The Inhibitory Effect of Premature Citrus unshiu Extract on Atopic Dermatitis In Vitro and In Vivo

Oleanolic acid (OA) is a pentacyclic triterpenoid, abundantly found in plants of the Oleaceae family, and is well known for its beneficial pharmacological activities. Previously, we reported the inhibitory effect of OA on mast cell-mediated allergic inflammation. In this study, we investigated the effects of OA on atopic dermatitis (AD)-like skin lesions and its underlying mechanism of action. We evaluated the inhibitory effect of OA on AD-like responses and the possible mechanisms using a 1-chloro-2,4-dinitrochlorobenzene (DNCB)-induced AD animal model and tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated HaCaT keratinocytes. We found that OA has anti-atopic effects, including histological alterations, on DNCB-induced AD-like lesions in mice. Moreover, it suppressed the expression of Th2 type cytokines and chemokines in the AD mouse model and TNF-α/IFN-γ-induced HaCaT keratinocytes by blocking the activation of serine-threonine kinase Akt, nuclear factor-κB, and the signal transducer and activator of transcription 1. The results demonstrate that OA inhibits AD-like symptoms and regulates the inflammatory mediators; therefore, it may be used as an effective and attractive therapeutic agent for allergic disorders, such as AD. Moreover, the findings of this study provide novel insights into the potential pharmacological targets of OA for treating AD.

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The Effect of Barbituric Acid Derivatives on Platelet Function in Vitro and in Vivo

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649080 ◽

1973 ◽

Vol 30 (02) ◽

pp. 315-326

Author(s):

J. Heinz Joist ◽

Jean-Pierre Cazenave ◽

J. Fraser Mustard

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Barbituric Acid ◽

Platelet Rich Plasma ◽

Inhibitory Effect ◽

Primary Response ◽

Sodium Pentobarbital ◽

Barbituric Acid Derivatives

SummarySodium pentobarbital (SPB) and three other barbituric acid derivatives were found to inhibit platelet function in vitro. SPB had no effect on the primary response to ADP of platelets in platelet-rich plasma (PRP) or washed platelets but inhibited secondary aggregation induced by ADP in human PRP. The drug inhibited both phases of aggregation induced by epinephrine. SPB suppressed aggregation and the release reaction induced by collagen or low concentrations of thrombin, and platelet adherence to collagen-coated glass tubes. The inhibition by SPB of platelet aggregation was readily reversible and isotopically labeled SPB did not become firmly bound to platelets. No inhibitory effect on platelet aggregation induced by ADP, collagen, or thrombin could be detected in PRP obtained from rabbits after induction of SPB-anesthesia.

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Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648055 ◽

1976 ◽

Vol 36 (02) ◽

pp. 401-410 ◽

Cited By ~ 6

Author(s):

Buichi Fujttani ◽

Toshimichi Tsuboi ◽

Kazuko Takeno ◽

Kouichi Yoshida ◽

Masanao Shimizu

Keyword(s):

Guinea Pig ◽

Acetylsalicylic Acid ◽

Guinea Pigs ◽

Glass Bead ◽

Animal Species ◽

Inhibitory Effect ◽

Rabbit Platelet ◽

Platelet Adhesiveness

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.

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Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

Current Alzheimer Research ◽

10.2174/1567205014666171128102557 ◽

2018 ◽

Vol 15 (6) ◽

pp. 531-543 ◽

Cited By ~ 4

Author(s):

Dominik Szwajgier ◽

Ewa Baranowska-Wojcik ◽

Kamila Borowiec

Keyword(s):

Phenolic Acids ◽

Ex Vivo ◽

Amyloid Β ◽

Inhibitory Effect ◽

In Vivo Studies ◽

Amyloid Β Peptide ◽

Beneficial Effects ◽

Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

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Traditional Herbal Medicines, Newer Herbs and Other Novel Approaches Integrated in Herbal Medicine for Atopic Dermatitis-A Narrative Review

Current Drug Therapy ◽

10.2174/1574885514666191018165209 ◽

2020 ◽

Vol 15 (3) ◽

pp. 194-208

Author(s):

Pravin Kumar ◽

Dinesh Kumar Sharma ◽

Mahendra Singh Ashawat

Keyword(s):

Atopic Dermatitis ◽

Herbal Medicines ◽

Developed Countries ◽

Skin Lesions ◽

Scientific Data ◽

Herbal Drugs ◽

Biological Drugs ◽

Alternative Treatment Option

Atopic Dermatitis (AD) is a prolonged reverting skin ailment with characteristically distributed skin lesions. In the previous decades, researchers had shown a marked interest in AD due to its increased prevalence in developed countries. Although different strategies including biological and immune modulators are available for the treatment of AD, each has certain limitations. The researchers had shown considerable interest in the management of AD with herbal medicines. The establishment of herbal drugs for AD might eliminate local as well as systemic adverse effects associated with long term use of corticosteroids and also higher cost of therapy with biological drugs. The present review discusses the traditional East Asian herbal medicines and scientific data related to newer herbal extracts or compositions for the treatment of AD. In vivo animal models and in vitro cell cultures, investigated with herbal medicines to establish a possible role in AD treatment, have also been discussed in the paper. The paper also highlights the role of certain new approaches, i.e. pharmacopuncture, a combination of allopathic and herbal medicines; and novel carriers (liposomes, cubosomes) for herbal drugs on atopic skin. In conclusion, herbal medicines can be a better and safe, complementary and alternative treatment option for AD.

