Anti-Nociceptive Effect in Mice of Thillai Flavonoid Rutin

We investigated the anti-nociceptive effect of Excoecorio ogollocho （E.ogollocho） against chemically and thermally induced nociception, Albino mice received a dose of 10, 15, 20, or 25 mg/kg of alkaline chloroform fraction （Alk-CF） of E.ogollocho by oral administration. Compared with controls, AIk-CF decreased the writhing numbers （P〈0.01） in a dose dependent manner. Further we determined that, AIk-CF contained, a potent compared to control, also potent anti-nociceptive agent that acted via opioid receptors and using HPLC, identified this compound as Rutin. Docking simulation demonstrated that Rutin interacted strongly with cyclooxygenase, forming a number of specific hydrogen bonds. In conclusion we have identified peripheral and central anti-nociceptive activities of E.ogollocho that involve opioid receptor, and in which the active compound is Rutin.

Antidepressant and anti-nociceptive effects of Nigella sativa and its main constituent,thymoquinone:A literature review

Medicinal plants and their ingredients have beneficial effects on human health.Nigella sativa is a herbal plant with multiple biological and pharmacological activities.Previous studies demonstrated the anti-inflammatory and antioxidant properties of Nigella sativa and its main constituent thymoquinone significantly contributes to the antidepressant and anti-nociception effects of this plant.It has been reported that thymoquinone may achieve its antidepressant effect by preventing the elimination of brain neurotransmitters affecting depression such as serotonin.The role of brain-derived neurotrophic factors in the antidepressant effects of thymoquinone has also been documented.Additionally,thymoquinone can attenuate pain by upregulation of intracellular signaling pathways related to nitric oxide and K_(ATP)^(+)channels.The present review summarizes the antidepressant and anti-nociceptive activity of Nigella sativa and its main constituent thymoquinone by searching literature on electronic databases such as PubMed,Web of Science,Scopus,and Google Scholar from the beginning of 2010 until the end of August 2022.

Curculigo recurvata W.T.Aiton exhibits anti-nociceptive and anti-diarrheal effects in Albino mice and an in silico model

Background: Curculigo recurvata(C. recurvata) is an enthnomedicinally important herb reported to have significant medicinal values. The present study aimed to explore the in vivo and in silico anti-nociceptive and anti-diarrheal effects of a C. recurvate rhizome methanol extract(Me-RCR).Methods: The analgesic effects of Me-RCR were assessed using acetic acid-induced writhing and the formalin-induced flicking test. The drugs were administered intraperitoneally(IP) at doses of 200 and 400 mg/kg body weight(bw). Anti-diarrheal activity was evaluated by assessing intestinal motility, hypersecretion, and fecal score in mice at oral doses of 200 and 400 mg/kg·bw. Computer facilitated analyses for anti-nociceptive and anti-diarrheal activities of three isolated compounds from C. recurvata were undertaken to identify the best-fit phytoconstituents.Results: The Me-RCR showed significant(P <.05) peripheral anti-nociception at the highest dose. The extract inhibited both early and late phases of nociception in the formalin-induced writhing test. In the castor oil-induced diarrhoea model, the extract significantly(P <.05) prolonged the onset time of diarrhoea, inhibited percentage of diarrhoea, and decreased both the volume and weight of intestinal contents. Rates of intestinal fluid accumulation inhibition were(33.61 ± 1.00)% and(46.44 ± 0.89)% at Me-RCR doses of 200 and 400 mg/kg·bw, respectively. Moreover, a significant(P <.05) reduction in gastrointestinal motility was observed. An absorption, distribution, metabolism, excretion and/or toxicity(ADME/T) test showed that the selected compounds yielded promising results, satisfying Lipinski's rule of five for predicting drug-like potential. Notably, of the three phytoconstituents curculigine and isocurculigine possessed the highest affinity for the COX-1 and COX-2. Isocurculigine was also identified as the most effective anti-diarrheal compound in the computer-facilitated model.Conclusion: An extract of the plant C. recurvata showed potential analgesic and antidiarrheal activity due to the presence of one or more active secondary metabolite(s).

