This delivers an outline of thymoquinone role in cancer inhibition and prevention of cancer.

PMID: 

Curr Pharm Biotechnol. 2020 Apr 15. Epub 2020 Apr 15. PMID: 32297580

Abstract Title: 

Thymoquinone, an Active Compound of Nigella Sativa: Role in Prevention and Treatment of Cancer.

Abstract: 

BACKGROUND: Cancer is the leading cause of death worldwide and current mode of cancer treatment causes side effects on normal cells and are still the key challenges in cancer treatment. However, natural products or active compound of medicinal plants are being safe, affordable, and effective in diseases cure.METHODS: In this context, scientific studies evidence the health promoting effects of natural products, which work through its anti-oxidant, anti-inflammatory and anti-cancer activity. Thymoquinone (TM), a predominant active compound of Nigella sativa, has confirmed antineoplastic activity through its ability to regulate various genetic pathways. In addition, thymoquinone has established anti-cancerous effects through killing of various cancerous cells, inhibit the initiation, migration, invasion and progression of the cancer. The anti-cancer effects of TM are chiefly mediated via regulating various cell signaling pathways such as VEGF, bcl2/bax ratio, p53, NF-kB and oncogenes.RESULTS: The anti-cancer drugs have limitations in efficacy and also causes adverse side effects on normal cells. The combination of anti-cancer drugs and thymoquinone improve the efficacy of drugs as evidences by decrease resistance to drugs and regulating various cell signaling pathways. Moreover, combination of anti-cancer drugs as well as thymoquinone shows synergistic effect on killing of cancer cells and cells viability. Thus TM in combination with anti-cancer drugs can be a good strategy in the management of various types of cancer.CONCLUSION: In this review article, we deliver an outline of thymoquinone role in cancer inhibition and prevention of cancer based on in vivo and in vitro studies. Further studies on thymoquinone based on clinical trials are highly required to explore the benefits of thymoquinone in cancer management.

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Investigation of the protective effect of Nigella sativa oil in cisplatin induced oral mucositis.

PMID: 

Turk Arch Otorhinolaryngol. 2020 Mar ;58(1):10-15. Epub 2019 Sep 2. PMID: 32313889

Abstract Title: 

Investigation of the Protective Effect of Nigella Sativa Oil in Cisplatin Induced Oral Mucositis: An Experimental Study.

Abstract: 

Objective: The aim of this experimental study was to investigate the histopathologic effect of Nigella Sativa oil (NSO) on cisplatin (Cis) induced oral mucositis (OM) in rats.Methods: Twenty-four rats were divided into four equal groups. The animals in Group 1 and Group 2 were given 5 mg/kg intraperitoneal (ip) Cis systemically on the 1, 3and 5days of the study. Additionally, 15 mL NSO were given to the rats in Group 2, with gavage feeding on days 1, 3, 5, 7, and 9. The animals in Group 3 were given per oral 15 ml NSO on days 1, 3, 5, 7 and 9. As the control group, Group 4 received a total of 15 mL 0.9% saline solution divided into 5 doses on days 1, 3, 5, 7 and 9 by oral gavage. On the 14day, animals were euthanized and buccal mucosa from both sides, including submucosal tissues, were excised and taken to histopathological examination.Results: The mean mucosal thicknesses of the groups were 224.58μm, 276.1 μm, 323.33 μm, and 331.33 μm, respectively for Groups 1, 2, 3, and 4 (p

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Antibiotic resistance in acne has been increasing worldwide.

PMID: 

Eur J Dermatol. 2016 Apr 1 ;26(2):127-32. PMID: 26711531

Abstract Title: 

Bacteriological resistance in acne: A call to action.

