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Biomedicine & pharmacotherapy
Masson Pub. USA, Inc.
Biomedicine & pharmacotherapy

Masson Pub. USA, Inc.

0753-3322

Biomedicine & pharmacotherapy/Journal Biomedicine & pharmacotherapySCIISTP
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    Pheophorbide a identified in an Eupatorium perfoliatum extract is a novel lymphatic vascular activator

    Jihye KimEpameinondas GousopoulosTeresa M. FaleschiniMatthias Hamburger...
    1页
    查看更多>>摘要：The lymphatic vascular system is crucial for maintaining tissue fluid homeostasis and immune surveillance. Promoting lymphatic function represents a new strategy to treat several diseases including lymphedema, chronic inflammation and impaired wound healing. By screening a plant extract library, a petroleum ether extract from the aerial parts of Eupatorium perfoliatum (E. perfoliatum) was found to possess lymphangiogenic properties. With the aid of HPLC activity profiling the active compound was identified as pheophorbide a. Both plant extract and pheophorbide a induced the sprouting and tube formation of human primary lymphatic endothelial cells (LECs). The proliferation of the LECs was increased upon treatment with pheophorbide a but not the E. perfoliatum extract. Treatment with the MEK1/2 inhibitor U0126 reduced the LEC sprouting activity, indicating a potential mechanism of action. These studies suggest that pheophorbide a could represent novel natural therapeutic agent to treat human lymphatic vascular insufficiencies.
      原文链接:
    • NSTL

    Salvadora persica attenuates DMBA-induced mammary cancer through downregulation oxidative stress, estrogen receptor expression and proliferation and augmenting apoptosis

    Alaaeldin Ahmed HamzaMohammad Ahmad KhasawnehHanan Mohamed ElwySoha Osama Hassanin...
    1页
    查看更多>>摘要：Naturally occurring phytochemicals especially polyphenolic compounds have received increasing attention as chemopreventive agents. The chemopreventive potential of the ethanolic extract of Salvadora persica L. fruits SP, (the arak tree or miswak) on 7,12-dimethylbenz (a) anthracene (DMBA)-induced mammary carcinogenesis in female albino rats was investigated in this work. Ethanolic extract of SP fruits was supplemented to the experimental groups at a concentration of 500 mg/kg body weight for 22 weeks. Administration of SP extract suppressed DMBA-induced mammary carcinogenesis as revealed by incidence of tumors in histological investigation. There was a significant reduction in cell proliferation and an increase in apoptosis with down-regulation of estrogen receptor expression in the mammary tissue of SP-treated animals. Additionally, SP extract prevented the oxidative damage induced in breast tissues of DMBA-treated rats. SP treatment also decreased the viability of MCF-7 breast cancer cells and induced early and late apoptosis and induced S cell cycle arrest. The chemo-preventive properties and anticancer effects of SP could be attributed to its anti-oxidative and a high percentage of phenolic compounds and esters which were detected here in the SP fruit extract.
      原文链接:
    • NSTL

    On an association between fear-induced aggression and striatal-enriched protein tyrosine phosphatase (STEP) in the brain of Norway rats

    Vitalii S. MoskaliukRimma V. KozhemyakinaDarya V. BazovkinaElena Terenina...
    1页
    查看更多>>摘要：Striatal-enriched protein tyrosine phosphatase (STEP) is a signal transduction protein involved in the patho-genesis of neuropathologies. A STEP inhibitor (TC-2153) has antipsychotic and antidepressant effects. Here, we evaluated the role of STEP in fear-induced aggression using Norway rats selectively bred for 90 generations for either high aggression toward humans (aggressive rats) or its absence (tame rats). We studied the effects of acute administration of TC-2153 on behavior and STEP expression in the brain of these animals and the influence of chronic treatment with TC-2153 on the behavior and STEP expression in aggressive rats in comparison with classic antidepressant fluoxetine, which is known to exert antiaggressive action. Acute TC-2153 administration decreased the aggressive reaction to humans in aggressive rats, while having no impact on the friendly behavior of tame rats. Moreover, in the elevated plus-maze test, the drug had an anxiolytic effect on both aggressive and tame rats. Aggressive rats demonstrated elevated levels of a STEP isoform (STEP46) as compared to tame animals, whereas acute TC-2153 administration significantly reduced STEP46 protein concentration in the brain of aggressive rats. Chronic treatment of aggressive rats with either TC-2153 or fluoxetine attenuated fear-induced aggression. Chronic administration of fluoxetine enhanced the exploratory activity in the elevated plus-maze test and decreased the STEP46 protein level in aggressive rats' hippocampus, whereas chronic TC-2153 administration did not affect these parameters. Thus, STEP46 can play an important role in the mechanisms of aggression and may mediate antiaggressive effects of TC-2153 and fluoxetine.
      原文链接:
    • NSTL

