Dodonaea viscosa Jacq. induces cytotoxicity, antiproliferative activity, and cell death in colorectal cancer cells via regulation of caspase 3 and p53.

Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide and is the second leading cause of cancer-related death due to an insufficiency prognosis and is generally diagnosed in the last step of development. The Peruvian flora has a wide variety of medicinal plants with therapeutic potential in several diseases. Dodonaea viscosa Jacq. is a plant used to treat inflammatory process as well as gastrointestinal diseases. The aim of this study was to examine the cytotoxic, antiproliferative, and cell death-inducing effects of D. viscosa on colorectal cancer cells (SW480 and SW620). The hydroethanolic extract was obtained by maceration at 70% ethanol, the phytochemical constituents were identified by LC-ESI-MS. D. viscosa revealed 57 compounds some of them are: isorhamnetin, kaempferol, quercetin, methyl dodovisate B, hardwickiic acid, viscosol, and dodonic acid. Regarding the antitumoral activity, D. viscosa induced cytotoxic and antiproliferative activity in both SW480 and SW620 cancer cells, accompanied with, important changes in mitochondrial membrane potential, formation of the Sub G0/G1 population and increasing levels of apoptotic biomarkers (caspase 3 and the tumor suppressor protein p53) in the metastatic derivative cell line (SW620), suggesting an intrinsic apoptotic process after the treatment with the hydroethanolic extract of D. viscosa.

Maytenus octogona Superoxide Scavenging and Anti-Inflammatory Caspase-1 Inhibition Study Using Cyclic Voltammetry and Computational Docking Techniques.

The relationship between oxidative stress and inflammation is well known, and exogenous antioxidants, primarily phytochemical natural products, may assist the body's endogenous defense systems in preventing diseases due to excessive inflammation. In this study, we evaluated the antioxidant properties of ethnomedicines from Peru that exhibit anti-inflammatory activity by measuring the superoxide scavenging activity of ethanol extracts of Maytenus octogona aerial parts using hydrodynamic voltammetry at a rotating ring-disk electrode (RRDE). The chemical compositions of these extracts are known and the interactions of three methide-quinone compounds found in Maytenus octogona with caspase-1 were analyzed using computational docking studies. Caspase-1 is a critical enzyme triggered during the activation of the inflammasome and its actions are associated with excessive release of cytokines. The most important amino acid involved in active site caspase-1 inhibition is Arg341 and, through docking calculations, we see that this amino acid is stabilized by interactions with the three potential methide-quinone Maytenus octogona inhibitors, hydroxytingenone, tingenone, and pristimerin. These findings were also confirmed after more rigorous molecular dynamics calculations. It is worth noting that, in these three compounds, the methide-quinone carbonyl oxygen is the preferred hydrogen bond acceptor site, although tingenone's other carbonyl group also shows a similar binding energy preference. The results of these calculations and cyclovoltammetry studies support the effectiveness and use of anti-inflammatory ethnopharmacological ethanol extract of Maytenus octogona (L'Héritier) DC.

The Essential Oil of Petroselinum crispum (Mill) Fuss Seeds from Peru: Phytotoxic Activity and In Silico Evaluation on the Target Enzyme of the Glyphosate Herbicide.

