PMID: 

Med Glas (Zenica). 2020 Aug 1 ;17(2). Epub 2020 Aug 1. PMID: 32153156

Abstract Title: 

A therapeutic effect of Nigella sativa extract on female Wistar rats vulvovaginal candidiasis model.

Abstract: 

Aim Vulvovaginal candidiasis (VVC) is a disease mostly caused by Candida albicans and affects the quality of life of women especially in the form of chronic recurrent vulvovaginal candidiasis(RVVC). Nigella sativa is known to have several effects such as antimicrobial, anti-inflammatory, immune stimulation and anticancer properties. The aim of this study was to evaluate the effect of Nigella sativa on vulvovaginal candidiasis. Methods This study is a true experimental design, we used 28 Wistar strain rats divided into 4 groups, all groups were conditioned in a pseudoestrus state. Candida albicans was inoculated into the rats' vagina for 3 consecutive days. All groups were observed every 24 hours, 48 hours and 72 hours to evaluate the number of Candida albicans colonies, IgG and IgM anti Candida. Results After administration of intervention, there was a significant difference in the amount of fungal colonization after the treatment in each group (p

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PMID: 

Drug Res (Stuttg). 2020 Mar 20. Epub 2020 Mar 20. PMID: 32198742

Abstract Title: 

Thymoquinone Loaded Solid Lipid Nanoparticles Demonstrated Antidepressant-Like Activity in Rats via Indoleamine 2, 3- Dioxygenase Pathway.

Abstract: 

The World Health Organization (WHO) has ranked depression the 4leading cause of disability worldwide. Thymoquinone (TQ), is an active constituent ofhaving various medicinal properties but has poor solubility and bioavailability. This problem was overcome by developing nanoformulation of TQ. Previously TQ reported good antioxidant and anti-inflammatory effects. Recently TQ's anti-depressant effect was demonstrated. However, the mechanisms underlying the antidepressant effect of TQ still needs evaluation. Activation of Indoleamine-2,3-dioxygenase (IDO), (an enzyme that participates in the tryptophan metabolism), leads to a decrease of serotonin (5-HT) levels. The expression of this enzyme is associated with immune system activation, which has been proposed as a common mechanism that links depression. The present study was performed in stressed animals where hippocampal levels of pro-inflammatory cytokines (IL-6 and TNFα levels), brain derived neurotropic factor (BDNF) and hippocampal kynurenine (KYN), tryptophan (TRP) and serotonin (5-HT) levels were estimated. Treatment with TQ solid lipid nanoparticles (TQSLN 20 mg/kg p.o) and TQ suspension (20 mg/kg p.o) demonstrated antidepressant-like activity in chronic forced-swim stress model. Further, it reduced the elevated hippocampal IL-6&TNFα and reversed the increased activity of IDO as measured by ratio of hippocampal KYN/TRP and 5HT/TRP in stressed rats. The results of the present study confirm anti-inflammatory and neuroprotective effects of TQ which may be associated with 5-HT pathway. Thus, the present study offers a newer approach to reduce symptoms of depression using TQSLN. Our results are preliminary, further research is needed for more conclusive view.

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PMID: 

Biotech Histochem. 2020 Mar 24:1-8. Epub 2020 Mar 24. PMID: 32207631

Abstract Title: 

Thymoquinone protection against 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin induced nephrotoxicity in rats.

Abstract: 

We investigated the effects of thymoquinone (TQ) on kidney tissues of Wistar rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced nephrotoxicity. We used 50 rats divided into five groups; control, corn oil, TCDD, TQ, TCDD + TQ. We found that malondialdehyde (MDA), total oxidant status (TOS), blood urea nitrogen (BUN), creatinine, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) levels in the TCDD treated group increased significantly compared to the other groups, while reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and total antioxidant status (TAS) levels decreased in the TCDD group. In the TQ treated group, we found that GSH, SOD, CAT,TAS levels increased and MDA, TOS, IL-6 and TNF-α levels decreased compared to the other groups. The effects of TCDD on oxidative stress parameters, inflammatory markers and histological changes were ameliorated by TQ treatment.

