PMID: 

Lung Cancer. 2019 Sep ;135:10-15. Epub 2019 Jul 4. PMID: 31446980

Abstract Title: 

Residential radon, genetic polymorphisms in DNA damage and repair-related.

Abstract: 

OBJECTIVES: To analyze the relationship of GSTT1, GSTM1, XRCC1 (rs25487), ERCC1 (rs11615, rs3212986), ERCC2 (rs13181), XRCC3 (rs861539), OGG1 (rs1052133), and Alpha-1-Antitrypsin mutations (AAT) with the risk of lung cancer in never-smokers, and ascertain if there is an effect modification between these polymorphisms and residential radon exposure.MATERIAL AND METHODS: We designed a multicenter hospital-based case-control study in a radon-prone area. 322 cases and 338 controls, all never-smokers, were included. They were selected using a frequency sampling based on sex and age distribution of the cases. Participants donated 3 ml. of whole blood used to determine genotype for polymorphisms. They placed a radon detector to measure residential radon exposure in their dwelling.RESULTS: The OR for deleted GSTM1 patients was 3.46 (95% CI = 1.52-7.89) at residential radon exposures above 200 Bq/m. The ERCC1 rs3212986 polymorphism was the most associated with the risk of developing lung cancer, both for low and high radon exposures. The ERCC1 rs321986 GT and TT genotypes (at radon concentrations>200 Bq/m) were more significantly associated with higher lung cancer risk (OR = 2.40, 95% CI = 1.29-4.45; OR = 4.45, 95% CI = 1.26-15.7, respectively).CONCLUSIONS: These findings support the hypothesis that certain polymorphisms in genes involved in DNA-repair and carriers of GSTM1 deletion have an increased risk of lung cancer in never-smokers exposed to residential radon.

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PMID: 

Neuroreport. 2019 Oct 30. Epub 2019 Oct 30. PMID: 31688419

Abstract Title: 

Berberine alleviates rotenone-induced cytotoxicity by antioxidation and activation of PI3K/Akt signaling pathway in SH-SY5Y cells.

Abstract: 

Berberine, an isoquinoline alkaloid isolated from traditional Chinese medicine, has been widely studied for its efficacy in the treatment of neurodegenerative diseases. However, berberine-mediated neuroprotection in the pathogenesis of Parkinson's disease is still uncertain. In this study, the effects of berberine on rotenone-induced neurotoxicity in SH-SY5Y cells were investigated. The results showed that berberine treatment significantly alleviated rotenone-induced decrease in the cell viability in SH-SY5Y cells. Further studies demonstrated that berberine suppressed the production of intracellular reactive oxygen species, restored the mitochondrial transmembrane potential, increased Bcl-2/Bax ratio, and decreased caspase-3 activation that induced by rotenone. Furthermore, berberine also restored the phosphorylation of Akt, which was downregulated by rotenone in SH-SY5Y cells. These results suggest that berberine protects rotenone-treated SH-SY5Y cells by antioxidation and activation of PI3K/Akt signaling pathway.

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PMID: 

J Pak Med Assoc. 2019 Aug ;69(Suppl 3)(8):S88-S92. PMID: 31603885

Abstract Title: 

Berberine attenuates olanzapine induced-metabolic syndrome.

Abstract: 

Objective: To elucidate the protective effect of berberine on olanzapine induced-metabolic syndrome.Methods: This prospective experimental study involved thirty Sprague-Dawley male rats which were divided into three groups. Group A (n=10): Rats treated with distilled water, Group B (n=10): Rats treated with olanzapine, Group C (n=10): Rats treated with olanzapine plus berberine. The duration of the study was 8 weeks, baseline and follow up data were evaluated. Fasting blood glucose(FBG) total cholesterol (TC), triglyceride (TG) and high-density lipoprotein (HDL), Low density lipoprotein (LDL), atherogenic index of plasma (AI), fasting serum insulin level, insulin resistance,β- cell function and insulin sensitivity were evaluated.SPSS 20.Results: Olanzepine led to significant deterioration in gluco-metabolic profile compared with control P

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PMID: 

Psychopharmacology (Berl). 2019 Nov 29. Epub 2019 Nov 29. PMID: 31784805

Abstract Title: 

Embedding existential psychology within psychedelic science: reduced death anxiety as a mediator of the therapeutic effects of psychedelics.

