Acid-induced Pain Model Research Articles

Boswellia dalzielii Methanol Stem Bark Extract Demonstrates Significant Analgesic Activity in Swiss Albino Mice

Medicinal plants are gaining popularity as safer and more natural alternatives to orthodox medicines for managing health challenges and diseases. One such plant is Boswellia dalzielii, a renowned tree in northern Nigeria extensively used due to its ethnomedicinal importance. To determine the analgesic properties of Boswellia dalzielii methanol extract (BDME), the extract was screened in mice using thermal and acetic acid-induced pain models. The extract's acute toxicity and phytochemical constituents were determined using standard protocols. The results showed that the acute toxicity of the methanol stem bark extract was greater than 2000 mg/kg. Phytochemical screening of BDME revealed the presence of flavonoids, tannins, saponins, and glycosides. The extract, at the dose of 50 mg/kg significantly (p < 0.05) prolonged the pain reaction time at 15 and 30 minutes in the hot plate test, and reduced acetic acid-induced writhing at the 12.5, 25, and 50 mg/kg doses. The analgesic activity of the extract may be attributed to the phytochemical contents. The findings suggest that BDME have analgesic properties and could be beneficial in alleviating painful conditions.

Phytochemical and biological studies of Panicum antidotale aerial parts ethanol extract supported by molecular docking study.

Panicum antidotale has traditionally been used as a poultice to alleviate local inflammation and painful diseases. This study aimed to evaluate the anti-inflammatory, wound-healing, analgesic, and antipyretic potential of its ethanol extract (PAAPEE) in vivo for the first time. In vitro antioxidant assays of Panicum antidotale using a 2,2-diphenyl-1-picrylhydrazyl assay revealed that it showed IC50 of 62.50 ± 6.85μg/mL in contrast to standard, ascorbic acid, that showed IC50 of 85.51 ± 0.38μg/mL. Administration of PAAPEE at a dose of 500mg/kg (PAAPEE-500) displayed 78.44% and 75.13% inhibition of paw edema in carrageenen and histamine-induced edema models. respectively, 6h post-treatment compared to that of the untreated group. Furthermore, it showed 68.78% inhibition of Freund's complete adjuvant-induced edema 21 days after treatment. It reduced the animal's rectal temperature in the yeast-induced fever model to 99.45 during the fourth h post-treatment. It significantly inhibited abnormal writhing by 44% in the acetic acid-induced pain model. PAE-500 also showed enhancement in wound closure by 72.52% with respect to that of the untreated group on the 10thday post-treatment using the excision healing of wound model. Histopathological examination of skin samples confirmed this improvement, showing enhanced tissue architecture with minimal infiltration of inflammatory cells. High-performance liquid chromatography (HPLC) of PAAPEE revealed the presence of quercetin, gallic, p-coumaric, benzoic, chlorogenic, syringic, ferulic, cinnamic, and sinapic acids. Molecular docking of 5-lipoxygenase and glycogen synthase kinase-3 β protein indicated their potential interaction within the active sites of both enzymes. Thus, P. antidotale serves as an effective natural wound-healing, anti-inflammatory, analgesic, and antipyretic agent.

Discovery of highly functionalized grayanane diterpenoids from the flowers of Rhododendron molle as potent analgesics

A systematical investigation on the chemical constituents of the flowers of Rhododendron molle (Ericaceae) led to the isolation and characterization of thirty-eight highly functionalized grayanane diterpenoids (1–38), including twelve novel analogues molleblossomins A−L (1–12). Their structures were elucidated by comprehensive methods, including 1D and 2D NMR analysis, calculated ECD, 13C NMR calculations with DP4+ probability analysis, and single crystal X-ray diffraction. Molleblossomins A (1), B (2), and E (5) are the first representatives of 2β,3β:9β,10β-diepoxygrayanane, 2,3-epoxygrayan-9(11)-ene, and 5,9-epoxygrayan-1(10),2(3)-diene diterpenoids, respectively. Molleblossomins G (7) and H (8) represent the first examples of 1,3-dioxolane-grayanane conjugates furnished with the acetaldehyde and 4-hydroxylbenzylidene acetal moieties, respectively. All grayanane diterpenoids 1–38 were screened for their analgesic activities in the acetic acid-induced writhing model, and all of them exhibited significant analgesic activities. Diterpenoids 6, 13, 14, 17, 20, and 25 showed more potent analgesic effects than morphine at a lower dose of 0.2 mg/kg, with the inhibition rates of 51.4%, 68.2%, 94.1%, 66.9%, 97.7%, and 60.0%, respectively. More importantly, even at the lowest dose of 0.04 mg/kg, rhodomollein X (14), rhodojaponin VI (20), and rhodojaponin VII (22) still significantly reduced the number of writhes in the acetic acid-induced pain model with the percentages of 61.7%, 85.8%, and 64.6%, respectively. The structure–activity relationship was summarized and might provide some hints to design novel analgesics based on the functionalized grayanane diterpenoids.

