The possible role of nuclear factor erythroid-2-related factor 2 activators in the management of Covid-19.

COVID-19 is caused by a novel SARS-CoV-2 leading to pulmonary and extra-pulmonary manifestations due to oxidative stress (OS) development and hyperinflammation. COVID-19 is primarily asymptomatic though it may cause acute lung injury (ALI), acute respiratory distress syndrome (ARDS), systemic inflammation, and thrombotic events in severe cases. SARS-CoV-2-induced OS triggers the activation of different signaling pathways, which counterbalances this complication. One of these pathways is nuclear factor erythroid 2-related factor 2 (Nrf2), which induces a series of cellular interactions to mitigate SARS-CoV-2-mediated viral toxicity and OS-induced cellular injury. Nrf2 pathway inhibits the expression of pro-inflammatory cytokines and the development of cytokine storm in COVID-19. Therefore, Nrf2 activators may play an essential role in reducing SARS-CoV-2 infection-induced inflammation by suppressing NLRP3 inflammasome in COVID-19. Furthermore, Nrf2 activators can attenuate endothelial dysfunction (ED), renin-angiotensin system (RAS) dysregulation, immune thrombosis, and coagulopathy. Thus this mini-review tries to clarify the possible role of the Nrf2 activators in the management of COVID-19. Nrf2 activators could be an effective therapeutic strategy in the management of Covid-19. Preclinical and clinical studies are recommended in this regard.

In vivo hepatoprotective and nephroprotective effects of Stenocarpus sinuatus leaf extract against ifosfamide-induced toxicity in rats.

Ifosfamide (IFOS) is a broad-spectrum chemotherapeutic agent that has been extensively used for breast cancer and other solid tumors. Unfortunately, its use is associated with toxicities of several organs. Stenocarpus sinuatus is an Australian tree belonging to the Proteaceae family. In the current study, the phytochemical constituents of S. sinuatus methanol leaf extract (SSLE) were assessed. In addition, the protective effect of SSLE against IFOS-induced nephrotoxicity and hepatotoxicity was evaluated. Rats were randomly divided into six groups: control, IFOS (50 mg/kg), IFOS + SSLE (100 mg/kg), IFOS + SSLE (200 mg/kg), IFOS + SSLE (400 mg/kg), and SSLE (400 mg/kg). Hepatoprotective and nephroprotective potency of SSLE was assessed using different biochemical parameters. The phytochemical investigation resulted in the isolation of four flavonoid glycosides (kaempferol 3-O-ß- d-glucopyranosyl-(1→2)-α- l-rhamnopyranoside, kaempferol 3-O-α-rhamnopyranoside, isorhamnetin 3-O-ß- d-glucopyranosyl-(1→2)-α- l-rhamnopyranoside, and quercetin 3-O-ß- d-glucopyranosyl-(1→2)-α- l-rhamnopyranoside) and a coumarin (scopoletin). This is the first report on the isolated compounds from the genus Stenocarpus. SSLE showed enhancement of kidney and liver functions and reduction of oxidative stress and inflammation. The histopathology of the investigated organs confirmed the protective effect of SSLE. In conclusion, SSLE is considered as a promising candidate that can be used in defense against the toxic effects of IFOS after further clinical trials.

Sweroside: An iridoid glycoside of potential neuroprotective, antidiabetic, and antioxidant activities supported by molecular docking.

