Natural Products Journal, The - Volume 9, Issue 4, 2019

Background: Morinda morindoides (Baker) (Rubiaceae) is a medicinal plant with antimicrobial properties currently used in Côte d'Ivoire and other countries. These properties have been described but most of the studies are dealing with crude extracts. Objective: The chemical structures of the bioactive compounds extracted from Morinda morindoides roots have been characterized. Methods: The root extracts were analyzed by using HPLC. Fourteen fractions were detected among which 11 compounds have been structurally identified by using a combination of 1H-NMR and 13CNMR and LC-HRMS methodologies. Results: All these compounds belong to anthraquinone family. The antibacterial activity of the eleven compounds was tested against six strains of microorganisms with ofloxacin as standard (two Gram-negative bacteria, two Gram-positive bacteria and two yeasts). The Minimal Inhibitory Concentrations recorded, varies from 8 to 128 μg / ml. Staphylococcus aureus was the most susceptible organism. Conclusion: We highlight the chemo-diversity of the antibacterial anthraquinones in the roots of Morinda morindoides.

Background: In recent decades, natural products are an important source of chemotherapeutics as more than half of the effective cancer drugs can be traced to natural origins. Objective: Moreover, the modification of natural products is one of the most common and fruitful approaches to obtain novel therapeutic agents in medicinal chemistry. Methods: Continuing with a research project based on the support of Moroccan plant resources. we report herein the use of α-isocostic acid extracted in enantiomerically pure form from Dittrichia viscosa as a convenient starting material for the synthesis of new eudesmane derivatives. Results: Novel spiro derivatives with a natural scaffold were prepared. Spiro-isoxazolidine derivatives were generated on the exocyclic double bond adjacent to the ester α,β-unsaturated function by 1,3-dipolar cycloaddition of methyl α-isocostate 1 derived from sesquiterpenic isocostic acid, with nitrones 2. Conclusion: This procedure allowed us to generate enantiomerically pure spiro compounds in one diastereoisomer form with a limited number of steps. These compounds were fully characterized by spectroscopic methods.

Background: Plant extracts are important products in the world and have been widely used for isolation of important biologically active products. Because of their significant environmental impact, extensive research has been explored to determine the antimicrobial activity of plant extracts. Methods: Acetone extracts of the bark and leaf of Cupressus sempervirens and Juniperus phoenicea, collected from three different altitudes (125, 391, and 851 m high of sea level) at Al- Jabel Al-Akhdar area, Libya were obtained and analyzed by GC/MS. The antimicrobial activity of the extracts was further evaluated against plant bacteria Rhizobium radiobacter, Erwinia carotovora, Rhodococcus fascians and Ralstonia solanacearum and fungus Botrytis cinerea. Results: The impact of the altitude from the sea level on the quantity and chemical constituents of the extracts was investigated. The yield was largely dependent on tree species and the highest yield (6.50%) was obtained with C. sempervirens L bark of altitude III (851 m of the sea level), while the lowest (1.17%) was obtained with the leaf extract of C. sempervirens L from altitude I (125 m). The chemical composition analyzed by GC/MS confirmed that the leaf extracts of C. sempervirens and J. phoenicea contained a complex mixture of monoterpene hydrocarbons, sesquiterpenes, diterpenes, diterpenoids, terpenophenolic, steroids and phthalates. However, the bark extracts of both trees contained a mixture of sesquiterpenes, diterpenes, diterpenoids, terpenophenolics, phthalates, retinol and steroids. These constituents revealed some variability among the extracts displaying the highest interesting chemotype of totarol (terpenophenolic) in all extracts (14.63-78.19% of the total extract). The extracts displayed a noteworthy antifungal potency with varying degrees of inhibition of growth with EC50 values ranged from 78.50 to 206.90 mg/L. The extracts obtained from the leaves of C. sempervirens showed that the highest inhibitory activity was obtained with the extract of altitude II (391 m) with MIC 565, 510, 380 and 710 mg/L against E. carotovora, R. fascians, and R. radiobacter and R. solanacearum, respectively. Conclusion: Based on antimicrobial activity, raw plant extracts can be a cost-effective way to protect crops from microbial pathogens. Because plant extracts contain several antimicrobial compounds, the development of resistant pathogens can be delayed.

