Hot Plate Model Research Articles

Stryphnodendron rotundifolium Mart. bark: Antiedematogenic and antinociceptive activity

Background: Stryphnodendron rotundifolium Mart., known as “barbatimão” in folk medicine, it's used as an astringent, antiseptic, diuretic, cicatrizing, and intestinal deseases as leukorrhea and diarrhea. Objective: Then, this purpose of this research is to evaluate the antiedematogenic and antinociceptive activity of the S. rotundifolium bark hydroalcoholic extract (EHSR). Methods: For this, the animal model the acute ear edema induced by 10% phenol, capsaicin, histamine, croton oil by single and multiple applications and, abdominal contortions by acetic acid and hot plate models were assayed. Results: The EHSR (10 mg/mL) presented significant topical antiedematogenic activity when reducing ear edema following single (35.12%) and multiple croton oil applications on days 6, 7, 8 and 9 with a 34.60, 31.08, 31.69 and 27.90% reduction in ear thickness, respectively, and reducing masses by 29.8%. The EHSR also reduced phenol (40.55%) and histamine (64.87%) induced edema. The EHSR (100 mg/kg) demonstrated antinociceptive activity by significantly reducing the number of contortions (59.5%) and increasing the animal's time of permanence on the plate by 41.9% (T:90min). Conclusion: We conclude, therefore, that the S. rotundifolium hydroalcoholic extract possesses antiedematogenic and central and peripheral influence in antinociceptive action. Therefore, given the results presented herein, we suggest new in vivo assays be performed to evaluate the possible mechanism of actions involved in these activities.

Anti-peptic Ulcer of the N-hexane Fraction from Sanchezia nobilis Hook.F. Leaves and its Isolated Compounds

The n-hexane fraction of the Sanchezia nobilis Hook.f. leaves was evaluated for its effect on the gastric ulcer with pyloric ligation (Shay) rat model, analgesia effect on hot plate model and pain threshold meter, and inhibitory effect on Helicobacter pylori (H.P). The data showed a significant reduction in ulcer score, gastric volume, and total acidity and tended to reduce free acidity and increase gastric pH. In addition, the n-hexane fraction had a central analgesic effect and H.P inhibition. Chemical investigation of the n-hexane fraction resulted in the isolation of the four compounds (1 – 4). By using NMR and ESI-MS spectra, these compounds were identified chemical structures (3β, 5α, 22E)-stigmasta-7,22-dien-3-ol (1), coccinic acid (2), 7-hydroxy-6-methoxy coumarin (3), and betulinic acid (4). All compounds were reported for the first time from the Sanchezia genus.
 
 

Synthesis and Investigation of the Analgesic Potential of Enantiomerically Pure Schiff Bases: A Mechanistic Approach.

Schiff bases are a class of organic compounds with azomethine moiety, exhibiting a wide range of biological potentials. In this research, six chiral Schiff bases, three ‘S’ series (H1–H3) and three ‘R’ series (H4–H6), were synthesized. The reaction was neat, which means without a solvent, and occurred at room temperature with a high product yield. The synthesized compounds were evaluated for analgesic potential in vivo at doses of 12.5 and 25 mg/kg using acetic-acid-induced writhing assay, formalin test, tail immersion and hot plate models, followed by investigating the possible involvement of opioid receptors. The compounds H2 and H3 significantly (*** p < 0.001) reduced the writhing frequency, and H3 and H5 significantly (*** p < 0.001) reduced pain in both phases of the formalin test. The compounds H2 and H5 significantly (*** p < 0.001) increased latency at 90 min in tail immersion, while H2 significantly (*** p < 0.001) increased latency at 90 min in the hot plate test. The ‘S’ series Schiff bases, H1–H3, were found more potent than the ‘R’ series compounds, H4–H6. The possible involvement of opioid receptors was also surveyed utilizing naloxone in tail immersion and hot plate models, investigating the involvement of opioid receptors. The synthesized compounds could be used as alternative analgesic agents subjected to further evaluation in other animal models to confirm the observed biological potential.

