PMID: 

Mol Med Rep. 2019 Nov 19. Epub 2019 Nov 19. PMID: 31746359

Abstract Title: 

Berberine ameliorates lipopolysaccharide‑induced inflammatory responses in mouse inner medullary collecting duct‑3 cells by downregulation of NF‑κB pathway.

Abstract: 

The major role of inner medullary collecting duct (IMCD) cells is to maintain water and sodium homeostasis. In addition to the major role, it also participates in the protection of renal and systemic inflammation. Although IMCD cells could take part in renal and systemic inflammation, investigations on renal inflammation in IMCD cells have rarely been reported. Although berberine (BBR) has been reported to show diverse pharmacological effects, its anti‑inflammatory and protective effects on IMCD cells have not been studied. Therefore, in the present study, we examined the anti‑inflammatory and protective effects of BBR in mouse IMCD‑3 (mIMCD‑3) cells against lipopolysaccharide (LPS). An MTT assay was carried out to investigate the toxicity of BBR on mIMCD‑3 cells. Reverse transcription quantitative‑PCR and western blotting were performed to analysis pro‑inflammatory molecules and cytokines. Mechanisms of BBR were examined by western blotting and immunocytochemistry. According to previous studies, pro‑inflammatory molecules,such as inducible nitric oxide synthase and cyclooxygenase‑2, and pro‑inflammatory cytokines, such as interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α are increased in LPS‑exposed mIMCD‑3 cells. However, the production of these pro‑inflammatory molecules is significantly inhibited by treatment with BBR. In addition, BBR inhibited translocation of nuclear factor (NF)‑κB p65 from the cytosol to the nucleus, and degradation of inhibitory κ‑Bα in LPS‑exposed mIMCD‑3 cells. In conclusion, BBR could inhibit renal inflammatory responses via inhibition of NF‑κB signaling and ultimately contribute to amelioration of renal injury during systemic inflammation.

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PMID: 

Aging Cell. 2019 Nov 26:e13060. Epub 2019 Nov 26. PMID: 31773901

Abstract Title: 

Berberine ameliorates cellular senescence and extends the lifespan of mice via regulating p16 and cyclin protein expression.

Abstract: 

Although aging and senescence have been extensively studied in the past few decades, however, there is lack of clinical treatment available for anti-aging. This study presents the effects of berberine (BBR) on the aging process resulting in a promising extension of lifespan in model organisms. BBR extended the replicative lifespan, improved the morphology, and boosted rejuvenation markers of replicative senescence in human fetal lung diploid fibroblasts (2BS and WI38). BBR also rescued senescent cells with late population doubling (PD). Furthermore, the senescence-associatedβ-galactosidase (SA-β-gal)-positive cell rates of late PD cells grown in the BBR-containing medium were ~72% lower than those of control cells, and its morphology resembled that of young cells. Mechanistically, BBR improved cell growth and proliferation by promoting entry of cell cycles from the Gor Gphase to S/G-M phase. Most importantly, BBR extended the lifespan of chemotherapy-treated mice and naturally aged mice by ~52% and ~16.49%, respectively. The residual lifespan of the naturally aged mice was extended by 80%, from 85.5 days to 154 days. The oral administration of BBR in mice resulted in significantly improved health span, fur density, and behavioral activity. Therefore, BBR may be an ideal candidate for the development of an anti-aging medicine.

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PMID: 

Regul Toxicol Pharmacol. 2019 Nov 25:104544. Epub 2019 Nov 25. PMID: 31778716

Abstract Title: 

Berberine decreases insulin resistance in a PCOS rats by improving GLUT4: Dual regulation of the PI3K/AKT and MAPK pathways.

