inhibitory concentration values of 1.56 mg/mL and 6.25 mg/mL and minimum fungicidal concentration values of 6.25 mg/mL and 12.5 mg/mL, respectively. The S. squamulosus extract presented the highest rutin content (222.5 µg/g fern). In addition, the ethanolic extract of H. dentatum inhibited 91% of DPPH radicals. Therefore, both types of ferns can be used in the food industry.

Novel bioactive extract from yarrow obtained by the supercritical antisolvent-assisted technique inhibits lipid metabolism in colorectal cancer.

Background: Altered lipid metabolism in cancer is associated to dissemination and prognosis. Bioactive compounds naturally occurring in Achillea millefolium L. (yarrow) have been reported to exert antitumour activities. Food biotechnology may provide on-demand mixtures of bioactive compounds with complementary activities in cancer treatment. Methods: Supercritical-antisolvent-precipitation (SAS) has been applied to fractionate the bioactive compounds from an Ultrasound-Assisted-Extraction yarrow extract resulting in two extracts with distinct polarity, yarrow-precipitate-(PP) and yarrow-separator-(Sep). Total phenolic content and relevant essential oils have been characterized. Antioxidant, anti-inflammatory and antiproliferative activities have been compared. Moreover, the effect on the inhibition of colorectal cancer cells' bioenergetics has been evaluated. Results: Yarrow-PP exerted the highest antioxidant activity, even higher than the complete UAE-yarrow extract, meanwhile yarrow-Sep showed the highest anti-inflammatory activity, even higher than the complete UAE-yarrow extract. Interestingly, yarrow-Sep inhibited key lipid metabolic targets in CRC cells extensively shown to be implicated in cancer dissemination and prognosis -SREBF1, FASN, ABCA1 and HMGCR- and epithelial to mesenchymal targets-CDH1, ATP1B1, CDH2 and Vimentin-augmenting cell adhesion. Conclusions: In summary, SAS technology has been applied to provide a novel combination of bioactive compounds, yarrow-Sep, which merits further research to be proposed as a potential complementary nutraceutical in the treatment of CRC.

High value-added lignin extracts from sugarcane by-products.

This study evaluates the production of lignin bioactive extracts from sugarcane bagasse (SCB) and straw (SCS) alkaline black liquors using greener precipitating agents (methane sulfonic acid (MSA), formic acid (FA) and lactic acid (LA)) as replacers of sulfuric acid (SA), the most common one used in industry. Results showed that the highest precipitation yield was achieved by LA when applied to SCB (14.5 g extract/100 g SCB). Lignin SCB extracts were similar in composition in terms of total carbohydrates (61-70 %), lignin (22-30 %) and inorganics (1.6-2.6 %). Regarding the SCS extracts, similar yields were obtained among all extracts, however, differences in composition were observed between SA and greener precipitating agents, particularly in terms of sugar content. All extracts exhibited radical scavenging activity; overall the extracts were more effective in the scavenging of ABTS radical. FA was the most promising alternative to SA to recover lignin bioactive extracts. This work suggests organic acids as good candidates for obtaining valuable extracts from alkaline pulping of SCB and SCS instead of the conventional sulfuric acid.

Sustainable valorization of co-products from asparagus cultivation by obtaining bioactive compounds.

