Antioxidant, Analgesic and CNS Depressant Activities of Commelina diffusa Burm. f.

Commelina diffusa Burm. f. is a member of Commelinaceae family, which is widely grown in crop land and treated as a weed. This plant has several important medicinal properties which have not been studied extensively. In this study, the crude powder of C. diffusa whole plant was extracted with 95% ethanol and different solvent fractions (n-hexane, chloroform and methanol) were prepared from the crude extract by solvent-solvent partitioning. All these plant samples were subjected to bioassays for evaluating the antioxidant, central analgesic, peripheral analgesic and CNS depressant activities. The crude extract and its methanol soluble fraction showed mild free DPPH scavenging property with IC50 values of 98.49- and 84.77-μg/ml, respectively as compared to the standard ascorbic acid (IC50 = 2.67 μg/ml). In the analgesic activity test, the n-hexane fraction of C. diffusa at doses of 200- and 400-mg/kg body weight exhibited significant (p<0.05) central analgesic activity (tail flick test) in mice. Similarly, all the test samples showed statistically significant (p<0.05) reduction in abdominal writhing induced by acetic acid. C. diffusa showed significant CNS depressant activity which was measured by ‘open field test’ and ‘hole cross test’. Considering the potential bioactivities, the plant materials can be further studied elaborately to explore the activities of the purified compounds to aid in future drug development. Dhaka Univ. J. Pharm. Sci. 20(2): 159-166, 2021 (December)

CNS Depressant and Analgesic Activities of Thysanolaena maxima Roxb. Available in Bangladesh

In Bangladesh, numerous tribal people of Chittagong Hill Tracts have been using different parts of Thysanolaena maxima Roxb. for many years. The present study was designed to investigate CNS depressant and analgesic activities of methanol extract of the aerial parts of the plant in mice models. CNS depressant activity of the crude extract (200 and 400 mg/kg) was evaluated using open field, hole cross and thiopental-induced sleeping time tests using diazepam as the standard. Analgesic activity was determined using acetic acid-induced writhing and hot plate tests using diclofenac sodium as the standard. The extract showed dose dependent suppression of locomotion in open field and hole cross tests and exerted sedative action in thiopental induced sleeping time. In the open field and the hole-cross tests, maximum CNS depressant activity was observed at 90 min after administration of extract and the standard drug. The extract significantly induced the onset of sleep and prolonged the sleeping time in thiopental induced sleeping test compared to the control group. The extract produced significant (p < 0.05) analgesic activity by inhibiting writhing by 41.89% and 60.81%, at doses of 200 and 400 mg/kg body weight, respectively, which was comparable to the inhibition of diclofenac sodium (73.64%). Additionally, in hot plate test, the extract exhibited a significant (p < 0.05) increase in pain threshold in a dose dependent manner. The findings of the study are encouraging and demands further investigation of other bioactivities with isolation of pure compounds. Dhaka Univ. J. Pharm. Sci. 20(2): 227-233, 2021 (December)

The Role of Andrographolide in Andrographis paniculata as a Potential Analgesic for Herbal Medicine based Drug Development

