Flavonoids of Chromolaena odorata (L.) R.M.King & H.Rob. as potential leads for treatment against tuberculosis.

Tuberculosis (TB) is currently rated as the 13th leading cause of mortality and the second leading cause of death after COVID-19, and above AIDS. Existing challenges relating to the development of multidrug-resistant strains and dangerous side effects of currently used drugs add impetus to the search for additional TB treatments. Hence, interest has grown in the use of medicinal plants as a source of bioactive preparations with efficacy against TB-causing organisms, and also with the ability to ameliorate the negative effects of TB drugs. This study aimed to evaluate the antimycobacterial and hepatoprotective potentials of extracts and isolated flavonoid compounds from invasive Chromolaena odorata. Test organisms used were pathogenic Mycobacterium bovis and M. tuberculosis H37RV, and the fast-growing M. aurum, M. fortuitum and M. smegmatis. The selectivity index (SI) values of the test substances were determined through cytotoxicity assays to promote these extracts and compounds as leads for the development of effective and safe anti-tubercular drugs. The antimycobacterial activity was evaluated using a serial microdilution method, and the SI was calculated from the 50% lethal concentrations calculated from cytotoxicity tests. Hepatoprotective activity was determined using HepG2 liver cells treated with rifampicin as a toxin. The extracts and compounds had a range of antimycobacterial activity with minimum inhibitory concentration (MIC) values ranging from 0.031 to 2.5 mg/mL. Two flavonoid compounds, 5,7,4'-trimethoxy flavanone and 5­hydroxy-3,7,4'-trimethoxyflavone showed promising antimycobacterial potential, and minimal toxicity was observed, as most SI values were higher than 1. The flavonoid compound 5,7,4'-trimethoxy flavanone had the highest SI (6.452), which was against M. tuberculosis H37RV. The HepG2 cells were reduced to 65% due to toxicity by rifampicin, however, the flavonoid compounds were able to improve cell viability to between 81 and 89% at different concentrations tested. Results obtained indicate that C. odorata may serve as a lead for the development of safe and effective antimycobacterial and hepatoprotective drugs.

Scientific rationale for traditional use of plants to treat tuberculosis in the eastern region of the OR Tambo district, South Africa.

ETHNOPHARMACOLOGICAL RELEVANCE: Tuberculosis (TB) remains a major health problem for humans worldwide, and was responsible for 1.4 million human deaths in 2015 alone. Although there is treatment for TB, emerging multi-drug, extensively drug and totally drug resistant forms of this disease, as well as co-infection with human immunodefiency virus (HIV) continue to worsen the situation. South Africa is among countries with reported traditional use and published documentation of such knowledge concerning the use of plants against TB. Based on a previous study where plants used traditionally for treating TB in the eastern region of OR Tambo district, South Africa, were documented, the present study aimed to determine the antimycobacterial effect, cytotoxicity and genotoxicity of plants selected from that list. MATERIAL AND METHODS: Acetone, 70% ethanol, cold and hot water extracts were tested for antimycobacterial activity against saprophytic Mycobacterium species including M. aurum, M. bovis BCG, M. gordonae, M. fortuitum, and M. smegmatis using a microdilution method. Extracts with MIC values less than 1 mg/ml against at least three Mycobacterium strains were evaluated for antimycobacterial activity against pathogenic Mycobacterium strains including M. tuberculosis H37RV, M. tuberculosis and M. bovis, cytotoxicity (against Vero monkey kidney and bovine dermis cells), and genotoxicity (against Salmonella typhimurium TA98 and TA100). RESULTS: The MIC values of the extracts ranged from 0.02 to 2.50 mg/ml, LC50 values of twenty-nine extracts ranged from 0.001 to > 1 mg/ml and the highest selectivity index was 79.50, an extremely promising value. Phymaspermum acerosum roots and leaves (ethanol and water) extracts had the best MIC value (0.02 mg/ml) against at least one Mycobacterium strain. It was interesting to note the lack of cytotoxicity of these extracts with the highest selectivity index value of 39.75. Pterocelastrus echinatus bark acetone and Protorhus longifolia leaf hot water extracts were the most cytotoxic with LC50 = 0.001 and 0.008 mg/ml, respectively, whereas Pittosporum viridiflorum bark water extract was genotoxic. Among non-pathogenic strains, M. gordonae, M. aurum, M. smegmatis showed good correlation of activity with pathogenic M. tuberculosis H37Rv, M. tuberculosis and M. bovis, however, M. aurum was the best predictor with Mycobacterium tuberculosis H37Rv (correlation coefficient value = 0.73). CONCLUSION: The results indicate that Heteromorpha trifoliata and Phymaspermum acerosum should be investigated further for antimycobacterial efficacy against drug resistant strains of Mycobacterium.