Background: Over exposure to Ultra Violet (UV) radiation is one of the most significant external stress-inducing factors resulting into occurrence of skin pigmentation among others in human body. The biological implication of such disorders is not only limited to premature skin aging and cancer, but also resulted into economic loss of perishable agricultural products. Methods: Methanol extracts of ten (10) medicinal plants with skin health traditional history were selected for this study. The biological profile of the extracts was assessed in an in-vitro system using colorimetric assays: tyrosinase inhibition, Ferric-ion Reducing Antioxidant Power (FRAP), Trolox Equivalent Absorbance Capacity (TEAC) and Fe II-induced microsomal lipid peroxidation. Results: Representative of asteraceae such as Laggera pterodonta (S3); Ageratum conyzoides (S4) and Chromolaena odorata (S5), while Euphorbia convoluloides (S8) were found to possess good anti- tyrosinase activity (IC50 = 177.50; 125.08; 167.58; 161.92) μg/ml respectively, in which the rate of formation of dopachrome proceeded via pseudo second order kinetic using the Largergren model. Other notable inhibition of oxidative stress displayed by the methanol extracts includes S7 (FRAP = 1905.12 ± 2.85 μM AAE/g); S1 & S6 (TEAC = 2163.48 ± 2.80; 1044.35 ± 28.99) μM TE/g, while S7 & S9 showed highest inhibitory activities on Fe II-induced microsomal lipid peroxidation (IC50 = 33.625; 35.125) μg/ml, respectively in competitive manner to that of the commercial anti-oxidant EGCG (IC50 = 36.250 μg/ml). Conclusion: The outcome of the biological properties of the selected plant extracts in this study suggested the existence of relationship between the traditional claims and the scientific data therein.

Background: Plants are rich and cheap source of active phytoconstituents. Present study was performed in order to authenticate the traditional use of Cocos nucifera in malaria treatment as well as to search an alternative for drug resistant parasites. Objective: In the present investigation, ethanolic (ACN) and hydroalcoholic (HACN) extracts of Cocos nucifera endocarp were evaluated for antimalarial potential as well as subjected to GC-MS analysis to characterize the bioactive components. Methods: In vitro antiplasmodial activity of ACN and HACN was assessed against P. falciparum strains MRC-02 (CQ sensitive) and RKL-09 (CQ resistant) and percentage schizont maturation inhibition was determined. To confirm the antimalarial potential, in vivo Peter’s 4-Day suppressive test using P. berghei strain was performed at a dose of 25 and 50 mg/kg/day for 4 consecutive days. Bioactive components were characterized by the application of Gas chromatography and Mass spectrometric technique to the extracts. Results: Promising in vitro antiplasmodial activity was exhibited by both alcoholic (ACN) and hydroalcoholic (HACN) extracts against P. falciparum strains MRC-02 (CQ sensitive) with IC50 values < 5 μg/mL. HACN (% Suppression = 75.43 ± 0.18; MST=19.21 days) and ACN (% Suppression = 34.65 ± 0.11; MST=10.11 days) showed moderate in vivo antimalarial activity (p < 0.05) at dose 50 mg/Kg while standard drug chloroquine (8mg/kg) suppressed 100% parasitaemia. Twenty compounds have been identified and characterized by GC-MS studies.

Background: Natural products or naturally derived compounds are invaluable to human and animal lives either for nutritional value or for medicinal purposes. Indeed, natural products including extracts containing polychemical mixtures play a leading role in the discovery and development of drugs. However, the increasing interest in natural medicines is also attracting a growing concern about the safety of naturally derived medications. Objective: In the present study, we evaluated several naturally derived compounds for in vitro cytotoxicity in mammalian cells. Methods: A total of 54 compounds were evaluated for in vitro cytotoxic and apoptotic action in Human Fibroblast Foreskin (HFF) cells. Results: Of the 54 natural compounds screened for cellular toxicity, only nonactin and cephaeline. HBr reduced cellular viability by ≥60% with IC50 value <3 μg/ml. Addition of trolox antioxidant to the assay medium failed to abate cellular toxicity by both nonactin and cephaeline.HBr treatments. Fluorescence evaluation for Reactive Oxygen Species (ROS) production as well as Mitochondrial Membrane Potential (MMP) was negative for both nonactin and cephaeline.HBr treatments. In contrast, both nonactin and cephaeline.HBr caused cellular apoptosis and this was not attenuated even in the presence of trolox. Conclusion: Taken together, we show evidence supporting that cytotoxic and apoptotic action of nonactin and cephaeline.HBr precludes oxidative stress or ROS production.