The aconitine analog bulleyaconitine A exhibits anti-hypersensitivity through direct stimulation of dynorphin A release from spinal microglia in the rat model of neuropathy

Aim Aconitine and its structurally-related diterpenoid alkaloids have been shown to interact differential- ly with neuronal voltage-dependent sodium channels and be responsible for their analgesia and toxicity. Bulleya- conitine A （ BAA or BLA） is an aconitine analog and has been prescribed for the management of pain. The present study aimed to evaluate the inhibitory effects of BAA on pain hypersensitivity and morphine anti-nociceptive toler- ance, and explore whether the release of dynorphin A from spinal microglia was associated with its mechanism of actions. Methods Rat models of neuropathic pain, formalin test and bone cancer pain were used, and spinal dynorphin A level and expression were measured. Sample size of animals was six in each study group. Resultes A single intrathecal or subcutaneous （but not intraventricular or local） injection of BAA blocked spinal nerve liga- tion-induced painful neuropathy, bone cancer-induced pain and formalin-induced hyperalgesia by 60% - 100% with the ED50 values of 94 - 126 ng/rat （intrathecal） and 42 - 59 μg · kg^-1 （ subcutaneous）, respectively. Follow- ing chronic treatment, BAA did not induce either self-tolerance to anti-nociception or cross-tolerance to morphine anti-nociception, and completely prevented morphine tolerance. Spinal BAA anti-nociception, but not neurotoxici- ty, was completely blocked by the specific microglial inhibitor minocycline. In a minocycline-sensitive and lido- BAA stimulated the release of dynorphin A from the spinal cord, and the caine- or ropivacaine-insensitive manner, primary culture of microglia but not from neurons or astrocytes. The blockade effects of BAA on nociception and morphine tolerance were completely blocked by the specific dynorphin A antiserum and/or K-opioid receptor antago- nist. Conclusions Our results demonstrated that BAA eliminated pain hypersensitivity and morphine tolerance through the direct stimulation of dynorphin A release from spinal microglia, which was not dependent on the interac- tions with sodium channels.

The coastal medicinal plant Vitex rotundifolia: a mini-review on its bioactive compounds and pharmacological activity

Humans have long used natural remedies like plants and herbs to treat disease.Furthermore,research has been ongoing to find alternative pharmaceutical drugs based on traditionally used plants,as natural products show fewer side effects compared to synthetic drugs.Medicinal plants have long been targeted in drug development due to their bioactive compounds like alkaloids,flavonoids,and terpenoids.This is not only the case for terrestrial plants,but marine environments also provide a larger diversity of flora and fauna with medicinal bioactive compounds.Vitex rotundifolia,also known as Beach Vitex,is a coastal plant that has been traditionally used to treat a variety of diseases including premenstrual syndrome,headaches,migraines,colds,and eye pain.There have been many review papers on V.rotundifolia,emphasizing its taxonomy,distribution,and biological activity.Our current mini-review not only summarizes the pharmacology and bioactivity of V.rotundifolia,but it also provides new information on the main bioactive compounds of V.rotundifolia such as flavonoids,phenolic acid,and terpenes and their current pharmacological activity in vitro and in vivo research.This information can be useful for developing new pharmaceutical and nutraceutical agents to treat and manage disease.

Electroacupuncture at Fengchi(GB20) inhibits calcitonin gene-related peptide expression in the trigeminovascular system of a rat model of migraine

Most migraine patients suffer from cutaneous allodynia; however, the underlying mechanisms are unclear. Calcitonin gene-related peptide（CGRP） plays an important role in the pathophysiology of migraine, and it is therefore, a potential therapeutic target for treating the pain. In the present study, a rat model of conscious migraine, induced by repeated electrical stimulation of the superior sagittal sinus, was established and treated with electroacupuncture at Fengchi（GB20）（depth of 2–3 mm, frequency of 2/15 Hz, intensity of 0.5–1.0 m A, 15 minutes/day, for 7 consecutive days）. Electroacupuncture at GB20 significantly alleviated the decrease in hind paw and facial withdrawal thresholds and significantly lessened the increase in the levels of CGRP in the trigeminal ganglion, trigeminal nucleus caudalis and ventroposterior medial thalamic nucleus in rats with migraine. No CGRP-positive cells were detected in the trigeminal nucleus caudalis or ventroposterior medial thalamic nucleus by immunofluorescence. Our findings suggest that electroacupuncture treatment ameliorates migraine pain and associated cutaneous allodynia by modulating the trigeminovascular system ascending pathway, at least in part by inhibiting CGRP expression in the trigeminal ganglion.

