Cinnamaldehyde-Rich Cinnamon Extract Induces Cell Death in Colon Cancer Cell Lines HCT 116 and HT-29.

Cinnamon is a natural spice with a wide range of pharmacological functions, including anti-microbial, antioxidant, and anti-tumor activities. The aim of this study is to investigate the effects of cinnamaldehyde-rich cinnamon extract (CRCE) on the colorectal cancer cell lines HCT 116 and HT-29. The gas chromatography mass spectrometry analysis of a lipophilic extract of cinnamon revealed the dominance of trans-cinnamaldehyde. Cells treated with CRCE (10-60 µg/mL) showed significantly decreased cell viability in a time- and dose-dependent manner. We also observed that cell proliferation and migration capacity were inhibited in CRCE-treated cells. In addition, a remarkable increase in the number of sub-G1-phase cells was observed with arrest at the G2 phase by CRCE treatment. CRCE also induced mitochondrial stress, and finally, CRCE treatment resulted in activation of apoptotic proteins Caspase-3, -9, and PARP and decreased levels of mu-2-related death-inducing gene protein expression with BH3-interacting domain death agonist (BID) activation.

Soybean Processing Wastes: Novel Insights on Their Production, Extraction of Isoflavones, and Their Therapeutic Properties.

Soybean processing waste (SPW) has potential as a sustainable source of phytochemicals and functional foods. A variety of phytochemicals, nutrients, and minerals have been characterized from SPW using various analytical methods. SPW utilization strategies may provide a new way to increase production of bioactive compounds, nutritional supplements, and cosmetic ingredients. SPW has the potential for value-added processing, to improve commercial use, and to lower environmental pollution through proper use. Okara, a byproduct generated during soybean processing of tofu and soy milk, is rich in dietary fiber, isoflavones, and saponins. Isoflavones, an important class of biologically active compounds owing to their multifunctional and therapeutic effects, are extracted from SPW. Further, studies have shown that okara has potential prebiotic and therapeutic value in lowering the risk of noncommunicable diseases. Therefore, in this review, we focus on several extraction methods and pharmacotherapeutic effects of different SPWs. Their effective uses in functional foods, nutraceuticals, and health applications, as biocatalysts, and as value-added resources have been discussed.

Comparative analysis of metabolic variations, antioxidant potential and cytotoxic effects in different parts of Chelidonium majus L.

Metabolic variations, antioxidant potential and cytotoxic effects were investigated in the different plant parts like the leaf, stem, flower, pod, and root of C. majus L. using spectroscopic and chromatographic methods. Total phenolics and flavonoids were studied in the different parts of C. majus L., leaf showed higher flavonoid content (137.43 mg/g), while the pod showed the highest phenolic (23.67 mg/g) content, when compared with the stem, flower and root. In the ABTS antioxidant assay, the flower extract showed 57.94% effect, while the leaf, pod and root extract exhibited 39.10%, 36.08% and 28.88% activity, respectively. The pod and leaf extracts demonstrated the potential effect, exhibiting 45.46 and 41.61% activity, respectively, for the DPPH assay. Similar to the phosphomolybdenum assay, the flower revealed higher antioxidant activity (46.82%) than the other plant parts. The in vitro SRB assay facilitated evaluation of the cytotoxic effect against the HeLa and CaSki human cervical cancerous cells. The extract displayed dose-dependent inhibitory effect on both the cell lines. The highest cytotoxic effect was observed in the pod and flower extracts post 48 h of exposure at 1000 µg/mL. The results of C. majus L. offered new insights in the preliminary steps regarding the development of a high value product for phytomedicine applications though promising metabolic variations with antioxidant and anticancer potentials.

Spiraeoside extracted from red onion skin ameliorates apoptosis and exerts potent antitumor, antioxidant and enzyme inhibitory effects.

