Current Bioactive Compounds - Volume 16, Issue 9, 2020

Background: Pyrazolines are five-membered heterocycles with two adjacent nitrogen atoms present in the ring and they have attracted many researchers all over the world to assess their potential therapeutic significance. Pyrazolines are known for their crucial role in numerous diseases like cancer via various mechanisms. Pyrazoline and its derivatives have been found to have potent anticancer activity by inhibiting EGFR (Epidermal Growth Factor Receptor Tyrosine Kinase) and other types of RTKs. Rapid advances in the understanding of cellular signaling by EGFR in normal and malignant cells have brought to light the EGFR as a selective anticancer target. The review enlists some recently developed pyrazolines as EGFR tyrosine kinase inhibitor along with their structure-activity relationships. Methods: The structure-activity relationship of different pyrazoline derivatives was discussed along with their epidermal growth factor receptor inhibitory activity. Both review and research articles have been considered and cited in the paper. Results: Pyrazolines have assisted medicinal chemistry by their diverse biological activities which make them a beneficial scaffold. The structure-activity relationship studies on pyrazolines revealed that the structural characteristics and different substitutions on pyrazoline ring alter the EGFR inhibitory activity. Conclusion: In the present review, pyrazoline derivatives with EGFR kinase inhibitory activity are described based on their structure-activity relationships based on their structural substitution pattern around the pyrazoline scaffold.

Background: Colorectal cancer represents one of the prominent causes of mortality worldwide in men and women. The objective of this study was to search for new potential anticancer compounds, both in prevention and treatment of colorectal cancer. The anticancer potential of marine bacterial extracts against Human colorectal carcinoma cell line (HCT116) was evaluated as well as the partial identification of bioactive metabolites. Methods: All bacterial extracts were tested for their cytotoxicity against HCT116 cell line by means of MTT assay. The highly cytotoxic dichloromethane extracts of marine sponge-associated bacteria Vibrio sp. and Bacillus sp. were analyzed by GC-MS. Results: Two fractions, Vib3 and Bac3, exhibited a very interesting cytotoxicity against human colorectal carcinoma (HCT116) cell line, with a percentage of cytotoxicity of 96.04 % and 29.48 %, respectively. Discussion: The GC-MS analysis revealed the presence of two major fatty acids, palmitic and oleic acids, in Vib3 fraction and fatty acid esters and phenolic compounds in Bac3 fraction. Conclusion: Based on previous literature, it may be hypothesized that the anticancer activity of bacterial extracts could be, at least partially, to the fatty acids fraction.

Background: Lavandula stoechas is the main member of Labiatae (Lamiaceae) family. People use this medicinal plant in the treatment of several diseases around the world. The purpose of this work was to evaluate the cytotoxic effect of different fractions like ethanol, ethyl acetate and n-hexane from methanol extract of Lavandula stoechas aerial parts on HepG2 cell line and analysis of chemical composition of the most active fraction of the Lavandula stoechas aerial parts. Methods: Methanolic extract was prepared by cold maceration. Fractions from extract were prepared in solvents of increasing polarity i.e. n-hexane, ethyl acetate and ethanol. In order to evaluate the cytotoxic effect of Lavandula stoechas, MTT assay method was used. For this purpose, HepG2 cells line were treated with the above mentioned Lavandula stoechas aerial parts fractions with different concentrations 10, 25, 50, 100, 250, 500 and 1000 μg/ml. The cells without treatment were served as a control. Results: The result of this study showed that ethanolic fraction showed major reduction in % cell survival compared to other fractions. These results showed that Lavandula stoechas Ethanolic fraction was highly inhibitory. Further, phyto chemical analysis of ethanolic fraction was carried out using GC-MS technique and the reports showed Lupeol, Phytol, α-Cadinol, Lup-20(29)-en-3-one, hydrocoumarin, Lup-20(29)-en-3-one. Other compounds included fatty acids and their esters. Some of these compounds are being first time reported here from this plant. Conclusion: MTT assay showed morphological changes, which clearly support Lavandula stoecha ethanolic fraction possesses anticancer effect which may be due to the presence of phytosterols.

