Current Bioactive Compounds - Volume 19, Issue 8, 2023

Background: The tubers of Gloriosa superba L. (Colchicaceae) are previously well known for their alkaloidal constituents. The present work aimed to investigate the non-alkaloidal constituents and evaluate their in vitro and in silico antibacterial and antioxidant activities from the tuber. Methods: The chloroform: methanol (1:1) tuber extract was fractionated over silica gel column chromatography, and isolated compounds were characterized by NMR spectroscopy. Various extracts and isolated compounds were evaluated for their antibacterial and antioxidant activities against certain pathogenic strains and oxidants. The in silico drug-likeness properties of isolated compounds were also studied against 6F86 antibacterial and 1HD2 antioxidant protein models. Results: Three non-alkaloidal compounds, β-sitosterol (1), 3-(cyclopenta-2,4-dienyloxy) β- sitosterol (2) and 1,2-n-dipropyl phthalate (3), were reported herein. The n-hexane and chloroform extracts displayed better antibacterial activity against E. coli (9.83 ± 0.28 mm) and P. aeruginosa (10.65 ± 0.79 mm), and S. aureus (10.33 ± 0.3 mm), respectively, at 100,000 μg/mL concentration. Compound 3 established a better activity against all bacterial strains (9.78 ± 0.63-11.07 ± 0.09 mm) at 1000 μg/mL (IC50 values of 1.5-3.2 μg/mL). All the extracts exhibited a DPPH free radical scavenging activity comparable to ascorbic acid (IC50 value of 1.2 μg/mL), whereas isolated compounds were found with negligible DPPH scavenging activity and weak ferric ion reduction power up to 500 μg/mL dose. The docking study revealed that all the compounds fulfilled Lipinski’s rule of five by contravening no more than one rule with strong binding affinity shown by compound 1 (-8.2 kcal/mol) and compound 3 (-4.5 kcal/mol) to the 6F86 bacterial and 1HD2 antioxidant protein models, respectively, which are comparable to the ciprofloxacin (-7.2 kcal/mol) and ascorbic acid (- 4.5 kcal/mol) drugs. All the compounds also did not show any cytotoxicity properties. Whereas compound 1 showed an immunotoxicity and mutagenicity properties; and compounds 2 and 3 were found as immunotoxic and carcinogenic isolates, respectively. Conclusion: The promising antioxidant activity result of the various tubers extracts may highlight the potential use of Gloriosa superba as a source of foods by conducting further phytochemical investigation and additional bioassay evaluation, including the cytotoxicity effect of the whole part of the plant.

Bioactive compounds derived from food or plants have become a natural source with the potential for producing functional, nutraceutical, and pharmaceutical foods due to their biological functions and beneficial health effects. However, to perform such physiological processes, these compounds need to be absorbed through the gastrointestinal tract. Among the existing technologies, nanoencapsulation increases physical stability, protection, and the contact surface, facilitating the solubility and bioavailability of such compounds. In this type of encapsulation, lipid nanocarriers are promising carriers due to their lipid structure and containing hydrophilic surfactant, capable of facilitating the intestinal absorption of active compounds. However, in food or drugs, one of the significant challenges for applying bioactive compounds on a nanoscale is the lack of in vivo studies that establish safety limits for cytotoxicity. This review covered recent studies on the encapsulation of natural bioactive compounds in different types of lipid nanocarriers. In addition to methods for obtaining and characterizing nanocarriers, bioactivities with beneficial potential for human health, such as antioxidant, antimicrobial, antihypertensive, antidiabetic, and neuroprotective, are mentioned. The manuscript deals with the bioaccessibility of active compounds, new perspectives, and challenges for applying lipid nanocarriers.

