Analgesic Test Research Articles

A mathematical multiple-dimensional strategy for Q-markers identification based on “five principles”: Tianshu Capsule for migraine treatment as an example

Ethnopharmacological relevanceQuality control is a critical element for Traditional Chinese medicine (TCM). Due to the varied chemical components, mechanisms of action, and pharmacological functions in TCM, ensuring quality is more challenging compared to chemical drugs. Then, the concept of quality markers (Q-markers) was proposed and ideal Q-markers for TCM prescriptions need to compliant with “five principles”, including pharmacological effectiveness, specificity, transfer and traceability, measurability, and prescription compatibility. Aim of the studyTo establish a mathematical multiple-dimensional “spider-web” strategy and identify the Q-markers of Tianshu capsule (TSC), a Chinese patent medicine for the treatment of migraine, following the “five principles” rules. Materials and methodsQ-marker candidates of TSC were firstly screened according to the HPLC fingerprints. Their contents in 10 batches of TSC and stabilities under high temperature, high humidity and in work solutions were determined quantitatively by HPLC-UV (measurability). Their existences in Gastrodiae Rhizoma, Chuanxiong Rhizoma, TSC, rat plasma and brain samples were investigated using HPLC-Q-TOF/MS (transfer and traceability). Their anti-migraine efficacies were evaluated by network pharmacology and mice hot-plate analgesia test; and their relationships with the property (flavor) of Gastrodiae Rhizoma or Chuanxiong Rhizoma were studied by molecular docking (effectiveness). Their contributions were defined based on their herb source according to the compatibility theories of Da Chuan Xiong Fang (compatibility). Their biosynthetic pathways were studied, and their frequencies detected in different plant families were calculated (specificity). Finally, an eight dimensional “spider-web” mode was developed for 10 components, and the regression area (RA) and the coefficient variation (CV) of each candidate were calculated after data normalization. ResultsTen components including gastrodin, parishin E, chlorogenic acid, ferulic acid, isochlorogenic acid A, senkyunolide I, H, A, Z-ligustilide and levistilide A were selected and evaluated as the Q-marker candidates. The results showed that gastrodin, senkyunolide I, and senkyunolide A had the higher RA and lower CV than other compounds with the established “spider-web” mode, indicating that they could be used as the Q-markers of TSC. ConclusionThe multi-dimensional “spider-web” mode based on “five principles” was firstly applied to identify the Q-markers of TSC, and it can be used as a practical strategy to discover Q-markers of other compounded prescriptions.

Long-term d-allose administration ameliorates age-related cognitive impairment and loss of bone strength in male mice

Age-related physical and cognitive decline may be ameliorated by consuming functional foods. d-Allose, reported to have multiple health benefits, may temper aging phenotypes, particularly brain function. We investigated whether d-allose supplementation improves cognitive function. A standard battery of behavioral tests was administered to 18-month-old male mice after consuming diet containing 3 % d-allose for 6 months. Following a wire-hanging test, an open-field test, Morris water maze, fear-conditioning, and an analgesia test were sequentially performed. Bone density and strength were assessed afterwards. Possible mechanism(s) under-lying memory changes in hippocampus were also examined with a DNA microarray. d-Allose failed to influence muscle strength, locomotor activity and anxiety, fear memory, or pain sensitivity. However, d-allose improved hippocampus-dependent spatial learning and memory, and it may contribute to increase bone strength. d-Allose also changed the expression of some genes in hippocampus involved in cognitive functions. Long-term d-allose supplementation appears to modestly change aging phenotypes and improve spatial memory.

Prevalence of movement asymmetries in high-performing riding horses perceived as free from lameness and riders' perception of horse sidedness.

