PMID: 

Oxid Med Cell Longev. 2019 ;2019:4098674. Epub 2019 Nov 14. PMID: 31814875

Abstract Title: 

Zerumbone Exhibits Antiphotoaging and Dermatoprotective Properties in Ultraviolet A-Irradiated Human Skin Fibroblast Cells via the Activation of Nrf2/ARE Defensive Pathway.

Abstract: 

Ultraviolet A (UVA) irradiation (320-400 nm range) triggers deleterious consequences in skin cell microenvironment leading to skin damage, photoaging (premature skin aging), and cancer. The accumulation of intracellular reactive oxygen species (ROS) plays a key role in this effect. With rapid progress in cosmetic health and quality of life, use of safe and highly effective phytochemicals has become a need of the hour. Zerumbone (ZER), a natural sesquiterpene, fromrhizomes is well-known for its beneficial effects. We investigated the antiphotoaging and dermatoprotective efficacies of ZER (2-8 M) against UVA irradiation (3 J/cm) and elucidated the underlying molecular mechanisms in human skin fibroblast (HSF) cells. ZER treatment prior to low dose of UVA exposure increased cell viability. UVA-induced ROS generation was remarkably suppressed by ZER with parallel inhibition of MMP-1 activation and collagen III degradation. This was due to the inhibition of AP-1 (c-Fos and c-Jun) translocation. Furthermore, ZER alleviated UVA-induced SA–galactosidase activity. Dose- or time-dependent increase of antioxidant genes, HO-1 and-GCLC by ZER, was associated with increased expression and nuclear accumulation of Nrf2 as well as decreased cytosolic Keap-1 expressions. Altered luciferase activity of ARE could explain the significance of Nrf2/ARE pathway underlying the dermatoprotective properties of ZER. Pharmacological inhibition of various signaling pathways suppressed nuclear Nrf2 activation in HSF cells confirming that Nrf2 translocation was mediated by ERK, JNK, PI3K/AKT, PKC, AMPK, casein kinase II, and ROS signaling pathways. Moreover, increased basal ROS levels and Nrf2 translocation seem crucial in ZER-mediated Nrf2/ARE signaling pathway. This was also evidenced from Nrf2 knocked-out studies in which ZER was not able to suppress the UVA-induced ROS generation in the absence of Nrf2. This study concluded that in the treatment of UVA-induced premature skin aging, ZER may consider as a desirable food supplement for skin protection and/or preparation of skin care products.

read more

PMID: 

Molecules. 2017 Nov 3 ;22(11). Epub 2017 Nov 3. PMID: 29099789

Abstract Title: 

Atractylenolide II Inhibits Proliferation, Motility and Induces Apoptosis in Human Gastric Carcinoma Cell Lines HGC-27 and AGS.

Abstract: 

Atractylenolide II (AT-II) exhibits several biological and pharmacological functions, especially anti-cancer activity as the major sesquiterpene lactones isolated from(also namedin Chinese). However, the effects and mechanisms of AT-II on human gastric cancer remain unclear. Cell Counting Kit-8 (CCK-8) assay, morphological changes, flow cytometry, wound healing assay and Western blot analysis were used to investigate the effects of AT-II on cell proliferation, apoptosis and motility of human gastric carcinoma cell lines HGC-27 and AGS. Our results indicated that AT-II could significantly inhibit cell proliferation, motility and induce apoptosis in a dose and time-dependent manner. Western blot analysis showed that the expression level of Bax was upregulated and the expression levels of B-cell lymphoma-2 (Bcl-2), phosphorylated-protein kinase B (p-Akt) and phosphorylated-ERK (p-ERK) were downregulated compared to control group. In conclusion, the findings suggested that AT-II exerted significant anti-tumor effects on gastric carcinoma cells by modulating Akt/ERK signaling pathway, which might shed light on therapy of gastric carcinoma.

read more

PMID: 

Int Immunopharmacol. 2018 Jan ;54:103-111. Epub 2017 Nov 6. PMID: 29121532

Abstract Title: 

Paeoniflorin inhibits VSMCs proliferation and migration by arresting cell cycle and activating HO-1 through MAPKs and NF-κB pathway.

Abstract: 

The proliferation, migration and inflammation of vascular smooth muscle cells (VSMCs) contributes to the pathogenesis and progression of atherosclerosis. Paeoniflorin (PF) as active compound in the Rhizoma Atractylodes macrocephala has been used for various diseases like cancer, splenic asthenia, anaphylaxis and anorexia. This study aimed to explore whether and how PF regulated the inflammation, proliferation and migration of VSMCs under ox-LDL stimulation. Here, we found that PF dose-dependently inhibited ox-LDL-induced VSMCs proliferation and migration, and decreased inflammatory cytokines and chemokine overexpression. Mechanistically, PF prevented p38, ERK1/2 and NF-κB phosphorylation, and arrested cell cycle in S phase. Meanwhile, PF regulated the HO-1 and PCNA expression. Furthermore, PF blocked the foam cell formation in macrophages induced by ox-LDL. These results indicate that PF antagonizes the ox-LDL-induced VSMCs proliferation, migration and inflammation through activation of HO-1, cell cycle arrest and then suppression of p38, ERK1/2/MAPK and NF-κB signaling pathways.

read more

PMID: 

Mol Med Rep. 2018 Feb ;17(2):2607-2613. Epub 2017 Nov 21. PMID: 29207045

Abstract Title: 

Effect of Atractylodes macrocephala rhizoma on isoproterenol‑induced ventricular remodeling in rats.

