Network pharmacology-based approach to investigate the molecular targets of essential oil obtained from lavender for treating breast cancer.

Lavender essential oil (LEO) is known for its medicinal use in the development of pharmaceuticals. Further investigations were demonstrated that LEO has many biological properties including apoptosis. However, The anti-breast cancer activity and mechanism of LEO are still unclear. we aim to elucidate the elusive anti-breast cancer activity and mechanism of LEO by unveiling the intricate molecular targets that it engages with, thereby priming it for effective therapeutic intervention against breast carcinoma. In this paper, we extracted LEO from lavender and analyzed it's chemical constituents by using hydro-distillation and gas chromatography-mass spectrometry (GS-MS/MS) method, respectively. The active components against breast cancer and it's molecular targets were selected and biological process, molecular function, cellular component and involving pathways were evaluated via network pharmacology approach. Cell viability, apoptosis and cell cycle assay were used to evaluate anti-breast cancer effect of LEO. Employing the western blotting method to validate target protein expression following LEO treatment in vitro. We found the 21 effective components and 213 drug-disease common targets of LEO. Amoung them, 7 active components and 19 targets were identified as potential therapeutic targets. Gene ontology results revealed that the drug-disease common targets of LEO were mainly distributed in membrane region, involved in peptide-tyrosine phosphorylation, and primarily associated with protein tyrosine kinase. We also found that drug-disease common targets might contribute to the regulation of PI3K-AKT signaling pathway by using KEGG pathway analysis. Besides, our study demonstrated reduced cell viability, induced apoptosis in MCF-7 and MDA-MB-231 treated with LEO while cell cycle arrest was not altered. The AKT1 expression down-regulated while PIK3CA expression was increased in both cell lines. Our findings indicate that LEO has the ability to induce apoptosis by modulating the expression of PI3K-AKT signaling pathway in these cell lines.

Corrigendum to "4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis".

[This corrects the article DOI: 10.1155/2016/4592346.].

4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis.

Endoplasmic reticulum (ER) stress is a particular process with an imbalance of homeostasis, which plays an important role in pancreatitis, but little is known about how ER stress is implicated in severe acute pancreatitis (SAP) induced pancreatic beta-cell injury. To investigate the effect of 4-phenylbutyric acid (4-PBA) on the beta-cell injury following SAP and the underlying mechanism, twenty-four Sprague-Dawley rats were randomly divided into sham-operation (SO) group, SAP model group, and 4-PBA treatment group. SAP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. 4-PBA or normal saline was injected intraperitoneally for 3 days in respective group before successful modeling. Results showed that 4-PBA attenuated the following: (1) pancreas and islet pathological injuries, (2) serum TNF-α and IL-1ß, (3) serum insulin and glucose, (4) beta-cell ultrastructural changes, (5) ER stress markers (BiP, ORP150, and CHOP), Caspase-3, and insulin expression in islet. These results suggested that 4-PBA mitigates pancreatic beta-cell injury and endocrine disorder in SAP, presumably because of its role in inhibiting excessive endoplasmic reticulum stress. This may serve as a new therapeutic target for reducing pancreatic beta-cell injury and endocrine disorder in SAP upon 4-PBA treatment.

Severity of pancreatitis­associated intestinal mucosal barrier injury is reduced following treatment with the NADPH oxidase inhibitor apocynin.

Recent studies demonstrated that apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) inhibitor, significantly decreased acute pancreatitis­associated inflammatory and oxidative stress parameters. In addition, apocynin was able to reduce ischemic reperfusion injury­associated damage; however, the exact effects of apocynin on acute pancreatitis­associated intestinal mucosal injury have yet to be fully clarified. The present study aimed to investigate the protective effects of apocynin on intestinal mucosal injury in a rat model of severe acute pancreatitis (SAP). A total of 60 male Sprague Dawley rats were randomly divided into four groups (n=15/group): Sham operation group (SO), SAP group, apocynin treatment (APO) group and drug control (APO­CON) group. SAP was induced by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. Apocynin was administered 30 min prior to SAP induction in the APO group. All rats were sacrificed 12 h after SAP induction. Intestinal integrity was assessed by measuring diamine oxidase (DAO) levels. Morphological alterations to intestinal tissue were determined under light and transmission electron microscopy. NOX2, p38 mitogen­activated protein kinases (MAPK) and nuclear factor (NF)­κB expression levels were detected in the intestine by immunohistochemical staining. Oxidative stress was detected by measuring intestinal malondialdehyde (MDA) and superoxide dismutase content. In addition, blood inflammatory cytokines, and amylase (AMY) and lipase (LIP) levels were evaluated. The results demonstrated that apocynin attenuated the following: i) Serum AMY, LIP and DAO levels; ii) pancreatic and intestinal pathological injury; iii) intestinal MDA content; iv) intestinal ultrastructural alterations; v) serum interleukin (IL)­1ß, IL­6 and tumor necrosis factor (TNF)­α levels; and vi) NOX2, p38 MAPK and NF­κB expression in intestinal tissues. These results suggested that apocynin may attenuate intestinal barrier dysfunction in sodium taurocholate­induced SAP, presumably via its role in the prevention of reactive oxygen species generation and inhibition of p38 MAPK and NF­κB pathway activation. These findings provide novel insight suggesting that pharmacological inhibition of NOX by apocynin may be considered a novel therapeutic method for the treatment of intestinal injury in SAP.

