为进一步了解孤啡肽在脊髓水平是否具有抗伤害及抗炎作用,本实验在具有多种痛行为表现的蜜蜂毒模型上观察了鞘内注射孤啡肽对大鼠一侧后足底注入蜜蜂毒所诱致的同侧自发缩足反射、原发热和机械性痛敏以及注射部位炎症反应的影响,同时观...为进一步了解孤啡肽在脊髓水平是否具有抗伤害及抗炎作用,本实验在具有多种痛行为表现的蜜蜂毒模型上观察了鞘内注射孤啡肽对大鼠一侧后足底注入蜜蜂毒所诱致的同侧自发缩足反射、原发热和机械性痛敏以及注射部位炎症反应的影响,同时观察了新的高选择性孤啡肽受体拮抗剂CompB的作用。结果表明:与生理盐水对照组比较,鞘内注射孤啡肽(3、10、30nmol/10μl)对蜜蜂毒诱发的自发缩足反射次数的抑制作用随剂量提高而增大,抑制率分别为37±7,43±6 and 57±11%(三个剂量vs对照,P<0.05);而对蜜蜂毒诱发的注射部位炎症反应(爪体积、爪背腹厚度和蛋白渗出的增加)无显著影响。CompB(30nmol)可完全翻转10nmol孤啡肽对自发缩足反射的抑制作用。鞘内单次或重复注射孤啡肽(10nmol/10μl)对蜜蜂毒诱致的原发性热和机械性痛敏的发生和维持均无作用。本实验结果提示,外源性孤啡肽在脊髓通过孤啡肽受体的介导产生一定的镇痛作用,但是它可能仅对持续性自发痛有抑制作用,而对热和机械性痛敏及炎症反应均无影响。展开更多
Voltage-gated sodium channels(VGSCs) are transmembrane proteins responsible for generation and conduction of action potentials in excitable cells.Physiological and pharmacological studies have demonstrated that VGSCs ...Voltage-gated sodium channels(VGSCs) are transmembrane proteins responsible for generation and conduction of action potentials in excitable cells.Physiological and pharmacological studies have demonstrated that VGSCs play a critical role in chronic pain associated with tissue or nerve injury.Many long-chain peptide toxins(60-76 amino acid residues) purified from the venom of Asian scorpion Buthus martensii Karsch(BmK) are investigated to be sodium channel-specific modulators.The α-like neurotoxins that can bind to receptor site 3 of sodium channels,named as BmK I and BmK abT,could induce nociceptive effects in rats.On the contrast,the β-like neurotoxins that can bind to receptor site 4 of sodium channels,named as BmK AS,BmK AS-1 and BmK IT2,could produce potent anti-nociceptive effects in animal pain models.BmK I could strongly prolong the fast inactivation of tetrodotoxin(TTX)-sensitive Na+ currents on the rat dorsal root ganglia(DRG) neurons together with the augmentation of peak current amplitude.However,BmK IT2 and BmK ASs,potently suppressed both the peak TTX-resistant and TTX-sensitive Na+ currents on rat small DRG neurons.Moreover,BmK ASs could decrease the excitability of small DRG neurons.Thus,the nociception/anti-nociception induced by scorpion neurotoxins may attribute to their distinct modulation on sodium channels in primary afferent sensory neurons.Therefore,the sodium channel-specific modulators from BmK venom could be used as not only pharmacological tools for better understanding the roles of VGSCs in pain signal conduction,but also lead molecules in the development of ideal analgesics targeting VGSCs.展开更多
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 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.展开更多
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 ...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.展开更多
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 the...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.展开更多
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 techn...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.展开更多
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 t...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.展开更多
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 oral...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.展开更多
基金The present work is partially supported by the National Basic Brain Research Program (No. G1999054004) sponsored by Chinese National Ministry of Science and Technology (CMOST), National Natural Science Foundation of China (NSFC) (No.30000051, 30100052, 3
