4-Hydroxybenzoic Acid and β-Sitosterol from Cucurbita ficifolia Act as Insulin Secretagogues, Peroxisome Proliferator-Activated Receptor-Gamma Agonists, and Liver Glycogen Storage Promoters: In Vivo, In Vitro, and In Silico Studies

Wendoline Rosiles-Alanis,Alejandro Zamilpa,Rebeca Garcı´a-Macedo,Miguel A. Zavala-Sa´nchez,Sergio Hidalgo-Figueroa,Beatriz Mora-Ramiro,Rube´n Roma´n-Ramos,Samuel E. Estrada-Soto,Julio C. Almanza-Perez 한국식품영양과학회 2022 Journal of medicinal food Vol.25 No.6

Insulin secretion and GLUT4 expression are two critical events in glucose regulation. The receptors G-protein-coupled receptor 40 (GPR40) and peroxisome proliferator-activated receptor-gamma (PPARγ) modulate these processes, and they represent potential therapeutic targets for new antidiabetic agent's design. Cucurbita ficifolia fruit is used in traditional medicine for diabetes control. Previous studies demonstrated several effects: a hypoglycemic effect mediated by an insulin secretagogue action, antihyperglycemic effect, and promoting liver glycogen storage. Anti-inflammatory and antioxidant effects were also reported. Moreover, some of its phytochemicals have been described, including d-chiro-inositol. However, to understand these effects integrally, other active principles should be investigated. The aim was to perform a chemical fractionation guided by bioassay to isolate and identify other compounds from C. ficifolia fruit that explain its hypoglycemic action as insulin secretagogue, its antihyperglycemic effect by PPARγ activation, and on liver glycogen storage. Three different preparations of C. ficifolia were tested in vivo. Ethyl acetate fraction derived from aqueous extract showed antihyperglycemic effect in an oral glucose tolerance test and was further fractioned. The insulin secretagogue action was tested in RINm5F cells. For the PPARγ activation, C2C12 myocytes were treated with the fractions, and GLUT4 mRNA expression was measured. Chemical fractionation resulted in the isolation and identification of β-sitosterol and 4-hydroxybenzoic acid (4-HBA), which increased insulin secretion, GLUT4, PPARγ, and adiponectin mRNA expression, in addition to an increase in glycogen storage. 4-HBA exhibited an antihyperglycemic effect, while β-sitosterol showed hypoglycemic effect, confirming the wide antidiabetic related results we found in our in vitro models. An in silico study revealed that 4-HBA and β-sitosterol have potential as dual agonists on PPARγ and GPR40 receptors. Both compounds should be considered in the development of new antidiabetic drug development.

The Edible Mushroom Pleurotus djamor Produces Metabolites with Lethal Activity Against the Parasitic Nematode Haemonchus contortus

Jesus Antonio Pineda-Alegrıa,Jose Ernesto Sa´nchez-Vazquez,Manases Gonzalez-Cortazar,Alejandro Zamilpa,Marıa Eugenia Lopez-Arellano,Edgar Josue Cuevas-Padilla,Pedro Mendoza-de-Gives,Liliana Aguilar-Ma 한국식품영양과학회 2017 Journal of medicinal food Vol.20 No.12

Pleurotus djamor is an edible mushroom that has medicinal properties. This study aimed to assess the in vitro activity of P. djamor extracts and fractions against Haemonchus contortus eggs and exsheathed infective larvae (L3). Crude hydroalcoholic extracts were obtained by maceration and fractions were obtained through chromatography. Metabolite identity was determined using gas chromatography/mass spectrometry (GC-MS) analysis. The results showed that P. djamor extracts had no significant activity against eggs at the concentrations used. However, the extract showed 98.7% and 77% larval mortality 72 h postconfrontation at 320 and at 160 mg/mL, respectively. The chromatography analysis resulted in 23 fractions that were eventually grouped into three fractions (E1, E2, and E3). These fractions showed the following egg hatching inhibition percentages: E1 = 100, E2 = 38.7, and E3 = 5.5 at 10 mg/mL concentration 72 h postexposure. Likewise, larval mortality percentages after this period were 90.6, 100, and 0.44 at 40 mg/mL (P < .05), respectively. The GC-MS showed five major compounds in E1 fraction, including four fatty acids: (i) pentadecanoic, (ii) hexadecanoic, (iii) octadecadienoic, (iv) octadecanoic acid, and one terpene identified as β-sitosterol. We concluded that the edible mushroom P. djamor possesses nematicidal metabolites, which could be used as an alternative anthelmintic treatment.