A high proportion of horses in training, perceived as free from lameness by their owner, exhibit vertical movement asymmetries. These types of asymmetries are sensitive measures of lameness, but their specificity as indicators of orthopaedic pathology or locomotor function remains unclear. Equine athletes performing at a high level could be assumed to exhibit a higher degree of movement symmetry compared with the general horse population, but this has not been confirmed. This study investigated the prevalence of movement asymmetries in horses performing at a high level in three equestrian disciplines; show jumping, dressage and eventing, as well as the association between riders' perception of horse sidedness and said movement asymmetries. Using an inertial measurement unit-based system (Equinosis), gait analysis was performed on 123 high-performing horses. The mean difference between the two vertical minimum and between the two maximum values of each stride was recorded for the head (HDmin, HDmax) and pelvis (PDmin, PDmax). The horses were defined as asymmetric if one or multiple asymmetry parameters exceeded an absolute trial mean of: >6mm for HDmin or HDmax, and >3mm for PDmin or PDmax, with standard deviation less than the respective mean value. Based on the results, 70% of the horses were classified as asymmetric, which is similar to previous findings for young riding horses and horses competing at a lower level. More than one-third of these high-performing horses had asymmetry values of similar magnitude to those seen in clinically lame horses. No clear associations were observed between rider-perceived sidedness and the vertical movement asymmetry values, indicating that the perceived unevenness between sides is not a determinant of vertical movement asymmetry. Longitudinal studies on movement asymmetries in relation to training intensity and full clinical examinations with local or systemic analgesic testing are desired as further research to determine whether these movement asymmetries indicate a welfare problem.

Ferroptosis inhibitor ferrostatin-1 attenuates morphine tolerance development in male rats by inhibiting dorsal root ganglion neuronal ferroptosis.

Ferrostatin-1 and liproxstatin-1, both ferroptosis inhibitors, protect cells. Liproxstatin-1 decreases morphine tolerance. Yet, ferrostatin-1's effect on morphine tolerance remains unexplored. This study aimed to evaluate the influence of ferrostatin-1 on the advancement of morphine tolerance and understand the underlying mechanisms in male rats. This experiment involved 36 adult male Wistar albino rats with an average weight ranging from 220 to 260 g. These rats were categorized into six groups: Control, single dose ferrostatin-1, single dose morphine, single dose ferrostatin-1 + morphine, morphine tolerance (twice daily for five days), and ferrostatin-1 + morphine tolerance (twice daily for five days). The antinociceptive action was evaluated using both the hot plate and tail-flick tests. After completing the analgesic tests, tissue samples were gathered from the dorsal root ganglia (DRG) for subsequent analysis. The levels of glutathione, glutathione peroxidase 4 (GPX4), and nuclear factor erythroid 2-related factor 2 (Nrf2), along with the measurements of total oxidant status (TOS) and total antioxidant status (TAS), were assessed in the tissues of the DRG. After tolerance development, the administration of ferrostatin-1 resulted in a significant decrease in morphine tolerance (P < 0.001). Additionally, ferrostatin-1 treatment led to elevated levels of glutathione, GPX4, Nrf2, and TOS (P < 0.001), while simultaneously causing a decrease in TAS levels (P < 0.001). The study found that ferrostatin-1 can reduce morphine tolerance by suppressing ferroptosis and reducing oxidative stress in DRG neurons, suggesting it as a potential therapy for preventing morphine tolerance.

Anti-inflammatory and analgesic activities of the ethanolic extract of Seaweed Asparagopsis spp. Isolated from the Bay of Bengal, Bangladesh

The marine zone of Bangladesh covers a great diversity of natural ecosystems including a marine environment rich in commercially important seaweeds. Seaweeds are widely used in the pharmaceutical, cosmetics, chemical, antibacterial, and food industries globally. According to the Food and Agriculture Organization of the United Nations (FAO), China, Indonesia, Korea, the Philippines, and Japan are the top five nations in the world for seaweed production. In recent times, Bangladesh has initiated comprehensive research endeavours focused on seaweed, recognizing its immense potential across diverse sectors. Seaweed in Bangladesh is primarily harvested for various purposes, including food, medicine, and industrial applications. In this study, red seaweed Asparagopsis collected from the coast of Saint Martin’s island of the Bay of Bengal was tested for its bioactive properties like anti-inflammatory and analgesic activity. Anti-inflammatory test was done using carrageenan suspension and three analgesic tests e.g. hot plate test, acetic acid-induced writhing test, and formic acid-induced test were performed in mice model in the laboratory with 50% ethanol extract of Asparagopsis. Following in vivo testing, no significant activity was observed. However, Asparagopsis was found to be rich in phytochemicals like phenols, flavonoids, saponin, glycoside, steroids, tannins, and alkaloids suggesting its importance for future scientific study. This may create a door to a new world in the Blue Economy sector of Bangladesh. Bioresearch Commu. 10(2): 1583-1591, 2024 (July)

Painless transdermal delivery of neurotoxin by using dissolving microneedles: Preparation, evaluation and analgesic effect study

