Journal of Basic and Clinical Physiology and Pharmacology

doi: 10.1515/jbcpp-2017-frontmatter6pmid: N/A

Roth, Joachim; Horowitz, Michal

doi: 10.1515/jbcpp-2017-0175pmid: 29125830

Oluwole, Oluwafemi Gabriel; Ologe, Olufunmilayo; Alabi, Akinyinka; Tunde Yusuf, Ganiyu; Umukoro, Solomon

doi: 10.1515/jbcpp-2016-0114pmid: 28350536

AbstractBackground:Inflammation is involved in various diseases; search for safe treatments is warranted. Anti-inflammatory effects of ethanol extract of Myrathius arboreus (EEMa) were studied in carrageenan-induced model, formaldehyde sub-acute-induced model, and in 48 h lipopolysaccharide-induced air pouch model of inflammation. EEMa membrane-stabilizing activities and anti-oxidant capacity were determined in vitro.Methods:In the carrageenan model EEMa (125, 250, or 500 mg/kg), indomethacin (5 mg/kg), or vehicle 3 mL/kg was administered orally in rats (n=5). After 1 h, 0.1 mL of 1% carrageenan was injected into the right hind paw of rats. Change in edema sizes was measured for 3 h with plethysmometer. One-tenth milliliter (0.1 mL) of 2.5% formaldehyde was injected into the rat paw on the first day and the third day to induce sub-acute inflammation; changes in the edema sizes were determined, and percentages of inhibitions were calculated. Anti-inflammatory effects of EEMa were further examined in lipopolysaccharide (LPS)-induced air-pouch based on leukocytes count, volume of exudates, levels of malondialdehyde, glutathione, superoxide dismutase, nitric oxides, and tumor necrosis factor released into the inflammatory fluids. EEMa-free radicals scavenging activities were studied in DPPH and reducing power tests. Membrane-stabilizing activities of EEMa were evaluated in the red blood cell lysis induced by thermal and hypotonic solution.Results:EEMa (250, 500 mg/kg) produced significant (p<0.001; p<0.05) inhibition of inflammation when compared with vehicle. Also, EEMa (250, 500, or 1000 μg/mL) significantly stabilized membrane and produced free radical scavenging activities.Conclusions:M. arboreus possesses anti-inflammatory and the anti-oxidant properties that might benefit translational medicine.

Ajayi, Abayomi M.; Ologe, Mary O.; Ben-Azu, Benneth; Okhale, Samuel E.; Adzu, Bulus; Ademowo, Olusegun G.

doi: 10.1515/jbcpp-2016-0096pmid: 28328528

AbstractBackground:Ocimum gratissimum leaf is used in managing rheumatism and other inflammatory conditions. In this study, we investigated the antioxidant and anti-inflammatory effects of phenolic extract obtained by sequential methanol extraction of O. gratissimum leaves (MEOg).Methods:The methanol extract (MEOg) was obtained after sequential maceration (n-hexane, chloroform and methanol) of dried O. gratissimum leaves. The fingerprint of the extract was obtained using a high-performance liquid chromatrographic method. In vitro effects were tested by 1,1-Diphenyl-2-picryl-hydrazyl (DPPH), nitric oxide (NO) free radical scavenging, lipoxygenase, and xanthine oxidase inhibitory assays. MEOg was studied for anti-inflammatory activity in carrageenan-induced paw edema and air pouch inflammation in rats.Results:HPLC fingerprint of the extract shows the presence of caffeic acid, rutin, ferulic acid, apigenin, and quercetin. Antioxidant activity of MEOg revealed an IC50 value in DPPH (31.5±0.03 μg/mL) and NO assay (201.6±0.01 μg/mL), respectively. The extract demonstrated strong xanthine oxidase inhibitory and weak antilipoxygenase activities. MEOg (100 mg/kg) significantly inhibited carrageenan-induced paw edema by 43.2%. Furthermore, MEOg (50 and 100 mg/kg) significantly reduced exudate volume, leucocyte count, neutrophil infiltration, TNF-α, nitrites, myeloperoxidase, and malondialdehyde in carrageenan-induced air pouch inflammation. MEOg also elevated the glutathione levels in the inflammatory exudates.Conclusions:MEOg shows potential therapeutic benefits in slowing down inflammation and oxidative stress in chronic diseases, such as arthritis.