Oxidative stress can be a series burden on human health and may lead to many chronic diseases such as diabetes and neurological disorders. The use of natural products to scavenge the reactive oxygen species has attracted the attention of many researchers, to safely manage these conditions with fewer side effects, in available and cost-effective ways. The current study aimed at the isolation and structure elucidation of sweroside from Schenkia spicata (Gentianaceae) and the evaluation of its antioxidant, antidiabetic, neuroprotective, and enzyme inhibitory potential via in vitro and in silico studies. The antioxidant potential was evaluated by a variety of assays as ABTS, CUPRAC and FRAP, showing values of 0.34 ± 0.08, 21.14 ± 0.43, and 12.32 ± 0.20 mg TE/g, respectively, while demonstrating 0.75 ± 0.03 mmol TE/g for phosphomolybdenum (PBD) assay. Acetylcholinestrase (AChE), butyrylcholinesterase (BChE) and tyrosinase inhibitory activities were used to evaluate the neuroprotective effect, while the antidiabetic potential was evaluated by measuring α-amylase and glucosidase inhibitory activities. Results revealed that sweroside showed antioxidant and inhibitory effects on the enzymes tested with the exception of AChE. It demonstrated good tyrosinase inhibitory ability with 55.06 ± 1.85 mg Kojic acid equivalent /g. Regarding the antidiabetic ability, the compound displayed both amylase and glucosidase (0.10 ± 0.01 and 1.54 ± 0.01 mmol Acarbose equivalent/g, respectively) inhibitory activities. Molecular docking studies of sweroside on the active sites of the aforementioned enzymes in addition to NADPH oxidase were performed using Discovery Studio 4.1 software. Results revealed good binding affinities of sweroside to these enzymes mainly through hydrogen bonds and van der Waals interactions. Sweroside can be an important antioxidant and enzyme inhibitory supplement, yet further in vivo and clinical studies are required.

Antioxidant and Enzyme Inhibitory Activities of Rhoifolin Flavonoid: In Vitro and in Silico Studies.

Rhoifolin (apigenin-7-O-ß-neohesperidoside) belongs to the class of flavonoids and was reported to exhibit anti-inflammatory, cytotoxic, antidiabetic, hepatoprotective, and cardioprotective activities. The current study presents the in-vitro evaluation of the antioxidative effects of rhoifolin by many assays, namely DPPH, CUPRAC, ABTS, phosphomolybdenum, and FRAP. Enzyme inhibitory potential was also evaluated for acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, amylase, and glucosidase enzymes. While results revealed weak antioxidant activities for rhoifolin, the compound demonstrated some promising enzyme inhibitory effects against BChE (4.03 mg GALAE/g) and tyrosinase (7.44 mg KAE/g) but was not active on AChE. Regarding anti-diabetic enzymes, the compound was active on amylase but did not show any inhibition effect on glucosidase. In-silico molecular docking study was performed for rhoifolin on the active site of NADPH oxidase, BChE, and amylase enzymes to verify the observed enzyme inhibitory effect. Good binding affinities were observed for rhoifolin on all the docked enzymes, revealing numerous hydrogen bonds, carbon-hydrogen, van der Waals interactions. This is the first study to evaluate the enzyme inhibition potential of rhoifolin. We concluded that the increase in the degree of glycosylation might decrease the antioxidant abilities of flavonoids and that rhoifolin had moderate enzyme inhibition abilities to be investigated in future studies.

Essential Oil of Cestrum diurnum L.: GC/MS Analysis, in Vitro and in Silico Anti-HCoV-229E Effects and Inhibitory Activity against LPS-Induced Inflammation.

Cestrum diurnum L. (Solanaceae) is a fragrant ornamental tree cultivated in different parts around the world. In this study, the essential oil (EO) of the aerial parts was extracted by hydrodistillation (HD), steam distillation (SD) and microwave-assisted hydro-distillation (MAHD). GC/MS analysis of the three EOs revealed that phytol represents the major component in SD-EO and MAHD-EO (40.84 and 40.04 %, respectively); while in HD-EO it only represented 15.36 %. The SD-EO showed a strong antiviral activity against HCoV-229E with IC50 of 10.93 µg/mL, whereas, MAHD-EO and HD-EO showed a moderate activity with IC50 values of 119.9 and 148.2 µg/mL, respectively. The molecular docking of EO major components: phytol, octadecyl acetate and tricosane showed a strong binding to coronavirus 3-CL (pro). Moreover, the three EOs (50 µg/mL) decreased the levels of NO, IL-6 and TNF-α and suppressed IL-6 and TNF-α gene expression in LPS-induced inflammation model in RAW264.7 macrophage cell lines.

LC-MS/MS and GC-MS profiling, antioxidant, enzyme inhibition, and antiproliferative activities of Thymus leucostomus H ausskn. & V elen. extracts.

