Antipyretic, Analgesic and Anti-inflammatory Activity of Qurs Afsanteen Saghir (A Polyherbal Unani Tablet) in Experimental Animals

Qurs Afsanteen Saghir is a polyherbal Unani formulation in the form of tablet. This formulation consists of multiple medicinal plants like Afsanteen (Artemisia absinthium L.), Badam Talkh (Prunus dulcis (Mill.) D.A.Webb), Asaroon (Asarum europaeum L.), Anisoon (Pimpinella anisum L.) and Tukhm-e-Karafs (Apium graveolens L.). The clinical adult dose of study drug is 3.5 –7 g per day as mentioned in Unani literature. The present study evaluated the antipyretic, analgesic and anti-inflammatory potential of Qurs Afsanteen Saghir using different animal models. Antipyretic activity was measured using yeast-induced pyrexia model in rats at 360 and 720 mg/kg bw dose of test drug and paracetamol (70 mg/kg bw p.o.) as standard control. Analgesic effect was evaluated using acetic acid-induced writhing test in mice using test drug at dose 720 and 1440 mg/kg bw and diclofenac sodium (15 mg/kg bw p.o.) as standard control. Eddy’s hot plate test was conducted in rats using test drug at the dose of 360 and 720 mg/kg bw and buprenorphine (0.10 mg/kg s.q.) as standard control. Anti-inflammatory activity was assessed by carrageenan-induced paw edema model in rats with the dose of 360 and 720 mg/kg of test drug and Indomethacin (10 mg/kg p.o.) as standard control. The study drug significantly reduced the temperature and pain at both dose levels in a time-dependent manner as compared to normal control. However, the reduction of inflammation was observed at low dose (360 mg/kg bw) only after 3 hours of carrageenan administration. These findings indicated that tested drug showed potential activity as antipyretic and analgesic; whereas the drug may not be considered quite effective as an anti-inflammatory agents.

Design and evaluation of pharmacological properties of a new 1,3,4-thiadiazolylamide derivative of 2-propylpentanoic acid

Introduction: The use of the pharmacophoric approach is a promising direction for modifying the chemical structure of 2-propylpentanoic (valproic) acid in order to obtain new drugs. Materials and methods: In the experiments on mice, acute toxicity, neurotoxicity, antiepileptic activity and analgesic effect of N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propylpentanamide (valprazolamide) were evaluated. LD50 was determined by probit analysis. Neurotoxicity was determined in a rotarod test and a bar test in mice. The effects of valprazolamide on the exploratory behavior of mice in open field test and in a light/dark transition test were evaluated. Its antiepileptic activity was tested in mice against seizures induced by maximal electroshock, pentylenetetrazole (scPTZ); isoniazid, thiosemicarbazide, pilocarpine, and camphor. The analgesic effect was studied in a hot plate test. Results and discussion: N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propylpentanamide was obtained by introducing pharmacophores into the structure of 2-propylpentanoic acid: a substituted amide group and an electron-donor domain of 1,3,4-thiadiazole. The LD50 value for intraperitoneal administration of a new 2-propylpentanoic acid: derivative to mice was 924.8 mg/kg, and the TD50 value in the rotarod test and the bar test were 456.7 mg/kg and 546.7 mg/kg, respectively. The suppression of orienting responses in the animals was noted when it was administered in neurotoxic doses. Valprazolamide showed the most antiepileptic activity on models of MES, scPTZ and isoniazid antagonism tests. The ED50 values were 138.4 mg/kg, 74.5 mg/kg, and 126.8 mg/kg, respectively. The therapeutic indices for these models of epilepsy were 6.7; 12.4; 7.3, and protective index – 3.3; 6.1 and 3.6, respectively. In the hot plate test, valprazolamide increased the latency period before a defensive response to a thermal stimulus (ED50 165 mg/kg). Conclusion: N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propylpentanamide is a new 1,3,4-thiadiazolylamide derivative of 2-propylpentanoic acid with antiepileptic and analgesic activities, which belongs to the group of low-toxic agents. Graphic abstract N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propylpentanamide (3D) LD50=924.8 mg/kg (mice, intraperitoneally) TD50=456.7 mg/kg (rotarod, mice, intraperitoneally) ED50=138.4 mg/kg (MES, mice, intraperitoneally) ED50=74.5 mg/kg (scPTZ, mice, intraperitoneally)