Esketamine Anesthetizes Mice With a Similar Potency to Racemic Ketamine.

Esketamine, the right-handed optical isomer of racemic ketamine, has recently become widely used for anesthesia and analgesia as a replacement for racemic ketamine. However, there are limited studies comparing the anesthetic and analgesic effects of esketamine and racemic ketamine in mice. This research was conducted to analyze the dose-dependent anesthetic and analgesic efficacy of esketamine in mice and to compare its potency with that of the racemate. We tested the anesthetic effects of different doses of esketamine and compared its potency with that of the racemate using righting reflex tests. Then, the acetic acid-induced pain model and formalin-induced pain model were used to investigate the analgesic effect. Compared with racemic ketamine, an equivalent dose of esketamine at 100mg/kg was required to induce stable anesthesia. In contrast, 5mg/kg esketamine was sufficient to provide analgesic effects similar to those of 10mg/kg ketamine. Together, esketamine had a similar potency to racemic ketamine for anesthesia and a stronger potency for analgesia in mice.

Neoline, fuziline, songorine and 10-OH mesaconitine are potential quality markers of Fuzi: In vitro and in vivo explorations as well as pharmacokinetics, efficacy and toxicity evaluations

Ethnopharmacological relevanceFuzi, the lateral roots of Aconitum carmichaelii Debx, plays an irreplaceable role in treating Yang deficiency and cold coagulation syndromes. However, Fuzi has a narrow margin of safety since its pharmacological constituents, Aconitum alkaloids, have potential cardiotoxicity and neurotoxicity. The current quality markers (Q-markers) for the control of Fuzi's efficacy and toxicity are 3 monoester-diterpenoid alkaloids, namely, benzoylaconine (BAC), benzoylhypaconine and benzoylmesaconine (BMA) and 3 diester-diterpenoid alkaloids, namely, aconitine (AC), hypaconitine and mesaconitine (MA). However, mounting evidence indicates that the current 6 Q-markers may not be efficacy- or toxicity-specific enough for Fuzi. Aim of the studyThe aim of this study was to explore and evaluate efficacy- or toxicity-specific potential quality markers (PQ-markers) of Fuzi. Materials and methodsPQ-markers were explored by analyzing 30 medicinal samples and alkaloids exposed in mouse. Pharmacokinetics of PQ-markers on C57BL/6J mice were determined. Anti-inflammatory effects of PQ-markers were evaluated by λ-carrageenan-induced paw edema model and lipopolysaccharide-induced RAW264.7 cell inflammatory model, while analgesic effects were assessed by acetic acid-induced pain model and Hargreaves test. Cardiotoxicity and neurotoxicity of PQ-markers were assessed by histological and biochemical analyses, while acute toxicity was evaluated by modified Kirschner method. ResultsAfter in vitro and in vivo explorations, 7 PQ-markers, namely, neoline (NE), fuziline (FE), songorine (SE), 10-OH mesaconitine (10-OH MA), talatizamine, isotalatizidine and 16β-OH cardiopetalline, were found. In the herbal medicines, NE, FE, SE and 10-OH MA were found in greater abundance than many other alkaloids. Specifically, the amounts of NE, FE and SE in the Fuzi samples were all far higher than that of BAC, and the contents of 10-OH MA in 56.67% of the samples were higher than that of AC. In mouse plasma and tissues, NE, FE, SE, talatizamine, isotalatizidine and 16β-OH cardiopetalline had higher contents than the other alkaloids, including the 6 current Q-markers. The pharmacokinetics, efficacy and toxicity of NE, FE, SE and 10-OH MA were further evaluated. The average oral bioavailabilities of NE (63.82%), FE (18.14%) and SE (49.51%) were higher than that of BMA (3.05%). Additionally, NE, FE and SE produced dose-dependent anti-inflammatory and analgesic effects, and their actions were greater than those of BMA. Concurrently, the toxicities of NE, FE and SE were lower than those of BMA, since no cardiotoxicity or neurotoxicity was found in mice after NE, FE and SE treatment, while BMA treatment notably increased the creatine kinase activity and matrix metalloproteinase 9 level in mice. The average oral bioavailability of 10-OH MA (7.02%) was higher than that of MA (1.88%). The median lethal dose (LD50) of 10-OH MA in mice (0.11 mg/kg) after intravenous injection was close to that of MA (0.13 mg/kg). Moreover, 10-OH MA produced significant cardiotoxicity and neurotoxicity, and notable anti-inflammatory and analgesic effects that were comparable to those of MA. ConclusionsSeven PQ-markers of Fuzi were found after in vitro and in vivo explorations. Among them, NE, FE and SE were found to be more efficacy-specific than BMA, and 10-OH MA was as toxicity-specific as MA.