The analgesic effects of neurotoxin (NT) found in snake venom are well-documented. However, their clinical use is hindered by the pain experienced after intramuscular injection. Dissolving microneedles (DMNs) offer a way for transdermal drug delivery by directly penetrating the stratum corneum (SC) with micron-sized needles. Importantly, the penetration depth of DMNs does not stimulate nerve endings associated with pain, rendering this method painless during drug administration. In this study, we prepared NT-loaded DMNs (DMN-NT) using different materials and evaluated their properties and analgesic effects. The manufactured DMN-NT exhibited a square pyramid morphology, with a length of 475 μm, a width of 300 μm, and a uniformly smooth surface. The DMN-NT demonstrated favorable mechanical properties, capable of penetrating hairless mice skin to a depth of 70–80 μm. Additionally, they showed a sustained-release profile upon transdermal penetration through the SC, enabling a continuous release of the drug for a duration of 4 h. The analgesic effects of the DMN-NT were found to be adequate in both peripheral and central analgesia tests. In conclusion, the use of DMN-NT enables painless transdermal drug delivery and prolongs the duration of the analgesic effect of NT.

Pharmacological evaluation of anti-inflammatory, antipyretic, analgesic, and antioxidant activities of Castanopsis costata leaf fractions (water, ethyl acetate, and n-hexane fractions): the potential medicinal plants from North Sumatra, Indonesia.

Inflammation, fever, and pain can be associated with several diseases, and the synthetic drugs used in the treatment of these conditions often have severe side effects. As a result, there is a need for effective, economical, and safe alternative drugs, such as those derived from medicinal plants. Therefore, this study aimed to evaluate the anti-inflammatory, antipyretic, analgesic, and antioxidant activities of Castanopsis costata leaf fractions (CcLF), as well as its acute toxicity. For anti-inflammatory, antipyretic, and analgesic tests, rats were given CcLF (WFCC, EAFcC, and n-HFCC) at 50 and 100 mg/kg, diclofenac sodium (10 mg/kg), paracetamol (150 mg/kg), aspirin (100 mg/kg), and tramadol (20 mg/kg). For the antioxidant activity test, various concentrations of CcLF were used ranging from 25 to 200 μg/mL. This study also looked into whether there could be any acute toxicity and histopathology of the liver, stomach, and kidneys in experimental animals. The administration of CcLF significantly inhibited the increase in foot edema volume, and CcLF (EAFCC at 100 mg/kg) considerably decreased rectal temperature and was proportional to the standard drug paracetamol, and significantly inhibited pain sensation in various models. Additionally, CcLF showed strong antioxidant activity, and its administration at a dose limit of 5000 mg/kg/day did not show any toxic effects or death in test animals. The results of the current confirmed that CcLF has demonstrated anti-inflammatory, antipyretic, analgesic, and antioxidant properties in experimental models, and is practically non-toxic.

Polyphenols and extracts from Zingiber roseum (Roxb.) Roscoe leaf mitigate pain, inflammation and pyrexia by inhibiting cyclooxygenase-2: an in vivo and in silico studies.

Zingiber roseum (Roxb.) Roscoe, a perennial herb from the Zingiberaceae family, has a long history of traditional use in the treatment of several ailments including pain, inflammation, fever, cough, arthritis, skin diseases, and liver infections. This study sought to confirm the efficacy of Zingiber roseum (Roxb.) Roscoe leaves methanol extract (ZrlME) as reported in traditional usage by evaluating its analgesic, anti-inflammatory, and antipyretic capabilities. In addition, in silico molecular docking of the metabolites identified in ZrlME was studied to verify the experimental outcomes. ZrlME demonstrated strong dose-dependent analgesic efficacy against all analgesic tests. ZrlME (400mg/kg) showed higher anti-inflammatory activity than the standard in the carrageenan-induced paw edema test model. A significant reduction of rectal temperature (3.97°F↓) was also recorded at the same dose of ZrLME after 24h of treatment. Seven polyphenolic metabolites were identified and quantified by HPLC-DAD analysis, including 3, 4- dihydroxy benzoic acid, (-) epicatechin, rutin hydrate, p-coumaric acid, trans-ferulic acid, rosmarinic acid, and myricetin. Strong binding affinities (ranges from -5.8 to -8.5Kcal/mol) between the aforesaid polyphenols and cyclooxygenase-2 were discovered. Moreover, molecular dynamics simulations (MDS) demonstrated that these polyphenols exhibit significant COX-2 inhibitory activity due to their high stability in the COX-2 active site. In computational prediction, the polyphenols were also found to be nontoxic, and a variety of biological activities, such as antioxidant, analgesic, anti-inflammatory, antipyretic, and hepatoprotective, were observed. The results of this study revealed that ZrlME possesses notable analgesic, anti-inflammatory, and antipyretic properties.