Background: Current anticancer therapeutics comes with significant side effects and thus focus is shifting towards minimizing the side effects or to avoid the disease altogether. Thus, various natural products are being investigated for their potential therapeutic values which can be easily included in daily diet of a person. Citrullus colocynthis (L.) fruit is commonly used in traditional medicines and is known to have antioxidant effects, thus may possess potent anticancer activity as well. Objectives: To establish the anticancer potential of fruit belonging to Citrullus colocynthis (L.) and delineate the potential targets. Results: In the present study it was found that seed and pulp extracts of the fruit are effective against various cancer cell lines while the normal cells, with lower rate of division, remain largely unaffected. The current study for the first time shows that these extracts function via regulation of p53 pathways and the mode of apoptosis is mostly via mitochondrial (intrinsic) pathway. The biological profiling of the extracts was also validated using molecular modelling studies utilizing the two major polyphenols constituents from colocynths i.e., Isoorientin and Isovitexin. Conclusion: The study suggested that the constituent has a multiple target approach for the inhibition of cancer cell proliferation and inhibition of ROS production via the major apoptotic proteins. All of these outcomes suggest and establish a critical role of ROS accumulation and mitochondrial function in the p53-dependent cell.

Background: Phytochemical studies of Annona muricata showed the presence of bioactive components with anticancer activity. We compared the anticancer properties of crude acetonic and methanolic A. muricata leaf extracts. Methods: The viabilities of different cell lines (A549, U87, U251, K562 and VERO) treated with A. muricata acetonic or methanolic leaf extracts were measured using the MTT assay. Apoptosis induction, cell cycle and cytoskeleton rearrangements were evaluated in K562 by flow cytometry or fluorescence microscopy. Results: Chemical analyses of the A. muricata extracts showed differences in their composition. The K562 cell line was the most sensitive to the treatment with the acetonic and methanolic extracts, and the IC50 values, respectively were 28.82 (24.41 - 34.69) and 32.49 (27.21 - 40.16) μg/mL. Both extracts induced apoptotic cell death and G0/G1 phase cell cycle arrest. For the first time, cytoskeleton rearrangements were observed in the K562 cell line treated with methanolic extract. Conclusion: These findings suggest that both A. muricata extracts exhibit antileukemic potential and represent a promising source of novel compounds with anticancer activity.

Background: Developing new antimicrobial medicines is one of the strategic objectives of the global action plan adopted by the World Health Organization to tackle antimicrobial resistance. Objective: Considering the fact that natural products derived from medicinal plants are an important source for discovering new antimicrobial compounds, we investigated here the antimicrobial properties and the mode of action of various extracts from Fredolia aretioides, an endemic medicinal plant of Morocco and Algeria, and belonging to the Chenopodiaceae family. Methods: Various extracts from F. aretioides were prepared and evaluated for their antibacterial activity against six bacterial species, and their antifungal activity against five fungi species. Chemicalgenetic screens were performed using a collection of Saccharomyces cerevisiae viable haploid deletion mutants spanning diverse biological processes. Results: The diethyl ether extract of roots was found to be active against Citobacter freundii, with a MIC of 400 μg/ml. Hydro-methanol, methanol and residual extracts from aerial parts and roots were active against all five fungi species tested. Our results showed that residual extracts were the most effective against the fungi tested. Residual extract from aerial parts was more potent than the residual root extract, with IC50’s of 60 μg/ml and 440 μg/ml, respectively. Chemical-genetic analysis in S. cerevisiae revealed that residual extracts might affect fatty acid and sphingolipid biosynthesis. Conclusion: All these findings suggest that F. aretioides is a promising source for the isolation of novel antimicrobial agents with novel mechanisms of action against human pathogens.