Pharmacological insights into Chukrasia velutina bark:Experimental and computer-aided approaches

Background:Chukrasia velutina is an enthnomedicinally used plant reported to have significant medicinal values.The present study aimed to explore the pharmacological activities of bark methanol extract using in vitro,in vivo and in silico models.Methods:The study was designed to investigate the pharmacological effects of methanol extract of Chukrasia velutina bark(MECVB)through in vitro,in vivo and in silico assays.Analgesic activity was tested using formalin-i nduced nociception and acetic acid-i nduced writhing assays while the antipyretic effect was tested using yeast-i nduced hyperthermia in mice model.The antioxidant effect was tested using the DPPH and reducing power assay and the cytotoxic screening was tested using the brine shrimp lethality bioassay.In addition,in silico studies were conducted using computer aided methods.Results:In the acetic acid-i nduced writhing assay,the extract showed 28.36%and 56.16%inhibition of writhing for doses of 200 and 400 mg/kg,respectively.Moreover,a dose-dependent formalin-i nduced licking response was observed in both early and late phase.In yeast-i nduced pyrexia,the MECVB exhibited(p<0.05)antipyretic effect.The extract demonstrated an ICvalue of 78.86μg/ml compared with ascorbic acid(IC23.53μg/ml)in the DPPH scavenging assay.The compounds sitosterol,5,7-dimethoxycoumarin and scopoletin were seen be effective in molecular docking scores against COX-I(2OYE),COX-II(6COX)and human peroxiredoxin 5(1HD2).In ADME/T analysis,5,7-dimethoxycoumarin and scopoletin satisfied Lipinski’s rule of five and thus are potential drug candidates.Conclusion:The bark of Chukrasia velutina showed significant analgesic and antipyretic properties and is a potential source of natural anti-oxidative agents.

Overcoming the Bell‐Shaped Dose‐Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol

Cannabidiol (CBD), a major constituent of Cannabis, has been shown to be a powerful anti-inflammatory and anti-anxiety drug, without exerting a psychotropic effect. However, when given either intraperitoneally or orally as a purified product, a bell-shaped dose-response was observed, which limits its clinical use. In the present study, we have studied in mice the anti-inflammatory and anti-nociceptive activities of standardized plant extracts derived from the Cannabis sativa L., clone 202, which is highly enriched in CBD and hardly contains any psychoactive ingredients. In stark contrast to purified CBD, the clone 202 extract, when given either intraperitoneally or orally, provided a clear correlation between the anti-inflammatory and anti-nociceptive responses and the dose, with increasing responses upon increasing doses, which makes this plant medicine ideal for clinical uses. The clone 202 extract reduced zymosan-induced paw swelling and pain in mice, and prevented TNFα production in vivo. It is likely that other components in the extract synergize with CBD to achieve the desired anti-inflammatory action that may contribute to overcoming the bell-shaped dose-response of purified CBD. We therefore propose that Cannabis clone 202 (Avidekel) extract is superior over CBD for the treatment of inflammatory conditions.

Protective effects of crude and alkaloidal extracts of Tamarindus indica against acute inflammation and nociception in rats

Objective: To investigate the anti-inflammatory and antinociceptive effects of total alkaloids extracted from the leaf of Tamarindus indica (T. indica) in rats. Methods:Acetic acid-induced pain and egg albumin-induced inflammation were used to inspect the anti-nociceptive and anti-inflammatory effects of the crude and alkaloidal extracts of T. indica at doses of 40 and 400 mg/kg, respectively. Sodium diclofenac was used as the control drug. Results:The percentage yields of crude methanol and alkaloidal extracts of T. indicawere 2.85% and 0.98%, respectively. Screening of secondary metabolite of the crude extract revealed the presence of saponins, alkaloids, tannins, steroids, phenols and terpenes, while phlobatannins was not detected. The safe dose and LD50 were 400 and 750 mg/kg for crude methanol extract, respectively, while the safe dose and LD50 of alkaloidal extract were 40 and 57 mg/kg, respectively. The anti-inflammatory and antinociceptive effects of crude methanol extract and alkaloid extract of T. indica were significantly (P < 0.05) different from those of control rats. The standard drug (sodium diclofenac), crude extract and alkaloidal extract showed percentage inhibition of 89.36%, 53.92% and 81.37% in paw edema, respectively. Conclusions:The results obtained indicated that the crude and alkaloidal extracts of the plant exhibited significant anti-inflammatory and antinociceptive activities, thus, supporting its folkloric use for the treatment of these conditions.

Effect of SRD-P401 on the Discomfort of Neck and/or Shoulder Stiffness

SRD-P401 is a newly developed healthy food supplement which has an anti-inflammatory and analgesic effect. In this report, the effects of SRD-P401 on neck and shoulder stiffness were assessed by an inquiry method in the public field. The stiffness symptoms of all participants were improved after taking SRD-P401. The symptoms of the participants who took 3 g/day and/or 9 g/day of SRD-P401 improved in a week after taking it. Unpleasant adverse effects in stomach and alimentally organs were not found during the test period. SRD-P401 showed the anti-nociceptive effect on the acetic-acid-induces abdominal writhing in rats. The potency was equivalent to aspirin. Moreover, to investigate the ability of the anti-inflammatory effects of SRD-P401, we exerted by inhibiting the Cyclooxygenase (COX) enzyme activity. SRD-P401 and its constituents inhibit the COX activity. The results of this field test indicated SRD-P401 would be a beneficial and useful healthy food supplement for a person with stiffness in neck and/or shoulder.

