PMID: 

Molecules. 2017 Jun 20 ;22(6). Epub 2017 Jun 20. PMID: 28632185

Abstract Title: 

The Effects of Selected Sesquiterpenes from Myrica rubra Essential Oil on the Efficacy of Doxorubicin in Sensitive and Resistant Cancer Cell Lines.

Abstract: 

β-caryophyllene oxide (CAO), α-humulene (HUM), trans-nerolidol (NER) and valencene (VAL) are constituents of the essential oil of(MEO), which has significant antiproliferative effect in various cancer cell lines. In the present study, we compared the antiproliferative effect of these sesquiterpenes alone and in combination with the cytostatic drug doxorubicin (DOX) in cancer cell lines with different sensitivity to DOX. Two ovarian cancer cell lines (sensitive A2780 and partly resistant SKOV3) and two lymphoblast cancer cell lines (sensitive CCRF/CEM and completely resistant CEM/ADR) were used. The observed effects varied among sesquiterpenes and also differed in individual cell lines, with only VAL being effective in all the cell lines. A strong synergism of DOX with NER was found in the A2780 cells, while DOX acted synergistically with HUM and CAO in the SKOV3 cells. In the CCRF/CEM cells, a synergism of DOX with CAO and NER was observed. In resistant CEM/ADR cells, sesquiterpenes did not increase DOX efficacy, although they significantly increased accumulation of DOX (up to 10-times) and rhodamine-123 (substrate of efflux transporter ABCB1) within cancer cells. In conclusion, the tested sesquiterpenes were able to improve DOX efficacy in the sensitive and partly resistant cancer cells, but not in cells completely resistant to DOX.

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PMID: 

Molecules. 2017 Jul 24 ;22(7). Epub 2017 Jul 24. PMID: 28737731

Abstract Title: 

Study on Chemical Profile and Neuroprotective Activity of Myrica rubra Leaf Extract.

Abstract: 

The chemical profile of(a native species in China) leaf extract was investigated by UPLC-PDA-HRMS, and the neuroprotective activity of two characteristic constituents, myricanol and myricetrin, was evaluated with N2a cells using H₂O₂-inducedoxidative challenge through a series of methods, e.g., MTT assay, ROS assay and [Ca]i assay. Among the 188 constituents detected in the extract ofleaf, 116 were identified definitely or tentatively by the comprehensive utilization of precise molecular weight and abundant multistage fragmentation information obtained by quadrupole orbitrap mass spectrometry. In addition, 14 potential new compounds were reported for the first time. This work established an example for the research of microconstituents in a complex analyte and revealed that suppression of H₂O₂-induced cytotoxicity in N2a cells was achieved by the pretreatment with myricanol. The evidence suggested myricanol may potentially serve as a remedy for prevention and therapy of neurodegenerative diseases induced by oxidative stress.

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PMID: 

Food Funct. 2018 Jan 24 ;9(1):525-533. PMID: 29256569

Abstract Title: 

Dietary compound proanthocyanidins from Chinese bayberry (Myrica rubra Sieb. et Zucc.) leaves attenuate chemotherapy-resistant ovarian cancer stem cell traits via targeting the Wnt/β-catenin signaling pathway and inducing G1 cell cycle arrest.

Abstract: 

Cancer stem cells (CSCs) represent a small population of cancer cells characterized by self-renewal ability, tumorigenesis and drug resistance. Ovarian cancer is one of the leading causes of death related to the female reproductive system in Western countries and has been evaluated as a type of CSC-related cancer in recent years. Natural products have attracted great attention in cancer treatment in recent years due to drug resistance and a high relapse rate of ovarian cancer. Chinese bayberry leaf proanthocyanidins (BLPs) contain epigallocatechin-3-O-gallate as their terminal and major extension units, which is quite unusual in the plant kingdom. BLPs showed strong antioxidant and antiproliferative abilities in previous studies. In the present study, chemotherapy-resistant OVCAR-3 spheroid (SP) cells were obtained by sphere culturing and exhibited CSC-like properties by showing a higher ALDHpopulation and higher expression of stemness-related proteins. BLPs exhibited inhibitory effects on the growth and CSC characteristics of OVCAR-3 SP cells by showing decreased cell viability, sphere and colony formation ability, ALDHpopulation and expression of stemness-related proteins. BLPs also targeted the Wnt/β-catenin pathway by reducing the expression of β-catenin, cyclin D1 and c-Myc and thus inhibited the self-renewal ability of OVCAR-3 SP cells. Furthermore, BLPs also induced G1 cell cycle arrest in OVCAR-3 SP cells. Taken together, these findings suggested that BLPs may be an important agent in the development of therapeutics for ovarian cancer patients.

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PMID: 

J Funct Foods. 2018 Jan ;40:573-581. Epub 2017 Dec 22. PMID: 29576805

Abstract Title: 

Dietary Compound Proanthocyanidins from Chinese bayberry (Sieb. et Zucc.) leaves inhibit angiogenesis and regulate cell cycle of cisplatin-resistant ovarian cancer cells via targeting Akt pathway.