Is It Time to Step outside the Laboratory? The Feasibility of Field-Based Examination of Exercise-Induced Hypoalgesia in Elite Badminton Athletes with and without Knee Pain.

To investigate the feasibility of testing exercise-induced hypoalgesia (EIH) in a field setting. The effect of knee pain on EIH was also explored. Within-group pre-post design. Fourteen athletes (8 male, 6 female) competing at an international level in badminton were tested on the sideline during an in-season training session. Participants completed questionnaires and a single leg decline squat to evaluate the presence of knee pain. A blinded examiner measured PPT over the quadriceps muscle before and after two conditions (3-minute quiet rest and 3-minute isometric wall squat). The exercise protocol was completed by 13 (93%) participants. Mean (SD) exertion was 8.4 (1.7), and mean thigh pain was 7.9 (2.0) at 3 minutes. Very high reliability was observed for PPT collected before and after rest (ICC 0.94, 95% CI 0.85, 0.98). PPT significantly increased by 22.4% (95% CI 15.1, 29.7) after wall squat but not after rest. Relative increases in PPT were similar in participants with and without knee pain on single leg decline squat (22.2% versus 22.6%, 7 participants each). Simple, field-based tests of endogenous analgesia are feasible and could provide new opportunities to evaluate an athlete's risk of persistent pain.

Deciphering In Vitro and In Vivo Pharmacological Properties of Seed and Fruit Extracts of Flacourtia jangomas (Lour.) Raeusch.

The objective of the study was to evaluate the pharmacological properties of the methanolic extract of Flacourtia jangomas (Lour.) Raeusch fruits (PFJM) and seeds (SFJM), along with their soluble fractions in ethyl acetate (fruit: PFJE; seed: SFJE) and chloroform (fruit: PFJC; seed: SFJC). Our phytochemical analysis of the examined extracts confirmed the presence of various therapeutically active phytoconstituents, including flavonoids, tannins, glycosides, and alkaloids. Employing the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical quenching method, SFJC exhibited the highest antioxidative potential, with an IC50 of 48.84, compared to ascorbic acid (IC50 21.77). The thrombolytic activity was assessed through rapid clot analysis of human blood samples, revealing that SFJC demonstrated the highest thrombolytic activity (60.99 ± 2.28%) compared to streptokinase (72.89 ± 2.19%). In the protein denaturation antiarthritic test, the PFJE and SFJC extracts exhibited significant potency, achieving results of 74.28 ± 1.16% and 79.25 ± 0.83%, respectively, at a dose of 500 μg/mL. All samples displayed notable anthelmintic activity by reducing Pheretima posthuma paralysis and death time in a dose-dependent manner compared to albendazole. In both in vivo analgesic tests, SFJC demonstrated substantial (p < 0.01) pain inhibition percentages (tail immersion: 49.46%; acetic acid writhing: 66.43%) at a dose of 600 mg/kg. During neuropharmacological screening, all extracts significantly (p < 0.01; p < 0.05) and dose-dependently decreased the mice's locomotion activity and motor balance. In the thiopental-induced sedation assay, SFJC significantly decreased the sleep latency time (4.18 ± 0.24 min) and increased the duration of sleep time (85.20 ± 2.39 min) at a higher dose. All samples notably reduced blood glucose levels in the oral glucose tolerance test in a dose-responsive manner, and SFJC exhibited a considerable hypoglycemic impact (7.38 ± 0.44 mmoles/L at 600 mg/kg). The frequency of diarrheal episodes in mice during the antidiarrhea assessment was significantly decreased by the tested plant samples. These findings can serve as a reference for future endeavors to isolate pure bioactive compounds from this plant for the development of novel phytomedicines.