Pittosporum viridiflorum Sims (Pittosporaceae): A review on a useful medicinal plant native to South Africa and tropical Africa.

ETHNOPHARMACOLOGICAL RELEVANCE: Pittosporum viridiflorum Sims, a Pittosporaceae species, is used extensively in African traditional medicine (ATM) by various tribes. This review is an appraisal of the information concerning the description, distribution, conservation status, traditional uses, phytochemistry, pharmacology and toxicology of this species with the aim of reconciling it with its traditional use. MATERIALS AND METHODS: A wide-ranging literature search was conducted using database platforms such as Scopus, Google Scholar, Web of Science, ScienceDirect, PubMed and books including local reports and thesis submissions. RESULTS: Ten categories to which P. viridiflorum finds use in traditional medicine (TM) were found, and they include well-being, wounds, treatment of veterinary ailments, gastrointestinal and sexually transmitted diseases, kidney, circulatory and inflammatory disorders, as well as diseases such as cancer, tuberculosis, and malaria. Pharmacological tests conducted include those investigating antimicrobial, antidiarrhoeal, antimalarial, anticancer, anti-inflammatory, antioxidant and acaricidal properties. Promising activity was shown in a number of assays. Toxicological effects have also been reported from this species. However, it is recommended to conduct a detailed toxicological study, including genotoxicity, as this has not yet been evaluated. Compound(s) with antimalarial, anticancer and acaricidal properties have been isolated from P. viridiflorum. CONCLUSIONS: The collective pharmacological and phytochemical properties of P. viridiflorum gives credence to the use of this plant species against various diseases in ATM, thus steering significant interest towards in vivo studies and further research.

Isolation and characterization of antimicrobial compounds from Terminalia phanerophlebia Engl. & Diels leaf extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: The emergence of drug resistant-tuberculosis and other pathogenic diseases over the past decades, constitutes a serious threat to human health worldwide. According to a 2012 report by the World Health Organization (WHO), South Africa, China, India and Russia are the countries with the highest prevalence of Multi-Drug Resistant tuberculosis (MDR-tuberculosis) as they represented 60% of the total. Several reports have documented antimycobacterial properties of Terminalia species but only a few species from this genus have been explored for their antimycobacterial constituents. The crude extracts of Terminalia phanerophlebia showed good antimicrobial activities in our previous study against two Mycobacterium as well as two other bacterial strains responsible for opportunistic infections related to respiratory ailments. This paper studies the isolation of compounds responsible for such activities and to isolate compounds responsible for antimicrobial activities from the crude extracts of Terminalia phanerophlebia leaves. MATERIALS AND METHODS: Terminalia phanerophlebia crude extracts obtained from 80% methanol was successively extracted with hexane, dichloromethane (DCM), ethyl acetate (EtOAc) and n-butanol. The fractions obtained and isolated compounds were tested for their antibacterial activities against Mycobacterium aurum, Mycobacterium tuberculosis, Staphylococcus aureus and Klebsiella pneumoniae. Bioguided fractionation of the EtOAc fraction afforded two bioactive compounds. Structure elucidation was carried out using NMR (1D and 2D) spectroscopic methods. RESULTS: EtOAc fraction exhibited highest antimicrobial activities and its fractionation afforded methyl gallate (methyl-3,4,5-trihydroxybenzoate) (1) and a phenylpropanoid glucoside, 1,6-di-O-coumaroyl glucopyranoside (2) These compounds are reported from Terminalia phanerophlebia for the first time. Both compounds showed good antimicrobial activity against all bacterial strains tested with minimum inhibitory concentration (MIC) values ranging from 63 to 250 µg/mL. Inhibition of Mycobacterium tuberculosis by 1,6-di-O-coumaroyl glucopyranoside (2) at a MIC value of 63 µg/mL was noteworthy, as this bacterial strain is reported to be the leading cause of tuberculosis worldwide. CONCLUSIONS: Good antimicrobial activities exhibited by the compounds isolated from Terminalia phanerophlebia authenticate the traditional use of this plant in treating tuberculosis and its related symptoms. Compound (2), 1,6-di-O-coumaroyl glucopyranoside could serve as a lead compound for tuberculosis drug discovery.

