The Journal of pharmacy and pharmacology最新文献

Objectives: This review summarises the current findings regarding the therapeutic effects of GBE and its active ingredients in relation to the Nrf2 antioxidant cascade, to provide scientific insights into the clinical applications of GBE in treating oxidative stress-induced diseases.

Key findings: We found that GBE or its active ingredients activate several signalling mechanisms in cells, including the Nrf2 pathway, which is the master controller of the antioxidant defence that detoxifies reactive oxygen species (ROS). ROS-mediated cell and tissue damage contributes to ageing and pathological conditions that underlie several important human diseases, such as diabetic nephropathy (DN), ischemic stroke and age-related macular degeneration (AMD).

Summary: GBE or its component antioxidants could be applied for the treatment and/or prevention of DN, ischemic stroke and AMD due to their capacity to activate Nrf2 signalling. These strategies may also be applicable to the treatment of other similar conditions that are induced by oxidative stress. Thus, the therapeutic applications of GBE could be expanded.

Objectives: Doxorubicin (Dox) belongs to the anthracycline drug classification and is a widely administered chemotherapeutic. However, Dox use in therapy is limited by its cardiotoxicity, representing a significant drawback of Dox treatment applicability. A large amount of current research is on reducing Dox-induced cardiotoxicity by developing targeted delivery systems and investigating cardiotoxicity mechanisms. Recently, discrepancies have challenged the traditional understanding of Dox metabolism, mechanisms of action and cardiotoxicity drivers. This review summarises the current knowledge around Dox's metabolism, mechanisms of anticancer activity, and delivery systems and offers a unique perspective on the relationships between several proposed mechanisms of Dox-induced cardiotoxicity.

Key findings: While there is a strong understanding of Dox's pharmacokinetic properties, it is unclear which enzymes contribute to Dox metabolism and how Dox induces its cytotoxic effect in neoplastic and non-neoplastic cells. Evidence suggests that there are several potentially synergistic mechanisms involved in Dox-induced cardiotoxicity.

Summary: It has become clear that Dox operates in a multifactorial fashion dependent on cellular context. Accumulation of oxidative stress appears to be a common factor in cardiotoxicity mechanisms, highlighting the importance of novel delivery systems and antioxidant therapies.

Introduction: Azithromycin has been used as an ocular toxoplasmosis alternative treatment due to its pharmacokinetic profiles. However, sufficient concentrations to promote toxoplasmosis eradication is still unknown. This study was aimed to evaluate azithromycin levels in rabbits after three regimens equivalent to human doses for ocular toxoplasmosis.

Methods: Three groups of New Zealand albino rabbits were given one of the following: azithromycin at 26 mg/kg BW daily (Group 1), 26 mg/kg BW every two days (Group 2), and 50 mg/kg BW once weekly (Group 3) for 14 days. Plasma and ocular azithromycin concentrations were examined.

Results: Following 14 days, median ratio of plasma maximum azithromycin concentration to the minimum inhibitory concentration for Toxoplasma gondii (C-max/MIC) for Group 1, and 2 were 51.29, 5.33, while Group 3 was undetected. The median azithromycin concentration in the retina-choroid was higher than the MIC in Group 1 (1356.0 ng/ml) and Group 2 (189.0 ng/ml), but not in Group 3.

Conclusion: Azithromycin administered orally at the dose of 26 mg/kg BW daily or 26 mg/kg BW every two days resulted a sufficient criteria of C-max/MIC as well as retina-choroid concentration needed for its parasiticidal activity. However, well-conducted clinical trial is warranted to support its therapeutic potential in ocular toxoplasmosis.

