Displaying publications 1 - 20 of 66 in total

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  1. Janbaz KH, Arif J, Saqib F, Imran I, Ashraf M, Zia-Ul-Haq M, et al.
    BMC Complement Altern Med, 2014 Feb 22;14:71.
    PMID: 24559094 DOI: 10.1186/1472-6882-14-71
    BACKGROUND: Isodon rugosus is used in folk Pakistan traditional practices to cure ailments related to gastrointestinal, respiratory and cardiovascular problems. Present study was undertaken to validate these folkloric uses.

    METHODS: A crude methanol extract of the aerial parts of Isodon rugosus (Ir.Cr.) was used for both in vitro and in vivo experiments. The plant extract was tested on isolated rabbit jejunum preparations for possible presence of spasmolytic activity. Moreover, isolated rabbit tracheal and aorta preparations were used to ascertain the relaxant effects of the extract. Acetylcholinesterase and butyrylcholinesterase inhibitory activities of Ir.Cr were also determined as well as its antioxidant activity. The in vivo antiemetic activity of the extract was evaluated by using the chick emesis model, while the analgesic and antipyretic activities were conducted on albino mice.

    RESULTS: The application of the crude extract of I. rugosus to isolated rabbit jejunum preparations exhibited relaxant effect (0.01-0.3 mg/ml). The Ir.Cr also relaxed K+(80 m M)-induced spastic contractions in isolated rabbit jejunum preparations and shifted the Ca+2 concentration response curves towards right (0.01-0.3 mg/ml). Similarly, the extract, when applied to the isolated rabbit tracheal preparations relaxed the carbachol (1 μM)--as well as K+ (80 mM)-induced contractions in a concentration range of 0.01-1.0 mg/ml. Moreover, it also relaxed (0.01-3.0 mg/ml) the phenylephrine (1 μM)- and K+ (80 mM)-induced contractions in isolated rabbit aorta preparations. The Ir.Cr (80 mg/kg) demonstrated antipyretic activity on pyrogen-induced pyrexia in rabbits as compared to aspirin as standard drug. The Ir.Cr also exhibited anti-oxidant as well as inhibitory effect on acetyl- and butyryl-cholinesterase and lipoxygenase (0.5 mg/ml).

    CONCLUSIONS: The observed relaxant effect on isolated rabbit jejunum, trachea and aorta preparations caused by Ir.Cr is possibly to be mediated through Ca+2 channel blockade and therefore may provided scientific basis to validate the folkloric uses of the plant in the management of gastrointestinal, respiratory and cardiovascular ailments. The observed antioxidant activity as well as the lipoxygenase inhibitory activity may validate its traditional use in pain and inflammations.

    Matched MeSH terms: Muscle, Smooth/drug effects*
  2. Ajay M, Achike FI, Mustafa MR
    Pharmacol Res, 2007 May;55(5):385-91.
    PMID: 17317209
    In this study, we report the effects of a non-antioxidant flavonoid flavone on vascular reactivity in Wistar-Kyoto (WKY) rat isolated aortae. Whether flavone directly modulates vascular reactivity in spontaneously hypertensive rat (SHR) and streptozotocin-induced diabetic-WKY rat isolated aortae was also determined. Thoracic aortic rings were mounted in organ chambers and exposed to various drug treatments in the presence of flavone (10 microM) or its vehicle (DMSO), which served as control. Pretreatment with flavone enhanced relaxant effects to endothelium-dependent vasodilator acetylcholine (ACh) and attenuated contractile effects to alpha(1)-receptor agonist phenylephrine (PE) in WKY aortae compared to those observed in control aortic rings. Flavone had no effect on relaxations to ACh in WKY aortae incubated with either L-NAME or methylene blue, but enhanced relaxations to ACh in WKY aortae incubated with indomethacin or partially depolarized with KCl. Relaxations to ACh are totally abolished in both control or flavone pretreated endothelium-denuded WKY aortae. Flavone attenuated the inhibition by beta-NADH of ACh-induced relaxation in WKY aortae, but it had no significant effect on the transient contractions induced by beta-NADH nor the pyrogallol-induced abolishment of ACh-induced relaxation in WKY aortae. Flavone enhanced endothelium-independent relaxation to sodium nitroprusside (SNP) in both endothelium-intact and -denuded WKY aortae. Flavone enhanced relaxation to ACh and SNP as well as attenuated contractile effects to PE in SHR and diabetic aortae, a finding similar to that observed in normal WKY aortae. From these results, we conclude that flavone modulates vascular reactivity in normal as well as hypertensive and diabetic aortae. These effects of flavone results probably through enhanced bioactivity of nitric oxide released from the endothelium.