Different plants are rich in medicinal properties, which nature has provided in abundance for the living beings of this earth. Since the dawn of time, nature has proven to be a rich source of bioactive scaffolds that have been exploited in the creation of pharmaceuticals. Osthole is a natural coumarin derivative and potential bioactive compound found in plants. Herein, we aimed to review the origins, biology and pharmacological profiles of osthole, a plant-derived coumarin that is found in a variety of therapeutic plants, including Cnidium monnieri. Osthole, also called 7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one, is a naturally occurring coumarin found to be present in different plants of the Apiaceae family, i.e., Cnidium monnieri and Angelica pubescens. The biological potential of the osthole in medicine has been investigated using a variety of literature databases. This study gathered diverse scientific research data on osthole from various literature sources and analysed, including Scopus, Google Scholar, Web of Science and PubMed. From the collected data, it was found that osthole have potential pharmacological activities, such as anticancer, antioxidant, osteogenic, cardioprotective, antimicrobial, antiparasitic, anti-hyperglycaemic, neuroprotective, and antiplatelet. The data in this review paper supports the pharmacological potential of osthole, but to completely appreciate the pharmacological potential of this therapeutically powerful chemical, researchers must focus their efforts on further experimentation, biosafety profiling and synergistic effects of this compound. The purpose of this study was to learn more about the origins, biology, and therapeutic benefits of osthole in medicine in order to develop better treatments for human diseases.

Orthosiphon aristatus has been known for its medicinal uses. One of the compounds responsible for the pharmacological activities of O. aristatus is a flavonoid called Eupatorin (EUP). EUP has been studied for its pharmacological activities, including anti-inflammatory, vasodilating, antiproliferative, hepatoprotective, analgesic, and antidiabetic properties. Despite its importance and abundance, currently, there is no published paper that reviews the characteristics, pharmacological activities and isolation methods of EUP. This review summarizes the botanical origin, phytochemical characteristics, pharmacological activities, isolation, as well as identification and characterization methods of EUP from O. aristatus. This paper also compares different isolation methods based on the parameters and the resulting yields. Various isolation methods had been used to obtain EUP. Reverse-phase high-performance liquid chromatography (HPLC) is the most commonly used method to isolate EUP, followed by preparative thin layer chromatography (TLC) and crystallization for the purification. Various spectroscopic methods, including UV-Vis, FT-IR, Mass, and NMR spectroscopy have been commonly used to identify and characterize EUP. This paper provides a comprehensive insight into EUP from O. aristatus which might be beneficial for future research using this compound.

Introduction: Thiamine, often known as vitamin B1, is a water-soluble vitamin that can be added to food or purchased as a supplement. It plays an important role in many cellular processes and is crucial for overall human health. The synthesis and characterization of Thiamineencapsulated chitosan nanospheres for sustained release and improved bioavailability is the major objective of this study. Materials and Methods: The chitosan nanospheres were prepared using sodium tripolyphosphate (TPP) as cross-linking agent. Results: The ionic interactions between chitosan and TPP produced small-sized stable nanospheres for the incorporation of Thiamine. The conjugate was characterized through a UV spectrophotometer and Fourier Transform Infrared spectroscopy (FTIR). The size and morphology were determined using Zetasizer and Scanning Electron Microscopy (SEM). An average size of 504 nm size was obtained for the nanospheres. The in vitro release studies were performed for 30 days to assess the sustained release of thiamine from nanoencapsulates. Cellular uptake of the thiamine-encapsulated chitosan nanoparticles was studied in the human cervical cancer cell lines (HeLa) and mus-musculus 3T3 L1 cell lines. Conclusion: This study is an early design and development of a technology for encapsulating water-soluble vitamins in biodegradable polymers, which can be examined for the vitamin's long-term bioavailability.

Introduction: There is growing interest in alternative therapies for managing inflammatory bowel disorders (IBD) that offer efficacy and a suitable safety profile. The present study aimed to evaluate the intestinal anti-inflammatory effect of the alkaloid extract of Linum usitatissimum (ALU) on the acetic acid (AA) experimental model of colitis. Methods: For in vivo experiments, an 8-day 5% acetic acid administration protocol was used in BALB/c mice to induce colitis. The intestinal anti-inflammatory effect of oral ALU (12.5, 25, and 50mg/kg) was evaluated after 8 days. Colon damage was evaluated macroscopically (colon weight/ colon length), and the histological alterations were also assessed. Results: ALU treatment significantly reduced signs of intestinal inflammation compared to the Acetic acid control mice, confirmed by histological examination. Conclusion: These results suggest that the total alkaloid extract from Linum usitatissimum seeds has potent intestinal anti-inflammatory properties and may be a promising treatment for ulcerative colitis.