Phoenixin-14 (PNX) is a neuropeptide that has been shown to prevent oxidative damage and stimulates insulin secretion. We investigated the effects of PNX on pancreatic injury induced by streptozotocin (STZ), and nicotinamide (NAD). Male Sprague-Dawley rats, in control (C) and diabetic (STZ) groups, were treated with either saline, or PNX (0.45 nmol/kg, or 45 nmol/kg) daily for 3 days 1 week after STZ injection. Fasting blood glucose (FBG) and gastric emptying rate (GER) were measured. Tissue and blood samples were collected. PNX treatments prevented pancreatic damage and β cell loss. Increased luminol and lucigenin levels in the pancreas, ileum and liver tissues of STZ groups were alleviated by PNX treatment in pancreatic and ileal tissues. PNX0.45 decreased FBG without any change in insulin blood level and pancreatic mRNA. GER increased in all diabetic rats while PNX0.45 delayed GER only in the C group. PNX diminishes pancreatic damage and lowers FBG by reducing oxidative load.

Objectives Due to its high morbidity, high mortality, and high disability, stroke has been the first cause of death and the major cause of adult disability in China. Natural borneol has been widely utilized in Traditional Chinese Medicine to promote drug absorption. Formononetin is a natural isoflavonoid with potent neuroprotective activity but poor brain delivery. Methods This study aimed to screen the optimum proportion that natural borneol promotes formononetin entry into the brain, evaluate the anti-cerebral ischaemia efficacy of formononetin/natural borneol combination in middle cerebral artery occlusion/reperfusion model rats, and clarify the possible mechanism for natural borneol's promoting formononetin delivery in the brain. Key findings Our studies exhibited that natural borneol remarkably promoted formononetin entry into the brain when combined with formononetin in a 1 : 1 molar ratio and notably improved neuro-behavioural scores and reduced the infarct of middle cerebral artery occlusion/reperfusion model rats. This study further discovered that the enhanced anti-cerebral ischaemia effect resulted from natural borneol increasing the permeability of the blood-brain barrier to elevate formononetin concentration in the brain rather than the pharmacodynamic synergy or addition between formononetin and natural borneol. Conclusions The study provides a good strategy to screen drug combinations for the treatment of brain disease by combining natural borneol with other drugs.

Objectives: Paeonol (PAE) is an active ingredient with anti-inflammatory and antioxidant properties. This study was designed to investigate the effect of PAE on acute pancreatitis (AP).

Methods: AP was induced by the intraperitoneal injection of 20% l-arginine (4 g/kg) for 6 h. Mice were pretreated with PAE (25, 50 or 100 mg/kg) intragastrically for 5 days. The histological damage and alterations of biochemical indicators, inflammatory cytokines and oxidative stress factors in AP mice were detected. The Nrf2 and NF-κB pathways were examined to illustrate the potential mechanism.

Key findings: In AP model, we found that PAE attenuated histological injury of pancreatic tissues, reduced the serum levels of α-amylase and increased Ca2+ contents in a dose-dependent manner. The white blood cell content, and IL-1β, IL-6 and TNF-α levels in the serum of AP mice were reduced by PAE. Furthermore, PAE caused a reduction of MPO and MDA levels, accompanied by an increase in SOD activity in the pancreas of AP mice. We also demonstrated that the alterations of Nrf2 and NF-κB pathways in AP mice were reversed by PAE.

Conclusions: PAE attenuates inflammation and oxidative stress in the development of AP by the regulation of Nrf2 and NF-κB pathways.

Objectives: Ageing is a major cause of multiple age-related diseases. Several mechanisms have been reported to contribute to these abnormalities including glycation, oxidative stress, the polyol pathway and osmotic stress. Glycation, unlike glycosylation, is an irregular biochemical reaction to the formation of active advanced glycation end-products (AGEs), which are considered to be one of the causes of these chronic diseases. This study provides a recent and comprehensive review on the possible causes, mechanisms, types, analytical techniques, diseases and treatments of the toxic glycation end products.

Key findings: Several mechanisms have been found to play a role in generating hyperglycaemia-induced oxidative stress including an increase in the levels of reactive oxygen species (ROS), increase in the levels of AGEs, binding of AGEs and their receptors (RAGE) and the polyol pathway and thus have been investigated as promising novel targets.

