Analgesic, Anti-inflammatory and Antipyretic Activity of Rotula aquatica Lour Leave

The present study was aimed to evaluate analgesic, anti-inflammatory and anti pyretic activity of methanolic extract and aqueous extract of leave of Rotula aquatica L. in mice and rats. The methanolic extract of R. aquatica L. leave at a dose of 200mg/kg body weight has shown significant analgesic, antipyretic and anti-inflammatory activity as compared to aqueous extract. The result of hot plate method indicated that the total methanolic extract showed significant increase (P<0.01) in reaction time at a 3,4and 6 hours comparable to the reference drug Pentazocin but lesser (P<0.05) after 2hr. The tail immersion and hot plate tests revealed that plant has high analgesic activity. Both tests showed highest degree of analgesia in methanolic extract compared to aqueous extract. The total methanolic extract of R.aquatica L. leave at the a dose of 200mg/kg body weight has shown significant (p<0.01) antipyretic activity as compared to aqueous extract, methanolic extract also found to have significant result in Carrageenin-induced paw oedema; suspect edmodeo faction may be due to possible inhibition of lipooxygenase pathway.

Synthesis and Antinociceptive activity of Newly Modified Amine analogs of Phencyclidine in Mice

Background: Phencyclidine (PCP, I) and its substituted analogs are significant and broadly abused psychotomimetic drugs that affect the central nervous system. They show many pharmacological properties due to the presence of specific receptors in the brain. Aim and Objective: Methyl group, despite strong electron-donating and characters of dipole moments, were placed on various positions of phenyl and amine moieties of Phencyclidine along with the substitution of benzylamine, piperazine, and aniline derivatives in place of piperidine ring of Phencyclidine to create novel compounds of the core with analgesic properties. Material and methods: For evaluation of the Analgesic activities of newly synthesized compounds, they were screened by tests of tail immersion (thermal) and formalin (chemical) pains. The obtained data with the control and PCP groups were compared too. Results: The outcomes indicated that some new compounds have more antinociceptive effects than PCP in tail immersion and formalin tests. In the tail immersion test, the methyl piperazine analog (III) shows more efficacy than others. In the formalin test, none of the compounds are as effective as phencyclidine at the earliest time-point, but compounds IV and V do show more effective during the second stage of formalin pain. Conclusion: It can be concluded that the methyl-piperazine analog of phencyclidine was the best candidate to decrease acute thermal and benzylamine derivatives were suitable candidates to reduce chemical pains.

Phytochemical and pharmacological investigations of different extracts of leaves and stem barks of Macropanax dispermus (Araliaceae): a promising ethnomedicinal plant

Background Macropanax dispermus is traditionally used to treat various diseases by ethnic people. The present research reports the pharmacological properties with phytochemical profiling of the crude extracts of M. dispermus leaves (MDML), its n-hexane (MDHL), carbon tetrachloride (MDTL), chloroform (MDCL), ethyl acetate (MDEL), and aqueous (MDAL) fractions, and crude methanol extracts of its stem barks (MDMS). The in vitro thrombolytic activity was done on human erythrocytes whereas the cytotoxic activity was done by brine shrimp lethality assay. The in vivo analgesic activity was examined by acetic acid-induced writhing, tail immersion, and formalin-induced paw licking method. In contrast, antipyretic activity was done by the brewer’s yeast-induced pyrexia method. Results MDHL and MDMS showed 37.05% and 42.21% of significant (p < 0.01) thrombolytic activity, respectively. MDCL and MDMS showed the lower LC50 values of 23.15 and 37.11 µg/ml during cytotoxicity test, respectively. In acetic acid writhing method, MDTL and MDEL showed significant (p < 0.001) inhibition of writhing by 79.34% and 80.17%, respectively. MDMS showed significant (p < 0.001) maximal possible effect (%MPE) of 45.95%, 62.26%, 65.79%, 89.69% and elongation of time in pain reaction of 48.53%, 60.28%, 58.76%, and 70.14% at 30, 60, 90, and 120 min intervals, respectively. MDML at 400 mg/kg exhibited significant (p < 0.001) 82.72% of inhibition of pain at the late phases. MDEL at 400 mg/kg of dose exhibited significant (p < 0.001) reduction of rectal temperature by 36.31%, 62.42%, 89.81%,, and 96.82% at 1, 2, 3, and 4 h intervals, respectively. Conclusion The current research suggests that the plant extracts possess potential thrombolytic, cytotoxic, analgesic, and antipyretic activities.

