Degradation of β-Carbolines Harman and Norharman in Edible Oils during Heating

The β-carbolines, mainly including harman and norharman, are a group of naturally occurring, plant-derived alkaloids, and are also considered as nonpolar heterocyclic aromatic amines. Sesame seed oils contain a high level of β-carbolines (harman and norharman). In China, sesame seed oil blends are one of the most popular types of vegetable oils blends, which can be used as cooking oils or frying oils. Thus, it is meaningful to investigate the degradation of β-carbolines (harman and norharman) in sesame seed oil blends as frying oils during heating. In this work, the loss of harman and norharman in different types of sesame seed oil blends have been investigated. The results showed that the degradation of harman and norharman were dependent both on the type of oil blends, heating temperature and time. Harman and norharman were more degraded during heating (150 °C, 180 °C) in oleic acid-rich oil blends compared to polyunsaturated acid-rich oil blends. Mechanistic investigation suggested that the reduction in harman and norharman in oil blends during heating was mainly due to the oxidative degradation reaction between β-carbolines and lipid oxidation products. Therefore, the contents of β-carbolines (harman and norharman) in sesame seed oil blends when used as frying oils and heated can be decreased with prolonged cooking time.     

Helical versus Flat Bis-Ferrocenyl End-Capped Peptides: The Influence of the Molecular Skeleton on Redox Properties

Despite the fact that peptide conjugates with a pendant ferrocenyl (Fc) have been widely investigated, bis-ferrocenyl end-capped peptides are rarely synthetized. In this paper, in addition to the full characterization of the Fc-CO-[_L-Dap(Boc)]_n-NH-Fc series, we report a comparison of the three series of bis-ferrocenyl homopeptides synthesized to date, to gain insights into the influence of α-amino isobutyric (Aib), 2,3-diamino propionic (Dap) and C^α,β-didehydroalanine (ΔAla) amino acids on the peptide secondary structure and on the ferrocene redox properties. The results obtained by 2D NMR analysis and X-ray crystal structures, and further supported by electrochemical data, evidence different behaviors depending on the nature of the amino acid; that is, the formation of 3₁₀-helices or fully extended (2.0₅-helix) structures. In these foldamers, the orientation of the carbonyl groups in the peptide helix yields a macrodipole with the positive pole on the N-terminal amino acid and the negative pole on the C-terminal amino acid, so that oxidation of the Fc moieties takes place more or less easily depending on the orientation of the macrodipole moment as the peptide chain grows. Conversely, the fully extended conformation adopted by ΔAla flat peptides neither generates a macrodipole nor affects Fc oxidation. The utilization as electrochemical and optical (Circular Dichroism) probes of the two terminal Fc groups, bound to the same peptide chain, makes it possible to study the end-to-end effects of the positive charges produced by single and double oxidations, and to evidence the presence “exciton-coupled” CD among the two intramolecularly interacting Fc groups of the _L-Dap(Boc) series.     

Chemical Composition of Essential Oils from Leaves and Fruits of Juniperus foetidissima and Their Attractancy and Toxicity to Two Economically Important Tephritid Fruit Fly Species,Ceratitis capitata and Anastrepha suspensa

The present study analyzed the chemical composition of Juniperus foetidissima Willd. essential oils (EOs) and evaluated their attractancy and toxicity to two agriculturally important tephritid fruit flies. The composition of hydrodistilled EOs obtained from leaves (JFLEO) and fruits (JFFEO) of J. foetidissima was analyzed by GC–FID and GC–MS. The main compounds were α-pinene (45%) and cedrol (18%) in the JFLEO and α-pinene (42%), α-thujone (12%), and β-thujone (25%) in the JFFEO. In behavioral bioassays of the male Mediterranean fruit fly, Ceratitis capitata (Wiedemann), both JFLEO and JFFEO showed strong attraction comparable to that observed with two positive controls, Melaleuca alternifolia and Tetradenia riparia EOs. In topical bioassays of the female Caribbean fruit fly, Anastrepha suspensa (Loew), the toxicity of JFFEO was two-fold higher than that of JFLEO, with the LD₅₀ values being 10.46 and 22.07 µg/µL, respectively. This could be due to differences in chemical components between JFLEO and JFFEO. The JFFEO was dominated by 48% monoterpene hydrocarbons (MH) and 46% oxygenated monoterpenes (OM), while JFLEO consisted of 57% MH, 18% OM, and 20% oxygenated sesquiterpenes (OS). This is the first study to evaluate the attractancy and toxicity of J. foetidissima EOs to tephritid fruit flies. Our results indicate that JFFEO has the potential for application to the management of pest tephritid species, and further investigation is warranted.     