Abstract: 

Acne is common in adolescence but is also increasingly seen in adulthood, with about 40% of adults being affected. Topical and systemic oral antibiotics have been used for more than 40 years in the treatment of acne lesions. In the 1970s, evidence of resistance to topical erythromycin and clindamycin was reported and, since then, antibiotic resistance in acne has been increasing worldwide. Antibiotic exposure can be significant in acne treatment because the patient population is large and there is a tendency for prolonged treatment regimens to be prescribed. The overuse of antibiotics is now considered a major public health problem. Action is therefore required to encourage judicial and appropriate use of antibiotics in acne management in line with available evidence-based guidelines. Alternatives to topical antibiotics for the treatment of acne should be considered. Topical antibiotics should no longer be used as monotherapy in acne treatment and use in combination regimens should be limited to a maximum of four weeks. Evidence from studies suggests that, as for topical antibiotics, oral antibiotics should not be used as monotherapy, but instead should be combined with a topical retinoid or benzoyl peroxide for a maximum of four months. Correct and appropriate use of antibiotics in the treatment of acne will help to preserve their utility in the face of increasing antibiotic resistance but greater awareness of the issues is required among prescribing physicians.

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There is evidence that suggests topically-applied green tea polyphenols may reduce sebum secretion and be beneficial in the treatment of acne.

PMID: 

Antioxidants (Basel). 2016 Dec 29 ;6(1). Epub 2016 Dec 29. PMID: 28036057

Abstract Title: 

Green Tea and Other Tea Polyphenols: Effects on Sebum Production and Acne Vulgaris.

Abstract: 

Polyphenols are antioxidant molecules found in many foods including nuts, fruits, vegetables, chocolate, wine, and tea. Polyphenols have antimicrobial, anti-inflammatory, and antineoplastic properties. Recent studies suggest that tea polyphenols may be used for reducing sebum production in the skin and for treatment of acne vulgaris. This review examines the evidence for use of topically and orally ingested tea polyphenols against sebum production and for acne treatment and prevention. The PubMed database was searched for studies on tea polyphenols, sebum secretion, and acne vulgaris. Of the 59 studies found, eight met the inclusion criteria. Two studies evaluated tea polyphenol effects on sebum production; six studies examined tea polyphenol effects on acne vulgaris. Seven studies evaluated topical tea polyphenols; one study examined systemic tea polyphenols. None of the studies evaluated both topical and systemic tea polyphenols. Tea polyphenol sources included green tea (six studies) and tea, type not specified (two studies). Overall, there is some evidence that tea polyphenols in topical formulation may be beneficial in reducing sebum secretion and in treatment of acne. Research studies of high quality and with large sample sizes are needed to assess the efficacy of tea polyphenols in topical and oral prevention of acne vulgaris and lipid synthesis by the sebaceous glands.

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Identification of berberine as a novel drug for the treatment of multiple myeloma via targeting UHRF1.

PMID: 

BMC Biol. 2020 03 25 ;18(1):33. Epub 2020 Mar 25. PMID: 32213189

Abstract Title: 

Identification of berberine as a novel drug for the treatment of multiple myeloma via targeting UHRF1.

Abstract: 

BACKGROUND: Current therapies for multiple myeloma (MM) are associated with toxicity and resistance, highlighting the need for novel effective therapeutics. Berberine (BBR), a botanical alkaloid derived from several Berberis medicinal plants, has exhibited anti-tumor effects, including against multiple myeloma (MM); however, the molecular mechanism underlying the anti-MM effect has not been previously described. This study aimed to identify the target of berberine and related mechanisms involved in its therapeutic activity against MM.RESULTS: Here, we demonstrated that BBR treatment killed MM cells in vitro and prolonged the survival of mice bearing MM xenografts in vivo. A screening approach integrating surface plasmon resonance (SPR) with liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified UHRF1 (ubiquitin-like with PHD and RING Finger domains 1) as a potential target of BBR. Combining molecular docking and SPR analysis, we confirmed UHRF1 as a BBR-binding protein and discovered that BBR binds UHRF1 in the tandem tudor domain and plant homeodomain (TTD-PHD domain). BBR treatment induced UHRF1 degradation via the ubiquitin-dependent proteasome system and reactivated p16and p73 in MM cells. Overexpression of UHRF1 promoted the MM cell proliferation and rendered MM cells more resistant to BBR, while silencing of UHRF1 with siRNA attenuated BBR-induced cytotoxicity.CONCLUSIONS: In summary, our study has identified UHRF1 as a direct target of BBR and uncovered molecular mechanisms involved in the anti-MM activity of BBR. Targeting UHRF1 through BBR may be a novel therapeutic strategy against MM.

