Evaluation of the antimalarial properties of Solanum incanum L. leaf extract fractions and its ability to downregulate delta aminolevulinate dehydratase to prevent the establishment of malaria infection.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum incanum L. is commonly used in traditional herbal medicine (THM) in Kenya for treating various ailments. Recent developments in disease treatment have introduced the concept of host-directed therapy (HDT). This approach involves targeting factors within the host cell that can impede the growth or replication of a pathogen. One such host factor is delta aminolevulinate dehydratase (δ-ALAD), the second enzyme in the heme biosynthesis pathway utilized by Plasmodium for growth. Studies using mice models have shown an increase in δ-ALAD expression during Plasmodium berghei infection. Another plant in the Solanum genus, S. guaranticum, has been found to inhibit δ-ALAD in red blood cells in vitro and in the brain in vivo. Is it possible that the bioactive compounds in S. incanum extracts could also be effective in HDT for malaria treatment? AIM OF STUDY: To better assess the effectiveness of S. incanum leaf extracts as a curative and prophylaxis in malaria parasite infection, and to test the plant's ability to decrease δ-ALAD expression. MATERIALS AND METHODS: The leaves of S. incanum were collected, dried, and pulverized before being subjected to a successive extraction protocol to obtain crude, hexane, ethyl acetate, and aqueous extract fractions. Phytochemical analysis was conducted on all extract fractions, followed by GC-MS analysis of the fraction with the most potent antimalarial activity. An acute toxicity study was also performed on the extracted fractions. The potency of the extract fractions as curative and prophylactic antimalarial was then evaluated in THM using Plasmodium berghei-infected mice at a dose of 100 mg/kg. The extract fraction with the highest activity was further evaluated at varying doses and its effect on δ-ALAD was measured using RT-qPCR. The percentage of parasitemia and chemosuppression, and mean survival time were used as indices of activity. RESULTS: Phytochemical analysis revealed that the ethyl acetate and aqueous extract fractions contained high terpenoids, flavonoids, and phenols levels. However, alkaloids were only present in moderate quantities in the aqueous extract, and quinones were found in high levels only in the crude extract. Additionally, all extract fractions contained saponins in high levels but lacked tannins. While the plant extracts were found to be non-toxic, they did not exhibit curative antimalarial activity. However, all extract fractions showed prophylactic antimalarial activity, with the ethyl acetate extract having the highest percentage of chemosuppression even at doses of 250 and 1000 mg/kg. In the negative control, the expression of δ-ALAD was 5.4-fold, but this was significantly reduced to 2.3-fold when mice were treated with 250 mg/kg of the ethyl acetate fraction. GC-MS analysis of the ethyl acetate fraction revealed high percentages of 2-methyloctacosane, tetracosane, and decane. CONCLUSION: The fractions extracted from S. incanum leaves have been found to possess only antimalarial prophylactic properties, with the ethyl acetate extract fraction showing the most effective results. The activity of this fraction may be attributed to its ability to decrease the expression of δ-ALAD, as it contains an alkane compound implicated with enzyme-inhibitory activity.

Evaluation of the antimicrobial activity and safety of Rhus vulgaris (Anacardiaceae) extracts.

BACKGROUND: Medicinal plants have been used in the treatment of various ailments in most developing countries. Oral infections are the most prevalent diseases in man. The Rhus family has been found to have antimicrobial, antimalarial, and anti-inflammatory properties. Few studies have been done on Rhus vulgaris Meikle. A study was conducted to determine the effect of Rhus vulgaris Meikle stem bark extracts against selected oral pathogenic microorganisms and the safety of the extracts in vitro and in vivo. METHODS: Methanol:dichloromethane (1:1), methanol and aqueous extracts were tested for bacteriostatic and bactericidal effects against Methicillin Resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Streptococcus mutans and Candida albicans. Cytotoxicity of the active extracts was determined using Vero E6 cell lines while safety was evaluated in mice and rats. Phytochemical screening was performed on the methanol extracts. One-way ANOVA and Tukey's multiple comparisons tests were performed using IBM SPSS statistics 20.0 for antimicrobial assay and acute toxicity testing. One-way ANOVA and Dunnett's multiple comparison tests were conducted using GraphPad Prism 8.0 for cytotoxicity assay. RESULTS: Methanol extract of Rhus vulgaris showed significant antimicrobial activity against MRSA (12.00 ± 0.00 mm; p-value of < 0.005; Minimum Inhibitory Concentration of 0.391 mg/ml; Minimum Bactericidal Concentration of 1.563 mg/ml). The extract were not cytotoxic at 100 µg/ml which was the highest tested concentration. In acute dermal irritation testing, the methanol extract resulted in mild irritation with erythema and flaking that cleared within 8 days. There were no observable adverse effects from oral administration of the extracts (acute oral toxicity testing) at concentrations of 50 mg/kg, 300 mg/kg and 2000 mg/kg. Tannins, saponins, flavonoids, terpenoids, glycosides, alkaloids and phenols were detected in the methanol extract. CONCLUSIONS: Antimicrobial activity of R. vulgaris extracts supports its traditional use as a toothbrush. Cytotoxicity demonstrated by the extracts as well as the mild skin irritation warrants further study before R. vulgaris can be recommended for the development of effective and safe mouthwashes.