    Matched MeSH terms: Muscle, Smooth, Vascular/drug effects; Muscle, Smooth, Vascular/physiopathology
  3. Armenia A, Munavvar AS, Abdullah NA, Helmi A, Johns EJ
    Br J Pharmacol, 2004 Jun;142(4):719-26.
    PMID: 15172958
    1. Diabetes and hypertension are both associated with an increased risk of renal disease and are associated with neuropathies, which can cause defective autonomic control of major organs including the kidney. This study aimed to examine the alpha(1)-adrenoceptor subtype(s) involved in mediating adrenergically induced renal vasoconstriction in a rat model of diabetes and hypertension. 2. Male spontaneously hypertensive rats (SHR), 220-280 g, were anaesthetized with sodium pentobarbitone 7-day poststreptozotocin (55 mg x kg(-1) i.p.) treatment. The reductions in renal blood flow (RBF) induced by increasing frequencies of electrical renal nerve stimulation (RNS), close intrarenal bolus doses of noradrenaline (NA), phenylephrine (PE) or methoxamine were determined before and after administration of nitrendipine (Nit), 5-methylurapidil (5-MeU), chloroethylclonidine (CEC) and BMY 7378. 3. In the nondiabetic SHR group, mean arterial pressure (MAP) was 146+/-6 mmHg, RBF was 28.0+/-1.4 ml x min(-1) x kg(-1) and blood glucose was 112.3+/-4.7 mg x dl(-1), and in the diabetic SHR Group, MAP was 144+/-3 mmHg, RBF 26.9+/-1.3 ml(-1) min x kg(-1) and blood glucose 316.2+/-10.5 mg x dl(-1). Nit, 5-MeU and BMY 7378 blunted all the adrenergically induced renal vasoconstrictor responses in SHR and diabetic SHR by 25-35% (all P<0.05), but in diabetic rats the responses induced by RNS and NA treated with 5-MeU were not changed. By contrast, during the administration of CEC, vasoconstrictor responses to all agonists were enhanced by 20-25% (all P<0.05) in both the SHR and diabetic SHR. 4. These findings suggest that alpha(1A) and alpha(1D)-adrenoceptor subtypes contribute in mediating the adrenergically induced constriction of the renal vasculature in both the SHR and diabetic SHR. There was also an indication of a greater contribution of presynaptic adrenoceptors, that is, alpha(1B)-, and/or alpha(2)-subtypes.
    Matched MeSH terms: Muscle, Smooth, Vascular/drug effects; Muscle, Smooth, Vascular/physiopathology
  4. Vijakumaran U, Yazid MD, Hj Idrus RB, Abdul Rahman MR, Sulaiman N
    Front Pharmacol, 2021;12:663266.
    PMID: 34093194 DOI: 10.3389/fphar.2021.663266
    Objective: Hydroxytyrosol (HT), a polyphenol of olive plant is well known for its antioxidant, anti-inflammatory and anti-atherogenic properties. The aim of this systematic search is to highlight the scientific evidence evaluating molecular efficiency of HT in halting the progression of intimal hyperplasia (IH), which is a clinical condition arises from endothelial inflammation. Methods: A systematic search was performed through PubMed, Web of Science and Scopus, based on pre-set keywords which are Hydroxytyrosol OR 3,4-dihydroxyphenylethanol, AND Intimal hyperplasia OR Neointimal hyperplasia OR Endothelial OR Smooth muscles. Eighteen in vitro and three in vitro and in vivo studies were selected based on a pre-set inclusion and exclusion criteria. Results: Based on evidence gathered, HT was found to upregulate PI3K/AKT/mTOR pathways and supresses inflammatory factors and mediators such as IL-1β, IL-6, E-selectin, P-selectin, VCAM-1, and ICAM-1 in endothelial vascularization and functioning. Two studies revealed HT disrupted vascular smooth muscle cells (SMC) cell cycle by dephosphorylating ERK1/2 and AKT pathways. Therefore, HT was proven to promote endothelization and inhibit vascular SMCs migration thus hampering IH development. However, none of these studies described the effect of HT collectively in both vascular endothelial cells (EC) and SMCs in IH ex vivo model. Conclusions: Evidence from this concise review provides an insight on HT regulation of molecular pathways in reendothelization and inhibition of VSMCs migration. Henceforth, we propose effect of HT on IH prevention could be further elucidated through in vivo and ex vivo model.
