PMID: 

Life Sci. 2019 Aug 27:116795. Epub 2019 Aug 27. PMID: 31470002

Abstract Title: 

The neuroprotective effects of carvacrol on ischemia/reperfusion-induced hippocampal neuronal impairment by ferroptosis mitigation.

Abstract: 

OBJECTIVE: Cerebral ischemia is the most common type of neuronal injury and is characterized by a reduction in the function and number of hippocampal neurons. Carvacrol has a significant neuroprotective effect in cerebral ischemia. However, the mechanisms by which carvacrol affects cerebral ischemia, especially with respect to the regulation of neuronal damage by iron levels, have never been systematically studied. This study aimed to reveal the mechanisms by which carvacrol protects against hippocampal neuron impairment after ischemic stroke in gerbils.MATERIALS AND METHODS: The Morris water maze test was performed to evaluate learning and memory impairments. Iron ion content and oxidative stress index were detected by the kit. MTT assay was performed to assess the cell viability. The morphology and molecular characteristics were detected by electron micrographs and western blot.RESULTS: In the present study, we demonstrated the neuroprotective effects of carvacrol in vivo and in vitro. The Morris water maze test showed that the learning and memory abilities of the gerbils treated with carvacrol were significantly improved. Lipid peroxide injury was evaluated by measuring the levels of lipid peroxide biomarkers; the results indicated that carvacrol decreased the level of lipid peroxide in ischemic gerbil brain tissue. Histopathological examinations and western blotting were performed to evaluate injury in neurons, and carvacrol reduced cell death. Moreover, ferroptosis in the hippocampus was evaluated by measuring the levels of proteins involved in this iron-dependent form of regulated cell death. These results indicated that carvacrol reduced cell death and that carvacrol inhibited ferroptosis by increasing the expression of glutathione peroxidase 4(GPx4). This study showed that carvacrol may be a valuable drug for treating cerebral ischemia.CONCLUSION: Carvacrol provides protection for hippocampal neurons against I/R in gerbils by inhibiting ferroptosis through increasing the expression of GPx4.

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PMID: 

Mol Nutr Food Res. 2019 03 ;63(6):e1800649. Epub 2019 Jan 3. PMID: 30575271

Abstract Title: 

6-Gingerol Improves Ectopic Lipid Accumulation, Mitochondrial Dysfunction, and Insulin Resistance in Skeletal Muscle of Ageing Rats: Dual Stimulation of the AMPK/PGC-1α Signaling Pathway via Plasma Adiponectin and Muscular AdipoR1.

Abstract: 

SCOPE: This study investigates the dual actions of 6-gingerol in stimulating both plasma adiponectin and muscular adiponectin receptor signaling in naturally ageing rats.METHODS AND RESULTS: Twenty-two-month-old male SD rats were treated with 6-gingerol (0.2 mg kg, once daily) for 7 weeks. 6-Gingerol can attenuate age-associated high plasma triglyceride, glucose, and insulin concentrations under fasting conditions as well as suppress the increase in the HOMA-IR index and inhibit the decrease of muscular p-Akt/Akt protein in ageing rats, which indicates an improvement of systemic and muscular insulin sensitivity. Accompanying these changes, treatment with 6-gingerol attenuates excessive triglyceride accumulation, enhances mitochondrial function, and promotes a transition from a fast- to slow-fiber type and muscle oxidative metabolism in the red gastrocnemius of ageing rats. More importantly, 6-gingerol not only increases the plasma and adipose tissue adiponectin concentrations, but also elevates muscular AdipoR1 expression and activates downstream AMPK phosphorylation as well as upregulates PGC-1α in vivo and in vitro.CONCLUSION: 6-Gingerol may improve ectopic lipid accumulation, mitochondrial dysfunction, and insulin resistance in skeletal muscle of ageing rats. These effects rely, at least in part, on the elevated plasma adiponectin concentration and muscle AdipoR1 level to dually activate the AMPK/PGC-1α signaling pathway.

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PMID: 

Inflammopharmacology. 2019 Mar 2. Epub 2019 Mar 2. PMID: 30826930

Abstract Title: 

Anti-inflammatory and renal protective effect of gingerol in high-fat diet/streptozotocin-induced diabetic rats via inflammatory mechanism.