Abstract: 

Berberine has been found to exhibit an array of pharmacological activities relating to the lowering of blood glucose and the treatment of polycystic ovarian syndrome (PCOS). The mechanism underlying these activites, however, is poorly understood. In the present study, female Sprague-Dawley (SD) rats were given oral letrozole to establish a model of insulin-resistant PCOS, and animals were then randomized into untreated or berberine-treated groups (400, 200, or 100 mg/kg). After 28 days, we measured homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) values in these animals. We further conducted H&E staining of ovarian tissues, assessed mRNA expression of glucose transporter 4 (GLUT4) via real time PCR, and used Western blotting to measure GLUT4 and PI3K/AKT and MAPK pathway protein levels. Berberine treatment was able to help restore HOMA-IR and ISI values to normal levels while simultaneously bolstering the expression of GLUT4. Normal ovarian morphology was also restored upon berberine treatment. We further found that 400 mg/kg berberine treatment was associated with activation of PI3K/AKT signaling and suppression of the MAPK pathway. In conclusion, berberine has the potential to reduce PCOS pathology and IR values in a rat model system through a mechanism linked to GLUT4 upregulation via PI3K/AKT activation andMAPK pathway suppression.

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PMID: 

Med Sci Monit. 2019 Nov 28 ;25:9058-9066. Epub 2019 Nov 28. PMID: 31779025

Abstract Title: 

Berberine Inhibits Proliferative Ability of Breast Cancer Cells by Reducing Metadherin.

Abstract: 

BACKGROUND Breast cancer is a common malignant tumor worldwide. Despite the huge advances in modern medicine, many patients still face a high risk of recrudescent and metastatic breast cancer. Berberine was widely implemented in clinic treatment of breast cancer. This study was performed to contribute to a better understanding on the mechanisms underlying berberine affecting breast cancer. MATERIAL AND METHODS We mined survival data of metadherin (MTDH) in breast cancer patients through Kaplan-Meier Plotter and analyzed the transcriptional and posttranscriptional expression profile of MTDH in several breast cancer cell lines. The cell viability and MTDH mRNA level were detected under the si-MTDH vector and different concentrations of berberine. The MTDH-expression vector was transfected into MCF-7 and MDA-MB-231 cells, and the changes of cell viability and apoptosis were determined after berberine (50μM) treatment. RESULTS High MTDH expression was related to worse relapse-free survival (RFS) of breast cancer (P-value=6.2e-08). High-expressed MTDH is common in breast cancer cells, compared with that in normal breast cells (P

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PMID: 

Evid Based Complement Alternat Med. 2019 ;2019:2580207. Epub 2019 Nov 3. PMID: 31781264

Abstract Title: 

Berberine Modulates LPA Function to Inhibit the Proliferation and Inflammation of FLS-RA via p38/ERK MAPK Pathway Mediated by LPA.

Abstract: 

Objective: This study aimed to investigate whether berberine exerted anti-inflammatory and antiproliferative effects on the fibroblast-like synoviocytes of rheumatoid arthritis (FLS-RA) through regulating the lysophosphatidic acid (LPA) function.Methods: Firstly, the expression levels of LPA and lysophosphatidic acid receptor 1 (LPA) in RA patients, osteoarthritis (OA) patients, and healthy controls were detected. Moreover, molecular docking was employed to characterize the binding sites of berberine in the predicted protein targets. Later, FLS-RA were stimulated using berberine, LPA, and the specific inhibitor (Ki16425) of LPAthereafter, the effects on the proliferation, apoptosis, the release of inflammatory mediators of FLS-RA, and the MAPK pathway were observed.Results: Compared with healthy controls ( = 25), the plasma LPA level ( = 28) and synovial fluid ( = 10) were markedly higher in RA patients. LPAwas highly expressed in RA patients ( = 4) relative to that in OA patients ( = 4). Berberine remarkably inhibited the proliferation and the excessive production of IL-6 and TNF-in FLS-RA, whereas suppressing the expression of K-ras, c-Raf, and p-38/ERK-phosphorylation. In addition, berberine inhibited the LPA-induced p-38/ERK-phosphorylation through binding to LPA.Conclusions: LPA plays a certain role in promoting the proliferation and inflammation of FLS-RA. Berberine potentially modulates LPA function to suppress the proliferation and inflammation of FLS-RA through blocking the p38/ERK MAPK pathway mediated by LPA. These findings suggest that, berberine possesses potential lipid-regulating, antiarthritis, and synovial hyperplasia inhibition activities against RA, which may provide a promising therapeutic target for the clinical drug development for RA patients with dyslipidemia and high CVD risk.

