Displaying publications 1 - 20 of 55 in total

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  1. Chin, V.K., Chong, W.C., Hassan, H., Zakaria, Z.A., Nordin, N., Basir, R., et al.
    JUMMEC, 2019;22(2):4-12.
    MyJurnal
    Background: The cytokine cascade in the immunopathogenesis of malaria infection had been widely studied.
    However, their specific association with survival and severe infection remained obscure.

    Methods: The study investigated the cytokine profiles and histopathological features of malaria in the severe
    infection and survival models by using male ICR mice and male Sprague Dawley rats respectively.

    Results: The severe model, the infected ICR mice, exhibited a high parasitemia with 100% mortality after
    peak parasitemia at day 5 post-infection. The survival model, the infected Sprague Dawley rats, showed
    mild parasitemia with full recovery by day 14 of infection. Both severe and survival models showed similar
    histopathological severity during peak parasitemia. The severe model produced highly elevated levels of proinflammatory
    cytokines, TNF-α and IL-1α, and low levels of the anti-inflammatory cytokine, IL-4; while the
    survival model showed low levels of TNF-α and IL-1α with high levels of IL-4.

    Conclusion: There were differences in the pathogenesis of the severe and survival models of malaria infection.
    These could be a basis for immunotherapy of malaria in the future.
  2. Yam MF, Asmawi MZ, Basir R
    J Med Food, 2008 Jun;11(2):362-8.
    PMID: 18598181 DOI: 10.1089/jmf.2006.065
    Anti-inflammatory and analgesic activities of a standardized Orthosiphon stamineus methanol:water (50:50 vol/vol) leaf extract (SEOS) were evaluated in animal models. Oral administration of SEOS at doses of 500 and 1,000 mg/kg significantly reduced the hind paw edema in rats at 3 and 5 hours after carrageenan administration (P < .01 and P < .01; P < .01 and P < .05, respectively). SEOS (1,000 mg/kg, p.o.) also produced significant (P < .05) analgesic activity in both the acetic acid-induced writhing test and the formalin-induced licking test (late phase) in mice and rats, respectively. However, SEOS showed no effect on the tail flick and hot plate tests in mice. The results of the present study support the proposal that O. stamineus has anti-inflammatory and non-narcotic analgesic activities. These findings justify the traditional use of the plant for treating pain and inflammation.
  3. Chong WC, Basir R, Fei YM
    Asian Pac J Trop Med, 2013 Feb;6(2):85-94.
    PMID: 23339908 DOI: 10.1016/S1995-7645(13)60001-2
    Malaria is an intra-cellular parasitic protozoon responsible for millions of deaths annually. Host and parasite genetic factors are crucial in affecting susceptibility to malaria and progression of the disease. Recent increased deployment of vector controls and new artemisinin combination therapies have dramatically reduced the mortality and morbidity of malaria worldwide. However, the gradual emergence of parasite and mosquito resistance has raised alarm regarding the effectiveness of current artemisinin-based therapies. In this review, mechanisms of anti-malarial drug resistance in the Plasmodium parasite and new genetically engineered tools of research priorities are discussed. The complexity of the parasite lifecycle demands novel interventions to achieve global eradication. However, turning laboratory discovered transgenic interventions into functional products entails multiple experimental phases in addition to ethical and safety hurdles. Uncertainty over the regulatory status and public acceptance further discourage the implementation of genetically modified organisms.
  4. Ibraheem ZO, Abd Majid R, Noor SM, Sedik HM, Basir R
    Malar Res Treat, 2014;2014:950424.
    PMID: 25506039 DOI: 10.1155/2014/950424
    Emergence of drugs resistant strains of Plasmodium falciparum has augmented the scourge of malaria in endemic areas. Antimalaria drugs act on different intracellular targets. The majority of them interfere with digestive vacuoles (DVs) while others affect other organelles, namely, apicoplast and mitochondria. Prevention of drug accumulation or access into the target site is one of the mechanisms that plasmodium adopts to develop resistance. Plasmodia are endowed with series of transporters that shuffle drugs away from the target site, namely, pfmdr (Plasmodium falciparum multidrug resistance transporter) and pfcrt (Plasmodium falciparum chloroquine resistance transporter) which exist in DV membrane and are considered as putative markers of CQ resistance. They are homologues to human P-glycoproteins (P-gh or multidrug resistance system) and members of drug metabolite transporter (DMT) family, respectively. The former mediates drifting of xenobiotics towards the DV while the latter chucks them outside. Resistance to drugs whose target site of action is intravacuolar develops when the transporters expel them outside the DVs and vice versa for those whose target is extravacuolar. In this review, we are going to summarize the possible pfcrt and pfmdr mutation and their role in changing plasmodium sensitivity to different anti-Plasmodium drugs.
