Antidiabetic effects of Psidium x durbanensis Baijnath & Ramcharun ined. (Myrtaceae) leaf extract on streptozotocin-induced diabetes in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Psidium guajava L. leaves are used to treat diabetes in South African folkloric medicine and in other parts of the world. Psidium x durbanensis Baijnath & Ramcharun ined. (PD) is a natural sterile hybrid and congener of Psidium guajava that is expected to share the medicinal properties of the genus Psidium and is widely distributed in South Africa. AIM OF THE STUDY: This study investigates the antioxidant, antidiabetic effects, and mechanisms of action of hydro-methanolic leaf extracts of PD on streptozotocin-induced diabetes in rats. MATERIAL AND METHODS: Phytochemical constituents of hydro-methanolic extract of PD were analyzed by gas chromatography-mass spectrometry (GC-MS). Male Wistar rats 250-300 g body weight (BW) were rendered diabetic after a single intraperitoneal injection with streptozotocin, 45 mg/kg BW. The diabetic rats were treated with hydro-methanolic (20:80 v/v) leaf extracts of PD (400 mg/kg/BW) or subcutaneous injections of regular insulin (2.0U/kg/BW, bid) for 56 days. The body weights of the animals were recorded daily. Fasting blood glucose, glucose tolerance tests, and insulin resistance index were measured. The effects of the extracts on total superoxide dismutase, catalase, and reduced glutathione activities, histopathology, and gene expression of insulin receptor substrate 1 and glucose transporter 4 were determined in the liver, pancreas, and gastrocnemius muscles of the rats. RESULTS: In the acute toxicity studies, there were no signs of toxicity observed for PD up to 2000 mg/kg BW doses. Diabetic animals showed significant weight loss, elevated and reduced fasting blood glucose and insulin, respectively, impaired glucose tolerance and diminished antioxidant enzymes' activities compared to controls. Treatment with PD hydro-methanolic leaf extracts improved body weight, glucose tolerance, insulin resistance, and antioxidant enzymes but not plasma insulin in diabetic animals compared to controls, respectively. GC-MS analysis identified organic acids, alcohols, vitamins, terpenoids, and esters in the extracts. Treatment with PD improved glucose uptake by stimulating mRNA expression of GLUT 4 in gastrocnemius muscles of diabetic animals compared to the untreated control and also restored histological aberrations in the pancreas and liver of diabetic rats compared with the untreated control rats. CONCLUSION: Collectively, the present study suggests that treatment with PD leaf extracts significantly ameliorated diabetes symptoms and oxidative stress in rats, and these effects may be linked to the bioactive phytoconstituents present in the plant. This study further suggests that PD improves insulin resistance by increasing glucose uptake in gastrocnemius muscles in an insulin-independent manner.

New Alk(en)ylhydroxycyclohexanes with Tyrosinase Inhibition Potential from Harpephyllum caffrum Bernh. Gum Exudate.

This work presents the first report on the phytochemical investigation of Harpephyllum caffrum Bernh. gum exudate. A known cardanol, 3-heptadec-12'-Z-enyl phenol (1) and three new alk(en)ylhydroxycyclohexanes, namely, (1R,3R)-1,3-dihydroxy-3-[heptadec-12'(Z)-enyl]cyclohexane (2) (1S,2S,3S,4S,5R)-1,2,3,4,5-pentahydroxy-5-[octadec-13'(Z)-enyl]cyclohexane (3) and (1R,2S,4R)-1,2,4-trihydroxy-4-[heptadec-12'(Z)-enyl]cyclohexane (4) were isolated from the gum. The structures of the compounds were determined by extensive 1D and 2D NMR spectroscopy and HR-ESI-MS data. The ethanolic extract of the gum was found to be the most potent tyrosinase inhibitor with IC50 of 11.32 µg/mL while compounds 2 and 3, with IC50 values of 24.90 and 26.99 µg/mL, respectively, were found to be potential anti-tyrosinase candidates from the gum. Gum exudate may be a potential source for non-destructive harvesting of selective pharmacologically active compounds from plants. The results also provide evidence that H. caffrum gum may find application in cosmetics as a potential anti-tyrosinase agent.

Identification of potential SARS-CoV-2 inhibitors from South African medicinal plant extracts using molecular modelling approaches.