Identification of Molecules from Coffee Silverskin That Suppresses Myostatin Activity and Improves Muscle Mass and Strength in Mice

Coffee has been shown to attenuate sarcopenia, the age-associated muscle atrophy. Myostatin (MSTN), a member of the TGF-β growth/differentiation factor superfamily, is a potent negative regulator of skeletal muscle mass, and MSTN-inhibition increases muscle mass or prevents muscle atrophy. This study, thus, investigated the presence of MSTN-inhibitory capacity in coffee extracts. The ethanol-extract of coffee silverskin (CSE) but not other extracts demonstrated anti-MSTN activity in a pGL3-(CAGA)₁₂-luciferase reporter gene assay. CSE also blocked Smad3 phosphorylation induced by MSTN but not by GDF11 or Activin A in Western blot analysis, demonstrating its capacity to block the binding of MSTN to its receptor. Oral administration of CSE significantly increased forelimb muscle mass and grip strength in mice. Using solvent partitioning, solid-phase chromatography, and reverse-phase HPLC, two peaks having MSTN-inhibitory capacity were purified from CSE. The two peaks were identified as ^βN-arachinoyl−5-hydroxytryptamide (C₂₀−5HT) and ^βN-behenoyl−5-hydroxytryptamide (C₂₂−5HT) using mass spectrometry and NMR analysis. In summary, the results show that CSE has the MSTN-inhibitory capacity, and C₂₀−5HT and C₂₂−5HT are active components of CSE-suppressing MSTN activity, suggesting the potential of CSE, C₂₀−5HT, and C₂₂−5HT being developed as agents to combat muscle atrophy and metabolic syndrome.     

Cembranolides and Related Constituents from the Soft Coral Sarcophyton cinereum

In an attempt to explore the bioactive metabolites of the soft coral Sarcophyton cinereum, three new cembranolides, cinerenolides A–C (1–3), and 16 known compounds were isolated and identified from the EtOAc extract. The structures of the new cembranolides were elucidated on the basis of spectroscopic analysis, and the NOE analysis of cinerenolide A (1) was performed with the assistance of the calculated lowest-energy molecular model. The relative configuration of cinerenolide C (3) was determined by the quantum chemical NMR calculation, followed by applying DP4+ analysis. In addition, the cytotoxic assays disclosed that some compounds exhibited moderate to potent activities in the proliferation of P388, DLD-1, HuCCT-1, and CCD966SK cell lines.     

Catalyst-Controlled Selectivity Switch in Three-Component Reaction: An NHC-Catalyzed Strategy for the Synthesis of δ-Lactone-Fused Spirobenzofuran-3-ones

An efficient, three-component reaction of aldehydes and benzofuran-3-ones was developed. This process provides a new approach for the preparation of synthetically and biologically important spirobenzofuran-3-one derivatives with moderate-to-good yields under mild conditions. A switch of intramolecular to intermolecular domino Michael–aldol–lactonization leading to differential product formation was achieved by different NHCs catalysis.     