Antinociceptive effect, acute toxicity and chemical analysis of cold mechanically extracted N. Sativa seed oil

Nigella sativa L. (Ranunculaceae), seed oil is traditionally used for pain, stiffness in the joints and eczema. The N. sativa seed oil (NSSO) contains an abundance of monoterpenes and essential fatty acids of various pharmacological actions. The objective of this study is to investigate the antinociceptive effect of single oral dose of NSSO on acetic acid-induced writhing and hot plate induced algesia in mice. Further, the study also, aims to characterize the chemical constituents of NSSO by using GC/MS. Swiss albino mice were divided into two sets of three groups consisting of six animals per group for the assessment of analgesic effect by hot plate and by acetic acid induced writhing methods. Group I, received distilled water (10 ml/kg, p.o.); group II, received diclofenac sodium (2.5 mg/100g, p.o.); and group III, received NSSO (0.5 ml/100g, p.o.). After NSSO administration the animals were placed on the hot plate and their response was noted down at different time interval. Further, another set of animals of other three groups were subjected to acetic acid induced writhing test after 30 minutes of drug administration. The results of the study showed that NSSO significantly (p&lt;0.05) increased the latency to thermal stimulus, and also, there was significant (p&lt;0.01) reduction in the number of writhes induced by 0.07% acetic acid. The GC/MS chromatogram of NSSO showed a total of 50 compounds. The LD50 of NSSO was greater than 5 g/kg. Thus in conclusion, NSSO (0.5ml/100g, p.o.) showed a significant analgesic effect against acetic acid induced writhing and also in hot plate model in mice. The phytochemical analysis of NSSO showed the presence of several active principles, primarily linoleic acid and thymoquinone. The presence of linoleic acid and thymoquinone in NSSO, possibly contributed to its analgesic effect that needs further investigation in other animal models of algesia.

Analgesic and Anti-inflammatory Activities of Trayodashang Guggulu, an Ayurvedic Formulation

• Analgesic and anti-inflammatory activity of trayodashang guggulu . • Analgesic activity by Eddy's hot plate, tail immersion and formalin-induced pain models • Anti-inflammatory activity by carrageenan and formalin-induced inflammation models. • TG did not reduced centrally acting pain models i.e. Eddy's hot plate and tail immersion. • In formalin-induced pain model, TG significantly decreased both flinching and licking pain responses in early and late phase. • TG showed significant reduction in formalin and carrageenan-induced inflammation • Study substantiates the traditional use of TG in various painful inflammatory conditions. Background: Trayodashang guggulu (TG) is a compound Ayurvedic formulation used in Indian traditional system of medicine for the treatment of various inflammatory conditions like arthritis and associated pain. Purpose: To study the analgesic and anti-inflammatory effects of trayodashang guggulu . Methods: Trayodashang guggulu (TG) was standardized as per standard procedures and TLC profile was carried as per Ayurvedic Pharmacopoeia of India and LC-MS analysis was done to identify its bioactive constituents. Trayodashang guggulu was suspended in water and administered orally at 270 and 540 mg/kg dose for evaluating pain and inflammation in rats. Analgesic activity was assessed by Eddy's hot plate, tail immersion and formalin-induced pain models while anti-inflammatory activity was assessed by carrageenan and formalin-induced inflammation models. Further, the mechanism of anti-inflammatory action is predicted through various in silico methods like molecular docking and dynamics studies using AutodockVina and AMBER, respectively. Results: TG was found compliant as per pharmacopoeial standards. TG (270 and 540 mg/kg, orally) did not cause significant reduction in pain in centrally acting pain models i.e. Eddy's hot plate and tail immersion tests as like Pentazocin (10 mg/kg). In formalin-induced pain model, TG (270 and 540 mg/kg, orally) significantly decreased both flinching and licking pain responses in early and late phase while indomethacin (10 mg/kg) only affected late phase flinching and licking. Further, TG showed significant time-dependent reduction in formalin and carrageenan-induced inflammation as compared to vehicle control. Indomethacin (10 mg/kg), standard drug also showed significant reduction in pain and inflammation. LC-MS analysis revealed the presence of 17 phytoconstituents in TG. Further, in silico studies revealed that some of the identified phytochemicals may have inhibitory activity against COX-2 enzyme and the synergistic effects due to multi components may be responsible for the anti-inflammatory properties of TG. Conclusion: In conclusion, trayodashang guggulu inhibited the inflammatory pain as well as showed anti-inflammatory activity in rats. The effect may be attributed to the presence of anti-inflammatory phytoconstituents through the inhibition of anti-inflammatory enzymes like COX-2. The study further validates its traditional use in various painful inflammatory conditions.

