Mechanistic insight into immunomodulatory effects of food-functioned plant secondary metabolites.

Medicinally important plant-foods offer a balanced immune function, which is essential for protecting the body against antigenic invasion, mainly by microorganisms. Immunomodulators play pivotal roles in supporting immune function either suppressing or stimulating the immune system's response to invading pathogens. Among different immunomodulators, plant-based secondary metabolites have emerged as high potential not only for immune defense but also for cellular immunoresponsiveness. These natural immunomodulators can be developed into safer alternatives to the clinically used immunosuppressants and immunostimulant cytotoxic drugs which possess serious side effects. Many plants of different species have been reported to possess strong immunomodulating properties. The immunomodulatory effects of plant extracts and their bioactive metabolites have been suggested due to their diverse mechanisms of modulation of the complex immune system and their multifarious molecular targets. Phytochemicals such as alkaloids, flavonoids, terpenoids, carbohydrates and polyphenols have been reported as responsible for the immunomodulatory effects of several medicinal plants. This review illustrates the potent immunomodulatory effects of 65 plant secondary metabolites, including dietary compounds and their underlying mechanisms of action on cellular and humoral immune functions in in vitro and in vivo studies. The clinical potential of some of the compounds to be used for various immune-related disorders is highlighted.

Bioactive metabolites of Blumea lacera attenuate anxiety and depression in rodents and computer-aided model.

Blumea lacera is an edible plant with imperative medicinal values. However, the anxiolytic and antidepressant roles of B. lacera have not been well-explained. Therefore, the current study aims to explore the impending bioactive metabolites and roles of B. lacera methanol leaf extract (Me-BLL) in attenuating anxiety and depression through several experimental and computer-aided approaches. The chemical characterization of Me-BLL was performed through standard phytochemical and GC-MS analyses. To explore the neuropharmacological insights, Swiss albino mice were treated with Me-BLL at doses of 200-400 mg/kg, p.o. The anxiolytic effects were observed employing elevated plus maze (EPM), light-dark box (LDB), and hole-board (HBT) tests, while antidepressant effects were evaluated using forced swimming (FST) and tail suspension tests (TST). Diazepam (1 mg/kg, i.p.) and fluoxetine HCl (20 mg/kg, p.o.) were used as the reference standard. The phytochemical analyses revealed several bioactive metabolites, including higher contents of total phenolics and flavonoids. The EPM and LDB tests demonstrated an increased time spent in open arms and light box, and the HBT showed an increased number of head dipping, indicating the anxiolytic effects of Me-BLL. The TST and FST revealed a decrease in immobility time, meaning the persuasive antidepressant effects. The antioxidative effects of Me-BLL have also been observed prominently. Correspondingly, the computer-aided investigation confirmed several bioactive lead molecules. Specifically, thymol and cuminol revealed potential anxiolytic and antioxidant effects, while stigmast-5-en-3.beta.-ol and gamma-sitosterol possessed promising antidepressant effects. Taken these results as a base, the plant has imperative potentials in managing anxiety and depression-like disorders.

In vivo anxiolytic and in vitro anti-inflammatory activities of water-soluble extract (WSE) of Nigella sativa (L.) seeds.

The WSE is a highly polar, gummy and mucilaginous bioactive content of the Nigella sativa (L.) seeds. This study reports the anxiolytic and anti-inflammatory effects of WSE investigated using Elevated Plus Maze (EPM) and Hole-Board Test (HBT) in adult mice and human RBCs haemolysis inhibition and protein denaturation respectively. The oral WSE treatment (100 & 200 mg/kg b.w/day) for 72 hours has exhibited slightly better anxiolytic effect (p < 0.05) through the time span (92.33 & 93.33 s) spent in the opened arms of EPM vs. diazepam (1 mg/kg b.w i.p/day; 69.33 s). In HBT, only WSE (200 mg/kg b.w/day) has shown a promising number of mean head pokes (13.27 times/min) vs. diazepam (12.87 times/min). The WSE (62.5-500 µg/mL) exposure has exhibited 40.14-72.18% protection against lysis of RBCs vs. aspirin (57.04-71.48%) whilst 62.67-67.66% inhibition of protein denaturation vs. diclofenac sodium (43.11-80.64%). The current findings suggested WSE has promising anxiolytic and anti-inflammatory activities.

Corrigendum to "Chemical profiles, pharmacological properties, and in silico studies provide new insights on Cycas pectinata" [Heliyon 6 (6), (June 2020) Article e04061].

[This corrects the article DOI: 10.1016/j.heliyon.2020.e04061.].

Chemical profiles, pharmacological properties, and in silico studies provide new insights on Cycas pectinata.

