HIV-1 Reverse Transcriptase Inhibition by Major Compounds in a Kenyan Multi-Herbal Composition (CareVid™): In Vitro and In Silico Contrast

• Main Authors: Winnie Rotich (Author), Nicholas J. Sadgrove (Author), Eduard Mas-Claret (Author), Guillermo F. Padilla-González (Author), Anastasia Guantai (Author), Moses K. Langat (Author)
• Format: Book
• Published: MDPI AG, 2021-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

CareVid is a multi-herbal product used in southwest Kenya as an immune booster and health tonic and has been anecdotally described as improving the condition of HIV-positive patients. The product is made up of roots, barks and whole plant of 14 African medicinal plants: <i>Acacia nilotica</i> (L.) Willd. ex Delile (currently, <i>Vachelia nilotica</i> (L.) P.J.H Hurter & Mabb.), <i>Adenia gummifera</i> (Harv.) Harms, <i>Anthocleista grandiflora</i> Gilg, <i>Asparagus africanus</i> Lam., <i>Bersama abyssinica</i> Fresen., <i>Clematis hirsuta</i> Guill. & Perr., <i>Croton macrostachyus</i> Hochst. ex Delile, <i>Clutia robusta</i> Pax (accepted as <i>Clutia kilimandscharica</i> Engl.), <i>Dovyalis abyssinica</i> (A. Rich.) Warb, <i>Ekebergia capensis</i> Sparm., <i>Periploca linearifolia</i> Quart.-Dill. & A. Rich., <i>Plantago palmata</i> Hook.f., <i>Prunus africana</i> Hook.f. Kalkman and <i>Rhamnus prinoides</i> L'Her. The objective of this study was to determine the major chemical constituents of CareVid solvent extracts and screen them for in vitro and in silico activity against the HIV-1 reverse transcriptase enzyme. To achieve this, CareVid was separately extracted using CH₂Cl₂, MeOH, 80% EtOH in H₂O, cold H₂O, hot H₂O and acidified H₂O (pH 1.5-3.5). The extracts were analysed using HPLC-MS equipped with UV diode array detection. HIV-1 reverse transcriptase inhibition was performed in vitro and compared to in silico HIV-1 reverse transcriptase inhibition, with the latter carried out using MOE software, placing the docking on the hydrophobic pocket in the subdomain of p66, the NNRTI pocket. The MeOH and 80% EtOH extracts showed strong in vitro HIV-1 reverse transcriptase inhibition, with an EC₅₀ of 7 μg·mL⁻¹. The major components were identified as sucrose, citric acid, ellagic acid, catechin 3-hexoside, epicatechin 3-hexoside, procyanidin B, hesperetin <i>O</i>-rutinoside, pellitorine, mangiferin, isomangiferin, 4-<i>O</i>-coumaroulquinic acid, ellagic acid, ellagic acid <i>O</i>-pentoside, crotepoxide, oleuropein, magnoflorine, tremulacin and an isomer of dammarane tetrol. Ellagic acid and procyanidin B inhibited the HIV-1 reverse transcription process at 15 and 3.2 µg/mL⁻¹, respectively. Docking studies did not agree with in vitro results because the best scoring ligand was crotepoxide (ΔG = −8.55 kcal/mol), followed by magnoflorine (ΔG = −8.39 kcal/mol). This study showed that CareVid has contrasting in vitro and in silico activity against HIV-1 reverse transcriptase. However, the strongest in vitro inhibitors were ellagic acid and procyanidin B.

Item Description

10.3390/ph14101009
1424-8247