  5. Chuah YK, Basir R, Talib H, Tie TH, Nordin N
    Int J Inflam, 2013;2013:403460.
    PMID: 24102034 DOI: 10.1155/2013/403460
    The receptor for advanced glycation end products (RAGE) is a transmembrane receptor of the immunoglobulin superfamily, capable of binding a broad repertoire of ligands. RAGE-ligands interaction induces a series of signal transduction cascades and lead to the activation of transcription factor NF-κB as well as increased expression of cytokines, chemokines, and adhesion molecules. These effects endow RAGE with the role in the signal transduction from pathogen substrates to cell activation during the onset and perpetuation of inflammation. RAGE signaling and downstream pathways have been implicated in a wide spectrum of inflammatory-related pathologic conditions such as arteriosclerosis, Alzheimer's disease, arthritis, acute respiratory failure, and sepsis. Despite the significant progress in other RAGE studies, the functional importance of the receptor in clinical situations and inflammatory diseases still remains to be fully realized. In this review, we will summarize current understandings and lines of evidence on the molecular mechanisms through which RAGE signaling contributes to the pathogenesis of the aforementioned inflammation-associated conditions.
  6. Yam MF, Loh YC, Oo CW, Basir R
    Int J Mol Sci, 2020 Jun 19;21(12).
    PMID: 32575378 DOI: 10.3390/ijms21124355
    Pain is the most common sensation installed in us naturally which plays a vital role in defending us against severe harm. This neurological mechanism pathway has been one of the most complex and comprehensive topics but there has never been an elaborate justification of the types of analgesics that used to reduce the pain sensation through which specific pathways. Of course, there have been some answers to curbing of pain which is a lifesaver in numerous situations-chronic and acute pain conditions alike. This has been explored by scientists using pain-like behavioral study methodologies in non-anesthetized animals since decades ago to characterize the analgesic profile such as centrally or peripherally acting drugs and allowing for the development of analgesics. However, widely the methodology is being practiced such as the tail flick/Hargreaves test and Von Frey/Randall-Selitto tests which are stimulus-evoked nociception studies, and there has rarely been a complete review of all these methodologies, their benefits and its downside coupled with the mechanism of the action that is involved. Thus, this review solely focused on the complete protocol that is being adapted in each behavioral study methods induced by different phlogogenic agents, the different assessment methods used for phasic, tonic and inflammatory pain studies and the proposed mechanism of action underlying each behavioral study methodology for analgesic drug profiling. It is our belief that this review could significantly provide a concise idea and improve our scientists' understanding towards pain management in future research.
  7. Hassan WRM, Basir R, Ali AH, Embi N, Sidek HM
    Trop Biomed, 2019 Sep 01;36(3):776-791.
    PMID: 33597499
    Malarial pathogenesis involves among others, uncontrolled or excessive cytokine production arising from dysregulated immune responses mounted by the host to eliminate the plasmodial parasite. The ubiquitous serine/threonine kinase, glycogen synthase kinase3β (GSK3β) is a crucial regulator of the balance between pro- and anti-inflammatory cytokine productions in the inflammatory response to pathogenic infections. Andrographolide, a bioactive compound in Andrographis paniculata, displays GSK3- inhibitory effects. A previous study elsewhere has shown that this compound has antimalarial activity but the molecular basis of its action is yet to be elucidated. Here we aimed to study the anti-malarial activity of andrographolide in a murine model of malarial infection to investigate whether its mechanism of action involves cytokine modulation and inhibition of GSK3β. Andrographolide showed strong and selective anti-plasmodial activity (IC50 = 13.70±0.71 µM; SI = 30.43) when tested against cultures of P. falciparum 3D7. Intraperitoneal administration of andrographolide (5 mg/kg body weight (bw)) into P. berghei NK65-infected ICR mice resulted in chemo-suppression of 60.17±2.12%, and significantly (P<0.05) improved median survival time of infected mice compared to nontreated control. In addition, andrographolide treatment significantly (P<0.05) decreased the level of serum pro-inflammatory cytokine, IFN-γ (1.4-fold) whilst the anti-inflammatory cytokines, IL-10 and IL-4 were increased 2.3- and 2.6-fold respectively. Western blot analyses revealed that andrographolide treatment of P. berghei NK65-infected mice resulted in an increased level of phosphorylated GSK3β (Ser9) in liver of infected mice. Andrographolide administration also decreased the levels of phosphorylated NF-κB p65 (Ser536) and phosphorylated Akt (Ser473) in liver of malaria- infected animals. Taken together, our findings demonstrate that the cytokine-modulating effect of andrographolide in experimental malarial infection involves at least in part inhibition of NF-κB activation as a consequence of GSK3β inhibition. Based on its cytokine-modulating effects, andrographolide is thus a plausible candidate for adjunctive therapy in malaria subject to clinical evaluations.
