A Natural Isoquinoline Alkaloid With Antitumor Activity: Studies of the Biological Activities of Berberine

Li, Da; Meng, Xue; Wu, Donglu; Qiu, Zhidong; Luo, Haoming

doi:10.3389/fphar.2019.00009

Cited by 127 publications

(90 citation statements)

References 129 publications

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“…As a central regulator of antioxidant stress defenses, Nrf2 can activate antioxidant genes and protect liver cells against oxidative stress [8,26]. Dysregulation or deficiency of Nrf2 in the liver is associated with the development of liver diseases, including hepatitis, fibrosis and, hepatocarcinogenesis [27][28][29][30]. Therefore, several studies have examined the abilities of antioxidants targeting Nrf2 to improve various liver diseases [31,32].…”

Section: Discussionmentioning

confidence: 99%

Kahweol activates the Nrf2/HO-1 pathway by decreasing Keap1 expression independently of p62 and autophagy pathways

Seo

Lee

et al. 2020

PLoS ONE

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Kahweol is a diterpene found in coffee beans and unfiltered coffee drinks. Several studies have demonstrated that kahweol induces the nuclear factor erythroid-2 related factor 2/ hemeoxygenase-1 (Nrf2/HO-1) pathway; however, the mechanisms involved are currently unknown. Kelch-like ECH-associated protein 1 (Keap1) is a major regulator of Nrf2 expression and is degraded mostly by autophagy. The p62 protein enhances binding to Keap1 and contributes to the activation of Nrf2. Here, we examined the role of Keap1 regulation in the effect of kahweol on the Nrf2/HO-1 pathway in hepatocytes. In AML12 cells and primary mouse hepatocytes, kahweol increased the levels of Nrf2 and HO-1 protein without increasing expression of the Nrf2 mRNA. In addition, kahweol reduced Keap1 protein levels significantly without decreasing Keap1 mRNA levels. Although regulation of the Keap1-Nrf2pathway by p62-dependent autophagy is well known, we confirmed here that the reduction of Keap1 protein levels by kahweol does not involve p62-dependent autophagy degradation or ubiquitination. In conclusion, kahweol increases the expression of Nrf2 in hepatocytes by inhibiting translation of the Keap1 mRNA.

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Section: Discussionmentioning

confidence: 99%

Kahweol activates the Nrf2/HO-1 pathway by decreasing Keap1 expression independently of p62 and autophagy pathways

Seo

Lee

et al. 2020

PLoS ONE

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“…Molecules 2019, 24, x FOR PEER REVIEW 2 of 18 and cervical cancer cells through apoptosis induction and cell cycle arrest, inhibition of migration and invasion, reduction of the expression of VEGF mRNA and inhibition of angiogenesis [8].…”

Section: Berberine Inhibits Proliferation Of Triple Negative Breast Cmentioning

confidence: 99%

Berberine Impairs the Survival of Triple Negative Breast Cancer Cells: Cellular and Molecular Analyses

et al. 2020

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Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype. Non-available targeted therapy for TNBC represents its biggest treatment challenge. Thus, finding new promising effective drugs is urgently needed. In the present study, we investigated how berberine, a natural isoquinoline, impairs the survival of TNBC cells in both cellular and molecular levels. Our experimental model was based on the use of eight TNBC cell lines: MDA-MB-468, MDA-MB-231, HCC70, HCC38, HCC1937, HCC1143, BT-20, and BT-549. Berberine was cytotoxic against all treated TNBC cell lines. The most sensitive cell lines were HCC70 (IC 50 = 0.19 µM), BT-20 (IC 50 = 0.23 µM) and MDA-MB-468 (IC 50 = 0.48 µM). Using flow cytometry techniques, berberine, at 0.5 and 1 µM for 120 and 144 h, not only induced cell cycle arrest, at G1 and/or G2/M phases, but it also triggered significant apoptosis. At the molecular level, these results are consistent with the expression of their related proteins using Western blot assays. Interestingly, while berberine was cytotoxic against TNBC cells, it had no effect on the viability of normal human breast cells MCF10A cultured in a 3D matrigel model. These results suggest that berberine may be a good potential candidate for TNBC drug development.

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“…Present day drug has affirmed that berberine ( Figure 35) has pharmacological exercises, for example, calming, pain relieving, antimicrobial, hypolipidemic, and pulse bringing down impacts. Critically, the dynamic element of berberine has clear inhibitory impacts on different malignancies, including colorectal disease, lung malignant growth, ovarian disease, prostate malignant growth, liver malignancy, and cervical disease [94]. In China, Rhizoma Coptidis is a typical segment in conventional meds used to treat CVD related issues including heftiness, diabetes mellitus, hyperlipidemia, hyperglycemia and disarranges of lipid metabolism [95].…”

Section: Pyrrole: Stachydrinementioning

confidence: 99%

Chemistry of Secondary Metabolites

Mohiuddin¹

2019

ACT

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Medicinal plants, are known to deliver a wide scope of Plant Secondary Metabolites (PSMs) connected as bug sprays, medications, colors and poisons in farming, prescription, industry and biofighting in addition to bio-fear mongering, separately. Be that as it may, creation of PSMs is for the most part in little amounts, so we have to discover novel approaches to increment both amount and nature of them. Luckily, biotechnology proposes a few choices through which secondary metabolism in plants can be built in imaginative approaches to: 1) over-produce the valuable metabolites, 2) down-produce the poisonous metabolites, 3) produce the new metabolites. Secondary metabolites are extensively characterized as natural products integrated by a life form that is not basic to help development and life. The plant kingdom fabricates more than 200,000 unmistakable chemical compounds, a large portion of which emerge from particular metabolism. While these compounds assume critical jobs in interspecies challenge and safeguard, many plant natural products have been abused for use as prescriptions, scents, flavors, supplements, repellants, and colorants. In spite of this immense chemical decent variety, numerous secondary metabolites are available at low focuses in plant a, taking out yield based assembling as methods for achieving these imperative products. The basic and stereo chemical unpredictability of particular metabolites frustrates most endeavors to get to these compounds utilizing chemical blend. Albeit local plants can be built in amass target pathway metabolites. This Update gives a concise outline of designing plant secondary metabolism in microbial frameworks. We quickly diagram biosynthetic pathways intervening arrangement of the real classes of natural products with an accentuation on high-esteem terpenoids, alkaloids, phenylpropanoids, and polyketides. We additionally feature basic topics, techniques, and provoke hidden endeavors to reproduce and build these pathways in microbial hosts. We center mostly around again biosynthetic methodologies in which plant specific metabolites are combined straightforwardly from sugar feed stocks instead of enhanced forerunners or intermediates.

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A Natural Isoquinoline Alkaloid With Antitumor Activity: Studies of the Biological Activities of Berberine

Cited by 127 publications

References 129 publications

Kahweol activates the Nrf2/HO-1 pathway by decreasing Keap1 expression independently of p62 and autophagy pathways

Kahweol activates the Nrf2/HO-1 pathway by decreasing Keap1 expression independently of p62 and autophagy pathways

Berberine Impairs the Survival of Triple Negative Breast Cancer Cells: Cellular and Molecular Analyses

Chemistry of Secondary Metabolites

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