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Systematic review and meta-analysis on efficacy and safety of berberine for dyslipidemia

PMID: 

Zhongguo Zhong Yao Za Zhi. 2020 Feb ;45(3):664-673. PMID: 32237527

Abstract Title: 

[Systematic review and Meta-analysis on efficacy and safety of berberine for dyslipidemia].

Abstract: 

To evaluate the clinical efficacy and safety of berberine in the treatment of dyslipidemia. In this review, CNKI, WanFang, VIP, CBM, PubMed, Cochrane Library, EMbase, and Medline(OVID) were retrieved from database establishment to January, 2019 in any language. Randomized controlled trials(RCTs) of berberine with or without lipid-lowering drugs vs placebo, without drugs or lipid-lowering drugs only in treatment of dyslipidemia were collected. Data extraction and paper quality assessment were conducted according to the Cochrane Handbook. Then RevMan 5.3 software was used for Meta-analysis. A total of 25 trials were included, covering 3 042 cases, including 1 552 cases in the experimental group and 1 490 cases in the control group. The clinical heterogeneity of the included trials was relatively high, and the methodological quality of most trials was generally low, with bias in terms of random sequence generation, allocation hiding, blind method and result data. Interventions were divided into different subgroups for analysis. Meta-analysis suggested that use berberine alone or along with lipid lowing drugs could reduce TC, TG, LDL-C levels and increased HDL-C levels with statistically significant difference as compared with control group. As compared with control group, there was no statistically significant difference in the incidence of adverse events. No severe adverse effects were reported in all trials. Berberine has good efficacy and safety in the treatment of dyslipidemia. Due to the quality limitations of the included trials, the above conclusions need to be further verified by high-quality, large sample size and multi-center clinical trials.

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Novel regulation of miR-34a-5p and HOTAIR by the combination of berberine and gefitinib leading to inhibition of EMT in human lung cancer.

PMID: 

J Cell Mol Med. 2020 Apr 5. Epub 2020 Apr 5. PMID: 32248643

Abstract Title: 

Novel regulation of miR-34a-5p and HOTAIR by the combination of berberine and gefitinib  leading to inhibition of EMT in human lung cancer.

Abstract: 

HOTAIR is an important carcinogenic lncRNA and involves in tumorigenesis, and invasion. MiR-34a-5p functions as a tumour suppressor. However, the underlying mechanism of HOTAIR regulation especially in association with miR-34a-5p in non-small-cell lung cancer (NSCLC) has not been explored. Herein, we performed series of in vitro experiments, including viability, migration, invasion, apoptosis and in vivo xenograft model, and identified that HOTAIR was remarkably elevated in NSCLC cells. Enforced HOTAIR expression promoted migration and invasion, while depleted HOTAIR diminished the ability of migration and invasion of NSCLC cells. We also observed that miR-34a-5p was dramatically inhibited in NSCLC cells and the binding correlation between HOTAIR and miR-34a-5p was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. We also showed that induction of miR-34a-5p and reduction of HOTAIR, and the interaction between miR-34a-5p and HOTAIR resulted in the suppression of epithelial-mesenchymal transition (EMT) as illustrated by induction of key epithelial markers E-cadherin expression, reduction of vimentin and EMT-inducing transcription factor snail. Excessive expression of snail resisted miR-34a-5p-inhibited cell growth. Snail binds to E-cadherin promoter and regulates E-cadherin expression. There was a synergy in combination of berberine and gefinitib in this process. Similar findings were also observed in a tumour xenograft model. Collectively, this is the first report demonstrating reciprocal interaction of miR-34a-5p- and HOTAIR-mediated regulation of snail resulting in inhibition of EMT process by the combination of berberine and gefitinib suggesting that regulation of miR-34a-5p- and HOTAIR-mediated inhibition of EMT may provide novel treatment paradigms for lung cancer.