Red onion skin waste (ROSW) was analyzed for extraction of naturally occurring 4'-O-glucoside of quercetin, spiraeoside (SPI) with promising biological activities. Reversed-phase high-performance liquid chromatography was used to determine the SPI content in three different solvent extracts of ROSW: water (12.2 mg/g), methanol (27.6 mg/g), and ethanol (32.5 mg/g). The ethanol extract and SPI showed significant radical-scavenging and anti-inflammatory activities. In addition, the anti-cancer effects of SPI on a HeLa cells was investigated. The results indicated that SPI treatment significantly inhibited cell growth, and the dose of 50 µg/mL exhibited the highest anti-cancer activity. SPI inhibited the expression of B-cell lymphoma 2 and BH3-interacting domain-death agonist and promoted apoptosis by activating caspase-9/-3 expression. Notably, SPI inhibited the expression of mu-2-related death-inducing gene, a molecule involved in death receptor-mediated apoptotic signaling. Cyclin-dependent kinase 2-cyclin-E expression was also inhibited after SPI treatment, particularly at the G2/M checkpoint. Our findings provide novel insights into the apoptotic potential with promising anticancer and enzyme inhibitory effects of ROSW SPI.

Novel insights on the multi-functional properties of flavonol glucosides from red onion (Allium cepa L) solid waste - In vitro and in silico approach.

Flavonol glucosides was extracted from red onion solid waste (ROSW) and multi-functional properties were determined to develop alternative strategy for therapeutic beneficiation and utilisation as functional food. The major flavonol glucosides extracted from ROSW were confirmed as quercetin-3, 4'-O-diglucoside (QDG), quercetin-3-O-glucoside (isoquercetin), quercetin-4'-O-glucoside (spiraeoside), isorhamnetin- 4'-glucoside (IMG), quercetin glycoside (QG), and quercetin (Q) using a combination of chromatographic, spectroscopic and scientific literature data. The ROSW solvent fractions and extracted flavonol glucosides showed significant antioxidant effect with DPPH, ABTS, FRAP, and ORAC radical scavenging assays. The in vitro and in silico study revealed that the QG, QDG, isoquercetin, and spiraeoside from ROSW exhibited potent α-glucosidase, tyrosinase and xanthine oxidase enzyme inhibitory activity. In addition, QG, QDG, isoquercetin, and spiraeoside showed potent anticancer effect on HeLa cancer lines. Considering these results, the utilization of ROSW and their flavonol glucosides might be helpful for developing potential antioxidant, anticancer and enzyme inhibitory agents.

The MUDENG Augmentation: A Genesis in Anti-Cancer Therapy?

Despite multitudes of reports on cancer remedies available, we are far from being able to declare that we have arrived at that defining anti-cancer therapy. In recent decades, researchers have been looking into the possibility of enhancing cell death-related signaling pathways in cancer cells using pro-apoptotic proteins. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Mu-2/AP1M2 domain containing, death-inducing (MUDENG, MuD) have been established for their ability to bring about cell death specifically in cancer cells. Targeted cell death is a very attractive term when it comes to cancer, since most therapies also affect normal cells. In this direction TRAIL has made noteworthy progress. This review briefly sums up what has been done using TRAIL in cancer therapeutics. The importance of MuD and what has been achieved thus far through MuD and the need to widen and concentrate on applicational aspects of MuD has been highlighted. This has been suggested as the future perspective of MuD towards prospective progress in cancer research.

Subcritical water extraction of withanosides and withanolides from ashwagandha (Withania somnifera L) and their biological activities.

Subcritical water extraction (SWE) applied to analyses the bioactives from ashwagandha (W. somnifera) at varying temperature (100-200 °C) and extraction time (10-30 min). The effect of temperature and time has been investigated in terms of extraction yield (EY), total phenolic content (TPC), cytotoxicity, antioxidant, and enzyme inhibitory activities. The withanosides and withanolides responsible for various biological effects were quantified using high performance liquid chromatography (HPLC). The HPLC analysis revealed Withanoside V, Withanoside IV, 12-Deoxywithastramonolide, Withanolide A, and Withaferin A as a principle bioactive compounds in SWE, with high in concentration compared to microwave-assisted extraction (MAE), Soxhlet extraction (SE) and maceration (MC). For SWE the highest EY (65.6%; 200 °C for 30 min), TPC (82.5 mg GAE/g DE), antioxidant activity (DPPH: 80.3%, FRAP: 60.5% and ABTS: 78.9), and potent enzyme inhibitory effects were observed. The SWE and Withaferin A showed significant reduction in cell viability of cervical cancer (HeLa) cells, with IC50 values 10 mg/ml and 8.5 µM/ml, respectively but no cytotoxic effect for normal cells (MDCK). Thus, SWE can provide effective extraction for ashwagandha withanosides and withanolides compared MAE, SE and MC to conventional methods, which could be used for extraction of pharmacologically active fractions with therapeutic applications.