Background: Andrographis paniculata is a herbaceous plant in the Acanthaceae family, that is widely used as a traditional medicine in Asian countries and known to exhibit a wide range of pharmacological effects. Recent studies have provided an overview of the great potential of A. paniculata as an analgesic. The ethanol extract and ethyl acetate (EA) fraction of A.paniculata were shown to contain diterpene lactone compounds, which may be useful as a potential active ingredient in analgesic drugs. The development of a herbal medicine based drug requires an effective and high quality active ingredient. Therefore, this research was aimed to compare the analgesic activity of ethanol extract and EA fraction based on their andrographolide content and further to determine the more viable active substance for analgesic herbal medicine based drug development. Method: The andrographolide content in the ethanol extract and EA fraction was determined by High Pressure Liquid Chromatography (HPLC). Measurement of analgesic activity was performed by writhing test. The experimental animals were randomly divided into eight groups consisting of 5 mice in each. Group 1 (negative control) received 1% Tween-80 in normal saline. Group 2 (positive control) received a standard analgesic drug (diclofenac sodium) at a dose of 40 mg/kg body weight. Group 3, 4, and 5 received ethanol extract while Group 6, 7, and 8 received EA fraction, each at a dose of 12.5, 25, and 50 mg andrographolide/kg body weight, respectively. Each mouse was injected intraperitoneally with 1% acetic acid at a dose of 10 ml/kg body weight 30 minutes after oral administration of the treatments. The number of writhes were counted 5 min after acetic acid injection over a period of 45 min. Results: Andrographolide content in ethanol extract and EA fraction was 15.66±0.28 and 21.25±1.08 % w/w, respectively. Ethanol extract and EA fraction displayed analgesic activity of 67.68% and 70.91% respectively, at a dose of 50 mg andrographolide/kg body weight. The positive control at a dose of 40 mg/kg body weight showed an analgesic activity of 74.33%. Statistical analysis showed no significant differences between EA fraction at a dose of 50 mg andrographolide/kg body weight and ethanol extract at the same dose as well as the positive control (P> 0.05). The effective dose 50% (ED50) of the ethanol extract and EA fraction was determined to be 29.49 and 25.55 mg/kg body weight, respectively. Conclusion: It was possible to use andrographolide content as an indicator for the analgesic activity of A.paniculata. Ethanol extract and EA fraction of A. paniculata at the same dose of andrographolide showed similar analgesic activity. The amount of ethanol extract which needed to reach similar analgesic activity was higher than EA fraction. Therefore, EA fraction likely has greater potential as an analgesic active substance due to its higher content of andrographolide; however further study is needed to develop it as a dosage form.

Study of Correction of Somatic Pain under the Conditions of Experimental Pathology of Multiple Sclerosis

The purpose of the study was to experimentally substantiate the ways of pharmacological correction of somatic pain syndrome in conditions of the experimental equivalent of multiple sclerosis through a comparative system analysis and the use of complex methodological approaches. Materials and methods. To study multiple sclerosis, we used an experimental model with autoimmune mechanisms of inflammatory demyelination – a model of experimental allergic encephalomyelitis. To assess the antinociceptive activity of painkillers, we used the method of electrical stimulation of the rats’ tail root. The activity of the enzyme prostaglandin H-synthetase was also determined. Results and discussion. A comparative analysis of the analgesic activity indicators of combinations of methylprednisolone with analgesics under the condition of the formed experimental allergic encephalomyelitis showed that their antinociceptive potential (taking into account the basic therapy with methylprednisolone) decreased in the series meloxicam > lornoxicam ≈ ketorolac ≈ paracetamol > celecofenacoxib ≈ sodium diclofupene ≈ diclofupene ≈ diclofupene. Accordingly, the maximum effect on the threshold of nociception under these experimental conditions was exerted by meloxicam and lornoxicam. The combined administration of methylprednisolone with diclofenac sodium, celecoxib and meloxicam reduced the activity of prostaglandin N-synthetase in the brain structures by 49.8% (p <0.05), 50.4% (p <0.05) and 51% (p <0.05), respectively, compared with the indicators of the control group. The same drugs markedly reduced the activity of prostaglandin N-synthetase in the spinal cord by 23.9% (p <0.05) (Methylprednisolone + diclofenac), by 34% (p <0.05) (Methylprednisolone + celecoxib) and by 47.4% (p <0.05) (Methylprednisolone + meloxicam) compared with the control group. Our analysis of the analgesic activity of antidepressants and anticonvulsants as means of correcting nociceptive pain in experimental allergic encephalomyelitis found that their antinociceptive potential was inferior to the severity of the analgesic effect of nonsteroidal anti-inflammatory drugs. Conclusion. Among the studied non-steroidal anti-inflammatory drugs, antidepressants and anticonvulsants, the maximum therapeutic efficacy as a means of correcting nociceptive pain in experimental allergic encephalomyelitis against the background of basic methylprednisolone therapy was shown by meloxicam, which gives grounds to recommend it as the analgesic of choice for eliminating somatic pain syndromes

The sodium 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydropyrimidine-4-olate quantitative content determination in a standard sample