The Development of Maillard Reaction,and Advanced Glycation End Product (AGE)-Receptor for AGE (RAGE) Signaling Inhibitors as Novel Therapeutic Strategies for Patients with AGE-Related Diseases

Advanced glycation end products (AGEs) are generated by nonenzymatic modifications of macromolecules (proteins, lipids, and nucleic acids) by saccharides (glucose, fructose, and pentose) via Maillard reaction. The formed AGE molecules can be catabolized and cleared by glyoxalase I and II in renal proximal tubular cells. AGE-related diseases include physiological aging, neurodegenerative/neuroinflammatory diseases, diabetes mellitus (DM) and its complications, autoimmune/rheumatic inflammatory diseases, bone-degenerative diseases, and chronic renal diseases. AGEs, by binding to receptors for AGE (RAGEs), alter innate and adaptive immune responses to induce inflammation and immunosuppression via the generation of proinflammatory cytokines, reactive oxygen species (ROS), and reactive nitrogen intermediates (RNI). These pathological molecules cause vascular endothelial/smooth muscular/connective tissue-cell and renal mesangial/endothelial/podocytic-cell damage in AGE-related diseases. In the present review, we first focus on the cellular and molecular bases of AGE–RAGE axis signaling pathways in AGE-related diseases. Then, we discuss in detail the modes of action of newly discovered novel biomolecules and phytochemical compounds, such as Maillard reaction and AGE–RAGE signaling inhibitors. These molecules are expected to become the new therapeutic strategies for patients with AGE-related diseases in addition to the traditional hypoglycemic and anti-hypertensive agents. We particularly emphasize the importance of “metabolic memory”, the “French paradox”, and the pharmacokinetics and therapeutic dosing of the effective natural compounds associated with pharmacogenetics in the treatment of AGE-related diseases. Lastly, we propose prospective investigations for solving the enigmas in AGE-mediated pathological effects.     

Supersaturation-Dependent Formation of Amyloid Fibrils

The supersaturation of a solution refers to a non-equilibrium phase in which the solution is trapped in a soluble state, even though the solute’s concentration is greater than its thermodynamic solubility. Upon breaking supersaturation, crystals form and the concentration of the solute decreases to its thermodynamic solubility. Soon after the discovery of the prion phenomena, it was recognized that prion disease transmission and propagation share some similarities with the process of crystallization. Subsequent studies exploring the structural and functional association between amyloid fibrils and amyloidoses solidified this paradigm. However, recent studies have not necessarily focused on supersaturation, possibly because of marked advancements in structural studies clarifying the atomic structures of amyloid fibrils. On the other hand, there is increasing evidence that supersaturation plays a critical role in the formation of amyloid fibrils and the onset of amyloidosis. Here, we review the recent evidence that supersaturation plays a role in linking unfolding/folding and amyloid fibril formation. We also introduce the HANABI (HANdai Amyloid Burst Inducer) system, which enables high-throughput analysis of amyloid fibril formation by the ultrasonication-triggered breakdown of supersaturation. In addition to structural studies, studies based on solubility and supersaturation are essential both to developing a comprehensive understanding of amyloid fibrils and their roles in amyloidosis, and to developing therapeutic strategies.     

Action Sites and Clinical Application of HIF-1α Inhibitors

Hypoxia-inducible factor-1α (HIF-1α) is widely distributed in human cells, and it can form different signaling pathways with various upstream and downstream proteins, mediate hypoxia signals, regulate cells to produce a series of compensatory responses to hypoxia, and play an important role in the physiological and pathological processes of the body, so it is a focus of biomedical research. In recent years, various types of HIF-1α inhibitors have been designed and synthesized and are expected to become a new class of drugs for the treatment of diseases such as tumors, leukemia, diabetes, and ischemic diseases. This article mainly reviews the structure and functional regulation of HIF-1α, the modes of action of HIF-1α inhibitors, and the application of HIF-1α inhibitors during the treatment of diseases.     