    Targeting neuroinflammation by polyphenols: A promising therapeutic approach against inflammation-associated depression

    Mohammed Abu TayabMohammad Nazmul IslamKazi Ashfak Ahmed ChowdhuryFarhin Muntaha Tasnim...
    1页
    查看更多>>摘要：Depression is the most prevalent and debilitating mental disorder that affects a substantial number of people globally, hindering all aspects of their lives and leading to a high number of suicides each year. Despite the availability of an array of antidepressant medications, taking these medications does not relieve depressive symptoms in a considerable number of patients, implying that an incomplete understanding of the patho-mechanisms involved in the development of depression. Besides that, a subset of those non-responsive patients exhibits an increased systemic and central inflammatory response, which has collectively led to the evolvement of the inflammatory theory of depression. Indeed, peripherally generated inflammatory mediators, as well as insults within the brain, can activate the brain's resident immune cells, resulting in a neuroinflammatory response that interferes with the multitude of neurobiological domains implicated in the pathogenesis of depression. Polyphenols, a group of plant-derived bioactive molecules, have been shown to exert neuroprotective functions on the brain by influencing an array of neuropathological mechanisms, including neuroinflammation. From these perspectives, this review mechanistically provides an overview of the neuropathological roles of sustained neuroinflammatory response in the development of depression and elucidates the therapeutic potential of flavonoid and nonflavonoid polyphenols in modulating inflammatory mediators and signaling cascades as well as promoting other neurophysiological and neuroprotective functions underlying inflammation-associated depressive symptoms. Therefore, given their significant anti-neuroinflammatory effects, polyphenols could be a promising and effective adjunctive therapy for the treatment of neuropsychiatric symptoms associated with inflammation-related depression.
      原文链接:
    • NSTL

    Anti-diabetic potential of β-boswellic acid and 11-keto-β-boswellic acid: Mechanistic insights from computational and biochemical approaches

    Ajmal KhanImran KhanSobia Ahsan HalimNajeeb Ur Rehman...
    1页
    查看更多>>摘要：β-Boswellic acid (β-BA) and 11-keto-β-boswellic acid (β-KBA) are crucial bioactive compounds, mostly isolated from frankincense. These compounds are known for their potent anticancer and anti-inflammatory activities. Herein, we have explored the complete anti-diabetic potential of β-BA and β-KBA with detailed parameters. This research revealed that treatment with β-BA and β-KBA at a dose of 1, 2, and 10 mg/kg body weight for 21 days significantly improved body weight loss, water consumption, and specifically the concentration of blood glucose level (BGL) in diabetic animals, which indicated that the β-BA and β-KBA possess strong anti-diabetic activities. Serum total superoxide dismutase (SOD) and malondialdehyde (MDA) assays were also performed to evaluate the antioxidant effects. The biochemical analysis revealed that these compounds improve an abnormal level of several biochemical parameters like serum lipid values including total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C) to a normal level and the high-density lipoprotein cholesterol level (HDL-C). To understand the mechanism of action of β-BA and β-KBA, their most probable biological targets were searched through the inverse docking approach. Our computational analysis reflects that among other probable targets, the Dipeptidyl peptidase 4 (DPP-4) enzyme could be one of the possible binders of β-BA and β-KBA to produce their anti-diabetic activities. These in-silico results were validated by an in-vitro experiment. It indicates that the anti-diabetic effects of β-BA and β-KBA are produced by the inhibition of DDP-4. Thus, these anti-diabetic, antioxidant, and anti-hyperlipidemic effects ofβ-BA and β-KBA suggest these compounds as potential therapeutics for diabetic conditions.
      原文链接:
    • NSTL

    Prevention, inhibition, and degradation effects of melittin alone and in combination with vancomycin and rifampin against strong biofilm producer strains of methicillin-resistant Staphylococcus epidermidis