Study of analgesic activity and effects of new dipharmacophores – nebracetam and cyclooxygenase-2 inhibitors derivatives on the cognitive abilities of rats

Introduction: The aim of the present study was to research the analgesic activity and effect of new dipharmacophore compounds consisting of substances with proven therapeutic activity, namely nebracetam–ibuprofen (NRIP), nebracetam–dexibuprofen (NRDIP), nebracetam–niflumic acid (NRNFA), and nebracetam–mefenamic acid (NRMFA), on the cognitive abilities of rats. Materials and methods: The experimental study was performed in 110 Wistar rats (male/female ratio 50/50%), weighing 180–200 g, and 50 laboratory mice (male/female ratio 50/50%) weighing 18–22 g. The study of the analgesic activity was carried out using the acetic acid writhing test and the hot plate test. The effect on the cognitive abilities of rats was studied using the pattern recognition test in a model of neurotrauma caused by a drop-weight. Results and discussion: It has been shown that the administration of dipharmacophores nebracetam–ibuprofen (NRIP), nebracetam–dexibuprofen (NRDIP), nebracetam–niflumic acid (NRNFA) as well as nebracetam–mefenamic acid (NRMFA) in the tested dosages leads to a statistically significant (p<0.05) analgesic action in acetic acid writhing tests and hot plate tests. At the same time, the analgesic activity of the compounds has been shown to conjoin with a statistically significant influence on cognitive functions in the experimental animal groups after simulating a neurotrauma. Conclusion: The dipharmacophore compounds studied in the present research, having analgesic and nootropic effects, can be used as effective and safe analgesics and can also be used for the treatment and prevention of pain syndrome, enhancing the cognitive abilities of healthy people in complicated professional conditions.

Preparation and Analysis of New 1,3,5-Trisubstituted-2-Pyrazolines Derivative for Their Analgesic Potential

The goal of the study was to develop, synthesise, and characterise a novel 1,3,5-trisubstituted-2-pyrazolines derivative, as well as to assess its analgesic potential. The reaction of chalcone derivatives with 4-hydrazinylbenzene sulfonamide hydrochloride and phenyl hydrazine hydrochloride yielded 1,3,5-tri-substituted-2-pyrazolines derivatives. The IR, 1HNMR, and mass spectrum analyses were used to characterise a total of sixteen substances. Analgesic activity of the proposed substances has been tested. The analgesic effect of the produced compounds was tested using two methods: the hot plate test technique and acetic acid induced writhing in mice. To compare the effectiveness, pentazocine and acetyl acetic acid were utilised as reference drugs. The hot plate test technique and acetic acid induced writhing in mice were used to assess the analgesic effect of the 16 produced chemical series A1-A8, and B1-B8. The evaluation's outcomes were viewed using Pentazocine and acetyl acetic acid as the standard drugs. In a 90-minute hot plate test, compounds A2 (10.30 s), A4 (9.45 s), A7 (11.65 s), and A8 (11.26 s) showed a delay in paw withdrawal latency time. Compounds B2 (9.10 s) and B7 (10.42 s) prolong the paw withdrawal latency time after 90 minutes in series B1-B8, reduce the pain feeling, and inhibit pain induced by heat methods. Compounds A2, A5, A6, A7, and A8 from Series A1-A8 showed 83.00, 76.01, 80.34, 86.99, 88.15 percent inhibition, substantially (p0.05 and p0.001, respectively), and decreased the number of wriths caused by 0.6 percent acetic acid at a dosage of 10 mg/kg. Acetylsalicylic acid (10 mg/kg) appears to be more successful in lowering the number of wriths, with a 99.0% reduction in the number of wriths (p0.001). B1, B3, and B4 have the least amount of active activity. These all finding suggest that these synthesized compounds have the potential as analgesic agent.