Abstract: 

P38 mitogen-activated protein kinase (p38 MAPK), a tissue inflammatory factor can be activated under oxidative stress and in conditions associated with hyperglycemia. Gingerol containing various natural herbs has been extensively studied for its pharmacological actions both in reducing the inflammation and as immunity booster. The aim of the current investigation was to examine the renal protective effect of gingerol in high-fat diet/streptozotocin-induced type II diabetes mellitus in a rat model.NRK 52E cells were divided into normal and high glucose group treated with gingerol. The methylthiazotetrazolium assay was used to establish the cell proliferation progress. Streptozotocin-inducted diabetes in rats was treated with gingerol for 16 weeks. The blood glucose, serum creatinine, body weight, food intake, biochemical, antioxidant and haematological parameters were assayed to establish the correlation. Pro-inflammatory cytokines including Il-1β, IL-6, TNF-α; inflammatory mediator COX-2, PGE, NF-kB, p38MAPK, and TGF-β, were also determined to assess the molecular mechanism. Gingerol exhibited the protective effect on the high glucose level induced NRK 52E cells and did not show any effect on the normal cells. Gingerol significantly (P 

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PMID: 

J Nat Med. 2019 Sep ;73(4):745-760. Epub 2019 Jun 8. PMID: 31177355

Abstract Title: 

Suppression of colorectal cancer cell growth by combined treatment of 6-gingerol andγ-tocotrienol via alteration of multiple signalling pathways.

Abstract: 

Our previous study reported that combined treatment ofγ-tocotrienol with 6-gingerol showed promising anticancer effects by synergistically inhibiting proliferation of human colorectal cancer cell lines. This study aimed to identify and elucidate molecular mechanisms involved in the suppression of SW837 colorectal cancer cells modulated by combined treatment of γ-tocotrienol and 6-gingerol. Total RNA from both untreated and treated cells was prepared for transcriptome analysis using RNA sequencing techniques. We performed high-throughput sequencing at approximately 30-60 million coverage on both untreated and 6G + γT3-treated cells. The results showed that cancer-specific differential gene expression occurred and functional enrichment pathway analysis suggested that more than one pathway was modulated in 6G + γT3-treated cells. Combined treatment with 6G + γT3 augmented its chemotherapeutic effect by interfering with the cell cycle process, downregulating the Wnt signalling pathway and inducing apoptosis mainly through caspase-independent programmed cell death through mitochondrial dysfunction, activation of ER-UPR, disruption of DNA repair mechanisms and inactivation of the cell cycle process through the downregulation of main genes in proliferation such as FOXM1 and its downstream genes. The combined treatment exerted its cytotoxic effect through upregulation of genes in stress response activation and cytostatic effects demonstrated by downregulation of main regulator genes in the cell cycle. Selected genes involved in particular pathways including ATF6, DDIT3, GADD34, FOXM1, CDK1 and p21 displayed concordant patterns of gene expression between RNA sequencing and RT-qPCR. This study provides new insights into combined treatment with bioactive compounds not only in terms of its pleiotropic effects that enhance multiple pathways but also specific target genes that could be exploited for therapeutic purposes, especially in suppressing cancer cell growth.

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PMID: 

Artif Cells Nanomed Biotechnol. 2019 Dec ;47(1):2016-2023. PMID: 31223035

Abstract Title: 

6-Gingerol protects cardiocytes H9c2 against hypoxia-induced injury by suppressing BNIP3 expression.

Abstract: 

Cardiomyocytes loss is the predominant pathogenic characteristic in the hypoxia-induced injury. Meanwhile, it has been corroborated that Bcl-2 E1B 19-KDa interacting protein 3 (BNIP3) provokes apoptosis and autophagy. For moderating cardiomyocytes loss, we initially probed the cyto-protection effects of 6-Gingerol (6 G), meanwhile, its potential mechanisms associated with BNIP3 were elucidated in our studies.We pretreated cardiomyocytes H9c2 cells with 6 G at different concentrations (0-100 μM) before exposure to hypoxia. Thereafter, the cell viability, lactate dehydrogenase (LDH), apoptosis and protein expression were respectively assessed using cell counting kit-8 and methyl thiazolyl tetrazolium (MTT) assay, LDH assay kit, Annexin V-fluorescein isothiocyannate/propidium iodide (Annexin V-FITC/PI) apoptosis detection kit and Western blotting analysis. In addition, we also analyzed BNIP3 level after treatment. Moreover, we enforced the exogenous overexpression of BNIP3 and then evaluated the cell viability, apoptosis, and protein levelagain.In our present work, we observed that the cell viability was promoted by 6 G in the hypoxia-induced H9c2 cells in a dose-dependent manner. Moreover, hypoxia-induced LDH release, apoptosis and autophagy were inhibited by 6 G pretreatment through promoting phosphorylation of PI3K, AKT and mTOR. Remarkably, accumulation of BNIP3 protein was significantly reduced by 6 Gin hypoxia-induced H9c2 cells. Mechanistically, 6 G initiated the phosphorylated expression of PI3K, AKT and mTOR by down-regulating BNIP3 with reducing cardiomyocytes apoptosis and autophagy.Hypoxia-induced cardiomyocytes injury was ameliorated by 6 G through suppressing BNIP3 expression with triggering PI3K/AKT/mTOR signalling pathway.