Prophylactic effects of asiaticoside-based standardized extract of Centella asiatica(L.) Urban leaves on experimental migraine: Involvement of 5HT1A/1B receptors

The present study aimed at evaluation of prophylactic efficacy and possible mechanisms of asiaticoside （AS） based standardized extract of Centella asiatica （L.） Urban leaves （INDCA） in animal models of migraine. The effects of oral and intranasal （i.n.） pretreatment of INDCA （acute and 7-days subacute） were evaluated against nitroglycerine （NTG, 10 mg·kg^-1, i.p.） and bradykinin （BK, 10 μg, intra-arterial） induced hyperalgesia in rats. Tail flick latencies （from 0 to 240 rain） post-NTG treatment and the number of vocalizations post-BK treatment were recorded as a measure of hyperalgesia. Separate groups of rats for negative （Normal） and positive （sumatriptan, 42 mg.kg ^-1, s.c.） controls were included. The interaction of 1NDCA with selective 5-HT1A, 5-HT1B, and 5-HTI D receptor antagonists （NAN-190, Isamoltane hemifumarate, and BRL-15572 respectively） against NTG-induced hyperalgesia was also evaluated. Acute and sub-acute pre-treatment of INDCA [10 and 30 mg.kg^-1 （oral） and 100 μg/rat （i.n.） showed significant anti-nociception activity, and reversal of the NTG-induced hypera｜gesia and brain 5-HT concentration decline. Oral pre-treatment with INDCA （30 mg·kg ^-1, 7 d） showed significant reduction in the number of vocalization. The anti-nociceptive effects of INDCA were blocked by 5-HTIA and 5-HT1B but not 5-HT1D receptor antagonists. In conclusion, 1NDCA demonstrated promising anti-nociceptive effects in animal models of migraine, probably through 5-HT1A/1B medicated action.

Design and synthesis of 4-(1-(4-chlorobenzyl)-2,3-dioxoindolin-5-yl)-1 -(4-substituted/unsubstituted benzylidene) semicarbazide:Novel agents with analgesic,anti-inflammatory and ulcerogenic properties

A new series of isatin semicarbazide derivatives（7a-7j） were synthesized and characterized by spectroscopic means and elemental analysis.Analgesic and anti-inflammatory screening was performed using tail-flick technique and the carrageenan-induced foot paw edema test respectively.The ulcerogenicity was also determined for all the compounds.Some of the compounds showed moderate enhancement of the activity.Among the synthesized derivatives,compound 7d showed higher analgesic, antiinflammatory and one-third of ulcer index of the reference drug.

Evaluation of Antinociceptive Activity of Methanol Extract from Cleome rutidosperma in Mice

Objective C/eome rutidosperma （Capparidaceae）, commonly known as ＂Fringed Spider Flower＂, is a medicinal plant found in Southeast Asia. C. rutidosperma is used in folk medicine for diuretic, laxative, analgesic, anti-inflammatory, antipyretic, antimicrobial, anti-oxidant, hypoglycemic, and anthelmintic activities. We have evaluated the anti-nociceptive properties of methanol extract from C. rutidosperma （MECR） in vivo. Methods Thermal method （hot plate test and tail flick test） was induced to judge the anti-inflammatory effect and couple of chemical method also used （formalin induced licking test; writhing test carried by acetic acid） to evaluate analgesic effect. Both of these tests were made over animal models, like mice and rats. Two different doses （1 O0 and 200 mg/kg） were used for each case of test, while morphine sulphate （5mg/kg, ip） was used as reference drug. Results MECR demonstrated the significantly anti-nociceptive activity in the analgesic and anti-inflammatory tests by reducing nociception in mice models （P 〈 0.001）. in the hot-plate and tail-flick tests, MECR significantly elongated the time to response to the thermal stimuli （100 and 200 mg/kg with P 〈 0.05, 0.001）. The remarkable increase in the latency was observed at 90 and 120 min. In acetic acid-induced writhing test and formalin induced licking test for anti-inflammatory activity, MECR at 100 and 200 mg/kg doses exhibited significant （P〈 0.001） reduction of writhing and licking response. Conclusion The anti-inflammatory and analgesic effects of C. rutidosperma propose that this effect may be a result of both peripheral and central mechanisms. Further study is required to ensure the proper mechanism of action as well as the active ingredient.