Abstract: 

Psychedelic therapies can engender enduring improvements in psychological well-being. However, relatively little is known about the psychological mechanisms through which the salutary effects of psychedelics emerge. Through integrating extant research on psychedelics with contemporary existential psychology, we present a novel hypothesis that reduced death anxiety may be a key mechanism underpinning the therapeutic effects of psychedelics. In developing this hypothesis, we also provide a complementary review of mechanisms through which psychedelics may reduce death anxiety. We conclude that an awareness of the role of death anxiety in psychopathology has the potential to guide future research into psychedelic therapies.

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PMID: 

Lipids. 2019 Nov 6. Epub 2019 Nov 6. PMID: 31691998

Abstract Title: 

Berberine Inhibits Adipogenesis in Porcine Adipocytes via AMP-Activated Protein Kinase-Dependent and -Independent Mechanisms.

Abstract: 

Excessive adipogenesis in adipocytes results in obesity. Berberine, a natural isoquinoline alkaloid, has antiobesity properties. However, the underlying molecular mechanisms have remained unclear up to now. In this study, porcine adipocytes were cultured and treated with berberine. Cellular lipid content was measured by Oil Red O staining extraction. The role of an adenosine monophosphate-activated protein kinase (AMPK) signaling pathway was evaluated by the phosphorylation detection of AMPKα protein and knockdown of AMPK alpha1 (Ampka1) gene. Gene expressions were analyzed by Western blot and real-time reverse transcription-polymerase chain reaction (RT-PCR). The results showed that berberine reduced lipid accumulation in porcine adipocytes in a dose- and time-dependent manner and increased phosphorylation of AMPKα. Furthermore, berberine significantly downregulated the mRNA expression of related genes to adipogenesis including peroxisome proliferator activated receptor gamma 2 (Pparg2), CCAAT/enhancer-binding protein alpha (Cebpa), Cebp beta (Cebpb), sterol regulatory elementbinding transcription factor 1 (Srebf1), acetyl-CoA carboxylase-1 (Acc-1), fatty acid synthase (Fas), fatty acid binding protein 4 (Fabp4), and stearoyl-CoA desaturase 1 (Scd1). Knockdown of Ampka1 markedly reversed the inhibitory effect of berberine on lipid accumulation and mRNA expression of theabove genes except Cebpb in porcine adipocytes. Meanwhile, the protein expression of these adipogenic genes in response to berberine and Ampka1 knockdown paralleled the alterations of their mRNA level. These results suggest that berberine inhibits adipogenesis in porcine adipocytes via AMPK-dependent and -independent multiple mechanisms, which would provide an important idea for the reduction of porcine body fat, as well as the prevention and treatment of human obesity.

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PMID: 

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2019 Jul 28 ;35(4):359-362. PMID: 31701723

Abstract Title: 

[Effects of berberine on learning and memory ability in vascular cognitive impairment rats].

Abstract: 

OBJECTIVE: To investigate the effects of berberine on learning and memory ability in vascular cognitive impairment rats.METHODS: Sixty-eight Wistar rats were randomly divided into control group (n=10), sham operated group (n=10) and the modeling group of vascular cognitive impairment rat (n=48), then the rats in modeling group were randomly divided into four groups (n=10): vehicle group, berberine low dose group (20 mg/kg), medium dose group (40 mg/kg) and high dose group (60 mg/kg). Bilateral common carotid arteries were occluded in rats to establish vascular cognitive impairment (VCI) model. Different doses of berberine were intraperitoneally injected into the treatment group and normal saline was intraperitoneally injected into the other groups once a day for a total of 34 days. After 28 days of administration, Morris water maze was used to test the learning and memory ability of rats. After the water maze experiment, the levels of superoxide dismutase (SOD) activity, glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor alpha(TNF-α), interleukin-1 beta (IL-1β), 5-hydroxytryptamine (5-HT) and monoamine oxidase (MAO) in the forebrain cortex were detected.RESULTS: Compared to sham group, the escape latency in VCI group was significantly extended (P＜0.01) and the times of passing through the platform were decreased remarkably (P＜0.01). The levels of SOD, GSH and 5-HT in the hippocampus or anterior cortex were decreased significantly (P＜0.01), while the contents of MDA, TNF-α, IL-1β and MAO were increased remarkably (P＜0.01). Comparedwith VCI group, the escape latency in berberine-treated groups was shortened significantly (P＜0.01, P＜0.05) and the times of passing through the platform were increased remarkably (P＜0.01, P＜0.05), the levels of SOD, GSH and 5-HT were increased significantly (P＜0.01), while the contents of TNF-α, IL-1β and MAO were decreased remarkably (P＜0.01).CONCLUSION: Berberine could significantly improve the spatial learning and memory abilities of rats with vascular cognitive impairment. The mechanism may be related to the effects of berberine on the hippocampal antioxidant stress, anti-inflammatory response and the monoamine neurotransmitter system in the forebrain cortex. Berberine 60 mg/kg dose group had better effect.