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PMID: 

Med Sci Monit. 2019 Nov 10 ;25:8465-8471. Epub 2019 Nov 10. PMID: 31707402

Abstract Title: 

Anti-Proliferative Effect of Wogonin on Ovary Cancer Cells Involves Activation of Apoptosis and Cell Cycle Arrest.

Abstract: 

BACKGROUND The present study was designed to investigate the effect of wogonin on Caov-3 and A2780 ovary cancer cell proliferation and the mechanisms involved. MATERIAL AND METHODS Cell viability changes and apoptosis induction by wogonin were assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenytetrazolium bromide) assay and fluorescence microscopy. Morphological examination of cells was performed using transmission electron microscopy. RESULTS Wogonin exhibited inhibitory effect on Caov-3 and A2780 cancer cell proliferation in a concentration-based manner. Caov-3 and A2780 cell proliferation was reduced to 18% and 21%, respectively on treatment with 200μM concentration of wogonin. Treatment with wogonin significantly enhanced the percentage of A2780 cells showing apoptosis. The nuclear membrane degradation and condensation of chromatin material was evident in A2780 cells on treatment with wogonin. Treatment of A2780 cells with wogonin suppressedthe migration potential significantly. The proportion of A2780 cells in G1/G0 phase was markedly raised on exposure to wogonin for 48 hours. CONCLUSIONS In summary, this study demonstrated that wogonin acts as an ovary cancer cell proliferation inhibiting agent through activation of apoptosis. Wogonin, therefore, can be investigated further for the development of ovary cancer treatment.

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PMID: 

Colloids Surf B Biointerfaces. 2019 Nov 10:110635. Epub 2019 Nov 10. PMID: 31744760

Abstract Title: 

Cardio protective role of wogonin loaded nanoparticle against isoproterenol induced myocardial infarction by moderating oxidative stress and inflammation.

Abstract: 

Wogonin, one of the main active ingredients of Scutellaria radix, is a kind of flavonoid compound. In the present study, we report that wogonin nanoparticles (Wog np) protect Isoproterenol (ISO) induced Myocardial Infarction (MI) rats. Nanoparticles of sizes less than 200 nm with spherical shape were prepared using Polylactic-co-glycolic acid (PLGA) and Polyvinyl alcohol (PVA) respectively as polymer and stabilizer. Male Wistar rats were divided into 4 groups. Group 1 as a control group administered with physiological saline solution with 0.5 % carboxymethylcellulose (1 mL/day). Group 2 served as toxic group; rats received physiological saline solution with 0.5 % carboxymethylcellulose (1 mL/day) orally for 21 days Groups 3 and 4 received Wog np (25 and 50 mg/kg/day) orally for 21 days and on the 20th and 21 st days group 2, 3, and 4 were administered with ISO (85 mg/kg) through s.c. route at 24 h interval. pre-treatment with Wog np (25 and 50 mg/kg) could significantly reduce the cardiac infarct size, serum cardiac markers, lipid peroxidation product (MDA) and inflammatory markers as well as markedly upregulated the protein expression ofnuclear factor erythroid 2-related factor (Nrf2)and heme oxygenase-1 (HO-1) to confer its strong cardioprotective activity against ISO induced myocardial damage.

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PMID: 

Biofactors. 2019 Nov 12. Epub 2019 Nov 12. PMID: 31721330

Abstract Title: 

Wogonin ameliorate complete Freund's adjuvant induced rheumatoid arthritis via targeting NF-κB/MAPK signaling pathway.

Abstract: 

Rheumatoid arthritis (RA) is a chronic and accelerated autoimmune illness with proliferative and damaging synovitis, resulting in joint death and cartilage and bone erosion. This study focused on the potential therapeutic effect of wogonin on complete Freund's adjuvant (CFA) induced RA in rats and the underlying mechanisms. Arthritis was experimentally caused in rats by subcutaneously injecting 0.1 mL of CFA into the subplantar area of the left hind paw under moderate anesthesia on day zero. The regular oral doses of indomethacin/wogonin began on day zero and proceeded after injection to day 35. Wogonin reduced arthritic score considerably, enhanced body weight, and reduced paw thickness. Wogonin also boosted red blood cell considerably along with hemoglobin and reduced white blood cell count and erythrocyte sedimentation rate. Wogonin substantially improved an altered level of oxidative stress markers, antioxidant proteins, and inflammatory cytokines in a dose-dependent way. Wogonin inhibited p38 phosphorylation triggered by CFA and p65 nuclear translocation.