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Berberine attenuates Aβ42-induced neuronal damage through regulating circHDAC9/miR-142-5p axis in human neuronal cells.

PMID: 

Life Sci. 2020 Apr 3 ;252:117637. Epub 2020 Apr 3. PMID: 32251633

Abstract Title: 

Berberine attenuates Aβ42-induced neuronal damage through regulating circHDAC9/miR-142-5p axis in human neuronal cells.

Abstract: 

BACKGROUND: Berberine plays a neuroprotective role in neurodegenerative diseases, including Alzheimer's disease (AD). Circular RNAs (circRNAs) function as crucial players in AD pathogenesis. In the current work, we aimed to investigate whether circRNA histone deacetylase 9 (circHDAC9) was involved in the regulation of berberine in AD.METHODS: Cell viability and apoptosis were determined by the Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to assess caspase-3 activity and the production of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α). The levels of circHDAC9 and miR-142-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Subcellular fractionation assays were performed to evaluate the localization of circHDAC9. The direct interaction between circHDAC9 and miR-142-5p was confirmed by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays.RESULTS: Our data indicated that circHDAC9 was indeed a circular transcript and mainly localized in the cytoplasm. 42-residueβ-amyloid (Aβ42) triggered a significant down-regulation in circHDAC9 and a striking up-regulation in miR-142-5p in human neuronal (HN) cells. Berberine relieved Aβ42-induced HN cell neurotoxicity. Moreover, berberine resulted in increased circHDAC9 expression and decreased miR-142-5p level in Aβ42-treated HN cells. Berberine alleviated Aβ42-induced neuronal damage in HN cells by up-regulating circHDAC9. Furthermore, circHDAC9 acted as a molecular sponge of miR-142-5p. CircHDAC9 overexpression alleviated Aβ42-induced HN cell neurotoxicity via miR-142-5p.CONCLUSION: Our current study suggested that berberine protected HN cell from Aβ42-induced neuronal damage at least partly through regulating the circHDAC9/miR-142-5p axis, highlighting novel evidence for the neuroprotective effect of berberine in AD.

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Mechanisms of berberine for the treatment of atherosclerosis based on network pharmacology.

PMID: 

Evid Based Complement Alternat Med. 2020 ;2020:3568756. Epub 2020 Mar 19. PMID: 32256641

Abstract Title: 

Mechanisms of Berberine for the Treatment of Atherosclerosis Based on Network Pharmacology.

Abstract: 

Atherosclerosis is a common metabolic disease characterized by lipid metabolic disorder. The processes of atherosclerosis include endothelial dysfunction, new endothelial layer formation, lipid sediment, foam cell formation, plaque formation, and plaque burst. Owing to the adverse effects of first-line medications, it is urgent to discover new medications to deal with atherosclerosis. Berberine is one of the most promising natural products derived from traditional Chinese medicine. However, the panoramic mechanism of berberine against atherosclerosis has not been discovered clearly. In this study, we used network pharmacology to investigate the interaction between berberine and atherosclerosis. We identified potential targets related to berberine and atherosclerosis from several databases. A total of 31 and 331 putative targets for berberine and atherosclerosis were identified, respectively. Then, we constructed berberine and atherosclerosis targets with PPI data. Berberine targets network with PPI data had 3204 nodes and 79437 edges. Atherosclerosis targets network with PPI data had 5451 nodes and 130891 edges. Furthermore, we merged the two PPI networks and obtained the core PPI network from the merged PPI network. The core PPI network had 132 nodes and 3339 edges. At last, we performed functional enrichment analyses including GO and KEGG pathway analysis in David database. GO analysis indicated that the biological processes were correlated with G1/S transition of mitotic cells cycle. KEGG pathway analysis found that the pathways directly associated with berberine against atherosclerosis were cell cycle, ubiquitin mediated proteolysis, MAPK signaling pathway, and PI3K-Akt signaling pathway. After combining the results in context with the available treatments for atherosclerosis, we considered that berberine inhibited inflammation and cell proliferation in the treatment of atherosclerosis. Our study provided a valid theoretical foundation for future research.

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