Antinociceptive effect of aqueous leaves extract of Fagara tessmannii on acetic acid-induced pain in Wistar albino rats

The study was designed to investigate the analgesic effect of the aqueous leaf extract of Fagara tessmannii engl using the acetic acid-induced pain model in Wistar rats. Twenty rats were divided into five groups of four rats each. Group 1 received distilled water while groups 2-5 received 0.2 ml/kg BW of 0.6% intraperitoneal injection of acetic acid 30 mins after treatment with extracts and reference drug and writhing counted. Rats were sacrificed and blood was collected for biochemical and heamatological analyses. Also, Gas chromatography and phytochemical characterization of alkaloids in the aqueous leaf extract were done. The result revealed a significant decrease (p≤0.05) in the mean number of writhing in group 4 and non-significant decrease (p≥0.05) in groups 3 and 5 when compared to control group. Percentage inhibition of nociception in groups 3, 4, and 5 were 2%, 41.7%, and 10.5%, respectively. Non-significant differences (p≥0.05) in WBC, lymphocyte, neutrophil, eosinophil, and basophil counts in groups 5, 4, and 3 were observed when compared to normal and negative control groups. Monocyte count and ESR significantly decreased (p≤0.05) when negative was compared to normal control. CRP, IL-6, and PTG-S1 concentrations significantly increased (p≤0.05) when the negative control group was compared to the normal control. Groups 5 and 4 for CRP and 3 and 4 for IL-6 concentrations were significantly reduced (p≤0.05) while PTG-S1 was none significantly reduced in a dose-dependent manner when compared to the negative control. Some abundant alkaloids identified were acetic acid (12.3442%), benzoic acid (11.7984%), phenol, 4-methoxy-, acetate (6.8281), and phenol (4.3901%). Aqueous leaf extract of Fagara tessmannii Engl exhibited antinociceptive potential through the action of bioactive constituents.

Phytochemical investigation on Vitex negundo leaves and their anti-inflammatory and analgesic activities

The phytochemical investigation on Vitex negundo leaves has led to the isolation of one new iridoid glucoside (8α-hydroxy-4-carboxyl-5βH-9βH-iridoid-1α-O-(6′-O-(6,7-dihydrofoliamenthonyl)-β-ᴅ-glucopyranoside, 3), together with three known compounds, namely agnuside (1), 6′-O-E-caffeoylmussaenosidic acid (2), and 3,5-dicaffeoylquinic acid (4). The HPLC analytical study was also performed to quantify the content of agnuside (1) in dried leaves. The results indicated the very high content of 1 (3.04 ± 0.02%). The method was also validated by various parameters, including linearity (R2= 0.9999), precision (intra-day RSD ≤ 2.50%, inter-day RSD= 0.76%), and accuracy (recovery rates 96.58-101.86%). The animal testing data showed that the extract did not reduce pain at the doses of 9.6 and 28.8 g /kg (leaf weight/body weight) in the hot plates and pain measuring models but showed the pain reduction in the acetic acid-induced pain model. The extract at the dose of 5.6 g/kg (leaf weight/body weight) also had effects on the acute inflammation in the carrageenin-induced edema model. The extract at the dose 9.6 and 28.8 g/kg (leaf weight/body weight) also showed significant chronic anti-inflammation, comparable to methylprednisolone at the dose 10 mg/kg on the mouse peritoneal.