    Matched MeSH terms: Muscle, Smooth, Vascular
  5. Kimura TE, Duggirala A, Hindmarch CC, Hewer RC, Cui MZ, Newby AC, et al.
    J Mol Cell Cardiol, 2014 Jul;72(100):9-19.
    PMID: 24534707 DOI: 10.1016/j.yjmcc.2014.02.001
    AIMS: Cyclic AMP inhibits vascular smooth muscle cell (VSMC) proliferation which is important in the aetiology of numerous vascular diseases. The anti-mitogenic properties of cAMP in VSMC are dependent on activation of protein kinase A (PKA) and exchange protein activated by cAMP (EPAC), but the mechanisms are unclear.

    METHODS AND RESULTS: Selective agonists of PKA and EPAC synergistically inhibited Egr1 expression, which was essential for VSMC proliferation. Forskolin, adenosine, A2B receptor agonist BAY60-6583 and Cicaprost also inhibited Egr1 expression in VSMC but not in endothelial cells. Inhibition of Egr1 by cAMP was independent of cAMP response element binding protein (CREB) activity but dependent on inhibition of serum response element (SRE) activity. SRF binding to the Egr1 promoter was not modulated by cAMP stimulation. However, Egr1 expression was dependent on the SRF co-factors Elk1 and 4 but independent of MAL. Inhibition of SRE-dependent Egr1 expression was due to synergistic inhibition of Rac1 activity by PKA and EPAC, resulting in rapid cytoskeleton remodelling and nuclear export of ERK1/2. This was associated with de-phosphorylation of the SRF co-factor Elk1.

    CONCLUSION: cAMP inhibits VSMC proliferation by rapidly inhibiting Egr1 expression. This occurs, at least in part, via inhibition of Rac1 activity leading to rapid actin-cytoskeleton remodelling, nuclear export of ERK1/2, impaired Elk1-phosphorylation and inhibition of SRE activity. This identifies one of the earliest mechanisms underlying the anti-mitogenic effects of cAMP in VSMC but not in endothelial cells, making it an attractive target for selective inhibition of VSMC proliferation.

    Matched MeSH terms: Muscle, Smooth, Vascular/cytology; Muscle, Smooth, Vascular/drug effects; Muscle, Smooth, Vascular/metabolism
  6. Chan KM, Rajab NF, Siegel D, Din LB, Ross D, Inayat-Hussain SH
    Toxicol. Sci., 2010 Aug;116(2):533-48.
    PMID: 20498002 DOI: 10.1093/toxsci/kfq151
    Goniothalamin (GN), a styryl-lactone isolated from Goniothalamus andersonii, has been demonstrated to possess antirestenostic properties by inducing apoptosis on coronary artery smooth muscle cells (CASMCs). In this study, the molecular mechanisms of GN-induced CASMCs apoptosis were further elucidated. Apoptosis assessment based on the externalization of phosphatidylserine demonstrated that GN induces CASMCs apoptosis in a concentration-dependent manner. The GN-induced DNA damage occurred with concomitant elevation of p53 as early as 2 h, demonstrating an upstream signal for apoptosis. However, the p53 elevation in GN-treated CASMCs was independent of NAD(P)H: quinone oxidoreductase 1 and Mdm-2 expression. An increase in hydrogen peroxide and reduction in free thiols confirmed the role for oxidative stress in GN treatment. Pretreatment with the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-FMK) that significantly abrogated GN-induced CASMCs apoptosis suggested the involvement of caspase(s). The role of apical caspase-2, -8, and -9 was then investigated, and sequential activation of caspase-2 and -9 but not caspase-8 leading to downstream caspase-3 cleavage was observed in GN-treated CASMCs. Reduction of ATP level and decrease in oxygen consumption further confirmed the role of mitochondria in GN-induced apoptosis in CASMCs. The mitochondrial release of cytochrome c was seen without mitochondrial membrane potential loss and was independent of cardiolipin. These data provide insight into the mechanisms of GN-induced apoptosis, which may have important implications in the development of drug-eluting stents.
    Matched MeSH terms: Muscle, Smooth, Vascular/drug effects*
  7. Muharis SP, Top AG, Murugan D, Mustafa MR
    Nutr Res, 2010 Mar;30(3):209-16.