Exploitation of apple pomace towards extraction of triterpenic acids, antioxidant potential, cytotoxic effects, and inhibition of clinically important enzymes.

Apple pomace (AP) utilised for analysis of triterpenic acids (TTAs) using HPLC-MS/MS. The methanol, ethanol and ethyl acetate extracts showed high phenolic content with significant antioxidant activity compared to chloroform and n-hexane. AP TTAs; ursolic acid, betulinic acid and maslinic acid showed potent antioxidant and enzyme inhibitory effects. The IC50 values were 13.2-30.8 µg/mL (tyrosinase), 19.6-42.5 µg/mL (xanthine oxidase) and 16.6-38.6 µg/mL (urease) for AP extracts and 8.4-25.8 µg/mL (tyrosinase), 12.6-30.2 µg/mL (xanthine oxidase) and 10.1-28.6 µg/mL (urease) for TTAs, compared to the positive controls; kojic acid (10.4 ±â€¯0.06 µg/mL), allopurinol (9.6 ±â€¯0.04 µg/mL) and thiourea (8.9 ±â€¯0.02 µg/mL) towards respective enzymes. UA showed a competitive type of inhibition for tyrosinase, while BA showed a noncompetitive type of inhibition towards xanthine oxidase. In addition, the AP extracts and TTAs exerted significant cytotoxic effects towards the proliferation of cancer cell lines. AP methanol extract (IC50 of 38.5 ±â€¯4.1, 47.1 ±â€¯3.5, 70.6 ±â€¯2.3, and 50.5 ±â€¯3.9 µg/mL) and ursolic acid (IC50 of 6.5 ±â€¯0.7, 15.5 ±â€¯1.4, 20.8 ±â€¯1.3, and 5.6 ±â€¯0.8 µg/mL) showed prominent anticancer activity on Hela, Skov-3, Caski, and NCL cancer cell lines, respectively. Thus, this study shows that the AP & TTAs could be utilized for functional food development and as a potent antioxidant, anticancer, skin whitening, and anti-urolithic agents.

Horticultural oils: possible alternatives to chemical pesticides and insecticides.

The farmers and agrochemical industries lack science-based knowledge about sustainable utilization of pesticides and insecticides. The investigation on rising use of chemical pesticides and insecticides has remarkable issue related to environment pollution, soil fertility, and human health; as such, nowadays, many people prefer natural alternatives over synthetic chemicals. Natural products, like horticultural oils, play a significant role for sustainable and safe integrated pest management, providing natural alternatives to chemical pesticides and insecticides. For several decades, both plant- and petroleum-based spray oils have been always used to control various pests, mites, and insects. Currently, these horticultural oils are used as a part of the integrated pest management, which utilizes secure and non-chemical pesticides rather than conventional pesticides. Horticultural oil refers to a complex mixture of hydro-carbons with traces of sulfur- and nitrogen-based compounds, extracted from plants. The key components of horticultural oils include paraffin and olefin. The horticultural oils are considered suitable since they are non-toxic to both plants and animals, are applied easily, have low risk properties, cost-effective, and play significant role in pest control, but show little effects on the beneficial insects. As a result, these attributes make horticultural oils to be considered as secure and effective alternative for chemical insecticides and pesticides for both commercial and domestic agriculture.

Utilization of Dianthus superbus L and its bioactive compounds for antioxidant, anti-influenza and toxicological effects.