Asparagus cultivation generates every year a significant amount of by-products that consist of root and frond. Leaving these residues on the fields after harvesting negatively affects the following asparagus crops, since they release autotoxic (allelopathic) substances into the soil, whose accumulation causes that asparagus yields gradually decrease over the years, becoming an unprofitable crop in a period of about 10 to 15 years. This phenomenon is known as decay and forces the entire asparagus plantation to be lifted (abandoned). On the other hand, once a certain plantation has been lifted, it is not profitable to immediately re-plant new asparagus plants, since the yields that are achieved are never more than half of normal ones. It is necessary to wait an average of 4 or 5 years before replanting asparagus in these lands. This phenomenon is known as the replanting problem, and causes the need to continually search for new land for growing asparagus. Another added problem for farmers is that the elimination of those plant residues from asparagus cultivation entails significant economic costs. For all these reasons, it is essential to seek alternatives for the management of that waste that improve the sustainability of the crop within the scope of the circular economy. In this context, this work proposes the valorization of asparagus by-products by obtaining bioactive compounds. Main objectives of the present work include: i) phytochemical analyses of asparagus fronds and roots; ii) obtaining bioactive extracts, with distinct technological and nutritional functionalities, by using an environmentally sustainable extraction process, easy to implement in the practice of a food industry and with methods compatible with food use. Characterization of asparagus by-products shown that fronds had an average flavonoid content of 2.637 ± 0.014 g/Kg fresh weight, which is up to 5-6 times higher than that of the spears; and roots contained up to 10 times more saponins (2.25 g/Kg fresh weight), which were accompanied by lower quantities of phenolic acids (368 mg/Kg fresh weight). Statistical analysis revealed that those phytochemical contents were mainly determined by location and phase of the vegetative cycle, whereas genetic factors did not significantly influence them. Based on the results of the present work, the proposal for the recovery and valorization of asparagus by-products is based on obtaining two bioactive extracts, the first being an antioxidant extract enriched in flavonoids, with an average yield of 10.7 g/Kg fresh frond and a flavonoid richness of 17%; and the second, a saponins extract with an average yield of 10.3 g/Kg fresh root and a richness of 51%. These natural extracts have great techno-functional potential in the agri-food industry and some of them are already being tested as additives in the preparation of soups, breads and meat products.

Nutraceutical Properties of Medicago sativa L., Agave spp., Zea mays L. and Avena sativa L.: A Review of Metabolites and Mechanisms.

Plants are the main sources of bioactive compounds (nutraceuticals) that function under different mechanisms of action for the benefit of human health. Mexico ranks fifth in the world in biodiversity, offering opportunities for healthy food. An important variety of crops are produced in the state of Hidalgo, e.g., based on the 2021 production, alfalfa, oats, maguey, and corn. The present review presents the latest findings of these crops, regarding the benefits they provide to health (bioactivity, nutraceuticals), and presents the compounds and mechanisms identified by which the benefit is provided. The knowledge compiled here is for the benefit of the recovery of the crops, the recognition of their bioactivities, in search of identifying the best routes of action for prevention, treatment and possible cure of chronic degenerative diseases (thereby promoting crop valorization). Exhaustive bibliographic research was carried out by means of engines and scientific databases. Articles published between 2001 and 2022 that included specific keywords (Scopus, EMBASE, EBSCO, PubMed, Science Direct, Web of Science, Google Scholar). Outstanding activities have been identified for the compounds in the crops, such as antiinflammatory, anticholesterolemic, antihypertensive, antidiabetic, anticancer, antimicrobial, antioxidant, and chelating. The compounds that provide these properties are total phenols, phenolic acids, tannins, anthocyanins, carotenoids, iso-flavones, phytosterols, saponins, fructans, glycosides, glucans, avenanthramides, and polysaccharides.

Multifunctional cellulosic aerogels from Posidonia oceanica waste biomass with antioxidant properties for meat preservation.

Posidonia oceanica waste biomass has been valorized to develop bioactive multifunctional cellulosic aerogels (HCAG) by simpler and greener protocols. Hydrophobization of cellulosic aerogels was achieved through PLA coating, while bioactivity was imparted by the incorporation of hydrophilic (E2) and hydrophobic extracts (E3) produced from the same biomass. The incorporation of extracts led to denser aerogels, with less porous structures. These aerogels showed outstanding water and oil sorption capacities (1500-1900%), being able to release the adsorbed liquid almost completely after 7 days. Interestingly, all the aerogels showed a positive inhibition effect (23-91%) on the ß-carotene bleaching assay. Moreover, the aerogels loaded with extracts, especially when combining E2 and E3, were able to reduce the oxidation of lipids and oxymyoglobin in red meat after 10 days of storage. This evidences the potential of these multifunctional aerogels as bioactive adsorbing pads to preserve the quality of fresh packaged foods.

Bioprospection for antiplasmodial activity, and identification of bioactive metabolites of native plants species from the Mata Atlântica biome, Brazil.

A total of 33 extracts of eleven different plants species from Mata Atlântica biome, Brazil, and different fractions of the bioactive extracts were evaluated against chloroquine-resistant Plasmodium falciparum W2 strain by PfLDH method and cytotoxicity to HepG2 cells by the MTT assay, and chemically characterized by LC-DAD-ESI-MS/MS analysis. The results allowed the identification of Alchornea glandulosa, Miconia latecrenata, and Psychotria suterella as the most active plant species. Different flavonoids and tannins in Alchornea glandulosa and Miconia latecrenata besides alkaloids in Psychotria suterella were identified. Bioguided fractionation of A. glandulosa and M. latecrenata leaves extracts led to fractions exhibiting high parasite growth inhibition. Seven known alkaloids were identified in the P. suterella extract, and of these, only 5-carboxystrictosidine had been assayed for antiplasmodial activity what points to this species as the most promising among the eleven one assayed.