  8. Soo KM, Tham CL, Khalid B, Basir R, Chee HY
    Trop Biomed, 2019 Dec 01;36(4):1027-1037.
    PMID: 33597472
    Dengue is a common infection, caused by dengue virus. There are four different dengue serotypes, with different capacity to cause severe dengue infections. Besides, secondary infections with heterologous serotypes, concurrent infections of multiple dengue serotypes may alter the severity of dengue infection. This study aims to compare the severity of single infection and concurrent infections of different combinations of dengue serotypes in-vitro. Human mast cells (HMC)-1.1 were infected with single and concurrent infections of multiple dengue serotypes. The infected HMC-1.1 supernatant was then added to human umbilical cord vascular endothelial cells (HUVEC) and severity of dengue infections was measured by the percentage of transendothelial electrical resistance (TEER). Levels of IL10, CXCL10 and sTRAIL in HMC-1.1 and IL-8, IL-10 and CXCL10 in HUVEC culture supernatants were measured by the ELISA assays. The result showed that the percentage of TEER values were significantly lower in single infections (p< 0.05), compared to concurrent infections on day 2 and 3, indicating that single infection increase endothelial permeability greater than concurrent infections. IL-8 showed moderate correlation with endothelial permeability (r > 0.4), indicating that IL-8 may be suitable as an in-vitro severity biomarker. In conclusion, this in-vitro model presented few similarities with regards to the conditions in dengue patients, suggesting that it could serve as a severity model to test for severity and levels of severity biomarkers upon different dengue virus infections.
  9. Chin VK, Basir R, Nordin SA, Abdullah M, Sekawi Z
    Int Microbiol, 2020 May;23(2):127-136.
    PMID: 30875033 DOI: 10.1007/s10123-019-00067-3
    Human leptospirosis is considered as one of the most widespread and potentially fatal zoonotic diseases that causes high mortality and morbidity in the endemic regions of tropical and subtropical countries. The infection can arise from direct or indirect exposure of human through contaminated environment that contains leptospires or animal reservoirs that carry leptospires. The clinical manifestations during human leptospirosis ranges from asymptomatic, mild infections to severe and life-threatening complications involving multi-organ failures with kidneys, lungs and liver severely affected. Despite much efforts have been put in to unravel the pathogenesis during human leptospirosis, it remains obscure to which extent the host factors or the pathogen itself contribute towards the pathogenesis. Host innate immunity, especially, polymorphonuclear neutrophils and complement system are involved in the first line of defense during human leptospirosis. However, pathogenic Leptospira has acquired diverse evasion strategies to evade from host immunity and establish infection in infected hosts. Hence, in this review, we focus on organs pathology during human leptospiral infection and host evasion strategies employed by Leptospira. A profound understanding on leptospiral immunity and how Leptospira subvert the immune system may provide new insights on the development of therapeutic regimens against this species in future.
  10. Yam MF, Basir R, Asmawi MZ, Ismail Z
    Am J Chin Med, 2007;35(1):115-26.
    PMID: 17265556
    Orthosiphon stamineus (OS), Benth. (Lamiaceae) is widely used in Malaysia for treatments of various kidney and liver ailments. In the experiment, DPPH* radicals scavenging, Fe(3+)-induced lipid peroxidation inhibiting activities and trolox equivalent antioxidant capacity (TEAC) of methanol/water extract of Orthosiphon stamineus (SEOS) were determined. The results indicated that SEOS exhibited antioxidant, lipid peroxidation inhibition and free radical scavenging activities. The hepatoprotective activity of the SEOS was studied using CCl(4)-induced liver toxicity in rats. The activity was assessed by monitoring liver function tests through the measurement of alanine transaminase (ALT) and aspartate transaminase (AST). Furthermore, hepatic tissues were also subjected to histopathological studies. Pretreatment of SEOS (125, 250, 500 and 1000 mg/kg p.o.) dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of serum ALT and AST activities. The results of the present study indicated that the hepatoprotective effect of Orthosiphon stamineus might be ascribable to its antioxidant and free radical scavenging property.