The chemical composition as well as antioxidant, antiproliferative, and enzyme inhibition activities of extracts from aerial parts of Thymus leucostomus H ausskn. & V elen. obtained with hexane, methanol, and water were evaluated. Results showed that the methanol extract had significantly (p < 0.05) the highest total phenolic content (TPC; 107.80 mg GAE/g) and total flavonoids content (TFC; 25.21 mg RE/g) followed by the aqueous extract (102.72 mg GAE/g and 20.88 mg RE/g, respectively). LC-MS/MS-guided profiling of the three extracts revealed that rosmarinic acid (34.8%), hesperetin (42.9%), and linoleic acid (18%) were the dominant compounds in the methanol, aqueous and hexane extracts, respectively. GC-MS analysis of the hexane extract showed that É£-sitosterol (29.9%) was the major constituent. The methanol extract displayed significantly (p < 0.05) the highest Cu++ , Fe+++ , and Mo(VI) ions scavenging and reducing properties while the aqueous extract exerted significantly (p < 0.05) the highest metal chelating power (42.51 mg EDTAE/g). Both the hexane and methanol extracts effectively inhibited the acetylcholinesterase enzyme (2.63 and 2.65 mg GALAE/g, respectively) while the former extract exerted significantly (p < 0.05) the highest butyrylcholinesterase (2.32 mg GALAE/g), tyrosinase (19.73 mg KAE/g), and amylase (1.16 mmol ACAE/g) inhibition capacity. The aqueous extract exhibited the best glucosidase inhibition property (0.49 mmol ACAE/g). The methanol and hexane extracts exerted a higher cytotoxic effect on HT-29 (IC50 : 8.12 µg/mL) and HeLa (IC50 = 8.08 µg/mL) cells, respectively. In conclusion, these results provide valuable insight into the potential use of T. leucostomus bioactive extracts in different pharmaceutical applications.

GC/MS Analysis, Cytotoxicity, and Antiviral Activities of Annona glabra Hexane Extract Supported by In Silico Study.

Annona glabra Linn is employed in conventional medicine to treat a number of human disorders, including cancer and viruses. In the present investigation, the significant phytochemical components of Annona glabra hexane extract were identified using gas chromatography-mass spectrometry (GC-MS) analysis. Three major compounds were identified in the hexane extract: tritriacontane (30.23%), 13, 17-dimethyl-tritriacontane (22.44%), and limonene (18.97%). MTT assay was used to assess the cytotoxicity of the extract on six human cancer cell lines including liver (HepG-2), pancreas (PANC-1), lung (A-549), breast (MCF-7, HTB-22), prostate (PC-3), and colon (CACO-2, ATB-37). The extract exhibited significant cytotoxic activity against both CACO-2 and A-549 cancer cell lines (IC50 = 47 ± 0.74 µg/mL and 56.82 ± 0.92 µg/mL) in comparison with doxorubicin (IC50 = 31.91 ± 0.81 µg/mL and 23.39 ± 0.43 µg/mL) and of SI of 3.8 and 3.1, respectively. It also induced moderate-to-weak activities against the other cancerous cell lines: PC-3, PANC-1, MCF-7, and HepG-2 (IC50 = 81.86 ± 3.26, 57.34 ± 0.77, 80.31 ± 4.13, and 57.01 ± 0.85 µg/mL) in comparison to doxorubicin (IC50 = 32.9 ± 1.74, 19.07 ± 0.2, 15.48 ± 0.84 and 5.4 ± 0.22 µg/mL, respectively) and SI of 2.2, 3.1, 2.2, and 3.1, respectively. In vitro anti-HSV1 (Herpes simplex 1 virus) and HAV (Hepatitis A virus) activity was evaluated using MTT colorimetric assay with three different protocols to test protective, anti-replicative, and anti-infective antiviral activities, and three separate replications of each experiment were conducted. The plant extract showed promising protective and virucidal activity against HSV1 with no significant difference with acyclovir (79.55 ± 1.67 vs. 68.44 ± 7.62 and 70.91 ± 7.02 vs. 83.76 ± 5.67), while it showed mild protective antiviral activity against HAV (48.08 ±3.46) with no significant difference vs. acyclovir (36.89 ± 6.61). The selected main compounds were examined for their bioactivity through in silico molecular docking, which exhibited that limonene could possess the strongest antiviral properties. These findings support Annona glabra's conventional use, which is an effective source of antiviral and anticancer substances that could be used in pharmaceuticals.