Antioxidant, anti-inflammatory, analgesic and anti-proliferating activities of Grewia heterotricha Mast.

Introduction and Aim: Plants are considered to be novel source of active compounds having pharmacological properties and help in the development of therapeutic agents. Hence, this study was undertaken to evaluate the antioxidant, anti-inflammatory, analgesic and anti-proliferating activity of aqueous and methanolic leaf extracts of Grewia heterotricha Mast.
 Materials and Methods: The aqueous and methanolic leaf extracts of the plant were assessed for their in-vitro antioxidant activity by DPPH radical scavenging activity, in-vivo anti-inflammatory activity by carrageenan induced rat paw edema method, in-vivo analgesic activity by acetic acid-induced writhing test and in-vitro anti- proliferating activity by MTT assay.
 Results: The methanolic extract had shown very significant DPPH radical scavenging activity with IC50 value 98.95?g/ml than aqueous extract and showed a significant reduction in the paw volume of rats at the concentration of 100 mg/kg body weight indicating potent anti-inflammatory activity compared with the reference standard Diclofenac sodium. Both the extracts showed significant analgesic effect (p<0.001) in acetic acid-induced pain models in a dose dependent manner. The methanolic extract showed higher analgesic activity compared to aqueous extract by inhibiting the pain indicated by a decrease in the number of writhes. In addition, both the extracts showed a decrease in MCF-7 cell viability at the concentration of 550µg/ml. Compared to the aqueous extract, MEGH has shown more cytotoxic effect on the cancer cell lines.
 Conclusion: The results suggest that both aqueous and methanolic extracts of Grewia heterotricha Mast. leaves possess potent antioxidant, analgesic, anti-inflammatory and anti-proliferating properties, which supports the use of the plant in traditional medicine. Further investigation is required to illuminate on its active compounds.
 
 Keywords: Analgesic; anti-inflammatory; DPPH; cytotoxic.

Characterization of anti-plasmodial, analgesic and anti-inflammatory fraction of Maytenus senegalensis (lam.) Exell leaf extract in mice

BackgroundThe treatment inadequacy and toxicity associated with conventional anti-malarial, anti-inflammatory and analgesic drugs has called for the search of alternatives from medicinal plants, particularly, their phytochemicals with inherent pharmacological properties. In the present study, purified fraction of M. senegalensis leaf was evaluated for antimalarial, anti-inflammatory and analgesic properties.MethodAntimalarial study was conducted against Plasmodium chabaudi and Plasmodium berghei using 4 days suppressive test, while anti-inflammatory and analgesic studies were conducted using egg albumin induced paw oedema and acetic acid induced pain model respectively. Sub-acute toxicity was assessed using serum biochemical parameters following 3 weeks administrations of the purified fraction.ResultsThe purified fraction of M. senegalensis leaf shows dose dependent antiplasmodial activity with percentage curative effects of 15.24 ± 0.89, 45.70 ± 3.43 and 48.50 ± 4.56 at 75, 150 and 300 mg/kg bw against Plasmodium chabaudi and % curative effects of 44.25 ± 3.21, 72.74 ± 6.54 and 76.30 ± 8.32 respectively against Plasmodium berghei. The purified fraction exhibited 53.16 ± 4.09 and 60.76 ± 7.54 anti-inflammatory effect, 43.35 ± 4.98% and 44.83 ± 3.86% analgesic effect at 75 and 150 mg/kg bw respectively. GC-MS analysis confirmed the presence of 20α)-3-hydroxy-2-oxo-24-nor-friedela-1(10),3,5,7-tetraen-carboxylic acid-(29)-methylester, 2(4H)-Benzofuranone, 5,6,7,7a-tetrahydro- and 3-hydroxy-20(29)-lupen-28-ol and a terpenes (phytol) as the major antimalarial compounds in the fraction. The purified fraction increases the serum total proteins and transaminases concentrations but had no effect on serum levels of sodium, potassium, chloride, alkaline phosphatase, triglyceride and glucose in the mice.ConclusionThe purified fraction of M. senegalensis leaf exhibited promising antimalarial, analgesic and anti-inflammatory activities. Thus, could serve as a template for the synthesis of new drug.