Abstract: 

Ovarian cancer is the leading cause of death from gynecological malignancy and natural products have drawn great attention for cancer treatment. Chinese bayberry leaves proanthocyanidin (BLPs) with epigallocatechin-3-O-gallate (EGCG) as its terminal and major extension units is unusual in the plant kingdom. In the present study, BLPs showed strong growth inhibitory effects on cisplatin-resistant A2780/CP70 cells by inhibiting angiogenesis and inducing G1 cell cycle arrest. BLPs reduced the tube formation in HUVECs and attenuated the wound healing ability in A2780/CP70 cells. BLPs further reduced the level of ROS and targeted Akt/mTOR/p70S6K/4E-BP-1 pathway to reduce the expression of HIF-1α and VEGF, and thus inhibited angiogenesis. Furthermore, BLPs induced G1 cell cycle arrest by reducing the expressions of c-Myc, cyclin D1 and CDK4, which was also in accordance with the flow cytometry analysis. Overall, these results indicated that BLPs could be a valuable resource of natural compounds for cancer treatment.

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PMID: 

Molecules. 2018 Jul 20 ;23(7). Epub 2018 Jul 20. PMID: 30036952

Abstract Title: 

Protection of Anthocyanin fromagainst Cerebral Ischemia-Reperfusion Injury via Modulation of the TLR4/NF-κB and NLRP3 Pathways.

Abstract: 

(MR) is rich in anthocyanins, and it has good anti-cancer, anti-aging, antioxidant, and antiviral effects. The proportion of disability and death caused by ischemic stroke gradually increased, becoming a major disease that is harmful to human health. However, research on effects of anthocyanin from MR on cerebral ischemia-reperfusion (I/R) injury is rare. In this study, we prepared eight purified anthocyanin extracts (PAEs) from different types of MR, and examined the amounts of total anthocyanin (TA) and cyanidin-3–glucoside (C-3-G). After one week of PAE treatment, the cerebral infarction volume, disease damage, and contents of nitric oxide and malondialdehyde were reduced, while the level of superoxide dismutase was increased in I/R mice. Altogether, our results show that Boqi¹ MR contained the most TA (22.07%) and C-3-G (21.28%), and that PAE isolated from Dongkui MR can protect the brain from I/R injury in mice, with the mechanism possibly related to the Toll-like receptor 4 (TLR4)/ nuclear factor-κB (NF-κB) and NOD-like receptor pyrin domain-containing 3 protein (NLRP3) pathways.

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PMID: 

Food Chem. 2019 Jan 1 ;270:305-314. Epub 2018 Jul 18. PMID: 30174051

Abstract Title: 

Myricanol mitigates lipid accumulation in 3T3-L1 adipocytes and high fat diet-fed zebrafish via activating AMP-activated protein kinase.

Abstract: 

Myricanol is a diarylheptanoid isolated from Chinese bayberry. Through virtual docking strategy, myricanol was discovered as an AMP-activated protein kinase (AMPK) activator among a series of structural analogs, with high affinity for theγ subunit of AMPK. Myricanol was also evaluated for regulatory effects on lipid accumulation and insulin sensitivity in 3T3-L1 adipocytes and adiposity in high-fat diet-fed zebrafish. Myricanol suppressed lipid accumulation in 3T3-L1 cells in the initial stage (days 0-2) by suppressing adipogenesisand in the terminal stage (days 4-7) by inducing lipolysis and lipid combustion through activating AMPK. Moreover, myricanol enhanced insulin-stimulated glucose uptake by activating the insulin signaling pathway. In high-fat diet-fed zebrafish, myricanol inhibited lipid accumulation by suppressingadipogenic factors including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα). In summary, the results indicate that myricanol could be a potential therapeutic agent against obesity by activating the AMPK signaling pathway.

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PMID: 

Int J Mol Med. 2019 May ;43(5):2133-2143. Epub 2019 Mar 12. PMID: 30864694

Abstract Title: 

Protective effects of Myrica rubra flavonoids against hypoxia/reoxygenation-induced cardiomyocyte injury via the regulation of the PI3K/Akt/GSK3β pathway.

Abstract: 

Myrica rubra is well known for its delicious taste and high nutritional value. The present study investigated the potential protective effects and mechanisms of M. rubra flavonoids (MRF) extract on isoproterenol (ISO)‑induced myocardial injury in rats and hypoxia/reoxygenation (H/R) injury in H9c2 cardiomyocytes. An in vivo study revealed that MRF decreased serum cardiac enzyme levels, ameliorated pathological heart alterations and increased the antioxidant potential. The in vitro investigation demonstrated that MRF inhibited cell death, reactive oxygen species (ROS) accumulation, mitochondrial membrane depolarization, apoptosis rate and caspase‑3 activation and enhanced the Bcl‑2/Bax ratio during H/R injury. These effects were accompanied by the phosphorylation of protein kinase B (Akt) and glycogensynthase kinase (GSK)‑3β. Further mechanism studies demonstrated that LY294002, a specific inhibitor of phosphoinositide 3‑kinase (PI3K), abolished the MRF‑mediated cardioprotection against H/R‑induced apoptosis and ROS overproduction. Collectively, these results suggested that MRF exertscardioprotective effects by attenuating oxidative damage and cardiomyocyte apoptosis most likely via a PI3K/Akt/GSK3β‑dependent mechanism.