Bioactive β-Carbolines Harman and Norharman in Sesame Seed Oils in China

The β-carbolines in our diet, mainly including harman and norharman, are a group of biologically active, naturally occurring plant-derived alkaloids. Fragrant sesame seed oil is one of the most popular flavor edible oils in China. Considering that sesame seeds are roasted at 200–240 °C during the processing of flavor sesame seed oils, it is meaningful to investigate the levels of β-carboline compounds in various sesame seed oils. In this work, the levels of β-carbolines (harman and norharman) in different types of sesame seed oils in China (e.g., pressed fragrant sesame oil, ground fragrant sesame oil) have been determined systematically. The results showed that the levels of total β-carbolines in pressed fragrant sesame oils (700.5~2423.2 μg/kg) were higher than that in ground fragrant sesame oils (660.4~1171.7 μg/kg). Roasting sesame seeds at high temperatures (200–240 °C) led to higher levels of β-carbolines (660~2400 μg/kg) in fragrant sesame seed oils. In addition, the loss of tryptophan might be attributed to the formation of β-carbolines in sesame seeds during the roasting process. In general, fragrant sesame seed oils (pressed fragrant sesame oils, ground fragrant sesame oils) contain higher levels of β-carbolines due to the formation of harman and norharman during the roasting sesame seed process.     

The Fumarprotocetraric Acid Inhibits Tau Covalently,Avoiding Cytotoxicity of Aggregates in Cells

Neurodegenerative disorders, including Tauopathies that involve tau protein, base their pathological mechanism on forming proteinaceous aggregates, which has a deleterious effect on cells triggering an inflammatory response. Moreover, tau inhibitors can exert their mechanism of action through noncovalent and covalent interactions. Thus, Michael’s addition appears as a feasible type of interaction involving an α, β unsaturated carbonyl moiety to avoid pathological confirmation and further cytotoxicity. Moreover, we isolated three compounds from Antarctic lichens Cladonia cariosa and Himantormia lugubris: protolichesterinic acid (1), fumarprotocetraric acid (2), and lichesterinic acid (3). The maleimide cysteine labeling assay showed that compounds 1, 2, and 3 inhibit at 50 µM, but compounds 2 and 3 are statistically significant. Based on its inhibition capacity, we decided to test compound 2 further. Thus, our results suggest that compound 2 remodel soluble oligomers and diminish β sheet content, as demonstrated through ThT experiments. Hence, we added externally treated oligomers with compound 2 to demonstrate that they are harmless in cell culture. First, the morphology of cells in the presence of aggregates does not suffer evident changes compared to the control. Additionally, the externally added aggregates do not provoke a substantial LDH release compared to the control, indicating that treated oligomers do not provoke membrane damage in cell culture compared with aggregates alone. Thus, in the present work, we demonstrated that Michael’s acceptors found in lichens could serve as a scaffold to explore different mechanisms of action to turn tau aggregates into harmless species.     

Structure-Acid Lability Relationship of N-alkylated α,α-dialkylglycine Obtained via a Ugi Multicomponent Reaction

Using the classical Ugi four-component reaction to fuse an amine, ketone, carboxylic acid, and isocyanide, here we prepared a short library of N-alkylated α,α-dialkylglycine derivatives. Due to the polyfunctionality of the dipeptidic scaffold, this highly steric hindered system shows an interesting acidolytic cleavage of the C-terminal amide. In this regard, we studied the structure-acid lability relationship of the C-terminal amide bond (cyclohexylamide) of N-alkylated α,α-dialkylglycine amides 1a–n in acidic media and, afterward, it was established that the most important structural features related to its cleavage. Then, it was demonstrated that electron-donating effects in the aromatic amines, flexible acyl chains (Gly) at the N-terminal and the introduction of cyclic compounds into dipeptide scaffolds, increased the rate of acidolysis. All these effects are related to the ease with which the oxazolonium ion intermediate forms and they promote the proximity of the central carbonyl group to the C-terminal amide, resulting in C-terminal amide cleavage. Consequently, these findings could be applied for the design of new protecting groups, handles for solid-phase synthesis, and linkers for conjugation, due to its easily modulable and the fact that it allows to fine tune its acid-lability.     