Abstract: 

Myocardial infarction (MI) is the primary cause of ventricular remodeling (VR). The aim of the present study was to determine the effect of Atractylodis macrocephalae rhizoma (AMR) on VR induced by isoproterenol (ISO) in rats. Male Sprague Dawley rats were randomly divided into the normal control, ISO‑induced and AMR groups. Rats in the ISO‑induced and AMR groups were subcutaneously injected with 85 mg/kg/day ISO for two consecutive days. Compared with the ISO‑induced group, AMR normalized the levels of hemodynamic parameters, markedly attenuated myocardial pathological damage, decreased the level of N‑terminal prohormone of brain natriuretic peptide, and inhibited cardiac hypertrophy and myocardial fibrosis. In addition, AMR inhibited oxidative stress and activation of the rennin‑angiotensin‑aldosterone system (RAAS) when compared with the ISO‑induced group. The results of the present study suggest that AMR may reverse VR via its antioxidative effect and inhibition of RAAS activation.

read more

PMID: 

Chin J Nat Med. 2018 Sep ;16(9):674-682. PMID: 30269844

Abstract Title: 

Polysaccharide extracts of Astragalus membranaceus and Atractylodes macrocephala promote intestinal epithelial cell migration by activating the polyamine-mediated Kchannel.

Abstract: 

Astragalus membranaceus (Radix Astragali, RA) and Atractylodes macrocephala (Rhizoma Atractylodis Macrocephalae, RAM) are often used to treat gastrointestinal diseases. In the present study, we determined the effects of polysaccharides extracts from these two herbs on IEC-6 cell migration and explored the potential underlying mechanisms. A migration model with IEC-6 cells was induced using a single-edged razor blade along the diameter of cell layers in six-well polystyrene plates. The cells were grown in control media or media containing spermidine (5μmol·L, SPD), alpha-difluoromethylornithine (2.5 mmol·L, DFMO), 4-Aminopyridine (40μmol·L, 4-AP), the polysaccharide extracts of RA or RAM (50, 100, or 200 mg·L), DFMO plus SPD, or DFMO plus polysaccharide extracts of RA or RAM for 12 or 24 h. Next, cytosolic free Ca([Ca]) was measured using laser confocal microscopy, and cellular polyamine content was quantified with HPLC. Kv1.1 mRNA expression was assessed using RT-qPCR and Kv1.1 and RhoA protein expressions were measured with Western blotting analysis. A cell migration assay was carried out using Image-Pro Plus software. In addition, GC-MS was introduced to analyze the monosaccharide composition of both polysaccharide extracts. The resutls showed that treatment with polysaccharide extracts of RA or RAM significantly increased cellular polyamine content, elevated [Ca]and accelerated migration of IEC-6 cells, compared with the controls (P

read more

PMID: 

Carbohydr Polym. 2019 Dec 15 ;226:115136. Epub 2019 Sep 3. PMID: 31582084

Abstract Title: 

An alcohol-soluble polysaccharide from Atractylodes macrocephala Koidz induces apoptosis of Eca-109 cells.

Abstract: 

In this study, polysaccharides from Atractylodes macrocephala Koidz (APA) which were soluble in alcohol were prepared, purified, analyzed the structure and investigated the antitumor activity in vitro cell experiment. Results of high-performance gel permeation chromatography (HPGPC), fourier-transform infrared spectroscopy (FT-IR), and gas chromatography (GC) showed that APA was a 2.1KDa neutral hetero polysaccharide composed of arabinose and glucose (molar ratio, 1.00:4.57) with pyranose rings andα-type and β-type glycosidic linkages. Results by MTT experiments showed that the proliferation inhibition was 74.63% in Eca109 cells treated with 2 mg/mL dose of APA. Annexin V/PI assay, Hoechst 33,258 staining, cell cycle distribution, rhodamine 123 dye assay and western blot assay clarified that APA could accelerate the apoptosis of Eca109 cells by mitochondrial pathway and stocked cells at S phase. These data indicated that APA is a promising potential candidate for therapeutic treatment of esophageal cancer.

read more

PMID: 

Onco Targets Ther. 2019 ;12:7111-7121. Epub 2019 Sep 4. PMID: 31564895

Abstract Title: 

polysaccharides regulate the innate immunity of colorectal cancer cells by modulating the TLR4 signaling pathway.