    PMID: 20417882 DOI: 10.1016/j.nutres.2010.03.005
    Diabetes and hypertension are closely associated with impaired endothelial function. Studies have demonstrated that regular consumption of edible palm oil may reverse endothelial dysfunction. The present study investigates the effect of palm oil fractions: tocotrienol rich fraction (TRF), alpha-tocopherol and refined palm olein (vitamin E-free fraction) on the vascular relaxation responses in the aortic rings of streptozotocin-induced diabetic and spontaneously hypertensive rats (SHR). We hypothesize that the TRF and alpha-tocopherol fractions are able to improve endothelial function in both diabetic and hypertensive rat aortic tissue. A 1,1-diphenyl picryl hydrazyl assay was performed on the various palm oil fractions to evaluate their antioxidant activities. Endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) relaxations were examined on streptozotocin-induced diabetic and SHR rat aorta following preincubation with the different fractions. In 1-diphenyl picryl hydrazyl antioxidant assay, TRF and alpha-tocopherol fractions exhibited a similar degree of activity while palm olein exhibited poor activity. TRF and alpha-tocopherol significantly improved acetylcholine-induced relaxations in both diabetic (TRF, 88.5% +/- 4.5%; alpha-tocopherol, 87.4% +/- 3.4%; vehicle, 65.0 +/- 1.6%) and SHR aorta (TRF, 72.1% +/- 7.9%; alpha-tocopherol, 69.8% +/- 4.0%, vehicle, 51.1% +/- 4.7%), while palm olein exhibited no observable effect. These results suggest that TRF and alpha-tocopherol fractions possess potent antioxidant activities and provide further support to the cardiovascular protective effects of palm oil vitamin E. TRF and alpha-tocopherol may potentially improve vascular endothelial function in diabetes and hypertension by their sparing effect on endothelium derived nitric oxide bioavailability.
    Matched MeSH terms: Muscle, Smooth, Vascular/physiopathology
  8. Khoo JJ, Gunn A
    Malays J Pathol, 2005 Jun;27(1):9-16.
    PMID: 16676687
    AIM: To study the clinical features, histology and immunohistochemical properties of gastrointestinal stromal tumours (GISTs); and establish any parameters that can help prognosticate the malignant potential.
    METHODS: Twenty-six patients with GISTs who were seen in Sultanah Aminah Hospital Johor, Malaysia from 1999 to 2003 were selected for study. Patient, clinical characteristics and outcome based on surgical records were analysed. Tumour variables (tumour size, cellularity, mitotic count, necrosis and haemorrhage) were compared between very low to low risk groups and intermediate to high risk groups. The immunohistochemical properties of GISTs were also studied.
    RESULTS: Patients with GISTs presented mainly with pain, palpable mass or gastrointestinal tract bleeding. The tumours were seen in stomach (50%) followed by small intestine (38.5%) and rectum (11.5%). In the period of study, six patients had metastasis, mainly in the liver or peritoneum. Immunoreactivity for CD117, CD34, vimentin, S100, neuron specific enolase, alpha-smooth-muscle-actin and desmin were observed in 100%, 76.9%, 61.5%, 46.1%, 80.8%, 11.5% and 0% of tumours respectively. The behaviour of GISTs was largely dependent on tumour size and number of mitosis. Necrosis and haemorrhage were seen in tumours with high risk potential.
    Matched MeSH terms: Muscle, Smooth/metabolism
  9. Harith HH, Di Bartolo BA, Cartland SP, Genner S, Kavurma MM
    J Diabetes, 2016 Jul;8(4):568-78.
    PMID: 26333348 DOI: 10.1111/1753-0407.12339
    BACKGROUND: Insulin regulates glucose homeostasis but can also promote vascular smooth muscle (VSMC) proliferation, important in atherogenesis. Recently, we showed that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) stimulates intimal thickening via accelerated growth of VSMCs. The aim of the present study was to determine whether insulin-induced effects on VSMCs occur via TRAIL.

    METHODS: Expression of TRAIL and TRAIL receptor in response to insulin and glucose was determined by polymerase chain reaction. Transcriptional activity was assessed using wild-type and site-specific mutations of the TRAIL promoter. Chromatin immunoprecipitation studies were performed. VSMC proliferation and apoptosis was measured.

