Amelioration of PM2.5-induced lung toxicity in rats by nutritional supplementation with biochanin A.

Epidemiological studies have shown that particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) is closely associated with human health issues, especially pulmonary diseases such as chronic obstructive pulmonary disease (COPD), asthma and lung cancer. In this study, particles were characterized by scanning electron microscopy (SEM), microbeam energy-dispersive X-ray spectroscopy (EDS), inductively coupled plasma mass spectrometry (ICP-MS) and high-performance liquid chromatography (HPLC). A rat model of PM2.5 exposure was established by nonsurgical intratracheal instillation, and the effects of biochanin A (BCA) treatment were examined. BCA showed a protective effect; it reduced PM2.5-induced apoptosis and the production of proinflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), and the chemokine interleukin-8 (IL-8), as measured using ELISA. These effects were accompanied by increases in the levels of antioxidant enzymes and decreases in the levels of malondialdehyde (MDA), lactate dehydrogenase (LDH) and alkaline phosphatase (AKP). Furthermore, isobaric tag for relative and absolute quantitation (iTRAQ)-based analytical techniques and bioinformatics tools were used to identify putative biomarkers, including XRCC1, MP2K5, IGJ, and F1LQ12, and the results were verified by Western blot analysis. In conclusion, our findings have scientific significance for the application of flavonoids in preventive and therapeutic strategies for PM2.5-associated pulmonary diseases and for the promotion of human health.

Pharmacokinetic study of precisely representative antidepressant, prokinetic, anti-inflammatory and anti-oxidative compounds from Fructus aurantii and Magnolia Bark.

BACKGROUND: Currently, few herbal pharmacokinetic (PK) parameters have been applied successfully for therapeutic monitoring because of the complexity of consistency when there are multiple chemicals and efficacies. PURPOSE: The present study aims to evaluate the herbal PK properties by investigating the PK parameters of the 8 absorbed bioactive compounds (ABCs), which can represent its parent herbal holistic efficacy, to achieve a PK therapeutic monitoring of herbs. METHOD: First, we tested the hypothesis that the antidepressant and prokinetic effects and related anti-inflammation and anti-oxidation activity (APIO) by Fructus aurantii-Magnolia Bark (FM) formula are related to 8 compounds according to the absorbable evidence and the determined contents. Subsequently, stable and representative APIO from 8ABCs allowed us to develop a sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of 8 compounds following the oral administration of FM decoction (20 g/kg) in rats. RESULT: 8 compounds either including Meranzin hydrate (MH) or MH alone almost identically (8 compounds: 91.62-108.82%)or nearly(MH: 65.38-88.41%) replicated the parent formula FM in terms of efficacy for inducing APIO. CONCLUSION: This unifying strategy shows how multi-herb formulas pharmacokinetic therapeutic monitoring can be achieved by the method we established.

Separable Microneedles for Synergistic Chemo-Photothermal Therapy against Superficial Skin Tumors.

It is extremely important to develop a minimally invasive and efficient approach for treatment of superficial skin tumors (SSTs). In this work, a near-infrared (NIR)-triggered transdermal therapeutic system based on two-stage separable microneedles (MNs) has been proposed for synergistic chemo-photothermal therapy against SSTs. Lauric acid and polycaprolactone as phase-change materials have been used to prepare the arrowheads of the two-stage separable MNs in which an anticancer drug (doxorubicin, DOX) and photothermal agent (indocyanine green, ICG) were embedded. The arrowheads are capped on the dissolvable support bases that consisted of poly(vinyl alcohol)/polyvinyl pyrrolidone (PVA/PVP). After inserting into skin tissue, the PVA/PVP support bases can be dissolved quickly owing to the absorption of the interstitial fluid, leading the arrowheads to be left in the skin tissue. Under NIR irradiation, the arrowheads embedded in the skin can be ablated because of the photothermal conversion of the ICG, resulting in liberation and penetration of the DOX from the MNs into the tumor tissue. A mouse model of melanoma tumor has been established to evaluate the synergistic effect of two-stage separable MN phototherapy and chemotherapy in the treatment of skin cancer.

Identification and Evaluation of Bioactivity of Compounds from the Mushroom Pleurotus nebrodensis (Agaricomycetes) against Breast Cancer.

Breast cancer affects millions of women annually worldwide and is the leading cause of cancer death in women. Various bioactive phytochemicals based on natural products are considered to be an important source of chemopreventive agents. In this study we report-to our knowledge for the first time-9 phytochemicals isolated by nuclear magnetic resonance spectroscopy and mass spectrometry from the acetic ether extract of Pleurotus nebrodensis and identified as (1) ergosterol, (2) uracil, (3) ergosterol-3-O-ß-D-glucopyranoside, (4) cerevisterol, (5) cerebroside B, (6) 5'-methylthioadenosine, (7) adenosine, (8) hypoxanthine, and (9) uridine. Their bioactivities were screened with an MTT assay using breast cancer MCF-7 cells in vitro. As a result, about half of the isolated compounds demonstrated moderate or strong inhibitory activity in a concentration-dependent manner. Among them, compound 1 (ergosterol) exhibited superior activity and the lowest half-maximal inhibitory concentration (112.65 µmol/L). Further mechanistic study elucidated that compound 1 led to significant S-phase cell cycle arrest and induced apoptosis in MCF-7 cells. Our study shows the mycochemical composition of the P. nebrodensis mushroom and provides guidance for use of compound 1 as a promising lead in cancer therapy.

Anti-inflammatory effect of Guan-Xin-Er-Hao via the nuclear factor-kappa B signaling pathway in rats with acute myocardial infarction.