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PMID: 

J Food Biochem. 2020 Mar 24:e13216. Epub 2020 Mar 24. PMID: 32212163

Abstract Title: 

Thymoquinone attenuates IgE-mediated allergic response via pi3k-Akt-NFκB pathway and upregulation of the Nrf2-HO1 axis.

Abstract: 

IgE-dependent reactions mediate the majority of allergic diseases. This study explores the effects of thymoquinone (Tq) on IgE-mediated allergic response in activated mast cells, basophils, and neutrophils. Tq treatment resulted in a dose-dependent decrease in levels of TNF-α and IL-4 in activated RBL-2H3 cells. Tq inhibited the degranulation of these cells with an ICvalue of 56.37 µM. Moreover, the compound suppressed basophil activation induced through FcεRI receptors with an ICvalue of 45.76 µM in heparinized human whole blood. Likewise, neutrophil migration and elastase activity were dose-dependently reduced. While Tq decreased the phosphorylation of Akt and NFκB in activated RBL-2H3 cells, it increased nuclear Nrf2 and HO-1 antioxidant proteins. Our results indicate that Tq possesses demonstrable activity in cellular models of IgE-mediated allergic reactions. PRACTICAL APPLICATIONS: The current study sheds light on the mechanistic pathways of Tq on IgE-based response in activated mast cells, basophils, and neutrophils. The output of this preclinical in vitro study may be translated into better chemotherapeutic applications of Tq and its analogs in the treatment of allergic inflammation. However, a detailed investigation of in vivo models is recommended.

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PMID: 

Nutr Cancer. 2020 Mar 28:1-8. Epub 2020 Mar 28. PMID: 32223348

Abstract Title: 

Low Doses of Thymoquinone and Ferulic Acid in Combination Effectively Inhibit Proliferation of Cultured MDA-MB 231 Breast Adenocarcinoma Cells.

Abstract: 

Thymoquinone (TQ) and Ferulic Acid (FA) are natural ingredients fromand, respectively. Individually both TQ and FA have shown anticancer properties in a variety of cancer cell lines. We investigated the combination effect of lower doses of TQ and FA on proliferation, apoptosis, and cell cycle of a breast cancer cell line MDA-MB 231. Cells were treated with various concentrations of TQ, FA and various combinations of TQ + FA for 48 hrs. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, whereas cell cycle and apoptosis were measured with flow-cytometry after propidium iodide staining and Annexin-V/FITC staining, respectively. TQ (50 and 100 µM) andFA (450 µM), and all the doses of TQ and FA in combination significantly decreased cell proliferation. 25 µM TQ and 250 µM FA individually did not affect cell proliferation but in combination significantly reduced cell proliferation. TQ at 50 µM caused significant apoptosis, whereas, FAdid not affect apoptosis. Thesedata suggest that in combination, relatively lower doses of TQ and FA are effective in decreasing cancer cell proliferation, and thus have anticancer therapeutic potential. Further research is needed to corroborate these findings in an animal model of breast cancer.

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PMID: 

Int Immunopharmacol. 2020 Mar 12 ;83:106379. Epub 2020 Mar 12. PMID: 32172206

Abstract Title: 

Ferulic acid isolated from propolis inhibits porcine parvovirus replication potentially through Bid-mediate apoptosis.

Abstract: 

Propolis from honeybee hives, which is a traditional Chinese medicine, is widely used in veterinary clinics. Many compounds have been identified and isolated from propolis. Ferulic acid (FA), one of the propolis components, previous studies have proven that it has antiviral effects. To study the mechanism of FA antiviral effects, experiments such as immunofluorescence, quantitative real-time PCR and immunoblotting were introduced. In porcine kidney (PK-15) cells, PPV infection induced the expression of the proapoptotic genes Bid, Bad, Bim and Bak, disrupted mitochondrial membrane potential, promoted mitochondria-mediated, caspase-dependent apoptotic signaling and induced apoptosis. Furthermore, the infected PK-15 cells had increased intracellular reactive oxygen species (ROS) generation. FA treatment, however, reversed these effects and increased cell viability. FA treatment also significantly decreased the PPV-induced expression of Bid, Cyt-c and Apaf-1, suggesting that ROS were involved in the activation of the mitochondria-mediated apoptosis pathway. This in vitro study showed that the antiviral activity of FA was probably associated with inhibiting the replication of PPV by blocking proapoptotic factors such as Bid, Bcl-2 and Mcl-1, and attenuating the mitochondria-mediated response by inhibiting the activation of the Bid-related signaling pathway. Pharmacological inhibitors inhibited PPV-induced apoptosis by blocking Bid, and also suppressed the expression of Caspase family proteins in ppv-induced apoptosis. Taken together, our results suggested that PPV induced PK-15 cell apoptosis via activation of Bid and Bid-related signaling pathways and that the mitochondria act as the mediators of these pathways. FA effectively and extensively attenuated this PPV action, and thus is a potential antiviral agent against PPV.