Investigations of the anti-inflammatory, analgesic, and anti-malarial activities of extract from the leaf of Halea ciliata (Abura leaves)

Background: Halea ciliata (Abura leaves) is a medicinal plant and has long been used for the treatment of several diseases including malaria, pains and inflammation, However, no complete pharmacological study to confirm these effects have been reported. In this study, the anti-inflammatory, analgesic, and antimalarial effects of Halea ciliata were investigated. Methods: The leaf of Halea ciliata was extracted with ethanol. The anti-inflammatory activity was tested using the egg albumin induced paw oedema while the analgesic activities were investigated using the hot-plate and Tail flick tests in mice. The anti-malaria activities were evaluated in Plasmodium berghei infected mice. Results: The crude methanol extract of Halea ciliata had LD50 greater than 5000 mg/kg and contains alkaloid, tannin, flavonoid, glycoside, steroid, terpenoid and saponin. In vivo analysis revealed that the crude extract demonstrated 78.64±4.32 % and 78.09±2.34% inhibition of the Plasmodium berghei parasite, while chloroquine, exhibited 92.12±3.45 % activities. The extract also significantly (p&lt;0.05) suppressed the egg albumin induce paw oedema with percentage inhibition of 13.55±0.34, and 11.88±1.34 at 200 and 400 mg/kg respectively, while the standard drug caused 64.40±2.34 inhibition of paw oedema when compared to the non-treated controls. Similarly, the crude extract demonstrated significant analgesic activities in both the hot plate and tail-flick models. Conclusion: These results suggest that crude methanol extract of Halea ciliata has potent anti-malaria, anti-inflammatory and anti-nociceptive activities.

Phyllanthus seeds Methanolic extract: In vivo evaluation of Analgesic activity

Phyllanthus amarus is a small herb used in tradicinal medicine worldwide. The phytoconstituents of seeds of this plant is evaluated for various medicinal properties.This study was done to evaluate analgesic activity of Phyllanthus amarus seeds in albino mice.Analgesic activity of methanolic extract of Phyllanthus seeds was evaluated using hot plate and Tail clip animal models. Normal saline was used as control drug and standard drug was Morphine and 50 mg,100 and 200 mg/kg of methanolic extract of Phyllanthus seeds was used as test drugs. Phyllanthus seed extract showed statistically significant (p&lt;0.05) increase in the reaction time of animals as compared to control at doses of 100mg/kg and 200 mg/kg at 60 min of drug administration in hot plate method and at 30 min and 60 min of drug administration in tail clip method.The results of the present study shows that methanolic extract of seeds of Phyllanthus amarus showed central analgesic activity in both hot plate and tail clip models in albino mice.

Total phenolic, flavonoid contents, and biological activities of stem extracts of Astragalus spinosus (Forssk.) Muschl. grown in Northern Border Province, Saudi Arabia

Background and objectiveGenus Astragalus belongs to the family Fabaceae and is one among the largest genera consisting of around 3000 species. The plants have been used traditionally in treatment of various ailments in folklore. The study was planned to assess the analgesic and inflammatory activity of Astragulus spinosus (Forssk.) Muschl extract of the stem. Materials and methodsCourse powder of stems of Astragulus spinosus was extracted using chloroform and methanol as solvents. Folin ciocalteu method was employed for determination of the phenolic acid content. Aluminum chloride colorimetric procedure was followed for estimating the flavonoid content. Both chloroform and methanolic extracts at 250 and 500 mg/kg, were tested for the analgesic activity, however, only methanolic extract was selected for anti-inflammatory property based on the results of analgesic activity. The analgesic effect was executed on male rats by the hot plate model. The anti-inflammatory effect was studied in the carrageenan rat paw edema model. The experimental information was interpreted statistically using one-way ANOVA and p < 0.05 was used to express importance of the results. ResultsThe total phenolics of the methanol extract was 420 µg and that of chloroform extract was 265 µgwhile total flavonoid content in terms of quercetin was found to be 68 µg and 17.5 µg for methanol and chloroform extract respectively. Only methanolic extract exhibited significant (p < 0.001) analgesic activity by elevating the pain threshold starting from 15 min. The methanolic extract inhibited (p < 0.001) the edema in carrageenan induced model. The performance of higher dose (500 mg/kg) was better with reference to lower dose (250 mg/kg). ConclusionOutcome of the results show that the methanolic stem extracts exhibited significant analgesic and anti-inflammatory-like activity with reference to chloroform extract. Credit of which is given to flavonoids and phenolic content present in the methanolic extract. However, more research is suggested to establish the safety and effectiveness of the herbal drug to manage diseased states including pain and inflammation.

