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

Abstract

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.

Bio-guided isolation of a new sesquiterpene fromArtemisia cinawith anthelmintic activity againstHaemonchus contortusL3infective larvae

“…These compounds are responsible for a wide range of biological activities, including hepatoprotective, neuroprotective, antidepressant, cytotoxic, antitumor, digestion-stimulating and antiparasitic effects [10]. The n- hexane ( n -HE) extract of Artemisia cina has been documented for its anthelmintic activity against H. contortus , targeting eggs and L 3 infective larvae [8], transitional larvae L 3 -L 4 [4], and naturally infected periparturient goats [3]. Those activities are attributed to the presence of two lignans, 3′-Demethoxy-6-O-Demethylisoguaiacin and norisoguaiacin [8].…”

“…The n- hexane ( n -HE) extract of Artemisia cina has been documented for its anthelmintic activity against H. contortus , targeting eggs and L 3 infective larvae [8], transitional larvae L 3 -L 4 [4], and naturally infected periparturient goats [3]. Those activities are attributed to the presence of two lignans, 3′-Demethoxy-6-O-Demethylisoguaiacin and norisoguaiacin [8]. However, the low yield percentage of the n -HE and the lignans make it challenging to use for formulating or creating A. cina -based pharmaceutical preparations.…”

“…In an in vivo study conducted on naturally infected periparturient goats, the administration of an n -HE derived from A. cina resulted in a notable reduction in the fecal egg count of H. contortus and Teladorsagia circumcincta . This extract was found to contain two previously unidentified compounds for A. cina , namely isoguaiacin and norisoguaiacin [8].…”

“…According to previous findings, the EAE presents anthelmintic activity against H. contortus L 3 infective larvae [8], however the bioactives compounds remain unidentified. Therefore, the objective of this study was to isolate and identify a compound with anthelmintic activity against H. contortus L 3 infective larvae from the EAE of A. cina through bio-guided separation.…”

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

“…The bio-guided assays showed that the molecules responsible for the effect are 3′-demethoxy-6-O-demethylisoguaiacin and norisoguaiacin separated and isolated from an n -hexane extract of A. cina . The compounds showed 100% mortality against infective larvae of H. contortus 14 .…”