Introduction. The standard samples (SS) use is a necessary condition for the medicines' quality control implementation. Their development is an urgent problem for the pharmaceutical industry, especially for new biologically active compounds that can be further used as pharmaceuticals.Aim. This work aim is to establish the 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydro pyrimidone-4-olate sodium quantitative content, for which anti-inflammatory and analgesic activity was previously proven, in a standard sample.Materials and methods. This work aim is to establish the 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydro pyrimidone-4-olate sodium quantitative content, for which anti-inflammatory and analgesic activity was previously proven, in a standard sample. The main method for establishing a substance quantitative content in the SS is the material balance method. The water determination was carried out according to K. Fisher's method (semimicro method). Sulphated ash was determined according to the XIV edition Russian Federation State Pharmacopoeia General Pharmacopoeia Monograph "Sulphated ash". Related impurities and their content were assessed using the HPLC method on a Flexar liquid chromatograph equipped with a diode array detector (Perkin Elmer, USA). The residual solvents' determination was carried out by the headspace method using a gas chromatograph GC-2010Plus Shimadzu with a flame ionization detector. As an additional method for establishing the main component quantitative content, acidimetric titration with the equivalence point potentiometric indication was carried out.Results and discussion. The percentage was determined for the following indicators: water, residual organic solvents, related impurities, sulphated ash. Using the material balance method, it was found that the 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydropyrimidin-4-olate sodium percentage in a standard sample is 96.01 ± 0.50 %. It was found by acidimetric titration that the 5-butyl-1,2-diphenyl-6-oxo 1,6-dihydropyrimidin- 4-olate sodium quantitative content in SS is 95.12 ± 0.02 %. The difference in the certified value can be explained by the fact that during titration, the SS aciform is released, which precipitates in an aqueous medium and contributes to a shift in the equilibrium and pH value. Consequently, the equivalence point is reached somewhat earlier. However, the data are practically comparable, but it is necessary to use the value obtained by the material balance method.Conclusion. A standard sample certification parameters were determined: water content, residual organic solvents, sulphated ash, related impurities. The main component quantitative content was determined using the material balance method and titrimetry (acidimetry with the equivalence point potentiometric indication).

Water Mediated One-Pot, Stepwise Green Synthesis, Anti-Inflammatory and Analgesic Activities of (3-Amino-1-Phenyl-1H-Benzo[f]Chromen-2-yl) (1H-Indol-3-yl) Methanone Catalysed by L-Proline

Aim: The reactions were carried out by one pot three-component synthesis, 3-cyanoacetylindole (1) on reaction with aromatic aldehydes (2) and β-naphthol (3) in an aqueous medium in presence of L-proline as a catalyst under reflux for 30 min, resulted (3-amino-1-phenyl-1H-benzo[f]chromen-2-yl) (1H-indol-3-yl)methanone (4). The method has many advantages like short reaction times, good yields and simple workup procedure besides being green in nature. Pharmacological evaluation of title compounds was done for anti-inflammatory and analgesic activities. Anti-inflammatory activity was carried carrageenan-induced paw edema model in which indomethacin was used as standard and analgesic activity was evaluated by eddy's hot plate method using diclofenac as standard drug. Background: Benzopyrans or chromenes are an important class of heterocyclic compounds due to their broad spectrum of biological activity and a wide range of applications in medicinal chemistry. The chromene moiety is found in various natural products with interesting biological properties. Chromenes constitute the basic backbone of various types of polyphenols and are widely found in alkaloids, tocopherols, flavonoids and anthocyanins. Indoles are omnipresent in various bioactive compounds like alkaloids, agrochemicals and pharmaceuticals. Objective: To synthesize one-pot stepwise Green synthesis, anti-inflammatory and analgesic activities of 3-amino-1-phenyl-1H-benzo[f]chromen-2-yl) (1H-indol-3-yl)methanones Methods: The acute anti-inflammatory effect was evaluated by carrageenan-induced mice paw edema (Ma Rachchh et al., 2011). Edema was induced by injecting carrageenan (1% w/v, 0.1 ml) in the right hind paw of mice. The test compounds 1-12, indomethacin (10 mg/kg) and the vehicle were administered orally one hour before injection of carrageenan. Paw volume was measured with digital plethysmometer at 0, 30, 60, 90, 120 min after injection. Percentage increase =A-B/ A *100 Results: Carrageenan Induced paw edema model was used for Anti-inflammatory activity in which animals treated with standard (indomethacin) and test compounds showed a significant decrease in the paw edema. Analgesic activity was estimated by using Eddy’s hot plate method; animals were treated with standard (diclofenac) and test compounds showed a significant increase in the reaction time. Conclusion: A green, One-pot, step-wise and three-component synthesis of 3-amino-1-phenyl-1H-benzo[f]chromen-2-yl) (1H-indol-3-yl) methanone was achieved by using water as a solvent, L-proline as catalyst under reflux conditions. The reactions were carried out in eco-friendly conditions with shorter reaction times, easier workup and high yields. Anti-inflammatory activity was evaluated by carrageenan-induced paw edema model where significant anti-inflammatory activity is shown by all the test compounds (4a-l) when compared to standard drug. Analgesic activity was studied by Eddy’s Hot plate method and Test compounds 4e, 4f, 4h, 4i, 4j, 4k, 4l showed significant activities when compared to the reference drug.