Background: In both the developed and developing world, the mortality rates of people afflicted with cryptococcosis are unacceptably high despite the availability of antifungal therapy. The disease is caused by Cryptococcus neoformans (predominantly in immunocompromised individuals) and by Cryptococcus gattii. Globally the disease is estimated to cause around 600,000 deaths annually. Antifungal therapy is available, but in the developing world, may be unaffordable to many people, there is an increasing threat of resistance to the available drugs and our repertoire of antifungal drugs is very limited. Consequently, more research has been focusing on the use of medicinal plants as therapeutic agents. The originality of the current study is that although Tulbaghia violacea is a well-documented medicinal plant, the chemical composition of aqueous extracts and their antifungal potential against pathogenic yeasts are unknown. This is the first study that evaluates the chemical constituents of aqueous T. violacea root, leaf, rhizome and tuber extracts and their corresponding antifungal activities against C. neoformans and C. gattii. Objectives: The study aimed to investigate the phytochemical composition and antifungal potential of Tulbaghia violacea root, leaf, rhizome and tuber extracts against Cryptococcus neoformans and Cryptococcus gattii. Methods: Roots, leaves, rhizomes and tubers were extracted with water only for 48 h at room temperature with continuous shaking. Extracts were filter sterilized, freeze-dried and, chemically analyzed for saponin, flavonol, phenolic and tannin content. Chemical constituents of each extract were also identified by GC-MS analysis. The Minimum Inhibitory Concentration (MIC) of suitably diluted extracts of each plant part were also performed against C. neoformans and C. gattii, yeast pathogens commonly associated with HIV/AIDS sufferers. Results: Phytochemical analysis showed different concentrations of saponins (between 1023 and 2896.73 μg/ml), phenolics (between 16.48 and 51.58 μg/ml) and tannins (between 122.30 and 543.07 μg/ml) present in the different extracts. No flavonols were detected. GC-MS analysis identified a complex mixture of phytochemicals composed predominantly of sulphide, pyran, furan and ketone containing compounds to be present in the different plant parts. All extracts were dominated by the presence of 4 H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl, a pyran known to have antifungal properties. Although the root, leaf, rhizome and tuber extracts exhibited antifungal activities against both fungi, the rhizome and tuber extract were found to possess the lowest MIC’s of 1.25 mg/ml and 2.5 mg/ml against Cryptococcus neoformans and Cryptococcus gattii respectively. Conclusion: T. violacea extracts have a complex constituent of phytochemicals and each plant part exhibited a strong antifungal activity against C. neoformans and C. gattii. The rhizome and tuber extracts showed the highest antifungal activity against C. neoformans and C. gattii respectively. Thus, T. violacea aqueous extracts are strong candidates for further development into an antifungal chemotherapeutic agent.

Background: Breast cancer and human colon cancer are the most common types of cancer in females and males, respectively. Breast cancer is the most common type of cancer after lung and colon cancers. Natural products are an important source for drug discovery. Boesenbergia rotunda (L.) Mansf. is commonly known as finger root, belonging to the Zingiberaceae family. Objective: The aim of this study to isolate some natural compounds from the rhizomes of B. rotunda (L.) Mansf., and to investigate their cytotoxicity against the human triple-negative breast cancer cell (MDA-MB-231) and HT-29 colon cancer cell lines. Methods: The dried rhizomes of B. rotunda were extracted with methanol. The methanolic extract was further used for solvent-solvent extraction. Bioassay-guided extraction and isolation of the rhizomes of the B. rotunda exhibited cytotoxic properties of hexane and dichloromethane fractions. Results: Six major chemical constituents, pinostrobin (1), pinostrobin chalcone (2), cardamonin (3), 4,5-dihydrokawain (4), pinocembrin (5), and alpinetin (6) were isolated from the rhizomes of the B. rotunda. All the chemical constituents were screened against the human triple-negative breast cancer cell (MDA-MB-231) and HT-29 colon cancer cell lines. The compound cardamonin (3) (IC50 = 5.62±0.61 and 4.44±0.66 μg/mL) and pinostrobin chalcone (2), (IC50 = 20.42±2.23 and 22.51±0.42 μg/mL) were found to be potent natural cytotoxic compounds against MDA-MB-231 and HT-29 colon cancer cell lines, respectively. Conclusion: Cardamonin (3) and pinostrobin chalcone (2) were found to be the most potential natural compounds against breast cancer cell line MDA-MB-231 and colon cancer HT-29 cell line.