    Rasoul MirzaeiMohammad Yousef AlikhaniCarla Renata ArciolaIraj Sedighi...
    1页
    查看更多>>摘要：Methicillin-resistant Staphylococcus epidermidis (MRSE) bacteria are being recognized as true pathogens as they are able to resist methicillin and commonly form biofilms. Recent studies have shown that antimicrobial peptides (AMPs) are promising agents against biofilm-associated bacterial infections. In this study, we aimed to explore the antibiofilm activity of melittin, either alone or in combination with vancomycin and rifampin, against biofilm-producing MRSE strains. Minimum biofilm preventive concentration (MBPC), minimum biofilm inhibition concentration (MBIC), and minimum biofilm eradication concentration (MBEC), as well as fractional biofilm preventive-, inhibitory-, and eradication concentrations (FBPCi, FBICi, and FBECi), were determined for the antimicrobial agents tested. Cytotoxicity and hemolytic activity of melittin at its synergistic concentration were examined on human embryonic kidney cells (HEK-293) and Red Blood Cells (RBCs), respectively. The effect of melittin on the downregulation of biofilm-associated genes was explored using Real-Time PCR. MBPC, MBIC, and MBEC values for melittin were in the range of 0.625-20, 0.625-20, and 10-40 μg/μL, respectively. Melittin showed high synergy (FBPCi, FBICi and FBECi < 0.5). The synergism resulted in a 64-512-fold, 2-16 and 2-8-fold reduction in melittin, rifampicin and vancomycin concentrations, respectively. The synergistic melittin concentration found to be effective did not manifest either cytotoxicity on HEK-293 or hemolytic activity on RBCs. Results showed that melittin downregulated the expression of biofilm-associated icaA, aap, and psm genes in all isolates tested, ranging from 0.04-folds to 2.11-folds for icaA and from 0.05 to 3.76-folds for aap and psm. The preventive and therapeutic indexes of melittin were improved 8-fold when combined with vancomycin and rifampin. Based on these findings, the combination of melittin with conventional antibiotics could be proposed for treating or preventing biofilm-associated MRSE infections.
      原文链接:
    • NSTL

    Treatment and diagnosis of chemotherapy-induced peripheral neuropathy: An update

    Allison D. DesforgesChance M. HebertAllyson L. SpenceBailey Reid...
    1页
    查看更多>>摘要：When peripheral neuropathy occurs due to chemotherapy treatment, it is referred to as chemotherapy-induced peripheral neuropathy (CIPN). Typically, symptoms are sensory rather than motor and include reduced feeling and heightened sensitivity to pressure, pain, temperature, and touch. The pathophysiology of CIPN is very complex, and it involves multiple mechanisms leading to its development which will be described specifically for each chemotherapeutic class. There are currently no approved or effective agents for CIPN prevention, and Duloxetine is the only medication that is an effective treatment against CIPN. There is an unavoidable necessity to develop preventative and treatment approaches for CIPN due to its detrimental impact on patients' lives. The purpose of this review is to examine CIPN, innovative pharmacological and nonpharmacological therapy and preventive strategies for this illness, and future perspectives for this condition and its therapies.
      原文链接:
    • NSTL

    SiRNA-circFARSA-loaded porous silicon nanomaterials for pancreatic cancer treatment via inhibition of CircFARSA expression

    Huixiao YuanXin HuangQingqing LiCici Luo...
    1页
    查看更多>>摘要：Novel functions and involvement of circFARSA have not been reported in pancreatic cancer; in addition, its inhibitor screening has not yet been conducted. The purpose of this study was to (1) verify circFARSA as a novel anti-cancer target for pancreatic cancer and (2) to prepare a novel anti-pancreatic cancer agent targeting circFARSA. In this study, we designed and synthesized a small interfering RNA (siRNA, named siRNA-circFARSA), which specifically inhibits circFARSA expression. Using liposomes and porous silicon nanoparticles (pSiNPs) as siRNA delivery system, we prepared liposome-siRNA-circFARSA and pSiNP-PEI-siRNA-circFARSA and investigated their anti-cancer mechanism by quantitative real-time PCR and western blotting. Cell proliferation curves and transwell migration assays were performed to investigate the effect of siRNAs proliferation and migration capabilities of cancer cells. Patient-derived tumor xenograft mouse models were used to investigate the anti-cancer effects in vivo. The data showed that both liposome-siRNA-circFARSA and pSiNP-PEI-siRNA-circFARSA (Si: 0.7 μg/mL) significantly inhibited the proliferation and migration of pancreatic cancer cells in vitro. However, the biological safety and in vivo anti-cancer effects of pSiNP-PEI-siRNA-circFARSA (Si: 22.4 μg/ mL) were higher than those of liposome-siRNA-circFARSA. The results showed that siRNA-circFARSA could inhibit the expression of circFARSA and then BCL-2 protein expression, thereby leading to pancreatic cancer cell apoptosis after transportation into pancreatic cancer cells. Therefore, this study provides tools for pancreatic cancer treatment in the future, as it (1) verified circFARSA as a novel target for pancreatic cancer treatment, and (2) prepared a novel anti-pancreatic cancer agent (pSiNP-PEI-siRNA-circFARSA).
      原文链接:
    • NSTL