Petroselinum crispum (Mill) Fuss is an aromatic plant belonging to the Apiaceae family and used in gastronomy as a spice. Several studies have been developed in leaves but studies are limited in seeds, especially the essential oils obtained from seeds. The aim of this study was to determine the phytochemical profile of the volatile compounds of this essential oil by gas-chromatography-mass spectrometry (GC-MS) in order to evaluate its phytotoxic activity on Lactuca sativa seeds and to carry out an in silico analysis on the target enzyme of the herbicide glyphosate 5-enolpyruvylshikimate 3-phosphate synthase (EPSP). The essential oil was obtained by steam distillation for two hours and then was injected into a GC-MS, the phytotoxic assay was carried out on Lactuca seeds and the in silico evaluation on the EPSP synthase focused on the volatile compounds similar to glyphosate, docking analysis, and molecular dynamics to establish the protein-ligand stability of the most active molecule. The chromatographic analysis revealed 47 compounds, predominated by three compounds with the most abundant percentage in the total content (1,3,8-ρ-menthatriene (22.59%); apiole (22.41%); and ß-phellandrene (15.02%)). The phytotoxic activity demonstrated that the essential oil had a high activity at 5% against L. sativa seed germination, inhibition of root length, and hypocotyl length, which is comparable to 2% glyphosate. The molecular docking on EPSP synthase revealed that trans-p-menth-6-en-2,8-diol had a high affinity with the enzyme EPSP synthase and a better stability during the molecular dynamic. According to the results, the essential oil of P. crispum seeds presented a phytotoxic activity and might be useful as a bioherbicide agent against weeds.

Volatile Components, Antioxidant and Phytotoxic Activity of the Essential Oil of Piper acutifolium Ruiz & Pav. from Peru.

Piper acutifolium Ruiz & Pav is known as "matico" and belongs to the Piperaceae family, and in Peru it is traditionally used as an infusion or decoction to ameliorate wound healings or ulcers. In this study, the aim was to investigate the volatile components, the antioxidant profile, and the phytotoxic activity of the essential oil (EO) of P. acutifolium from Peru. To identify the phytoconstituents, the EO was injected into a Gas Chromatography-Mass Spectrometry (GC-MS) to obtain the chemical profile of the volatile components, followed by the antioxidant activity carried out by the reaction with three organic radicals (2,2-diphenyl-1-picrylhydrazyl (DPPH); 2,2'-azinobis-(3-ethylbenzothiazoline)-6- sulfonic acid (ABTS); ferric reducing/antioxidant power (FRAP)). Finally, the phytotoxic capabilities of the EO were tested on two model plants, Lactuca sativa seeds and Allium cepa bulbs. As a result, the analysis identified α-phellandrene as its main volatile chemical at 38.18%, followed by ß-myrcene (29.48%) and ß-phellandrene (21.88%). Regarding the antioxidant profile, the half inhibitory concentration (IC50) in DPPH was 160.12 ± 0.30 µg/mL, for ABTS it was 138.10 ± 0.06 µg/mL and finally in FRAP it was 450.10 ± 0.05 µg/mL. The phytotoxic activity demonstrated that the EO had high activity at 5% and 10% against L. sativa seed germination, the inhibition of root length, and hypocotyl length. Additionally, in A. cepa bulbs, the inhibition root length was obtained at 10%, both comparable to glyphosate, which was used as a positive control. The molecular docking on 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) revealed that α-phellandrene had -5.8 kcal/mol, being near to glyphosate at -6.3 kcal/mol. The conclusion shows that the EO of P. acutifolium presented antioxidant and phytotoxic activity and might be useful as a bioherbicide in the future.

CYP2D6 and CYP2C19 Genes Associated with Tricontinental and Latin American Ancestry of Pe-ruvians.

Precision medicine seeks to individualize the dose from the beginning of phar-macological therapy based on the characteristics of each patient, genes involved in the metabolic phenotype, ethnicity or miscegenation, with the purpose to minimize adverse effects and optimize drug efficacy. The objective was to re-view studies that describe the association of the CYP2D6 and CYP2C19 genes with the tricontinental and Latin American ancestry of Peruvians. A biblio-graphic search was carried out in PubMed/Medline and SciELO, with various descriptors in Spanish and English. The results of this review confirm that the ethnic origin of Peruvians is triconti-nental due to European (mainly Spanish), African and Asian migration, in addi-tion to Latin American migration, being 60.2% mixed, 25.8% Amerindian, 5.9% white, 3.6% African descent, 1.2% Chinese and Japanese descent, and 3.3% unspecified. Studies on CYP2C19*3, CYP2D6*2, *3 and *6 have been reported in Peruvians, and the frequency is similar to that studied in Ecuadori-ans and Colombians. The CYP2C19*3, CYP2D6*3, and CYP2D6*6 alleles found in Peruvians are common in Europeans, Africans, and Asians; while CYP2D6*4 in Africans and CYP2D6*2 related to Asians. In some studies, the ethnic/gene association has not been demonstrated; while others have shown a significant association, which is why further investigation is warranted. It is concluded that the studies on CYP2D6 and CYP2C19 genes associated with the tricontinental and Latin American ancestry of Peruvians are little, and ac-cording to what has been investigated, the CYP2C19*3, CYP2D6*2, *3, *4 and *6 alleles have more related to their ancestry.