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.

Preclinical evaluation of Zanthoxylum piperitum Benn., traditional muscle pain remedy, for joint inflammation

Ethnopharmacological relevanceZanthoxylum piperitum has been used as a traditional Asian medicine to treat hypertension, stroke, bruise and muscle pain. It has been known to induce detoxification; affect anti-bacterial, anti-oxidant, and tyrosinase activity; inhibit osteosarcoma proliferation; anti-osteoarthritis inflammation. In this study, we aim to identify the therapeutic effect of Z. piperitum 90% EtOH extract (ZPE-LR) on rheumatoid arthritis. Material and methodsWe investigated the anti-rheumatoid arthritis and -immunomodulatory activities of the ZPE-LR in collagen-induced arthritic (CIA) mice, a rheumatoid arthritis animal model. In order to assess the analgesic effects of ZPE-LR in vivo, acetic acid injection, formaldehyde injection, hot plate model was used. The mechanism for anti-inflammatory activity of ZPE-LR was identified with LPS-stimulated Raw 264.7 cells. ResultsPharmacologically, oral administration of ZPE-LR into CIA mice resulted in a significant and dose-dependent decrease in clinical arthritis score and paw swelling compared to untreated negative control. Pathologic examination showed that ZPE-LR prevented morphological change in cartilage and destruction of phalanges in CIA mice. This protective effect was associated with reduced pain, inflammatory mediators such as NO, TNF-α, IL-1β, and IL-6, as well as COX-2 and iNOS expression. Furthermore, reduction of phosphor-ERK and BDNF indicates a novel rheumatoid arthritis-regulating mechanism by ZPE-LR treatment. ConclusionsThese data suggest that the administration of ZPE-LR remarkably inhibited CIA progression and might be helpful in suppressing inflammation and pain in rheumatoid arthritis.

Assessment of Analgesic, Anti-Inflammatory And Anti-Pyretic Activities of Malva Neglecta Wallr. In Animal Model

Analgesic, anti-inflammatory and anti-pyretic activities of n-hexane and aqueous ethanolic extracts of Malva neglecta in Swiss albino mice was evaluated. For each activity, the mice were divided into 4 groups: Group 1 served as control, Groups 2 and 3 were given n-hexane and aqueous ethanol extracts, respectively whereas Group 4 was treated with the standard drug. Analgesic activity was evaluated against acetic acid induced writhing, Eddy's hot plate method, and Formalin induced paw licking. Anti-inflammatory activity was evaluated by carrageenan-induced paw edema. The extracts were also examined for their anti-pyretic activities against yeast-induced pyrexia. Results showed that the n-hexane (p &lt; 0.05) and aqueous ethanolic (p &lt; 0.005) extracts of M. neglecta exhibited analgesic activity by reducing acetic acid-induced writhing, mean reaction time on hot plate model and formalin-induced paw licking in mice as compared to the control. The n-hexane extract (p &lt; 0.05) as well as aqueous ethanolic (p &lt; 0.005) extracts produced significant antiinflammatory activity as compared to the control. Both the n-hexane and aqueous ethanolic extracts revealed significant antipyretic activity (p &lt; 0.005 and p &lt; 0.05, respectively) in mice model. The results of the present study demonstrated that the n-hexane and aqueous ethanol extracts of M. neglecta possess analgesic, antiinflammatory and anti-pyretic activities. Bangladesh J. Bot. 50(3): 577-583, 2021 (September)

Evaluation of antinociceptive activity of Ilex dipyrena Wall. in mice

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

An Effective and Safe Enkephalin Analog for Antinociception.