GC/MS analysis and potential synergistic effect of mandarin and marjoram oils on Helicobacter pylori.

Helicobacter pylori can cause chronic gastritis, peptic ulcer, and gastric carcinoma. This study compares chemical composition and anti-H. pylori activity of mandarin leaves and marjoram herb essential oils, and their combined oil. GC/MS analysis of mandarin oil revealed six compounds (100% identified), mainly methyl-N-methyl anthranilate (89.93%), and 13 compounds (93.52% identified) of marjoram oil, mainly trans-sabinene hydrate (36.11%), terpinen-4-ol (17.97%), linalyl acetate (9.18%), and caryophyllene oxide (8.25%)). Marjoram oil (MIC = 11.40 µg/mL) demonstrated higher activity than mandarin oil (MIC = 31.25 µg/mL). The combined oil showed a synergistic effect at MIC of 1.95 µg/mL (same as clarithromycin). In-silico molecular docking on H. pylori urease, CagA, pharmacokinetic and toxicity studies were performed on major compounds from both oils. The best scores were for caryophyllene oxide then linalyl acetate and methyl-N-methyl anthranilate. Compounds revealed high safety and desirable properties. The combined oil can be an excellent candidate to manage H. pylori.

Sweroside Ameliorated Memory Deficits in Scopolamine-Induced Zebrafish (Danio rerio) Model: Involvement of Cholinergic System and Brain Oxidative Stress.

Sweroside is a secoiridoid glycoside and belongs to a large group of naturally occurring monoterpenes with glucose sugar attached to C-1 in the pyran ring. Sweroside can promote different biological activities such as antifungal, antibacterial, hepatoprotective, gastroprotective, sedative and antitumor, antioxidant, and neuroprotective activities. Zebrafish were given sweroside (12.79, 8.35, and 13.95 nM) by immersion once daily for 8 days, along with scopolamine (Sco, 100 µM) 30 min before the initiation of the behavioral testing to cause anxiety and memory loss. Employing the novel tank diving test (NTT), the Y-maze, and the novel object recognition test (NOR), anxiety-like reactions and memory-related behaviors were assessed. The following seven groups (n = 10 animals per group) were used: control, Sco (100 µM), sweroside treatment (2.79, 8.35, and 13.95 nM), galantamine (GAL, 2.71 µM as the positive control in Y-maze and NOR tests), and imipramine (IMP, 63.11 µM as the positive control in NTT test). Acetylcholinesterase activity (AChE) and the antioxidant condition of the brains were also evaluated. The structure of sweroside isolated from Schenkia spicata was identified. Treatment with sweroside significantly improved the Sco-induced decrease of the cholinergic system activity and brain oxidative stress. These results suggest that sweroside exerts a significant effect on anxiety and cognitive impairment, driven in part by the modulation of the cholinergic system activity and brain antioxidant action.

Phytonutrients, Colorant Pigments, Phytochemicals, and Antioxidant Potential of Orphan Leafy Amaranthus Species.

