Current Bioactive Compounds - Volume 18, Issue 8, 2022

Background: Plants from the genus Nymphaea L. have been used for decades to treat various diseases, including dysentery, diarrhea, uterine cancer, gonorrhea, inflammation conditions, etc. The present study aims to critically analyze comprehensive literature on ethnopharmacological uses, phytochemistry, pharmacology, and toxicity of Nymphaea L. Methods: The available information on Nymphaea L. was obtained from textbooks, theses, as well as published articles through libraries and electronic databases. Results: More than 150 compounds, including flavonoids, phenolics, alkaloids, miscellaneous compounds, etc. were identified from Nymphaea L. extracts, and pure molecules from Nymphaea L. exhibited a wide range of pharmacological activities, including antimicrobial, anti-inflammatory, anticancer, immunomodulatory, hepatoprotective, antioxidant, cytotoxic, etc. Conclusion: According to in vitro and in vivo studies, Nymphaea sp. are very promising medicinal plants. However, more in vivo experiments, cytotoxicity tests, and detailed mechanisms of action of their extracts and compounds are recommended to translate their ethnomedicinal claims into scientific rationale-based information.

Background: Vepris dainelli (Rutaceae) is an endemic medicinal plant of Ethiopia, traditionally used for the treatment of abdominal cramps, intestinal worms, skin diseases, and tooth pain. Methods: Roots and fruit extracts were subjected to silica gel column chromatographic separation to afford five alkaloids, reported for the first time from the species. The cytotoxic effects of alkaloids (2-4) were evaluated in vitro against the estrogen-responsive MCF-7 and estrogen-unresponsive MDA-MB-231 human breast cancer cell lines by MTS assay. Results: The results revealed that alkaloids (2-4) induced a significant reduction in cell growth of both breast cancer cell lines in a dose-dependent manner. Evodiamine (4) showed the highest potency against the aggressive metastatic MDA-MB-231 cell line at low micromolar concentrations. In addition, it highly arrested the cells in the G2/M phase, especially the MCF-7 cell line. By contrast, evoxanthine (2) and arborinine (3) exhibited higher cytotoxicity against MCF-7 than MDA-MB- 231 and influenced the cell cycle in both cell lines by arresting some cells in the G2/M phase, preventing cells with damaged DNA from entering mitosis. Molecular docking analysis showed that all alkaloids inhibit human topoisomerase II α, compared with vosaroxin’s anti-cancer agent under clinical trial. The ADMET studies revealed that the alkaloids showed the highest drug-likeness properties, suggesting that these alkaloids act as a drug and exhibit remarkable biological activities, except (5). DFT calculations indicated that the studied alkaloids showed the lowest gap energy and were chemically reactive. Conclusion: The results obtained from molecular docking, drug-likeness properties, ADMET analysis, and DFT calculation are in good agreement with experimental studies. Hence, evoxanthine (2), arborinine (3), and evodiamine (4) may serve as lead molecules that could be developed into potent topoisomerase II α inhibitors against human breast cancer cells.

Background: Genistein is one of many new cytotoxic drug leads that have been discovered recently. It is a well-studied chemopreventive drug that has attracted the attention of the scientific community due to its favourable effects on grave illnesses in humans such as cancer. Objective: The present study focuses on the methanolic extraction, isolation, and characterization of an isoflavone, genistein, from the weed plant of Cytisus scoparius Linn. (family: Fabaceae). Methods: The phytochemical structure of genistein was confirmed by its spectral and chromatography analysis through IR, HPTLC, LCMS, NMR, etc. The total flavonoid fraction of methanolic extracts containing genistein was evaluated for in-vitro cytotoxic activity on cervical cancer HeLa cells using MTT assay, cell cycle analysis, and topoisomerase II inhibitory activity. Results: The result of the in-vitro cytotoxicity study showed the IC50 value of 4.5 μg/ml, which shows that the isolated compound is cytotoxic. The result of cell cycle analysis revealed the cell arrest at a sub-G phase, which shows that the isolated compound was apoptotic. Moreover, the human topoisomerase II assay proved that it is an excellent human topoisomerase II inhibitor at 10 μg/ml. Conclusion: These findings revealed that genistein increased cytotoxicity and cell arrest owing to human topoisomerase II inhibitory activity and thus it may be an anti-cancer component. The relationship between the phytochemical structural analysis of this compound and its bioactivities is discussed.

Background: Jordan is a country well-known for its diversity in wild plants, and for many decades, folk medicines have represented part of its cultural heritage. In the present study, investigations have been focused on the therapeutic potential of Silybum marianum and Pergularia tomentosa on type 2 diabetes mellitus. In type 2 diabetes, which is considered a global health problem, the body cannot respond to or produce insulin hormonem, which raises the blood glucose level, resulting in mortality, morbidity, healthcare expenses, and reduced life quality. Dipeptidyl peptidase-IV (DPP-IV) enzyme, a serine protease, is responsible for deactivating incretin hormones that promote insulin secretion. Accordingly, the DPP-IV inhibitory activity of these plant extracts that prolong the hypoglycemic effect of incretins was evaluated. Methods: The aerial parts of S. marianum and P. tomentosa were dried, ground, and extracted with ethanol. The ethanol extract was dried under reduced pressure and was partitioned by methanol, butanol, and hexane according to a systematic procedure. The inhibition of the DPP-IV enzyme by the different extracts was studied (at 10.0 mg/mL concentration). Sitagliptin was used as the positive control. Results: Fortunately, most of the plant extracts have noticeable inhibitory activity against the DPPIV enzyme. It was found that the tested methanol extract of S. marianum has an inhibitory activity of 75.6% and the butanol extract of P. tomentosa has an inhibitory activity of 73.6%, which are analogous to DPP-IV inhibition of sitagliptin (78.5%), the used positive inhibitor. A superior inhibition of 98.1% was displayed for the butanol extract of S. marianum at 10.0 mg/ mL concentration. Conclusion: The revealed DPP-IV inhibitory activity of tested extracts advocates that their active constituents, particularly flavonoids, are capable of binding to the enzyme’s active cleft.