Phytochemical & Pharmacological Investigation of Stems of Passiflora foetida

Aims: To carry out extraction, preliminary phytochemical analysis and invivo analgesic screening of extract of the stem of Passiflora foetida L. Methodology: Passiflora foetida L; Family: Passifloraceae, is an exotic fast-growing perennial and medicinal vine occurring in Germany, France and other European countries and USA and grown in different parts of India. Dried stems of Passiflora foetida L was coarsely powdered and maceration was done using Soxhlet apparatus. The ethanolic extract of stems of Passiflora foetida L was subjected to preliminary phytochemical tests. Then subjected to in vivo analgesic activity. Results: Phytochemical investigation of the stem of Passiflora foetida L preliminary test showed the presence of carbohydrates, glycosides, flavonoids and steroids. Acute toxicity study of ethanolic extract of stems of Passiflora foetida L was carried out and extracts were found to be safe up to 2000 mg/kg body weight. Pharmacological activities of stems of Passiflora foetida L was carried out from ethanolic extract. Conclusion: Phytochemical investigation of ethanolic extract of stems were carried out and Analgesic activity by tail flick method in rats and acetic acid induced writhing method in mice, showed statistically significant activity (P=.05) when compared to control. The ethanolic stem extract of Passiflora foetida L proved to have significant pain relieving action in a dose dependent manner.

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&lt;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.

EXPERIMENTAL EVALUATION OF ANALGESIC ACTIVITY OF AQUEOUS EXTRACT OF TERMINALIA PANICULATA BARK IN RATS

This study was conducted to determine the analgesic activity of aqueous extract of Terminalia paniculata (Tp) bark. Analgesic activity was determined using hot plate and tail flick method. Thirty adult Wistar rats were divided into 5 groups of 6 rats each. Group I (control) received 2 mL water, Group II -codeine 5 mg kg-1, Group III, IV and V 100, 200 and 400 mg kg-1 of Tp, respectively. Latency time to pain sensation was noted. In hot plate model, group 5 showed significant increase in reaction time compared to groups 3 and 4 at all-time points and was comparable to standard codeine at 120th and 180th min. In tail flick method, standard codeine showed significant increased latency time compared to all three doses of Tp at 90th, 120th and 180th min. Group 5 showed significant increased reaction time compared to groups 3 and 4 from 60th min to 180th min. Group 4 showed increased analgesic activity compared to group 3 at 90th, 120th and 180th min but group 3 was significantly better at 30th min. Thus T. paniculata possesses analgesic potential.

Phytochemical Investigation and Analgesic Activity of Stem Bark Extract of Sapindus trifoliatus Linn

Aims: The study is designed to isolate and charecterize the phytoconstituents, and screen for the analgesic activity of stem bark extracts of Sapindus trifoliatus Linn. Methodology: The cleaned, dried and powdered stem barks of Sapindus trifoliatus were subjected to extraction by maceration process. The concentrated ethanolic extract of stem bark on was further subjected to preliminary phytochemical studies. The fractionated extracts were then packed into column chromatography for the isolation of phytoconstituents and they were characterized by IR, 1HNMR, 13CNMR and mass spectroscopy.Acute toxicity was performed to establish the lethal dose of the extract and In vivo analgesic activity was performed by tail flick and acetic acid induced writhing methods in experimental animals. Results: Preliminary phytochemical studies showed the presence of steroids, terpenoids, flavonoids, saponins and carbohydrates. Isolation of extracts led to give compounds like saponin glycoside, a steroid and triterpenoids. The extract was found to be safe up to 2000 mg kg bodyweight. Analgesic activity was found significant at level P = 05 when compared with control by tail flick and acetic acid induced writhing models in experimental animals. Conclusion: From ethanolic extract isolated a saponin glycoside,from petroleum ether stigmasterol and triterpenoids ursolic acid. The presence of saponin glycoside, triterpenoids, steroids might be responsible for the analgesic activity of the stem bark extract of Sapindus trifoliatus Linn.