TailTimer: A device for automating data collection in the rodent tail immersion assay

The tail immersion assay is a widely used method for measuring acute thermal pain in a way which is quantifiable and reproducible. It is non-invasive and measures response to a stimulus that may be encountered by an animal in its natural environment. However, quantification of tail withdrawal latency relies on manual timing of tail flick using a stopwatch, and precise temperatures of the water at the time of measurement are most often not recorded. These two factors greatly reduce the reproducibility of tail immersion assay data and likely contribute to some of the discrepancies present among relevant literature. We designed a device, TailTimer, which uses a Raspberry Pi single-board computer, a digital temperature sensor, and two electrical wires, to automatically record tail withdrawal latency and water temperature. We programmed TailTimer to continuously display and record water temperature and to only permit the assay to be conducted when the water is within ± 0.25°C of the target temperature. Our software also records the identification of the animals using a radio frequency identification (RFID) system. We further adapted the RFID system to recognize several specific keys as user interface commands, allowing TailTimer to be operated via RFID fobs for increased usability. Data recorded using the TailTimer device showed a negative linear relationship between tail withdrawal latency and water temperature when tested between 47–50°C. We also observed a previously unreported, yet profound, effect of water mixing speed on latency. In one experiment using TailTimer, we observed significantly longer latencies following administration of oral oxycodone versus a distilled water control when measured after 15 mins or 1 h, but not after 4 h. TailTimer also detected significant strain differences in baseline latency. These findings valorize TailTimer in its sensitivity and reliability for measuring thermal pain thresholds.

Pharmacological Evaluation of Antipyretic, Analgesic and Anti-inflammatory Activities of Ethanolic Extract of Cassia fistula

Background: The antipyretic, analgesic and anti-inflammatory activities of two concentrations (100 and 200 mg/kg) of ethanolic extract of leaf, bark, flower and fruit pulp of C. fistula were determined in male wistar albino rats. Methods: Antipyretic activity was assessed by E. coli endotoxin induced pyrexia. Analgesic activity was assessed by hot plate, tail immersion and acetic acid induced writhing test. Anti-inflammatory activity was evaluated by carrageenan-induced rat paw edema assay. Result: Significant (p less than 0.05) antipyretic activity was exhibited from 2h onwards by bark extract @ 200 mg/kg and from 3h onwards by bark extract @100 mg/kg and leaves extract @ 200mg/kg as compared to control group. Significant (p less than 0.05) analgesic activity was shown by extract of bark @ 200 mg/kg as it is evident by increase in reflex time in hot plate (90,120,180 min), tail immersion test (120,180 min) and inhibition of writhing (32.12%). Significant (p less than 0.05) anti-inflammatory activity was exhibited from 3h post administration by bark @ 200 and leaves @ 100 and 200 mg/kg.

Anti-nociceptive Potential of Ethanol Extract of Terminalia macroptera Guill&Perr (Combretaceae) Stem Bark in Mice