  11. Ali AH, Sudi S, Basir R, Embi N, Sidek HM
    J Med Food, 2017 Feb;20(2):152-161.
    PMID: 28146408 DOI: 10.1089/jmf.2016.3813
    Curcumin, a bioactive compound in Curcuma longa, exhibits various pharmacological activities, including antimalarial effects. In silico docking simulation studies suggest that curcumin possesses glycogen synthase kinase-3β (GSK3β)-inhibitory properties. The involvement of GSK3 in the antimalarial effects in vivo is yet to be demonstrated. In this study, we aimed to evaluate whether the antimalarial effects of curcumin involve phosphorylation of host GSK3β. Intraperitoneal administration of curcumin into Plasmodium berghei NK65-infected mice resulted in dose-dependent chemosuppression of parasitemia development. At the highest dose tested (30 mg/kg body weight), both therapeutic and prophylactic administrations of curcumin resulted in suppression exceeding 50% and improved median survival time of infected mice compared to control. Western analysis revealed a 5.5-fold (therapeutic group) and 1.8-fold (prophylactic group) increase in phosphorylation of Ser 9 GSK3β and 1.6-fold (therapeutic group) and 1.7-fold (prophylactic group) increase in Ser 473 Akt in liver of curcumin-treated infected animals. Following P. berghei infection, levels of pro- and anti-inflammatory cytokines, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-10, and IL-4 were elevated by 7.5-, 35.0-, 33.0-, and 2.2-fold, respectively. Curcumin treatment (therapeutic) caused a significant decrease (by 6.0- and 2.0-fold, respectively) in serum TNF-α and IFN-γ level, while IL-10 and IL-4 were elevated (by 1.4- and 1.8-fold). Findings from the present study demonstrate for the first time that the antimalarial action of curcumin involved inhibition of GSK3β.
  12. Suliman NA, Taib CNM, Moklas MAM, Basir R
    Neurotox Res, 2018 02;33(2):402-411.
    PMID: 28933048 DOI: 10.1007/s12640-017-9806-x
    Neurogenesis is influenced by various external factors such as enriched environments. Some researchers had postulated that neurogenesis has contributed to the hippocampal learning and memory. This project was designed to observe the effect of Delta-9-tetrahydrocannabinol (∆9-THC) in cognitive performance that influenced by the neurogenesis. Different doses of ∆9-THC were used for observing the neurogenesis mechanism occurs in the hippocampus of rats. The brains were stained with antibodies, namely BrdU, glial fibrillary acidic protein (GFAP), nestin, doublecortin (DCX) and class III β-tubulin (TuJ-1). The cognitive test was used novel-object discrimination test (NOD) while the proteins involved, DCX and brain-derived neurotrophic factor (BDNF), were measured. Throughout this study, ∆9-THC enhanced the markers involved in all stages of neurogenesis mechanism. Simultaneously, the cognitive behaviour of rat also showed improvement in learning and memory functions observed in behavioural test and molecular perspective. Administration of ∆9-THC was observed to enhance the neurogenesis in the brain, especially in hippocampus thus improved the cognitive function of rats.
  13. Movahedi A, Basir R, Rahmat A, Charaffedine M, Othman F
    PMID: 25197311 DOI: 10.1155/2014/726724
    The term cancer has been concomitant with despair, agony, and dreadful death. Like many other diseases, herbal therapy has been used to prevent or suppress cancer. The present study investigated the capability of the decoction of Teucrium polium L. from Lamiaceae family to protect liver cells against hepatocellular carcinoma in carcinogenesis-induced animal model. After 28 weeks of treatment with decoction of Teucrium polium L., serum biochemical markers including ALT, AST, AFP, GGT, ALP, HCY, TNF-α, α2MG, and CBG have been regulated auspiciously. Total antioxidant status also has been increased intensely. Liver lesion score in treated group was lessened and glucocorticoid activity has been intensified significantly. In conclusion, Teucrium polium L. decoction might inhibit or suppress liver cancer development.
