Understanding Artemisia cina Ethyl Acetate Extract's Anthelmintic Effect on Haemonchus contortus Eggs and L3 Larvae: The Synergism of Peruvin Binary Mixtures.

Haemonchus contortus, a blood-feeding parasite in grazing sheep, causes economic losses. Drug resistance necessitates exploring plant-based anthelmintics like Artemisia cina (Asteraceae). The plant, particularly its ethyl acetate extract, shows anthelmintic activity against H. contortus. However, there is limited information on pharmacodynamic interactions in ethyl acetate compounds. The study aims to identify pharmacodynamic interactions in the ethyl acetate extract of A. cina with anthelmintic effects on H. contortus eggs and L3 larvae using binary mixtures. Bioactive compounds were isolated via chromatography and identified using spectroscopic techniques. Pharmacodynamic interactions were assessed through binary mixtures with a main compound. Four bioactive compounds were identified: 1-nonacosanol, hentriacontane, peruvin, and cinic acid. Binary mixtures, with peruvin as the main compound, were performed. Peruvin/1-nonacosanol-hentriacontane and peruvin/cinic acid mixtures demonstrated 1.42-fold and 4.87-fold increased lethal effects in H. contortus L3 infective larvae, respectively, at a 0.50LC25/0.50LC25 concentration. In this work, we determined the synergism between bioactive compounds isolated from the ethyl acetate extract of A. cina and identified unreported compounds for the specie.

Biochemical parameters, oxidative stress biomarkers, and anatomopathological changes in Wistar rats treated with 3'-demethoxy-6-O-demethylisoguaiacin and norisoguaiacin.

Artemisia cina (Ac) is a plant with anthelmintic compounds such as 3'-demethoxy-6-O-demethylisoguaiacin (D) and norisoguaiacin (N). Three major objectives were proposed: (1) To evaluate biochemical parameters in blood (2) to determine the tissue oxidative stress by biomarkers as TBARS and glutathione peroxidase activity, and (3) to evaluate anatomopathological changes in organs such as the brain, liver, kidney, and lung after oral administration of n-hexane extract of Ac and D and N. D and N were administrated following the OECD guides for acute oral toxicity evaluation (Guide 420). Fifty Wistar rats were distributed into ten groups as follows: Group 1 (G1): 4 mg/Kg; G2: 40 mg/Kg; G3: 240 mg/Kg; G4: 1600 mg/Kg of n-hexane extract of Ac. G5: 2 mg/Kg; G6: 20 mg/Kg; G7: 120 mg/Kg; G8: 800 mg/Kg of D and N, G9: water and G10: polyvinylpyrrolidone at 2000 mg/Kg. At 14 days, the rats were euthanized, and the blood, liver, brain, kidney, and lung were taken for biochemical analysis, anatomopathological changes, and TBARS and GSH evaluation. Glucose, cholesterol, and phosphorus were altered. Histopathological analysis showed multifocal neuronal degeneration in the brain (G2). The kidney and lungs had changes in G7. The GSH and TBARS increased in G6 and G7. The TBARS activity was higher in G1 and G2. In conclusion, extract and D and N of Ac did not have damage at therapeutic doses. D, N, and n-hexane extract of A. cina do not cause histopathological damage at pharmaceutical doses. Still, the brain, kidney, and liver are related to biochemical parameters at higher doses. However, compounds are proposed as antioxidant agents.

3'-Demethoxy-6-O-Demethylisoguaiacin and Norisoguaiacin Nematocidal Lignans from Artemisia cina against Haemonchus contortus Infective Larvae.

Artemisia cina is a plant used in traditional Chinese medicine as a remedy for parasitic diseases. This study describes the isolation and chemical characterization of anthelmintic compounds of A. cina against Haemonchus contortus infective larvae (L3) through lethal testing. Previously, three extracts-n-hexane (HexAc), ethyl acetate (EtOAc) and methanol (MeOAc)-were evaluated at concentrations of 4 to 0.5 mg/mL, resulting in the HexAc extract with the greatest effect of 76.6% mortality of the larvae at 4 mg/mL. Then, this was chemically fractioned by polarity, obtaining seven fractions (C1F1-C1F7), and, when evaluated at concentrations from 2 to 0.25 mg/mL, the 2 mg/mL C1F5 fraction produced an effect against the nematode H. contortus of 100% mortality of the larvae. Thus, this fraction was fractionated again by column chromatography, obtaining twelve subfractions (C2F1-C2F12) which were evaluated from 1 to 0.125 mg/mL, with the C2F5 subfraction causing a nematicidal effect of 100% mortality. NMR analysis of one (1H, 13C and DEPT) and two dimensions (COSY, HSQC and HMBC) and mass spectrometry of this fraction allowed us to identify the mixture of 3'-demethoxy-6-O-demethylisoguaiacin and norisoguaiacin. Therefore, it can be assumed that the mixture of these compounds is responsible for the anthelmintic effect. These results indicate that A. cina containing anthelmintic compounds and might be used as an antiparasitic drug against H. contortus.

Development of the first georeferenced map of Rhipicephalus (Boophilus) spp. in Mexico from 1970 to date and prediction of its spatial distribution.

The tick genus Ripicephalus (Boophilus), particularly R. microplus, is one of the most important ectoparasites that affects livestock health and considered an epidemiological risk because it causes significant economic losses due, mainly, to restrictions in the export of infested animals to several countries. Its spatial distribution has been tied to environmental factors, mainly warm temperatures and high relative humidity. In this work, we integrated a dataset consisting of 5843 records of Rhipicephalus spp., in Mexico covering close to 50 years to know which environmental variables mostly influence this ticks' distribution. Occurrences were georeferenced using the software DIVA-GIS and the potential current distribution was modelled using the maximum entropy method (Maxent). The algorithm generated a map of high predictive capability (Area under the curve = 0.942), providing the various contribution and permutation importance of the tested variables. Precipitation seasonality, particularly in March, and isothermality were found to be the most significant climate variables in determining the probability of spatial distribution of Rhipicephalus spp. in Mexico (15.7%, 36.0% and 11.1%, respectively). Our findings demonstrate that Rhipicephalus has colonized Mexico widely, including areas characterized by different types of climate. We conclude that the Maxent distribution model using Rhipicephalus records and a set of environmental variables can predict the extent of the tick range in this country, information that should support the development of integrated control strategies.