Bioactivity Guided Study for the Isolation and Identification of Antidiabetic Compounds from Edible Seaweed—Ulva reticulata

Managing diabetes is challenging due to the complex physiology of the disease and the numerous complications associated with it. As part of the ongoing search for antidiabetic chemicals, marine algae have been demonstrated to be an excellent source due to their medicinal properties. In this study, Ulva reticulata extracts were investigated for their anti-diabetic effect by examining its inhibitory effects on α-amylase, α-glucosidase, and DPP-IV and antioxidant (DPPH) potential in vitro and its purified fraction using animal models. Among the various solvents used, the Methanolic extract of Ulva reticulata (MEUR) displayed the highest antidiabetic activity in both in vitro and in vivo; it showed no cytotoxicity and hence was subjected to bioassay-guided chromatographic separation. Among the seven isolated fractions (F1 to F7), the F4 (chloroform) fraction exhibited substantial total phenolic content (65.19 μg mL⁻¹) and total flavonoid content (20.33 μg mL⁻¹), which showed the promising inhibition against α-amylase (71.67%) and α-glucosidase (38.01%). Active fraction (F4) was further purified using column chromatography, subjected to thin-layer chromatography (TLC), and characterized by spectroscopy techniques. Upon structural elucidation, five distinct compounds, namely, Nonane, Hexadecanoic acid, 1-dodecanol, Cyclodecane methyl, and phenol, phenol, 3,5-bis(1,1-dimethylethyl) were identified. The antidiabetic mechanism of active fraction (F4) was further investigated using various in vitro and in vivo models. The results displayed that in in vitro both 1 and 24 h in vitro cultures, the active fraction (F4) at a concentration of 100 μg mL⁻¹ demonstrated maximum glucose-induced insulin secretion at 4 mM (0.357 and 0.582 μg mL⁻¹) and 20 mM (0.848 and 1.032 μg mL⁻¹). The active fraction (F4) reduces blood glucose levels in normoglycaemic animals and produces effects similar to that of standard acarbose. Active fraction (F4) also demonstrated outstanding hypoglycaemic activity in hyperglycemic animals at a dose of 10 mg/kg B.wt. In the STZ-induced diabetic rat model, the active fraction (F4) showed a (61%) reduction in blood glucose level when compared to the standard drug glibenclamide (68%). The results indicate that the marine algae Ulva reticulata is a promising candidate for managing diabetes by inhibiting carbohydrate metabolizing enzymes and promoting insulin secretion.     

Synthesis,Antibacterial, and Antioxidant Evaluation of Novel Series of Condensed Thiazoloquinazoline with Pyrido,Pyrano, and Benzol Moieties as Five- and Six-Membered Heterocycle Derivatives

A novel synthesis of thiazolo[2,3-b]quinazolines 4(a–e), pyrido[2′,3′:4,5]thiazolo[2,3-b]quinazolines {5(a–e), 6(a–e), and 7(a–e)}, pyrano[2′,3′:4,5]thiazolo[2,3-b]quinazolines 8(a–e), and benzo[4,5]thiazolo[2,3-b]quinazoloine9(a–e) derivatives starting from 2-(Bis-methylsulfanyl-methylene)-5,5-dimethyl-cyclohexane-1,3-dione 2 as efficient α,α dioxoketen dithioacetal is reported and the synthetic approaches of these types of compounds will provide an innovative molecular framework to the designing of new active heterocyclic compounds. In our study, we also present optimization of the synthetic method along with a biological evaluation of these newly synthesized compounds as antioxidants and antibacterial agents against the bacterial strains, like S. aureus, E. coli, and P. aeruginosa. Among all the evaluated compounds, it was found that some showed significant antioxidant activity at 10 μg/mL while the others exhibited better antibacterial activity at 100 μg/mL. The results of this study showed that compound 6(c) possessed remarkable antibacterial activity, whereas compound 9(c) exhibited the highest efficacy as an antioxidant. The structures of the new synthetic compounds were elucidated by elemental analysis, IR, ¹H-NMR, and ¹³C-NMR.     

5-Amino-3-methyl-Isoxazole-4-carboxylic Acid as a Novel Unnatural Amino Acid in the Solid Phase Synthesis of α/β-Mixed Peptides

The hybrid peptides consisting of α and β-amino acids show great promise as peptidomimetics that can be used as therapeutic agents. Therefore, the development of new unnatural amino acids and the methods of their incorporation into the peptide chain is an important task. Here, we described our investigation of the possibility of 5-amino-3-methyl-isoxazole-4-carboxylic acid (AMIA) application in the solid phase peptide synthesis. This new unnatural β-amino acid, presenting various biological activities, was successfully coupled to a resin-bound peptide using different reaction conditions, including classical and ultrasonic agitated solid-phase synthesis. All the synthesized compounds were characterized by tandem mass spectrometry. The obtained results present the possibility of the application of this β-amino acid in the synthesis of a new class of bioactive peptides.     