Antimycobacterial, anti-inflammatory and genotoxicity evaluation of plants used for the treatment of tuberculosis and related symptoms in South Africa.

ETHNOPHARMACOLOGICAL RELEVANCE: Emergence of drug-resistant tuberculosis strains and long duration of treatment has established an urgent need to search for new effective agents. The great floral diversity of South Africa has potential for producing new bioactive compounds, therefore pharmacological screening of plant extracts within this region offers much potential. To assess the in vitro antimycobacterial, anti-inflammatory and genotoxicity activity of selected plants that are used for the treatment of TB and related symptoms in South Africa. MATERIALS AND METHODS: Ground plant materials from 10 plants were extracted sequentially with four solvents (petroleum ether, dichloromethane, 80% ethanol and water) and a total of 68 extracts were produced. A broth microdilution method was used to screen extracts against Mycobacterium tuberculosis H37Ra. The cyclooxygenase-2 (COX-2) enzyme was used to evaluate the anti-inflammatory activity of the extracts and the Salmonella microsome assay using two Salmonella typhimurium strains (TA98 and TA100) to establish genotoxicity. RESULTS: Six out of 68 extracts showed good antimycobacterial activity. Three extracts showed good inhibition (>70%) of COX-2 enzyme. All the extracts tested were non-genotoxic against the tested Salmonella strains. CONCLUSION: The results observed in this study indicate that some of the plants such as Abrus precatorius subsp. africanus, Ficus sur, Pentanisia prunelloides and Terminalia phanerophlebia could be investigated further against drug-resistant TB strains.

Ethnopharmacological study of plants from Pondoland used against diarrhoea.

ETHNOPHARMACOLOGICAL RELEVANCE: Waterborne diseases such as diarrhoea are common world wide, including in Bizana, South Africa where the majority of rural dwellers depend largely on water from unprotected sources. The people from Bizana use medicinal plants as their first line of health care to cure and prevent diarrhoea. AIM OF THE STUDY: To record and document plants used for the treatment of diarrhoea in Bizana, to evaluate antibacterial and anti-inflammatory activities of selected plant extracts as well as to perform genotoxicity testing of evaluated plants. MATERIALS AND METHODS: An ethnobotanical approach was used to select plants used for treating diarrhoea in Bizana for pharmacological assays using questionnaires. Nine plants were selected for bioassays based on their frequency index and the fact that they have never been evaluated against diarrhoea causing-microorganisms. The petroleum ether (PE), dichloromethane (DCM), 70% ethanol (EtOH), and water extracts were evaluated for antibacterial (Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli and Shigella flexneri) activity using the microdilution technique, their ability to inhibit COX-1 and COX-2 enzymes. Genotoxicity was evaluated using the Salmonella microsome assay. RESULTS: This study revealed that 34 plant species belonging to 27 families are used for the treatment of diarrhoea in Bizana. The extracts showed good inhibitory activity with MIC values ranging from 0.39 to 12.5mg/ml. The best activity was exhibited by DCM extracts of Rapanea melanophloeos, and EtOH extracts of Ficus craterostoma and Maesa lanceolata with MIC values of 0.098mg/ml. The inhibitory activity against COX-1 enzyme was higher than COX-2, with 19 plant extracts for the former and 7 for the latter. All the tested plant extracts were not mutagenic at all concentrations tested against all tester strains of bacteria. CONCLUSION: In view of the fact that the plants were selected based on their ethnobotanical usage for treating diarrhoea, the activities reported here goes a long way in validating the plants for traditional use.