Shetty, Yashashri C.; Patil, Amol E.; Jalgaonkar, Sharmila V.; Rege, Nirmala N.; Salgaonkar, Sweta; Teltumbde, Prachi A.; Kshirsagar, Sarang; Koli, Paresh G.; Brahma, Smita

doi: 10.1515/jbcpp-2016-0135pmid:

Bastos-Pereira, Amanda Leite; Fraga, Daniel; Dreifuss, Arturo Alejandro; Zampronio, Aleksander Roberto

doi: 10.1515/jbcpp-2017-0061pmid: 28981444

AbstractBackground:Zymosan is a fungal cell wall protein-carbohydrate complex that is known to activate inflammatory pathways through the Toll-like receptors and is commonly used to induce fever. Nevertheless, the central mediators that are involved in the zymosan-induced febrile response are only partially known.Methods:The present study evaluated the participation of prostaglandins, substance P, endothelin-1 (ET-1), and endogenous opioids (eOPs) in the zymosan-induced febrile response by using inhibitors and antagonists in male Wistar rats.Results:Both nonselective (indomethacin) and selective (celecoxib) cyclooxygenase inhibitors reduced the febrile response induced by an intraperitoneal (i.p.) injection of zymosan. Indomethacin also blocked the increase in the prostaglandin E2 levels in the cerebrospinal fluid. An intracerebroventricular injection of the neurokinin-1, ETB, and μ-opioid receptor antagonists also reduced the febrile response induced by the i.p. injected zymosan. Moreover, the μ-opioid receptor antagonist CTAP also reduced the febrile response induced by intra-articular injection of zymosan.Conclusions:These results demonstrate that prostaglandins, substance P, ET-1, and eOPs are central mediators of the zymosan-induced febrile response.

Damm, Jelena; Roth, Joachim; Gerstberger, Rüdiger; Rummel, Christoph

doi: 10.1515/jbcpp-2017-0017pmid: 28820735

AbstractBackground:Studies with NF-IL6-deficient mice indicate that this transcription factor plays a dual role during systemic inflammation with pro- and anti-inflammatory capacities. Here, we aimed to characterize the role of NF-IL6 specifically within the brain.Methods:In this study, we tested the capacity of short interfering (si) RNA to silence the inflammatory transcription factor nuclear factor-interleukin 6 (NF-IL6) in brain cells under in vitro and in vivo conditions.Results:In cells of a mixed neuronal and glial primary culture from the rat area postrema (AP), short interfering RNA (siRNA) directed against NF-IL6 strongly reduced basal and lipopolysaccharide (LPS)-induced nuclear immunoreactivity of this transcription factor, with the strongest effect on astrocytes. The siRNA did not exert inflammatory effects in the primary culture as confirmed by unaltered levels of IL-6 in supernatants. In vivo, intracerebroventricular (i.c.v.) injections of fluorochrome labelled siRNA caused its appearance in relevant brain structures for fever induction pathways such as the vascular organ of lamina terminalis, the subfornical organ, the median preoptic nucleus (MnPO) and the AP in several cell types, including microglial cells. However, i.c.v. injections of siRNA per se caused signs of fever, anorexia and reduced locomotor activity, i.e. sickness behavior.Conclusions:This approach was, thus, not suitable to characterize the role NF-IL6 in the brain in vivo, namely during experimentally induced systemic inflammation.

Adeyemi, Wale J.; Olayaki, Luqman A.

doi: 10.1515/jbcpp-2017-0032pmid: 28917083

AbstractBackground:There is a continuous search for a better therapy in osteoarthritis (OA) management. Therefore, this study investigated the effects of salmon calcitonin (Sct) and/or omega-3 fatty acids (N-3) relative to diclofenac sodium (DF) in induced knee osteoarthritic male Wistar rats.Methods:The 40 rats that were used in this study were divided into 8 groups (n=5 rats), viz: Normal control; OA control; OA+N-3; OA+Low dose of Sct (Sct.Lw); OA+High dose of Sct (Sct.Hi); OA+N-3+SCt.Lw; OA+N-3+Sct.Hi; and, OA+DF. OA was induced with 4 mg of sodium monoiodoacetate in 40 μL of saline. The solution was injected into the left knee joint space of anaesthetised rats. Sct was administered at 2.5 and 5.0 IU/kg b.w. (im), whereas N-3 and DF were administered at 200 and 1 mg/kg b.w. (p.o.), respectively. Treatments commenced 9 days after the induction of OA, and they lasted for 28 days.Results:Sct and/or N-3 significantly reduced c-telopeptide of type 1 collagen (CTX-1), collagen type 2 α-1 (C2M), malondialdehyde (MDA), uric acid (UA), and interleukin-6 (IL-6), but, significantly increased superoxide dismutase (SOD) after OA induction. Both therapies had additive effects on C2M, MDA, SOD, and catalase (CAT), but, non-additive actions on UA, IL-6, and CTX-1. Like the Sct and N-3, DF significantly reduced CTX-1, C2M, UA, and IL-6. However, it had no significant effect on SOD and MDA, even though it significantly reduced CAT activity. None of the therapies had significant effect on total alkaline phosphatase activity, except N-3+Sct.Lw.Conclusions:The combined, and sometimes the single administration of Sct and N-3 proved to be better therapies in OA management than DF.