Development of a rule-based automatic five-sleep-stage scoring method for rats

BackgroundSleep problem or disturbance often exists in pain or neurological/psychiatric diseases. However, sleep scoring is a time-consuming tedious labor. Very few studies discuss the 5-stage (wake/NREM1/NREM2/transition sleep/REM) automatic fine analysis of wake–sleep stages in rodent models. The present study aimed to develop and validate an automatic rule-based classification of 5-stage wake–sleep pattern in acid-induced widespread hyperalgesia model of the rat.ResultsThe overall agreement between two experts’ consensus and automatic scoring in the 5-stage and 3-stage analyses were 92.32% (κ = 0.88) and 94.97% (κ = 0.91), respectively. Standard deviation of the accuracy among all rats was only 2.93%. Both frontal–occipital EEG and parietal EEG data showed comparable accuracies. The results demonstrated the performance of the proposed method with high accuracy and reliability. Subtle changes exhibited in the 5-stage wake–sleep analysis but not in the 3-stage analysis during hyperalgesia development of the acid-induced pain model. Compared with existing methods, our method can automatically classify vigilance states into 5-stage or 3-stage wake–sleep pattern with a promising high agreement with sleep experts.ConclusionsIn this study, we have performed and validated a reliable automated sleep scoring system in rats. The classification algorithm is less computation power, a high robustness, and consistency of results. The algorithm can be implanted into a versatile wireless portable monitoring system for real-time analysis in the future.

Features of the pharmacological activity of polypeptide modulators on acid-sensitive ion channels in the experiment

Introduction: TRPV1 receptors play a significant physiological role. To study pharmacological activity of new agonists and antagonists is important for the development of new drugs. This paper reports on the features of polypeptide antagonists of TRPV1 based on in vivo data.
 Materials and methods: The study was performed on 250 mature white ICR male mice weighing 25–30 g. Tests were conducted to evaluate the pharmacological activity and biological properties of APHC1-3 and a hybrid polypeptide A13 in thermal pain,, inflammation and body temperature tests.
 Results and discussion: APHC1-3 polypeptides showed significant antinociceptive and analgesic activity in the dose range of 0.01–0.1 mg/kg, without causing hyperthermia. A single substitution of the aspartic acid residue of АРНС1 polypeptide at position 23 by transferring one asparagine residue from the cognate peptide АРНС3 led to a significant change in the properties of the molecule. A new polypeptide A13 did not alter the thermal sensitivity of the mice, but showed the most significant analgesic activity in the acid-induced pain model, unlike АРНС1. A13 inhibits TRPV1 and affects body temperature as a classic antagonist of this receptor.
 Conclusion: Antagonistic properties of A13 became different from the properties of both initial analgesic polypeptides. Polypeptides APHC1-3 can be referred to as a new class of modulators of TRPV1, which produce a pronounced analgesic effect without hyperthermia.

Erding Formula in hyperuricaemia treatment: unfolding traditional Chinese herbal compatibility using modern pharmaceutical approaches

Traditional Chinese herbal formulas are difficult to be understood because of complex compositions and specific therapeutic principles. To better understand herbal compatibility in Traditional Chinese medicine (TCM), this study was conducted to investigate the effects of a Chinese pharmacopoeia-listed formula, Erding Formula (EF) and its constituent herbs for a new indication, hyperuricaemia. A hypoxanthine and potassium oxonate-induced hyperuricemic mouse model, a xylene-induced inflammatory mouse model and an acetic acid-induced pain model were used to test the effects of EF and its constituent herbs. In addition, we investigated whether EF and/or its relevant herbs had an impact on the expression of URAT1 and OAT3 mRNA. The results showed EF and individual herbs had pharmacological effects on selected targets. Only Viola yedoensis Makino (Viola) lowered uric acid levels, while all four herbs had anti-inflammatory and analgesic effects. The EF may lower the uric acid level through inhibiting the expression of URAT1 mRNA and enhancing the expression of OAT3 mRNA. These findings provide pharmacological insights into the effects of EF and individual herbs on UA excretion. This study suggests that Viola is the main herb in EF. This study facilitates better understanding of TCM principles and theories using modern pharmaceutical approaches.

Acid-induced experimental knee pain and hyperalgesia in healthy humans.