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PMID: 

Molecules. 2020 Mar 14 ;25(6). Epub 2020 Mar 14. PMID: 32183404

Abstract Title: 

Anticatabolic and Anti-Inflammatory Effects of Myricetin 3-O-β-d-Galactopyranoside in UVA-Irradiated Dermal Cells via Repression of MAPK/AP-1 and Activation of TGFβ/Smad.

Abstract: 

UV irradiation is one of the main causes of extrinsic skin aging. UV-mediated skin aging, also known as photoaging, causes excessive breakdown of extracellular matrix which leads skin to lose its elasticity and strength. Several phytochemicals are known to exert anti-photoaging effects via different mechanisms, partly due to their antioxidant properties. The current study has been carried out to determine the potential anti-photoaging properties of myricetin 3-O-β-d-galacto-pyranoside (M3G), a flavonol glycoside isolated from, in UVA-irradiated in vitro models; HaCaT keratinocytes and human dermal fibroblasts (HDFs). UVA-induced changes in MMP-1 and collagen production have been observed in HaCaT keratinocytes and HDFs. Further, UVA-induced activation of MAPK signaling, and pro-inflammatory cytokine production have been investigated. TGFβ/Smad pathway has also been analyzed in UVA-irradiated HDFs. Treatment with M3G reversed the UVA-induced changes in MMP-1 and collagen production both in HaCaT keratinocytes and HDFs. UVA-mediated activation of p38, ERK and JNK MAPK activation was also inhibited by M3G treatment in HaCaT keratinocytes. In HDFs, M3G was able to upregulate the TGFβ/Smad pathway activation. In addition, M3G downregulated the UVA-induced pro-inflammatory cytokines in keratinocytes and HDFs. It has been suggested that the M3G has exerted potential antiphotoaging properties in vitro, by attenuating UVA-induced changes in MMP-1 and collagen production in keratinocytes and dermal fibroblasts.

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PMID: 

Front Med (Lausanne). 2020 ;7:71. Epub 2020 Mar 4. PMID: 32195263

Abstract Title: 

Myricetin Modulates Macrophage Polarization and Mitigates Liver Inflammation and Fibrosis in a Murine Model of Nonalcoholic Steatohepatitis.

Abstract: 

This study aimed to investigate the beneficial effects of myricetin in a diet-induced nonalcoholic steatohepatitis (NASH) model and the underlying mechanism. C57BL/6J mice were fed a standard chow or the choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for 8 weeks with the treatment of myricetin (100 mg/kg) or vehicle by daily gavage. Hepatic inflammation, steatosis, fibrosis, and hepatic stellate cells (HSC) activation were assessed. We also analyzed M1 and M2 macrophages and its related markers in livers from NASH mice and in RAW264.7 macrophages stimulated by lipopolysaccharide (LPS) or interleukin 4 (IL-4). Furthermore, we determined the effect of myricetin on the triggering receptor expressed on myeloid cells-1 (TREM-1), toll like receptor (TLR) 2 and 4, and myeloid differentiation factor 88 (MyD88) signaling both in livers from mice and in RAW264.7 cells stimulated by LPS. Our results revealed that myricetin remarkably ameliorated hepatic steatosis, inflammation, and inhibited hepatic macrophage infiltration in CDAHFD-fed mice. Myricetin-treated to CDAHFD-fed mice also inhibited liver fibrosis and HSC activation when compared with vehicle-treated to those mice. Moreover, myricetin inhibited M1 macrophage polarization and its relative markers in livers of NASH mice while induced M2 polarization. Similarly,study, myricetin inhibited the LPS-induced mRNA expression of M1 macrophages marker genes and induced IL-4-induced M2 macrophage marker genes in RAW264.7 macrophages. Mechanically, myricetin inhibited the expression of TREM-1 and TLR2/4-MyD88 signaling molecules in livers from NASH mice and in RAW264.7 macrophages stimulated by LPS. Additionally, myricetin inhibited the activation of nuclear factor (NF)-κB signaling and the phosphorylation of the signal transducer and activation of transcription 3 (STAT3) in LPS-stimulated RAW264.7 macrophages. Taken together, our data indicated that myricetin modulated the polarization of macrophages via inhibiting the TREM-1-TLR2/4-MyD88 signaling molecules in macrophages and therefore mitigated NASH and hepatic fibrosis in the CDAHFD-diet-induced NASH model in mice.