The underutilized Amaranthus leafy vegetables are a unique basis of pigments such as ß-cyanins, ß-xanthins, and betalains with radical scavenging capacity (RSC). They have abundant phytonutrients and antioxidant components, such as pigments, vitamins, phenolics, and flavonoids. Eight selected genotypes (four genotypes from each species) of underutilized Amaranthus leafy vegetables were evaluated for phytonutrients, pigments, vitamins, phenolics, flavonoids, and antioxidants in a randomized complete block design under ambient field conditions with three replicates. The studied traits showed a wide range of variations across eight genotypes of two species of Amaranthus leafy vegetables. The highest fat, ß-xanthins, K, dietary fiber, Mg, ß-cyanins, Mn, chlorophyll ab, Zn, TP, TF, betalains, chlorophyll a content, and (RSC) (DPPH) and RSC (ABTS+) were obtained from A. tricolor accessions. Conversely, the highest protein, Cu, carbohydrates, Ca, and chlorophyll b content were obtained from A. lividus accessions. The highest dry matter, carotenoids, Fe, energy, and ash were obtained from A. tricolor and A. lividus. The accession AT2 confirmed the highest vit. C and RSC (DPPH) and RSC (ABTS+); AT5 had the highest TP content; and AT12 had the highest TF content. A. tricolor accessions had high phytochemicals across the two species, such as phytopigments, vitamins, phenolics, antioxidants, and flavonoids, with considerable nutrients and protein. Hence, A. tricolor accessions can be used as high-yielding cultivars comprising ample antioxidants. The correlation study revealed that vitamin C, pigments, flavonoids, ß-carotene, and phenolics demonstrated a strong RSC, and showed a substantial contribution to the antioxidant potential (AP) of A. tricolor. The investigation exposed that the accessions displayed a plentiful origin of nutritional values, phytochemicals, and AP with good quenching ability of reactive oxygen species (ROS) that provide enormous prospects for nourishing the mineral-, antioxidant-, and vitamin-threatened community.

Phytochemical Constituents, Folk Medicinal Uses, and Biological Activities of Genus Angelica: A Review.

Genus Angelica is one of the widely distributed and well-known genera of family Umbelliferae. It is utilized mainly by Chinese and Korean populations especially in their folk medicine. Angelica comprises a lot of medicinally important phytoconstituents such as coumarins, furanocoumarins, flavonoids, essential oils, verbascosides, polysaccharides, etc. Members of this genus play important roles, namely antioxidant, anti-inflammatory, anti-microbial, anti-diabetic, skin-whitening, cytotoxic, hepatoprotective, and many others. This review draws attention to many species of genus Angelica with much focus on A. dahurica being one of the highly medicinally used species within this genus.

Chemical Constituents, Antioxidant, and Enzyme Inhibitory Activities Supported by In-Silico Study of n-Hexane Extract and Essential Oil of Guava Leaves.

Psidium guajava (Guava tree) is one of the most widely known species in the family Myrtaceae. The Guava tree has been reported for its potential antioxidant, anti-inflammatory, antimicrobial, and cytotoxic activities. In the current study, the chemical compositions of the n-hexane extract and the essential oil of P. guajava were investigated using the GC/MS analysis, along with an evaluation of their antioxidant potential, and an investigation into the enzyme inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BchE), tyrosinase, α-amylase, and α-glucosidase. Moreover, molecular docking of the major identified active sites of the target enzymes were investigated. The chemical characterization of the n-hexane extract and essential oil revealed that squalene (9.76%), α-tocopherol (8.53%), and γ-sitosterol (3.90%) are the major compounds in the n-hexane extract. In contrast, the major constituents of the essential oil are D-limonene (36.68%) and viridiflorol (9.68%). The n-hexane extract showed more antioxidant potential in the cupric reducing antioxidant capacity (CUPRAC), the ferric reducing power (FRAP), and the metal chelating ability (MCA) assays, equivalent to 70.80 ± 1.46 mg TE/g, 26.01 ± 0.97 mg TE/g, and 24.83 ± 0.35 mg EDTAE/g, respectively. In the phosphomolybdenum (PM) assay, the essential oil showed more antioxidant activity equivalent to 2.58 ± 0.14 mmol TE/g. The essential oil demonstrated a potent BChE and tyrosinase inhibitory ability at 6.85 ± 0.03 mg GALAE/g and 61.70 ± 3.21 mg KAE/g, respectively. The α-amylase, and α-glucosidase inhibitory activity of the n-hexane extract and the essential oil varied from 0.52 to 1.49 mmol ACAE/g. Additionally, the molecular docking study revealed that the major compounds achieved acceptable binding scores upon docking with the tested enzymes. Consequently, the P. guajava n-hexane extract and oil can be used as a promising candidate for the development of novel treatment strategies for oxidative stress, neurodegeneration, and diabetes mellitus diseases.