Annexin A1 Mimetic Peptide and Piperlongumine: Anti-Inflammatory Profiles in Endotoxin-Induced Uveitis.

Uveitis is one of the main causes of blindness worldwide, and therapeutic alternatives are worthy of study. We investigated the effects of piperlongumine (PL) and/or annexin A1 (AnxA1) mimetic peptide Ac2-26 on endotoxin-induced uveitis (EIU). Rats were inoculated with lipopolysaccharide (LPS) and intraperitoneally treated with Ac2-26 (200 µg), PL (200 and 400 µg), or Ac2-26 + PL after 15 min. Then, 24 h after LPS inoculation, leukocytes in aqueous humor, mononuclear cells, AnxA1, formyl peptide receptor (fpr)1, fpr2, and cyclooxygenase (COX)-2 were evaluated in the ocular tissues, along with inflammatory mediators in the blood and macerated supernatant. Decreased leukocyte influx, levels of inflammatory mediators, and COX-2 expression confirmed the anti-inflammatory actions of the peptide and pointed to the protective effects of PL at higher dosage. However, when PL and Ac2-26 were administered in combination, the inflammatory potential was lost. AnxA1 expression was elevated among groups treated with PL or Ac2-26 + PL but reduced after treatment with Ac2-26. Fpr2 expression was increased only in untreated EIU and Ac2-26 groups. The interaction between Ac2-26 and PL negatively affected the anti-inflammatory action of Ac2-26 or PL. We emphasize that the anti-inflammatory effects of PL can be used as a therapeutic strategy to protect against uveitis.

Antibacterial potential assessment of Nalca (Gunnera tinctoria Mol.) ethanolic extracts.

Nalca is an edible rhubarb-type plant from the southern of Chile; with studies focussing on petiole chemical and biological properties. This work evaluated for the first time the antibacterial capacities of three organs of nalca against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Petiole (P), root (R) and flower (F) ethanolic extracts at three different concentrations (25, 50, 100 mg/mL) were evaluated by means of agar diffusion assay and MIC. The result showed that antibacterial activities are bacteria and concentration dependent, with root having the highest antimicrobial activity of the organs plant studied. Compared to commercial antibiotics, nalca extracts show promising control over Ps. aeruginosa. The main polyphenolics of the extracts were identified by UPLC-MS/MS, observing for the first time caffeic, coumaric and gallic acids presence in all samples, with quercetin and rutin determined in petiole and flower extracts only. Our results contribute to better understanding of nalca attributes as potential source of antibacterial compounds to be used in nutraceutical, cosmetic and food industry.

Role of Whole Plant Extract of Nelumbo nucifera Gaertn in the Treatment of Thrombolysis.

AIM: This study aims to find out the components responsible for the antithrombotic activity of Nelumbo nucifera. MATERIAL AND METHODS: Petroleum ether, chloroform and hydroalcoholic extracts of whole plant of Nelumbo nucifera (Lotus) were prepared and assessed for its thrombolytic, anti-platelet aggregation activity and bleeding time. The extracts were further analyzed through HPTLC and GC-MS. Statistical analysis was conducted through ANOVA trailed by Tukey's multiple comparison test test. RESULTS: Hydroalcoholic extract showed the highest activity at the concentration of 400µg/ml in thrombolytic assay (42.03 ± 5.76), anti-platelet aggregation assay (57.93 ± 1.68) and bleeding time (70.17 ± 2.16) in comparison to clopodigrel (33.76 ± 3.43), aspirin (66.55 ± 1.86) and aspirin (93.85 ± 2.75) at the concentration of 100 µg/ml respectively. 25 peaks were identified through GC-MS, out of which, ferulic acid (14.2µ/g) and quercetin (5.4 µ/g) are active chemical compounds. HPTLC showed different chromatograms in hydroalcoholic extracts like (1) chlorogenic, (2) quercetin, (3) benzoic acid, (4) caffeic acid, (5) ferulic acid, (6) kaempferol, and (7) gallic acid. CONCLUSION: Based on these findings, flavonoids present in hydroalcoholic extract may be developed into a drug for clinical application for the treatment of thrombosis in patients.