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Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽

10.1182/blood.v76.6.1250.1250 ◽

1990 ◽

Vol 76 (6) ◽

pp. 1250-1255 ◽

Cited By ~ 36

Author(s):

S Whitehead ◽

TE Peto

Keyword(s):

Plasmodium Falciparum ◽

Growth Inhibition ◽

Antimalarial Activity ◽

Clinical Malaria ◽

Inhibitory Effect ◽

Parasite Development ◽

And Control ◽

Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

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A novel BRD4 inhibitor suppresses osteoclastogenesis and ovariectomized osteoporosis by blocking RANKL-mediated MAPK and NF-κB pathways

Cell Death and Disease ◽

10.1038/s41419-021-03939-7 ◽

2021 ◽

Vol 12 (7) ◽

Author(s):

Ying Liu ◽

Wenjie Liu ◽

Ziqiang Yu ◽

Yan Zhang ◽

Yinghua Li ◽

...

Keyword(s):

Bone Loss ◽

Osteoporosis Treatment ◽

Inhibitory Effect ◽

Specific Gene ◽

Actin Ring ◽

Treatment Target ◽

Significant Inhibitory Effect ◽

Promising Treatment

AbstractBromodomain-containing protein 4 (BRD4) has emerged as a promising treatment target for bone-related disorders. (+)-JQ1, a thienotriazolodiazepine compound, has been shown to inhibit pro-osteoclastic activity in a BRD4-dependent approach and impede bone loss caused by ovariectomy (OVX) in vivo. However, clinical trials of (+)-JQ1 are limited because of its poor druggability. In this study, we synthesized a new (+)-JQ1 derivative differing in structure and chirality. One such derivative, (+)-ND, exhibited higher solubility and excellent inhibitory activity against BRD4 compared with its analogue (+)-JQ1. Interestingly, (-)-JQ1 and (-)-ND exhibited low anti-proliferative activity and had no significant inhibitory effect on RANKL-induced osteoclastogenesis as compared with (+)-JQ1 and (+)-ND, suggesting the importance of chirality in the biological activity of compounds. Among these compounds, (+)-ND displayed the most prominent inhibitory effect on RANKL-induced osteoclastogenesis. Moreover, (+)-ND could inhibit osteoclast-specific gene expression, F‐actin ring generation, and bone resorption in vitro and prevent bone loss in OVX mice. Collectively, these findings indicated that (+)-ND represses RANKL‐stimulated osteoclastogenesis and averts OVX-triggered osteoporosis by suppressing MAPK and NF-κB signalling cascades, suggesting that it may be a prospective candidate for osteoporosis treatment.

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Gilteritinib overcomes lorlatinib resistance in ALK-rearranged cancer

Nature Communications ◽

10.1038/s41467-021-21396-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Hayato Mizuta ◽

Koutaroh Okada ◽

Mitsugu Araki ◽

Jun Adachi ◽

Ai Takemoto ◽

...

Keyword(s):

Gene Rearrangement ◽

Kinase Inhibitors ◽

Inhibitory Effect ◽

In Vivo Model ◽

Resistance Mutations ◽

Lung Cancer Patients ◽

Short Period ◽

Tki Resistance

AbstractALK gene rearrangement was observed in 3%–5% of non-small cell lung cancer patients, and multiple ALK-tyrosine kinase inhibitors (TKIs) have been sequentially used. Multiple ALK-TKI resistance mutations have been identified from the patients, and several compound mutations, such as I1171N + F1174I or I1171N + L1198H are resistant to all the approved ALK-TKIs. In this study, we found that gilteritinib has an inhibitory effect on ALK-TKI–resistant single mutants and I1171N compound mutants in vitro and in vivo. Surprisingly, EML4-ALK I1171N + F1174I compound mutant-expressing tumors were not completely shrunk but regrew within a short period of time after alectinib or lorlatinib treatment. However, the relapsed tumor was markedly shrunk after switching to the gilteritinib in vivo model. In addition, gilteritinib was effective against NTRK-rearranged cancers including entrectinib-resistant NTRK1 G667C-mutant and ROS1 fusion-positive cancer.

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