Insights on the Inhibitory Power of Flavonoids on Tyrosinase Activity: A Survey from 2016 to 2021.

Tyrosinase is a multifunctional copper-containing oxidase enzyme that initiates melanin synthesis in humans. Excessive accumulation of melanin pigments or the overexpression of tyrosinase may result in skin-related disorders such as aging spots, wrinkles, melasma, freckles, lentigo, ephelides, nevus, browning and melanoma. Nature expresses itself through the plants as a source of phytochemicals with diverse biological properties. Among these bioactive compounds, flavonoids represent a huge natural class with different categories such as flavones, flavonols, isoflavones, flavan-3-ols, flavanones and chalcones that display antioxidant and tyrosinase inhibitor activities with a diversity of mechanistic approaches. In this review, we explore the role of novel or known flavonoids isolated from different plant species and their participation as tyrosinase inhibitors reported in the last five years from 2016 to 2021. We also discuss the mechanistic approaches through the different studies carried out on these compounds, including in vitro, in vivo and in silico computational research. Information was obtained from Google Scholar, PubMed, and Science Direct. We hope that the updated comprehensive data presented in this review will help researchers to develop new safe, efficacious, and effective drug or skin care products for the prevention of and/or protection against skin-aging disorders.

Chemical constituents and gastro-protective potential of Pachira glabra leaves against ethanol-induced gastric ulcer in experimental rat model.

Gastric ulcer is a very common illness that adversely affects a significant number of people all over the globe. Phytochemical investigation of P. glabra leaf alcohol extract (PGLE) resulted in the isolation and Characterization of a new nature compound, quercetin-3- O-α -L-rhamnosyl-(1'''-6'')-(4''- O -acetyl)-ß -D-galactoside (4), in addition to seven known compounds. They are ferulic acid (1), p- coumaric acid (2), quercetin 3-O-α-L-rhamnoside-3'-O-ß-D-glucoside (3), quercetin-3- O-α -L-rhamnosyl-(1'''-6'')-(4''- O -acetyl)- ß -Dgalactoside (4), quercetin-3- O-ß -D-galactoside (5), 7-hydroxy maltol-3-O-ß-D-glucoside (6), maltol-3- O-ß -D-glucoside (7), and methyl coumarate (8) that were first to be isolated from the genus Pachira. PGLE demonstrated in vitro anti-Helicobacter pylori activity. Moreover, the in vivo gastroprotective assessment of PGLE at different dosses, 100, 200, and 400 mg/kg against ethanol induced ulceration revealed a dose-dependent gastroprotection comparable to omeprazole. PGLE attenuated gastric lesions and histopathological changes triggered by ethanol. Interestingly, PGLE exhibited an anti-inflammatory effect through down-regulating the expression of nuclear factor-ĸB and pro-inflammatory enzyme cyclooxygenase-2 in the ulcer group. It also hindered apoptosis through decreasing Bax and increasing Bcl-2 expression hence decreasing Bax/Bcl2 ratio with a subsequent reduction in caspase 3 expression. Collectively, P. glabra is a rich reservoir of various phytochemicals reflecting a promising potential for alleviation of gastric ulcer through the mediation of inflammatory and apoptotic cascades.

New Methoxyflavone from Casimiroa sapota and the Biological Activities of Its Leaves Extract against Lead Acetate Induced Hepatotoxicity in Rats.