Background: Terminalia macroptera Guill. &Perr. (Combretaceae) is a flowering plant with several ethno-medicinal claims. However, the dearth of information on its analgesic property has necessitated this study.Objectives: to evaluate the anti-nociceptive potential of ethanol extract of Terminalia macroptera stem bark (TMSB) in mice.Materials and Methods: Male and female mice of weight range 22 – 25g were randomly allotted into seven groups (n= 5) and treated as follows: Group I received 0.5 mL distilled water orally (negative control), Groups II-V were orally administered ethanol extract of T. macroptera stem bark (TMSB) at 50, 100, 200, and 400 mg/kg respectively while groups VI-VII received piroxicam 10 mg/kg and pentazocine 2 mg/kg intraperitoneally respectively as standards. The same treatment pattern was adopted for both pain models: tail immersion and acetic acid-induced writhing assays. Data were expressed as mean ± standard error of mean (SEM) using two-way analysis of variance (ANOVA) followed by Tukey’s and Bonferroni's multiple comparisons tests with p < 0.05 taken as significance.Results: The ethanolic extract of Terminalia macroptera stem bark showed significant dose-dependent anti-nociceptive activity at 100 and 400 mg/kg (2.95±0.41 and 2.9±0.31 respectively) 60 min post-treatment compared to the negative control group in the tail immersion test. Significant inhibition of nociception (0.20±0.20) was obtained at 400 mg/kg compared to the negative control group in the acetic acid-induced writhing test.Conclusions: The ethanol extract of Terminalia macroptera stem bark exhibited dose-dependent anti-nociceptive potential in both tail immersion and acetic acid-induced writhing assays in mice.

Phytochemical Screening and In vivo Analgesic Activity of Ampelocissus barbata (Wall.) Planch.

Ampelocissus barbata (Wall.) Planch. is a native medicinal herb in Bangladesh. The present study was aimed at exploring the phytochemical compositions and analgesic potential of the plant in vivo. The methanol extract of A. barbata along with its different fractions were subjected to phytochemical evaluation through established chemical tests for ascertaining the available pool of secondary metabolites within the plant. Eventually, the presence of at least eleven classes of phytoconstituents viz. alkaloids, flavonoids, phenolics, glycosides, saponins, starch, phytosterols, coumarins, tanins, resins and quinones were demonstrated. Among the four partitonates, ethyl acetate soluble fraction of A. barbata illustrated the maximum types of secondary metabolites qualitatively. The ability of the crude methanol extract (MEAB) and its ethyl acetate soluble fraction (EAAB) to suppress nociception both centrally and peripherally were investigated in Swiss albino mice by tail immersion method and acetic acid-induced writhing method, respectively. At the 90th minute of the tail immersion study, both MEAB and EAAB administered at the doses of 250 and 500 mg/kg body weight (MEAB1, MEAB2, EAAB1, EAAB2) exhibited 240.41%, 285.34%, 302.83% and 339.60% elongation of pain response, respectively, in comparison to the standard, pentazocine which effectuated 421.36% elongation at the same mark. Moreover, the test samples at the same doses as before exhibited reduction of pain sensation by 66.81%, 74.08%, 76.81%, and 83.52%, respectively, in the acetic acid-induced writhing response in mice. Both the central and peripheral analgesic potentials of EAAB were discernibly higher than those of MEAB at both doses. The findings of the study represents the pharmacological potential of this species in appropriate animal model for the first time and provides valid foundation to warrant future scientific endeavors into the plant. Bangladesh Pharmaceutical Journal 24(2): 117-124, 2021

Evaluation of antinociceptive activity of Ilex dipyrena Wall. in mice

Background In order to find a new natural resource for pain-relief, the analgesic effects of Ilex dipyrena crude extract, fractions, and subfractions were evaluated in in-vivo mouse models with possible mechanism of action. Methods Analgesic effects of crude extract (100 and 200 mg/kg body weight), fractions and subfractions (75 mg/kg body weight) were screened using heat-induced (tail-immersion and hot plate test) and chemical-induced (formalin and acetic acid) nociception models in mice. The samples were also tested for the elucidation of a possible mechanism through opioidergic and GABAergic systems. Results The administration of crude extract, fractions and subfractions produced analgesic responses in acetic acid, formalin, tail immersion, and hot plate model for pain similar to those obtained with the standard. Naloxone antagonized the antinociceptive effects of the tested samples, whereas bicuculline showed partial inhibition. Considering the analgesic response, crude extract, fractions, and subfractions demonstrated promising inhibitory activity against all test models for pain, which was further supported by the possible involvement of opioidergic and GABAergic systems. Conclusion The results suggest that this plant may be useful in the development of new analgesic drugs. Further research with regard to the isolation of bioactive compounds is required to verify these findings.