HPLC analysis and anti-inflammatory, antinociceptive, healing and antidepressant properties of Anchusa italica Retz extracts

BackgroundIn traditional herbal medicine, Anchusa italica has sometimes been used to treat inflammatory diseases, wounds and sooth pain, but the scientific evidence supporting these uses is not solid. Given its traditional uses, we aim to evaluate the anti-inflammatory, antinociceptive, healing and antidepressant pharmacological activities of root and leaf extracts from the A. italica. Methodsthe phytochemical study was carried out by HPLC-MS analysis. The anti-inflammatory, antinociceptive and antidepressant activities were studied on male Wister rats, and healing activity on mal New Zealand rabbits. Extracts were administered orally using doses 200 and 400 mg/kg for anti-inflammatory activity, 400 mg/kg for analgesic activity, 200 mg/kg for antidepressant activity. Healing activity was studied using a cream containing 5 % of the extract topically. ResultsThe HPLC analysis found six phenolic compounds in the root extract and nine in the leaf extract. The anti-inflammatory test gave significant results (p < 0.001), at 400 and 200 mg/kg doses, the leaf extract recorded a percentage of inhibition of (82.89 % and 69.73 % respectively, while the root extract gave a percentage of inhibition of 73.67 % and 65.78 % respectively. The analgesic test also showed a significant (p < 0.001), the rats treated with the extract of the leaves have a number of abdominal contractions (11.33 ± 0.94) very close to that of reference drug aspirin (10.33 ± 0.47). In antidepressant activity, the immobility time recorded in rats treated with leaf extract was 81.86 ± 3.71 and 86.8 ± 4.65 s for root extract. The healing test showed that the root extract was effective (p < 0.05) for the treatment of the burns, after 20 days of treatment, the percentage of contraction (100 %) was recorded in the extracts 5 % and madecassol compared to the negative control 89.51 ± 4.08 %. ConclusionThese results confirm the plant's traditional use in the treatment of inflammatory diseases, wounds and pain.

UJI EFEK ANALGETIK EKSTRAK ETANOL 96% DAUN KELAPA SAWIT (Elaeis guineensis Jacq) TERHADAP MENCIT (Mus Musculus) YANG DI INDUKSI ASAM ASETAT

In Indonesia, especially in Kalimantan, many oil palm plants (Elaeis guineensis Jacq) are found. The potential of this plant has not been fully exploited. A number of tests have been carried out, namely as an antioxidant, burn wound, larvicide and antibacterial. This research was conducted to identify the analgesic effectiveness of oil palm leaf extract (Elaeis guineensis Jacq) on white mice (mus musculus) given acetic acid. The extraction method used is meseration. The analgesic test uses a chemical stimulation method. 25 mice were divided into 5 groups (negative group Na CMC 0.5%, positive group Paracetamol, dose I 100 mg/kgBW, dose II 300 mg/kgBW, dose III 500 mg/kgBW). Each group was treated orally, after 30 minutes they were given 1% acetic acid intraperitoneally, then the total number of wriths, percent protection and one way ANOVA test were calculated. The experimental results showed that the positive control percent protection was 57.44%, dose I was 34.78%, dose II was 52.10%, and dose III was 70.87%. The results of the one way ANOVA test analysis showed significant differences between each treatment group except for dose II 300 mg/kgBB. It can be concluded that the ethanol extract of oil palm leaves (Elaeis guineensis Jacq) has effectiveness as an analgesic and at dose II 300 mg/kgBW is the most effective dose because it is close to the percent protection of the positive control (Paracetamol).

Enhancing fentanyl antinociception and preventing tolerance with α-2 adrenoceptor agonists in rats

Fentanyl (FEN) is a potent opioid analgesic used for pain management. Opioid analgesic tolerance poses a significant challenge to the clinical utility of opioid agonists. Preventing the development of tolerance to opioid analgesia is crucial for improving its efficacy and safety. The noradrenergic system is involved in pain regulation. This study examined the effects of α-2 adrenoceptor (AR) agonists, dexmedetomidine (DEX), and xylazine (XYL) on FEN tolerance and antinociception, and their impact on μ-opioid receptor (MOR) expression in the posterior horn of the spinal cord (SC). Male rats were divided into six groups and treated with different drug combinations for three consecutive days. Analgesia tests and motor performance assessments were conducted, followed by SC analysis using immunohistochemistry (IHC). Analgesia tests revealed the development of FEN tolerance on the second day, but the groups receiving combined drugs did not develop tolerance. Instead, FEN antinociception was enhanced, with a prolonged duration of its effects. None of the drugs caused sedation or motor impairment, and SC morphology appeared normal. MOR expression levels did not differ significantly between the groups based on IHC analysis. These findings suggest that changes in the secondary messenger system may play a role in the early development of FEN tolerance. Combining drugs can prevent tolerance, while enhancing FEN's antinociceptive effects. These results have promising implications for chronic pain management; however, further research is needed to explore the molecular effects of α-2 AR agonists on FEN tolerance. Overall, this study sheds light on the mechanism of FEN tolerance and identifies potential avenues for future research.