Inflammation and the related acidity in peri-articular structures may be involved in pain generation and hyperalgesia in knee osteoarthritis. This study investigated pain and associated hyperalgesia provoked by infusion of acidic saline into the infrapatellar fat pad. Twenty-eight subjects participated in two sessions in which acidic saline (AS, pH 5) or neutral saline (NS, pH 7.4) were infused into the infrapatellar fat pad for 15min. Pain intensity, pain area, mechanical and thermal sensitivity, and maximal voluntary knee extension force were recorded. Repeated infusions were performed in 14 subjects. Infusion of AS caused significantly higher pain intensity, larger pain areas, induced hyperalgesia around the infused knee, and reduced extension force. No significant pain facilitation or spreading of hyperalgesia was found after repeated infusions as compared with single infusions. Acidic saline infused into the infrapatellar fat pad provoked pain and localized mechanical hyperalgesia. Thus, this acid-induced pain model may mimic the early-stage responses to tissue injury of knee osteoarthritis.

Acid-induced experimental muscle pain and hyperalgesia with single and repeated infusion in human forearm

Background and purposeAcid has long been thought to play an important role in the pain process. Animal study showed that repeated acid stimulation induced central sensitization. The purpose of the study is to investigate muscle pain and hyperalgesia evoked by intramuscular infusion of saline at different pH levels, and to compare the effect of a single versus repeated acid infusions. MethodsTwenty healthy subjects received infusions of buffered saline (pH 5.0, 6.0, and 7.4) into the brachioradialis muscle in a randomized order. Twelve of the subjects received repeated infusions. The subjects rated the pain intensity on visual analogue scale (VAS). Thermal pain sensitivity, and pressure pain threshold (PPT) were assessed in both arm before, during, immediately after, one hour after, and one day after the infusion. A McGill Pain Questionnaire and pain mapping were completed after each infusion. ResultsThe pH 5 solution caused significantly higher pain and larger areas than pH 6.0 or 7.4. The local PPTs were significantly decreased (hyperalgesia) during and immediately after infusion of all three solutions. No significant differences were detected between the first and second infusion. ConclusionsThe intensity of acid-induced muscle pain is pH-dependent. All three solutions induced pressure hyperalgesia at the infusion site. Repeated infusions did not induce increased pain or prolonged hyperalgesia as compared with a single injection. Human intramuscular acidic saline infusion could not produce chronic pain model. ImplicationsThe acid-induced pain model may reflect the early stage responses to tissue injury of clinical conditions. Repeated intramuscular acidic saline injection model of prolonged hyperalgesia in rodents could not be translated into a human for modelling chronic musculoskeletal pain.

Antioxidant, Antinociceptive and CNS Activities of Viscum orientale and High Sensitive Quantification of Bioactive Polyphenols by UPLC.

Viscum orientale Willd. (Loranthaceae) has long been used in traditional medicine to treat pain, neuropharmacological disorders and various forms of tumor but not yet been reported. The aim of this study is to rationalize the traditional medicinal use of this plant by evaluating the methanol extract of V. orientale leaves (MEVOL) for anti-nociceptive, CNS depressant and antioxidant activities and to quantify the bioactive polyphenols present in this plant. Five polyphenolic compounds namely gallic acid, vanillic acid, caffeic acid, ellagic acid, and quercetin (17.54, 8.99, 99.61, 4523.31, and 100.15 mg/100 g of dry weight, respectively) have been identified in MEVOL using Ultra Performance Liquid Chromatography. Qualitative antioxidant activity determined by Thin Layer Chromatography indicated the presence of antioxidants. In quantitative antioxidant test using 2,2-diphenyl 1-picrylhydrazyl, MEVOL exhibited strong free antioxidant activity in a dose dependant manner (IC50 = 6.63 μg/ml) compared with ascorbic acid (IC50 = 1.91 μg/ml) and butylatedhydroxyanisole (IC50 = 2.27 μg/ml) controls. Total phenolic content determined using Folin Ciocaltu reagent was found to be 73.4 mg gallic acid equivalent/g of extract, while flavonoid content estimated using aluminum chloride colorimetric method was 170.7 mg quercetin equivalent/g of extract. Anti-nociceptive activity of MEVOL measured using acetic acid and formalin induced pain models in mice was significant (p < 0.001). MEVOL showed 65.6 and 88.8% writhing inhibition at 300 and 500 mg/kg body weight, respectively, comparing with standard diclofenac-Na (75.2% inhibition) at 25 mg/kg body weight in acetic acid induced pain model. In formalin induced pain model, paw licking was inhibited 45.93 and 56.4% in early phase and 55.66 and 72.64% in late phase at 300 and 500 mg/kg body weight, respectively, while diclofenac-Na inhibited 60.47 and 61.32% in early and late phase at 10 mg/kg body weight, respectively. In neuropharmacological activity test, overall behavioral test significantly reinforced CNS depressant activity. Spontaneous motor activities were reduced (p < 0.05) in both hole cross and open field tests compared with diazepam. Antioxidant activity of MEVOL is likely due to the phenolic and flavonoid compounds present within the leaf tissues. This study reveals significant in vivo anti-nociceptive and CNS depressant activities which justifies traditional medicinal applications of V. orientale.