The coronavirus is a group of viruses found in animals as well as humans and have been detected since the 1960s. However, a newly identified form, SARS-CoV-2, has triggered a recent pandemic of respiratory disease now called COVID-19. There is currently no specific antiviral drug for the treatment of this pandemic, with most treatment strategies focused on symptomatic management and supportive therapy. As such, several drug discovery efforts are ongoing for potent treatment agents, with medicinal plants gradually gaining prominence. Approximately 80% of the South African population use traditional medicines to meet their primary health care needs. The current study aimed to identify potential COVID-19 therapeutic agents from a list of 29 bioactive compounds isolated from commonly used South African medicinal plants using molecular docking and molecular dynamics. Molecular docking identified arabic acid from Acacia senegal and L-canavanine found in Sutherlandia frutescens as a potential inhibitor of SARS-CoV-2 3C-like main protease. Similarly, hypoxoside isolated from Hypoxis hemerocallidea and uzarin from Xysmalobium undulatum, were identified as a potential inhibitor of SARS-CoV-2 receptor binding domain and SARS-CoV-2 RNA-dependent polymerase. These four bioactive compounds exhibited favourable binding orientations characterized by strong molecular interactions within respective inhibitors binding pockets of the target enzymes. Molecular dynamics simulations revealed that the binding of the identified inhibitors are characterized by structural perturbations which favour the inhibitory potency of these bioactive compounds. Additionally, in silico pharmacokinetic assessment of the compounds demonstrated favourable anti-SARS-CoV-2 properties. Although not conclusive, further experimental exploration of these compounds could serve as a starting point for the discovery of novel SARS-CoV-2 therapeutic.

Cytotoxic activity of the bioactive principles from Ficus burtt-davyi.

Ficus burtt-davyi (Moraceae) is a medicinal plant species indigenous to Southern Africa. In this study, a phytochemical and cytotoxic investigation on F. burtt-davyi was conducted to evaluate its ethno-medicinal use. The phytochemical study of the fruits yielded triterpenoids (lupeol and α-amyrin). The cytotoxic evaluation was done on the methanolic extracts and selected compounds, lupeol, α-amyrin, lupeol acetate and (+)-catechin isolated from F. burtt-davyi stem bark and fruits. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay was carried out against two human cancer cell lines, breast adenocarcinoma (MCF-7) and colorectal adenocarcinoma (Caco-2), and normal human embryonic kidney cells (HEK293). The methanol extract from the stem bark was significantly cytotoxic to MCF-7 and Caco-2 cell lines (p < 0.05) in a concentration-dependent manner with IC50 values of 6.6 and 8.1 µg mL-1, respectively relative to the control. Lupeol and (+)-catechin showed cytotoxic activity against MCF-7 cell lines with IC50 values of 22.6 and 29.8 µg mL-1, respectively and greater cytotoxic activity against Caco-2 cell lines with IC50 values of 10.7 and 9.0 µg mL-1, respectively. Data from this study suggests that F. burtt-davyi exhibits cytotoxicity with no significant inhibitory effects against HEK293. The results also indicate that (+)-catechin and lupeol, the most abundant bioactive principles in the stem bark, are responsible for the synergistic cytotoxic effects against tested human cancer cell lines. This study provides evidence on the pharmaceutical potential of the medicinal plant, F. burtt-davyi, as a chemotherapeutic agent against cancer.

NEW INSIGHTS INTO THE PRESENCE OF BILIRUBIN IN A PLANT SPECIES STRELITZIA NICOLAI (STRELITZIACEAE).

BACKGROUND: The fortuitous discovery of an animal pigment bilirubin found in the plant Strelitzia nicolai has opened an enormous number of questions regarding bilirubin's formation and its ultimate function in the human body. MATERIALS AND METHODS: A methodical review of bilirubin in humans and animals was carried out, information was gathered using published scientific journals, books and conference proceedings. Articles based on case studies of elevated levels of bilirubin were analysed thoroughly. RESULTS: Even though for numerous years bilirubin was assumed to be merely a desecrate product of the heme catabolic pathway by greatest, and a likely lethal compound at worst; statistics from the last few decades clearly shows that placidly high serum bilirubin levels are robustly related to have abundant beneficial effects on the human body. CONCLUSION: This study reveals new insights into the presence of the only animal pigment found in Strelitzia nicolai arils, the potential advantages of bilirubin found in a plant and its therapeutic value indications. This review hopes to resuscitate researchers' credence regarding bilirubin as a toxic compound.

Nutritional evaluation, bioaccumulation and toxicological assessment of heavy metals in edible fruits of FicussurForssk (Moraceae).

Ficussur (Moraceae) is an indigenous medicinal plant with a wide distribution in Africa. In this study, the nutritional potential fruit of this indigenous plant to meet domestic food demands and reduce food insecurity in KwaZulu-Natal. South Africa, was investigated. The proximate composition and concentrations of metals in the edible fruits collected from eight different sites in KwaZulu-Natal were determined to assess for nutritional value and the concentrations of metals in the growth soil was determined to evaluate the impact of soil quality on elemental uptake. The fruits contained high levels of moisture (88.8%) and carbohydrates (65.6%). The concentrations of elements in the fruits were found to be in decreasing order of Ca>Mg >Fe >Zn>Cu >Mn> Se with low levels of toxic metals (As, Cd, Co and Pb). This study shows that the consumption of the fruits of F. sur can contribute positively to the nutritional needs of rural communities in South Africa for most essential nutrients without posing the risk of adverse health effects.