Anti-inflammatory and Analgesic Effect of 70% Cinnamon Bark (Cinnamomum burmannii Blume.) Ethanolic Extract In Vivo

Cinnamon bark is known as a medicinal plant to has anti-inflammatory and analgesic effects in vitro. This activity is due to bark of cinnamon containing several compounds including cinnamaldehyde, cinnamic alcohol, cinnamic acid and coumarin. The aim of this study was to observe anti-inflammatory and analgesic effects in vivo. Anti-inflammatory test using Winter method and rats. Rats were divided into five groups negative control (aquadest), positive control (sodium diclofenac), and three extract groups with different doses (300, 400, and 500 mg/kg BW). In an analgesic test using the Siegmund method and mice. Mice were also divided into five groups negative control (aquadest), positive control (sodium diclofenac), and three extract groups with different doses (300, 400, 500 mg/kg BW). Based on a statistical test, 70% ethanol extract of cinnamon bark has anti-inflammatory and analgesic effects, also showed that there was a significant difference between the positive controls and the three extract doses. This shows that the anti-inflammatory and analgesic activity of diclofenac sodium is better than the ethanol extract of cinnamon bark in reducing the edema volume of rats and the amount of mice stretch. In conclusion,cinnamon bark showed no significant increment in high doses of anti-inflammatory and analgesic.

Phytochemical characterization, anti-diarrhoeal, analgesic, anti-inflammatory activities and toxicity profile of Ananas comosus (L.) Merr (pineapple) leaf in albino rats

Ethnopharmacological relevanceAnanas comosus (pineapple) leaf is used in ethnomedicine to treat diarrhoea, inflammation, pain, bacterial infections and oedema. Aim of the studyThe aim of this study was to investigate the anti-diarrhoeal, anti-inflammatory and analgesic effects as well as the toxicity profile of the aqueous Ananas comosus leaf extract (AACLE) in rats. MethodsMethanol ACLE was subjected to gas chromatography-mass spectrometry (GC-MS) analysis. In the acute toxicity study, a single oral dose of up to 5000 mg/kg AACLE was administered. In the subacute toxicity study (28 days), rats in groups 2–4 received AACLE orally. The anti-diarrhoeal effect was studied using charcoal meal and castor oil-induced diarrhoea. Anti-inflammatory and analgesic tests were measured using egg albumin-induced paw oedema and acetic acid-induced writhing methods, respectively. For the subacute toxicity, anti-diarrhoeal, analgesic, and anti-inflammatory studies, AACLE was administered orally to rats at doses of 200, 400, and 600 mg/kg body weight. ResultsHexadecanoic acid methyl ester, 2-methoxy-4-vinylphenol, n-hexadecanoic acid and n-heptadecanol-1 were identified among other compounds with known pharmacological activities by GC-MS analysis. No deaths, behavioural changes, or signs of toxicity were observed in the acute toxicity study. Treatment with AACLE (28 days) decreased aspartate aminotransferase, alanine transaminase, total cholesterol, triglycerides, and low-density lipoprotein cholesterol, while high-density lipoprotein cholesterol, glutathione, and catalase increased when compared with control (P < 0.05). Treatment with AACLE did not cause significant changes in haematological or renal function parameters. Treatment with AACLE inhibited gastrointestinal motility and castor oil-induced diarrhoea in rats. Treatment with AACLE resulted in a dose-dependent (200–600 mg/kg) significant (P < 0.05) anti-diarrhoeal, analgesic, and anti-inflammatory effect compared to standard drugs. ConclusionOur study revealed that ACLE is not toxic but contains bioactive compounds with anti-diarrhoeal, anti-inflammatory, antimicrobial, and hepatoprotective activity. AACLE has antidiarrhoeal, analgesic and anti-inflammatory activity in rats, which justifies its therapeutic use in traditional medicine.