The study aimed to assess the radiosensitizing effect of lithium ascorbate on tumor cells. Background: Cancer cells radioresistance is an important factor restraining the success of X-ray therapy. Radiosensitizing drugs make tumor cells more sensitive to ionizing radiation and improve the effectiveness of radiotherapy. Although many chemical substances can potentiate the cytotoxic effects of X-ray radiation, their clinical applications are limited due to possible adverse reactions. Recently, several approaches have been proposed to develop new radiosensitizers that are highly effective and feature low toxicity. Among new enhancers of X-ray therapy, ascorbic acid, and its derivates demonstrate very low toxicity along with a wide therapeutic range. Lithium ascorbate is a promising X-ray therapy enhancer, but its mechanism of action is unknown. This research focuses on the radiosensitizing properties of lithium ascorbate and its effects on both tumor and normal irradiated cells. Methods: The viability of the radiosensitized cells was evaluated by fluorescence flow cytometry using Annexin V-FITC Apoptosis Detection Kit and Cellular ROS Assay Kit (Abcam, UK). The test cell cultures included normal human mononuclear and Jurkat cells. Results: Lithium ascorbate sensitizes normal human mononuclear and Jurkat cells towards ionizing radiation. The combined cytotoxic effect of X-ray irradiation (3 Gy) and lithium ascorbate (1,2 mmol/L) substantially exceeds the effects of the individual factors, i.e., synergetic action appears. The major types of cell death were late apoptosis and necrosis caused by excessive production of reactive oxygen species. Conclusion: Lithium ascorbate in combination with X-ray irradiation exhibited the cytotoxic effect on both normal and cancer lymphoid cells by activating reactive oxygen species (ROS)-induced apoptosis. These findings indicate that lithium ascorbate is a promising substance to develop a new radiosensitizing drug.

Background: Despite the development of numerous customized techniques for treating breast cancer, cancer patients' clinical results revealed adverse consequences in addition to chemotherapeutic drug resistance. Hence, finding therapeutic compounds with little or no side effects becomes essential in the fight against cancer. Resveratrol, a naturally occurring non-flavonoid polyphenol present in plants as a phytoalexin, is a promising therapeutic agent that has garnered the interest of several researchers due to its prodigious pharmacological and biological activities, but its unfavourable pharmacokinetic properties complicated its clinical studies. Along with several structural modifications, substitutions, etc., that have already been reported, this is the first time that a novel resveratrol analogue comprising an aromatic hetero moiety (ResD1) was synthesized using resveratrol isolated from grape (Vitis vinifera) peels as a precursor. Methods: ResD1 was synthesized by one-pot reaction using extracted and isolated resveratrol from grape peels. Structure confirmation of the isolated resveratrol and synthesized resveratrol derivative was elucidated by ¹H-NMR, ¹³C-NMR, FTIR, and LC-MS. In silico molecular docking and ADMET study of ResD1 were carried out using AutoDock 4.2 and ADMETLab 2.0. ResD1 was evaluated for in vitro antioxidant, antimicrobial, anticancer, and CAXII gene expression as per the standard methods. Results: In silico molecular docking results revealed that ResD1 is capable of attaching to the ERα (estrogen receptor alpha) protein via hydrogen and hydrophobic bonds and has -7.12 kcal/mol as docking score. The novel derivative (IC50 = 42.8 μg/ml) exhibited better radical scavenging ability than ascorbic acid (control). The antimicrobial activities exemplify that it can induce microbial cell death for all the strains at higher concentrations. MTT assay results portrayed the potent antiproliferative activity against MCF-7 cell lines (IC50 = 155.2 μg/ml) and non-cytotoxicity for MDA-MB- 231 cell lines. Moreover, the synthesized resveratrol derivative induced ROS (reactive oxygen species) levels in MCF-7 cells, indicating cytotoxicity. CAXII gene expression study showed that it downregulated the CAXII genes. Conclusion: This study serves as an example of how a newly proposed resveratrol analogue might be utilized as a viable pharmacophore for specifically targeting the ER alpha protein which will be beneficial in investigating a fresh batch of effective resveratrol mimics as prospective anticancer agents.