  14. Ibraheem ZO, Basir R, Aljobory AKh, Ibrahim OE, Alsumaidaee A, Yam MF
    Biomed Res Int, 2014;2014:823879.
    PMID: 25045706 DOI: 10.1155/2014/823879
    The current study evaluates the impact of high fructose feeding in rat model of gentamicin induced nephrotoxicity. Sprague-Dawley rats weighing 180-200 g were randomized into four groups; (C) received standard rodents chow with free access to ad libitum drinking water for 8 weeks and was considered as control, (F) received standard rodents chow with free access to drinking water supplemented with 20% (W/V) fructose for the same abovementioned period, (FG) was fed as group F and was given 80 mg/kg (body weight)/day gentamicin sulphate intraperitoneally during the last 20 days of the feeding period, and (G) was given gentamicin as above and fed as group C. Renal function was assessed at the end of the treatment period through measuring serum creatinine, uric acid and albumin, creatinine clearance, absolute and fractional excretion of both sodium and potassium, twenty-four-hour urinary excretion of albumin, and renal histology. For metabolic syndrome assessment, fasting plasma glucose and insulin were measured and oral glucose tolerance test was performed throughout the treatment period. Results showed that gentamicin enhances progression of fructose induced metabolic syndrome. On the other hand, fructose pretreatment before gentamicin injection produced a comparable degree of renal dysfunction to those which were given fructose-free water but the picture of nephrotoxicity was somewhat altered as it was characterized by higher extent of glomerular congestion and protein urea. Overall, more vigilance is required when nephrotoxic drugs are prescribed for patients with fructose induced metabolic syndrome.
  15. Saleem AM, Taufik Hidayat M, Jais AM, Fakurazi S, Moklas MA, Sulaiman MR, et al.
    Eur Rev Med Pharmacol Sci, 2013;17(15):2019-22.
    PMID: 23884821
    BACKGROUND: In our previous study, the aqueous extract of Channa striatus (family: Channidae) fillet (AECSF) showed an antidepressant-like effect in mice. However, the mechanism of the antidepressant-like effect is unknown.
    AIM: The objective of this study was to explore the involvement of monoamines in the antidepressant-like effect of AECSF in mice.
    MATERIALS AND METHODS: AECSF was prepared by steaming the fillets of C. striatus. The male ICR mice were pretreated with various monoaminergic antagonists viz., p-chlorophenylalanine (100 mg/kg, i.p.), prazosin (1 mg/kg, i.p.) and yohimbine (1 mg/kg, i.p.), SCH23390 (0.05 mg/kg, s.c.) and sulpiride (50 mg/kg, i.p.) followed by treatment with AECSF and tested in tail suspension test (TST). Two-way ANOVA with Tukey test were used at p < 0.05 for significance.
    RESULTS: The pretreatments with p-chlorophenylalanine, prazosin and yohimbine, but not with SCH23390 and sulpiride, were able to reverse the antidepressant-like effect of AECSF in TST.
    CONCLUSIONS: The antidepressant-like effect of AECSF may be mediated through the serotonergic and noradrenergic systems and not through the dopaminergic system.
  16. Yam MF, Ahmad M, Por LY, Ang LF, Basir R, Asmawi MZ
    Sensors (Basel), 2012;12(7):9603-12.
    PMID: 23012561
    The stepping forces of normal and Freund Complete Adjuvant (FCA)-induced arthritic rats were studied in vivo using a proposed novel analgesic meter. An infrared charge-coupled device (CCD) camera and a data acquisition system were incorporated into the analgesic meter to determine and measure the weight of loads on the right hind paw before and after induction of arthritis by FCA injection into the paw cavity. FCA injection resulted in a significant reduction in the stepping force of the affected hind paw. The stepping force decreased to the minimum level on day 4 after the injection and then gradually increased up to day 25. Oral administration of prednisolone significantly increased the stepping forces of FCA-induced arthritic rats on days 14 and 21. These results suggest that the novel device is an effective tool for measuring the arthritic pain in in vivo studies even though walking is a dynamic condition.
  17. Yam MF, Ang LF, Basir R, Salman IM, Ameer OZ, Asmawi MZ
    Inflammopharmacology, 2009 Feb;17(1):50-4.