The current study aimed to qualitatively and quantitatively determine the phytochemical components of Cycas pectinata methanol extract (MECP), along with its antioxidant, anti-inflammatory, thrombolytic, locomotor, anxiolytic, analgesic, and antidiarrheal activities. The in vitro antioxidant activity was evaluated by DPPH scavenging assay and the total phenol and total flavonoid contents, while the anti-inflammatory activity was evaluated by a protein denaturation assay. The in vivo locomotor effects were examined using the open field test and hole-cross test. The anxiolytic effect was examined using the elevated plus maze (EPM) test, hole-board test (HBT), and light-dark test (LDT), while the analgesic activity was investigated using the acetic acid-induced writhing test. The antidiarrheal effect was evaluated by castor oil-induced diarrhea and gastrointestinal motility. Ten bioactive compounds were selected on the basis of their biological activities and further investigated using in silico molecular docking simulation to correlate with the identified pharmacological properties. Additionally, the ADME properties of the compounds were evaluated according to their drug-likeness profile. MECP had a maximum total phenol content of 209.85 ± 3.40 gallic acid equivalents/g extract and a total flavonoid content of 105.17 ± 3.45 quercetin equivalents/g extract, with an IC50 value of 631.44 µg/mL. MECP (62.5-500 µg/mL) elicited 20.96-38.12% decreased protein denaturation compared to diclofenac sodium (65.40-83.50%), while a 35.72% (P < 0.001) clot lysis activity was observed for the 10 mg/mL concentration. MECP induced a dose-dependent reduction in locomotor activity, with a significant anxiolytic effect. In the analgesic test, MECP (200, 400 mg/kg) showed a 45.12% and 58.82% inhibition in analgesia, and the 400 mg/kg dose elicited a 27.5% inhibition in intestinal motility. These findings suggest that MECP might be effective in treating antioxidant, anti-inflammatory, and neuropharmacological defects, but this requires further study.

Antinociceptive and Anxiolytic and Sedative Effects of Methanol Extract of Anisomeles indica: An Experimental Assessment in Mice and Computer Aided Models.

Anisomeles indica (L.) kuntze is widely used in folk medicine against various disorders including allergy, sores, inflammation, and fever. This research investigated the antinociceptive, anxiolytic and sedative effects of A. indica methanol extract. The antinociceptive activity was assessed with the acetic acid-induced writhing test and formalin-induced flicking test while sedative effects with open field and hole cross tests and anxiolytic effects with elevated plus maze (EPM) and thiopental-induced sleeping time tests were assayed. Computer aided (pass prediction, docking) analyses were undertaken to find out the best-fit phytoconstituent of total 14 isolated compounds of this plant for aforesaid effects. Acetic acid treated mice taking different concentrations of extract (50, 100, and 200 mg/kg, intraperitoneal) displayed reduced the writhing number. In the formalin-induced test, extract minimized the paw licking time of mice during the first phase and the second phase significantly. The open field and hole-cross tests were noticed with a dose-dependent reduction of locomotor activity. The EPM test demonstrated an increase of time spent percentage in open arms. Methanol extract potentiated the effect of thiopental-induced hypnosis in lesser extent comparing with Diazepam. The results may account for the use of A. indica as an alternative treatment of antinociception and neuropharmacological abnormalities with further intensive studies. The compound, 3,4-dihydroxybenzoic acid was found to be most effective in computer aided models.

In vitro antioxidant and cholinesterase inhibitory activities of Elatostema papillosum leaves and correlation with their phytochemical profiles: a study relevant to the treatment of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD), one of the major causes of dementia, is an overwhelming neurodegenerative disease that particularly affects the brain, leading to memory loss and impairment of language and judgment capacity. The aim of the present study was to investigate the antioxidant and anticholinesterase properties of the leaves of Elatostema papillosum (EPL) and correlate with their phytochemical profiles, which are relevant to the treatment of AD. METHODS: The dried coarse powder of EPL was extracted with 80% methanol (EPL-M80) by cold extraction method. The resultant EPL-M80 was assessed for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity by the Ellman method. The antioxidant activity was determined by DPPH (1, 1-diphenyl-2-picrylhydrazyl) and hydroxyl radical scavenging assays. Quantitative phytochemical (phenolic and flavonoid contents) analysis of endogenous substances in EPL-M80 was performed by standard spectrophotometric methods. RESULTS: EPL-M80 significantly (p < 0.05) inhibited AChE and BChE activity with IC50 of 165.40 ± 4.01 and 213.81 ± 3.57 µg/mL, respectively in a dose-dependent manner. Additionally, EPL-M80 exhibited strong radical scavenging activity against DPPH (IC50 = 32.35 ± 0.68 µg/mL) and hydroxyl radical (IC50 = 19.67 ± 1.42 µg/mL) when compared to that of standards. EPL-M80 was found to be rich in phenolic (23.74 mg gallic acid equivalent/g of dry extract) and flavonoid (31.18 mg quercetin equivalent/g of dry extract) content. Furthermore, a positive correlation (p < 0.001) was observed between the total phenolics and antioxidant as well as the anticholinesterase potential. CONCLUSIONS: The marked inhibition of AChE and BChE, and potent antioxidant activity of the leaves of Elatostema papillosum highlight its potential to provide an effective treatment for AD.