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PMID: 

Sci Rep. 2015 Jul 9 ;5:11758. Epub 2015 Jul 9. PMID: 26156213

Abstract Title: 

Galangin attenuates airway remodelling by inhibiting TGF-β1-mediated ROS generation and MAPK/Akt phosphorylation in asthma.

Abstract: 

Galangin, a natural flavonol, has attracted much attention for its potential anti-inflammatory properties. However, its role in the regulation of airway remodelling in asthma has not been explored. The present study aimed to elucidate the effects of galangin on chronic inflammation and airway remodelling and to investigate the underlying mechanisms both in vivo and in vitro. Ovalbumin (OVA)-sensitised mice were administered with galangin 30 min before challenge. Our results showed that severe inflammatory responses and airway remodelling occurred in OVA-induced mice. Treatment with galangin markedly attenuated the leakage of inflammatory cells into bronchoalveolar lavage fluid (BALF) and decreased the level of OVA-specific IgE in serum. Galangin significantly inhibited goblet cell hyperplasia, collagen deposition and α-SMA expression. Lowered level of TGF-β1 and suppressed expression of VEGF and MMP-9 were observed in BALF or lung tissue, implying that galangin has an optimal anti-remodelling effect in vivo. Consistently, the TGF-β1-induced proliferation of airway smooth muscle cells was reduced by galangin in vitro, which might be due to the alleviation of ROS levels and inhibition of MAPK pathway. Taken together, the present findings highlight a novel role for galangin as a promising anti-remodelling agent in asthma, which likely involves the TGF-β1-ROS-MAPK pathway.

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PMID: 

J Med Food. 2015 Nov ;18(11):1187-97. Epub 2015 Jun 4. PMID: 26501381

Abstract Title: 

Galangin Prevents Acute Hepatorenal Toxicity in Novel Propacetamol-Induced Acetaminophen-Overdosed Mice.

Abstract: 

Acetaminophen (APAP) overdose causes severe liver and kidney damage. APAP-induced liver injury (AILI) represents the most frequent cause of drug-induced liver failure. APAP is relatively insoluble and can only be taken orally; however, its prodrug, propacetamol, is water soluble and usually injected directly. In this study, we examined the time-dependent effects of AILI after propacetamol injection in mice. After analyses of alanine aminotransferase and aspartate aminotransferase activities and liver histopathology, we demonstrated that a novel AILI mouse model can be established by single propacetamol injection. Furthermore, we compared the protective and therapeutic effects of galangin with a known liver protective extract, silymarin, and the only clinical agent for treating APAP toxicity, N-acetylcysteine (NAC), at the same dose in the model mice. We observed that galangin and silymarin were more effective than NAC for protecting against AILI. However, only NAC greatly improved both the survival time and rate consequent to a lethal dose of propacetamol. To decipher the hepatic protective mechanism(s) of galangin, galangin pretreatment significantly decreased the hepatic oxidative stress, increased hepatic glutathione level, and decreased hepatic microsomal CYP2E1 levels induced by propacetamol injection. In addition, propacetamol injection also reproduced the probability of APAP-induced kidney injury (AIKI), appearing similar to a clinical APAP overdose. Only galangin pretreatment showed the protective effect of AIKI. Thus, we have established a novel mouse model for AILI and AIKI using a single propacetamol injection. We also demonstrated that galangin provides significant protection against AILI and AIKI in this mouse model.

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