Shetty, Yashashri C.; Godbharle, Santosh; Brahma, Smita; Salgaonkar, Sweta; Rege, Nirmala N.

doi: 10.1515/jbcpp-2016-0141pmid: 29040066

AbstractBackground:Osteoarthritis (OA) is a chronic progressive disease commonly affecting the hip and knee joints. Although synthetic drugs are available and afford symptomatic relief, their side effects pose limitations to their continuous use. So, this research was focused on extracting drugs from indigenous medicinal plants that could have a beneficial effect on osteoarthritis. Dashmoolarishta is one such preparation whose effects have never been studied in comparison with recent drugs like hyaluronic acid (HA), hence this particular study was undertaken. The aim of this study was to evaluate the effects of Dashmoolarishta compared with HA on joint pathology and pain behavior in monosodiumiodoacetate (MIA)-induced OA in experimental mice.Methods:The study was initiated after obtaining permission from the Animal Ethics Committee. This study was based on the MIA model of osteoarthritis, with mice being divided into five groups viz.: disease control (DC), Dasahmoolarishta high dose (HD) and low dose (LD), sham control (SC) and HA. The OA of the knee joint was induced in these mice using monosodiumiodoacetate. Seven days after induction, animals were subjected to weekly behavioral tests, daily oral Dashmoolarishta, and biweekly HA administration from weeks 2–4. At the end of the 4th week, histopathological examination of the knee joints was done.Results:DC showed significant osteoarthritic changes. At week 4, the behavioral tests and histopathology results of all groups were found to be significant. A significant difference (p<0.05) was found between DC vs. SC, HA, HD, LD for open field test, Rota rod test, knee joint diameter, and Cat walk test. Dashmoolarishta HD and LD showed significant improvement in pain, as assessed by behavioral tests (p<0.05) and pathology, as assessed by knee joint histopathology (p<0.05).Conclusions:Oral Dashmoolarishta showed reduction in pain and disease activity in MIA-induced osteoarthritis in mice model.

Garg, Shanky; Deshmukh, Vishwajit Ravindra; Prasoon, Pranav

doi: 10.1515/jbcpp-2016-0108pmid: 28888088

AbstractBackground:Sciatic nerve ligation causes neuropathic pain with chronic constriction injury (CCI). However, there is no published report on the effect of pioglitazone as an antidepressant in the treatment of depression induced by neuropathic pain with CCI in rats. The aim of this study was to evaluate the effect of pioglitazone as an antidepressant by targeting oxidative stress by the peripheral neuropathic pain model using the CCI of the sciatic nerve.Methods:Behavioral studies were carried out to measure thermal hyperalgesia and cold allodynia as markers of neuropathic pain and force swim test for depression. These were followed by estimation of biochemical parameters which include lipid peroxidation (LPO), reduced glutathione, catalase, nitrite and superoxide dismutase (SOD) in the rat brains as a measure of oxidative stress. We administered two intraperitoneal doses of pioglitazone (4.5 and 9.0 mg/kg, i.p.) to the treated group for 28 consecutive days from the day of injury and behavioral as well as biochemical evaluations were performed.Results:The results suggested that the administration of pioglitazone significantly countered the neuropathic pain induced depression as interpreted through elevated pain threshold of tactile allodynia and thermal hyperalgesia followed by decreased immobility time in the 9.0 mg/kg dose group.Conclusions:It may be concluded that the oxidative stress plays a critical role in the pathogenesis of neuropathic pain and depression as evidenced by the behavioral studies and the changes in the levels of lipid peroxidase, nitrite, catalase, and glutathione and SOD.