    RESULTS: Insulin and glucose exposure to VSMC for 24 h stimulated TRAIL mRNA expression. This was also evident at the transcriptional level. Both insulin- and glucose-inducible TRAIL transcriptional activity was blocked by dominant-negative specificity protein-1 (Sp1) overexpression. There are five functional Sp1-binding elements (Sp1-1, Sp1-2, Sp-5/6 and Sp1-7) on the TRAIL promoter. Insulin required the Sp1-1 and Sp1-2 sites, but glucose needed all Sp1-binding sites to induce transcription. Furthermore, insulin (but not glucose) was able to promote VSMC proliferation over time, associated with increased decoy receptor-2 (DcR2) expression. In contrast, chronic 5-day exposure of VSMC to 1 µg/mL insulin repressed TRAIL and DcR2 expression, and reduced Sp1 enrichment on the TRAIL promoter. This was associated with increased cell death.

    CONCLUSIONS: The findings of the present study provide a new mechanistic insight into how TRAIL is regulated by insulin. This may have significant implications at different stages of diabetes-associated cardiovascular disease. Thus, TRAIL may offer a novel therapeutic solution to combat insulin-induced vascular pathologies.

    Matched MeSH terms: Muscle, Smooth, Vascular/cytology
  10. Ajay M, Gilani AU, Mustafa MR
    Life Sci, 2003 Dec 19;74(5):603-12.
    PMID: 14623031
    The potency, structure-activity relationship, and mechanism of vasorelaxation of a series of flavonoids, representing different subclasses (flavonols: fisetin, rutin, quercetin; flavones: chrysin, flavone, baicalein; flavanones: naringenin, naringin; isoflavones: diadzein and flavanes: epigallo catechin gallate), were examined in the isolated rat aorta. Most of the flavonoids tested showed concentration dependent relaxant effects against K+ (80 mM) and phenylephrine (PE, 0.1 microM)-induced contractions with a greater inhibition of the responses to the alpha1-adrenoceptor agonist. The relaxant effects of most of the flavonoids involve in part the release of nitric oxide and prostaglandins from the endothelium as pretreatment with L-NAME and indomethacin attenuated the responses. In addition, the relaxant action of the flavonoids includes inhibition of Ca+2 influx and release of Ca+2 from intracellular stores. A structure-activity relationship amongst the flavonoids was suggested.
    Matched MeSH terms: Muscle, Smooth, Vascular/drug effects*
  11. Ajay M, Achike FI, Mustafa AM, Mustafa MR
    Clin Exp Pharmacol Physiol, 2006 Apr;33(4):345-50.
    PMID: 16620299
    1. There is a growing interest in the anti-oxidant characteristics and use of flavonoids in the management of cardiovascular diseases. The cardiovascular mechanism of action of these plant derivatives remains controversial. This study compared the effects of the flavonoid quercetin with those of the anti-oxidant vitamin ascorbic acid (vitamin C) on the reactivity of aortic rings from spontaneously hypertensive rats (SHR). 2. The phenylephrine (PE)-induced contractile and the endothelium-dependent and independent relaxant responses of aortic rings from 21 to 22 week old SHR and age-matched normotensive Wistar (WKY) rats were observed in the presence of quercetin or ascorbic acid. All the experiments were performed in the presence of the cyclooxygenase inhibitor, indomethacin (10 micromol/L). 3. The endothelium-dependent and independent relaxations to acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were significantly lesser in the SHR compared to the WKY tissues whereas the contractile responses to PE were similar in both tissues. Pretreatment of WKY rings with quercetin or ascorbic acid had no effect on the responses to ACh or PE. In the SHR tissues, however, quercetin or ascorbic acid significantly improved the relaxation responses to ACh and reduced the contractions to PE with greater potency for quercetin. Both compounds lacked any effects on the responses to SNP in either aortic ring types. N(omega)-nitro-L-arginine methyl ester (l-NAME, 10 micromol/L) significantly attenuated the vasodepressor effects of quercetin and ascorbic acid, raising the responses to PE to a level similar to that observed in the control SHR tissues. In l-NAME pretreated aortic rings, quercetin and ascorbic acid inhibited the contractile responses to PE with the same magnitude in WKY and SHR tissues. 4. The present results suggest that acute exposure to quercetin improves endothelium-dependent relaxation and reduces the contractile responses of hypertensive aortae with a greater potency than ascorbic acid. This suggests a better vascular protection with this flavonoid than ascorbic acid in the SHR model of hypertension and possibly in human cardiovascular diseases.
