Toxicology and herb-drug interaction of selected anti-hypertension plants used by lay persons in Northern KwaZulu-Natal (South Africa)
A recent (2015) ethnobotanical study which was conducted in northern Maputaland showed that the lay people use medicinal plants singularly, in plant combinations, as well as concurrently with conventional drugs to treat hypertension. Because of the lack of studies validating the safety of South African medicinal plants and the limited interactive studies done between medicinal plants and conventional drugs this study was undertaken. The study was designed to validate the safety of 26 medicinal plants used singularly, in 19 plant combinations as well as when combined with conventional hypertension drugs (13 plants). Five medicinal plants (Citrullus lanatus, Cladostemon kirkii, Hyphaene coriacea and Pyrenacantha kaurabassana and Strychnos madagascariensis) investigated in the current study were evaluated for the first time for any toxicology. Apart from the combination between Aloe marlothii and Hypoxis hemerocallidea, none of the combinations investigated in the current study have been previously tested for any toxicity. Aqueous and organic (1:1 dichloromethane-methanol) extracts were prepared. The toxicity was evaluated using three assays [the brine shrimp lethality assay (BSLA), Ames test and MTT assay (human hepatocarcinoma cell line HepG2/C3A)]. The toxicity interaction of the plant combination was evaluated using the sum of fractional inhibitory concentration (ΣFIC). Herb-drug interaction was performed on the aqueous extracts of the 13 medicinal plants which were recorded to be used concurrently with conventional drugs (adcon napamol, aluminum hydroxide, amlodipine, aspirin, enalapril, pharmapress and ridaq). The three assays applied were the CYP3A4 inhibition assay, the beta-glucuronidase inhibition assay as well as the carboxylesterase inhibition assay. These assays were chosen according to the enzymes involved in the metabolism of the hypertension conventional drugs. The overall toxicity profile of the plant extracts tested in BSLA showed that 17 of the organic extracts were toxic while only two of the aqueous extracts were toxic. The aqueous extracts which were toxic were Catharanthus roseus and Citrus limon and these two extracts were further tested at varied concentrations to determine dosage. The results showed that as the concentration increases, the mortality percent also increased. For the extracts tested for mutagenicity, four of the organic extracts were mutagenic while two of the aqueous extracts (Catharanthus roseus and Ozoroa engleri) were mutagenic toward Salmonella typhimurium bacterial strain TA98 and TA100. For the 13 medicinal plants which were tested in MTT, the results showed that Sarcophyte sanguinea was hepatotoxic at the concentration of 100 μg/ml. Apart from Hypoxis hemerocallidea which had moderate hepatotoxicity, the aqueous extracts of the most frequently used medicinal plants were non-toxic thus considered safe to use as a traditional medicine. However, in vivo tests (at preclinical level) are necessary to confirm this assumption. For the plant combinations, the mortality percentage of the two concentrations tested in BSLA showed a significant correlation between dosage and toxicity i.e. toxicity was dosage dependant. The overall toxicity profile of the two concentrations tested indicated that organic extracts were more toxic than the aqueous extracts. The results of plant combinations when tested in the Ames test also showed that the organic extracts had more mutagenic effect than the aqueous extracts. The aqueous extract combination (Catharanthus roseus and Momordica balsamina) was the only combination to be toxic in both assays but also the most regularly use combination by the people. In the BSLA, six plant combinations showed antagonistic interactions (aqueous and organic extracts). In the Ames test five combinations from organic extracts had antagonistic interaction with only two aqueous combinations showing antagonistic response. For the herb-drug interaction studies, all the extracts tested had an inhibitory effect on either of the three enzymes. A high inhibition percentage (97%) was observed on the enzyme CYP3A4, with Sarcophyte sanguinea and Psidium guajava. The lowest overall inhibitory effect was observed on beta-glucuronidase. The inhibition of the enzymes by the plant extracts was dosage dependent. The outcome of this study established that low toxicity of the aqueous extracts was observed in most of the assays. Even though all the plant extracts tested for herb-drug interaction showed to inhibit beta-glucuronidase enzyme resulting in improved hypertensive drug efficacy, these medicinal plants cannot be recommended to be used concurrently with hypertensive drugs since they also inhibit the two enzymes which are responsible for the metabolism of hypertension drugs. It is thus best practice not to take any herbals concurrently with any allopathic medicine.
medicinal plants --Maputaland --hypertension --South Africa
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