Determination of Edible Vegetable Oil Adulterants in Sesame Oil Using 1H Nuclear Magnetic Resonance Spectroscopy

An NMR method is reported for the determination of sesamin to verify the authenticity of sesame oil. The intensity of the well-resolved H2′ sesamin signal resonating at approximately 5.95 ppm is strongly correlated with the amounts of other types of vegetable oils present in the adulterated sesame oil using the relationship, y = 4.020x + 1.516 (r ²  = 0.9967). The H2′ peak intensity of sesamin was measured for sesame oil extracted directly from the mill-sourced sesame seeds because the sesame oils purchased from local markets could be adulterated. Additionally, the oils used were obtained from the seeds native to China and the Republic of Korea, because the sesamin concentrations may vary from region to region. The proposed ¹H NMR method allows for the simple identification and determination of cheaper vegetable oils used as adulterants in sesame oil. High-performance liquid chromatography was used to confirm the validity of the results obtained by NMR.     

Eucalyptus gunnii and Eucalyptus pulverulenta ‘Baby Blue’ Essential Oils as Potential Natural Herbicides

The phytotoxicity and eco-compatibility of essential oils (EOs) from Eucalyptus gunnii (EG) and E. pulverulenta ‘Baby Blue’ (EP), cultivated in Italy for their cut foliage, were investigated. Leaf micromorphology, EOs phytochemical characterization, and phytotoxicity were analysed. EP revealed a significantly higher oil gland density and a higher EO yield with respect to EG. In both EOs, 1,8-cineole was the major compound (~75%), followed by α-pinene in EG (13.1%) and eugenol in EP (7.5%). EO phytotoxicity was tested on both weeds (Lolium multiflorum, Portulaca oleracea) and crops (Raphanus sativus, Lactuca sativa, Lepidium sativum, Solanum lycopersicum, Pisum sativum, Cucumis sativus). EG EO inhibited germination of P. oleracea, R. sativus, and S. lycopersicum seeds (ranging from 61.5 to 94.6% for the higher dose used), while affecting only radical elongation in S. lycopersicum (ranging from 66.7 to 82.6%). EP EO inhibited germination of P. oleracea and R. sativus (ranging from 41.3 to 74.7%) and affected radical elongation of L. sativum and L. multiflorum (ranging from 57.4 to 76.0%). None of the EOs affected the germination and radical growing of L. sativa, P. sativum, and C. sativus. Moreover, EP EO was more active than EG EO in inhibiting α-amylase, a key enzyme for seed growth regulation. Brine shrimp lethality assay showed that both EOs are safe for aquatic organisms, suggesting their high eco-compatibility. The data collected provide useful information for future applications of these EOs in agriculture as safe and selective bioherbicides.     

Chemical Diversity of Essential Oil of Valeriana jatamansi from Different Altitudes of Himalaya and Distillation Methods