    Investigations of the antipyretic effect and safety of Prasachandaeng, a traditional remedy from Thailand national list of essential medicines

    Nuntika PrommeeArunporn ItharatKrittiya ThisayakornKanmanee Sukkasem...
    1页
    查看更多>>摘要：Prasachandaeng (PSD) remedy from the Thailand National List of Essential Medicines (NLEM) has been used as an antipyretic for chronic fever in both adults and children for centuries. Its therapeutic effect in treating fever and its safety have not been studied in animal models. We evaluated its antipyretic activity on lipopolysaccharide (LPS)-induced fever and safety in the liver in comparison with acetaminophen (ACP). Correlation between biochemistry of liver function and the level of cytochrome P450 (CYP2E1) was also evaluated using an ELISA kit. All doses of PSD powder (PSDP) and a 95% ethanol extract of PSD (PSDE) (50, 200, and 400 mg/kg) showed a significant antipyretic effect (* p < 0.05) as compared to ACP. We investigated clinical biochemistry of liver and kidney functions, histopathology, and concentrations of CYP2E1. All treatment groups demonstrated a normal range of clinical biochemistry of liver and kidney functions in comparison with ACP on days 1, 3, 7, and 10. Serum AST, ALP, and LDH levels of PSDE and PSDP showed mean values less than that of ACP on the corresponding days (* p < 0.05). None of the treatment groups showed evidence of hepatocellular damage, nor did they affect CYPE21. The results of histopathology on liver tissue correlated with the biochemistry of liver functions which indicated no hepatotoxicity effect in liver tissue during the seven day treatment. These findings suggest that both forms of PSD remedy possessed marked antipyretic activity and were not hepatotoxic during the seven days of administration in rats.
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    • NSTL

    Mechanisms of cinnamic aldehyde against myocardial ischemia/hypoxia injury in vivo and in vitro: Involvement of regulating PI3K/AKT signaling pathway

    Bin ZhengJiaying QiYakun YangLi Li...
    1页
    查看更多>>摘要：To investigate the protection of cinnamic aldehyde (CA) against myocardial ischemia/hypoxia (I/H) injury and its potential mechanisms in vivo and in vitro. Mice were pretreated with CA for 7 days, and then isoproterenol (85 mg/kg) was administered for 2 consecutive days to assess its cardioprotection. Furthermore, an in vitro myocardial I/H model was established by administering CoCl_2 (600 μM) to H9c2 cells for 24 h. H9c2 cells were pretreated with CA for 12 h to assess its protection. We observed that CA improved electrocardiogram and histopathological changes and decreased creatine kinase and lactate dehydrogenase activities and oxidative stress levels. The TUNEL results showed that CA reduced the degree of apoptosis. Furthermore, CA could lead to a down-regulation of the Caspase-3 and Bax protein expressions, but an up-regulation of the Bcl-2 protein expressions. Importantly, CA increased p-PI3K and p-AKT protein expressions, indicating the activation of the PI3K/AKT signaling pathway. Moreover, treatment with CA improved the cell viability rate and mitochondrial membrane potential while markedly decreasing apoptosis and oxidative stress levels in vitro. Our results suggested that CA exerts cardioprotection on myocardial I/H injury, which possibly occurred in connection with inhibition of oxidative stress and apoptosis via activation of the PI3K/AKT signaling pathway.
      原文链接:
    • NSTL