Ondansetron and AS19 attenuate morphine tolerance by modulating serotonin 5-HT3 and 5-HT7 receptor expressions in rat dorsal root ganglia

PurposeOpioid drugs are frequently preferred drugs for severe pain, but their long-term use causes tolerance to their analgesic effects. However, the factors that contribute to the development of tolerance to opioids are diverse and not fully understood. In this study, our aim was to investigate the effects of 5-HT3 receptor antagonist ondansetron (ODN) and 5-HT7 receptor agonist AS19 on morphine analgesia and tolerance in rats. Material and methodsEighty-four randomly selected Wistar Albino (230–260 g) male rats were included in the study. To induce morphine tolerance in rats, morphine (10 mg/kg) was administered subcutaneously twice daily for 7 days, and tolerance was assessed by thermal analgesia tests on day 8 for 120 min. After thermal analgesia tests, dorsal root ganglia (DRGs) at spinal L4-S5 level were isolated. 5-HT3 and 5-HT7 receptor expressions in DRGs were measured by immunohistochemical method. ResultsThe results show that co-administration of ODN or AS19 with morphine indicated a significant increase in analgesic effect compared to morphine alone In addition, the difference between the mean of ODN or AS19 combined with morphine and the morphine-tolerant group was statistically significant. H-score analysis significantly increased 5-HT3 receptor expressions in the morphine-tolerant rats, and administration of ODN prevented this. Similarly, 5-HT7 receptor expressions were significantly decreased in the morphine tolerant group, and the administration of AS19 increased this expression. ConclusionThese study results suggest that both ODN and AS19 alter the 5-HT3 and 5-HT7 receptor expressions in the DRG and possibly attenuate morphine tolerance in this way.

Pharmacological Investigation of In-vitro Anti-inflammatory, Antimicrobial, Thrombolytic, Cytotoxic and In vivo Analgesic Activities of Ethanolic Leaf Extract of Diospyros malabarica

Aims: This study was designed to investigate the effects of leaf extracts of Diospyros malabarica plant (EEDML) on a number of in vitro activities, including antibacterial, anti-inflammatory, cytotoxic, and thrombolytic activities, as well as in vivo analgesic activities.&#x0D; Place and Duration of Study: The Laboratory of Phytochemistry and Pharmacology at the Department of Pharmacy and the Laboratory of Microbiology at Stamford University Bangladesh and the Bangladesh Council of Scientific and Industrial Research, Dhaka, conducted this investigation from January 2022 to June 2023.&#x0D; Methodology: The study employed the Egg Albumin Protein Denaturation Assay to evaluate the anti-inflammatory effects of various doses. The Disk Diffusion Method was employed for conducting an antimicrobial assay. Different tests were conducted to evaluate the effects of thrombolytic and cytotoxic substances. These tests included the Clot Lysis assay and the Brine Shrimp Lethality Assay. In-vivo analgesic testing was conducted using the hot plate method and the acetic acid-induced writhing test.&#x0D; Results: The experimental tests showed significant pain-relieving effects, with inhibition percentages of 46.2% and 66.61% observed at doses of 200 and 400 mg/kg, respectively. The anti-inflammatory test showed a significant inhibition of EEDML at a concentration of 1000μg/mL, with an inhibition rate of 85.45%. The antimicrobial test showed a moderate antimicrobial effect, with a zone of inhibition ranging from 07-15, depending on the microorganism and dosage. The thrombolytic test showed a clot lysis rate of 85.37%, while the cytotoxic test indicated an LC50 value of 1.47.&#x0D; Conclusion: EEDML's phytochemical displays strong pharmacological properties, suggesting its potential for drug discovery in diverse areas.

Antioxidant, analgesic, anti-inflammatory, and antipyretic potentialities of leaves of Artabotrys hexapetalus, established by in silico analysis

BackgroundArtabotrys hexapetalus is a rare plant in the Indian subcontinent. This plant is used for different therapeutic purposes in folk medicine and many bioactive compounds are reported in this plant. Considering its traditional uses and the presence of medicinal compounds, we aimed to evaluate some pharmacological properties of its leaves along with in silico analysis in scientific ways. MethodsAntioxidant tests were conducted in both qualitative and quantitative ways. 2,2-Diphenyl-1-picryl hydrazyl (DPPH), hydrogen peroxide, and superoxide radicals scavenging with FeCl3 reducing properties of A. hexapetalus extract were carried out. Acetic acid-induced writhing, tail immersion, formalin-induced paw edema, and Brewer's yeast-induced pyrexia methods were followed to conduct peripheral analgesic, central analgesic, anti-inflammatory, and antipyretic potentialities, respectively. Finally, molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of reported compounds were conducted. ResultsThe A. hexapetalus extract was found to possess a quite good amount of phenolics, flavonoids, and tannins. This extract also revealed good radical scavenging effects along with ferric chloride-reducing capabilities. In the analgesic tests, the extract showed excellent responses in writhing inhibition and elongation in tail withdrawal time. The extract also significantly lessened paw edema over time at both doses. A notable decrease in body temperature was also observed. Those responses revealed nice pharmacological potentialities. Along with these findings and conducting in silico analysis, we finally proposed seven molecules as lead compounds. ConclusionOur analysis revealed that A. hexapetalus leaves are highly enriched with antioxidants and the extract showed good pharmacological characteristics.