A traditional Chinese medicine, Guan-Xin-Er-Hao (GXEH), is a famous multiple target therapeutic polypharmaceutical. Our aim was to evaluate whether or not oral administration of GXEH has an anti-inflammatory effect associated with blockade of nuclear factor-kappa B (NF-kappaB), and to investigate the NF-kappaB-mediated pro-inflammatory cytokines expression pathway during acute myocardial infarction (AMI) in rats. Sprague-Dawley rats were randomly assigned to four groups: oral GXEH administered at 15 or 5 g/kg, the vehicle control and sham-operated groups. Thirty minutes after giving GXEH or 0.9% NaCl (p.o.) once, coronary arteries were occluded except for the sham-operated rats. We measured 24-h infarct size, 3-h expression of NF-kappaB protein in the myocardial left ventricular tissues and serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and C-reactive protein (CRP). Compared with rats receiving vehicle, rats administered 15 g/kg GXEH had significantly reduced 24-h infarct size, expression of NF-kappaB protein and serum concentrations of TNF-alpha, IL-6, and CRP. GXEH at 5 g/kg did not have a significant effect on these parameters. In conclusion, GXEH exhibited an anti-inflammatory effect through inhibition of the NF-kappaB-mediated signaling pathway leading to downregulation of pro-inflammatory cytokine expression. These findings provide new evidence of the cardioprotective effect of GXEH through reduction of infarct size by mediating lots of endogenous materials via multiple pathways to act on myocardial cells in the treatment of cardiovascular disease.

Pretreatment with a traditional Chinese formula, guanxin II, reduces cardiac apoptosis via the Akt survival pathway in rats with myocardial ischemia.

Guanxin II (GXII) is a traditional Chinese formula to treat coronary heart disease in China. Previous studies indicate cardioprotection of GXII are related to cardiomyocyte apoptosis. Akt is necessary and sufficient for inhibition of apoptosis in cardiomyocytes. Our aim was to examine whether or not the antiapoptotic mechanisms of GXII are related to the Akt pathway. Male Sprague-Dawley rats were randomly assigned to four groups: GXII administered at 2.5 or 0.5 g raw materials/kg, the vehicle control and sham-operated oral 0.9% NaCl. They were pretreated once a day for 15 consecutive days by gavage. Thirty min after the last administration, the left anterior descending coronary artery was occluded to induce myocardial ischemia except for the sham-operated rats. Compared with rats receiving vehicle, those rats pretreated with GXII at 2.5 g/kg significantly reduced infarct size and decrease apoptosis. Furthermore, GXII (2.5 g/kg) significantly activated Akt kinase, increased the Bcl-2/Bax ratio, inhibited cytochrome c release, reduced caspase-9 activation, and attenuated subsequent caspase-3 activation. GXII at 0.5 g/kg have no noticeable effect on these parameters. Meanwhile, GXII at 2.5 g/kg did not change myocardial blood flow of ischemic zone, indicating a direct action on cardiomyocytes. These results suggest GXII at 2.5 g/kg ensures the survival of myocardium by enhancing the Akt-mediated antiapoptosis pathway. The findings provide new evidence of the effective and safe therapy with GXII for patients with chronic coronary heart disease.

[Effects of Dan-Chuan-Hong decoction on myocardial apoptosis of acute myocardial ischemia in rats].

OBJECTIVE: To observe the effects of Dan-Chuan-Hong decoction on myocardial apoptosis of acute myocardial ischemia in rats. METHODS: Rats received Guan-Xin-Er-Hao, Dan-Chuan-Hong or normal saline at 30 minutes before ischemia. The model of acute myocardial infarction (AMI) in rats was set up by ligating the descending branch of left coronary artery. 3 hours after AMI, the hearts were isolated to detect the apoptosis of myocardial ischemia by TUNEL; 24 hours after AMI, the hearts were isolated to determine the area of myocardial infarction by quantitative histological assay (triphenyltetrazolium chloride, TTC stain). RESULTS: Comparing with model group,the myocardial infarct size and apoptosis index of all the treatment groups decreased. Comparing with Guan-Xin-Er-Hao (30 g/kg) or Dan-Chuan-Hong (10 g/kg), the myocardial infarct size and apoptosis index of Dan-Chuan-Hong (20 g/kg) had no statistic difference. And there was statistic difference between Guan-Xin-Er-Hao (30 g/kg)and Dan-Chuan-Hong (10 g/kg). CONCLUSION: Comparing with Guan-Xin-Er-Hao, the decoction of Dan-Chuan-Hong has similar effect, which could protect hearts from myocardial ischemia by inhibiting the myocardial apoptosis.

Cardioprotection by Guanxin II in rats with acute myocardial infarction is related to its three compounds.

AIM: We tested the hypothesis that cardioprotection afforded by traditional Chinese Guanxin II (GXII) formula is related to absorbed bioactive compounds (ABCs). METHODS: Sprague-Dawley rats with acute myocardial infarction (AMI) were induced by coronary occlusion. ABCs including ferulic acid (F), hydroxyl safflor yellow A (A), tanshinol (T), protocatechualdehyde (P) and paeoniflorin (E) were measured in blood after oral GXII. The effects of GXII and FATPE, alone and in combination, and of some components of FATPE on infarct size, myocardial apoptosis and caspase-3 activity were determined. Myocardial blood flow (MBF) in AMI rat was detected 2h after oral GXII and FAT. RESULTS: FATPE was found in rat blood. FAT was similar to FATPE and GXII in decreasing infarct size, myocardial apoptosis and caspase-3 activity of AMI. Both FAT and GXII were similar in increasing of MBF. CONCLUSION: GXII and FAT protect the heart from ischemic injury by increasing MBF, and decrease infarct size by inhibiting myocardial apoptosis and caspase-3 activity. These findings provide a potential cardioprotective cocktail.