GC-MS Profile, Antioxidant Activity, and In Silico Study of the Essential Oil from Schinus molle L. Leaves in the Presence of Mosquito Juvenile Hormone-Binding Protein (mJHBP) from Aedes aegypti.

Schinus molle is a medicinal plant used as an anti-inflammatory and for rheumatic pain in the traditional medicine of Peru. On the other hand, Aedes aegypti is the main vector of several tropical diseases and the transmitter of yellow fever, chikungunya, malaria, dengue, and Zika virus. In this study, the aim was to investigate the antioxidant activity in vitro and the insecticidal activity in silico, in the presence of the mosquito juvenile hormone-binding protein (mJHBP) from Aedes aegypti, of the essential oil from S. molle leaves. The volatile phytochemicals were analyzed by gas chromatography-mass spectrometry (GC-MS), and the profile antioxidants were examined by DPPH, ABTS, and FRAP assays. The evaluation in silico was carried out on mJHBP (PDB: 5V13) with an insecticidal approach. The results revealed that EO presented as the main volatile components to alpha-phellandrene (32.68%), D-limonene (12.59%), and beta-phellandrene (12.24%). The antioxidant activity showed values for DPPH = 11.42 ± 0.08 µmol ET/g, ABTS = 134.88 ± 4.37 µmol ET/g, and FRAP = 65.16 ± 1.46 µmol ET/g. Regarding the insecticidal approach in silico, alpha-muurolene and gamma-cadinene had the best biding energy on mJHBP (ΔG = -9.7 kcal/mol), followed by beta-cadinene (ΔG = -9.5 kcal/mol). Additionally, the volatile components did not reveal antioxidant activity, and its potential insecticidal effect would be acting on mJHBP from A. aegypti.

Cytotoxic triterpenoids from Maytenus retusa.

Seven new triterpenoids (1-7) and 36 known compounds were isolated from the root bark of Maytenus retusa. Their structures were determined by 1D and 2D spectroscopic studies. Several compounds were evaluated for their cytotoxicity against the human tumor cell lines HL-60 and MCF-7. Some of them were cytotoxic, with IC(50) values ranging between 0.2 and 4.7 µM.

Triterpenoids and a lignan from the aerial parts of Maytenus apurimacensis.

Five new triterpenes (1-5) and one new lignan (6) were isolated from the aerial parts of Maytenus apurimacensis. Their structures were determined on the basis of spectroscopic studies, including homonuclear and heteronuclear correlation NMR experiments (COSY, ROESY, HSQC, and HMBC).

New terpenoids from Maytenus apurimacensis as MDR reversal agents in the parasite Leishmania.

Two new sesquiterpenes (1-2) and one new lupane triterpene (3) have been isolated from the roots of Maytenus apurimacensis. The novel beta-dihydroagarofurans are the first sesquiterpenes with a basic polyhydroxy skeleton of 15-deoxyalatol and 4,15-dideoxyalatol that show high MDR reversing activity in the protozoan parasite Leishmania tropica.

New dammarane triterpenes from Maytenus macrocarpa.

Two new dammarane triterpenes have been isolated from the stem bark exudates of Maytenus macrocarpa. Their structures were determined by extensive 1D and 2D NMR spectroscopic studies as 24(Z)-3-oxodammara-20(21),24-dien-27-oic acid (1) and octa-nor-13-hydroxydammara-1-en-3,17-dione (2). These compounds were tested for antitumoral activity.