Ethanolic extract of Artemisia campestris subsp. glutinosa (Besser) Batt. inhibits HIV–1 replication in vitro through the activity of terpenes and flavonoids on viral entry and NF–κB pathway

Abstract

Ethno–pharmacological relevance The genus Artemisia spp. is well known for its anti–infectious properties and its high content in anti–infectious compounds, like the well–known sweet wormwood ( Artemisia annua L.). Another Artemisia species, Artemisia campestris subsp. glutinosa (Besser) Batt., field wormwood, has been traditionally used as medicinal plant in the Mediterranean region. Aim of the study The aim of this study is to investigate the anti–HIV activity of field wormwood, to identify the compounds responsible for this activity and their structure and mechanism of action. Materials and methods Antiviral activity of isolated compounds and extracts was evaluated in HIV–1 infections of lymphoblastoid cells. We also evaluated the mechanism of action of isolated compounds. Viral entry was studied comparing the inhibitory effect of isolated compounds on wild type HIV–1 and VSV pseudotyped HIV–1. To assess the viral transcriptional effect, plasmids encoding luciferase reporter genes under the control of the whole genome of HIV–1 or NF–κB or Sp1 transcription factors were transfected in the presence of the compounds under evaluation. Finally, antioxidant activity was assessed by quantitation of reduced and total glutathione in treated cell cultures. Results Ethanolic and aqueous extracts of Artemisia campestris subsp. glutinosa (Besser) Batt. subsp. g lutinosa displayed anti–HIV activity in vitro , although ethanolic extract was more powerful (IC 50 14.62 μg/mL). Bio–guided ethanolic extract fractionation leads to the isolation and characterization of two terpenes, damsin and canrenone, and four flavonoids, 6, 2′, 4′–trimethoxyflavone, acerosin, cardamonin and xanthomicrol. All the isolated compounds inhibited HIV–1 replication in vitro with IC 50 values between the middle nanomolar and the low micromolar range. Their anti–HIV mechanism of action is due to the bloking of viral entry and/or transcription inhibition, without correlation with the antioxidant activity, through interference with the cellular transcription factors NF–κB and Sp1, which are targets that are not currently reached by antiretroviral therapy. Conclusion We describe here the anti–HIV activity of field wormwood, Artemisia campestris subsp. glutinosa (Besser) Batt., and the isolation and study of the mechanism of action of two terpenes and four flavonoids, responsible, at least in part, for its activity, through the inhibition of two different cellular targets affecting the HIV replication cycle. The activity of these compounds in cellular targets could explain why plant extracts can be used in t...

Xanthomicrol Activity in Cancer HeLa Cells: Comparison with Other Natural Methoxylated Flavones

“…XAN is identified as an active compound in herbs/plants with a long application in traditional medicine, such as Baccharis pentlandii D.C. [ 15 ], Dracocephalum kotschyi Boiss [ 16 , 17 , 18 , 19 ], Ocimum gratissimum L. [ 20 ], Baccharis densiflora Wedd [ 21 ], and Artemisia campestris L. [ 22 ]. Several studies reported the antioxidant [ 7 ], anticancer [ 7 , 17 , 18 , 19 , 21 , 23 ], antimicrobial [ 7 , 22 ], and anti-inflammatory [ 7 ] properties of XAN.…”

“…XAN is identified as an active compound in herbs/plants with a long application in traditional medicine, such as Baccharis pentlandii D.C. [ 15 ], Dracocephalum kotschyi Boiss [ 16 , 17 , 18 , 19 ], Ocimum gratissimum L. [ 20 ], Baccharis densiflora Wedd [ 21 ], and Artemisia campestris L. [ 22 ]. Several studies reported the antioxidant [ 7 ], anticancer [ 7 , 17 , 18 , 19 , 21 , 23 ], antimicrobial [ 7 , 22 ], and anti-inflammatory [ 7 ] properties of XAN. The antitumoral activity of XAN has been related to its ability to inhibit cancer cell viability/proliferation [ 7 , 17 , 18 , 21 , 23 ], angiogenesis [ 16 ], cancer-related enzymes [ 19 ], and to induce apoptosis [ 17 , 23 ] and cell cycle arrest [ 23 ].…”

Medicinal plant-derived mtDNA via nanovesicles induces the cGAS-STING pathway to remold tumor-associated macrophages for tumor regression

“…Beyond anti-parasite activity, artemisinin and its derivatives exhibit the therapeutic potentials for viral infections, inflammatory disease, autoimmune diseases and cancer [44][45][46][47]. Also, the extracts of Artemisia annua, particularly artemisinin and flavonoids, have been reported to have numerous pharmacological properties [48,49]. However, we still know little about the action mode of Artemisinin and the relevant components.…”

Current Advances in Antiviral Potential of Artemisia Against Major Viral Infections

“…subsp. glutinosa exhibit in vitro inhibitory activity against HIV, with the ethanolic extract demonstrating greater potency (15). Bio-guided fractionation of the ethanolic extract resulted in the identification of two terpenes: canrenone and damsin, and four flavonoids: acerosin, xanthomicrol, cardamonin, and 6, 2′, 4′-trimethoxyflavone.…”

“…Artemisia campestris, commonly called field wormwood, underwent pharmacological reassessment (14). Traditionally utilized as an antiseptic (15), A. campestris found application in treating pleurisy, a condition arising from viral or bacterial infections (16). Additionally, indigenous North American communities employ extracts of A. campestris to alleviate common colds induced by coronavirus or rhinovirus, although the underlying mechanism and active compounds remain undisclosed (17).…”