Neuropharmacological Assessment of the Hydroethanolic Leaf Extract of Calotropis procera (Ait). R. Br. (Apocynaceae) in Mice

Background. Calotropis procera has been widely used traditionally for its analgesic and anti-inflammatory effects. It is also reportedly used in ethnomedicine for mental health disorders including epilepsy even in the absence of supporting scientific data. Thus, the potential of the plant to affect neurological functions was evaluated. Methods. Irwin’s test was performed to determine the effect of the oral administration of the extract (30–3000 mg kg−1) on gross behaviour and physiological function. The activity meter, rotarod, pentylenetetrazol- (PTZ-) induced convulsion, pentobarbitone-induced sleep test, and the tail immersion tests were used to evaluate the spontaneous activity, neuromuscular function, convulsive threshold, sedation, and analgesic effects of the Calotropis procera extract (30–1000 mg/kg), respectively, in mice. Results. Calotropis procera extract (CPE) exhibited significant ( p < 0.0001 ) anticonvulsant and analgesic effects. There was a significant increase in withdrawal latency of the CPE-treated animals in the tail immersion test for analgesia ( p < 0.0001 ), while latency and duration of PTZ-induced convulsions were positively modulated. Calotropis procera extract showed significant ( p < 0.0001 ) central nervous system depressant effects in pentobarbitone-induced hypnosis at 100–1000 mg/kg and spontaneous activity test (30–1000 mg/kg). The extract also depicted impaired motor coordination at 100–1000 mg/kg dose levels. LD50 was estimated to be above 1000 mg kg−1. Conclusions. Calotropis procera extract has significant central nervous system depressant and analgesic effects in mice.

In vitro and in vivo Evaluation of Pharmacological Potential of Lasia spinosa Linn.

Lasia spinosa Linn. (Family: Araceae) is an important medicinal plant, which is traditionally used for treatment of different human ailments. The present study was undertaken to evaluate the in vitro thrombolytic, antiinflammatory and in vivo analgesic and hypoglycemic potentials of n-hexane, chloroform and aqueous soluble fractions of methanol extract of L. spinosa whole plant. Additionally, phytochemical screening was carried out by qualitative tests, which confirmed the presence of alkaloids, glycosides, steroids, tannins, saponin in this plant. During in vitro thrombolytic assay, the aqueous fraction at a dose of 500 μg/100 μl showed the maximum 33.15% lysis of the blood clot, as compared to the standard streptokinase (80.10%). The in vitro anti-inflammatory test was performed by inhibition of egg albumin denaturation assay and RBC membrane stabilization method. The chloroform fraction exhibited maximum anti-inflammatory potential by inhibiting 51.53% denaturation of albumin and by inhibiting 54.8% hemolysis of RBC membrane against hypotonic solution. Analgesic activity was evaluated by tail immersion method for central mechanism and by formalin-induced lick test for peripheral mechanism in mice. In tail immersion method, all the solvent fractions of L. spinosa at a dose of 500 mg/kg body weight exhibited a significant (p<0.05) elongation in pain reaction time. In peripheral analgesic activity test, the chloroform fraction at a dose of 500 mg/kg body weight inhibited a maximum of 35.44% licking response induced by formalin, as compared to the standard aspirin (53.22%). In the hypoglycemic activity test, all the fractions showed a moderate effect in reducing the blood glucose level in mice treated with 10% glucose. In conclusion, the plant L. spinosa can be considered as a promising source of bioactive compounds for the development of new phytomedicine. Dhaka Univ. J. Pharm. Sci. 20(1): 111-119, 2021 (June)