Summary: This review focuses on the key mechanisms attributed to cumulative increases of glycation and pathological RAGE expression as a significant cause of multiple age-related diseases, and reporting on different aspects of antiglycation therapy as a novel approach to managing/treating age-related diseases. Additionally, historical, current and possible future antiglycation approaches will be presented focussing on novel drug delivery methods.

Objectives: Evaluating the effects of rosmarinic (RA) and cryptochlorogenic (CGA) acids isolated from Blechnum binervatum extract on stem cell viability, toxicity and the protective effect on oxidative cell damage.

Methods: MTT and LDH methods were employed, using stem cells from teeth. RA and CGA were evaluated at 100, 250 and 500 µM. The negative effect of hydrogen peroxide (H2O2) (200-2200 µM) and the capacity of RA and CGA (10-100 µM) as protective agents were also evaluated. DAPI followed by fluorescent microscopy was employed to photograph the treated and untreated cells.

Key findings: At all tested concentrations, RA and CGA demonstrated the ability to maintain cell viability, and with no cytotoxic effects on the treated stem cells. RA also induced an increase of the cell viability and a reduction in cytotoxicity. H2O2 (1400 µM) induced >50% of cytotoxicity, and both compounds were capable of suppressing H2O2 damage, even at the lowest concentration. At 100 µM, in H2O2 presence, total cell viability was observed through microscope imaging.

Conclusions: These findings contribute to the continued research into natural substances with the potential for protecting cells against oxidative injury, with the consideration that RA and CGA are useful in the regeneration of damaged stem cells.

Objectives: Crataegus pinnatifida (C. pinnatifida), including C. pinnatifida Bge. and its variant C. pinnatifida Bge. var. major N, E. Br., has traditionally been used as a homologous plant for traditional medicine and food in ethnic medical systems in China. Crataegus pinnatifida, especially its fruit, has been used for more than 2000 years to treat indigestion, stagnation of meat, hyperlipidemia, blood stasis, heart tingling, sores, etc. This review aimed to provide a systematic summary on the botany, traditional uses, phytochemistry, pharmacology and clinical applications of C. pinnatifida.

Key findings: This plant contains flavonoids, phenylpropanoids, terpenoids, organic acids, saccharides and essential oils. Experimental studies showed that it has hypolipidemic, antimyocardial, anti-ischemia, antithrombotic, anti-atherosclerotic, anti-inflammatory, antineoplastic neuroprotective activity, etc. Importantly, it has good effects in treating diseases of the digestive system and cardiovascular and cerebrovascular systems.

Summary: There is convincing evidence from both in vitro and in vivo studies supporting the traditional uses of C. pinnatifida. However, multitarget network pharmacology and molecular docking technology should be used to study the interaction between the active ingredients and targets of C. pinnatifida. Furthermore, exploring the synergy of C. pinnatifida with other Chinese medicines to provide new understanding of complex diseases may be a promising strategy.

Objective: This study aimed to explore whether the liver-targeting enhancing effect of vinegar-baked Radix Bupleuri (VBRB) on rhein was achieved by affecting transporters, metabolism enzymes as well as hepatocyte nuclear factor 1α/4α (HNF1α/HNF4α) in liver injury.

Methods: The effect of VBRB on the efficacy of rhein was performed with the LPS-induced acute liver injury rat model. Aspartate aminotransferase (AST), alanine transaminase (ALT) and superoxide dismutase (SOD) levels were determined and histopathological examination was taken. Drug concentrations in tissues were determined by high performance liquid chromatography (HPLC). The protein expressions of drug transporters, metabolic enzymes and hepatic nuclear factors were determined by Western blotting and ELISA assays.

Key finding: VBRB improved the liver protecting effect of rhein, which was consistent with its promoting effect on targeted enrichment of rhein in the liver. VBRB or in combination with rhein inhibited P-glycoprotein (Pgp) and multi-resistance related protein 2 (MRP2), while increased organic anion transporting polypeptide 2 (OATP2), which might be the reason why VBRB promoted liver-targeting effect of rhein.

Conclusion: VBRB enhances the liver-protecting effect of rhein by down-regulating Pgp, MRP2, and up-regulating OATP2.