Agave tequilana Counteracts Chronic Hypertension and Associated Vascular Damage

Maribel Herrera-Ruiz,Zu´lima Jannette Gutie´rrez-Nava,Celeste Trejo-Moreno,Alejandro Zamilpa,Manase´s Gonza´lez-Cortazar,Antonio Ruperto Jime´nez-Aparicio,Enrique Jime´nez-Ferrer 한국식품영양과학회 2022 Journal of medicinal food Vol.25 No.4

Systemic arterial hypertension (SAH) is a health problem of great importance worldwide, and endothelial dysfunction underlies SAH development. This condition's main characteristics include vasoconstriction, inflammation, oxidative stress, and procoagulant and proliferative states. This study's objective was to evaluate the antihypertensive, anti-inflammatory, and antioxidant effects of the whole extract and fractions of Agave tequilana in a murine model of SAH. SAH was induced in male ICR or CD-1 (Strain obtained from animals from Charles River Laboratories, Massachusetts) mice by intraperitoneal administration of angiotensin II (AGII) (0.1 μg/kg) for 4 weeks, and then A. tequilana treatments were co-administered with AGII. At the end of the experiment, systolic and diastolic blood pressure were measured and the kidneys were dissected to quantify interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha, IL-10, and malondialdehyde (MDA). The whole extract and the fractions of A. tequilana were chemically characterized using gas chromatography-mass spectrometry. The results indicate that the whole extract (At-W) and At-AcOEt fraction treatment are the most efficient in lowering blood pressure, although all the treatments had an immunomodulatory effect on the cytokines evaluated and an antioxidant effect on lipid peroxidation. Finally, the chromatographic profile shows that the integral extract and fractions of A. tequilana contained phytol (M)3,7,11,15-Tetramethyl-2-hexadecen-1-ol; 9,12-octadecadienoic acid; hentriacontane; 9,19-cyclolanost-24-en-3-ol,(3b); t-sitosterol; and stigmasta-3,5-dien-7-one.

Anti-inflammatory, antioxidant and anti-acetylcholinesterase activities of Bouvardia ternifolia: potential implications in Alzheimer’s disease

Giovanni Garcı ´a-Morales,Arturo Aguilar-Rojas,Maira Huerta-Reye,Manase ´s Gonza ´lez-Cortazar,Alejandro Zamilpa,Enrique Jime ´nez-Ferrer,Rau ´l Silva-Garcı ´a,Rube ´n Roma ´n-Ramos 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.7

Bouvardia ternifolia has been used medicinally to treat inflammation. In the present study, we investigate the anti-Alzheimer’s potential effect of the hydroalcoholic extract of B. ternifolia through evaluation of anti-inflammatory and antioxidant activities, quantification of the percentage inhibition of acetylcholinesterase activity, protection effect against b-amyloid fibrillar-induce neurotoxicity, and the identification of the main constituents. Our results show that B. ternifolia extract and ethyl acetate fraction induced anti-inflammatory effects by reducing inflammation by [70 %, while antioxidant test revealed significant IC50 values for flavonoid content fraction (30.67 ± 2.09 lg/ml) and ethyl acetate fraction (42.66 ± 0.93 lg/ml). The maximum inhibition of acetylcholinesterase was exhibited by scopoletin content fraction (38.43 ± 3.94 %), while ethyl acetate fraction exerted neuroprotective effect against b-amyloid peptide (83.97 ± 5.03 %). Phytochemical analysis, showed the presence of 3-O-quercetin glucopyranoside (415 mg/g), rutin (229.9 mg/g), ursolic and oleanolic acid (54 and 20.8 mg/g respectively), 3-O-quercetin rhamnopyranoside (12.8 mg/g), chlorogenic acid (9.5 mg/g), and scopoletin (1.38 mg/g). Our findings support the use of B. ternifolia since the extract induced significant neuroprotection against b-amyloid peptide, anti-inflammatory, antioxidant and antiacetylcholinesterase effects that could be attributed to its contents of polyphenols, coumarins, and triterpenes, and encourage further studies for development of this extract as therapeutic agent in treatment of Alzheimer’s disease.

In Vitro and In Vivo Nematicide Effect of Extract Fractions of Pleurotus djamor Against Haemonchus contortus

Manases González-Cortázar,José E Sánchez,Magaly Huicochea-Medina,Victor M Hernández-Velázquez,Pedro Mendoza-de-Gives,Alejandro Zamilpa,Ma Eugenia López-Arellano,Jesús Antonio Pineda-Alegría,Liliana Ag 한국식품영양과학회 2021 Journal of medicinal food Vol.24 No.3

Sheep haemonchosis is a disease that causes anemia, diarrhea, weight loss, low production, and even death of young animals. This represents a negative economic impact on the livestock sector. For decades, chemicals have been used to control this parasitic disease; however, cases of anthelmintic resistance have increased around the world. For this reason, the search for control alternatives is necessary. Several studies have shown that edible mushrooms of Pleurotus genus have different medicinal properties, including nematicidal activity. In this study, the chromatographic fractionation of the hydroalcoholic extract of fruiting bodies Pleurotus djamor was carried out to identify and isolate the metabolites responsible for nematicidal activity. From the fractionation of the extract, the fraction PdR2 and the subfraction PdB were obtained, which were evaluated against Haemonchus contortus under in vitro conditions. The nematicidal effect of the fraction PdB in gerbils infected artificially with H. contortus was evaluated. Finally, the analysis of the PdB fraction by gas chromatography-mass spectrometry and nuclear magnetic resonance was carried out. The results showed that the PdB had 100% of egg hatching inhibition from 5 mg/mL. Regarding larvicidal activity, it presented >97.2% from 24 h to 20 mg/mL. The in vivo evaluation of the PdB fraction showed a reduction of H. contortus larvae of 92.56%. The compounds present in this fraction were the mixture of allitol and an unidentified terpene in a ratio of 9:1. The PdB fraction is a potential alternative for the control of H. contortus, where allitol and a terpene could be responsible for nematicidal activity.