Drug‐induced suppression of phosphorylase kinase activity correlates with resolution of psoriasis as assessed by clinical, histological and immunohistochemical parameters

Abstract

Our results demonstrate that drug-induced suppression of PhK activity is associated with resolution of psoriatic activity as assessed by clinical, histological and immunohistochemical criteria, and support the hypothesis that effective antipsoriatic activity may be achieved through modulation of PhK activity.

Curcumin as “Curecumin”: From kitchen to clinic

“…In one particular study, Heng et al [182] evaluated curcumin's antipsoriatic effects indirectly by measuring its influence on phosphorylase kinase activity.…”

Curcumin and its allied analogues: epigenetic and health perspectives - a review

“…Supplementation of curcumin lowered the density of CD8 + T-cells and PK levels in a psoriatic model as compared to control rats (Heng et al 2000). Similarly, it also suppresses the keratinocyte proliferation and prevents from the psoriasis activity to rats (Pol et al 2003;Kurd et al 2008).…”

“…Antiplatelet effect Suppressed platelet-activating factor (PAF), ADP, epinephrine mediated platelet aggregation, collagen, and arachidonic acid (AA); Inhibited the AA and PAF mediated platelet aggregation Kim et al (2003); Lim et al (2004) Mediated the AA-induced platelet aggregation and preferential inhibition of PAF shows suppressing effects on and Ca 2+ signalling and TXA2 synthesis Srivastava et al (1995) Osteoprosis, osteoarthritis and akin disease Suppressed RANKL-induced osteoclastogenesis of rat monocyte-macrophage RAW264.7 cells Suda et al (1999) Induced the apoptosis in osteoclast rabbit, and inhibits the RANKL signalling and ultimately suppresses the RANKL-induced osteoclastogenesis in RAW 264.7 cells Ozaki et al (2000); Bharti et al (2004) Improved the bone microarchitecture and enhancing the mineral density in APP-PS1 transgenic rats Yang et al (2011) Significantly prevented from paw inflammation Ammon & Wahl (1991) Suppressed the COX-2 expression and also decreased the cellular protein kinases (JNK, protein kinase C), human epidermal growth factor receptors (EGFR & ErbB-2) and epidermal growth factor at the transcriptional level Goel et al (2001) Inhibited the NF-кB activation and hindered the c-jJun-AP-1 function Kim et al (2003) Decreased the expression of IL-6 and IL-8 pro-inflammatory cytokines Pol et al (2003) Showed inhibitory effect against different pro-inflammatory factors STAT3, NF-кB, and TNF Vamvouris & Hadi (2006); Abdou & Hanout (2008) Lowered the density of CD8+ T-cells and PK levels Heng et al (2000) Suppressed the keratinocyte proliferation and prevented from the posriais activity Pol et al (2003); Kurd et al (2008) Suppressed the lung fibroblasts through suppression of protein kinase C epsilon (PKC) Tourkina et al (2004) It induces apoptosis in scleroderma lung fibroblasts (SLFs) rats, and this effect was linked with the expression of PKC epsilon Xu et al (2007a) Suppressed GM-CSF, IL-4, and IL-5 production and inhibiting cytokines production that affect IgE synthesis, and eosinophil function Ram et al (2003) Inhibited the airway hyperreactivity, and OVA-induced airway constriction Yeon et al (2010) Kalpana and Menon (2004) stated that curcumin augmented an antioxidant defence system and modulated the biochemical marker enzymes. It also lowers the levels of free radicals and induction of detoxification enzymes and provides protection against life style related disorders (Manikandana et al 2004).…”

An evaluation of indirubin analogues as phosphorylase kinase inhibitors

“…In this regard, the crystal structure of the γ subunit of human PhK (hg2-PhK) in complex with sunitinib (pdb: 2Y7J) has been solved. This work has yet to be published, but this is the first successful crystallization of the γ-PhK catalytic site without the 4 presence of ATP. Recently, also, we have refined using molecular dynamics the structure of PhKγtrnc in complex with two indirubin and two staurosporine derivatives [5,11].…”

“…Genetic mutation on the genes coding for PhK induce severe disorders like glycogen storage diseases (i.e. VIII, IX and X) whereas physiological hyperactivity of the enzyme was shown to be linked with psoriasis [3,4]. The highly specific activity of PhK also makes it a potential target for drugs involved in the control of the glucose metabolism, such as type 2 diabetes (T2D) [2,5].…”