NADPH Oxidase Inhibitor Apocynin Attenuates PCB153-Induced Thyroid Injury in Rats.

PCBs, widespread endocrine disruptors, cause the disturbance of thyroid hormone (TH) homeostasis in humans and animals. However, the exact mechanism of thyroid dysfunction caused by PCBs is still unknown. In order to clarify the hypotheses that NADPH oxidase (NOX) and subsequent NF-κB pathway may play roles in thyroid dysfunction, sixty Sprague-Dawley rats were randomly divided into four groups: control group, PCB153 treated (PCB) group, received apocynin with PCB153 treatment (APO + PCB) group, and drug control (APO) group. Serum thyroid hormone levels were evaluated. The morphological change of thyroid tissue was analyzed under the light and transmission electron microscopy. NOX2, 8-OHdG, and NF-κB expression in the thyroid tissue was evaluated by immune-histochemical staining. Oxidative stress and inflammatory cytokines were detected. The following results were reduced after apocynin treatment: (1) serum thyroid hormone, (2) thyroid pathological injuries, (3) thyroid MDA, (4) thyroid ultrastructural change, (5) serum inflammatory cytokines, and (6) thyroid expression of NOX2, 8-OHdG, and NF-κB. These results suggested that NOX inhibition attenuates thyroid dysfunction induced by PCB in rats, presumably because of its role in preventing ROS generation and inhibiting the activation of NF-κB pathway. Our findings may provide new therapeutic targets for PCBs induced thyroid dysfunction.

Hydrogen-rich saline attenuates acute renal injury in sodium taurocholate-induced severe acute pancreatitis by inhibiting ROS and NF-κB pathway.

Hydrogen (H2), a new antioxidant, was reported to reduce (•)OH and ONOO(-) selectively and inhibit certain proinflammatory mediators to product, without disturbing metabolic redox reactions or ROS involved in cell signaling. We herein aim to explore its protective effects on acute renal injury in sodium taurocholate-induced acute pancreatitis and its possible mechanisms. Rats were injected with hydrogen-rich saline (HRS group) or normal saline (SO and SAP group) through tail intravenously (6 mL/kg) and compensated subcutaneously (20 mL/kg) after successful modeling. Results showed that hydrogen-rich saline attenuated the following: (1) serum Cr and BUN, (2) pancreatic and renal pathological injuries, (3) renal MDA, (4) renal MPO, (5) serum IL-1ß, IL-6, and renal TNF-α, HMGB1, and (6) tyrosine nitration, IκB degradation, and NF-κB activation in renal tissues. In addition, it increased the level of IL-10 and SOD activity in renal tissues. These results proved that hydrogen-rich saline attenuates acute renal injury in sodium taurocholate-induced acute pancreatitis, presumably because of its detoxification activity against excessive ROS, and inhibits the activation of NF-κB by affecting IκB nitration and degradation. Our findings highlight the potential value of hydrogen-rich saline as a new therapeutic method on acute renal injury in severe acute pancreatitis clinically.

Wortmannin, PI3K/Akt signaling pathway inhibitor, attenuates thyroid injury associated with severe acute pancreatitis in rats.

Increasing evidences suggest that PI3K/AKT pathway plays an important role in the pathogenesis of inflammatory diseases such as acute pancreatitis. However, the exact effect of PI3K/AKT on thyroid injury associated with acute pancreatitis has not been investigated. This study aimed to investigate the protective effects of wortmannin, PI3K/AKT inhibitor, on thyroid injury in a rat model of severe acute pancreatitis (SAP). Sixty male SD rats were randomly divided into four groups: sham operating group (SO), SAP group, wortmannin treatment (WOR) group and drug control (WOR-CON) group. Serum amylase (AMY), lipase (LIP) and thyroid hormone levels were evaluated. The morphological change of thyroid tissue was analyzed under the light and transmission electron microscopy. AKT, P38MAPK and NF-κB expression in the thyroid tissue was evaluated by immunohistochemical staining. Oxidative stress and inflammatory cytokines were detected. Results showed that wortmannin attenuated the following: (1) serum AMY, LIP and thyroid hormone (2) pancreatic and thyroid pathological injuries (3) thyroid MDA, (4) thyroid ultrastructural change, (5) serum TNF-α, IL-6 and IL-1ß (6) AKT, MAPKP38 and NF-κB expression in thyroid tissues. These results suggested that wortmannin attenuates thyroid injury in SAP rats, presumably because of its role on prevent ROS generation and inhibits the activation of P38MAPK, NF-κB pathway. Our findings provide new therapeutic targets for thyroid injury associated with SAP.