Dianthus superbus (DS) is a traditional medicinal herb well known for its medicinal and therapeutic potential and widely distributed in various Asian countries. The ethyl acetate (EA), butanol (Bu) and distilled water (DW) extracts of DS assessed for extraction of bioactive compounds and their biological activities. The chemical analysis was done using LC-MS/MS and antioxidant, anticancer and antiviral activities were determined. EA extracts showed strong anticancer activity with IC50 of 9.5, 13.8 and 69.9 µg/mL on SKOV, NCL-H1299 and Caski cancer cell lines, respectively. The Bu extracts exhibited strongest antiviral activity with respect to both influenza A and B viruses with IC50 values of 4.97 and 3.9 µg/mL, respectively. Also the metabolic profile for EA, Bu and DW extracts shows high variations and influence precisely the antioxidant, anticancer and antiviral properties. The quercetin 3- rutinoside and isorhamnetin 3- glucoside showed higher neuraminidase inhibition activity in dose dependent manner. Molecular docking study revealed that flavonol glycosides have higher binding activities towards influenza polymerase membrane glycoprotein. Correlation study showed that flavonol glycosides were linked to anti-influenza activity and cyclic peptides with anticancer activities. This study provides vital information for effective utilization of DS for medicinal, food and therapeutic purposes.

Valorization of onion solid waste and their flavonols for assessment of cytotoxicity, enzyme inhibitory and antioxidant activities.

Onion (Allium cepa L.) is rich with flavonols which perceived benefits to human health. Flavonols like quercetin and quercetin glycosides from onion solid waste (OSW) have been extracted and tested against enzymes of clinical importance in Alzheimer's disease and diabetes and be shown to have cytotoxic and antioxidant effects. A simple high-performance liquid chromatography-diode array detector method using a Zorbax Eclipse XDB C18 column was developed to separate quercetin-3, 4'-O-diglucoside, quercetin-4'-O-monoglucoside, and quercetin from OSW. These compounds were identified using infrared, ultra-violet, 1H, and 13C nuclear magnetic resonance spectroscopic techniques. The OSW solvent fractions and flavonols showed significant antioxidant activities using DPPH (1, 1-diphenyl-2-picrylhydrazyl), FRAP (ferric reducing antioxidant power), and ABTS (2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid) radical scavenging assays. The samples exhibited significant in vitro anti-cholinesterase activity with strong antidiabetic effects. OSW extracted with methanol and ethanol showed greater in vitro anti-cholinesterase and hypoglycemic effects than QDG, QMG, and Q possibly due to interactions between multiple compounds and/or complex multivariate interactions with other factors in OSW. In addition, cytotoxicity assays showed that OSW and QDG, QMG, and Q could inhibit the proliferation of selected cancer cell lines. Results indicate that OSW and flavonol glycosides are potential antioxidant, antidiabetic, anticancer, and sedative agents.

Potential cow milk xanthine oxidase inhibitory and antioxidant activity of selected phenolic acid derivatives.

Xanthine oxidase (XO) found in all mammals and excess activity leads to urolithiasis. The cow milk XO was purified to 305-fold with a specific activity of 8.76 EU/mg and overall yield of 87% by using DEAE-Sepharose chromatography. The phenolics showed potent XO inhibitory effect with Ki , P1 (0.412), P2 (0.632), P3 (0.585), P4 (0.886), P5 (1.633), P6 (0.503), P7 (2.882), P8 (3.761), P9 (4.487), and P10 (5.841) µM. The phenolics P9 and P10 exhibited uncompetitive inhibition; the phenolics P1, P2, P3, P4, and P6 showed competitive inhibition, and other phenolic acids showed noncompetitive inhibition. The studied phenolic compounds showed potent antioxidant activity and expressed as EC50 , ranged from, DPPH (4.2-25.8 µg mL-1 ), ABTS (10.2-42.5 mmol TE 100 g-1 ), and FRAP (6.3-36.8 mol Fe (II) 100 g-1 ). The results obtained from this study might be utilized for design of XO inhibitors and as antigout agent.

Nematicidal potential and specific enzyme activity enhancement potential of neem (Azadirachta indica A. Juss.) aerial parts.