Valeriana jatamansi is an important temperate herb that is used in the pharmaceutical and essential oil industries. In India, this species is now on the verge of extinction due to the over-exploitation of its rhizomes from its natural habitat. It is hypothesized that the variations in bioactive compounds in its essential oil are very high among the wild populations as well as cultivated sources. Thus, this study was conducted to evaluate the chemical profiling of essential oil of four wild populations (Rupena, Kugti, Garola, and Khani) and two cultivated sources (CSIR-IHBT, Salooni), which were distilled at three consecutive days. The variation in oil concentration in roots/rhizomes was found significant (p ≤ 0.05), and the maximum value (0.35%) was registered with the population collected from Kugti and Khani. In essential oil, irrespective of population and distillation day, patchouli alcohol was the major compound, which ranged from 19 to 63.1%. The maximum value (63.1%) was recorded with the essential oil obtained from Garola’s population and distilled on the first day. The percentage of seychellene was abruptly increased with subsequent days of extraction in all the populations. The multivariate analysis revealed that the essential oil profiles of Rupena, Kugti, Garola, and CSIR-IHBT populations were found to be similar during the first day of distillation. However, during the second day, Rupena, Kugti, Khani, and CSIR-IHBT came under the same ellipse of 0.95% coefficient. The results suggest that the population of Kugti is superior in terms of oil concentration (0.35%), with a higher proportion of patchouli alcohol (63% on the first day). Thus, repeated distillation is recommended for higher recovery of essential oil. Moreover, repeated distillation can be used to attain V. jatamansi essential oil with differential and perhaps targeted definite chemical profile.     

Tentatively Identified (UPLC/T-TOF–MS/MS) Compounds in the Extract of Saussurea costus Roots Exhibit In Vivo Hepatoprotection via Modulation of HNF-1α, Sirtuin-1, C/ebpα, miRNA-34a and miRNA-223

Saussurea costus is a plant traditionally used for the treatment of several ailments. Our study accomplished the UPLC/T-TOF–MS/MS analysis of a methanol extract of Saussurea costus roots (MESC), in addition to lipoidal matter determination and assessment of its in vivo hepatoprotective activity. In this study, we were able to identify the major metabolites in MESC rather than the previously known isolated compounds, improving our knowledge of its chemical constituents. The flavones apigenin, acacetin, baicalein, luteolin, and diosmetin, and the flavonol aglycones quercetin, kaempferol, isorhamnetin, gossypetin, and myricetin and/or their glycosides and glucuronic derivatives were the major identified compounds. The hepatoprotective activity of MESC was evaluated by measuring catalase activity using UV spectrophotometry, inflammatory cytokines and apoptotic markers using ELISA techniques, and genetic markers using PCR. Paracetamol toxicity caused a significant increase in plasma caspase 2, cytokeratin 18 (CK18), liver tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), miRNA-34a, and miRNA-223, as well as a significant decrease in liver catalase (CAT) activity and in the levels of liver nuclear factor 1α (HNF-1α), sirtuin-1, and C/ebpα. Oral pretreatment with MESC (200 mg/kg) showed a significant decrease in caspase 2, CK18, TNF-α, IL-6 and a significant increase in liver CAT activity. MESC decreased the levels of liver miRNA-34a and miRNA-223 and induced HNF-1α, sirtuin-1, and C/ebpα gene expression. The histological examination showed a significant normalization in rats pretreated with MESC. Our findings showed that Saussurea costus may exert a potent hepatoprotective activity through the modulation of the expression of cellular cytokines, miRNA-34a, and miRNA-223.     

Selected Species of the Cucurbitaceae Family Used in Mexico for the Treatment of Diabetes Mellitus

In Mexico, Diabetes mellitus (DM) is a serious health problem, and although the current pharmacological treatments for DM such as insulin and oral hypoglycemics are available, the Mexican population continues to use medicinal plants in the treatment of DM. The antidiabetic properties of the plant species that belong to the Cucurbitaceae family has already been recognized worldwide. Since Mexico is one of the most important centers of diversity of Cucurbitaceae, the present work contributes to the review of the most used species of Cucurbitaceae in the treatment of DM in Mexico. The reviewed species (Cucurbita ficifolia, C. maxima, C. moschata, C. pepo, Ibervillea sonorae, Sechium edule, Citrullus lanatus, Cucumis melo, and C. sativus) revealed that the antidiabetic effects exerted are effective in a number of mechanisms involved in the complex pathogenesis of DM: hypoglycemic, antioxidant, anti-inflammatory, anti-obesity, protective effects on diverse organs and cells, as well as in the control of dyslipidemias; furthermore, the select species of the Cucurbitaceae family could also be essential components of diets for the control of DM in patients with the disease. Thus, the Cucurbitaceae species selected in the present work represent a source of antidiabetic agents that perhaps establish the bases for novel clinical treatments.