Histopathological and analgesic effects of intrathecal dexmedetomidine, racemic ketamine, and magnesium sulfate in rats

Background This study aims to investigate the histopathological and analgesic effects of intrathecal administration of dexmedetomidine, preservative-free racemic ketamine, and magnesium sulfate in Sprague Dawley rats. This study included 40 male Sprague Dawley rats weighing between 240 and 260 g. After the intrathecal catheterization, the rats were randomly divided into four groups. Following the baseline measurements, no drugs were administered in the control group (group C). Simultaneously, 0.02 ml (1 μgr/kg) of dexmedetomidine was administered in group D, 0.02 ml (1 mg/kg) preservative-free racemic ketamine in group K and 0.02 ml (0.05 mg/kg) magnesium sulfate in group M via intrathecal route. Concomitantly, the hot-plate test was used to measure the analgesic effect of drugs. For histopathological evaluation, the rats were sacrificed to obtain the medulla spinalis. Results The hot-plate test revealed that the mean response time was 6.3 ± 1.2 s in baseline measurements without medication. However, prolongation in the mean response times of the drug-administered groups to the hot-plate test was also observed. Upon histopathological examination, myelin degeneration was detected in all study groups. No inflammation was observed in rats in group D, whereas inflammation was noted in only two rats in group K. Concerning the presence of red neurons, the only group that differed from the control group belonged to group K. Conclusions Dexmedetomidine, preservative-free racemic ketamine, and magnesium sulfate have an analgesic effect when administered intrathecally in rats. Of these drugs, preservative-free racemic ketamine stands out as the most histopathologically safe drug.

Antinociceptive and Antipruritic Effects of HSK21542, a Peripherally-Restricted Kappa Opioid Receptor Agonist, in Animal Models of Pain and Itch

Kappa opioid receptor (KOR) agonists have been promising therapeutic candidates, owing to their potential for relieving pain and treating intractable pruritus. Although lacking morphine-like central nervous system (CNS) effects, KOR agonists do elicit sedation, dysphoria and diuresis which seriously impede their development. Peripherally-restricted KOR agonists have a poor ability to penetrate into the CNS system, so that CNS-related adverse effects can be ameliorated or even abolished. However, the only approved peripherally-restricted KOR agonist CR845 remains some frequent CNS adverse events. In the present study, we aim to address pharmacological profiles of HSK21542, with an expectation to provide a safe and effective alternative for patients who are suffering from pain and pruritus. The in vitro experimental results showed that HSK21542 was a selective and potent KOR agonist with higher potency than CR845, and had a brain/plasma concentration ratio of 0.001, indicating its peripheral selectivity. In animal models of pain, HSK21542 significantly inhibited acetic acid-, hindpaw incision- or chronic constriction injury-induced pain-related behaviors, and the efficacy was comparable to CR845 at 15 min post-dosing. HSK21542 had a long-lasting analgesic potency with a median effective dose of 1.48 mg/kg at 24 h post-drug in writhing test. Meanwhile, the antinociceptive activity of HSK21542 was effectively reversed by a KOR antagonist nor-binaltorphimine. In addition, HSK21542 had powerful antipruritic activities in compound 48/80-induced itch model. On the other hand, HSK21542 had a weak ability to produce central antinociceptive effects in a hot-plate test and fewer effects on the locomotor activity of mice. HSK21542 didn’t affect the respiratory rate of mice. Therefore, HSK21542 might be a safe and effective KOR agonist and promising candidate for treating pain and pruritus.

Antinociceptive and Anti-Inflammatory Effects of Recombinant Crotamine in Mouse Models of Pain