A preliminary evaluation of cytotoxicity, antihyperglycemic and antinociceptive activity of Polygonum hydropiper L. ethanolic leaf extract

BackgroundPolygonum hydropiper L. is used by folk medicinal practitioners of Bangladesh. Juice of leaves is used in headache, pain, toothache, liver enlargement, gastric ulcer, dysentery, loss of appetite and dysmenorrhea; roots are used as stimulant; juice is applied to wounds, skin. In this study, we analyze the cytotoxicity property of aerial parts of the plant along with antihyperglycemic and antinociceptive activity.MethodsCytoxicity was determined by brine shrimp lethality assay and antihyperglycemic activity was measured by oral glucose tolerance tests. Antinociceptive activity was determined by observing decreases in abdominal writhings in intraperitoneally administered acetic acid-induced pain model in mice.ResultsAdministration of ethanol extract of leaf led to dose-dependent and significant reductions in blood glucose levels in glucose-loaded mice. Blood sugar levels of the tested mice were reduced significantly by 48.8, 51.5, 54.1, 58.2 % (p < 0.05) compared to control mice with the increasing dosage of the extract such as 50, 100, 200 and 400 mg/kg of body weight respectively. In contrast, when glibenclamide, a standard antihyperglycemic drug was administered at a dose of 10 mg/kg body weight, it reduced blood glucose level by 42.1 %. On the other hand stem extract only reduced 1.5 % of blood sugar level of the tested mice which was not significant. In the case of antinociceptive activity tests, the extract at the above four doses reduced the number of abdominal writhings by 14.10, 17.95, 29.49 and 41.02 % respectively in comparison with a standard drug Aspirin. In cytotoxicity tests, nauplli were treated with a gradually increased concentration of the extract, ranging from 10 to 45 μg/ml. The LC50 was found at a concentration of 16.22 μg/ml, compared with control.ConclusionThe results of the present study showed that Polygonum hydropiper L. ethanolic leaf extract possess antihyperglycemic and antinociceptive activity. All these effects could be due to the bioactive components of this plant and need to be identified for further research about this plant. This could justify its ethnomedical use.

Enhancement of skin permeation of flurbiprofen via its transdermal patches using isopulegol decanoate (ISO-C10) as an absorption enhancer: pharmacokinetic and pharmacodynamic evaluation.

The study aimed to prepare a transdermal patch for flurbiprofen using isopulegol decanoate (ISO-C10) as a permeation enhancer, and to evaluate the in-vitro and in-vivo percutaneous permeation of the drug, as well as the pharmacodynamic efficacy of the formulation. The permeation experiments were conducted on rabbit skin, and the pharmacokinetic profiles and synovial fluid drug concentration were measured after in-vivo transdermal administration. A deconvolution approach was employed to analyse the correlation between the in-vitro and in-vivo drug permeation. The anti-inflammatory and analgesic effects were, respectively, assessed using the adjuvant arthritis model and the acetic acid induced pain model. ISO-C10 could increase the in-vitro permeation of flurbiprofen from 46.22 ± 5.65 μg/cm(2) to 101.07 ± 10.85 μg/cm(2) . The in-vivo absorption of the drug was also improved by the enhancer, and a good linear correlation was observed between the in-vitro and in-vivo drug permeation. Meanwhile, the ISO-C10 contained patches increased the drug disposition in synovial fluid and enhanced the pharmacodynamic efficacy of the formulation. ISO-C10 would be a promising permeation enhancer for improving the in-vitro and in-vivo delivery of flurbiprofen from its transdermal patches.