基金The work was supported by National Brain Science Basic Research Programme (No. G1999054004) and National Nature Science Foundation of China (No. 30000051, 30100052 and 30200077)
文摘为进一步了解孤啡肽在脊髓水平是否具有抗伤害及抗炎作用,本实验在具有多种痛行为表现的蜜蜂毒模型上观察了鞘内注射孤啡肽对大鼠一侧后足底注入蜜蜂毒所诱致的同侧自发缩足反射、原发热和机械性痛敏以及注射部位炎症反应的影响,同时观察了新的高选择性孤啡肽受体拮抗剂CompB的作用。结果表明:与生理盐水对照组比较,鞘内注射孤啡肽(3、10、30nmol/10μl)对蜜蜂毒诱发的自发缩足反射次数的抑制作用随剂量提高而增大,抑制率分别为37±7,43±6 and 57±11%(三个剂量vs对照,P<0.05);而对蜜蜂毒诱发的注射部位炎症反应(爪体积、爪背腹厚度和蛋白渗出的增加)无显著影响。CompB(30nmol)可完全翻转10nmol孤啡肽对自发缩足反射的抑制作用。鞘内单次或重复注射孤啡肽(10nmol/10μl)对蜜蜂毒诱致的原发性热和机械性痛敏的发生和维持均无作用。本实验结果提示,外源性孤啡肽在脊髓通过孤啡肽受体的介导产生一定的镇痛作用,但是它可能仅对持续性自发痛有抑制作用,而对热和机械性痛敏及炎症反应均无影响。
基金grants from National Basic Research Development Program of China(No.2006CB500801)National Natural Sciences Foundation of China(No.30370446)
文摘Voltage-gated sodium channels(VGSCs) are transmembrane proteins responsible for generation and conduction of action potentials in excitable cells.Physiological and pharmacological studies have demonstrated that VGSCs play a critical role in chronic pain associated with tissue or nerve injury.Many long-chain peptide toxins(60-76 amino acid residues) purified from the venom of Asian scorpion Buthus martensii Karsch(BmK) are investigated to be sodium channel-specific modulators.The α-like neurotoxins that can bind to receptor site 3 of sodium channels,named as BmK I and BmK abT,could induce nociceptive effects in rats.On the contrast,the β-like neurotoxins that can bind to receptor site 4 of sodium channels,named as BmK AS,BmK AS-1 and BmK IT2,could produce potent anti-nociceptive effects in animal pain models.BmK I could strongly prolong the fast inactivation of tetrodotoxin(TTX)-sensitive Na+ currents on the rat dorsal root ganglia(DRG) neurons together with the augmentation of peak current amplitude.However,BmK IT2 and BmK ASs,potently suppressed both the peak TTX-resistant and TTX-sensitive Na+ currents on rat small DRG neurons.Moreover,BmK ASs could decrease the excitability of small DRG neurons.Thus,the nociception/anti-nociception induced by scorpion neurotoxins may attribute to their distinct modulation on sodium channels in primary afferent sensory neurons.Therefore,the sodium channel-specific modulators from BmK venom could be used as not only pharmacological tools for better understanding the roles of VGSCs in pain signal conduction,but also lead molecules in the development of ideal analgesics targeting VGSCs.
基金The work was financially supported by grants from Chinese National Brain Science Basic Research Program sponsored by the National Ministry of Science and Technology (G1999054004) fromNational Natural Science Foundation of China (30100052,30200077,3030
文摘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.
基金Author would like to thank School of Health Sciences,Universiti Sains Malaysia and Universiti Malaysia Terengganu for providing the facilities to support this projectThis project is fully supported by Fundamental Research Grant Scheme Vot No.59479 from Ministry of Higher Education Malaysia.
文摘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.
基金supported by the National Natural Science Foundation of China,No.81603683a grant from the National Basic Research Program of China,No.2014CB543203a grant from the Beijing Municipal Science&Technology Commission of China,No.Z171100001017033
文摘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.
文摘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.
文摘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.
文摘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.