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PMID: 

Cancer Manag Res. 2019 ;11:9005-9015. Epub 2019 Oct 21. PMID: 31695492

Abstract Title: 

Berberine induces apoptosis in non-small-cell lung cancer cells by upregulating miR-19a targeting tissue factor.

Abstract: 

Background: Berberine (BBR) from the widely used Chinese herbal medicine Huanglian has an array of pharmacological and biochemical properties, including anti-neoplastic activity. However, the specific mechanisms underlying these properties are unknown. The aim of this study was to explore the anti-tumor mechanisms of BBR in non-small cell lung cancer (NSCLC).Methods: The effects of BBR on NSCLC tumor development and programmed cell death were investigated both in vivo and in vitro. Luciferase reporter assays were used to determine whether tissue factor (TF) was a target of miR-19a.Results: BBR suppressed NSCLC growth and promoted apoptosis in NSCLC cells by modulating miR-19a and TF expression. Luciferase assays showed that TF was a direct inhibitory target of miR-19a in NSCLC cells. BBR induced apoptosis through the miR-19a/TF/MAPK axis.Conclusion: The results suggest that BBR induces apoptosis of NSCLC cells via the miR-19a/TF/MAPK signaling pathway.

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PMID: 

Br J Pharmacol. 2019 Nov 16. Epub 2019 Nov 16. PMID: 31734944

Abstract Title: 

Berberine protects against diabetic kidney disease via promoting PGC-1α-regulated mitochondrial energy homeostasis.

Abstract: 

BACKGROUND AND PURPOSE: Lipid metabolism disorder and disturbed mitochondrial bioenergetics play pivotal roles in the occurrence and development of diabetic kidney disease (DKD). Berberine (BBR) is a kind of alkaloid derived from Chinese herbal medicine. It has multiple therapeutic actions on diabetes mellitus and its complications, including regulation of glucose and lipid metabolism, improvement of insulin sensitivity and alleviation of oxidative damage. Here we investigated the renoprotective effects of BBR.EXPERIMENTAL APPROACH: Combined clinical study in DKD patients with experimental studies in diabetic mice and cultured podocytes, we characterized the energy metabolism profiles based on metabolomics, investigated molecular targets and mechanisms of BBR at regulating mitochondrial function and bioenergetics, and testified the effects of BBR on metabolic alterations in DKD animal model.KEY RESULTS: Metabolomics examination suggested altered mitochondrial fuel usage and generalized mitochondrial dysfunction in DKD patients. BBR intervention potently reversed metabolic disorders, podocyte damage and glomerulosclerosis in db/db mice. Lipid accumulation, excessive generation of mitochondrial reactive oxygen species, mitochondrial dysfunction and insufficient fatty acids oxidation in DKD mouse models and cultured podocytes were significantly suppressed by BBR. The protective mechanism of BBR might involve the activation of peroxisome proliferator-activated receptorγ coactivator-1α (PGC-1α) signaling pathway, thereby promoting mitochondrial energy homeostasis and fatty acid oxidation in podocytes.CONCLUSION AND IMPLICATIONS: Our research elucidated that PGC-1α-mediated mitochondrial bioenergetics might play a key role in lipid disorder-induced podocyte damage and development of DKD. Restoration of PGC-1α activity and the energy homeostasis by BBR might be a potential therapeutic strategy against DKD.