    Matched MeSH terms: Muscle, Smooth, Vascular/drug effects
  12. Zainudin S, Rajanthran SK, Azizan N, Hayati F, Ginawoi J, Suhaimi KA, et al.
    Oxf Med Case Reports, 2020 Oct;2020(10):omaa086.
    PMID: 33133619 DOI: 10.1093/omcr/omaa086
    Leiomyoma is a smooth muscle tumour that can arise in any part of the body especially the uterus. Even though it is traditionally linked with hormonal influence, it can also develop in extrauterine organs with a slight female predominance. It is indistinguishable with gastrointestinal stromal tumour (GIST) histologically. We report a case of a 30-year-old gentleman who presented with a huge painful mass in the right iliac fossa. Computed tomography revealed a 10 × 10 cm homogeneous mass arising from the terminal ileum; he subsequently underwent an open right hemicolectomy. Histology showed a well-circumscribed lesion composed of interlacing bundles of smooth muscle fibres of the submucosa with positive smooth muscle actin and H-Caldesmon stains but negative for DOG-1 and CD117 (c-kit) stains which were consistent with leiomyoma. Despite its rarity, this hormone-related tumour needs to be considered regardless of gender. Immunohistochemistry is paramount as it is histologically identical to GIST.
    Matched MeSH terms: Muscle, Smooth
  13. Rashidbenam Z, Jasman MH, Tan GH, Goh EH, Fam XI, Ho CCK, et al.
    Int J Mol Sci, 2021 Mar 25;22(7).
    PMID: 33805910 DOI: 10.3390/ijms22073350
    Long urethral strictures are often treated with autologous genital skin and buccal mucosa grafts; however, risk of hair ingrowth and donor site morbidity, restrict their application. To overcome this, we introduced a tissue-engineered human urethra comprising adipose-derived stem cell (ASC)-based self-assembled scaffold, human urothelial cells (UCs) and smooth muscle cells (SMCs). ASCs were cultured with ascorbic acid to stimulate extracellular matrix (ECM) production. The scaffold (ECM) was stained with collagen type-I antibody and the thickness was measured under a confocal microscope. Results showed that the thickest scaffold (28.06 ± 0.59 μm) was achieved with 3 × 104 cells/cm2 seeding density, 100 μg/mL ascorbic acid concentration under hypoxic and dynamic culture condition. The biocompatibility assessment showed that UCs and SMCs seeded on the scaffold could proliferate and maintain the expression of their markers (CK7, CK20, UPIa, and UPII) and (α-SMA, MHC and Smootheline), respectively, after 14 days of in vitro culture. ECM gene expression analysis showed that the ASC and dermal fibroblast-based scaffolds (control) were comparable. The ASC-based scaffold can be handled and removed from the plate. This suggests that multiple layers of scaffold can be stacked to form the urothelium (seeded with UCs), submucosal layer (ASCs only), and smooth muscle layer (seeded with SMCs) and has the potential to be developed into a fully functional human urethra for urethral reconstructive surgeries.
    Matched MeSH terms: Muscle, Smooth
  14. Shastri MD, Chong WC, Dua K, Peterson GM, Patel RP, Mahmood MQ, et al.
    Inflammopharmacology, 2021 Feb;29(1):15-33.
    PMID: 33152094 DOI: 10.1007/s10787-020-00770-y
    Asthma is a common, heterogeneous and serious disease, its prevalence has steadily risen in most parts of the world, and the condition is often inadequately controlled in many patients. Hence, there is a major need for new therapeutic approaches. Mild-to-moderate asthma is considered a T-helper cell type-2-mediated inflammatory disorder that develops due to abnormal immune responses to otherwise innocuous allergens. Prolonged exposure to allergens and persistent inflammation results in myofibroblast infiltration and airway remodelling with mucus hypersecretion, airway smooth muscle hypertrophy, and excess collagen deposition. The airways become hyper-responsive to provocation resulting in the characteristic wheezing and obstructed airflow experienced by patients. Extensive research has progressed the understanding of the underlying mechanisms and the development of new treatments for the management of asthma. Here, we review the basis of the disease, covering new areas such as the role of vascularisation and microRNAs, as well as associated potential therapeutic interventions utilising reports from animal and human studies. We also cover novel drug delivery strategies that are being developed to enhance therapeutic efficacy and patient compliance. Potential avenues to explore to improve the future of asthma management are highlighted.