Abstract: 

Background: It has been well-recognized that the polysaccharides from(PAM) are immune system enhancers, which can facilitate the proliferation of lymphocytes and stimulate immune cells. Nevertheless, the antitumor effects of PAM and their molecular mechanisms remain unclear.Aim: Our research aimed to evaluate the anti-cancer effects of PAM on colorectal cancer (CRC).Methods: We tested the effects of PAM on the growth and proliferation of CRC cells and macrophages by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The pro-inflammatory cytokines expression and secretion was analyzed by real-time RT-PCR and ELISA assay. We also used MC38 cells xenograft model to test the anti-cancer effects of PAM in vivo.Results: We found that although PAM treatment did not significantly affect the growth of CRC cells or enhance the proliferation of bone marrow-derived macrophages (BMDMs), it could enhance the phagocytosis of BMDMs by CRC cells. Biochemical tests and immunoblotting assays revealed that exposing BMDMs to PAM promoted the production of interleukin-6 (IL-6), interferonλ (IFN λ), tumor necrosis factor α (TNF-α), and nitric oxide (NO) through the MyD88/TLR4-dependent signaling pathway. One noteworthy observation is that PAM treatment could significantly prevent tumorigenesis of MC38 cells in C57BL/6J mice and increase the survival duration of mice with tumors,without influence on the weight of those mice. However, the anti-cancer effects of PAM were compromised in TLR4 KO mice, further suggesting that TLR4 signaling plays a vital role in the anti-cancer effects of PAM.Conclusion: Therefore, PAM may prove to be a potential candidate in cancer immunotherapy.

read more

PMID: 

Nan Fang Yi Ke Da Xue Xue Bao. 2019 Oct 30 ;39(10):1180-1185. PMID: 31801717

Abstract Title: 

[Effect of Atractylodes macrocephala polysaccharide on proliferation and invasion of hepatocellular carcinoma cells].

Abstract: 

OBJECTIVE: To investigate the inhibitory effect of polysaccharide of Atractylodes macrocephala (PAM) on the proliferation and invasion of hepatocellular carcinoma cells and the underlying mechanism.METHODS: Hepatocellular carcinoma HepG2 cells were treated with different concentrations of PAM, and their proliferation and invasive ability were examined using CCK-8 assay and Transwell assay. Immunofluorescence assay was performed to detect the expression level ofβ-catenin, and real-time PCR and Western blotting were used to detect the mRNA and protein expressions of AKT, GSK-3β and MMP-2 in the cells. The changes in the proliferation, invasiveness and the expressions of pGSK-3β and MMP2 were examined in the cells following treatment with LiCl/PAM/LiCl plus PAM.RESULTS: PAM treatment significantly reduced the cell viability, the number of migration cells, and the expression levels ofβ-catenin and MMP-2 (

read more

PMID: 

Molecules. 2020 Jan 7 ;25(2). Epub 2020 Jan 7. PMID: 31936160

Abstract Title: 

Caffeic Acid Attenuates Multi-Drug Resistance in Cancer Cells by Inhibiting Efflux Function of Human P-glycoprotein.

Abstract: 

Multidrug resistance (MDR) is a complicated ever-changing problem in cancer treatment, and P-glycoprotein (P-gp), a drug efflux pump, is regarded as the major cause. In the way of developing P-gp inhibitors, natural products such as phenolic acids have gotten a lot of attention recently. The aim of the present study was to investigate the modulating effects and mechanisms of caffeic acid on human P-gp, as well as the attenuating ability on cancer MDR. Calcein-AM, rhodamine123, and doxorubicin were used to analyze the interaction between caffeic acid and P-gp, and the ATPase activity of P-gp was evaluated as well. Resistance reversing effects were revealed by SRB and cell cycle assay. The results indicated that caffeic acid uncompetitively inhibited rhodamine123 efflux and competitively inhibited doxorubicin efflux. In terms of P-gp ATPase activity, caffeic acid exhibited stimulation in both basal and verapamil-stimulated activity. The combination of chemo drugs and caffeic acid resulted in decreased ICin/Flp-In-293 and KB/VIN, indicating that the resistance was reversed. Results of molecular docking suggested that caffeic acid bound to P-gp through GLU74 and TRY117 residues. The present study demonstrated that caffeic acid is a promising candidate for P-gp inhibition and cancer MDR attenuation.

read more

PMID: 

J Med Case Rep. 2020 Jan 29 ;14(1):23. Epub 2020 Jan 29. PMID: 31992329

Abstract Title: 

Acute kidney injury and hepatitis associated with energy drink consumption: a case report.

Abstract: 

INTRODUCTION: In the USA, energy drinks are commonly consumed among adults. The side effects of these drinks are not well studied but consumers have reported multiple adverse events to the US Food and Drug Administration including acute kidney injury and acute hepatitis.CASE PRESENTATION: A 62-year-old white woman presented with progressive weakness, fatigue, confusion, and delirium secondary to acute kidney injury and acute hepatitis associated with excessive energy drink use. Clinical improvement occurred with supportive care and discontinuation of energy drinks, with resolution of acute kidney injury and progressive improvement of liver function. The defined mechanism of injury is unknown but thought due to energy drink ingredients.CONCLUSION: Multiple cases of energy drink-induced acute kidney injury or acute hepatitis are reported in the literature but this case is the first to report them simultaneously. Ingredients and presumed doses to cause these events are outlined in this case report.

read more