Opioids account for 69,000 overdose deaths per annum worldwide and cause serious side effects. Safer analgesics are urgently needed. The endogenous opioid peptide Leu-Enkephalin (Leu-ENK) is ineffective when introduced peripherally due to poor stability and limited membrane permeability. We developed a focused library of Leu-ENK analogs containing small hydrophobic modifications. N-pivaloyl analog KK-103 showed the highest binding affinity to the delta opioid receptor (68% relative to Leu-ENK) and an extended plasma half-life of 37 h. In the murine hot-plate model, subcutaneous KK-103 showed 10-fold improved anticonception (142%MPE·h) compared to Leu-ENK (14%MPE·h). In the formalin model, KK-103 reduced the licking and biting time to ~50% relative to the vehicle group. KK-103 was shown to act through the opioid receptors in the central nervous system. In contrast to morphine, KK-103 was longer-lasting and did not induce breathing depression, physical dependence, and tolerance, showing potential as a safe and effective analgesic.

Discovery, Structure-Activity Relationship, and Mechanistic Studies of 1-((3R,4S)-3-((Dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)piperidin-1-yl)-2-(2,4,5-trifluorophenyl)ethan-1-one as a Novel Potent Analgesic.

Management of moderate to severe pain relies heavily on opioid analgesics such as morphine, oxycodone, and fentanyl in clinics. However, their prolonged use was associated with undesirable side effects. Many new strategies to reduce side effects have been proposed, but not without disadvantages. Using a hot plate model as a phenotypic screening method, our studies identified (3R,4S)-9d with a new scaffold as a potent analgesic with ED50 values of 0.54 mg/kg and 0.021 mg/kg in hot plate and antiwrithing models, respectively. Mechanistic studies showed that it elicited its analgesic effect via the active metabolite (3R,4S)-10a. The mechanism of (3R,4S)-10a-induced activation of the μ opioid receptor (MOR) was proposed by means of molecular dynamics (MD) simulation.

Investigating the thermal behaviour of geothermal pavements using Thermal Response Test (TRT)

Geothermal pavements represents a novel approach to shallow geothermal energy applications, in which horizontal ground heat exchangers are implemented within the pavement structure instead of traditional purpose-built trenches, thus decreasing capital costs. This study aims to better understand the feasibility and potential of these systems, by investigating the thermal response of the ground in a full scale geothermal pavements system, the first of its kind in Australasia. For this purpose, a fully instrumented geothermal pavements segment, measuring 20 m × 10 m, was constructed in the city of Adelaide, Australia. The geothermal pavement was subjected to Thermal Response Testing (TRT) and numerical modelling is adopted herein and validated using TRT data to further understand the ground response. In addition to providing insights on the capacity of energy provision for geothermal pavements, this work also introduces and discusses various methods of TRT data analysis for the geothermal pavement, specifically for obtaining the effective ground thermal conductivity, a key parameter in shallow geothermal design. The results indicate that from the considered methods, the conventional semi-log method can lead to overestimation of thermal conductivity, the guarded hot plate model tends to underestimate its value and detailed numerical modelling is most accurate, but computationally more expensive. The results also show that the radius of influence of the geothermal pavement in the examined case is close to 0.5 m and even though the geothermal pavement is considerably affected by the ambient temperature, it can be a viable solution for heating and cooling purposes, showing a heat exchange of 50.2 W/m2 and a rate per length of the pipe of 25 W/m in the case analysed here.

Two New βN-Alkanoyl-5-Hydroxytryptamides with Relevant Antinociceptive Activity.