Flavonoids are agents with strong antioxidant properties and ameliorate many diseases associated with oxidative stress. Leaves of Casimiroa sapota were investigated for components and antioxidant/anti-inflammatory activities against lead acetate ((AcO)2 Pb) induced hepatotoxicity in rats. Three groups of male albino rats were administrated orally with vehicle or C. sapota (100 and 200 mg/kg b.w/day) for 28 days; other group was injected with sub-acute dose (100 mg/kg b.w/day) of (AcO)2 Pb. Three protective groups were injected with (AcO)2 Pb (100 mg/kg b.w/day) for 7 days at day 22 after treatment with either C. sapota (100 or 200 mg/kg b.w/day) or silymarin (SILY) for 28 days. We isolated and identified, from C. sapota, a new compound for the 1st time in nature; 5,6,2',3'-tetramethoxyflavone in addition to the rare compound 5,6,3'-trimethoxyflavone (second report of isolation from nature) and the known compound 5,6,2',3',4'-pentamethoxyflavone. There is an improvement in all hemato-biochemical parameters, antioxidant defense system and anti-inflammatory cytokines of protective groups, which received C. sapota in dose dependent manner. The percentage of changes in all parameters measured in (AcO)2 Pb groups that received vehicle, CS100, CS200 or SILY were 109.2, 37.3, 12.5%, and 1.2% compared with the healthy control group. The C. sapota groups confer a better antioxidant activity by preventing oxidative stress and inflammation in (AcO)2 Pb treated rats. The compounds isolated are responsible at least in part for the observed protective effects.

Chemical Composition of Aqueous Ethanol Extract of Luffa cylindrica Leaves and Its Effect on Representation of Caspase-8, Caspase-3, and the Proliferation Marker Ki67 in Intrinsic Molecular Subtypes of Breast Cancer in Vitro.

Breast cancer constitutes the second most prevalent cancer in Egypt, the problem needs more trends in treatment and treatment development either by regimen modification or introducing new drugs, and the main objective of this study is to screen the effects of the aqueous ethanol herbal extract of Luffa cylindrica leaves on different types of breast cancer cell lines representing different molecular subtypes of the disease. The major active constituents of the extract were tentatively identified by LC/MS which revealed the presence of phenolic compound derivatives and saponin that may be responsible in part for the activity of the extract. The emphasis was laid on the main apoptotic pathways as well as the extract effect on the normal cell line. Results of phytochemical investigation, cell cycle analysis, and molecular analysis of apoptotic and proliferative markers have shown effective anticancer activity against MCF-7, BT-474, and MDA-MB-231 cell lines which represent three subtypes of breast cancer, luminal A, luminal B, and triple negative, respectively. On the other hand, the effects on normal lung fibroblast cell line are less prominent at the dose used for treating breast cancer cell lines.

Chemical Characteristics, Antimicrobial, and Cytotoxic Activities of the Essential Oil of Egyptian Cinnamomum glanduliferum Bark.

The essential oil isolated from the bark of Cinnamomum glanduliferum (Wall) Meissn grown in Egypt was screened for its composition as well as its biological activity for the first time. The chemical composition was analyzed by GC and GC/MS. The antimicrobial activity of the oil was assessed using agar-well diffusion method toward representatives for each of Gram-positive bacteria, Gram-negative bacteria, and fungi. The cytotoxic activity was checked using three human cancer cell lines. Twenty seven compounds were identified, representing 99.07% of the total detected components. The major constituents were eucalyptol (65.87%), terpinen-4-ol (7.57%), α-terpineol (7.39%). The essential oil possessed strong antimicrobial activities against Escherichia coli, with an activity index of one and minimum inhibitory concentration (MIC) equaling to 0.49 µg/ml. The essential oil possessed good antimicrobial activities against methicillin-resistant Staphylococcus aureus, Geotrichum candidum, Pseudomonas aeruginosa, Bacillus subtilis, Helicobacter pylori, Aspergillus fumigatus (MIC: 7.81, 1.95, 7.81, 0.98, 31.25, and 32.5 µg/ml, respectively). A considerable activity was reported against S. aureus and Mycobacterium tuberculosis (MIC; 32.5 and 31.25 µg/ml, respectively). The extracted oil was cytotoxic to colon (HCT-116), liver (HepG2), and breast (MCF-7) carcinoma cell lines with IC50 of 9.1, 42.4, and 57.3 µg/ml, respectively. These results revealed that Egyptian Cinnamomum glanduliferum bark oil exerts antimicrobial and cytotoxic activities mainly due to eucalyptol and other major compounds.