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PMID: 

Anticancer Drugs. 2019 Nov 15. Epub 2019 Nov 15. PMID: 31743135

Abstract Title: 

Berberine inhibits proliferation and migration of colorectal cancer cells by downregulation of GRP78.

Abstract: 

OBJECTIVE: Human colorectal cancer (CRC), a highly malignant and metastatic carcinoma, is resistant to many present anticancer therapies. The inhibition of tumor survival and growth through receptor suppression is a promising way to treat CRC. The study aimed to investigate the effect of a natural plant triterpenoid, berberine (BBR), on SW480 cells and whether its role is mediated by Glucose-regulated protein 78 (GRP78).METHODS: MTT assay, wound healing assay, and Annexin V-FITC assay were used to measure the effect of BBR on the proliferation, migration, and apoptosis of SW480 cells, respectively. Immunofluorescence and western blotting were used to evaluate both the downregulation of BBR on GRP78 and the role of GRP78 in the effect of BBR on SW480 cells.RESULTS: Our results revealed that BBR inhibited the proliferation and migration, as well as induced the apoptosis of SW480 cells, in a dose-dependent manner. BBR induced the dose-dependent inhibition of cell proliferation in HT-29 cells. BBR inhibited the expression of GRP78 and its localization on the cell surface. Moreover, BBR inhibited the expression of Bax, Bcl-2, c-Myc, and Vimentin and up-regulated the cytokeratin expression in SW480 cells. In addition, we found that the effects of BBR on cell proliferation, migration, and apoptosis in SW480 cells were reversed by the overexpression of GRP78.CONCLUSION: Our findings demonstrated that BBR inhibited the proliferation and migration and induced the apoptosis of SW480 cells by downregulating the expression of GRP78, and targeting GRP78 might be a potential way to develop the effective anticancer therapy.

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PMID: 

BMC Complement Altern Med. 2019 Nov 19 ;19(1):314. Epub 2019 Nov 19. PMID: 31744490

Abstract Title: 

Inhibitory effects of berberine on proinflammatory M1 macrophage polarization through interfering with the interaction between TLR4 and MyD88.

Abstract: 

BACKGROUNDS: Inflammation is recognized as the key pathological mechanism of type 2 diabetes. The hypoglyceamic effects of berberine (BBR) are related to the inhibition of the inflammatory response, but the mechanism is not completely clear.METHODS: The inflammatory polarization of Raw264.7 cells and primary peritoneal macrophages were induced by LPS, and then effects and underlying mechanisms of BBR were explored. An inflammatory model was established by LPS treatment at different concentrations for different treatment time. An ELISA assay was used to detect the secretions of TNF-α. RT-PCR was applied to detect M1 inflammatory factors. The F4/80ratio and CD11cratio of primary peritoneal macrophages were determined by flow cytometry. The expressions of p-AMPK and TLR4 were detected by Western blot. The cytoplasmic and nuclear distributions of NFκB p65 were observed by confocal microscopy. The binding of TLR4 to MyD88 was tested by CoIP, and the affinity of BBR for TLR4 was assessed by molecular docking.RESULTS: Upon exposure to LPS, the secretion of TNF-α and transcription of inflammatory factors in macrophages increased, cell morphology changed and protrusions appeared gradually, the proportion of F4/80CD11cM1 macrophages increased, and the nuclear distribution of NFκB p65 increased. BBR pretreatment partially inhibited the changes mentioned above. However, the expression of TLR4 and p-AMPK did not change significantly after LPS intervention for 3 h. Meanwhile, CoIP showed that the interaction between TLR4 and MyD88 increased, and BBR inhibited the binding.Molecular docking suggested that BBR might interact with TLR4.CONCLUSIONS: Inflammatory changes were induced in macrophages after LPS stimulation for 3 h, and BBR pretreatment inhibited inflammatory polarization. BBR might interact with TLR4 and disturb TLR4/MyD88/NFκB signalling pathway, and it might be the mechanism by which BBR attenuated inflammation in the early phase.

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