Background: The search for natural anticancer agents is a worthy scientific research goal, driven by the hope to lessen cancer's tremendous global burden. Objective: This study aimed at evaluating the cytotoxic activity of Gardenia latifolia Ait. (Rubiaceae) against lung (A549) and colon (HCT116) cancer cell lines. Cytotoxicity-guided isolation of the bioactive phytochemicals was conducted, followed by various mechanistic validations of the appealing cytotoxic metabolites. Methods: The cytotoxic effects were determined using an MTT assay. The two most cytotoxic compounds were further evaluated for their effects on cell cycle progression and apoptotic capabilities using the flow cytometry approach. Additionally, we conducted a molecular docking analysis to reveal their potential interactions with the human topoisomerase IIα. Results: The phytochemical investigation afforded nine compounds, including a new one, (-) 1- acetyl 4,5-di-O-caffeoylquinic acid. The latter compound was the most cytotoxic against the colon cancer cell line (IC50 1.9 μg/ml) with a remarkable tumor-selectivity (SI ≈ 15). Moreover, the isolated glycoside, 1-O- [6-O- (5-O-vanilloyl- β-#133;-apiofuranosy1)- β-#133;-glucopyranosy1]-3,4,5- trimethoxybenzene, showed selective cytotoxicity towards A549 and HCT116 cells (IC50 values of 3.8 and 3.3 μg/ml, respectively). Both compounds considerably affected the cell cycle distribution. They caused G2/M cell cycle arrest, showed apoptotic capabilities, and displayed significant in silico topoisomerase IIα inhibition. Conclusion: Two cytotoxic and apoptotic compounds were reported from Gardenia latifolia. Subsequent in vivo studies and clinical trials should be conducted to substantiate their anticipated therapeutic values.

Background: Marine algae produce bioactive compounds, including polyphenols. They have antioxidant, antibacterial, immune regulation and other biological activities. The aim of this study was to examine the antibacterial and antioxidant activities of extracts of five marine algae species: Cystoseira humilis, Halopteris scoparia, Pavonica padina, Sargassum vulgare and Rhodomela confervoides of Bejaia’s coast (northern Algeria). Methods: Phenolic content of the five marine algae was assessed using Folin Ciocalteu method and then characterized by HPLC-DAD and HPLC-ESI-QTOF-MS analyses. The antioxidant activity was evaluated by DPPH•, ABTS•+, NO• radical scavenging and FRAP assays. For the screening of the antibacterial activity, six strains were tested using three different methods: agar disc diffusion, agar well diffusion and spot methods. The minimum inhibitory concentrations (MICs) were also determined. Results: Protocatechuic acid was the phenolic compound identified in all the studied seaweeds, while Padina pavonica was the species where more phenolic compounds were identified (phloroglucinol, gallic acid, ferulic acid and syringic acid). Cystoseira humilis showed the highest antioxidant activity (DPPH•: 2237.50 ± 148.34 μM TE/100 g dw, ABTS•+: 1992.50 ± 165.97 μM TE/100 g dw, NO•: 2559.58 ± 42.08 μM TE/100 g dw, FRAP: 2081.20 ± 115.29 μM TE/100 g dw), which was also the richest in phenolic compounds (4.63 ± 0.23 mg PhlE/g dw). Rodomela confervoides showed an important activity against all the bacterial strains tested with the greatest diameter of inhibition zone (18 mm) against E. coli with a MIC equal to 20 mg/mL. The extract of Padina pavonica showed a moderate activity (13.5 mm) against P. aeruginosa with a MIC ≤ 10 mg/mL and a MBC > 10 mg/mL. Conclusion: The studied marine algae showed antioxidant and antibacterial activities. They could be potentially used for applications in medicine, food production and the cosmetic industry.

Background: Boswellia serrata is an important species from the Boswellia genus, which contains a variety of significant phytoconstituents. Numerous applications of the B. Serrata have been mentioned in the literature of the Indian ayurvedic system. Researchers reported abundant pharmacological activities of B. Serrata resins extract. The extract produces synergistic pharmacological activity due to the presence of the Boswellia acids and their derivatives. Among all Boswellia acids, 3-O-acetyl-11-keto-β-boswellic acid (AKBA) was found to be more potent. Traditionally, column chromatography was used for the isolation of AKBA from raw material as well as extracts. However, the column chromatography method was monotonous and timeconsuming. Objective: The main goal of the research was to develop a new, simple, rapid, and reproducible method for the isolation of AKBA from the resin extract of B. Serrata. Methods: The extraction and isolation of AKBA involved extraction of resins using hydroalcoholic solution followed by alkali treatment. The alkali solution was further treated with acid to precipitate the crude AKBA. Results: The obtained crude AKBA was subjected to the dry column vacuum chromatography to separate and yield the high purity of the AKBA. The purity of the isolated AKBA was established by TLC & UHPLC. Spectral characterization of the isolated compound was performed by employing IR, MS, and NMR. Conclusion: The proposed method can be used to isolate AKBA from resin extract of B. Serrata. Some modifications in this method lead to the large-scale production of highly pure AKBA for various pharmaceutical applications.