Synergistic Hepatoprotective and Antioxidant Effect of Artichoke, Fig, Blackberry Herbal Mixture on HepG2 Cells and Their Metabolic Profiling Using NMR Coupled with Chemometrics.

The edible plants have long been reported to possess a lot of biological activities. Herein, the hepatoprotective and the antioxidant activities of the aqueous infusion of the edible parts of Cynara cardunculus, Ficus carica, and Morus nigra and their herbal mixture (CFM) was investigated in vitro using CCl4 induced damage in HepG2 cells. The highest amelioration was observed via the consumption of CFM at 1 mg/ml showing 47.00% and 37.09% decline in aspartate transaminase and alanine transaminase and 77.32% and 101.02% increase in reduced glutathione and superoxide dismutase comparable to CCl4 treated cells. Metabolic profiling of their aqueous infusions was done using nuclear magnetic resonance spectroscopic experiments coupled with chemometrics particularly hierarchical cluster analysis (HCA) and principal component analysis (PCA). The structural closeness of the various metabolites existing in black berry and the mixture as reflected in the PCA score plot and HCA processed from the 1 H-NMR spectral data could eventually explained the close values in their biological behavior. For fig and artichoke, the existence of different phenolic metabolites that act synergistically could greatly interpret their potent biological behavior. Thus, it can be concluded that a herbal mixture composed of black berry, artichoke, and fig could afford an excellent natural candidate to combat oxidative stress and counteract hepatic toxins owing to its phenolic compounds.

Chemical Composition and Biological Activities of the Essential Oil from Leaves and Flowers of Pulicaria incisa sub. candolleana (Family Asteraceae).

The composition of the essential oil isolated from leaves and flowers of Pulicaria incisa sub. candolleana E. Gamal-Eldin, growing in Egypt, was analysed by GC and GC-MS. Forty-nine and 68 compounds were identified from the oils of the leaves and flowers accounting for 86.69 and 84.29%, respectively of the total detected constituents. Both leaves and flowers oils were characterized by the high content of carvotanacetone with 66.01, 50.87 and chrysanthenone 13.26, 24.3%, respectively. The cytotoxic activity of both essential oils was evaluated against hepatocellular carcinoma cell line HEPG-2, using MTT assay and vinblastine as a reference drug. Leaf oil showed higher activity with IC50 11.4 µg/ml compared with 37.4 µg/ml for flower oil. The antimicrobial activity of both oils was evaluated using agar well diffusion method towards two representatives for each of Gram positive and Gram negative bacteria as well as four representatives for fungi. The minimum inhibitory concentration of both essential oils against bacterial and fungal strains was obtained in the range of 0.49 - 15.63 µg/ml.

Phytochemical Investigation, Antitumor Activity, and Hepatoprotective Effects of Acrocarpus fraxinifolius Leaf Extract.

Preclinical Research Nine known phenolic compounds were isolated from an aqueous methanolic extract of Acrocarpus fraxinifolius Weight and Arn leaves (AFL) family Fabaceae. This extract of AFL contained approximately 169 mg gallic acid/g as assessed by HPLC. The AFL extract had marginal antitumor activity (IC50 > 200 µL/mL) but showed a concentration-dependent hepatoprotective effect against CCl4 -induced hepatotoxicity in vitro. Cell viability was increased, ALT and AST activity declined and reduced GSH concentration and SOD activity were restored as compared with silymarin. In vivo concurrent administration of AFL extract (500 mg/kg po) showed a hepatoprotective effect against gamma irradiation and CCl4 as evidenced by reduction of TNF-α, interleukin-6, malondialdehyde, nitric oxide, DNA fragmentation, caspase-3 activity, and downregulation of its m-RNA level and decreased proapoptotic protein Bax expression. AFL extract enhanced glutathione peroxidase, superoxide dismutase, and catalase activities, reduced glutathione concentrations and upregulated the expression of antiapoptotic Bcl-2. The extract could ameliorate hepatic injuries induced by gamma irradiation and CCl4 in rats suggesting potent hepatoprotective activity. Drug Dev Res 78 : 210-226, 2017. © 2017 Wiley Periodicals, Inc.