Background: Formulations containing two or more than two herbs are called polyherbal formulation. Single herb formulation has been well established due to its active phytoconstituents, which are usually present in minute amount and sometimes these are insufficient to achieve the desired therapeutic effects. The popularity of polyherbal formulation is due to its high effectiveness in a vast number of diseases. Methods: In this study, poly-herbal formulations were prepared by using different solvent extracts with the help of the hot extraction process through Soxhlet apparatus. The poly-herbal formulations were prepared by using traditional herbal plants namely, Bacopa monereri (BM), Embelica officinalis (EO), Mucuna pruriens (MP), & Withania somnifera (WS). Different combinations of PHFs (PHF1-5) were prepared by using the extracts in different ratios. The prepared PHFs were optimized for antioxidant potential by the DPPH assay. Eighteen Swiss albino mice (30-50 g) were grouped into Control, MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and MPTP+PHF1 (6 mice in each group). Experimental mice were given PHF1 (50 mg/kg body weight by intraperitoneal route). MPTP(1-methyl 4- phenyl 1,2,3,6-tetrahydropyridine) treatment was given orally for 2 weeks with prior use of 20 mg/kg body weight for 2 weeks. Results: After the treatment period, neurobehavioral study and evaluation of neuroprotective effects were done according to biochemical parameters. Discussion: In the above study, it was found that PHF1 has upgraded the dopaminic neurons in the brain. A significant diminution was found in SLA activity in MPTP treated mice as compared to the control group which was restored by MPTP+PHF1 treated group as compared to MPTP treated group. Conclusion: The result concluded that PHF1 enhanced the dopaminic neurons in the substantia nigra region of the brain. Hence, this poly-herbal formulation gives a better and novel treatment base for future drug discoveries in the case of Parkinson’s Disease (PD).

Background: This research tried to evaluate the chemical composition of the essential oil of Salvia limbata, and also bioactivity of essential oil and the plant extract. S. limbata is an aromatic plant with medicinal uses, such as analgesic, anti-inflammatory activities. Methods: The essential oils of the flowers of Salvia limbata were obtained using a Clevenger-type apparatus, and its chemical composition was identified by chromatography methods. The study was also conducted to evaluate antioxidant and antibacterial activities of the plant extracts. For this purpose, the leaves and flowers of S. limbata were extracted using methanol and then fractioned by n-hexane and Ethyl Acetate (EtOAc). Total Phenolic Content (TPC), Total Flavonoid Content (TFC), Radical Scavenging Activity (RSA) and the Disc-Diffusion (DD) assay were run to study the bioactivity of the plant extracts. Results: The oil was dominated by the oxygenated hydrocarbon of 5-methylene-2,3,4,4-tetramethylcyclopent- 2-enone (37.1%), oxygenated sesquiterpene of occidol (22.8%), and sesquiterpene hydrocarbon of β-bourbonene (12.1%). The EtOAc extract of the flowers showed the TPC with 66.2±0.62 mg GAE/g (mg of gallic acid equivalents per gram of extract) and RSA with IC50 of 17.96±0.54 μg/mL. Although the EtOAc extract of the leaves exhibited the highest TFC with 61.96±4.73 mg RuE/g (mg of rutin equivalents per gram of extract). The extracts inhibited the growth of Escherichia coli, Citrobacter frurdi, Pseudomonas aeruginosa, and Streptococcus pneumonia. The extracts were inactive against Staphylococcus coagulase, Enterobacter aerogenes, Acinetobacter baumannii, Serratia marcescens, and Klebsiella pneumoni. Conclusion: According to the results, the plant extracts were potent agant in antioxidant activity.

Context: Linum usitatissimum (Linn); known as Flaxseed, is one of the most important medicinal plants traditionally used for health benefits and also as nutritional purposes. Objective: Estimation of total phenolic and flavonoid contents, and evaluation of the antioxidant, antiinflammatory and anticancer activities have been performed on hexane, ethyl acetate, n-butanol, and methanol extracts and also on fractions of methanol extract (hexane, ethyl acetate, and n-butanol). Materials and Methods: Phenolic and flavonoid contents were detected using spectrophotometric and colorimetric assays. Antioxidant and anti-inflammatory activities were estimated in-vitro. Anticancer activity of extracts was tested on Hepatocellular carcinoma cell line (HepG2) and breast cancer cell line (MCF7). Results: The methanolic extract and its ethyl acetate fraction showed higher contents of total phenols and flavonoids. Also, the methanolic extract showed a higher antioxidant activity. The butanolic and ethyl acetate fractions at concentration 500μg/ml yielded a higher percent of inhibition of protein denaturation; 87.9% and 90%, respectively. The ethyl acetate fraction and the methanolic extract showed an obvious anticancer activity against HepG2 and MCF7 (IC50=60±0.24 and 29.4±0.12μg. ml-1) and (IC50=94.7±0.21 and 227±0.48μg. ml-1), respectively. The GC-MS analysis showed that the methanolic extract had 32 compounds whereas the ethyl acetate and butanol fractions contained 40 and 36 compounds, respectively. Conclusion: Flaxseed contains different biologically active compounds that have been found to possess various activities, which can protect the human body against several diseases.