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PMID: 

Mol Nutr Food Res. 2019 Jul 17:e1801356. Epub 2019 Jul 17. PMID: 31313461

Abstract Title: 

Treatment with 6-Gingerol Regulates Dendritic Cell Activity and Ameliorates the Severity of Experimental Autoimmune Encephalomyelitis.

Abstract: 

SCOPE: Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disorder, with increasing incidence worldwide but unknown etiology. 6-Gingerol (6-GIN), a major dietary compound found in ginger rhizome, has immunomodulatory activity. However, its role in autoimmune diseases, as well as the underlying mechanisms, are unclear. In this study, it is evaluated if 6-GIN can effectively ameliorate the clinical disease severity of experimental autoimmune encephalomyelitis, an animal model of MS.METHODS AND RESULTS: Clinical scores of experimental autoimmune encephalomyelitis (EAE) mice are recorded daily. Inflammation of periphery and neuroinflammation of EAE mice are determined by flow cytometry analysis, ELISA, and histopathological analysis, and results show that 6-GIN significantly inhibits inflammatory cell infiltration from the periphery into the central nervous system and reduces neuroinflammation and demyelination. Flow cytometry analysis, ELISA, and quantitative PCR show that 6-GIN could suppress lipolysaccharide-induced dendritic cell (DC) activation and induce the tolerogenic DCs. Immunoblot analysis reveals that the phosphorylation of nuclear factor-κB and mitogen-activated protein kinase, two critical regulators of inflammatory signaling, are significantly inhibited in 6-GIN-treated DCs.CONCLUSION: The results of this study demonstrate that 6-GIN has significant potential as a novel anti-inflammatory agent for the treatment of autoimmune diseases such as MS via direct modulatory effects on DCs.

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PMID: 

Curr Aging Sci. 2019 Aug 8. Epub 2019 Aug 8. PMID: 31418667

Abstract Title: 

Nigella sativa L., supplementary plant with anticholinesterase effect for cognition problems: A kinetic study.

Abstract: 

BACKGROUND: The average of lifespan and the aging population are rising worldwide. So neurodegenerative disease (ND) will be one of the most challenges associated with this population and would be more hot in future. The use of acetylcholinesterase (AChE) inhibitor s is one of the most important strategies for memory impairment. Medicinal plants are the most known natural source for accessing the new therapeutic agents.OBJECTIVE: In this work, we aimed to study in vitro anticholinesterase effect of different concentrations (10, 100, 250, 500, 750 and 1000µg/ml) of total extract of N. sativa (NTE) and its separated fractions and to study the kinetic of AChE enzyme in the presence of two concentrations of NTE (10 and 100 µg/ml).METHODS: Maceration with methanol 80% was used for NTE preparation and different fractions of petroleum ether (PTE), chloroform (CHF) and methanol (MF). NTE, fractions and the main component of the plant, thymoquinone (TQ), were assayed for AChE inhibition using Ellman's method. Kinetic study of the AChE enzyme was studied in presence of NTE at 10 and 100µg/ml using Linweaver-Burk plot too.RESULTS: NTE and all the separated fractions inhibited AChE enzyme in a concentration-dependent manner. The greatest inhibition was shown by CHF and PEF fractions (86.97% and 79.99% at 1000µg/ml respectively). With less intensity, NTE, TQ and MF exhibited 76.32%, 68.98 % and 48.39% enzyme inhibition at 1000µg/ml respectively. The least IC50 value was due to CHF fraction in AChE inhibition (98.28± 6.74 µg/ml). Kinetic profile exhibited the mixed mode of AChE inhibition by NTE. Thisindicates that a particular substance could not be responsible for AChE inhibition, and probably a collection of phytochemicals are involved in this process.CONCLUSIONS: N. sativa is a good candidate for seeking the new anticholinesterase agent and could be considered as a good supplement for the health of the elderly.

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PMID: 

Curr Pharm Biotechnol. 2019 Aug 21. Epub 2019 Aug 21. PMID: 31433749

Abstract Title: 

In-Vitro Anti-Proliferative, Apoptotic And Antioxidative Activities Of Medicinal Herb Kalonji (Nigella sativa).