Variation in biochemical and antioxidant attributes of Raphanus sativus in response to foliar application of plant leaf extracts as plant growth regulator.

The present study was aimed to appraise the variations in biochemical, antioxidant and nutritional attributes of radish (Raphanus sativus L.) under foliar application of plant leaf aqueous extracts i.e., mulberry leaf extract (MLE), brassica leaf extract (BLE), sorghum leaf extract (SLE) and moringa leaf extract (MoLE) as natural growth regulators. Samples were collected after three sprays of extracts and analyzed. Total phenolic constituents were determined using Folin-Ciocalteu reagent method, whereas antioxidant potential was evaluated by 1,1 diphenyl-2-picrylhydrazyl radical radical scavenging and reducing power assays. Results revealed that application of MLE, BLE, SLE, and MoLE not only improved growth, but also enhanced biochemical and antioxidant activities. Foliar spray of MoLE furnished relatively three folds higher amounts of extractable bioactive compounds (37.65 ± 0.94%), phenolic constituents (54.51-182.71 mg GAE/g f.w). The radical scavenging capacity (RSC) and reducing potential were also enhanced considerably. Furthermore, the moisture, dietary fiber, crude protein, and carotenoids were also enhanced in response of foliar spray of plant extracts. From results, it is concluded that plant extracts are effective sources of natural growth regulars and might be useful for the production of vegetables with improved nutritional value and antioxidant activity.

Prospecção fitoquímica de cruá vermelho (Sicana odorifera Naudin) e atividade antioxidante do fruto / Phytochemical prospection of cruá vermelho (Sicana odorifera Naudin) and antioxidant activity of the fruit

Originária da América Tropical, provavelmente do Brasil, a Sicana odorifera Naudin (Cucurbitaceae) é uma planta herbácea anual, vigorosa, rasteira ou trepadeira, cujos frutos exalam um odor intenso e agradável quando maduros. O presente trabalho visou caracterizar os metabólitos secundários em extratos obtidos das folhas, sementes, polpa e casca do fruto, e avaliar a atividade antioxidante do fruto. Diferentes classes de metabólitos secundários foram identificadas nas análises qualitativas e quantitativas, realizadas nos diferentes extratos obtidos. A atividade antioxidante do extrato aquoso da polpa do fruto foi determinada pela habilidade de sequestrar o radical estável 2,2-difenil-1-picrilhidrazil (DPPH). Os carotenoides foram extraídos com acetona, separados com éter de petróleo e quantificados em espectrofotômetro UV. A triagem fitoquímica dos extratos indicou a presença de compostos como açúcares redutores, depsídeos e depsidonas, esteroides e triterpenoides, polissacarídeos, proteínas e aminoácidos, saponinas, taninos, alcaloides e carotenoides, além de atividade antioxidante na polpa do fruto. De acordo com os resultados obtidos constata-se que S. odorifera possui propriedades de interesse farmacológico. O estudo serve como subsídio preliminar sobre o conhecimento da composição química e viabilidade de emprego dessa planta para fins medicinais.

Being native of Tropical America, probably from Brazil, the Sicana odorifera Naudin (Cucurbitaceae) is an annual herbaceous plant, vigorous, creeping or climbing, whose fruits exude an intense and pleasant odor when ripe. This study aimed at characterizing the secondary metabolites in the extracts obtained from the leaves, seeds, pulp and fruit peel, and to evaluate the fruit antioxidant activity. Different classes of secondary metabolites were identified by the qualitative and quantitative analyzes in the varied extracts. The antioxidant activity of the aqueous extract from the fruit pulp was determined by the ability to sequester the stable radical 2,2-diphenyl-1-picryl hydrazyl (DPPH). The carotenoids were extracted with acetone, separated with the petroleum ether, and quantified by UV spectrophotometer. Phytochemical screening of extracts indicated the occurrence of compounds as the reducing sugars, depsids and depsidones, steroids and triterpenoids, polysaccharides, proteins and amino acids, saponins, tannins, alkaloids and carotenoids, besides the antioxidant activity in the fruit pulp. According to the obtained results, S. odorifera possesses properties of pharmacological interest. This study provides a preliminary subsidy on the knowledge concerning the chemical composition and the feasibility of using this plant for medicinal purposes.