Pharmacokinetics and hepatoprotective effects of Lippia scaberrima Sond. and Aspalathus linearis (Burm.f.) R. Dahlgren

Abstract

In developing countries, the presence and impact created by tuberculosis (TB) is alarming. With the rise of resistant TB, initiatives such as adjunct host-directed therapy (AHDT) that aim to reduce treatment time, lower side-effects and costs involved, should be investigated. The Dutch East Indian Company mainly drank herbal medicinal teas in the Cape region during the settlement of the Cape. Many of the indigenous plants within the immediate area were used as substitutes for the much more expensive and imported tea. Lippia scaberrima Sond. (L. scaberrima) is an under investigated shrub which is endemic to South Africa. Although Lippia javanica may have been an obvious choice for testing in this regard, the fact that not much is known on L. scaberrima prompted the investigation into the biological properties of this specific species. Aspalathus linearis (Burm.f.) R. Dahlgren (A. linearis) a medicinal plant that has a variety of biological properties documented. Both these plants are consumed as teas and in this study an attempt was made to investigate their combined biological and therapeutic activity. The biological investigation in the present study included using a combination of ethanolic extracts of both L. scaberrima and A. linearis. L. scaberrima is known to be rich in volatile compounds and the essential oil was isolated and included in the study. The essential oil of L. scaberrima was incorporated as another sample to be tested for its biological activity, as this plant is known to be rich in volatile compounds. This study further included an investigation of the biological activity of verbascoside, a known compound, found in all endemic Lippia species. Lastly, the evaluation of synthesized gold nanoparticles from L. scaberrima were also included. Significant antimycobacterial activity was found for L. scaberrima against Mycobacterium tuberculosis H37Rv. Low to no cellular toxicity was observed against hepatocellular carcinoma cells (HepG2) at the tested concentrations. Hydro-steam distillation was effective in isolating the essential oils from the aerial parts of L. scaberrima, which showed effective hepatoprotective activity against acetaminophen-induced toxicity. The cytochrome P450 (CYP) inhibitory activity of L. scaberrima, combinations of L. scaberrima and A. linearis, and verbascoside has been reported in this study for the first time. Potent CYP inhibitory activity was found for L. scaberrima in combination with the green A. linearis. Verbascoside had no significant inhibitory activity against the CYP isoforms and therefore, it can be considered that it may have low risk for herb-drug interactions. This study included the cyclooxygenase-II (COX-II) inflammatory activity of L. scaberrima. All the samples, except L. scaberrima, that were investigated for their DPPH free radical scavenging potential were found to have significant activity. Moderate nitric oxide scavenging activity was found for verbascoside and green A. linearis in combination with L. scaberrima. Antioxidant and anti-inflammatory activity play a profound role in assisting with the adverse effects experienced during treatment for TB infection. This study provided a more comprehensive look into the specific biological properties of L. scaberrima relating to TB infection as well as its efficacy when combined with fermented and green A. linearis extracts. Synthesized nanoparticles of L. scaberrima provided the opportunity to lower the cytotoxicity towards HepG2 cells even more than was initially found. The investigated samples showed the potential to decrease drug-induced hepatotoxicity, one of the main adverse effects experienced. In addition, all the samples tested, showed potential as an adjuvant for host-directed therapies for TB. These initial results pave the way for further research into specialized avenues with endless possibilities for the discovery of new specialized treatment regimens that are tailored to be host specific and for specific stages of infection. Please note that all experiental studies and results reported on were on the ethanolic extracts of both L. scaberrima and A. linearis and not of the tea and/or the boiling water extract of L. scaberrima and A. linearis or otherwise stated.