In this work, we describe a new route for the synthesis and the antinociceptive effects of two new βN-alkanoyl-5-hydroxytryptamides (named C20:0-5HT and C22:0-5HT). The antinociceptive activities were evaluated using well-known models of thermal-induced (reaction to a heated plate, the hot plate model) or chemical-induced (licking response to paw injection of formalin, capsaicin, or glutamate) nociception. The mechanism of action for C20:0-5HT and C22:0-5HT was evaluated using naloxone (opioid receptor antagonist, 1 mg/kg), atropine (muscarinic receptor antagonist, 1 mg/kg), AM251 (cannabinoid CB1 receptor antagonist, 1 mg/kg), or ondansetron (5-HT3 serotoninergic receptor antagonist, 0.5 mg/kg) 30 min prior to C20:0-5HT or C22:0-5HT. The substances both presented significant effects by reducing licking behavior induced by formalin, capsaicin, and glutamate and increasing the latency time in the hot plate model. Opioidergic, muscarinic, cannabinoid, and serotoninergic pathways seem to be involved in the antinociceptive activity since their antagonists reversed the observed effect. Opioid receptors are partially involved due to tolerant mice demonstrating less antinociception when treated with both compounds. Our data showed a quicker and simpler route for the synthesis of the new βN-alkanoyl-5-hydroxytryptamides. Both compounds demonstrated significant antinociceptive effects. These new compounds could be used as a scaffold for the synthesis of analogues with promising antinociceptive effects.

Comparative Evaluation of Analgesic, Antipyretic &amp; Anti-Inflammatory Effects of Various Extracts of Dried Fruit of Illicium verum Hook.f (Star anise) in Rodents

The current investigation was designed to evaluate the analgesic, antipyretic, and anti-inflammatory effects of various extracts (methanol, ethanol, and aqueous) of dried fruit of Illicium verum hook.f, using 3 different doses (150, 250, and 350 mg/kg p.o) to verify the traditional uses of this spice. In the hot plate model of analgesia, ethanol extract showed a significant reduction in pain in a dose-dependent manner compared to the control group. The maximum effect was observed at 350 mg/kg dosage i.e., 16.90±0.17 s compared to the control group i.e., 5.03±0.05 s. The antipyretic activity was assessed in rats by Brewer’s yeast induction. The methanol and ethanol extracts produced a significant reduction in rectal temperature compared to the control group throughout the three doses. The maximum effect was observed at 350 mg/kg dosage of ethanol extract i.e., 37.1±0.8* compared to the control i.e., 39.1±0.3. In the paw edema model, methanol and ethanol extracts disclosed a significant reduction in paw edema at 350 mg/kg of dose. The maximum effect was observed at 350 mg/kg dosage of ethanol extract i.e., 0.25±0.23* compared to the control i.e., 0.97±0.4. In a behavioral study, locomotor activity (rearing) and exploratory activity (grooming) in mice was reduced significantly at higher doses (350 mg/kg p.o) involving the three extracts. However, scratching was increased non-significantly at all doses compared to the control group. This study concluded that various extracts of Illicium verum hook.f showed significant analgesic, antipyretic, and anti-inflammatory effects at different doses in a dose-dependent manner with varying potencies. The ethanol extract was found to be more potent among all, followed by methanol and aqueous extracts, whereas maximum effects were observed at 350 mg/kg of dose.

Effect of the Croton rhamnifolioides Essential Oil and the Inclusion Complex (OEFC/β-CD) in Antinociceptive Animal Models

This study aims to evaluate the antinociceptive effect of the C. rhamnifolioides leaf essential oil (OEFC) and the β-cyclodextrin inclusion complex (COEFC) and investigate the pain signaling pathways involved in the antinociceptive response. The effects of the OEFC and COEFC on the central nervous system (CNS) were determined by open field and rota-rod assays, and the antinociceptive effect was evaluated via the acetic acid-induced abdominal contortions, formalin, and hot plate models. Swiss (Mus musculus) male mice (20–30 g) were used in both trials. The OEFC (200 mg/kg/v.o-orally) and COEFC (83.5 mg/kg/v.o.) did not present alterations in the CNS. The OEFC (25, 50, 100, and 200 mg/kg/vo.) and COEFC (8.35, 41.75, and 83.5 mg/kg/v.o.) demonstrated antinociceptive effects in the abdominal contortions, formalin, and hot plate tests. The OEFC (25 mg/kg/v.o.) and COEFC (8.35 mg/kg/v.o.) doses showed that the antinociceptive effect involves the activation of the opioid, cholinergic, and vanilloid systems, as well as the L-arginine/NO and α-2 adrenergic receptor pathways. The antinociceptive potential the OEFC and COEFC demonstrate possible alternatives for the therapy of pain. However, the COEFC presented more significant effects at lower doses than the isolated OEFC, where this action may be justified by the properties and advantages of the complexation.