    Matched MeSH terms: Muscle, Smooth
  15. Govindaraju, Kayatri, Lee, Mei Kee, Mbaki, Yvonne, Ting, Kang Nee
    MyJurnal
    The general notion of activation of Gq-protein coupled receptors (GPCR) involves the mobilisation of stored and extracellular calcium and leads to smooth muscle tissue contraction. The aim of this study was to investigate the involvement of calcium mediated contractions in vascular and airway smooth muscles. Using standard organ bath procedures, aortic and tracheal rings were obtained from 6 to 8 week-old male Sprague Dawley rats. To activate the Gq protein receptors, phenylephrine (PE), an α1-adrenoceptor agonist, and carbachol, a M3 cholinoceptor agonist was added to baths containing the aortic and tracheal rings, respectively. The maximum response (Emax) to PE was reduced from 158.8 ± 11.8% (n=6) to 62.5 ± 12.4 % (n=8) upon removal of extracellular calcium in Krebs-Ringer solution. Maximal response to PE was also suppressed in the presence of nifedipine, a L-type Ca2+ channel inhibitor, (70.3 ± 11 %, n=8) and SKF96365, a canonical transient receptor potential cation channel inhibitor, (26.7 ± 13.2 %, n=5) when the influx of extracellular calcium was blocked. Removal of stored calcium also attenuated the PE contraction (p0.05). From these observations, we conclude that the role of stored and extracellular calcium in Gq protein activation is not the same across different types of smooth muscle tissues.
    Matched MeSH terms: Muscle, Smooth
  16. Mirmajidi T, Chogan F, Rezayan AH, Sharifi AM
    Int J Pharm, 2021 Mar 01;596:120213.
    PMID: 33493599 DOI: 10.1016/j.ijpharm.2021.120213
    Wound healing is a complicated process that takes a long time to complete. The three-layer nanofiber wound dressing containing melatonin is highly expected to show remarkable wound repair by reducing the wound healing time. In this study, chitosan (Cs)-polycaprolactone (PCL)/ polyvinylalcohol (PVA)-melatonin (MEL)/ chitosan-polycaprolactone three-layer nanofiber wound dressing was prepared by electrospinning for melatonin sustained release. The characteristics of the wound dressing were further evaluated. The wound dressing had a high water uptake after 24 h (401%), and the water contact angle results showed that it had hydrophilicity effect that supported the cell attachment. The wound healing effect of wound dressing was examined using a full-thickness excisional model of rat skin by the local administration of MEL. The gene expressions of transforming growth factor-beta (TGF-β1), alpha-smooth muscle actin (α-SMA), collagen type I (COL1A1), and collagen type III (COL3A1) were further studied. The histopathological evaluation showed the complete regeneration of the epithelial layer, remodeling of wounds, collagen synthesis, and reduction in inflammatory cells. The NF + 20% MEL significantly increased TGF-β1, COL1A1, COL3A1, and α-SMA mRNA expressions. This wound dressing may have a considerable potential as a wound dressing to accelerate the wound healing.
    Matched MeSH terms: Muscle, Smooth
  17. Larsson HM, Vythilingam G, Pinnagoda K, Vardar E, Engelhardt EM, Sothilingam S, et al.
    Sci Rep, 2018 07 03;8(1):10057.
    PMID: 29968749 DOI: 10.1038/s41598-018-27621-9
    There is a need for efficient and "off-the-shelf" grafts in urethral reconstructive surgery. Currently available surgical techniques require harvesting of grafts from autologous sites, with increased risk of surgical complications and added patient discomfort. Therefore, a cost-effective and cell-free graft with adequate regenerative potential has a great chance to be translated into clinical practice. Tubular cell-free collagen grafts were prepared by varying the collagen density and fiber distribution, thereby creating a polarized low fiber density collagen graft (LD-graft). A uniform, high fiber density collagen graft (HD-graft) was engineered as a control. These two grafts were implanted to bridge a 2 cm long iatrogenic urethral defect in a rabbit model. Histology revealed that rabbits implanted with the LD-graft had a better smooth muscle regeneration compared to the HD-graft. The overall functional outcome assessed by contrast voiding cystourethrography showed patency of the urethra in 90% for the LD-graft and in 66.6% for the HD-graft. Functional regeneration of the rabbit implanted with the LD-graft could further be demonstrated by successful mating, resulting in healthy offspring. In conclusion, cell-free low-density polarized collagen grafts show better urethral regeneration than high-density collagen grafts.