    PMID: 19127348 DOI: 10.1007/s10787-008-8038-3
    The anti-pyretic activity of a standardized methanol/water (50/50) extract of Orthosiphon stamineus Benth. (SEOS) was investigated for its effect on normal body temperature and yeast-induced pyrexia in Sprague Dawley (SD) rats. The SEOS showed no effect on normal body temperature. Doses of 500 and 1000 mg/kg body weight of SEOS significantly reduced the yeast-induced elevation in body temperature. This effect persisted up to 4 h following the administration of the extract. The anti-pyretic effect of SEOS was comparable with that of paracetamol (acetaminophen in U.S) (150 mg/kg p.o.), a standard anti-pyretic agent. HPLC study revealed that rosmarinic acid, sinensetin, eupatorin and tetramethoxyflavone were present in SEOS in the amounts of 7.58%, 0.2%, 0.34% and 0.24% respectively. The LD(50) of the extract in rats was higher than 5000 mg/kg body weight. Therefore, the present study ascertained that SEOS possesses a significant anti-pyretic activity.
  18. Ibraheem ZO, Abdul Majid R, Mohd Noor S, Mohd Sidek H, Basir R
    Iran J Parasitol, 2015 Oct-Dec;10(4):577-83.
    PMID: 26811724
    Nowadays, scourge of malaria as a fatalistic disease has increased due to emergence of drug resistance and tolerance among different strains of Plasmodium falciparum. Emergence of chloroquine (CQ) resistance has worsened the calamity as CQ is still considered the most efficient, safe and cost effective drug among other antimalarials. This urged the scientists to search for other alternatives or sensitizers that may be able to augment CQ action and reverse its resistance.
  19. Zaid OI, Abd Majid R, Sabariah MN, Hasidah MS, Al-Zihiry K, Yam MF, et al.
    Asian Pac J Trop Med, 2015 Jul;8(7):507-12.
    PMID: 26276279 DOI: 10.1016/j.apjtm.2015.06.007
    OBJECTIVE: To explore whether its antiplasmodium effect of andrographolide is attributed to its plausible effect on the plasma membrane of both Plasmodium falciparum infected and non-infected RBCs.

    METHODS: Anti-plasmodium effect of andrographolide against Plasmodium falciparum strains was screened using the conventional malaria drug sensitivity assay. The drug was incubated with uninfected RBCs to monitor its effect on their morphology, integrity and osmotic fragility. It was incubated with the plasmodium infected RBCs to monitor its effect on the parasite induced permeation pathways. Its effect on the potential of merozoites to invade new RBCs was tested using merozoite invasion assay.

    RESULTS: It showed that at andrographolide was innocuous to RBCs at concentrations approach its therapeutic level against plasmodia. Nevertheless, this inertness was dwindled at higher concentrations.

    CONCLUSIONS: In spite of its success to inhibit plasmodium induced permeation pathway and the potential of merozoites to invade new RBCs, its anti-plasmodium effect can't be attributed to these functions as they were attained at concentrations higher than what is required to eradicate the parasite. Consequently, other mechanisms may be associated with its claimed actions.

  20. Zakaria ZA, Roosli RAJ, Marmaya NH, Omar MH, Basir R, Somchit MN
    Biomolecules, 2020 02 12;10(2).
    PMID: 32059475 DOI: 10.3390/biom10020280
    Dicranopteris linearis leaf has been reported to exert antinociceptive activity. The present study elucidates the possible mechanisms of antinociception modulated by the methanol extract of D. linearis leaves (MEDL) using various mouse models. The extract (25, 150, and 300 mg/kg) was administered orally to mice for 30 min priot to subjection to the acetic acid-induced writhing-, hot plate- or formalin-test to establish the antinociceptive profile of MEDL. The most effective dose was then used in the elucidation of possible mechanisms of action stage. The extract was also subjected to the phytochemical analyses. The results confirmed that MEDL exerted significant (p < 0.05) antinociceptive activity in those pain models as well as the capsaicin-, glutamate-, bradykinin- and phorbol 12-myristate 13-acetate (PMA)-induced paw licking model. Pretreatment with naloxone (a non-selective opioid antagonist) significantly (p < 0.05) reversed MEDL effect on thermal nociception. Only l-arginine (a nitric oxide (NO) donor) but not N(ω)-nitro-l-arginine methyl ester (l-NAME; a NO inhibitor) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a specific soluble guanylyl cyclase inhibitor) significantly (p < 0.05) modified MEDL effect on the writhing test. Several polyphenolics and volatile antinociceptive compounds were detected in MEDL. In conclusion, MEDL exerted the opioid/NO-mediated antinociceptive activity, thus, justify D. linearis as a potential source for new analgesic agents development.
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