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PMID: 

J Med Food. 2019 Nov 8. Epub 2019 Nov 8. PMID: 31702423

Abstract Title: 

Anti-Inflammatory Effect of CrudeExtract on 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis Model in Rat and the Bioaccessibility of its Carotenoid Content.

Abstract: 

known as bitter melon (BM), is a plant that belongs to the family Cucurbitaceae. Aims of this study are to investigate the anti-inflammatory effect of crude BM extract on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis model in rat. It was also aimed to determine the content and bioaccessibility of carotenoids of BM. BM was purchased from local markets in Izmir, Turkey. Fruits of BM were lyophilized, powdered, and used in the experiment. Carotenoids were determined by high-performance liquid chromatography. To determine the bioaccessibility of-carotene,digestion was performed. Wistar albino rats were divided into four groups: group A (BM+TNBS), group B (BM), group C (TNBS), and group D (control). BM solution was given 300 mg/(kg·day) for 6 weeks orally. Colitis was induced by 0.25 mL of a solution containing 100 mg/kg 5% (w/v) TNBS in 50% ethanol (w/v) intrarectally after 6 weeks. After sacrification, macroscopic and microscopic evaluations were performed. Myeloperoxidase, cytokines levels (interleukin-17 [IL-17], TNF-alpha, and interleukin-10 [IL-10]) were measured in serum and colonic samples by ELISA test. Institutional Animal Ethics Committee approval was obtained. Total carotenoid content of BM was determined 11.7 mg/g dry weight as-carotene equivalents. Bioaccessibility of total carotenoids was determined as 2.1% withdigestion. Pretreatment with crude BM extract significantly reduced weight loss, macroscopic, and microscopic colitis damages in colonic samples ( = .000), ( = .015), and ( = .026), respectively. Serum anti-inflammatory cytokine IL-10 increased significantly in both treatment groups ( = .000). BM is a rich source of carotenoids, but the bioaccessibility of its carotenoids is low. This study displays that BM has protective anti-inflammatory effects on TNBS-induced colitis.

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PMID: 

Food Sci Nutr. 2019 Nov ;7(11):3443-3451. Epub 2019 Sep 10. PMID: 31762997

Abstract Title: 

Piperine as a neuroprotective functional component in rats with cerebral ischemic injury.

Abstract: 

Long pepper (L.) and black pepper (L.) plants are commonly used as spices around the world and have also been postulated to have medicinal effects. Piperine, as the major alkaloid ofand, has gained wide attention of the medical community and culinary enthusiasts. This study seeks to determine the effects of piperine on neuronal apoptosis in peri-infarcted cerebral cortices of rats with permanent middle cerebral artery occlusion (pMCAO) injury. Evaluation of the different behavioral components was conducted after pMCAO. 2, 3, 5-Triphenyltetrazolium chloride (TTC) was used to evaluate the area of cortical ischemia. Gross histopathological changes, as well as microscopic neuronal changes, were observed in brain tissue samples. The protein expression of Caspase-3, Caspase-9, Bax, Bcl-2, and Cytochrome C (Cyt-c) was analyzed using western blotting. The findings reveal that rats that received piperine treatment show markedly decreased neurological deficit, less ischemia-induced cellular damage, as well as smaller areas of cerebral infarction, with less severe macro and microcellular cerebral structural changes. Western blotting analysis reveals that piperine administration inhibits Bax, while enhancing Bcl-2 expression. The protein expression of Caspase-3, Caspase-9, and Cyt-c was also found to be significantly inhibited. We conclude that piperine may provide several beneficial neuroprotective effects that warrant further investigation.