Dihydroisocoumarins, Naphthalenes, and Further Polyketides from <i>Aloe vera</i> and <i>A. plicatilis</i>: Isolation, Identification and Their 5-LOX/COX-1 Inhibiting Potency

• Main Authors: Hans Wilhelm Rauwald, Ralf Maucher, Gerd Dannhardt, Kenny Kuchta
• Format: Article
• Language: English
• Published: MDPI AG 2021-07-01
• Series: Molecules
• Subjects: <i>Aloe vera</i>; <i>Aloe plicatilis</i>; dihydroisocoumarins; naphthalenes; polyketides; anti-inflammatory activity
• Online Access: https://www.mdpi.com/1420-3049/26/14/4223

The present study aims at the isolation and identification of diverse phenolic polyketides from <i>Aloe vera</i> (L.) Burm.f. and <i>Aloe plicatilis (L.)</i> Miller and includes their 5-LOX/COX-1 inhibiting potency. After initial Sephadex-LH20 gel filtration and combined silica gel 60- and RP18-CC, three dihydroisocoumarins (nonaketides), four 5-methyl-8-<i>C</i>-glucosylchromones (heptaketides) from <i>A. vera,</i> and two hexaketide-naphthalenes from <i>A. plicatilis</i> have been isolated by means of HSCCC. The structures of all polyketides were elucidated by ESI-MS and 2D ¹H/¹³C-NMR (HMQC, HMBC) techniques. The analytical/preparative separation of 3<i>R</i>-feralolide, 3′-<i>O</i>-β-<span style="font-variant: small-caps;">d</span>-glucopyranosyl- and the new 6-<i>O</i>-β-<span style="font-variant: small-caps;">d</span>-glucopyranosyl-3<i>R</i>-feralolide into their respective positional isomers are described here for the first time, including the assignment of the 3<i>R</i>-configuration in all feralolides by comparative CD spectroscopy. The chromones 7-<i>O</i>-methyl-aloesin and 7-<i>O</i>-methyl-aloeresin A were isolated for the first time from <i>A. vera,</i> together with the previously described aloesin (syn. aloeresin B) and aloeresin D. Furthermore, the new 5,6,7,8-tetrahydro-1-<i>O</i>-β-<span style="font-variant: small-caps;">d</span>-glucopyranosyl- 3,6<i>R</i>-dihydroxy-8<i>R</i>-methylnaphtalene was isolated from <i>A. plicatilis,</i> together with the known plicataloside. Subsequently, biological-pharmacological screening was performed to identify <i>Aloe</i> polyketides with anti-inflammatory potential in vitro. In addition to the above constituents, the anthranoids (octaketides) aloe emodin, aloin, 6′-(<i>E</i>)-p-coumaroyl-aloin A and B, and 6′-(<i>E</i>)-p-coumaroyl-7-hydroxy-8-<i>O</i>-methyl-aloin A and B were tested. In the COX-1 examination, only feralolide (10 µM) inhibited the formation of MDA by 24%, whereas the other polyketides did not display any inhibition at all. In the 5-LOX-test, all aloin-type anthranoids (10 µM) inhibited the formation of LTB₄ by about 25–41%. Aloesin also displayed 10% inhibition at 10 µM in this in vitro setup, while the other chromones and naphthalenes did not display any activity. The present study, therefore, demonstrates the importance of low molecular phenolic polyketides for the known overall anti-inflammatory activity of <i>Aloe vera</i> preparations.