Neuropharmacological assessment of the methanolic stem back extract of Anopyxis klaineana (Pierre) Engl. (Rhizophoraceae) in mice

BackgroundMedicinal plants have recently attracted attention on a global scale for therapeutic interventions in the field of neuroscience. Anopyxis klaineana, a medicinal plant widely used in West Africa, has been studied extensively for its anti-inflammatory effects. However, studies on its neuropharmacological effects are quite limited. This study therefore assessed the neuropharmacological potential of the methanolic stem bark extract of Anopyxis klaineana (EAK) in murine models. Materials and methodsMice were treated orally with a methanolic stem back extract of Anopyxis klaineana (EAK) at 10, 30 or 100 mg/kg followed by testing in the elevated plus-maze (EPM) and open field (OF) tests for anxiolytic-like effects. EAK's antidepressant-like potential was also evaluated in the tail suspension test (TST), while anticonvulsant and central analgesic effects were evaluated with the pentylenetetrazol (PTZ)-induced convulsion threshold and tail withdrawal tests respectively at 30, 100 or 300 mg/kg. The extract was additionally subjected to chromatographic analyses using high resolution HPLC-MS. ResultsTotal ion current chromatogram of EAK revealed several peaks suggestive of secondary metabolites of the plant extract. EAK significantly (p<0.05) reduced depression-like behaviours in the TST although not as potent as fluoxetine (ED50: EAK=43.39±2.5; fluoxetine=1.16±1.6) (F3,20=9.663, p = 0.0004). It also showed significant anticonvulsive effect by reducing the frequency and duration of PTZ-induced convulsions (ED50=48.53±2.5 mg/kg) (F3,19=5.136, p = 0.0091). This anticonvulsant effect was seen in both clonic and tonic convulsions at 30 and 300 mg/kg. Additionally, EAK-treated mice showed higher latency to tail withdrawal in the analgesia test. We also observed significant (p<0.05) dose-dependent increase in anxiolytic-like effects in EAK-treated animals in the EPM (F3,20=10.77, p = 0.0002) and OF tests (F3,22=5.079, p = 0.008). ConclusionsThe methanolic Anopyxis klaineana stem back extract exhibits anxiolytic-like, antidepressant-like, analgesic and anticonvulsant effects in murine models for assessing neuropharmacological activity and is a good source for novel neuroactive compounds.

Papaver rhoeas L. stem and flower extracts: Anti-struvite, anti-inflammatory, analgesic, and antidepressant activities

The Papaver rhoeas L. (P. rhoeas) plant, which belongs to the Papaveraceae family, is also used as food and is exploited to treat several health problems. The purpose of this research is to determine the anti-struvite, anti-inflammatory, analgesic, and antidepressant effects of the stem extract (SE) and flower extract (FE) of the plant P. rhoeas. We used polarizing microscopy and Fourier transform infrared spectrometry (FT-IR) to evaluate the anti-struvite effect of our plant. The edema approach induced by the carrageenan molecule was used to study the anti-inflammatory impact of our extracts. The analgesic test was determined by calculating the number of abdominal contractions induced by the intraperitoneal (IP) administration of acetic acid. To evaluate the antidepressant effect of our extracts, we used the forced swimming test (FST). According to the results of the secondary metabolite extraction, both extracts contained high contents of secondary metabolites, while the results of the screening test showed that flavonoids, alkaloids, phenols, tannins, coumarins, saponins, and terpenoids were present. The result of struvite crystallization inhibition observed by polarizing microscopy and FT-IR shows the inhibition of struvite crystal aggregation by SE by decreasing the amount and size of crystals in a manner similar to cystone. The results of anti-inflammatory activity show maximum inhibition of edema after six hours of carrageenan injection in rats (T6) for all extracts, with a maximum value of 86.36% for SE at the dose of 200 mg/kg. Regarding the analgesic effect of our plant, the lowest number of abdominal contractions was observed in rats treated with SE at a dose of 400 mg/kg. The FST results show that the lowest immobilization time was observed in rats treated with FE at a dose of 400 mg/kg. The results obtained show that the flowers and stems of P. rhoeas can constitute a rich source of bioactive molecules with potential pharmaceutical applications.