Development of Ecofriendly Carbon Dots for Improving Solubility and Antinociceptive Activity of Glycyrrhizic Acid.

The therapeutic potential of glycyrrhizic acid (GA) with various pharmacological properties is extremely limited owing to its poor water solubility. To solve this problem, nanocarrier-nontoxic Glycyrrhizae Radix et Rhizoma-derived carbon dots (GRR-CDs) with a narrow particle distribution of (1.90 ±0.44) nm were developed by an ecofriendly, simple and low-cost calcination method using GRR as the sole precursor. Then, the solubility of GA was shown to be prominently improved up to 27 times by GRR-CDs via a convenient and cost-effective ultrasonic dispersion method without needing to add any organic reagent. Various technologies were further used to demonstrate the interaction between GA and GRR-CDs. In addition, a release study in vitro exhibited a sustained release of GA for 24 h with a higher release ratio of up to 92.87% compared with that of pure GA. A significantly higher antinociceptive activity of the GRR-CDs-GA complexes compared to unprocessed GRR-CDs and GA was further demonstrated in both hot-plate model and acetic acid-induced writhing model. These results support the promising application of GRR-CDs as a potential tool for improving the solubility and antinociceptive activity of poorly water-soluble drugs, such as GA.

Phytochemical profiling of bioactive compounds, anti-inflammatory and analgesic potentials of Habenaria digitata Lindl.: Molecular docking based synergistic effect of the identified compounds

Ethnopharmacological relevanceMembers of Orchidaceae family has a long history in herbal and Chinese medicines. Members of this family are most commonly famous in the management of inflammation and analgesia in folk medicine. Habenaria digitata, an unexplored specie of Orchidaceae is found in North areas of Pakistan and is used by the local population for the management of analgesia and inflammation. Aim of the studyBased on the effective outcomes of the natural products as alternative therapies, we have evaluated Habenaria digitata for the management of analgesia and inflammation. The aim of the designed project is to provide a scientific basis of using this plant for the management of analgesia and inflammation. Materials and methodsThe H. digitata crude extract (Hd.Cr) and subfractions, i.e. n-hexane (Hd.Hex), chloroform (Hd.Chf), ethyl acetate (Hd.EtAc), n-butanol (Hd.Bt) and aqueous (Hd.Aq) were used. The GC-MS analysis was used for the identification of phytochemicals. The plants samples were subjected to cyclooxygenase (COX 2) and lipoxygenase (5-LOX) enzymes assays. The hot plate model, acetic acid induced writhing and formalin induced paw licking models were used for in-vivo analgesic studies. The in-vivo anti-inflammatory potential was determined with carrageenan induced paw edema test. Molecular docking studies of the identified compounds were carried out by using Molecular Operating Environment (MOE, 2016.08). ResultsThe GC-MS analysis confirmed sixty-five compounds in Hd.Cr. Among the fractions, Hd.Chf and Hd.EtAc displayed highest activities. The observed IC50 values were 21.30 and 32.39 μg/ml against COX 2 while 14.42and 16.40 μg/ml for 5-LOX respectively. The in-vivo inflammatory and analgesic studies were pre-requisited with acute toxicity tests. In carrageenan induced inflammation, Hd.Chf excelled the standard drug aspirin by giving 62.92% inhibition of paw edema at 4th h. Similarly, at highest concentration (75 mg/kg) of acetic acid induced analgesia, Hd.Chf was more potent than the standard drug. In formalin method, Hd.Chf exhibited 85.81% inhibition at phase-I and 74.15% at Phase-II. In hot plate model, Hd.Chf exhibited average reaction time of 10.90 at 15, 30, 45 and 60 min intervals. Docking studies supported our results and confirm the synergistic effects of phytochemicals. Conclusions:Our experimental results concluded that H. digitata contains several bioactive compounds. These bioactive compounds synergistically have therapeutic efficacy for the management of inflammation and analgesia. We have confirmed both of these potentials from the in-vitro and in-vivo experiments. Moreover, it is also obvious that the chloroform and ethyl acetate fractions are rich in these bioactive compounds. Specifically, the Hd.Chf is observed to be more practical in all the tested models of analgesia and inflammation. Computed binding energies of the compounds revealed that all the compounds have synergistic effect to prevent analgesia and inflammation.