Evaluation of Lippia scaberrima Sond. and Aspalathus linearis (Burm.f.) R. Dahlgren extracts on human CYP enzymes and gold nanoparticle synthesis: implications for drug metabolism and cytotoxicity.

BACKGROUND: Metabolism is an important component of the kinetic characteristics of herbal constituents, and it often determines the internal dose and concentration of these effective constituents at the target site. The metabolic profile of plant extracts and pure compounds need to be determined for any possible herb-drug metabolic interactions that might occur. METHODS: Various concentrations of the essential oil of Lippia scaberrima, the ethanolic extract of Lippia scaberrima alone and their combinations with fermented and unfermented Aspalathus linearis extract were used to determine the inhibitory potential on placental, microsomal and recombinant human hepatic Cytochrome P450 enzymes. Furthermore, the study investigated the synthesis and characterization of gold nanoparticles from the ethanolic extract of Lippia scaberrima as a lead sample. Confirmation and characterization of the synthesized gold nanoparticles were conducted through various methods. Additionally, the cytotoxic properties of the ethanolic extract of Lippia scaberrima were compared with the gold nanoparticles synthesized from Lippia scaberrima using gum arabic as a capping agent. RESULTS: All the samples showed varying levels of CYP inhibition. The most potent inhibition took place for CYP2C19 and CYP1B1 with 50% inhibitory concentration (IC50) values of less than 0.05 µg/L for the essential oil tested and IC50-values between 0.05 µg/L-1 µg/L for all the other combinations and extracts tested, respectively. For both CYP1A2 and CYP2D6 the IC50-values for the essential oil, the extracts and combinations were found in the range of 1 - 10 µg/L. The majority of the IC50 values found were higher than 10 µg/L and, therefore, were found to have no inhibition against the CYP enzymes tested. CONCLUSION: Therefore, the essential oil of Lippia scaberrima, the ethanolic extract of Lippia scaberrima alone and their combinations with Aspalathus linearis do not possess any clinically significant CYP interaction potential and may be further investigated for their adjuvant potential for use in the tuberculosis treatment regimen. Furthermore, it was shown that the cytotoxic potential of the Lippia scaberrima gold nanoparticles was reduced by twofold when compared to the ethanolic extract of Lippia scaberrima.

Targeting Acne Bacteria and Wound Healing In Vitro Using Plectranthus aliciae, Rosmarinic Acid, and Tetracycline Gold Nanoparticles.

Gold nanoparticles from plant extracts and their bioactive compounds to treat various maladies have become an area of interest to many researchers. Acne vulgaris is an inflammatory disease of the pilosebaceous unit caused by the opportunistic bacteria Cutibacterium acnes and Staphylococcus epidermis. These bacteria are not only associated with inflammatory acne but also with prosthetic-implant-associated infections and wounds. Studies have hypothesised that these bacteria have a mutualistic relationship and act as a multispecies system. It is believed that these bacteria form a multispecies biofilm under various conditions and that these biofilms contribute to increased antibiotic resistance compared to single-species biofilms. This study aimed to investigate the antibacterial and wound healing potential of synthesised gold nanoparticles (AuNPs) from an endemic South African plant, Plectranthus aliciae (AuNPPAE), its major compound rosmarinic acid (AuNPRA) and a widely used antibiotic, tetracycline (AuNPTET). Synthesised gold nanoparticles were successfully formed and characterised using ultraviolet-visible spectroscopy (UV-vis), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), zeta potential (ζ-potential), high-resolution transmission electron microscopy (HRTEM), and selected area electron diffraction (SAED), and they were investigated for stability under various biological conditions. Stable nanoparticles were formed with ζ-potentials of -18.07 ± 0.95 mV (AuNPPAE), -21.5 ± 2.66 mV (AuNPRA), and -39.83 ± 1.6 mV (AuNPTET). The average diameter of the AuNPs was 71.26 ± 0.44 nm, 29.88 ± 3.30 nm, and 132.6 ± 99.5 nm for AuNPPAE, AuNPRA, and AuNPTET, respectively. In vitro, biological studies confirmed that although no antibacterial activity or biofilm inhibition was observed for the nanoparticles tested on the multispecies C. acnes and S. epidermis systems, these samples had potential wound closure activity. Gold nanoparticles formed with rosmarinic acid significantly increased wound closure by 21.4% at 25% v/v (≈29.2 µg/mL) compared to the negative cell control and the rosmarinic acid compound at the highest concentration tested of 500 µg/mL. This study concluded that green synthesised gold nanoparticles of rosmarinic acid could potentially be used for treating wounds.

The Activity of Gold Nanoparticles Synthesized Using Helichrysum odoratissimum Against Cutibacterium acnes Biofilms.

The human skin is home to millions of bacteria, fungi, and viruses which form part of a unique microbiome. Commensal microbes, including Cutibacterium acnes can occasionally become opportunistic resulting in the onset of dermatological diseases such as acne. Acne is defined as a chronic inflammatory disorder based on its ability to persist for long periods throughout an individual's life. The synthesis of gold nanoparticles (AuNPs) was performed using the bottom-up approach by reduction of a gold salt (HAuCl4.3H2O) by the methanol extract (HO-MeOH) and aqueous decoction prepared from the dried aerial parts of Helichrysum odoratissimum (HO-Powder). The HO-MeOH and HO-Powder AuNPs were prepared as unstabilised (-GA) or stabilized (+GA) by the omission or addition of Gum Arabic (GA) as the capping agent. The characterization of the AuNPs was performed using Transmission Electron Microscopy (TEM), dynamic light scattering (DLS), Ultraviolet-Visual spectroscopy (UV-Vis), Thermogravimetric Analysis (TGA), X-Ray Diffraction (XRD) and Zeta-potential. The MBIC50 values for HO-MeOH - GA and HO-MeOH + GA were 1.79 ± 0.78% v/v and 0.22 ± 0.16% v/v, respectively. The HO-Powder AuNPs showed potent inhibition of C. acnes cell adhesion to the 96-well plates. The HO-MeOH - GA and HO-Powder + GA exhibited IC50 of 22.01 ± 6.13% v/v and 11.78 ± 1.78% v/v, respectively. The activity of the AuNPs validated the anti-adhesion activity of the methanol extract in the crude form. The study emphasizes the selectivity of H. odoratissimum AuNPs for the prevention of C. acnes cell adhesion and not antimicrobial activity, which may prevent the emergence of resistant strains of C. acnes through reduced bactericidal or bacteriostatic activity, while targeting mechanisms of pathogenesis.