Background: An imbalance between pro-oxidants and antioxidants determines the level of oxidative stress which is implicated in the etiopathogenesis of various neuropsychiatric disorders including depression. Therefore, treatment with antioxidants could potentially improve the balance between pro-oxidants and antioxidants. Objective: The objective of this study was to evaluate the ability of astaxanthin, a potential antioxidant, to reduce reserpine-induced depression in BALB/c mice (Mus musculus). Methods: On the behavioral level, antidepressant property of astaxanthin (50 mg/kg, orally) on reserpine (2 mg/kg, subcutaneously) induced depressed mice was evaluated by Forced Swim Test (FST) and Tail Suspension Test (TST). In the biochemical level, the ability of astaxanthin to mitigate reserpine-induced oxidative stress was evaluated by the measurement of Malondialdehyde (MDA) and nitric oxide (NO) in brain, liver and plasma samples. On the other hand, the efficiency of astaxanthin to replenish glutathione depletion and antioxidant enzyme activity augmentation in the same samples were also investigated. Results: Astaxanthin was able to lower reserpine induced immobility time significantly (p<0.05) in FST and TST. Mice treated with astaxanthin showed significantly (p<0.05) low level of oxidative stress markers such as Malondialdehyde (MDA), Nitric Oxide (NO). Consistently, the level of reduced Glutathione (GSH), and the activity of Superoxide Dismutase (SOD) and catalase were augmented due to the oral administration of astaxanthin. Conclusion: This study suggests that astaxanthin reduces reserpine-induced oxidative stress and therefore might be effective in treating oxidative stress associated depression.

Background: The present study was conducted on the Moroccan Juglans regia L. bark, in comparison with other Juglans regia collected in other countries, to study the effects of the use of different extraction solvents (water, ethanol, acetone, and diethyl ether), aqueous and organic extraction method, hot and cold extraction by maceration modalities on the presence and content of the different phytochemicals, and on the antioxidant activity. Methods: Various solvents of increasing polarity were used for the preparation of aqueous and organic extracts. Afterwards, a phytochemical screening, an estimation of phenolic compounds, flavonoids, and tannins contents was conducted. The in vitro antioxidant activity was carried out by five tests: H2O2, ABTS, FRAP, DPPH, and reducing power. Subsequently, Principal Component Analysis (PCA) was used to establish the correlation between phenol content and antioxidant activity. Results: Phytochemical analysis showed that the 9 extracts prepared are characterized by the presence of flavonoids, catechic tannins, saponins, anthraquinones, and quinones, and that the macerated acetone extract contains the highest content of phenolic compounds (327.972±0.06 μgEAG/mgE), flavonoids (1267.981±2.911 μgEQ/mgE), and tannins (38.056±1.886 μgEC/gE). The best antioxidant activity was obtained with the macerated acetone which was found to be the most active via the five different tests, with a percentage of scavenging of H2O2 equal at 24.13±1.81, a higher value of ABTS equal to 602.29±0.34 μgET/mgE. PCA allowed us to deduce that phenolic compounds, flavonoids, and tannins are strongly correlated with antioxidant activity. Conclusion: Moroccan Juglans regia may be one of the potential sources of antioxidant compounds.

Background: Despite lutein is unstable in light, heat, and oxygen, it is a good quencher of singlet oxygen. The present study evaluated the stability of lutein (92% of purity) in Lipid-core Nanocapsules (Lutein-LNC) prepared through interfacial deposition of preformed polymer, during photosensitization (5-25°C) and heating (70-90°C). Methods: The Lutein-LNC was characterized and presented a polydispersity index of 0.11, an average diameter of 191 nm (dynamic light scattering), zeta potential of -9.14 mV and entrapment efficiency of 100%. Results and Discussion: During photosensitization and heating, Lutein-LNC exhibited activation Energy (Ea) of 24.67 kcal/mol and 9.96 kcal/mol, respectively, and these values of Lutein-LNC were higher than free lutein values, reported in other studies for both experiments. Conclusion: The results obtained in this study suggested that nanotechnology can improve the stability of lutein for future applications in the food industry.

Background: Modern research on peripheral neuropathy circumstance utter that treatments with Vincristine (VCR) disturb the microtubular cells in sensory and motor neurons due to calcium over- load in sciatic nerve, unfortunately, VCR triggering the release of Tumor necrosis factor-α (TNFα) in central neurons causes excitotoxicity as well. Although ethnomedical information specifies that Pterocarpus marsupium Roxb (PM) is widely used for various nervous disorders, not yet justified on VCR induced peripheral neuropathy and in relation to central mechanism. Objective: This study is aimed to explore the possible central and peripheral mechanism of flavonoid enriched PM in VCR induced neuropathy model. Methods: Neuropathic pain was induced in female Wistar rats by VCR (75μg/ kg/day, i.p) for 10 days. Nociceptive thresholds were assessed by subjecting them to behavioral and biochemical estimation, proinflammatory cytokines along with morphological evaluation. Results: PM significantly increased the nociceptive threshold evident from various behavioral models in comparison to VCR group. More importantly, PM significantly reversed the VCR induced calcium elevation, glutamate and aspartate release in the brain. Discussion: It was also observed that the raised TNF-α, Interleukin-1β were controlled and interleukin- 10 was elevated in sciatic nerve after PM treatment. Evident from histology, PM markedly reversed the VCR induced axonal degeneration, Schwann cell hyperplasia, and myelin fibrosis. Conclusion: Flavonoid enriched PM both 100 & 200mg/kg post and co-administration exerted a preventive and curative effect in VCR induced neuropathic pain by controlling calcium-mediated excitotoxicity through peripheral and central mechanism.