Abstract: 

BACKGROUND: Natural product with apoptotic activity could serve as potential new sources for anti-cancer medicine. Numerous phytochemicals from plants have shown to exert antineoplastic effects via programmed cell death (apoptosis). Cancer is one of the leading causes of death in the prosperous countries. The subject study was intended to evaluate the anticancer properties of Kalonji extracts against cancer cell lines HeLa and HepG2 and normal cell lines BHK and VERO were used as normal controls.RESULTS: For the evaluation of anti-proliferative effects, cell viability and cell death in all groups of cells was evaluated via MTT, crystal violet and trypan blue assays. For the evaluation of Angiogenesis immunocytochemistry and ELISA of VEGF were done. Immunocytochemistry and ELISA of Annexin-V and p53 were performed for the estimation of apoptosis in all groups of cells. Furthermore LDH assay, Antioxidant enzymes activity (GSH, APOX, CAT and SOD) and Real Time PCR with proliferative and apoptotic markers along with internal control were also performed. Cancer cells of both cell lines HepG2 and HeLa cells showed reduced viability, angiogenesis and proliferation with increased apoptosis when treated with Kalonji extracts. Whereas anti-oxidative enzymes show enhanced levels in treated cancer cells as compared to untreated ones.CONCLUSION: It was observed that Kalonji extracts have ability to induce apoptosis and improve the antioxidant status of HeLa and HepG2 cells. They can also inhibit the proliferation and angiogenesis in both these cancer cell lines.

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PMID: 

Molecules. 2019 Aug 15 ;24(16). Epub 2019 Aug 15. PMID: 31443189

Abstract Title: 

Alpha-Hederin, the Active Saponin of, as an Anticancer Agent Inducing Apoptosis in the SKOV-3 Cell Line.

Abstract: 

Alpha-hederin (α-HN), a pentacyclic triterpene saponin, has recently been identified as one of the active compounds of, as a potential anticancer agent. However, no extensive studies onα-HN have been done as yet, as it was in the case of thymoquinone-the main ingredient of theessential oil. To our knowledge, there are also no data available on howα-HN acts on the human cancer ovarian cell line SKOV-3. In this study we attempt to present the cytotoxic influence of α-HN on the SKOV-3 cell line by means of two methods: Real-Time xCELLigence and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The obtained ICvalues are 2.62± 0.04 μg/mL and 2.48 ± 0.32 μg/mL, respectively. An induction of apoptosis in SKOV-3 cells was confirmed by staining cellular nuclei with Hoechst 33342 dye and by flow cytometry analysis by binding annexin V to the cell membranes. We found that α-HN induces apoptosis in a dose-dependent manner. In the first stages of apoptosis, the mitochondrial membrane potential was found to decrease. Also, inactivation of anti-apoptotic protein Bcl-2 was observed, as well as the caspase-9 and then caspase-3/7 activation. In addition, the treatment of SKOV-3 cells with α-HN induced the cell cycle arrest of cancer cells in G0/G1 phase. The results of our investigations indicate that α-HN induces apoptosis in the SKOV-3 cell line and that the intrinsic mitochondrial pathway is involved in the programmed cancer cell death.

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PMID: 

Antioxidants (Basel). 2019 Aug 25 ;8(9). Epub 2019 Aug 25. PMID: 31450670

Abstract Title: 

Anti-Inflammatory, Anti-Arthritic and Anti-Nociceptive Activities ofOil in a Rat Model of Arthritis.

Abstract: 

This study investigated the preventive efficacy of the crude oil extracted fromseeds in a rat model of arthritis induced by using complete Freund's adjuvant (CFA).oil at 1.82 mL/kg or 0.91 mL/kg (corresponding to 1596 and 798 mg/kg, respectively) was orally administered for 25 days from the day of immunization. One immunized group was treated orally with indomethacin (3 mg/kg) as a reference drug. Body weight growth rate, paw swelling, arthritis score, mechanical allodynia, locomotor activity and anxiety-like behavior were observed, and the levels of Interleukin 6 (IL-6), C-reactive protein, albumin and total cholesterol in plasma were measured on days 15 and 25.oil showed anti-inflammatory, anti-arthritic and anti-nociceptive activities that were significant as compared to untreated arthritic rats but less than indomethacin. These results indicated thatoil significantly attenuated adjuvant-arthritis in rats and the higher dose (1.82 mL/kg) prevented the development of arthritis with an inhibition of 56%.

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