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PMID: 

Nutrients. 2020 Jan 2 ;12(1). Epub 2020 Jan 2. PMID: 31906505

Abstract Title: 

Health-Promoting Properties of Proanthocyanidins for Intestinal Dysfunction.

Abstract: 

The intestinal barrier is constantly exposed to potentially harmful environmental factors, including food components and bacterial endotoxins. When intestinal barrier function and immune homeostasis are compromised (intestinal dysfunction), inflammatory conditions may develop and impact overall health. Evidence from experimental animal and cell culture studies suggests that exposure of intestinal mucosa to proanthocyanidin (PAC)-rich plant products, such as grape seeds, may contribute to maintaining the barrier function and to ameliorating the pathological inflammation present in diet-induced obesity and inflammatory bowel disease. In this review, we aim to update the current knowledge on the bioactivity of PACs in experimental models of intestinal dysfunction and in humans, and to provide insights into the underlying biochemical and molecular mechanisms.

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PMID: 

World Neurosurg. 2020 Jan 14. Epub 2020 Jan 14. PMID: 31953094

Abstract Title: 

Allicin inhibits proliferation and promotes apoptosis of human epidural scar fibroblasts.

Abstract: 

BACKGROUND: Allicin can suppress liver and cardiac fibrosis, thus we hypothesize that it may prevent scar tissue from extensive epidural fibrosis after laminectomy.METHODS: Human epidural scar fibroblasts were isolated from surgical specimen, and treated by allicin at a gradient of concentrations. The morphology, viability, migration rate, cell cycle and apoptosis rate were measured by fluorescence microscope, CCK-8 assay, scratch assay and flow cytometry. Western Blot was used to measure the expression level of proliferation-related proteins.RESULTS: After treated by allicin, cell viability (p=0.042*) and migration rate (p=0.010* in scratch assay, and p=0.025* in Transwell assay) decreased significantly in a dose-dependent manner. The percentage of G1 phase cells significantly decreased (p=0.017*), while that of S phase (p=0.096*) and G2 (p=0.038*) phase cells significantly increased in a dose-dependent manner. Similarly, the percentage of apoptotic cells increased significantly in a dose-dependent manner (p=0.036*). Comparing with control group, the expression level of PCNA protein (p=0.081) and Bcl-2 protein (p=0.029*) significantly decreased, while the Bax protein level significantly increased (p=0.017*).CONCLUSION: Allicin can suppress human epidural scar fibroblasts migration, induce cell apoptosis, and block cell proliferation at S phase and G2 phase.

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PMID: 

Nutrients. 2020 Jan 10 ;12(1). Epub 2020 Jan 10. PMID: 31936778

Abstract Title: 

Association of Total Flavonoid Intake with Hypo-HDL-Cholesterolemia among Korean Adults: Effect Modification by Polyunsaturated Fatty Acid Intake.

Abstract: 

The aim of this study was to examine the independent association between flavonoid intake and hypo-high-density lipoprotein (HDL)-cholesterolemia and the potential modifying effect of polyunsaturated fatty acid (PUFA) intake on this association among Korean adults. This cross-sectional analysis used data from 10,326 subjects who participated in the 2013-2016 Korean National Health and Nutrition Examination Survey. Multiple logistic regression analyses were used to assess the associations of flavonoid and PUFA intakes with hypo-HDL-cholesterolemia prevalence. Proanthocyanidins intake showed an inverse relationship with hypo-HDL-cholesterolemia only in men (Tertile (T) 3 vs. T1: odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.59-0.92,-trend = 0.0330). Total flavonoid and PUFA intakes were not associated with hypo-HDL-cholesterolemia in both men and women. However, when stratified by PUFA intake, there was an inverse relationship between total flavonoid intake and hypo-HDL-cholesterolemia prevalence in men with a high-3 PUFA intake (total flavonoid intakes T3 vs. T1: OR = 0.59, 95% CI = 0.42-0.82,-trend = 0.0004) or a low-6/-3 PUFA intake ratio (T3 vs. T1: OR = 0.67, 95% CI = 0.48-0.93,-trend = 0.0053), but not in those with a low-3 PUFA intake (-interaction = 0.0038) or a high-6/-3 PUFA intake ratio (-interaction = 0.1772). In women, no association was found between total flavonoid intake and hypo-HDL-cholesterolemia, regardless of PUFA intake. These results imply that the intake of proanthocyanidins might have beneficial effects on the HDL-cholesterol level in Korean men. In addition, n-3 PUFA intake might modify the association of total flavonoid intake with the hypo-HDL-cholesterolemia among Korean men.

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