Antileishmanial and Cytotoxic Compounds from Valeriana wallichii and Identification of a Novel Nepetolactone Derivative

Abstract

The chloroform extract of Valeriana wallichii (V. wallichii) rhizomes was investigated to elucidate the structures responsible for reported antileishmanial activity. Besides bornyl caffeate (1, already been reported by us previously), bioassay-guided fractionation resulted in two additional cinnamic acid derivatives 2–3 with moderate leishmanicidal activity. The structure of a novel nepetolactone derivative 4 having a cinnamic acid moiety was elucidated by means of spectral analysis. To the best of our knowledge villoside aglycone (5) was isolated from this plant for the first time. The bioassay-guided fractionation yielded two new (compounds 6–7) and two known valtrates (compounds 8–9) with leishmanicidal potential against Leishmania major (L. major) promastigotes. In addition, β-bisabolol (10), α-kessyl alcohol (11), valeranone (12), bornyl isovalerate (13) and linarin-2-O-methylbutyrate (14) were identified. This is the first report on the isolation of 4'-demethylpodophyllotoxin (15), podophyllotoxin (16) and pinoresinol (17) in V. wallichii. In total thirteen known and four new compounds were identified from the extract and their cytotoxic and antileishmanial properties were evaluated.

Valeriana jatamansi: An herbaceous plant with multiple medicinal uses

“…Few flavonoids and flavonoid glycosides, namely, linarin ( 146 ), linarin‐isovalerianate ( 147 ), linarin‐2‐ O ‐methylbutyrate ( 148 ), 6‐methylapigenin/hispidulin ( 149 ), hesperetin‐7‐ O ‐β‐rutinoside [2S(‐)hesperidin ( 150 )], and acacetin‐7‐O + rutinoside ( 151 ) have been isolated from the roots of V. jatamansi (Glaser, Schultheis, Moll, Hazra, & Holzgrabe, ; Marder et al, ; Thies, ). Two new flavone glycosides, acacetin 7‐ O ‐β‐sophoroside ( 152 ) and acacetin 7‐ O ‐(600‐ O ‐a‐L‐rhamnopyranosyl)‐β‐sophoroside ( 153 ) were also isolated from the rhizomes and roots of V. jatamansi (Tang et al, ).…”

“…A new lignan compound known as (+)-9′-isovaleroxylariciresinol (179) is isolated from V. jatamansi (Lin et al, 2010). Podophyllotoxin (180) and 4′demethylpodophyllotoxin (181) are the compounds for the first time isolated from V. jatamansi (Glaser et al, 2015).…”

“…], and acacetin-7-O + rutinoside (151) have been isolated from the roots of V. jatamansi(Glaser, Schultheis, Moll, Hazra, & Holzgrabe, 2015;Marder et al, 2003;Thies, 1968). Two new flavone glycosides, acacetin 7-O-β-sophoroside (152) and acacetin 7-O-(600-O-a-L-rhamnopyranosyl)-β-sophoroside (153) were also isolated from the rhizomes and roots of V. jatamansi (Tang et al, 2003).…”

Anti-HCV Activity from Semi-purified Methanolic Root Extracts ofValeriana wallichii

“…Recently, in a phase 1 dose escalation study with quercetin in 30 untreated patients with chronic HCV infection, clinically meaningful decrease in viral load was reported in eight patients (Lu et al ., ). We and others have previously reported bioassay‐guided fractionation of Valeriana wallichii root, leading to the isolation and synthesis of novel compounds with potent antiparasitic activity against the causative parasites of visceral and cutaneous leishmaniasis (Ghosh et al ., ; Glaser et al ., ; Glaser et al ., ). In the present study, we report for the first time anti‐HCV activity from crude methanolic extract of V. wallichii root and its chromatographically semi‐purified fraction in Huh‐7.5 cells, infected with J6/JFH chimeric HCV strain.…”

Anti-Schistosomal Activity of Cinnamic Acid Esters: Eugenyl and Thymyl Cinnamate Induce Cytoplasmic Vacuoles and Death in Schistosomula of Schistosoma mansoni

“…We recently discovered that bornyl caffeate (1) from the rhizomes of Valeriana (V.) wallichii possessed anti-leishmanial activity [14]. We followed up on this initial finding with the synthesis of a small compound library of 28 systematically varied derivatives [15].…”