Nematodes are considered as major plant parasites damaging most of the crops, and neem plant exhibits potential nematicidal and insecticidal properties. This study aimed to check nemato-toxic potential of neem (Azadirachta indica) plant using in vitro and in-planta trials against Meloidogyne incognita. The findings suggested that the neem extracts were lethal to second-stage juvenile (J2) and egg hatching with simultaneous enhancement in treated tomato plant growth. The egg numbers of M. incognita found less sensitive to the aqueous and alcoholic extracts than those of J2 as per LC50 values. Complete mortality of J2s was recorded at 40, 60, and 80% of neem standard extract (SE) dilutions and for undiluted SE of neem. The undiluted SE extract showed 100% inhibition of egg production. The highest reductions in the number of galls/root system, J2 population, and egg production were observed with 80, 85, and 82% SE as compared control (untreated distilled water). The maximum 250% growth increment was observed in the length of tomato roots supplemented with neem extracts. Resistance-related enzyme [phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), and peroxidase (POX)] activities in tomato plant have been increased significantly by supplementation with neem extracts. It appears that the aerial parts of neem (A. indica) extracts showed significant and sustainable eco-friendly nemato-toxic potential towards M. incognita growth inhibition and eradication using alcoholic extracts compared to aqueous. From this study, it was concluded that the neem aerial parts were useful for the control of M. incognita and could be a possible replacement for synthetic nematicides in crop protection with utilization in enhancement of specific enzyme activity in tomato plants.

Utilization of quercetin and quercetin glycosides from onion (Allium cepa L.) solid waste as an antioxidant, urease and xanthine oxidase inhibitors.

This study aimed to determine the flavonol glycosides from onion solid waste (OSW) using HPLC analysis, with antioxidant and enzyme inhibitory activities. We found considerable amount of quercetin-4'-O-monoglucoside (QMG: 254.85), quercetin-3,4'-O-diglucoside (QDG: 162.34), quercetin (Q: 60.44), and isorhamnetin-3-glucoside (IMG: 23.92) (mg/100g) dry weight (DW) of OSW. For OSW, the methanol and ethanol showed the strongest antioxidant activities, followed by ethyl acetate, chloroform, and n-hexane extracts. Among the flavonols, Q and QDG possessed higher antioxidant activities. OSW and flavonol glycosides displayed significant enzyme inhibitory activity, with IC50 values ranging from 12.5±0.11 to 32.5±0.28 for OSW, 8.2±0.07 to 16.8±0.02 for flavonol glycosides, and 4.2±0.05µg/mL for thiourea (positive control) towards urease; while 15.2±0.8 to 35.8±0.2 (µg/mL) for OSW, 10.5±0.06 to 20.8±0.05 (µg/mL) for flavonol glycosides, and 6.5±0.05µg/mL for allopurinol (positive control) towards xanthine oxidase, respectively. The OSW and flavonol glycosides may thus be considered as potential antioxidant and antigout agents.

Total phenolics, antioxidant, antitumor, and enzyme inhibitory activity of Indian medicinal and aromatic plants extracted with different extraction methods.

The phenolic content, antioxidant, antitumor, and enzyme inhibitory activities of commonly used medicinal herbs from a Unani system of medicine were investigated using four different extraction methods. Among the plants studied, the Hyssopus officinalis L, Origanum vulgare L, and Portulaca oleracea L. extracts showed the highest amount of total phenolics (64.40, 60.35, and 58.81 mg GAE/g) and revealed significant antioxidant activities. The plants also showed a maximum cytotoxic activity as indicated by H. officinalis (82%), O. vulgare (75%), and P. oleracea (72%) showed more than 70% cytotoxicity for breast cancer cells, 82% of the cells were dead at the concentration of 500 mg/mL. The plants H. officinalis, P. oleracea, O. vulgare, and Rubia cordifolia L. revealed more than 80% inhibition towards xanthine oxidase and comprising maximum 70% of inhibition for superoxide dismutase. From results we conclude that there is a strong correlation between phenolic content, antioxidant, and enzyme inhibitory activity among these plants, indicating phenolics are the major compounds for these biological activities. Furthermore, this study provides the basis for the therapeutic importance of studied plants as latent inhibitors of oxidative stress and antitumor cell proliferation which correlate with the ethnobotanical data contained in the Unani system of medicine.