Crotamine, a toxin found in the venom of the South American rattlesnake Crotalus durissus terrificus, has been reported to have antinociceptive effects. We purified recombinant crotamine expressed in Escherichia coli and investigated its antinociceptive and anti-inflammatory effects using the hot-plate test, acetic-acid-induced writhing method, and formalin test in mice. Recombinant crotamine was administered intraperitoneally (0.04–1.2 mg kg−1) or intraplantarly (0.9–7.5 μg 10 μL−1) before the tests. The paw volume was measured with a plethysmometer. To evaluate the antagonistic and anti-inflammatory effects of naloxone, subcutaneous naloxone (4 mg kg−1) or intraplantar naloxone (5 μg 10 μL−1) was administered before recombinant crotamine. For tumor necrosis factor (TNF)-α assays, blood was drawn 3 h after formalin injection and measured using enzyme-linked immunosorbent assay. Intraperitoneal and intraplantar recombinant crotamine had antinociceptive and anti-inflammatory effects, neither of which were affected by pre-treatment with naloxone. The mean serum TNF-α levels were significantly lower in the intraperitoneal recombinant crotamine (0.4 and 1.2 mg kg−1) or intraplantar (2.5 and 7.5 μg 10 μL−1) recombinant crotamine groups than in the saline group and were not affected by naloxone pre-treatment. In conclusion, recombinant crotamine possesses significant antinociceptive and anti-inflammatory effects that do not appear to be related to the opioid receptor. The antinociceptive and anti-inflammatory effects of intraperitoneal or intraplantar recombinant crotamine are related to TNF-α.

Pharmaceutical Standardization and Drug Dosage Modification of Laghu Sudarshan Churna with Comparative Assessment of its Antipyretic and Analgesic Activities in Albino Rats

Introduction: Laghu Sudarshan Churna is a Churna mentioned by Yogratnakar indicated in the treatment of all types of Jwara and its action is Tridoshanashak. Fever is bodys natural defense mechanism against infectious agents which can damage the tissue. Some studies have suggested that raising temperature may be harmful. Therefore, in clinical practices in which fever associated risk benefits, antipyretic treatment is necessary. Aim and Objective: Drug dosage modification and pharmaceutical standardization of Laghu Sudarshana Churna to Laghu Sudarshana Vati with comparative Assessment of its Antipyretic & Analgesic activities in albino rats. Materials and Methods: To evaluate antipyretic & analgesic activities of test drugs the most commonly employed method to induce fever in animals is brewers yeast induced pyrexia, Tail flick test & Hot plate test for analgesic in animal models. Observation and Results: Observation will be done on the basis of Physicochemical & Organoleptic characteristics of Laghu Sudarshan churna & Laghu Sudarshan vati. Results will be drawn on the basis of observations & applying suitable test. It will be noted & presented in the form of table, charts & graphs etc. Conclusion: If this Antipyretic & Analgesic study is successful then this data will be used in another clinical study for intervention of Antipyretic & Analgesic studies, as it is Herbal medicine so it will show no any toxic effect in animal models. Hence, it will be easily used in humans also.

The cytotoxicity, anti-inflammation, anti-nociceptive and oral ulcer healing properties of coconut shell liquid smoke

Introduction: Coconut shell liquid smoke (CS-LS) from Cocos nucifera L. has been traditionally used by Indonesians as a natural preservative. Besides that, liquid smoke is also used as a medicine to treat various types of wounds. During the storage, liquid smoke resulting from pyrolysis is still questionable in relation to the oxidation process and changes in its properties and potentials. We observed the physical characteristics, components, toxicity, anti-inflammatory, anti-nociceptive properties, and effect in oral ulcer healing of CS-LS. Methods: Acidity was analyzed using a digital pH meter, density test was analyzed using a pycnometer, and the components were determined using gas chromatography-mass spectrometry (GC-MS). Eight concentrations of CS-LS (1%, 2%, 4%, 6%, 8%, 10%, 12%, and 14%) were tested on baby hamster kidney (BHK21) for the extract toxicity, carrageenan-induced rat paw edema for its anti-inflammatory properties, hot-plate test for its anti-nociceptive, and traumatized labial fornix incisive inferior for its oral ulcer healing. Results: The acidity of CS-LS was 2.296 and the density was 1.0102 g/mL. The major components analyzed were phenol (32.75%), 2-methoxy-phenol (17.45%), and furfural (13.09%). The CS-LS 100% and CS-LS 8% were the optimum concentrations for maintaining the BHK21 and increasing the number of fibroblasts in oral ulcer healing. The CS-LS 100% showed potent anti-nociceptive ability compared to other concentrations (P = 0.001), but not for the anti-inflammation properties. Conclusion: CS-LS is a promising natural herb for oral medicine, especially oral ulcer medicine.