Is Acid Painful or not?

Acid (or proton) is an effective algogen to excite primary afferent nociceptors and evoke pain. Pain associated with tissue acidosis occurs where there is/are tissue injury, inflammation, ischemia, fatiguing exercise, or tumors. However, a recent study in mice has virtually changed our view regarding the significance of acid signaling in nociception. In the study, an acid-induced muscle pain model was used to probe the endogenous antinociceptive signaling pathway. Surprisingly, instead of acid-induced pain, the authors discovered that acid could also elicit an antinociceptive effect on mice, when specific acid sensors of muscle nociceptors, such as ASIC3 and TRPV1, were blocked. The acid-mediated antinociceptive pathway might act via a subset of acid-sensitive muscle afferent neurons to release substance P (SP), which would act on neurokinin 1 (NK1) receptors to reduce acid-induced depolarization via activation of an M-type potassium channel. The newly uncovered antinociceptive role for acid has largely changed our concept of pain biology and brought new insight for the analgesic drug development.

Analgesic and antihyperglycemic activity evaluation of Bambusa vulgaris aerial parts

Article history: Received on: 06/07/2015 Revised on: 14/08/2015 Accepted on: 04/09/2015 Available online: 27/09/2015 Bambusa vulgaris, also known as ‘Ora Bansh’ in Bangladesh is grown throughout the country for housing and scaffolding purposes. As part of our analgesic and antihyperglycemic plants of Bangladesh screening program, it was of interest to evaluate the analgesic and antihyperglycemic potential of aerial parts of the plant. Methanolic extract of aerial parts (MEBV) at doses of 50, 100, 200 and 400 mg per kg significantly reduced the number of writhings in acetic acid-induced pain model Swiss albino mice by 25.9, 29.6, 37.0, and 44.4%, respectively compared to reductions of 40.7 and 51.9%, respectively, obtained with 200 and 400 mg per kg of a standard analgesic drug, aspirin. MEBV, at doses of 100, 200 and 400 mg per kg also significantly lowered blood glucose levels in mice, respectively, by 32.8, 45.8, and 55.3% compared to control mice. A standard antihyperglycemic drug, glibenclamide, when administered at a dose of 10 mg per kg lowered blood glucose level by 50.8%. Taken together, the results indicate that the aerial parts of the plant possess considerable analgesic and antihyperglycemic potential, which can possibly be attributed to the presence of alkaloids and saponins in the extract.

A preliminary report on oral glucose tolerance and antinociceptive activity tests conducted with methanol extract of Xanthosoma violaceum aerial parts.

BackgroundXanthosoma violaceum is commonly observed in fallow areas of Bangladesh but almost no scientific studies exist on this plant. Rural people consume the plant on a frequent basis. The objective of this study was to scientifically analyze the antinociceptive property of methanol extract of aerial parts of the plant along with antihyperglycemic activity.MethodsAntihyperglycemic activity was measured by oral glucose tolerance test (OGTT). Antinociceptive activity was determined by observed decreases in abdominal constrictions in intraperitoneally administered acetic acid-induced pain model in mice.ResultsAdministration of methanol extract of aerial parts led to dose-dependent and significant reductions in blood glucose levels in glucose-loaded mice. At doses of 50, 100, 200 and 400 mg per kg body weight, the extract reduced blood sugar levels by 19.3, 23.2, 31.8, and 47.1%, respectively compared to control animals. By comparison, a standard antihyperglycemic drug, glibenclamide, when administered at a dose of 10 mg per kg body weight, reduced blood glucose level by 48.9%. In antinociceptive activity tests, the extract at the above four doses reduced the number of abdominal constrictions by 41.4, 44.8, 48.3, and 55.2%, respectively. A standard pain relieving (antinociceptive) drug, aspirin, reduced the number of writhings by 31.0 and 51.7%, respectively, when administered at doses of 200 and 400 mg per kg body weight.ConclusionTo our knowledge, this is the first report on oral glucose tolerance and antinociceptive activity evaluation of aerial parts of the plant. Since the plant is widely available in Bangladesh, the aerial parts can be a readily available source for particularly the rural population for lowering blood sugar in diabetic patients and for alleviating pain.