CHEMICAL CONSTITUENTS AND IN VITRO ANTIOXIDANT ACTIVITY OF CRUDE EXTRACTS AND COMPOUNDS FROM LEAVES AND STEM BARK OF FICUS BURTT-DAVYI.

Ficus buit-davyi, (Moraceae), is an endemic species of South Africa. In this study, a phytochemical analysis of the leaves and stem bark of F. burt-davyi resulted in the isolation of five triterpenes (lupeol, lupeol acetate, ß-sitosterol, stigmasterol and campesterol), one carotenoid (lutein), a pheophytin (phytyl-7-ethyl-25- (methoxycarbonyl)-3,8,13,17-tetramethyl-26-oxo- 12-vinyl-17,18-dihydro-2,20-ethanoporphyrin- 1 8-propanoate or pheophytin a) and one flavonoid (+)-catechin). The in viti antioxidant study of the methanol extracts of leaves and stem bark, (+)-catechin and pheophytin a using the 1,1-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay, ferric reducing antioxidant power (FRAP) assay and hydrogen peroxide (H202) assay showed significantly higher (p < 0.05) antioxidant activity for the methanol extract of the stem bark than the leaves, with IC55 values (in µg/mL) of 58.28 ? 5.05 for DPPH, 46.09 ± 0.06 for FRAP and 151.03 ± 1.60 pg/mL for H202,. The results suggest that the plant can be used as a therapeutic agent in alternative medicine for oxidative stress related degenerative diseases.

Antibacterial and anti-biofilm activity of flavonoids and triterpenes isolated from the extracts of Ficus sansibarica Warb. subsp. sansibarica (Moraceae) extracts.

BACKGROUND: Ficus species are used in African traditional medicine in the treatment of a wide variety of ailments and diseases such as convulsive disorder, wound healing, gonorrhea, tuberculosis, diabetes, diarrhoeal infections, dysentery, malaria and HIV. The aim of this study was to isolate the phytochemical constituents in the plant and test them for their antibacterial activity. MATERIALS AND METHODS: The fruits, leaves and stem bark were extracted with organic solvents and the compounds in the extracts separated and purified by column chromatography before being identified by NMR spectroscopy and by comparison of the NMR data against values reported in the literature. The antibacterial activity of the pure compounds and extracts were tested using the disk diffusion method. RESULTS: Three triterpenes and three flavonoids: lupeol acetate (1); cycloart-23-ene-3,25-diol (2); ß-sitosterol (3); 5,7,4'-trihydroxyflavan-3-ol (4); epicatechin (5); and isovitexin (6) were isolated in this study. Antimicrobial activity was observed at 8 mg mL(-1) for Staphylococcus aureus ATCC 29213 with four of the six isolated compounds, with no activity being observed at 1 - 4 mg mL(-1) against Escherichia coli ATCC 25922, E. coli ATCC 35218 and S. aureus ATCC 43300. Epicatechin (5) was found to decrease adhesion of E. coli ATCC 25922 and S. aureus ATCC 29213. Decreased adhesion of S. aureus ATCC 29213 was also observed with 5,7,4'-trihydroxyflavan-3-ol (4) and isovitexin (6). CONCLUSIONS: The results of this study provide baseline information on F. sansibarica's potential validity in the treatment of infections associated with Gram-positive microorganisms.

Effect of traditional leafy vegetables on the growth of lactobacilli and bifidobacteria.

Traditional leafy vegetables, apart from being a staple in the diet of most of sub-Saharan Africa, are an essential part of traditional medicine and are used daily by traditional healers in the region to treat a wide variety of ailments. In this study, a batch culture technique was used to investigate whether 25 infusions from 22 traditional leafy vegetables stimulated the growth of Lactobacillus bulgaricus, Lactobacillus lactis, Lactobacillus reuteri and Bifidobacterium longum in pure culture. High performance liquid chromatography was used to determine the inulin content of the infusions. Sonchus oleraceus stimulated all four strains and Taraxacum officinale stimulated three strains. In total, 18 plants stimulated at least one of the four probiotic strains. The inulin content of the infusions varied between 2.5% and 3.6%, with Asparagus sprengeri containing the highest percentage. These results indicate that traditional leafy vegetables do stimulate the growth of the selected lactobacilli and bifidobacteria in pure culture and contain inulin. These infusions can now be tested for prebiotic potential using mixed culture systems or human hosts.