    Matched MeSH terms: Muscle, Smooth
  18. Ch'ng YS, Loh YC, Tan CS, Ahmad M, Asmawi MZ, Wan Omar WM, et al.
    J Med Food, 2018 Mar;21(3):289-301.
    PMID: 29420109 DOI: 10.1089/jmf.2017.4008
    The seeds of Swietenia macrophylla King (SM) (Meliaceae) are used as a folk medicine for the treatment of hypertension in Malaysia. However, the antihypertensive and vasorelaxant effects of SM seeds are still not widely studied. Thus, this study was designed to investigate the in vivo antihypertensive effects and in vitro mechanism of vasorelaxation of a 50% ethanolic SM seed extract (SM50) and the fingerprint of SM50 was developed through tri-step Fourier transform infrared (FTIR) spectroscopy. The vasorelaxant activity and the underlying mechanisms of SM50 were evaluated on thoracic aortic rings isolated from Sprague-Dawley rats in the presence of antagonists. The pharmacological effect of SM50 was investigated by oral administration of spontaneously hypertensive rats (SHRs) with three different doses of SM50 (1000, 500, and 250 mg/kg/day) for 4 weeks and their systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were measured weekly using tail-cuff method. The tri-step FTIR macro-fingerprint of SM50 showed that SM50 contains stachyose, flavonoids, limonoids, and ester, which may contribute to its vasorelaxant effect. The results showed that the vasorelaxant activity of SM50 was mostly attributed to channel-linked receptors pathways through the blockage of voltage-operated calcium channels (VOCC). SM50 also acts as both potassium channels opener and inositol triphosphate receptor (IP3R) inhibitor, followed by β2-adrenergic pathway, and ultimately mediated through the nitric oxide/soluble guanylyl cyclase/cyclic 3',5'-guanosine monophosphate (NO/sGC/cGMP) signaling pathways. The treatment of SM50 also significantly decreased the SBP and DBP in SHRs. In conclusion, the antihypertensive mechanism of SM50 was mediated by VOCC, K+ channels, IP3R, G-protein-coupled β2-adrenergic receptor, and followed by NO/sGC/cGMP signaling mechanism pathways in descending order. The data suggested that SM50 has the potential to be used as a herbal medicament to treat hypertension.
    Matched MeSH terms: Muscle, Smooth, Vascular/drug effects; Muscle, Smooth, Vascular/physiology; Muscle, Smooth, Vascular/physiopathology
  19. Sakihama H, Lee GR, Chin BY, Csizmadia E, Gallo D, Qi Y, et al.
    Arterioscler Thromb Vasc Biol, 2021 Jun;41(6):1915-1927.
    PMID: 33853347 DOI: 10.1161/ATVBAHA.120.315558
    [Figure: see text].
    Matched MeSH terms: Muscle, Smooth, Vascular/drug effects*; Muscle, Smooth, Vascular/enzymology; Muscle, Smooth, Vascular/pathology
  20. Abdelwahab SI, Mohamed AH, Mohamed OY, Oall M, Taha MM, Mohan S, et al.
    PMID: 21747892 DOI: 10.1155/2012/137386
    Clerodendron capitatum (Willd) (family: verbenaceae) is locally named as Gung and used traditionally to treat erectile dysfunction. Therefore, the current study was designed to investigate the erectogenic properties of C. capitatum. The relaxation effect of this plant was tested on phenylephrine precontracted rabbit corpus cavernosum smooth muscle (CCSM). The effects of C. capitatum were also examined on isolated Guinea pig atria alone, in the presence of calcium chloride (Ca(2+) channel blocker), atropine (cholinergic blocker), and glibenclamide (ATP-sensitive K(+) channel blocker). These effects were confirmed on isolated rabbit aortic strips. The extract, when tested colorimetrically for its inhibitory activities on phosphordiesterase-5 (PDE-5) in vitro towards p-nitrophenyl phenyl phosphate (PNPPP), was observed to induce significant dose-dependent inhibition of PDE-5, with an ID(50) of 0.161 mg/ml (P < .05). In conclusion, our results suggest that C. capitatum possesses a relaxant effect on CCSM, which is attributable to the inhibition of PDE-5, but not mediated by the release calcium, activation of adrenergic or cholinergic receptors, or the activation of potassium channels.
    Matched MeSH terms: Muscle, Smooth
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